Miracle-dz/UniFAR-FTUs huggingface dataset:
Flavonoids as Human Intestinal α-Glucosidase Inhibitors

Certain flavonoids can influence glucose metabolism by inhibiting enzymes involved in carbohydrate digestion and suppressing intestinal glucose absorption. In this study, four structurally-related flavonols (quercetin, kaempferol, quercetagetin and galangin) were evaluated individually for their ability to inhibit human α-glucosidases (sucrase, maltase and isomaltase), and were compared with the antidiabetic drug acarbose and the flavan-3-ol(−)-epigallocatechin-3-gallate (EGCG). Cell-free extracts from human intestinal Caco-2/TC7 cells were used as the enzyme source and products were quantified chromatographically with high accuracy, precision and sensitivity. Acarbose inhibited sucrase, maltase and isomaltase with IC50 values of 1.65, 13.9 and 39.1 µM, respectively. A similar inhibition pattern, but with comparatively higher values, was observed with EGCG. Of the flavonols, quercetagetin was the strongest inhibitor of α-glucosidases, with inhibition constants approaching those of acarbose, followed by galangin and kaempferol, while the weakest were quercetin and EGCG. The varied inhibitory effects of flavonols against human α-glucosidases depend on their structures, the enzyme source and substrates employed. The flavonols were more effective than EGCG, but less so than acarbose, and so may be useful in regulating sugar digestion and postprandial glycaemia without the side effects associated with acarbose treatment.
The Lotus japonicus AFB6 Gene Is Involved in the Auxin Dependent Root Developmental Program

Auxin is essential for root development, and its regulatory action is exerted at different steps from perception of the hormone up to transcriptional regulation of target genes. In legume plants there is an overlap between the developmental programs governing lateral root and N2-fixing nodule organogenesis, the latter induced as the result of the symbiotic interaction with rhizobia. Here we report the characterization of a member of the L. japonicus TIR1/AFB auxin receptor family, LjAFB6. A preferential expression of the LjAFB6 gene in the aerial portion of L. japonicus plants was observed. Significant regulation of the expression was not observed during the symbiotic interaction with Mesorhizobium loti and the nodule organogenesis process. In roots, the LjAFB6 expression was induced in response to nitrate supply and was mainly localized in the meristematic regions of both primary and lateral roots. The phenotypic analyses conducted on two independent null mutants indicated a specialized role in the control of primary and lateral root elongation processes in response to auxin, whereas no involvement in the nodulation process was found. We also report the involvement of LjAFB6 in the hypocotyl elongation process and in the control of the expression profile of an auxin-responsive gene.
The potential prebiotic effect of 2‐Butyloctanol on the human axillary microbiome

The human axilla is colonized by a wide array of microorganisms that contribute to the generation of body odour. Traditional antiperspirant/deodorant products are used to reduce perspiration in the axillary region and to treat or prevent the growth of bacteria in this region, thereby reducing or eliminating body odour. However, they may also compromise the axillary microbiome balance. The personal care industry has been seeking new ingredients, such as prebiotics or probiotics, to maintain a healthy balance of the skin microbiome by inhibiting odour‐causing bacteria, whilst maintaining and promoting the growth of good bacteria. The aim of this study was to investigate the prebiotic effect of a skin‐care ingredient, 2‐butyloctanol, on the human axillary microbiome.
Immunonano-Lipocarrier-Mediated Liver Sinusoidal Endothelial Cell-Specific RUNX1 Inhibition Impedes Immune Cell Infiltration and Hepatic Inflammation in Murine Model of NASH

Background: Runt-related transcription factor (RUNX1) regulates inflammation in non-alcoholic steatohepatitis (NASH). Methods: We performed in vivo targeted silencing of the RUNX1 gene in liver sinusoidal endothelial cells (LSECs) by using vegfr3 antibody tagged immunonano-lipocarriers encapsulated RUNX1 siRNA (RUNX1 siRNA) in murine models of methionine choline deficient (MCD) diet-induced NASH. MCD mice given nanolipocarriers-encapsulated negative siRNA were vehicle, and mice with standard diet were controls. Results: Liver RUNX1 expression was increased in the LSECs of MCD mice in comparison to controls. RUNX1 protein expression was decreased by 40% in CD31-positive LSECs of RUNX1 siRNA mice in comparison to vehicle, resulting in the downregulation of adhesion molecules, ICAM1 expression, and VCAM1 expression in LSECs. There was a marked decrease in infiltrated T cells and myeloid cells along with reduced inflammatory cytokines in the liver of RUNX1 siRNA mice as compared to that observed in the vehicle. Conclusions: In vivo LSEC-specific silencing of RUNX1 using immunonano-lipocarriers encapsulated siRNA effectively reduces its expression of adhesion molecules, infiltrate on of immune cells in liver, and inflammation in NASH.
Multidimensional Prognostic Index and Outcomes in Older Patients Undergoing Transcatheter Aortic Valve Implantation: Survival of the Fittest

Selecting patients with a high chance of endured benefit from transcatheter aortic valve implantation (TAVI) is becoming relevant with changing indications and increasing number of TAVI being performed. The aim of our study was to investigate the association of the multidimensional prognostic index (MPI) based on a comprehensive geriatric assessment (CGA) on survival. The TAVI Care & Cure program is a prospective, observational registry of patients referred for TAVI at the Erasmus MC University Medical Center. Consecutive patients who underwent a complete CGA and TAVI were included. CGA components were used to calculate the MPI score. The impact of the MPI score on survival was evaluated using Cox regression. Furthermore, 376 patients were included, 143 (38.0%) patients belonged to the MPI-1 group and 233 (61.9%) patients to the MPI-2–3 group. After 3 years, 14.9% of the patients in the MPI-1 group and 30.5% of the patients in the MPI-2–3 group died (p = 0.001). Patients in MPI-1 had increased chances of overall survival in comparison with patients in MPI group 2–3 Hazard Ratio (HR) 0.57, (95% Confidence Interval (CI) 0.33–0.98)). In this study we found that the MPI tool could be useful to assess frailty and to predict which patient will have a higher chance of enduring benefit from a TAVI procedure.
Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk.

BACKGROUND The appropriate duration of dual antiplatelet therapy in patients at high risk for bleeding after the implantation of a drug-eluting coronary stent remains unclear. METHODS One month after they had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent, we randomly assigned patients at high bleeding risk to discontinue dual antiplatelet therapy immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy). The three ranked primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding; cumulative incidences were assessed at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population. RESULTS Among the 4434 patients in the per-protocol population, net adverse clinical events occurred in 165 patients (7.5%) in the abbreviated-therapy group and in 172 (7.7%) in the standard-therapy group (difference, -0.23 percentage points; 95% confidence interval [CI], -1.80 to 1.33; P<0.001 for noninferiority). A total of 133 patients (6.1%) in the abbreviated-therapy group and 132 patients (5.9%) in the standard-therapy group had a major adverse cardiac or cerebral event (difference, 0.11 percentage points; 95% CI, -1.29 to 1.51; P = 0.001 for noninferiority). Among the 4579 patients in the intention-to-treat population, major or clinically relevant nonmajor bleeding occurred in 148 patients (6.5%) in the abbreviated-therapy group and in 211 (9.4%) in the standard-therapy group (difference, -2.82 percentage points; 95% CI, -4.40 to -1.24; P<0.001 for superiority). CONCLUSIONS One month of dual antiplatelet therapy was noninferior to the continuation of therapy for at least 2 additional months with regard to the occurrence of net adverse clinical events and major adverse cardiac or cerebral events; abbreviated therapy also resulted in a lower incidence of major or clinically relevant nonmajor bleeding. (Funded by Terumo; MASTER DAPT ClinicalTrials.gov number, NCT03023020.).
Chemical Characterization of Kraft Lignin Prepared from Mixed Hardwoods

Chemical characterization of kraft lignin (KL) from mixed hardwoods (Acacia spp. from Vietnam and mixed hardwoods (mainly Quercus spp.) from Korea) was conducted for its future applications. To compare the structural changes that occurred in KL, two milled wood lignins (MWLs) were prepared from the same hardwood samples used in the production of KL. Elemental analysis showed that the MWL from acacia (MWL-aca) and mixed hardwood (MWL-mhw) had almost similar carbon content, methoxyl content, and C9 formula. KL had high carbon content but low oxygen and methoxyl contents compared to MWLs. The C9 formula of KL was determined to be C9H7.29O2. 26N0.07S0. 12(OCH3)1.24. The Mw of KL and MWLs was about 3000 Da and 12,000–13,000 Da, respectively. The structural features of KL and MWLs were investigated by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectrometry (1H, 13C NMR). The analyses indicated that KL underwent severe structural modifications, such as γ-carbon cleavage, demethylation, and polycondensation reactions during kraft pulping, which resulted in increased aromatic content and decreased aliphatic content. The main linkages in lignin, β-O-4 moieties, were hardly detected in the analysis as these linkages were extensively cleaved by nucleophilic attack of SH- and OH- during pulping.
Insights into the Molecular Mechanisms of Histone Code Recognition by the BRPF3 Bromodomain.

Bromodomains are evolutionarily conserved reader modules that recognize acetylated lysine residues on the histone tails to facilitate the transcription of target genes. The bromodomain and PHD finger containing protein 3 (BRPF3) is a scaffolding protein that preferentially forms a tetrameric complex with HBO1 histone acetyltransferase (HAT) and two other subunits. The BRPF3 is known to regulate the HAT activity and substrate specificity of HBO1. However, its molecular mechanism, histone ligands, and biological functions remain unknown. Herein, we report the novel interacting partners of BRPF3 bromodomain that specifically recognize mono- (H4K5ac), and di- (H4K5acK12ac) acetylated histone peptides. Consistent with this, pull-down assays confirm the interaction of BRPF3 bromodomain with the full-length histones. Further, our MD simulation studies highlight the binding mode of acetyllysine (Kac) and the stability of bromodomain-histone peptide complexes. Our findings collectively provide a key insight into how histone targets of the BRPF3 bromodomain direct the recruitment of HBO1 complex to chromatin for specific transcriptional regulation.
Automated Mesiodens Classification System Using Deep Learning on Panoramic Radiographs of Children

In this study, we aimed to develop and evaluate the performance of deep-learning models that automatically classify mesiodens in primary or mixed dentition panoramic radiographs. Panoramic radiographs of 550 patients with mesiodens and 550 patients without mesiodens were used. Primary or mixed dentition patients were included. SqueezeNet, ResNet-18, ResNet-101, and Inception-ResNet-V2 were each used to create deep-learning models. The accuracy, precision, recall, and F1 score of ResNet-101 and Inception-ResNet-V2 were higher than 90%. SqueezeNet exhibited relatively inferior results. In addition, we attempted to visualize the models using a class activation map. In images with mesiodens, the deep-learning models focused on the actual locations of the mesiodens in many cases. Deep-learning technologies may help clinicians with insufficient clinical experience in more accurate and faster diagnosis.
Time-Delay Identification Using Multiscale Ordinal Quantifiers

Time-delayed interactions naturally appear in a multitude of real-world systems due to the finite propagation speed of physical quantities. Often, the time scales of the interactions are unknown to an external observer and need to be inferred from time series of observed data. We explore, in this work, the properties of several ordinal-based quantifiers for the identification of time-delays from time series. To that end, we generate artificial time series of stochastic and deterministic time-delay models. We find that the presence of a nonlinearity in the generating model has consequences for the distribution of ordinal patterns and, consequently, on the delay-identification qualities of the quantifiers. Here, we put forward a novel ordinal-based quantifier that is particularly sensitive to nonlinearities in the generating model and compare it with previously-defined quantifiers. We conclude from our analysis on artificially generated data that the proper identification of the presence of a time-delay and its precise value from time series benefits from the complementary use of ordinal-based quantifiers and the standard autocorrelation function. We further validate these tools with a practical example on real-world data originating from the North Atlantic Oscillation weather phenomenon.
Is School Gardening Combined with Physical Activity Intervention Effective for Improving Childhood Obesity? A Systematic Review and Meta-Analysis

School gardening activities (SGA) combined with physical activities (PA) may improve childhood dietary intake and prevent overweight and obesity. This study aims to evaluate the effect of SGA combined with PA on children’s dietary intake and anthropometric outcomes. We searched studies containing randomized controlled trials up to January 2021 in Web of Science, PubMed, Cochrane Library, and the EBSCO database on this topic for children aged 7 to 12 years. Fourteen studies met the requirements for meta-analysis (n = 9187). We found that SGA has no obvious effect on improving children’s BMI (WMD = −0.49; p = 0.085; I2 = 86.3%), BMI z-score (WMD = −0.12; p = 0.235; I2 = 63.0%), and WC (WMD = −0.98; p = 0.05; I2 = 72.9%). SGA can effectively improve children’s FVs (WMD = 0.59, p = 0.003, I2 = 95.3%). SGA combined with PA can significantly increase children’s FVs but cannot greatly improve weight status. Although more studies on this topic are needed to prove the effectiveness of this method, the results of our review show that both SGA and SGA combined with PA has a modest but positive impact of reducing BMI and WC outcomes but can significantly increase children’s FVs.
A Self-Established “Machining-Measurement-Evaluation” Integrated Platform for Taper Cutting Experiments and Applications

Taper-cutting experiments are important means of exploring the nano-cutting mechanisms of hard and brittle materials. Under current cutting conditions, the brittle-ductile transition depth (BDTD) of a material can be obtained through a taper-cutting experiment. However, taper-cutting experiments mostly rely on ultra-precision machining tools, which have a low efficiency and high cost, and it is thus difficult to realize in situ measurements. For taper-cut surfaces, three-dimensional microscopy and two-dimensional image calculation methods are generally used to obtain the BDTDs of materials, which have a great degree of subjectivity, leading to low accuracy. In this paper, an integrated system-processing platform is designed and established in order to realize the processing, measurement, and evaluation of taper-cutting experiments on hard and brittle materials. A spectral confocal sensor is introduced to assist in the assembly and adjustment of the workpiece. This system can directly perform taper-cutting experiments rather than using ultra-precision machining tools, and a small white light interference sensor is integrated for in situ measurement of the three-dimensional topography of the cutting surface. A method for the calculation of BDTD is proposed in order to accurately obtain the BDTDs of materials based on three-dimensional data that are supplemented by two-dimensional images. The results show that the cutting effects of the integrated platform on taper cutting have a strong agreement with the effects of ultra-precision machining tools, thus proving the stability and reliability of the integrated platform. The two-dimensional image measurement results show that the proposed measurement method is accurate and feasible. Finally, microstructure arrays were fabricated on the integrated platform as a typical case of a high-precision application.
Genetic Background and Antibiotic Resistance Profiles of K. pneumoniae NDM-1 Strains Isolated from UTI, ABU, and the GI Tract, from One Hospital in Poland, in Relation to Strains Nationally and Worldwide

In recent years, there has been an observed increase in infections caused by carbapenem-resistant Klebsiella pneumonia (Kp) strains. The aim of this study was the phenotypic and genotypic analysis of eight K. pneumoniae NDM (Kp NDM) isolates, recovered in Poland during the years 2016 and 2018 from seven patients with urinary tract infections (UTIs), asymptomatic bacteriuria (ABU), or colonization of the gut. PCR melting profile genotyping indicated a close relationship between the strains derived from 2018, which were not related to the strain isolated in 2016. WGS results were analyzed in relation to international Kp isolates. Clonal and phylogenetic analyses were performed based on multilocus sequence typing (MLST) and single nucleotide polymorphisms (SNPs) of the core genome. The metallo-β-lactamase was assigned to the NDM-1 type and the sequence was identified as ST11. Eleven antimicrobial resistance genes were detected, mostly from plasmid contigs. Unprecedented profiles of plasmid replicons were described with the IncFII/pKPX-1 dominant replicon. In terms of the KL24 and O2v1 capsular antigen profiles, these isolates corresponded to Greek strains. Strains isolated from UTI, ABU, and colonization GI tract patients were not carrying environment-specific virulence genes. Based on the assessment of strain relationships at the genome level and their direction of evolution, the international character of the sublines was demonstrated, with a documented epidemic potential in Poland and Greece. In conclusion, some groups of patients, e.g., renal transplant recipients or those with complicated UTIs, who are frequently hospitalized and undergoing antibiotic therapy, should be monitored not only for the risk of UTI, but also for colonization by Kp NDM strains.
Interaction between SCP3 and JAB1 Confers Cancer Therapeutic Resistance and Stem-like Properties through EGF Expression

Synaptonemal complex protein 3 (SCP3), a member of the Cor1 family, has been implicated in cancer progression, and therapeutic resistance, as well as cancer stem cell (CSC)-like properties. Previously, we demonstrated that SCP3 promotes these aggressive phenotypes via hyperactivation of the AKT signaling pathway; however, the underlying mechanisms responsible for SCP3-induced AKT activation remain to be elucidated. In this study, we demonstrated that the EGF-EGFR axis is the primary route through which SCP3 acts to activate AKT signaling. SCP3 triggers the EGFR-AKT pathway through transcriptional activation of EGF. Notably, neutralization of secreted EGF by its specific monoclonal antibody reversed SCP3-mediated aggressive phenotypes with a concomitant reversal of EGFR-AKT activation. In an effort to elucidate the molecular mechanisms underlying SCP3-induced transcriptional activation of EGF, we identified Jun activation domain-binding protein 1 (JAB1) as a binding partner of SCP3 using a yeast two-hybrid (Y2H) assay system, and we demonstrated that SCP3 induces EGF transcription through physical interaction with JAB1. Thus, our findings establish a firm molecular link among SCP3, EGFR, and AKT by identifying the novel roles of SCP3 in transcriptional regulation. We believe that these findings hold important implications for controlling SCP3high therapeutic-refractory cancer.
Adolescents' Longitudinal School Engagement and Burnout Before and During COVID‐19—The Role of Socio‐Emotional Skills

This longitudinal study examined school engagement and burnout profiles among early and middle adolescents before and during COVID‐19, and within‐class latent change and stability in students’ socio‐emotional skills the profiles. The longitudinal data were collected in fall 2019 and 2020 from 1381 5th to 6th, and 1374 7th to 8th grade students. Using repeated measures latent profile analyses based on school engagement and burnout we identified five study well‐being change profiles in both samples showing structural similarity: normative (53% sample 1; 69% sample 2), moderate‐decreasing (4%; 5%), high‐decreasing (17%; 10%), low‐increasing (6%;7%) and moderate‐increasing (20%; 10%) groups. The groups with increasing study well‐being showed simultaneous increase in intrapersonal socio‐emotional competencies but showed less changes in interpersonal outcomes.