Miracle-dz/UniFAR-FTUs huggingface dataset:
Fragment-Based Quantum Mechanical Calculation of Excited-State Properties of Fluorescent RNAs

Fluorescent RNA aptamers have been successfully applied to track and tag RNA in a biological system. However, it is still challenging to predict the excited-state properties of the RNA aptamer–fluorophore complex with the traditional electronic structure methods due to expensive computational costs. In this study, an accurate and efficient fragmentation quantum mechanical (QM) approach of the electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) scheme was applied for calculations of excited-state properties of the RNA aptamer–fluorophore complex. In this method, the excited-state properties were first calculated with one-body fragment quantum mechanics/molecular mechanics (QM/MM) calculation (the excited-state properties of the fluorophore) and then corrected with a series of two-body fragment QM calculations for accounting for the QM effects from the RNA on the excited-state properties of the fluorophore. The performance of the EE-GMFCC on prediction of the absolute excitation energies, the corresponding transition electric dipole moment (TEDM), and atomic forces at both the TD-HF and TD-DFT levels was tested using the Mango-II RNA aptamer system as a model system. The results demonstrate that the calculated excited-state properties by EE-GMFCC are in excellent agreement with the traditional full-system time-dependent ab initio calculations. Moreover, the EE-GMFCC method is capable of providing an accurate prediction of the relative conformational excited-state energies for different configurations of the Mango-II RNA aptamer system extracted from the molecular dynamics (MD) simulations. The fragmentation method further provides a straightforward approach to decompose the excitation energy contribution per ribonucleotide around the fluorophore and then reveals the influence of the local chemical environment on the fluorophore. The applications of EE-GMFCC in calculations of excitation energies for other RNA aptamer–fluorophore complexes demonstrate that the EE-GMFCC method is a general approach for accurate and efficient calculations of excited-state properties of fluorescent RNAs.
The Mevalonate Pathway Is Important for Growth, Spore Production, and the Virulence of Phytophthora sojae

The mevalonate (MVA) pathway in eukaryotic organisms produces isoprenoids, sterols, ubiquinone, and dolichols. These molecules are vital for diverse cellular functions, ranging from signaling to membrane integrity, and from post-translational modification to energy homeostasis. However, information on the MVA pathway in Phytophthora species is limited. In this study, we identified the MVA pathway genes and reconstructed the complete pathway in Phytophthora sojae in silico. We characterized the function of the MVA pathway of P. sojae by treatment with enzyme inhibitor lovastatin, deletion of the geranylgeranyl diphosphate synthase gene (PsBTS1), and transcriptome profiling analysis. The MVA pathway is ubiquitously conserved in Phytophthora species. Under lovastatin treatment, mycelial growth, spore production, and virulence of P. sojae were inhibited but the zoospore encystment rate increased. Heterozygous mutants of PsBTS1 showed slow growth, abnormal colony characteristics, and mycelial morphology. Mutants showed decreased numbers of sporangia and oospores as well as reduced virulence. RNA sequencing analysis identified the essential genes in sporangia formation were influenced by the enzyme inhibitor lovastatin. Our findings elucidate the role of the MVA pathway in P. sojae and provide new insights into the molecular mechanisms underlying the development, reproduction, and virulence of P. sojae and possibly other oomycetes. Our results also provide potential chemical targets for management of plant Phytophthora diseases.
Assessment of Impact of Containment During the COVID-19 Epidemic and Coping Behaviours Using Newly Developed Assessment Tools

Background: The confinement measures during COVID-19 had a massive effect on physical and psychological health in public. This study assessed the impact of containment and coping behaviour among the Malaysia public during the COVID-19 pandemic. Questions assessing the impact of containment and coping behaviours were developed and psychometrically tested. Methods: Exploratory factor analysis (EFA) was conducted with the items using principal component analysis extraction and Varimax rotation. Partial least squares structural equation modelling was used to determine the relationship between coping and impact. Results: The 13-item of impact and 10-item coping instruments were developed with three dimensions identified through EFA. Both scales demonstrated excellent composite reliability and good convergent validity. The survey findings revealed that the impact on individual psychological aspects was prominent, followed by well-being and lifestyle. Mindfulness and physical coping strategies were most commonly reported. Coping through seeking help from health professionals and hotlines had a positive direct effect on well-being and lifestyle (b = 0.231, p < 0.001), psychological (B = 0.132, p < 0.001), and employment-related (0.194, p < 0.001) impacts. Coping through mindfulness practise had a negative effect on well-being and lifestyle-related impact (B = −0.180, p < 0.001) and employment-related impact (B = −0.096, p = 0.008). Conclusions: Despite some limitation, the scales for measuring impact and coping behaviours have the potential to be used as a measurement tool in future studies. Findings highlight the enormous impact of the pandemic on psychological well-being and lifestyles. Health authorities should support individual coping as it was found to be an important resilience-related factor to mitigate the impacts of containment during the pandemic.
Fatal Adverse Events of Dabigatran Combined With Aspirin in Elderly Patients: An Analysis Using Data From VigiBase

Introduction: The elderly are vulnerable to cardiovascular diseases and the incidence of atrial fibrillation (AF) and venous thromboembolism (VTE) increases significantly with age. Dabigatran is a commonly used new oral anticoagulant approved by the FDA for stroke prevention in patients with non-valvular AF and VTE treatment and prevention. Aspirin is commonly used as a preventive drug for cardiovascular diseases. AF and coronary heart disease share many risk factors, so these two diseases often coexist and thus dabigatran and aspirin are often combined in those people. The aim of this study was to analyze the clinical characteristics of fatal adverse events of dabigatran combined with aspirin in elderly patients, and to provide references for clinical rational use of drugs. Materials and Methods: Fatal adverse events related to the combined use of dabigatran and aspirin in elderly patients aged over 75 were extracted from the WHO global database of individual case safety reports (VigiBase). Well-documented reports, vigiGrade completeness score ≥0.80, or with an informative narrative, were analyzed with a focus on the clinical features of the cases. Results: From 1968 up to January 19, 2020, there were 112 eligible reports in VigiBase from 13 countries, of which 33 were identified as well-documented. Of these 33, 19 were male (58%) and 14 were female (42%), the average age of the patients was 84 (75–95 years), with five cases of extreme weights (>100 kg in one case, <50 kg in four cases). There were 31 cases of death by internal bleeding (mainly 15 of gastrointestinal hemorrhage and 12 of intracranial hemorrhage) and two cases of the sudden death of unknown cause. Medication errors existed in 15 patients. The times to onset (TTO) was provided in 24 cases, ranging from 2 days to 4 years, and in 12 patients occurred within a month. Of the 31 patients with fatal bleeding events, 29 were associated with other factors that increase the risk of bleeding, such as diseases (hypertension, renal impairment, stroke, gastrointestinal related diseases, hypothyroidism, and cancer), drugs (antiplatelets, anticoagulants, thrombolytics, P glycoprotein substrates, non-steroidal anti-inflammatory drugs, hormones, selective serotonin reuptake inhibitors, and acetaminophen) and other factors (low body weights and alcohol consumption), and 21 of these contained two or more risk factors. Conclusion: The fatal adverse events associated with the combined use of dabigatran and aspirin in elderly patients were mainly serious bleeding events, which often occurred within 1 month. Most of these cases had medication errors and most of the patients had multiple diseases, medications, or other conditions at the same time that increase the risk of bleeding. It is suggested that prescription of dabigatran and aspirin in elderly patients should go along with alertness for medication errors, care for correct dose or control of other bleeding risk factors, and the combined medication time should be as short as possible to minimise serious adverse events.
Collagen and Discoidin Domain Receptor 1 Partnership: A Multifaceted Role in the Regulation of Breast Carcinoma Cell Phenotype

Type I collagen, the major components of breast interstitial stroma, is able to regulate breast carcinoma cell behavior. Discoidin domain receptor 1 (DDR1) is a type I collagen receptor playing a key role in this process. In fact, collagen/DDR1 axis is able to trigger the downregulation of cell proliferation and the activation of BIK-mediated apoptosis pathway. The aim of this review is to discuss the role of two important factors that regulate these processes. The first factor is the level of DDR1 expression. DDR1 is highly expressed in epithelial-like breast carcinoma cells, but poorly in basal-like ones. Moreover, DDR1 undergoes cleavage by MT1-MMP, which is highly expressed in basal-like breast carcinoma cells. The second factor is type I collagen remodeling since DDR1 activation depends on its fibrillar organization. Collagen remodeling is involved in the regulation of cell proliferation and apoptosis through age- and proteolysis-related modifications.
The Role of Minor Pilins in Assembly and Function of the Competence Pilus of Streptococcus pneumoniae

The remarkable genomic plasticity of Streptococcus pneumoniae largely depends on its ability to undergo natural genetic transformation. To take up extracellular DNA, S. pneumoniae assembles competence pili composed of the major pilin ComGC. In addition to ComGC, four minor pilins ComGD, E, F, and G are expressed during bacterial competence, but their role in pilus biogenesis and transformation is unknown. Here, using a combination of protein-protein interaction assays we show that all four proteins can directly interact with each other. Pneumococcal ComGG stabilizes the minor pilin ComGD and ComGF and can interact with and stabilize the major pilin ComGC, thus, deletion of ComGG abolishes competence pilus assembly. We further demonstrate that minor pilins are present in sheared pili fractions and find ComGF to be incorporated along the competence pilus by immunofluorescence and electron microscopy. Finally, mutants of the invariant Glu5 residue (E5), ComGDE5A or ComGEE5A, but not ComGFE5A, were severely impaired in pilus formation and function. Together, our results suggest that ComGG, lacking E5, is essential for competence pilus assembly and function, and plays a central role in connecting the pneumococcal minor pilins to ComGC.
Influences of Spillway Section Morphologies on Landslide Dam Breaching

Spillway excavation is often adopted as a precautionary engineering measure for disaster mitigation before landslide dam breaching. Based on the landslide dam breach mechanisms, this paper focuses on developing a numerical model to comprehensively discuss the issue based on three documented landslide dam failures, such as Tangjiashan, Xiaogangjian, and Baige landslide dams. The spillway cross section morphologies were modeled with different sizes under common shape (i.e., an inverted trapezoid) and slope conditions. The influence of cross section on dam breach processes was analyzed under conditions of different depth, bottom width, slope ratio in the cross and longitudinal sections, with/without spillway. The following conclusions can be drawn: 1) excavation of a spillway can effectively reduce the peak breach flow, therefore delay the time to peak; 2) the peak breach flow dramatically decreases and the time to peak delays as the spillway depth increases; 3) the peak breach flow changes little and the time to peak occurs earlier with the increment in spillway bottom width; 4) the peak breach flow decreases and the time to peak delays with the decrease of slope ratio in cross section in the spillway; 5) the slope ratio in the longitudinal section has little influence on the breach process. Hence, if conditions permit, the spillway with large spillway depth, small bottom width, and gentle slope ratio in the cross section is the preferable section morphology for the emergency disposal of the landslide dam.
Blastocyst Morphology Based on Uniform Time-Point Assessments is Correlated With Mosaic Levels in Embryos

Avoiding aneuploid embryo transfers has been shown to improve pregnancy outcomes in patients with implantation failure and pregnancy loss. This retrospective cohort study aims to analyze the correlation of time-lapse (TL)-based variables and numeric blastocyst morphological scores (TLBMSs) with different mosaic levels. In total, 918 biopsied blastocysts with time-lapse assessments at a uniform time-point were subjected to next-generation sequencing–based preimplantation genetic testing for aneuploidy. In consideration of patient- and cycle-related confounding factors, all redefined blastocyst morphology components of low-grade blastocysts, that is, expansion levels (odds ratio [OR] = 0.388, 95% confidence interval [CI] = 0.217–0.695; OR = 0.328, 95% CI = 0.181–0.596; OR = 0.343, 95% CI = 0.179–0.657), inner cell mass grades (OR = 0.563, 95% CI = 0.333–0.962; OR = 0.35, 95% CI = 0.211–0.58; OR = 0.497, 95% CI = 0.274–0.9), and trophectoderm grades (OR = 0.29, 95% CI = 0.178–0.473; OR = 0.242, 95% CI = 0.143–0.411; OR = 0.3, 95% CI = 0.162–0.554), were less correlated with mosaic levels ≤20%, <50%, and ≤80% as compared with those of top-grade blastocysts (p < 0.05). After converting blastocyst morphology grades into scores, high TLBMSs were associated with greater probabilities of mosaic levels ≤20% (OR = 1.326, 95% CI = 1.187–1.481), <50% (OR = 1.425, 95% CI = 1.262–1.608), and ≤80% (OR = 1.351, 95% CI = 1.186–1.539) (p < 0.001). The prediction abilities of TLBMSs were similar for mosaic levels ≤20% (AUC = 0.604, 95% CI = 0.565–0.642), <50% (AUC = 0.634, 95% CI = 0.598–0.671), and ≤80% (AUC = 0.617, 95% CI = 0.576–0.658). In conclusion, detailed evaluation with TL monitoring at the specific time window reveals that redefined blastocyst morphology components and converted numeric TLBMSs are significantly correlated with all of the threshold levels of mosaicism. However, the performance of TLBMSs to differentiate blastocysts with aberrant ploidy risk remains perfectible.
Gut Microbiota and Serum Metabolic Signatures of High-Fat-Induced Bone Loss in Mice

Background Accumulating evidence indicates that high-fat diet (HFD) is a controllable risk factor for osteoporosis, but the underlying mechanism remains to be elucidated. As a primary biological barrier for nutrient entry into the human body, the composition and function of gut microbiota (GM) can be altered rapidly by HFD, which may trigger abnormal bone metabolism. In the current study, we analyzed the signatures of GM and serum metabolomics in HFD-induced bone loss and explored the potential correlations of GM and serum metabolites on HFD-related bone loss. Methods We conducted a mouse model with HFD-induced bone loss through a 12-week diet intervention. Micro-CT, Osmium-μCT, and histological analyses were used to observe bone microstructure and bone marrow adipose tissue. Quantitative Real-Time PCR was applied to analyze gene expression related to osteogenesis, adipogenesis, and osteoclastogenesis. Enzyme-linked immunosorbent assay was used to measure the biochemical markers of bone turnover. 16s rDNA sequencing was employed to analyze the abundance of GM, and UHPLC-MS/MS was used to identify serum metabolites. Correlation analysis was performed to explore the relationships among bone phenotypes, GM, and the metabolome. Results HFD induced bone loss accompanied by bone marrow adipose tissue expansion and bone formation inhibition. In the HFD group, the relative abundance of Firmicutes was increased significantly, while Bacteroidetes, Actinobacteria, Epsilonbacteraeota, and Patescibacteria were decreased compared with the ND group. Association analysis showed that thirty-two bacterial genera were significantly related to bone volume per tissue volume (BV/TV). One hundred and forty-five serum metabolites were identified as differential metabolites associated with HFD intervention, which were significantly enriched in five pathways, such as purine metabolism, regulation of lipolysis in adipocyte and cGMP-PKG signaling pathway. Sixty-four diffiential metabolites were matched to the MS2 spectra; and ten of them were positively correlated with BV/TV and five were negatively correlated with BV/TV. Conclusions These findings indicated that the alternations of GM and serum metabolites were related to HFD-induced bone loss, which might provide new insights into explain the occurrence and development of HFD-related osteoporosis. The regulatory effects of GM and metabolites associated with HFD on bone homeostasis required further exploration.
Potential Associations Between Microbiome and COVID-19

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis. The disease is characterized by strong infectivity, high morbidity, and high mortality. It is still spreading in some countries. Microbiota and their metabolites affect human physiological health and diseases by participating in host digestion and nutrition, promoting metabolic function, and regulating the immune system. Studies have shown that human microecology is associated with many diseases, including COVID-19. In this research, we first reviewed the microbial characteristics of COVID-19 from the aspects of gut microbiome, lung microbime, and oral microbiome. We found that significant changes take place in both the gut microbiome and airway microbiome in patients with COVID-19 and are characterized by an increase in conditional pathogenic bacteria and a decrease in beneficial bacteria. Then, we summarized the possible microecological mechanisms involved in the progression of COVID-19. Intestinal microecological disorders in individuals may be involved in the occurrence and development of COVID-19 in the host through interaction with ACE2, mitochondria, and the lung-gut axis. In addition, fecal bacteria transplantation (FMT), prebiotics, and probiotics may play a positive role in the treatment of COVID-19 and reduce the fatal consequences of the disease.
Melatonin Participates in Selenium-Enhanced Cold Tolerance of Cucumber Seedlings

Melatonin is an important and widespread plant hormone. However, the underlying physiological and molecular mechanisms of melatonin as a secondary messenger in improving cold tolerance by selenium are limited. This study investigated the effects of selenite on the cold stress of cucumber seedlings. The results showed that exogenous application of selenite improved the cold tolerance of cucumber seedlings, which was dependent on the concentration effect. In the present experiment, 1 μM of selenite showed the best effect on alleviating cold stress. Interestingly, we found that in the process of alleviating cold stress, selenite increased the content of endogenous melatonin by regulating the expression of melatonin biosynthesis genes (TDC, T5H, SNAT, and COMT). To determine the interrelation between selenite and melatonin in alleviating cold stress, melatonin synthesis inhibitor p-chlorophenylalanine and melatonin were used for in-depth study. This study provides a theoretical basis for cucumber cultivation and breeding.
Multi-Frequency Radar Micro-Doppler Based Classification of Micro-Drone Payload Weight

The use of drones for recreational, commercial and military purposes has seen a rapid increase in recent years. The ability of counter-drone detection systems to sense whether a drone is carrying a payload is of strategic importance as this can help determine the potential threat level posed by a detected drone. This paper presents the use of micro-Doppler signatures collected using radar systems operating at three different frequency bands for the classification of carried payload of two different micro-drones performing two different motions. Use of a KNN classifier with six features extracted from micro-Doppler signatures enabled mean payload classification accuracies of 80.95, 72.50 and 86.05%, for data collected at S-band, C-band and W-band, respectively, when the drone type and motion type are unknown. The impact on classification performance of different amounts of situational information is also evaluated in this paper.
Intention to Install Green Infrastructure Features in Private Residential Outdoor Space

Green infrastructure (GI) features in private residential outdoor space play a key role in expanding GI networks in cities and provide multiple co-benefits to people. However, little is known about residents' intended behavior concerning GI in private spaces. Resident homeowners in Toronto (Ontario, Canada) voluntarily participated in an anonymous postal survey (n = 533) containing questions related to likelihood to install additional GI features in their private outdoor space; experiences with this space, such as types of uses; and environmental concerns and knowledge. We describe the association between these factors and people's intention to install GI in private residential outdoor space. Factors such as environmental concerns and knowledge did not influence likelihood to install GI. However, experiences with private residential outdoor space, such as nature uses of this space, level of self-maintenance of this space, and previously installed GI features, were significant influences on the likelihood to install GI. These findings have important implications for managing GI initiatives and the adoption of GI in private residential spaces, such as orienting communication materials around uses of and experiences with outdoor space, having programs that generate direct experiences with GI features, and considering environmental equity in such programs.
Aspartate β-Hydroxylase (ASPH) Expression in Acute Myeloid Leukemia: A Potential Novel Therapeutic Target

Background Aspartate β-hydroxylase (ASPH) is an embryonic transmembrane protein aberrantly upregulated in cancer cells, associated with malignant transformation and, in some reports, with poor clinical prognosis. Objective To report the expression patterns of ASPH in acute myeloid leukemia (AML). Methods Cell surface expression of ASPH was measured via 8-color multiparameter flow cytometry in 41 AML patient samples (31 bone marrow, 10 blood) using fluorescein isothiocyanate (FITC)-conjugated anti-ASPH antibody, SNS-622. A mean fluorescent intensity (MFI) of 10 was used as a cutoff for ASPH surface expression positivity. Data regarding patient and disease characteristics were collected. Results ASPH surface expression was found on AML blasts in 16 samples (39%). Higher ASPH expression was seen in myeloblasts of African American patients (p=0.02), but no correlation was found between ASPH expression and other patient or disease characteristics. No association was found between ASPH status and CR rate (p=0.53), EFS (p=0.87), or OS (p=0.17). Conclusions ASPH is expressed on blasts in approximately 40% of AML cases, and may serve as a new therapeutically targetable leukemia-associated antigen.