Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytotoxicity of Different Nano Composite Resins on Human Gingival and Periodontal Ligament Fibroblast Cell Lines: An In Vitro Study

The aim of this study is to determine the cytotoxicity of three different nano composite resins (CRs) on human gingival fibroblast (hGF) and periodontal ligament fibroblast (hPDLF) cell lines. These CRs selected were nanohybrid organic monomer-based Admira Fusion (AF), nanohybrid Bis-(acryloyloxymethyl) tricyclo [5.2. 1.0. sup.2,6] decane-based Charisma Topaz (CT), and supra nano filled resin-based Estelite Quick Sigma (EQS). MTT assay was performed to assess the cytotoxicity of CRs at 24 h and one week. AF and EQS applied on hGF cells at 24 h and one week demonstrated similar cytotoxic outcomes. Cytotoxicity of CT on hGF cells at one week was higher than 24 h (p = 0.04). Cytotoxicity of CT on hGF cells was higher at 24 h (p = 0.002) and one week (p = 0.009) compared to control. All composites showed higher cytotoxicity on hPDLF cells at one week than the 24 h (AF; p = 0.02, CT; p = 0.02, EQS; p = 0.04). AF and EQS demonstrated lower cytotoxicity on hPDLF cells than the control group at 24 h (AF; p = 0.01, EQS; p = 0.001). CT was found more cytotoxic on hPDLF cells than the control (p = 0.01) and EQS group (p = 0.008) at one week. The cytotoxicity of CRs on hGF and hPDLF cells vary, according to the type of composites, cell types, and exposure time.
Predicting self-harm in an ethnically diverse sample of lesbian, gay and bisexual people in the United Kingdom

Background: Poor mental health is prevalent in lesbian, gay and bisexual (LGB) people due in part to social stigma. The social, psychological and clinical risk factors for self-harm among LGB people are unclear, which limits our ability to predict when and how this will occur and, crucially, how to prevent it. Aims: Drawing on the cognitive-behavioral approach in clinical psychology, this study identifies the predictors of self-harm in LGB people in the United Kingdom. Results: Women, lesbians, those with lower income and younger people were more likely to engage in self-harm. Self-harmers exhibited much more discrimination, LGB victimization and, thus, internalized homophobia and depressive symptomatology than non-self-harmers. The structural equation model showed direct effects of age and gender, and indirect effects of income and sexual orientation, on self-harm, through the mediating variables of discrimination, LGB victimization and internalized homophobia. Conclusions: Consistent with the cognitive-behavioral model, the results indicate that exposure to situational stressors can increase the risk of developing a self-hatred and depressive psychological self-schema, resulting in greater risk of self-harm as a maladaptive coping strategy. An integrative clinical intervention for enhancing psychological wellbeing in LGB people is proposed to mitigate the risk of self-harm in this population.
Plasmon-Emitter Hybrid Nanostructures of Gold Nanorod-Quantum Dots with Regulated Energy Transfer as a Universal Nano-Sensor for One-Step Biomarker Detection

Recently, biosensing based on weak coupling in plasmon-emitter hybrid nanostructures exhibits the merits of simplicity and high sensitivity, and attracts increasing attention as an emerging nano-sensor. In this study, we propose an innovative plasmon-regulated fluorescence resonance energy transfer (plasmon-regulated FRET) sensing strategy based on a plasmon-emitter hybrid nanostructure of gold nanorod-quantum dots (Au NR-QDs) by partially modifying QDs onto the surfaces of Au NRs. The Au NR-QDs showed good sensitivity and reversibility against refractive index change. We successfully employed the Au NR-QDs to fabricate nano-sensors for detecting a cancer biomarker of alpha fetoprotein with a limit of detection of 0.30 ng/mL, which displays that the sensitivity of the Au NR-QDs nano-sensor was effectively improved compared with the Au NRs based plasmonic sensing. Additionally, to demonstrate the universality of the plasmon-regulated FRET sensing strategy, another plasmon-emitter hybrid nano-sensor of Au nano-prism-quantum dots (Au NP-QDs) were constructed and applied for detecting a myocardial infarction biomarker of cardiac troponin I. It was first reported that the change of absorption spectra of plasmonic structure in a plasmon-emitter hybrid nanostructure was employed for analytes detection. The plasmon-regulated FRET sensing strategy described herein has potential utility to develop general sensing platforms for chemical and biological analysis.
High-Level Expression, Purification and Initial Characterization of Recombinant Arabidopsis Histidine Kinase AHK1

Plants employ a number of phosphorylation cascades in response to a wide range of environmental stimuli. Previous studies in Arabidopsis and yeast indicate that histidine kinase AHK1 is a positive regulator of drought and osmotic stress responses. Based on these studies AHK1 was proposed a plant osmosensor, although the molecular basis of plant osmosensing still remains unknown. To understand the molecular role and signaling mechanism of AHK1 in osmotic stress, we have expressed and purified full-length AHK1 from Arabidopsis in a bacterial host to allow for studies on the isolated transmembrane receptor. Purification of the recombinant protein solubilized from the host membranes was achieved in a single step by metal-affinity chromatography. Analysis of the purified AHK1 by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting show a single band indicating that the preparation is highly pure and devoid of contaminants or degradation products. In addition, gel filtration experiments indicate that the preparation is homogenous and monodisperse. Finally, CD-spectroscopy, phosphorylation activity, dimerization studies, and protein–protein interaction with plant phosphorylation targeting AHP2 demonstrate that the purified protein is functionally folded and acts as phospho-His or phospho-Asp phosphatase. Hence, the expression and purification of recombinant AHK1 reported here provide a basis for further detailed functional and structural studies of the receptor, which might help to understand plant osmosensing and osmosignaling on the molecular level.
Stimulus Onset Modulates Auditory and Visual Dominance

Investigations of multisensory integration have demonstrated that, under certain conditions, one modality is more likely to dominate the other. While the direction of this relationship typically favors the visual modality, the effect can be reversed to show auditory dominance under some conditions. The experiments presented here use an oddball detection paradigm with variable stimulus timings to test the hypothesis that a stimulus that is presented earlier will be processed first and therefore contribute to sensory dominance. Additionally, we compared two measures of sensory dominance (slowdown scores and error rate) to determine whether the type of measure used can affect which modality appears to dominate. When stimuli were presented asynchronously, analysis of slowdown scores and error rates yielded the same result; for both the 1- and 3-button versions of the task, participants were more likely to show auditory dominance when the auditory stimulus preceded the visual stimulus, whereas evidence for visual dominance was observed as the auditory stimulus was delayed. In contrast, for the simultaneous condition, slowdown scores indicated auditory dominance, whereas error rates indicated visual dominance. Overall, these results provide empirical support for the hypothesis that the modality that engages processing first is more likely to show dominance, and suggest that more explicit measures of sensory dominance may favor the visual modality.
Allies or Enemies: The Role of Reactive Oxygen Species in Developmental Processes of Black Cottonwood (Populus trichocarpa)

In contrast to aboveground organs (stems and leaves), developmental events and their regulation in underground organs, such as pioneer and fine roots, are quite poorly understood. The objective of the current study was to achieve a better understanding of the physiological and molecular role of reactive oxygen species (ROS) and ROS-related enzymes in the process of stem and pioneer root development in black cottonwood (Populus trichocarpa), as well as in the senescence of leaves and fine roots. Results of a transcriptomic analysis revealed that primary/secondary growth and senescence are accompanied by substantial changes in the expression of genes related to oxidative stress metabolism. We observed that some mechanisms common for above- and under-ground organs, e.g., the expression of superoxide dismutase (SOD) genes and SOD activity, declined during stems’ and pioneer roots’ development. Moreover, the localization of hydrogen peroxide (H2O2) and superoxide (O2•–) in the primary and secondary xylem of stems and pioneer roots confirms their involvement in xylem cell wall lignification and the induction of programmed cell death (PCD). H2O2 and O2•– in senescing fine roots were present in the same locations as demonstrated previously for ATG8 (AuTophaGy-related) proteins, implying their participation in cell degradation during senescence, while O2•– in older leaves was also localized similarly to ATG8 in chloroplasts, suggesting their role in chlorophagy. ROS and ROS-related enzymes play an integral role in the lignification of xylem cell walls in Populus trichocarpa, as well as the induction of PCD during xylogenesis and senescence.
Can Self-Determination Explain Dietary Patterns Among Adults at Risk of or with Type 2 Diabetes? A Cross-Sectional Study in Socio-Economically Disadvantaged Areas in Stockholm

Type 2 Diabetes (T2D) is a major health concern in Sweden, where prevalence rates have been increasing in socioeconomically disadvantaged areas. Self-Determination Theory (SDT) is posited as an optimal framework to build interventions targeted to improve and maintain long-term healthy habits preventing and delaying the onset of T2D. However, research on SDT, T2D and diet has been widely overlooked in socio-economically disadvantaged populations. This study aims to identify the main dietary patterns of adults at risk of and with T2D from two socio-economically disadvantaged Stockholm areas and to determine the association between those patterns and selected SDT constructs (relatedness, autonomy motivation and competence). Cross-sectional data of 147 participants was collected via questionnaires. Exploratory Factor Analysis was used to identify participants’ main dietary patterns. Multiple linear regressions were conducted to assess associations between the SDT and diet behaviours, and path analysis was used to explore mediations. Two dietary patterns (healthy and unhealthy) were identified. Competence construct was most strongly associated with healthy diet. Autonomous motivation and competence mediated the effect of relatedness on diet behaviour. In conclusion, social surroundings can promote adults at high risk of or with T2D to sustain healthy diets by supporting their autonomous motivation and competence.
MiR-202-5p Inhibits RIG-I-Dependent Innate Immune Responses to RGNNV Infection by Targeting TRIM25 to Mediate RIG-I Ubiquitination

The RIG-I-like receptors (RLRs) signaling pathway is essential for inducing type I interferon (IFN) responses to viral infections. Meanwhile, it is also tightly regulated to prevent uncontrolled immune responses. Numerous studies have shown that microRNAs (miRNAs) are essential for the regulation of immune processes, however, the detailed molecular mechanism of miRNA regulating the RLRs signaling pathway remains to be elucidated. Here, our results showed that miR-202-5p was induced by red spotted grouper nervous necrosis virus (RGNNV) infection in zebrafish. Overexpression of miR-202-5p led to reduced expression of IFN 1 and its downstream antiviral genes, thus facilitating viral replication in vitro. In comparison, significantly enhanced levels of IFN 1 and antiviral genes and significantly low viral burden were observed in the miR-202-5p-/- zebrafish compared to wild type zebrafish. Subsequently, zebrafish tripartite motif-containing protein 25 (zbTRIM25) was identified as a target of miR-202-5p in both zebrafish and humans. Ectopic expression of miR-202-5p suppressed zbTRIM25-mediated RLRs signaling pathway. Furthermore, we showed that miR-202-5p inhibited zbTRIM25-mediated zbRIG-I ubiquitination and activation of IFN production. In conclusion, we demonstrate that RGNNV-inducible miR-202-5p acts as a negative regulator of zbRIG-I-triggered antiviral innate response by targeting zbTRIM25. Our study reveals a novel mechanism for the evasion of the innate immune response controlled by RGNNV.
Long Non-Coding RNA H19 Promotes Porcine Satellite Cell Differentiation by Interacting with TDP43

Long non-coding RNAs (lncRNAs) have been implicated in fundamental and diverse biological processes, including myogenesis. However, the molecular mechanisms involved in this process remain largely unexplored. This study found that H19 affected the differentiation of porcine satellite cells (PSCs) by directly binding to the DNA/RNA-binding protein TDP43. Functional analyses showed that TDP43 knockdown decreased PSC differentiation, whereas TDP43 overexpression exerted opposite effects in vitro. Furthermore, rescue experiments demonstrated that TDP43 can rescue the decrease in PSC differentiation caused by H19 knockdown. Mechanistically, H19 may act as a scaffold to recruit TDP43 to the promoters of MYOD and thereby activate the transcription of MYOD, leading to PSC differentiation. In summary, we elucidate the molecular mechanism by which H19 and TDP43 regulate myogenesis.
HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naïve HIV-infected individuals

Background The presence of drug resistance mutations (DRMs) against antiretroviral agents is one of the main concerns in the clinical management of individuals with human immunodeficiency virus-1 (HIV-1) infection, especially in regions of the world where treatment options are limited. The current study aimed at assessing the prevalence of HIV-1 DRMs among naïve and treatment-experienced HIV-1-infected patients in Iran. Methods From April 2013 to September 2018, the HIV-1 protease and reverse transcriptase genes were amplified and sequenced in plasma specimens of 60 newly diagnosed antiretroviral-naive individuals and 46 participants receiving antiretroviral therapies (ARTs) for at least six months with an HIV viral load of more than 1000 IU/mL to determine the HIV-1 DRMs and subtypes. Results Among the 60 treatment-naïve HIV-1-infected participants, 8.3% were infected with HIV-1 variants with surveillance DRMs (SDRMs). The SDRMs, D67N and D67E, belonged to the NRTIs class in two patients and K103N and V106A belonged to the NNRTIs class in three patients. The phylogenetic analysis showed that 91.7% of the subjects were infected with subtype CRF35_AD, followed by subtype B (5.0%) and CRF01_AE (3.3%). Among the 46 ART-experienced participants, 33 (71.7%) carried HIV-1 variants with SDRMs (9.1% against PIs, 78.8% against NRTIs, and 100% against NNRTIs). M46I and I47V were the most common mutations for PIs, M184V was the most common mutation for the NRTIs, and K103N/S was the most common mutation for NNRTIs. Phylogenetic analysis of the polymerase region showed that all of the 46 HIV-1-infected patients who failed on ART carried CRF35_AD. Conclusions The moderate prevalence of SDRMs (8.3%) in treatment-naïve and ART-failed (77.1%) Iranian patients with HIV-1-infection emphasizes the need for systematic viral load monitoring, expanding drug resistance testing, carefully surveilling individuals on ART regimens, and facilitating access to new antiretrovirals by health authorities.
Medical emergency team interventions in patients with ST-segment elevation myocardial infarction throughout Poland in 2018.

BACKGROUND To reduce the burden of ST-segment elevation myocardial infarction (STEMI) in Poland the State Emergency Medical Services Management Support System (SEMS MSS), a unique teleinformatic system coordinating SEMS, was developed. According to the European Society of Cardiology (ESC) recommendations, medical emergency teams (METs) should diagnose STEMI using electrocardiogram (ECG) teletransmission and apply dual antiplatelet therapy (DAPT) as the initial treatment. AIM The aim of this work was to analyze MET interventions in patients with STEMI from January 1, 2018, to December 31, 2018, in Poland. METHODS MET interventions in Poland classified as I 21 (acute myocardial infarction) from January 1, 2018, to December 31, 2018, were analyzed retrospectively using emergency medical operation cards. RESULTS METs conducted 16 807 interventions classified as I 21 in 2018, which represented 0.5% of all MET interventions in this period in Poland. The most interventions were conducted in mazowieckie voivodeship (13.4%, P<0.001) and the fewest were conducted in podlaskie voivodeship (2.5%). 12-lead ECG was performed during 98.6% of interventions and ECG teletransmission was performed in 37.49% of interventions: most often in mazowieckie (59.62%, P<0.001) and least often in lubelskie (13.8%). DAPT was applied during 72.12% of interventions: in 49.68% of interventions, the purinergic signaling receptor Y12 (P2Y12) inhibitor used was clopidogrel and in 25.14% of interventions ticagrelor was used (P<0.001). A P2Y12 inhibitor was most often used in wielkopolskie (98.4%) and least often used in śląskie (40.34%). CONCLUSIONS Significant differences in the implementation of ESC recommendations regarding teletransmission and DAPT therapy were observed between particular voivodeships in Poland.
Prophylactic Anti-Cytomegalovirus Hyperimmunoglobulin in Critically Ill Liver Transplant Patients: Impact on Early Immunology and Survival

Background: Anti-cytomegalovirus hyperimmunoglobulin (CMVIg) was shown to provide beneficial immunodulatory properties beyond antiviral efficacies. The aim of this retrospective study was to assess the impact of prophylactic CMVIg treatment on early outcome following liver transplantation (LT) in critically ill patients. Methods: Forty-three cirrhotic patients requiring pre-LT intensive care due to multiorgan failure were analyzed. Twenty-eight patients with enhanced CMV risk (D+/R+; D+/R−; D−/R+) received prophylactic CMVIg for a minimum of 7 days, while 15 patients (D−/R−) did not. Results: Post-transplantation rates of intra-abdominal infections (28% vs. 61.1%; p = 0.03), Epstein–Barr virus infections (0% vs. 33.3%; p = 0.034), allograft rejections (0% vs. 22.2%; p = 0.013) and sepsis-related mortality (4% vs. 27.8%; p = 0.026) were significantly lower, whereas incidence of CMV infections (4% vs. 22.2%; p = 0.066) tended to be lower in the CMVIg subset. In multivariate analysis, only pretransplant elevated serum lactate level (hazard ratio = 34.63; p = 0.009) and absence of CMVIg therapy (hazard ratio = 21.76; p = 0.023) were identified as independent promoters of 3-month mortality. Conclusion: Prophylactic treatment with CMVIg reduces predisposition for severe immunological and septic events and, thereby, early mortality in critically ill liver recipients.
Integrity of Urine Specimens for Toxicological Analysis - Adulteration, Mechanisms of Action, and Laboratory Detection.

Drug testing in urine for employees is an important deterrent for drug abuse. Because of the dire consequences of a positive result, many individuals who might otherwise test positive will go to great lengths to escape detection. The term "adulteration" in this context refers to: substitution of drug-free urine, purposeful ingestion of agents or fluids designed to either accelerate drug clearance or dilute urine such that drug concentrations are below administrative cutoffs (in vivo adulterants), and adding foreign substances after urine collection (in vitro adulterants) to interfere with drug assays (immunoassay screening and gas chromatography/mass spectrometry confirmation). For immunoassays, adulterants can interfere photometrically or alter antibody-antigen binding. For GC/MS analysis, in vitro adulterants can chemically alter the targeted drug to an undetectable derivative. The laboratory must use different schemes to detect adulterants, including physical observations and tests (e.g., color, odor, and pH), and chemical analyses (e.g., creatinine or glutaraldehyde). If the identity of the donated urine sample itself is in question, DNA tests can be performed. The laboratory must continue to develop new adulteration detection schemes as new adulterants are encountered.
DNA polymerase δ proofreads errors made by DNA polymerase ε

Significance Polδ and Polε are the two major replicative polymerases in eukaryotes, but their precise roles at the replication fork remain a subject of debate. A bulk of data supports a model where Polε and Polδ synthesize leading and lagging DNA strands, respectively. However, this model has been difficult to reconcile with the fact that mutations in Polδ have much stronger consequences for genome stability than equivalent mutations in Polε. We provide direct evidence for a long-entertained idea that Polδ can proofread errors made by Polε in addition to its own errors, thus, making a more prominent contribution to mutation avoidance. This paper provides an essential advance in the understanding of the mechanism of eukaryotic DNA replication. During eukaryotic replication, DNA polymerases ε (Polε) and δ (Polδ) synthesize the leading and lagging strands, respectively. In a long-known contradiction to this model, defects in the fidelity of Polε have a much weaker impact on mutagenesis than analogous Polδ defects. It has been previously proposed that Polδ contributes more to mutation avoidance because it proofreads mismatches created by Polε in addition to its own errors. However, direct evidence for this model was missing. We show that, in yeast, the mutation rate increases synergistically when a Polε nucleotide selectivity defect is combined with a Polδ proofreading defect, demonstrating extrinsic proofreading of Polε errors by Polδ. In contrast, combining Polδ nucleotide selectivity and Polε proofreading defects produces no synergy, indicating that Polε cannot correct errors made by Polδ. We further show that Polδ can remove errors made by exonuclease-deficient Polε in vitro. These findings illustrate the complexity of the one-strand–one-polymerase model where synthesis appears to be largely divided, but Polδ proofreading operates on both strands.
CYP4A11 is involved in the development of nonalcoholic fatty liver disease via ROS-induced lipid peroxidation and inflammation

Nonalcoholic fatty liver disease (NAFLD) is a fat metabolism disorder that occurs in liver cells. The development of NAFLD is considered to be associated with hepatic oxidative stress. The present study aimed to investigate the role of cytochrome P450 4A11 (CYP4A11) in the pathogenesis of NAFLD. The levels of plasma CYP4A11 and lipid peroxidation products levels exhibited a high correlation, and were increased significantly compared with those from normal subjects. Further in vitro studies demonstrated that the expression levels of CYP4A11 and the content of reactive oxygen species (ROS) were increased in free fatty acid (FFA)-stimulated HepG2 cells. Clofibrate, a CYP4A11 inducer, aggravated cell damage. Opposite results were observed for the CYP4A11 inhibitor HET0016, which attenuated apoptosis in FFA-treated cells. Furthermore, CYP4A11 gene overexpression and silencing were used to investigate the effects on inflammatory cytokine secretion. The data demonstrated that CYP4A11 promoted an increase in the mRNA expression of tumor necrosis factor α, interleukin (IL)-1β and IL-6 in response to FFA. In addition, western blot analysis highlighted that CYP4A11 caused an upregulation of phosphorylated p65 levels and therefore affected the NF-κB signaling pathway. The data demonstrated that CYP4A11 may metabolize fatty acids to promote the production of ROS and accelerate the progression of NAFLD.