Alzheimer's disease (AD) is the most common late-onset neurodegenerative disorder. Identifying individuals at increased risk of developing AD is important for early intervention. Using data from the ...Alzheimer Disease Genetics Consortium, we constructed polygenic risk scores (PRSs) for AD and age-at-onset (AAO) of AD for the UK Biobank participants. We then built machine learning (ML) models for predicting development of AD, and explored feature importance among PRSs, conventional risk factors, and ICD-10 codes from electronic health records, a total of > 11,000 features using the UK Biobank dataset. We used eXtreme Gradient Boosting (XGBoost) and SHapley Additive exPlanations (SHAP), which provided superior ML performance as well as aided ML model explanation. For participants age 40 and older, the area under the curve for AD was 0.88. For subjects of age 65 and older (late-onset AD), PRSs were the most important predictors. This is the first observation that PRSs constructed from the AD risk and AAO play more important roles than age in predicting AD. The ML model also identified important predictors from EHR, including urinary tract infection, syncope and collapse, chest pain, disorientation and hypercholesterolemia, for developing AD. Our ML model improved the accuracy of AD risk prediction by efficiently exploring numerous predictors and identified novel feature patterns.
Background Hyperuricemia, as a very prevalent chronic metabolic disease with increasing prevalence year by year, poses a significant burden on individual patients as well as on the global health care ...and disease burden, and there is growing evidence that it is associated with other underlying diseases such as hypertension and cardiovascular disease. The association between hyperuricemia and dietary inflammatory index (DII) scores was investigated in this study. Methods This study enrolled 13, 040 adult subjects (aged ≥ 20 years) from the US National Health and Nutrition Survey from 2003 to 2018. The inflammatory potential of the diet was assessed by the DII score, and logistic regression was performed to evaluate the relationship between the DII score and the development of hyperuricemia; subgroup analyses were used to discuss the influence of other factors on the relationship. Results Participants in the other quartiles had an increased risk of hyperuricemia compared to those in the lowest quartile of DII scores. Stratification analyses stratified by body mass index (BMI), sex, hypertension, drinking, diabetes, education level and albumin-creatinine-ratio (ACR) revealed that the DII score was also associated with the risk of hyperuricemia (P<0.05). There was an interaction in subgroup analysis stratified by sex, age, and hypertension (P for interaction <0.05). The results showed a linear-like relationship between DII and hyperuricemia, with a relatively low risk of developing hyperuricemia at lower DII scores and an increased risk of developing hyperuricemia as DII scores increased. Conclusions This study showed that the risk of hyperuricemia increased at slightly higher DII scores (i.e., with pro-inflammatory diets), but not significantly at lower levels (i.e., with anti-inflammatory diets). The contribution of the DII score to the development of hyperuricemia increased with higher scores. The relationship between inflammatory diets and hyperuricemia requires more research on inflammation, and this study alerts the public that pro-inflammatory diets may increase the risk of developing hyperuricemia.
Pterosaurs were a unique clade of flying reptiles that were contemporaries of dinosaurs in Mesozoic ecosystems. The Pterodactyloidea as the most species-diverse group of pterosaurs dominated the sky ...during Cretaceous time, but earlier phases of their evolution remain poorly known. Here, we describe a 160 Ma filter-feeding pterosaur from western Liaoning, China, representing the geologically oldest record of the Ctenochasmatidae, a group of exclusive filter feeders characterized by an elongated snout and numerous fine teeth. The new pterosaur took the lead of a major ecological transition in pterosaur evolution from fish-catching to filter-feeding adaptation, prior to the Tithonian (145–152 Ma) diversification of the Ctenochasmatidae. Our research shows that the rise of ctenochasmatid pterosaurs was followed by the burst of eco-morphological divergence of other pterodactyloid clades, which involved a wide range of feeding adaptations that considerably altered the terrestrial ecosystems of the Cretaceous world.
Lacustrine deposits exposed at Daohugou, Inner Mongolia, China, have yielded superbly preserved vertebrate fossils. The fossil beds were first misinterpreted as of Early Cretaceous age, based on ...alleged occurrences of key fossils of the Jehol Biota. Compelling evidence revealed by more rigorous research involving regional biostratigraphy, radiometric dating, and paleontology supports the Middle Jurassic age of the fossil beds. Despite the awesome evidence for the Middle Jurassic age of the Daohugou beds, the age dispute has been resurrected recently by invoking an overturned stratigraphic sequence. A careful review of the data, however, found no evidence that this sequence has been overturned. In addition, many of the assumptions, on which the conjecture of the fossil beds being post- Middle Jurassic is imprudently based, are self-contradictory or otherwise misleading. Thus, the post- Middle Jurassic age of the Daohugou beds as an unfounded conclusion can readily be dismissed.
Peripheral nerve injury (PNI) is a common and complex clinical disease with high morbidity, limited treatment options and poor clinical outcomes. Several million cases of PNI in the world every year ...have brought a heavy burden to the patients and the social economy. Autologous nerve grafting has long been the “gold standard” in the treatment of PNI repair, but it still has some shortcomings, such as donor area injury, limited graft source and mismatch of nerve thickness after transplantation. In recent years, many artificial nerve guidance conduits (NGCs) have emerged for replacing autologous nerve grafts, and their effectiveness has been proven. Currently, there are already clinical products obtained from the European CE Certification, and approved by the Food and Drug Administration (FDA), China Food and Drug Administration (CFDA), Therapeutic Goods Administration (TGA) in Australia, etc. The preparation of NGCs requires interdisciplinary studies and has received considerable attention from researchers in recent years. At present, among emerging and mature manufacturing technologies, textile methods to prepare NGCs are relatively simple and have wide material sources, which has become a hotspot in textile research. This paper mainly reviewed the current situation and recent technological achievements of NGCs that were prepared by textile methods. Several other common methods were also briefly summarized. Furthermore, current NGCs products and their clinical applications were reported. Finally, the future development direction of textile-based NGCs is discussed in this review.
•Textile methods such as weaving, knitting, braiding etc. were with fast speed and had wide source of materials.•The progress of nerve guidance conduits (NGCs) based on textile methods were introduced in this review.•NGCs fabricated by electrospinning, and other techniques such as freeze-drying, 3D printing, micro-patterning etc. were also reviewed.•NGCs products on the market and their clinical applications and related clinical data were summarized.
In this study, fluorescent nitrogen-doped carbon dots (NCDs) were tuned via varying the sources with different number of carboxyl groups. Owing to the interaction between amino and carboxyl, more ...amino groups conjugate the surface of the NCDs by the source with more carboxyl groups. Fluorescent NCDs were tuned via varying the sources with different content of carboxyl groups. Correspondingly, the nitrogen content, fluorescence quantum yields and lifetime of NCDs increases with the content of carboxyl groups from the source. Furthermore, cytotoxicity assay and cell imaging test indicate that the resultant NCDs possess low cytotoxicity and excellent biocompatibility.
Polysaccharide of Cissus pteroclada Hayata (CPHP) was extracted and purified. Three major fractions (CPHP I, CPHP II-1 and CPHP II-2) from the CPHP were purified by column chromatography and ...investigated for their monosaccharide compositions, scavenging radical effects and hepatoprotective activities in vitro. The results showed that glucose and galactose were the main monosaccharides of three polysaccharide fractions, CPHP II-1 and CPHP II-2 were acidic polysaccharide fractions which contained glucuronic acid and galacturonic acid. Antioxidant activity determination suggested that CPHP I and CPHP II-1 had a higher scavenging effects on DPPH, superoxide radical, hydroxyl radical and ABTS radical. And the results of antioxidant test in vitro showed that CPHP II-2 could significantly increase (P<0.01) the activities of SOD and GSH-Px and decreased MDA level in human hepatocyte cell line (HL7702 cell), which indicating that CPHP II-2 possessed good hepatoprotective activity.
The origin of propylitic fluids in intermediate sulfidation mineralization has not been investigated in detail. Here, we present an extensive petrographic, geochemical, and isotopic (O-H-Sr) study of ...propylitic epidote, chlorite, and calcite from the Zhengguang intermediate sulfidation epithermal Au-Zn deposit, NE China. Propylitic minerals can be divided into three main types based on their different textural occurrences, namely interstitial cement of clasts of hydrothermal breccia, replacement of primary plagioclase or hornblende, and vein infill of cracks, with late, minor calcite as amygdules in vesicles of andesite representing a fourth textural occurrence. The H-O isotope compositions and mass balance calculations suggest that most propylitic epidote records a dominant (> 50%) contribution of magmatic fluids. The decrease of the average δ
18
O
H
2
O
values equilibrated with different types of epidote (cement 6.8 ± 0.7‰, replacement 5.1 ± 1.1‰, vein 4.5 ± 1.4‰, 1 SD), and the decreasing content of high-temperature elements (e.g., Cu-Mo) from cement, through replacement to vein epidote and chlorite, collectively indicates a decreasing role of magmatic fluids. Replacement epidote and chlorite are enriched in Sr-Mn-Y-Sb, whereas replacement epidote and calcite record similar (
87
Sr/
86
Sr)
i
values to the andesitic host rock, suggesting that replacement minerals inherit certain elements from plagioclase and hornblende, and the Sr isotope signature of the wall rocks. We highlight that propylitic alteration in epithermal deposits can involve significant proportions of magmatic fluids and texturally different alteration mineral types should be considered when using mineral isotopic or chemical compositions to track fluid sources or to vector towards the location of intrusive centers.
Summary
Nematode‐trapping fungi live mainly as saprobes in soil environments. When encountering nematodes, these fungi become ‘carnivorous’ and develop specialized trapping devices to attack their ...hosts for extracting nutrients, especially nitrogen source. Thus, nematode‐trapping fungi are model organisms for understanding the molecular mechanism of the switch between saprobic and parasitic phases of pathogen life cycles. Arthrobotrys oligospora, one of the best‐studied nematode‐trapping fungi, mainly lives as a saprobe. In the presence of nematodes, A. oligospora enters the parasitic stage by forming adhesive reticulate traps to capture nematodes. In filamentous fungi, autophagy has been shown to be involved in morphogenesis and morphology. In this study, we demonstrate that autophagy is induced by nematodes during the early stage of trap formation in A. oligospora. Disruption of atg8 gene not only abolishes the nematode‐induced autophagy, but also suppresses trap formation and reduces pathogenicity for nematodes. During the early stage of trap formation, the expression of genes involved in amino acid biosynthesis is upregulated and the transcriptional activity of GCN4 is induced in A. oligospora, suggesting that nematodes induce autophagy probably by triggering intracellular amino acid starvation. Autophagy is thus crucial for trap formation in A. oligospora during infection of nematodes.
Bronchiectasis has been associated with increased risks of cardiovascular disease, in which early-stage endothelial dysfunction might have played pivotal roles. We aimed to investigate endothelial ...function in bronchiectasis patients, by measuring flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT) as compared with control subjects, and to elucidate the impact of different risk factors on subclinical atherosclerosis.
The study included 80 bronchiectasis patients and 80 age- and sex-matched healthy subjects. Vascular endothelial function was evaluated with FMD in the brachial artery in response to reactive hyperemia, and CIMT was measured with high-resolution ultrasonography. Disease severity was evaluated with Bronchiectasis Severity Index and FACED scores. Demographic, disease duration, radiology, spirometry, sputum bacteriology and systemic inflammatory indices were also assessed.
FMD was significantly lower in bronchiectasis patients than in control subjects (8.92 ± 2.70% vs. 11.17 ± 3.44%, P < 0.001). FMD significantly correlated with Bronchiectasis Severity Index (rho = -0.60, P < 0.001) and FACED score (rho = -0.39, P < 0.001). In multivariate regression analysis, age, body-mass index, Pseudomonas aeruginosa colonization and high-resolution computed tomography scores were independent factors influencing on the FMD in bronchiectasis patients, even after adjustment for other clinical variables. No significant difference in CIMT was detected between bronchiectasis patients and healthy subjects (P > 0.05).
Compared with healthy subjects, bronchiectasis patients have greater risks of endothelial dysfunction which is independent of previously well-studied risk factors, calling for the vigilance to screen early for vascular changes to minimize the future risks of cardiovascular events.
•This study represents the first study which directly evaluates the functional and structural vascular abnormalities in patients with clinically sable bronchiectasis.•We showed that FMD in bronchiectasis patients was markedly lower than in healthy subjects, and that FMD was mainly determined by the age, BMI, PA colonization and HRCT scores.•In addition, there were negative, significant correlations between FMD% and bronchiectasis severity metrics, including the BSI and FACED scores.•However, bronchiectasis patients and healthy subjects did not differ in CIMT.•Considering these vascular markers have been linked with cardiovascular risk in generals, our results highlight the need to call for the vigilance to screen early for vascular changes to minimize the future risks of cardiovascular events.
PDF
