Design, synthesis, biological evaluation and molecular docking of alkoxyaurones as potent pancreatic lipase inhibitors.

Aurones are a minor subgroup of flavonoids. Unlike other subgroups such as chalcones, flavones, and isoflavones, aurones have not been extensively explored as pancreatic lipase inhibitors. In this work, we studied the pancreatic lipase inhibitory potency of synthetic aurone derivatives. Thirty-six compounds belonging to four series (4,6-dihydroxyaurone, 6-hydroxyaurone, 4,6-dialkoxyaurone, and 6-alkoxyaurone) were designed and synthesized. Their in vitro inhibitory activities were determined by spectrophotometric assay in comparison with quercetin and orlistat. Alkoxyaurone derivatives with long-chain (6-10 carbons) alkoxy substituents showed greater potency. Of them, 4,6-dialkoxyaurone 8 displayed the highest activity against pancreatic lipase (IC50 of 1.945 ± 0.520 µM) relative to quercetin (IC50 of 86.98 ± 3.859 µM) and orlistat (IC50 of 0.0334 ± 0.0015 µM). Fluorescence quenching measurement confirmed the affinity of alkoxyaurone derivatives to pancreatic lipase. Kinetic study showed that 8 inhibited lipase through a competitive mechanism (Ki of 1.288 ± 0.282 µM). Molecular docking results clarified the role of long-chain substituents on ring A in interacting with the hydrophobic pockets and pushing the inhibitor molecule closer to the catalytic triad. The findings in this study may contribute to the development of better pancreatic lipase inhibitors with aurone structure.

Towards in vivo applications of 111Ag perturbed angular correlation of γ-rays (PAC) spectroscopy.

111Ag-perturbed angular correlation of γ-rays (PAC) spectroscopy provides information on the nuclear quadrupole interactions, and thereby on the local structure and dynamics of the silver ion binding site. Brownian rotational motion, i.e. rotational diffusion, of 111Ag-labeled molecules will significantly affect the PAC spectra. Here we illustrate this effect, by simulating 111Ag PAC spectra for 111Ag-labeled molecules with molecular masses spanning from 102 to 106 g/mol, reflecting a span from fast (small molecules) to slow (large molecules) rotational diffusion on the PAC time scale. The simulated spectra are compared to 111Ag-PAC data obtained from a pilot study involving 111Ag(I) bound to a designed chelator exhibiting fast reorientation in solution, as well as to 111Ag-labeled species formed by 111Ag(I) in human serum, exhibiting slow (or no) reorientation on the PAC time scale. The simulated and experimental data illustrate typical PAC signals that are likely to be observed in vivo, when following the fate of 111Ag-labeled compounds. Potential in vivo applications are stability studies of 111Ag-radiopharmaceuticals, dissociation studies of 111Ag from the labeled molecule followed by binding to another (bio)molecule, or binding of 111Ag-labeled probes to larger carriers such as proteins.

Mediating Effects of Self-Esteem on the Relationship Between Self-Compassion and Empathy Among Vietnamese University Students.

Empathy is a critical element of subjective well-being and an important personality trait among undergraduate students. To improve empathy among undergraduate students, the current study examined the relationship between self-compassion and empathy and the mediating role of self-esteem in this relationship. Participants were six hundred and twenty-two (320 males and 302 females) students from five Vietnamese universities, aged 18-21 years (M age = 19.5; SD age = 0.95 years), who completed the self-compassion scale (SCS), empathy scale in adults (BES-A), and self-esteem scale of Toulouse (ETES). The results indicated that (1) self-compassion was positively associated with empathy; (2) self-esteem mediated the relationship between the two variables. Therefore, enhancing undergraduate students' self-compassion may be an effective way to improve their empathy. However, additional studies are required to elucidate the role of self-compassion in the educational context.

Retinal Vascular Occlusion after COVID-19 Vaccination: More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study.

BACKGROUND: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). METHODS: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June-31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case-control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. RESULTS: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA-1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case-control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60-1.45, p = 0.75) in connection with a vaccination within a 4-week window. CONCLUSIONS: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk.

Size Effects in Internal Friction of Nanocrystalline Aluminum Films.

Al thin film is extensively used in micro-electromechanical systems (MEMS) and electronic interconnections; however, most previous research has concentrated on their quasi-static properties and applied their designs on larger scales. The present study designed a paddle-like cantilever specimen with metal films deposited on the upper surface to investigate the quasi-static properties of Al thin film at room temperature under high vacuum conditions at microscopic scales. Energy loss was determined using a decay technique in the oscillation amplitude of a vibrating structure following resonant excitation. Grain size and film thickness size were strictly controlled considering the quasi-static properties of the films. This study found that the internal friction of ultra-thin and thin Al films was more dependent on the grain boundaries than film thickness.

[Differences in Use of Early Intervention by Adolescent Mother-Child Dyads Compared to Adult Mothers and their Children]. / Unterschiede in der Inanspruchnahme von Gesundheits- und Förderangeboten zwischen adoleszenten und erwachsenen Müttern und ihren Kindern.

Adolescent mothers and their children represent a high-risk group for unfavorable developmental outcomes. There are early health and support services for this group. The aim of the current study was to investigate and compare the use of these interventions by adolescent mother-child dyads compared to adult mothers and their children. N=99 mothers (age of children: 5.3±1.0 months) were interviewed regarding early interventions, which were sorted into three groups ("interaction interventions", "child development" and "maternal support interventions") and pooled according to costs. Group differences in utilization and, exploratively, differences in allocation paths between adolescent and adult mothers were investigated. "Interaction interventions" were significantly more frequently used by adolescent mothers (U: 605.50, p<0.001). Interventions concerning "child development" (U: 633.50, p<0.001) and "maternal support" (U: 477.50, p<0.001) and interventions to be paid for (U: 582.00, p<0.001) by adult mothers. Social contacts (U: 817.00, p=0.003) and general practitioners (GP)/gynecologists (U: 879.00, p = 0.054) directed the adult mothers significantly more often to interventions, whereas adolescent mothers significantly more frequently were directed to other professional contacts (U: 877.50, p=0.01) and the youth welfare service (U: 962.50, p=0.021) as intermediaries. Early interventions for child and maternal health and interventions with costs were used significantly less frequently by adolescent mothers. Healthcare professionals such as GPs, gynecologists and pediatricians, should expand their counselling services on health interventions and support services in the high-risk group of adolescent mothers.

T1 nuclear magnetic relaxation dispersion of hyperpolarized sodium and cesium hydrogencarbonate-13 C.

In vivo pH mapping in tissue using hyperpolarized hydrogencarbonate-13 C has been proposed as a method to study tumor growth and treatment and other pathological conditions related to pH changes. The finite spin-lattice relaxation times (T1 ) of hyperpolarized media are a significant limiting factor for in vivo imaging. Relaxation times can be measured at standard magnetic fields (1.5 T, 3.0 T etc.), but no such data are available at low fields, where T1 values can be significantly shorter. This information is required to determine the potential loss of polarization as the agent is dispensed and transported from the polarizer to the MRI scanner. The purpose of this study is to measure T1 dispersion from low to clinical magnetic fields (0.4 mT to 3.0 T) of different hyperpolarized hydrogencarbonate formulations previously proposed in the literature for in vivo pH measurements. 13 C-enriched cesium and sodium hydrogencarbonate preparations were hyperpolarized using dynamic nuclear polarization, and the T1 values of different samples were measured at different magnetic field strengths using a fast field-cycling relaxometer and a 3.0 T clinical MRI system. The effects of deuterium oxide as a dissolution medium for sodium hydrogencarbonate were also analyzed. This study finds that the cesium formulation has slightly shorter T1 values compared with the sodium preparation. However, the higher solubility of cesium hydrogencarbonate-13 C means it can be polarized at greater concentration, using less trityl radical than sodium hydrogencarbonate-13 C. This study also establishes that the preparation and handling of sodium hydrogencarbonate formulations in relation to cesium hydrogencarbonate is more difficult, due to the higher viscosity and lower achievable concentrations, and that deuterium oxide significantly increases the T1 of sodium hydrogencarbonate solutions. Finally, this work also investigates the influence of pH on the spin-lattice relaxation of cesium hydrogencarbonate-13 C measured over a pH range of 7 to 9 at 0.47 T.

Detection of antibiotics in chicken eggs obtained from supermarkets in Ho Chi Minh City, Vietnam.

The residual levels of antibiotics in Vietnamese eggs were monitored from 2014 to 2015. A total of 111 egg packages, distributed by 11 different companies, were collected from supermarkets in Ho Chi Minh City and the levels of 28 antibiotics were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening method. Sixteen samples tested positive for antibiotics; a total of eight compounds (enrofloxacin, ciprofloxacin, norfloxacin, sulfadimethoxine, sulfamethazine, sulfamonomethoxine, tilmicosin and trimethoprim) were detected. Enrofloxacin was detected in eight samples, with two samples exhibiting concentrations exceeding 1,000 µg kg-1. Tilmicosin was detected in three samples at a range of 49-568 µg kg-1. We observed that two of the 11 companies frequently sold antibiotic-contaminated eggs (detection rates of 56 and 60%), suggesting that a number of companies do not regulate the use of antibiotics in egg-laying hens. Our findings indicate that livestock farmers require instruction regarding antibiotic use and that continual antibiotic monitoring is essential in Vietnam.

Antibiotic residue monitoring results for pork, chicken, and beef samples in Vietnam in 2012-2013.

A monitoring plan of residual antibiotics in food of animal origin was conducted in Vietnam from 2012 to 2013. Meat samples were collected from slaughterhouses and retail stores in Ho Chi Minh City and Nha Trang. A total of 28 antibiotics were analyzed using a LC-MS/MS screening method. Sulfonamides, fluoroquinolones, and tilmicosin were detected in some of the samples. Sulfaclozine and fluoroquinolones were mainly detected in chicken samples, and sulfamethazine was mainly detected in pork samples. High levels of sulfonamide residues, ranging between 2500 and 2700 µg/kg sulfaclozine and between 1300 and 3600 µg/kg sulfamethazine, were present in two chicken and three pork samples, respectively. Tilmicosin was detected at ranges of 150-450 µg/kg in 10 chicken samples. Positive percentages were 17.3, 8.8, and 7.4% for chicken, pork, and beef, respectively, for an average of 11.9%. The results suggest an appropriate withdrawal period after drug administration had not been observed in some livestock.

Disruption of urogenital biofilms by lactobacilli.

The process that changes a relatively sparse vaginal microbiota of healthy women into a dense biofilm of pathogenic and potentially pathogenic bacteria is poorly understood. Likewise, the reverse step whereby an aberrant biofilm is displaced and returns to a healthy lactobacilli dominated microbiota is unclear. In order to study these phenomena, in vitro experiments were performed to examine the structure of biofilms associated with aerobic vaginosis, urinary tract infections, and bacterial vaginosis (BV). Uropathogenic Escherichia coli were able to form relatively thin biofilms within five days (6 µm height), while Atopobium vaginae and Gardnerella vaginalis formed thicker biofilms 12 µm in height within two days. Challenge of E. coli biofilms with lactobacilli did not result in pathogen displacement. However, the resulting thicker lactobacilli infused biofilms, caused significant E. coli killing. E. coli biofilms challenged with secreted products of L. rhamnosus GR-1 caused a marked decrease in cell density, and increased cell death. Similarly challenge of BV biofilms with lactobacilli infiltrated BV biofilms and caused bacterial cell death. Metronidazole produced holes in the biofilm but did not eradicate the organisms. The findings provide some evidence of how lactobacilli probiotics might interfere with an aberrant vaginal microbiota, and strengthen the position that combining probiotics with antimicrobials could better eradicate pathogenic biofilms.

Fusion partners can increase the expression of recombinant interleukins via transient transfection in 2936E cells.

The expression levels of five secreted target interleukins (IL-11, 15, 17B, 32, and IL23 p19 subunit) were tested with three different fusion partners in 2936E cells. When fused to the N-terminus, human serum albumin (HSA) was found to enhance the expression of both IL-17B and IL-15, cytokines which did not express at measurable levels on their own. Although the crystallizable fragment of an antibody (Fc) was also an effective fusion partner for IL-17B, Fc did not increase expression of IL-15. Fc was superior to HSA for the expression of the p19 subunit of IL-23, but no partner led to measurable levels of IL-32gamma secretion. Glutathione S-transferase (GST) did not enhance the expression of any target and suppressed the production of IL-11, a cytokine which expressed robustly both on its own and when fused to HSA or Fc. Cleavage of the fusion partner was not always possible. The use of HSA or Fc as N-terminal fusions can be an effective technique to express difficult proteins, especially for applications in which the fusion partner need not be removed.