Miracle-dz/UniFAR-FTUs huggingface dataset:
Nanotechnology SYNTHESIS AND CHARACTERIZATION OF POLYMER BRUSHES CONTAINING b-CYCLODEXTRIN GRAFTED TO MAGNETIC NANOPARTICLES FOR DETERMINATION OF NAPROXEN IN URINE

b-Cyclodextrin containing polymer brushes were grafted to magnetic nanoparticles following free radical copolymerization of N,N-dimethylacrylamide and allyl glycidyl ether on the surface. The products were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, elemental analysis, and transmission electron microscopy and employed for solid phase extraction of naproxen in human urine. The profile of the naproxen adsorbed by the nanoparticles demonstrated high accessibility of the b-cyclodextrin. Scatchard analysis indicated that the capacity of the nanoparticles was 112lmol g 1 at 25 C and a pH of 5. The adsorption data of naproxen were considered by Langmuir, Freundlich, Redlich–Peterson, and Temkin isotherms. Approximately 55% of naproxen was released in simulated gastric fluid in 30min and 94% in simulated intestinal fluid in 30 h. These data have indicated the utility of the naproxen loadedb-cyclodextrin containing polymer brushes grafted to magnetic nanoparticles for enteric drug delivery.
Adiponectin Improves In Vitro Development of Cloned Porcine Embryos by Reducing Endoplasmic Reticulum Stress and Apoptosis

Simple Summary Successful attenuation of endoplasmic reticulum (ER) stress signaling has a beneficial outcome in in vitro embryonal improvement. We evaluated the effect of adiponectin during in vitro culture in porcine embryos derived from parthenogenetic activation and somatic cell nuclear transfer (SCNT). We found that 15 and 30 μg/mL adiponectin treatment significantly improved cleavage rates, blastocyst formation rates, and total cell number (TCN) of blastocysts derived from parthenogenetic activation and reduced the expression levels of XBP1. In SCNT embryos, the cleavage rate, blastocyst formation rate, and TCN of blastocysts were significantly improved by 15 μg/mL adiponectin treatment compared to the control. In addition, the 15 μg/mL adiponectin treatment reduced the levels of XBP1 expression and ER stress-related genes, increased expression levels of pluripotency-related genes, and decreased apoptosis-related gene expression. Comprehensively, treatment with 15 μg/mL adiponectin enhanced the in vitro developmental capacity of early-stage SCNT porcine embryos by reducing ER stress and apoptosis. Abstract The main factor of embryonic demise is endoplasmic reticulum (ER) stress. Successful attenuation of ER stress results in an improvement in embryo development. We studied the impact of adiponectin in the in vitro culture (IVC) of porcine embryos derived from parthenogenetic activation and somatic cell nuclear transfer (SCNT). The first experiment revealed that 15 and 30 μg/mL adiponectin treatments improved cleavage, blastocyst rates, and total cell number (TCN) of parthenogenetic embryos and reduced the expression of XBP1 compared to the 5 μg/mL adiponectin treatment and control groups (p < 0.05). The second experiment showed that cleavage rate, blastocyst formation rate, and TCN of blastocysts were improved in the 15 μg/mL adiponectin treatment group compared with the control group, with significantly reduced XBP1 expression in ≥4-cell stage SCNT embryos and blastocysts (p < 0.05). Treatment with 15 μg/mL adiponectin significantly improved the expression of XBP1 and reduced the expression of ER stress-related genes (uXBP1, sXBP1, PTPN1, and ATF4), increased the expression levels of pluripotency-related genes (Nanog and SOX2), and decreased apoptosis-related gene expression (Caspase-3). These results suggest that 15 μg/mL adiponectin enhanced the in vitro developmental capacity of early-stage SCNT porcine embryos by reducing ER stress and apoptosis.
The SR-protein Npl3 is an essential component of the meiotic splicing regulatory network in Saccharomyces cerevisiae

Abstract The meiotic gene expression program in Saccharomyces cerevisiae involves regulated splicing of meiosis-specific genes via multiple splicing activators (e.g. Mer1, Nam8, Tgs1). Here, we show that the SR protein Npl3 is required for meiotic splicing regulation and is essential for proper execution of the meiotic cell cycle. The loss of Npl3, though not required for viability in mitosis, caused intron retention in meiosis-specific transcripts, inefficient meiotic double strand break processing and an arrest of the meiotic cell cycle. The targets of Npl3 overlapped in some cases with other splicing regulators, while also having unique target transcripts that were not shared. In the absence of Npl3, splicing defects for three transcripts (MER2, HOP2 and SAE3) were rescued by conversion of non-consensus splice sites to the consensus sequence. Methylation of Npl3 was further found to be required for splicing Mer1-dependent transcripts, indicating transcript-specific mechanisms by which Npl3 supports splicing. Together these data identify an essential function for the budding yeast SR protein Npl3 in meiosis as part of the meiotic splicing regulatory network.
Measurement properties of the one-minute sit-to-stand test in children and adolescents with cystic fibrosis: A multicenter randomized cross-over trial.

BACKGROUND Functional exercise capacity assessment is recommended in children with cystic fibrosis (CF). The six-minute walk test (6MWT) is a valid evaluation of exercise capacity but can be technically complex. Inversely, the sit-to-stand test (STST) is a simple method to evaluate exercise capacity, and is validated in healthy children and adults with CF. This study aimed to evaluate STST measurement properties in children and adolescents with CF. METHODS In this multicenter study, children with CF (6 to 18 years) performed two iterations of both the STST and the 6MWT in a randomized order. Criterion validity was determined by assessing correlations between STST repetitions and 6MWT distance (6MWD). Intra-rater reliability, test-retest repeatability, mean bias and limits of agreement were also assessed. Relationships with other outcomes (i.e. respiratory and quadriceps muscle strength) and cardio-respiratory responses were analysed for both tests. RESULTS Thirty-six children with CF were included (mean age 12.0 ±3.5 years and FEV1 95.8 ±25.0%). On average, 39.6 ±10.5 repetitions were performed during the STST and mean 6MWD was 596.0 ±102.6 meters. STST number of repetitions was significantly correlated with 6MWD (r = 0.48; p<0.01). Both tests had very good intra-rater reliability (ICCSTST = 0.91 (95%CI 0.76-0.96) and ICC6MWT = 0.94 (95%CI 0.85-0.97)), and a significant test-retest learning effect. The number of STST repetitions was not correlated with quadriceps or respiratory muscle strength test, and the STST induced fewer cardio-respiratory responses than the 6MWT. CONCLUSIONS The STST is an easy-to-use functional test with moderate criterion validity when compared to the 6MWT in children with CF, probably because both tests measure different components of functional exercise capacity. The STST is useful when the 6MWT is unfeasible, however further investigations are required to explore the clinical implications of STST results in children with CF. CLINICAL TRIAL REGISTRATION NCT03069625.
The Role of Biomarkers in Adrenocortical Carcinoma: A Review of Current Evidence and Future Perspectives

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy arising from the adrenal cortex often with unexpected biological behavior. It can occur at any age, with two peaks of incidence: in the first and between fifth and seventh decades of life. Although ACC are mostly hormonally active, precursors and metabolites, rather than end products of steroidogenesis are produced by dedifferentiated and immature malignant cells. Distinguishing the etiology of adrenal mass, between benign adenomas, which are quite frequent in general population, and malignant carcinomas with dismal prognosis is often unfeasible. Even after pathohistological analysis, diagnosis of adrenocortical carcinomas is not always straightforward and represents a great challenge for experienced and multidisciplinary expert teams. No single imaging method, hormonal work-up or immunohistochemical labelling can definitively prove the diagnosis of ACC. Over several decades’ great efforts have been made in finding novel reliable and available diagnostic and prognostic factors including steroid metabolome profiling or target gene identification. Despite these achievements, the 5-year mortality rate still accounts for approximately 75% to 90%, ACC is frequently diagnosed in advanced stages and therapeutic options are unfortunately limited. Therefore, imperative is to identify new biological markers that can predict patient prognosis and provide new therapeutic options.
A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats

SJP-005 (a combination of ketotifen and ibuprofen) is being developed as a potential treatment for pain and for opioid use disorder. It is therefore important to investigate the potential antinociceptive properties of SJP-005. Two studies were conducted to evaluate the potential effects of SJP-005 in rats. Study 1 applied the von Frey test to examine the antinociceptive effect of morphine with and without SJP-005 in adjuvant-induced hypersensitivity to tactile stimulation. In a double-blind, between-groups design, groups of rats (n = 10 each) received morphine at 3, 10, or 30 mg/kg bodyweight (bw) (subcutaneous injection) with or without SJP-005 (oral). Mechanic allodynia and paw volume were assessed before and after treatment. Study 2 utilized the hot plate test. Using a crossover design, groups of rats (n = 10 each) received either morphine at 3, 10, or 30 mg/kg bw (subcutaneous injection) preceded by oral administration of placebo (Week 1) or SJP-005 (Week 2). In Study 1, in the von Frey up-and-down test, Δ paw withdrawal responses in Group 1 (3 mg/kg bw morphine) were significantly lower compared to those in Group 4 (3 mg/kg bw morphine plus SJP-005), whereas the differences in Δ paw withdrawal between Group 2 and Group 5 (10 mg/kg bw morphine with and without SJP-005) and between Group 3 and Group 6 (10 mg/kg bw morphine with and without SJP-005) did not reach statistical difference. Trendline analysis of the dose–response relationship for the morphine + placebo groups and morphine + SJP-005 groups revealed no significant differences in the intercepts and slopes. In Study 2, no significant differences were observed on hot plate performance between morphine and morphine in combination with SJP-005. In conclusion, the findings in the von Frey up-and-down test (Study 1) suggest that animals can withstand higher levels of painful stimuli when SJP-005 is co-administered. This may also suggest a possible opioid sparing effect. However, in the hot plate test (Study 2), animals did not respond more adaptively to stronger painful stimuli after co-administering SJP-005. These observations warrant further investigation of the antinociceptive properties of SJP-005.
Mycobacterium tuberculosis PPiA interacts with host integrin receptor to exacerbate disease progression.

Attenuated intracellular survival of Mycobacterium tuberculosis (Mtb) secretory gene mutants exemplifies their role as virulence factors. Mtb peptidyl prolyl isomerase A (PPiA) assists in protein folding through cis/trans isomerization of prolyl bonds. Here, we show that PPiA abets Mtb survival and aids in the disease progression by exploiting host-associated factors. While the deletion of PPiA has no discernable effect on the bacillary survival in a murine infection model, it compromises the formation of granuloma-like lesions and promotes host cell death through ferroptosis. Overexpression of PPiA enhances the bacillary load and exacerbates pathology in mice lungs. Importantly, PPiA interacts with the integrin α5β1 receptor through a conserved surface-exposed RGD motif. The secretion of PPiA as well as interaction with integrin contributes to the disease progression by upregulating multiple host matrix metalloproteinases. Collectively, we identified a novel non-chaperone role of PPiA that is critical in facilitating host-pathogen interaction ensuing disease progression.
Molecular Aspects of Regeneration Mechanisms in Holothurians

Holothurians, or sea cucumbers, belong to the phylum Echinodermata. They show good regenerative abilities. The present review provides an analysis of available data on the molecular aspects of regeneration mechanisms in holothurians. The genes and signaling pathways activated during the asexual reproduction and the formation of the anterior and posterior parts of the body, as well as the molecular mechanisms that provide regeneration of the nervous and digestive systems, are considered here. Damage causes a strong stress response, the signs of which are recorded even at late regeneration stages. In holothurian tissues, the concentrations of reactive oxygen species and antioxidant enzymes increase. Furthermore, the cellular and humoral components of the immune system are activated. Extracellular matrix remodeling and Wnt signaling play a major role in the regeneration in holothurians. All available morphological and molecular data show that the dedifferentiation of specialized cells in the remnant of the organ and the epithelial morphogenesis constitute the basis of regeneration in holothurians. However, depending on the type of damage, the mechanisms of regeneration may differ significantly in the spatial organization of regeneration process, the involvement of different cell types, and the depth of reprogramming of their genome (dedifferentiation or transdifferentiation).
Efficient Amino Acid Conformer Search with Bayesian Optimization

Finding low-energy molecular conformers is challenging due to the high dimensionality of the search space and the computational cost of accurate quantum chemical methods for determining conformer structures and energies. Here, we combine active-learning Bayesian optimization (BO) algorithms with quantum chemistry methods to address this challenge. Using cysteine as an example, we show that our procedure is both efficient and accurate. After only 1000 single-point calculations and approximately 80 structure relaxations, which is less than 10% computational cost of the current fastest method, we have found the low-energy conformers in good agreement with experimental measurements and reference calculations. To test the transferability of our method, we also repeated the conformer search of serine, tryptophan, and aspartic acid. The results agree well with previous conformer search studies.
Active Game-Based Solutions for the Treatment of Childhood Obesity

Obesity is one of the biggest health problems globally that, together with sedentarism, requires solutions that increase the enthusiasm towards physical activity. Therefore, this paper describes two solutions based on active games using the Kinect sensor and biometric sensors, designed for the outpatient treatment of childhood obesity. The solutions were applied in an intervention program based on active video games and motor games, developed with children in treatment for childhood obesity. An ad hoc questionnaire was used to assess the level of satisfaction, fun, learning, and behavior changes in the children of the experimental group that developed the intervention. The results showed a high index of satisfaction with the intervention program, as well as with the games developed. It is concluded that active video games and group games are highly motivating and can promote behavior change towards healthier life habits in children.
Electrochemical behavior of samarium, europium, and ytterbium in hydrophobic room-temperature molten salt systems

The electrochemical behavior of samarium (Sm), europium (Eu), and ytterbium (Yb) was investigated in the hydrophobic room-temperature molten salts based on bis(trifluoromethylsulfonyl)imide (TFSI - ) combined with either 1-ethyl-3-methylimidazolium (EMI + ) or 1-n-butyl-l-methylpyrrolidinium (BMP + ). The redox reactions of Sm(III)/Sm(II), Eu(III)/Eu(II), and Yb(III)/Yb(II) were observed at -1.6, -0.3, and -1.0 V vs Ag/Ag(I), respectively. In all cases, the electrode reactions were found to be quasi-or irreversible by the cyclic voltammetry. The diffusion coefficients of these lanthanides were estimated to be ∼10 - 8 cm 2 s - 1 by chronoamperometry and chronopotentiometry, indicating that their mobility is rather low, probably due to the complex formation or the strong coulombic interaction with TFSI - . The redox potentials of these divalent and trivalent lanthanide couples suggested that the donor property of TFSI - -based room-temperature molten salts was lower than that of other conventional solvents.
Gender-specific association between non-alcoholic fatty liver disease and type 2 diabetes mellitus among a middle-aged and elderly Chinese population

Supplemental Digital Content is available in the text Abstract Limited data are available regarding the association of non-alcoholic fatty liver disease (NAFLD) with the risk of type 2 diabetes mellitus (T2DM) in China. Therefore, the purpose of this study is to evaluate the gender-specific association between NAFLD and T2DM risk in a middle-aged and elderly Chinese population. This cross-sectional study was carried out in a group of 1492 Chinese adults (60.30% males) aged between 45 and 69 years old, in Hangzhou city, Zhejiang province who were attending their annual health check-up from June 2015 to December 2016 in the Medical Center for Physical Examination, Zhejiang Hospital. Face-to-face interviews were conducted using a written questionnaire. NAFLD was divided into none, mild, moderate/severe based on ultrasound examination. Logistic regression analyses were employed to determine the relationship between NAFLD and the risk of T2DM, with adjustment of potential confounding variables. Of the 1492 participants, 163 (10.92%) were diagnosed with T2DM. Educational level, smoking, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose (FG), triglycerides (TG), alanine aminotransferase (ALT), asparagine aminotransferase (AST)and the prevalence of T2DM were significantly higher in males than in females (P < .05). Besides, females had significantly higher levels of high density lipoprotein-cholesterol (HDL-C) (1.51 ± 0.37 vs 1.29 ± 0.42, P < .001) than males. Pearson bivariate correlation analysis indicated that FG was positively associated with weight, BMI, WC, WHR, SBP, DBP, TG, TC, ALT and AST in both males and females (P < .05). Besides, FG was inversely associated with HDL-C in females (P < .001). After adjusting for confounding variables, NAFLD was positively associated with the risk of T2DM, and the effect of NAFLD on T2DM was stronger in males (OR = 2.442, 95%CI: 1.003–3.757) than in females (OR = 1.814, 95%CI: 1.011–3.257). Our data showed that NAFLD was significantly associated with the risk of T2DM in middle-aged and elderly males than in females. Further prospective cohort studies are needed to determine the causal effect of NAFLD on T2DM.
Pharmacology of Free Fatty Acid Receptors and Their Allosteric Modulators

The physiological function of free fatty acids (FFAs) has long been regarded as indirect in terms of their activities as educts and products in metabolic pathways. The observation that FFAs can also act as signaling molecules at FFA receptors (FFARs), a family of G protein-coupled receptors (GPCRs), has changed the understanding of the interplay of metabolites and host responses. Free fatty acids of different chain lengths and saturation statuses activate FFARs as endogenous agonists via binding at the orthosteric receptor site. After FFAR deorphanization, researchers from the pharmaceutical industry as well as academia have identified several ligands targeting allosteric sites of FFARs with the aim of developing drugs to treat various diseases such as metabolic, (auto)inflammatory, infectious, endocrinological, cardiovascular, and renal disorders. GPCRs are the largest group of transmembrane proteins and constitute the most successful drug targets in medical history. To leverage the rich biology of this target class, the drug industry seeks alternative approaches to address GPCR signaling. Allosteric GPCR ligands are recognized as attractive modalities because of their auspicious pharmacological profiles compared to orthosteric ligands. While the majority of marketed GPCR drugs interact exclusively with the orthosteric binding site, allosteric mechanisms in GPCR biology stay medically underexploited, with only several allosteric ligands currently approved. This review summarizes the current knowledge on the biology of FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41), FFAR4 (GPR120), and GPR84, including structural aspects of FFAR1, and discusses the molecular pharmacology of FFAR allosteric ligands as well as the opportunities and challenges in research from the perspective of drug discovery.
A glucose-supplemented diet enhances gut barrier integrity in Drosophila

ABSTRACT Dietary intervention has received considerable attention as an approach to extend lifespan and improve aging. However, questions remain regarding optimal dietary regimes and underlying mechanisms of lifespan extension. Here, we asked how an increase of glucose in a chemically defined diet extends the lifespan of adult Drosophila melanogaster. We showed that glucose-dependent lifespan extension is not a result of diminished caloric intake, or changes to systemic insulin activity, two commonly studied mechanisms of lifespan extension. Instead, we found that flies raised on glucose-supplemented food increased the expression of cell-adhesion genes, delaying age-dependent loss of intestinal barrier integrity. Furthermore, we showed that chemical disruption of the gut barrier negated the lifespan extension associated with glucose treatment, suggesting that glucose-supplemented food prolongs adult viability by enhancing the intestinal barrier. We believe our data contribute to understanding intestinal homeostasis, and may assist efforts to develop preventative measures that limit effects of aging on health. Summary: How diet affects lifespan has received much attention. We found that maintenance of intestinal barrier integrity is likely an important factor in glucose-dependent lifespan extension in flies.
A new restriction effect of aging time on the shrinkage of ordered mesoporous carbon during carbonization

A new effect of aging time (AT) on the shrinkage of ordered mesoporous carbon (OMC) prepared by an evaporation-induced triconstituent co-assembly method has been reported. Increasing AT from 0.5 to 2.0 h can gradually reduce framework shrinkage of the OMC during carbonization. This novel effect is effective and simple for preparing the OMC with large mesopore sizes, high pore volumes and surface area.