Miracle-dz/UniFAR-FTUs huggingface dataset:
COMT gene variants and β-endorphin levels contribute to ethnic differences in experimental pain sensitivity

This cross-sectional study investigated whether the catechol-O-methyltransferase (COMT) gene acts as a significant regulator of pain signaling pathways, regulates β-endorphin, and contributes to ethnic differences in pain sensitivity. One-hundred-sixty healthy subjects were enrolled in this study, with Han and Uyghur groups each consisting of 80 participants. Subjects went through six pain threshold experiments. From venous blood, COMT polymorphisms were genotyped, and serum β-endorphin levels were measured. Bivariate correlation analysis and multiple linear regression were used to identify the relationships among genotypes or β-endorphin levels and different types of pain thresholds. Han and Uyghur ethnic differences were determined in terms of acute-pressure pain-perception thresholds, blunt-pressure pain-perception thresholds, blunt-pressure pain-tolerance thresholds, electric pain-tolerance thresholds, β-endorphin levels, and distributions of rs4680 and rs4633 COMT polymorphisms. β-endorphin levels did not correlate with COMT rs4680 or rs4633 genotypes in both Han and Uyghur. Statistical predictors for a lower pain-threshold performance included being young, Uyghur, female, and having a low body mass index, low β-endorphin level, and the rs4680 GA or GG allele. There is the significant difference in pain sensitivity between healthy Han and Uyghur. COMT gene variants and β-endorphin levels contribute to ethnic differences in pain sensitivity.
Polyurea Dendrimer Folate-Targeted Nanodelivery of l-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance

Ovarian cancer is a highly lethal disease, mainly due to chemoresistance. Our previous studies on metabolic remodeling in ovarian cancer have supported that the reliance on glutathione (GSH) bioavailability is a main adaptive metabolic mechanism, also accounting for chemoresistance to conventional therapy based on platinum salts. In this study, we tested the effects of the in vitro inhibition of GSH synthesis on the restoration of ovarian cancer cells sensitivity to carboplatin. GSH synthesis was inhibited by exposing cells to l-buthionine sulfoximine (l-BSO), an inhibitor of γ-glutamylcysteine ligase (GCL). Given the systemic toxicity of l-BSO, we developed a new formulation using polyurea (PURE) dendrimers nanoparticles (l-BSO@PUREG4-FA2), targeting l-BSO delivery in a folate functionalized nanoparticle.
Curcumin Protects Human Trophoblast HTR8/SVneo Cells from H2O2-Induced Oxidative Stress by Activating Nrf2 Signaling Pathway

Pregnancy complications are associated with oxidative stress induced by accumulation of trophoblastic ROS in the placenta. We employed the human trophoblast HTR8/SVneo cell line to determine the effect of curcumin pre-treatment on H2O2-induced oxidative damage in HTR8/Sveo cells. Cells were pretreated with 2.5 or 5 μM curcumin for 24 h, and then incubated with 400 μM H2O2 for another 24 h. The results showed that H2O2 decreased the cell viability and induced excessive accumulation of reactive oxygen species (ROS) in HTR8/Sveo cells. Curcumin pre-treatment effectively protected HTR8/SVneo cells against oxidative stress-induced apoptosis via increasing Bcl-2/Bax ratio and decreasing the protein expression level of cleaved-caspase 3. Moreover, curcumin pre-treatment alleviated the excessive oxidative stress by enhancing the activity of antioxidative enzymes. The antioxidant effect of curcumin was achieved by activating Nrf2 and its downstream antioxidant proteins. In addition, knockdown of Nrf2 by Nrf2-siRNA transfection abolished the protective effects of curcumin on HTR8/SVneo cells against oxidative damage. Taken together, our results show that curcumin could protect HTR8/SVneo cells from H2O2-induced oxidative stress by activating Nrf2 signaling pathway.
Effects of Hot Air Treatments on Postharvest Storage of Newhall Navel Orange

The effects of hot air flow (HAF) treatment on the postharvest storage of ‘Newhall’ navel oranges were investigated in this study. Studies were conducted with two separate sections. First of all, the effects of HAF at 37 °C for 36 h, for 48 h, and for 60 h were tested on fruit decay and weight loss. Thus, the optimal treatment was found as HAF at 37 °C for 48 h based on the fruit decay percentage and weight loss, and further studies were carried out with this treatment. The HAF-treated and control fruits were flowed at 37 °C and 20 °C with relative humidity (RH) of 85–95% for 48 h, respectively. After flowing, fruits of both treatments were individually film-packed, precooled (10–12 °C, 12 h), and stored (6 ± 0.5 °C and 85–90% relative humidity) for 120 days. Regular (0, 15, 30, 45, 60, 90, and 120 days) measurements were carried out for analyzing total soluble solid (TSS) content, titratable acid (TA) content, vitamin C (VC) content, total sugar content, respiration rate, malondialdehyde (MDA) content, and protective enzyme activities. The results indicated that HAF treatment significantly inhibited the MDA content and respiration rate of navel orange fruits after 45 d storage. The superoxide dismutase (SOD) and peroxidase (POD) enzyme activities were enhanced after 60 d storage, while polyphenol oxidase (PPO) enzyme activities were enhanced throughout the storage period. Results suggested that the SOD and POD activities are highly related with respiratory activities and could be enhanced with hot air flow. Meanwhile, HAF treatment maintained high content of TSS, total sugar, TA, and VC.
Micro Fragmented Adipose Tissue Promotes the Matrix Synthesis Function of Nucleus Pulposus Cells and Regenerates Degenerated Intervertebral Disc in a Pig Model

Intervertebral disc (IVD) degeneration and consequent lower back pain is a common disease. Micro fragmented adipose tissue (MFAT) is promising for a wide range of applications in regenerative medicine. In this study, MFAT was isolated by a nonenzymatic method and co-cultured with nucleus pulposus cells (NPCs) using an indirect co-culture system in vitro. A pig disc degeneration model was used to investigate the regenerative effect of MFAT on degenerated IVDs in vivo. The mRNA expression of Sox9, Acan, and Col2 in NPCs was significantly increased, while no significant increase was observed in the mRNA expression of proinflammatory cytokine genes after the NPCs were co-cultured with MFAT. Nucleus pulposus (NP)-specific markers were increased in MFAT cells after co-culture with NPCs. After injection of MFAT, the disc height, water content, extracellular matrix, and structure of the degenerated NP were significantly improved. MFAT promoted the matrix synthesis function of NPCs, and NPCs stimulated the NP-like differentiation of MFAT cells. In addition, MFAT also partly regenerated degenerated IVDs in the pig model.
Human Capital and Administrative Burden: The Role of Cognitive Resources in Citizen‐State Interactions

Abstract One means by which the state reinforces inequality is by imposing administrative burdens that loom larger for citizens with lower levels of human capital. Integrating insights from various disciplines, this article focuses on one aspect of human capital: cognitive resources. The authors outline a model that explains how burdens and cognitive resources, especially executive functioning, interrelate. The article then presents illustrative examples, highlighting three common life factors—scarcity, health problems, and age‐related cognitive decline. These factors create a human capital catch‐22, increasing people's likelihood of needing state assistance while simultaneously undermining the cognitive resources required to negotiate the burdens they encounter while seeking such assistance. The result is to reduce access to state benefits and increase inequality. The article concludes by calling for scholars of behavioral public administration and public administration more generally to incorporate more attention to human capital into their research.
Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia

Abstract Background A novel coronavirus of zoonotic origin (2019-nCoV) has recently been identified in patients with acute respiratory disease. This virus is genetically similar to SARS coronavirus and bat SARS-like coronaviruses. The outbreak was initially detected in Wuhan, a major city of China, but has subsequently been detected in other provinces of China. Travel-associated cases have also been reported in a few other countries. Outbreaks in health care workers indicate human-to-human transmission. Molecular tests for rapid detection of this virus are urgently needed for early identification of infected patients. Methods We developed two 1-step quantitative real-time reverse-transcription PCR assays to detect two different regions (ORF1b and N) of the viral genome. The primer and probe sets were designed to react with this novel coronavirus and its closely related viruses, such as SARS coronavirus. These assays were evaluated using a panel of positive and negative controls. In addition, respiratory specimens from two 2019-nCoV-infected patients were tested. Results Using RNA extracted from cells infected by SARS coronavirus as a positive control, these assays were shown to have a dynamic range of at least seven orders of magnitude (2x10−4-2000 TCID50/reaction). Using DNA plasmids as positive standards, the detection limits of these assays were found to be below 10 copies per reaction. All negative control samples were negative in the assays. Samples from two 2019-nCoV-infected patients were positive in the tests. Conclusions The established assays can achieve a rapid detection of 2019n-CoV in human samples, thereby allowing early identification of patients.
Ancestry specific associations of FTO gene variant and metabolic syndrome

Abstract Cross-sectional studies indicate that the fat mass and obesity-associated (FTO) rs9939609 gene variant is associated with metabolic syndrome (MetS) primarily in European ancestry. However, the association is not fully elucidated in African Americans. We hypothesized that rs9939609 (AT = moderate-risk carriers or AA = high-risk carriers compared to TT = low-risk carriers) is associated with MetS and its component risk factors over time; and that its association is ancestry-specific. A secondary hypothesis was that higher levels of physical activity can decrease the deleterious effect of rs9939609 at higher body mass index (BMI). Atherosclerosis Risk in Communities study repeated measures data from 4 visits (1987–1998) were obtained from the database of Genotypes and Phenotypes for 10,358 participants (8170 Whites and 2188 African Americans) aged 45 to 64 years at baseline. Guidelines for elevated blood pressure by the American College of Cardiology and American Heart Association Task Force were updated within the MetS criteria. Risk ratios (RR) and 95% confidence intervals from generalized estimating equations assessed population-average risks. MetS was present among 3479 (42.6%) Whites and 1098 (50.2%) African Americans at baseline, and 50.3% Whites and 57% African Americans over 11-years of follow-up. Among MetS component risk factors, high waist circumference was most prevalent among White AT (RR = 1.07; 1.06–1.09) and AA (RR = 1.12; 1.10–1.14) higher-risk carriers. High triglycerides were elevated among African American AA high-risk carriers (RR = 1.11; 1.02–1.21) compared to TT low-risk carriers. Over time, White AT-and AA higher-risk carriers had 1.07 and 1.08-fold increase (P < .0001) in MetS risk. Physical activity had independent protective effects on MetS among both races (P < .05). White AA high-risk carriers with normal BMI and low vs high physical activity had higher MetS risk (RR = 1.69; 1.25–2.30 and RR = 0.68;0.53–0.87, respectively). In rs9939609 × BMI× physical activity interaction, White A-allele high-risk carriers had lower MetS risk (RR = 0.68; 0.53–0.87). Among Whites, physical activity can lessen the effect of rs9939609 and high BMI on risk for MetS.
Parvalbumin Interneuron Dysfunction in a Thalamo-Prefrontal Cortical Circuit in Disc1 Locus Impairment Mice

Abstract Altered cortical excitation-inhibition (E-I) balance resulting from abnormal parvalbumin interneuron (PV IN) function is a proposed pathophysiological mechanism of schizophrenia and other major psychiatric disorders. Preclinical studies have indicated that disrupted-in-schizophrenia-1 (Disc1) is a useful molecular lead to address the biology of prefrontal cortex (PFC)-dependent cognition and PV IN function. To date, PFC inhibitory circuit function has not been investigated in depth in Disc1 locus impairment (LI) mouse models. Therefore, we used a Disc1 LI mouse model to investigate E-I balance in medial PFC (mPFC) circuits. We found that inhibition onto layer 2/3 excitatory pyramidal neurons in the mPFC was significantly reduced in Disc1 LI mice. This reduced inhibition was accompanied by decreased GABA release from local PV, but not somatostatin (SOM) INs, and by impaired feedforward inhibition (FFI) in the mediodorsal thalamus (MD) to mPFC circuit. Our mechanistic findings of abnormal PV IN function in a Disc1 LI model provide insight into biology that may be relevant to neuropsychiatric disorders including schizophrenia.
Carfentanil Outbreak — Florida, 2016–2017

Increased prevalence of illicitly manufactured fentanyl and fentanyl analogs has contributed substantially to overdose deaths in the United States (1-3). On October 26, 2015, CDC issued a Health Advisory regarding rapid increases in deaths involving fentanyl. This CDC Health Advisory has been updated twice to address increases in fentanyl and fentanyl analog overdoses and their co-occurrence with nonopioids (4). Deaths involving carfentanil, an analog reportedly 10,000 times more potent than morphine and 100 times more potent than fentanyl, were first reported in Florida, Michigan, and Ohio in 2016 and described in an August 2016 CDC Health Advisory (1,5). Carfentanil is used to rapidly immobilize large animals in veterinary medicine and has no U.S. approved therapeutic use in humans. Carfentanil's street price per dose is likely lower than that of heroin. During 2016 and 2017, an outbreak of carfentanil-involved fatal overdoses in Florida emerged, and the Medical Examiner jurisdiction serving Sarasota, Manatee, and DeSoto counties (the Sarasota area) was the outbreak epicenter. This report describes toxicology profiles, sociodemographic information, and geographic distributions of carfentanil-involved fatal overdoses (carfentanil deaths) in the Sarasota area compared with those in the rest of Florida (i.e., all Florida counties excluding Sarasota area) from January 2016 to December 2017. The Sarasota area accounted for 19.0% of 1,181 statewide carfentanil deaths that occurred during this time and experienced a peak in carfentanil deaths preceding the larger Florida outbreak. The report of a single carfentanil death from August to December 2017 (compared with 73 reported deaths during the same period in 2016) appeared to mark the end of the outbreak in the area. The threat of such rapid, intense fatal overdose outbreaks highlights the need for accelerated reporting, reliable data sharing systems, and novel proactive surveillance to support targeted prevention and response efforts by public health and safety organizations (6).
Gammaherpesvirus-infected germinal center cells express a distinct immunoglobulin repertoire

Germinal center B cells infected with gammaherpesvirus display altered repertoire with biased usage of lambda light chain and skewed utilization of IGHV genes. The gammaherpesviruses (γHVs), human Kaposi sarcoma-associated herpesvirus (KSHV), EBV, and murine γHV68 are prevalent infections associated with lymphocyte pathologies. After primary infection, EBV and γHV68 undergo latent expansion in germinal center (GC) B cells and persists in memory cells. The GC reaction evolves and selects antigen-specific B cells for memory development but whether γHV passively transients or manipulates this process in vivo is unknown. Using the γHV68 infection model, we analyzed the Ig repertoire of infected and uninfected GC cells from individual mice. We found that infected cells displayed the hallmarks of affinity maturation, hypermutation, and isotype switching but underwent clonal expansion. Strikingly, infected cells displayed distinct repertoire, not found in uninfected cells, with recurrent utilization of certain Ig heavy V segments including Ighv10-1. In a manner observed with KSHV, γHV68 infected cells also displayed lambda light chain bias. Thus, γHV68 subverts GC selection to expand in a specific B cell subset during the process that develops long-lived immunologic memory.
Combustion Behavior and Mechanism of Ti14 Titanium Alloy

The combustion behavior and mechanism of Ti14 titanium alloy are studied by promoted ignition combustion tests at different oxygen pressures in this paper. The burning velocity increases at higher oxygen pressures and also increases with longer burning times instead of a constant at the same pressure. The Cu atoms are found enriched in two zones—i.e., the heat affected zone and melting zone during the combustion process—which can prevent the diffusion process of oxygen atoms. The different combustion behavior of Ti14 and Ti-Cr-V alloys is basically controlled by the characteristics of phase structures and chemical reactions.
[Gene expression levels of cytokines in different phenotypes of CRSwNP].

INTRODUCTION Rhinosinusitis with nasal polyps (CRSwNP) is often followed by a range of comorbid states, influence of which on the course of the main pathology process remains insufficiently studied. PURPOSE To study the gene expression level of cytokines potentially talking part in the development of inflammation in nasal polyps with different phenotypes of CRSwNP. MATERIAL AND METHODS All the patients with CRSwNP were divided into 4 equal groups, 36 patients in each subgroup: group 1 - CRSwNP without comorbid pathology; group 2 - CRSwNP+atopy; group 3 - CRSwNP + non-allergic bronchial asthma (BA); control group 4 - 36 patients diagnosed with hypertrophic rhinitis without atopy and without bronchial asthma. Using the real-time polymerase chain reaction (Real-Time PCR) method, the study of expression level of mRNA genes coding proteins IL-1β, IL-4, IL-5, IL-13, IL-17F, IL-25, IFN-y, TSLP in polyp tissue was conducted. RESULTS The statistically proved difference of expression level of cytokines depending on the CRSwNP phenotype was educed. If CRSwNP and atopy were combined, the gene expression level of all studied cytokines was statistically higher than that of CRSwNP without comorbid pathology; and the expression level of IL-17F, IL-25 and TSLP was more intense that in the group of CRSwNP + BA. There was no difference between the patients with comorbid allergy and comorbid BA regarding the gene expression of IFN-y, IL-5 and IL-13 cytokines. Among different phenotypes of CRSwNP no difference in IL-1β expression level was detected, which evidences of persisting inflammatory process, and the IL-4 gene expression level was lower than the detection level in all the groups. CONCLUSION With different CRSwNP phenotypes different inflammatory patterns are detected, which indicates different character of the pathology process course among these groups of patients. Higher expression level of cytokine genes, which are a marker of epithelial damage of IL-25 and TSLP, is found only among the patients with CRSwNP and atopy. It suggests that forming of CRSwNP without comorbid pathology is connected with other pathologic mechanisms, not with the damage to epithelial barrier. If CRSwNP + BA and CRSwNP + atopy were combined, the expression level of IFN-y, IL-5, IL-13 and IL-17F genes was higher than the one in the group of patients with CRSwNP without comorbid pathology. In view of obtained data, all the patients with CRSwNP shall be screened for bronchial asthma and the allergy diagnostic shall be conducted.
Pharmacokinetics and Intestinal Metabolism of Compound K in Rats and Mice

We aimed to investigate the plasma concentration, tissue distribution, and elimination of compound K following the intravenous administration of compound K (2 mg/kg) in rats and mice. The plasma concentrations of compound K in mice were much higher (about five-fold) than those in rats. In both rats and mice, compound K was mainly distributed in the liver and underwent biliary excretion. There was 28.4% fecal recovery of compound K in mice and 13.8% in rats, whereas its renal recovery was less than 0.1% in both rats and mice. Relative quantification of compound K and its metabolite protopanaxadiol (PPD) in rat bile and intestinal feces indicated that the metabolism from compound K into PPD occurred in the intestine but not in the plasma. Therefore, PPD detected in the plasma samples could have been absorbed from the intestine after metabolism in control rats, while PPD could not be detected in the plasma samples from bile duct cannulated rats. In conclusion, mice and rats shared common features such as exclusive liver distribution, major excretion pathway via biliary route, and intestinal metabolism to PPD. However, there were significant differences between rats and mice in the plasma concentrations of compound K and the fecal recovery of compound K and PPD.
Canadian Arctic Contaminants and Their Effects on the Maternal Brain and Behaviour: A Scoping Review of the Animal Literature

Background: Environmental toxicants such as methylmercury, polychlorinated biphenyls, and organochlorine pesticides are potentially harmful pollutants present in contaminated food, soil, air, and water. Exposure to these ecologically relevant toxicants is prominent in Northern Canadian populations. Previous work focused on toxicant exposure during pregnancy as a threat to fetal neurodevelopment. However, little is known about the individual and combined effects of these toxicants on maternal health during pregnancy and post-partum. Methods: A scoping review was conducted to synthesize the current knowledge regarding individual and combined effects of methylmercury, polychlorinated biphenyls, and organochlorine pesticides on maternal behaviour and the maternal brain. Relevant studies were identified through the PubMed, Embase, and Toxline databases. Literature involving animal models and one human cohort were included in the review. Results: Research findings indicate that exposures to these environmental toxicants are associated with neurochemical changes in rodent models. Animal models provided the majority of information on toxicant-induced alterations in maternal care behaviours. Molecular and hormonal changes hypothesized to underlie these alterations were also addressed, although studies assessing toxicant co-exposure were limited. Conclusion: This review speaks to the limited knowledge regarding effects of these persistent organic pollutants on the maternal brain and related behavioural outcomes. Further research is required to better comprehend any such effects on maternal brain and behaviour, as maternal care is an important contributor to offspring neurodevelopment.