Explaining colour variation among animals at broad geographic scales remains challenging. Here we demonstrate how deep learning-a form of artificial intelligence-can reveal subtle but robust patterns ...of colour feature variation along an ecological gradient, as well as help identify the underlying mechanisms generating this biogeographic pattern. Using over 20,000 images with precise GPS locality information belonging to nearly 2,000 moth species from Taiwan, our deep learning model generates a 2048-dimension feature vector that accurately predicts each species' mean elevation based on colour and shape features. Using this multidimensional feature vector, we find that within-assemblage image feature variation is smaller in high elevation assemblages. Structural equation modeling suggests that this reduced image feature diversity is likely the result of colder environments selecting for darker colouration, which limits the colour diversity of assemblages at high elevations. Ultimately, with the help of deep learning, we will be able to explore the endless forms of natural morphological variation at unpreceded depths.
Antimicrobial peptides (AMPs) have potential antifungal activities; however, their intracellular protein targets are poorly reported. Proteome microarray is an effective tool with high-throughput and ...rapid platform that systematically identifies the protein targets. In this study, we have used yeast proteome microarrays for systematical identification of the yeast protein targets of Lactoferricin B (Lfcin B) and Histatin-5. A total of 140 and 137 protein targets were identified from the triplicate yeast proteome microarray assays for Lfcin B and Histatin-5, respectively. The Gene Ontology (GO) enrichment analysis showed that Lfcin B targeted more enrichment categories than Histatin-5 did in all GO biological processes, molecular functions, and cellular components. This might be one of the reasons that Lfcin B has a lower minimum inhibitory concentration (MIC) than Histatin-5. Moreover, pairwise essential proteins that have lethal effects on yeast were analyzed through synthetic lethality. A total of 11 synthetic lethal pairs were identified within the protein targets of Lfcin B. However, only three synthetic lethal pairs were identified within the protein targets of Histatin-5. The higher number of synthetic lethal pairs identified within the protein targets of Lfcin B might also be the reason for Lfcin B to have lower MIC than Histatin-5. Furthermore, two synthetic lethal pairs were identified between the unique protein targets of Lfcin B and Histatin-5. Both the identified synthetic lethal pairs proteins are part of the Spt-Ada-Gcn5 acetyltransferase (SAGA) protein complex that regulates gene expression via histone modification. Identification of synthetic lethal pairs between Lfcin B and Histatin-5 and their involvement in the same protein complex indicated synergistic combination between Lfcin B and Histatin-5. This hypothesis was experimentally confirmed by growth inhibition assay.
Piwi-interacting RNAs (piRNAs) are the small non-coding RNAs (ncRNAs) that silence genomic transposable elements. And researchers found out that piRNA also regulates various endogenous transcripts. ...However, there is no systematic understanding of the piRNA binding patterns and how piRNA targets genes. While various prediction methods have been developed for other similar ncRNAs (e.g., miRNAs), piRNA holds distinctive characteristics and requires its own computational model for binding target prediction. Recently, transcriptome-wide piRNA binding events in C. elegans were probed by PRG-1 CLASH experiments. Based on the probed piRNA-messenger RNAs (mRNAs) binding pairs, in this research, we devised the first deep learning architecture based on multi-head attention to computationally identify piRNA targeting mRNA sites. In the devised deep network, the given piRNA and mRNA segment sequences are first one-hot encoded and undergo a combined operation of convolution and squeezing-extraction to unravel motif patterns. And we incorporate a novel multi-head attention sub-network to extract the hidden piRNA binding rules that can simulate the biological piRNA target recognition process. Finally, the true piRNA-mRNA binding pairs are identified by a deep fully connected sub-network. Our model obtains a supreme discriminatory power of AUC formula omitted 93.3% on an independent test set and successfully extracts the verified binding pattern of a synthetic piRNA. These results demonstrated that the devised model achieves high prediction performance and suggests testable potential biological piRNA binding rules. In this research, we developed the first deep learning method to identify piRNA targeting sites on C. elegans mRNAs. And the developed deep learning method is demonstrated to be of high accuracy and can provide biological insights into piRNA-mRNA binding patterns. The piRNA binding target identification network can be downloaded from http://cosbi2.ee.ncku.edu.tw/data_download/piRNA_mRNA_binding.
Background Acute respiratory distress syndrome (ARDS) is characterized by alveolar epithelial disruption. Lipoxins (LXs), as so-called "braking signals" of inflammation, are the first mediators ...identified to have dual anti-inflammatory and inflammatory pro-resolving properties. Methods In vivo, lipoxinA.sub.4 was administrated intraperitoneally with 1 mug/per mouse after intra-tracheal LPS administration (10 mg/kg). Apoptosis, proliferation and epithelial-mesenchymal transition of AT II cells were measured by immunofluorescence. In vitro, primary human alveolar type II cells were used to model the effects of lipoxin A.sub.4 upon proliferation, apoptosis and epithelial-mesenchymal transition. Results In vivo, lipoxin A.sub.4 markedly promoted alveolar epithelial type II cells (AT II cells) proliferation, inhibited AT II cells apoptosis, reduced cleaved caspase-3 expression and epithelial-mesenchymal transition, with the outcome of attenuated LPS-induced lung injury. In vitro, lipoxin A.sub.4 increased primary human alveolar epithelial type II cells (AT II cells) proliferation and reduced LPS induced AT II cells apoptosis. LipoxinA.sub.4 also inhibited epithelial mesenchymal transition in response to TGF-beta.sub.1, which was lipoxin receptor dependent. In addition, Smad3 inhibitor (Sis3) and PI3K inhibitor (LY294002) treatment abolished the inhibitory effects of lipoxinA.sub.4 on the epithelial mesenchymal transition of primary human AT II cells. Lipoxin A.sub.4 significantly downregulated the expressions of p-AKT and p-Smad stimulated by TGF-beta.sub.1 in primary human AT II cells. Conclusion LipoxinA.sub.4 attenuates lung injury via stimulating epithelial cell proliferation, reducing epithelial cell apoptosis and inhibits epithelial-mesenchymal transition. Keywords: Acute respiratory distress syndrome, Alveolar type II cells, Proliferation, Apoptosis, Epithelial to mesenchymal transition
Objective
To compare
Pneumocystis jirovecii
pneumonia (PJP) risk between patients with autoimmune rheumatic diseases (ARD) and the general population
Methods
We identified patients with ARD recorded ...in the National Health Insurance Research Database of Taiwan from 2002 to 2015 and randomly selected a comparison cohort from the general population matched for age and sex. We analyzed PJP risk stratified by sex, age, comorbidities, and medications using Cox proportional hazard model.
Results
We enrolled 103,117 patients with ARD. PJP risk significantly increased in patients with any ARD and with each individual ARD like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren’s syndrome (SjS), polymyositis and dermatomyositis (PM/DM), systemic sclerosis (SSc), and systemic vasculitis. Patients with PM/DM showed prominent risk with incidence rate of 12.47/100,000 patient year (95% confidence interval (CI), 32.16–86.70). In a time-dependent Cox proportional hazard model with comorbidities and medications as covariates, PM/DM, SSc, SLE, and SjS significantly increased adjusted hazard ratios (aHR) of 5.40, 5.12, 4.09, and 3.64, respectively (95% CI of 2.82–10.35, 2.16–12.13, 2.41–6.95, and 2.06–6.42, respectively). AHR after adjusting for male sex, cancer, human immunodeficiency virus infection (HIV), and interstitial lung disease also significantly increased. Use of daily oral steroid dose of >10 mg conferred the highest risk followed by mycophenolate. Use of injected steroids, cyclophosphamide, biological agents, methotrexate, and cyclosporine conferred a significantly higher risk.
Conclusion
Underlying ARD significantly predisposes patients to PJP, with PM/DM posing the highest threat. In addition to underlying disease, comorbidities and concomitant immunosuppressants are major risks. The strongest risk is recent daily steroid dose of >10 mg. Mycophenolate seems to be a more prominent risk factor than cyclophosphamide.
Key Points
• Autoimmune rheumatic diseases (ARD) significantly increased the overall risk of PJP, and so did each individual ARD.
• Use of steroids, mycophenolate, cyclophosphamide, biological agents, methotrexate, and cyclosporine all significantly increased risk of PJP.
• Male, elderly, malignancy, HIV, and interstitial lung disease are also related to increased risk of PJP.
• Underlying ARD, comorbidities, and use of immunosuppressant should all be considered in determining the overall risk of PJP.
Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Analysis of The Cancer Genome Atlas database and clinical tissue microarray ...staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. Silencing of URB1 hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment indicated that activating transcription factor 4 (ATF4) and X‐box binding protein 1 (XBP1) are potential downstream targets of URB1 and could transcriptionally interact through direct binding. Silencing of URB1 significantly decreased ATF4 and cyclin A2 (CCNA2) expression in vivo and in vitro. Restoration of ATF4 effectively reversed the malignant proliferation phenotype of URB1‐silenced CRC cells. Dual‐luciferase reporter and ChIP assays indicated that XBP1 transcriptionally activated ATF4 by binding with its promoter region. X‐box binding protein 1 colocalized with ATF4 in the nuclei of RKO cells, and ATF4 mRNA expression was positively regulated by XBP1. This study shows that URB1 contributes to oncogenesis and CRC growth through XBP1‐mediated transcriptional activation of ATF4. Therefore, URB1 could be a potential therapeutic target for CRC.
The classic ribosome assembly factor URB1 is overexpressed and related to unfavorable clinicopathological characteristics in colorectal cancer (CRC). URB1 silencing significantly hampered human CRC cell proliferation and decreased ATF4, CCNA2, and XBP1 expression in vivo and in vitro. Briefly, our study shows that URB1 contributes to oncogenesis and growth of CRC through XBP1‐medaited transcriptional activation of ATF4 and URB1 could be a potential therapeutic target for CRC.
Objective
To evaluate Pneumocystis jirovecii pneumonia (PJP) infection risk in patients with systemic lupus erythematosus (SLE) in Taiwan.
Methods
We identified 24,367 patients with SLE from the ...National Health Insurance research database between 1997 and 2012 and compared the PJP incidence rates (IRs) with those in 243,670 age‐ and sex‐matched non‐SLE controls. PJP risk in the patients was evaluated using a Cox multivariate proportional hazards model.
Results
The SLE patients exhibited a significantly higher PJP risk than the controls, with an IR of 2.63 per 10,000 person‐years and IR ratio of 27.65 (95% confidence interval 17.2–45.3; P < 0.001). Male sex (hazard ratio HR 2.42, P < 0.01), end‐stage renal disease (ESRD; HR 1.74, P = 0.01), recent use of mycofenolate mofetil (MMF; HR 4.43, P < 0.001), intravenous steroid pulse therapy (HR 108.73, P < 0.001), and average oral dosage of >7.5 mg/day prednisolone or equivalent treatment (HR 4.83, P < 0.001) were associated with PJP in SLE, whereas hydroxychloroquine use reduced its risk (HR 0.51, P = 0.01). Of note, cyclophosphamide was not associated with PJP infection in the multivariate Cox proportional hazard model.
Conclusion
Patients with SLE have a considerably high PJP risk. Cyclophosphamide does not increase PJP risk. Male sex, ESRD, MMF use, intravenous steroid pulse therapy, and oral prednisolone or equivalent treatment (>7.5 mg/day) are risk factors for PJP, whereas hydroxychloroquine use reduces PJP risk.
•An overview from the regulatory, technological and management aspects is provided.•The requirements on both water quantity and quality for irrigation are summarized.•Reuse of non-conventional water ...such as cooling and wastewater is evaluated.•Available water technologies, such as RO, CDI and UV, are comprehensively reviewed.•Three priority research directions based on the provided overviews are proposed.
Due to the growing and diverse demands on water supply, exploitation of non-conventional sources of water has received much attention. Since water consumption for irrigation is the major contributor to total water withdrawal, the utilization of non-conventional sources of water for the purpose of irrigation is critical to assuring the sustainability of water resources. Although numerous studies have been conducted to evaluate and manage non-conventional water sources, little research has reviewed the suitability of available water technologies for improving water quality, so that water reclaimed from non-conventional supplies could be an alternative water resource for irrigation. This article provides a systematic overview of all aspects of regulation, technology and management to enable the innovative technology, thereby promoting and facilitating the reuse of non-conventional water. The study first reviews the requirements for water quantity and quality (i.e., physical, chemical, and biological parameters) for agricultural irrigation. Five candidate sources of non-conventional water were evaluated in terms of quantity and quality, namely rainfall/stormwater runoff, industrial cooling water, hydraulic fracturing wastewater, process wastewater, and domestic sewage. Water quality issues, such as suspended solids, biochemical/chemical oxygen demand, total dissolved solids, total nitrogen, bacteria, and emerging contaminates, were assessed. Available technologies for improving the quality of non-conventional water were comprehensively investigated. The potential risks to plants, human health, and the environment posed by non-conventional water reuse for irrigation are also discussed. Lastly, three priority research directions, including efficient collection of non-conventional water, design of fit-for-purpose treatment, and deployment of energy-efficient processes, were proposed to provide guidance on the potential for future research.
Display omitted
Abstract
Background
Use of combinations of long-acting β
2
agonists/long-acting muscarinic antagonists (LABA/LAMA) in patients with chronic obstructive pulmonary disease (COPD) is increasing. ...Nevertheless, existing evidence on cardiovascular risk associated with LABA/LAMA versus another dual combination, LABA/inhaled corticosteroids (ICS), was limited and discrepant.
Aim
The present cohort study aimed to examine comparative cardiovascular safety of LABA/LAMA and LABA/ICS with a target trial emulation framework, focusing on dual fixed-dose combination (FDC) therapies.
Methods
We identified patients with COPD who initiated LABA/LAMA FDC or LABA/ICS FDC from a nationwide Taiwanese database during 2017–2020. The outcome of interest was a hospitalized composite cardiovascular events of acute myocardial infarction, unstable angina, heart failure, cardiac dysrhythmia, and ischemic stroke. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for composite and individual cardiovascular events after matching up to five LABA/LAMA FDC initiators to one LABA/ICS FDC initiator using propensity scores (PS).
Results
Among 75,926 PS-matched patients, use of LABA/LAMA FDC did not show a higher cardiovascular risk compared to use of LABA/ICS FDC, with a HR of 0.89 (95% CI, 0.78–1.01) for the composite events, 0.80 (95% CI, 0.61–1.05) for acute myocardial infarction, 1.48 (95% CI, 0.68–3.25) for unstable angina, 1.00 (95% CI, 0.80–1.24) for congestive heart failure, 0.62 (95% CI, 0.37–1.05) for cardiac dysrhythmia, and 0.82 (95% CI, 0.66–1.02) for ischemic stroke. The results did not vary substantially in several pre-specified sensitivity and subgroup analyses.
Conclusion
Our findings provide important reassurance about comparative cardiovascular safety of LABA/LAMA FDC treatment among patients with COPD.
In autoimmune rheumatic diseases (ARDs), the levels of inflammatory mediators are increased and microglia may be activated, resulting in an inflammatory state and the degeneration of dopaminergic ...neurons. We investigated the association between ARDs and Parkinson disease (PD).
We identified ARD patients through the Taiwan National Health Insurance Research Database from 2001 to 2012. From the general population, we randomly selected a comparison cohort that was frequency-matched by age (in 5-year increments), sex and index year. We analysed the risk of PD, stratified by sex, age and comorbidities, by using a Cox regression model.
The risk of PD was 1.37 times greater in ARD patients than in controls after adjustment for age, sex, and comorbidities. ARD subgroups, such as the rheumatoid arthritis and Sjogren syndrome (SS) cohorts, were associated with a significantly higher risk of PD (adjusted hazard ratio HR, 1.14; 95% confidence interval CI, 1.03-1.2 and adjusted HR, 1.56; 95% CI, 1.35-1.79, respectively). Furthermore, primary and secondary SS patients had significantly higher risks of PD (adjusted HR, 1.58; 95% CI, 1.32-1.88 and adjusted HR, 1.53, 95% CI, 1.23-1.90, respectively).
The risk of PD was significantly higher in the ARD patients. Prospective studies are needed to confirm whether ARDs indeed increase the risk of PD.
PDF
