Resveratrol relieves HFD-induced insulin resistance in skeletal muscle tissue through antioxidant capacity enhancement and the Nrf2-Keap1 signaling pathway.

BACKGROUND: Resveratrol has received much attention due to its beneficial effects including antioxidant activity. The purpose of this study was to investigate the therapeutic effects of resveratrol treatment on oxidative stress and insulin resistance in the skeletal muscle of high-fat diet (HFD)-fed animals. METHODS AND RESULTS: A total of 30 six-week-old C57BL/6J mice were randomly allocated to three groups (10 animals in each group): The control group in which mice were fed a normal chow diet (NCD); the HFD group in which mice were fed an HFD for 26 weeks; and the HFD-resveratrol group in which HFD was replaced by a resveratrol supplemented-HFD (400 mg/kg diet) after 10 weeks of HFD feeding. At the end of this period, gastrocnemius muscle samples were examined to determine insulin resistance and the oxidative status in the presence of HFD and resveratrol. Resveratrol supplementation in HFD-fed mice reduced body and adipose tissue weight, improved insulin sensitivity, and decreased oxidative stress as indicated by lower malonaldehyde (MDA) levels and higher total antioxidant capacity. The supplement also increased the expression and activity of antioxidative enzymes in gastrocnemius muscle and modulated Nrf2 and Keap1 expression levels. CONCLUSIONS: These results suggest that resveratrol is effective in improving the antioxidant defense system of the skeletal muscle in HFD-fed mice, indicating its therapeutic potential to combat diseases associated with insulin resistance and oxidative stress.

Mechanistic Observation of Interactions between Macrophages and Inorganic Particles with Different Densities.

Many different types of inorganic materials are processed into nano/microparticles for medical utilization. The impact of selected key characteristics of these particles, including size, shape, and surface chemistries, on biological systems, is frequently studied in clinical contexts. However, one of the most important basic characteristics of these particles, their density, is yet to be investigated. When the particles are designed for drug delivery, highly mobile macrophages are the major participants in cellular levels that process them in vivo. As such, it is essential to understand the impact of particles' densities on the mobility of macrophages. Here, inorganic particles with different densities are applied, and their interactions with macrophages studied. A set of these particles are incubated with the macrophages and the outcomes are explored by optical microscopy. This microscopic view provides the understanding of the mechanistic interactions between particles of different densities and macrophages to conclude that the particles' density can affect the migratory behaviors of macrophages: the higher the density of particles engulfed inside the macrophages, the less mobile the macrophages become. This work is a strong reminder that the density of particles cannot be neglected when they are designed to be utilized in biological applications.

Violation of Boltzmann Equipartition Theorem in Angular Phonon Phase Space Slows down Nanoscale Heat Transfer in Ultrathin Heterofilms.

Heat transfer through heterointerfaces is intrinsically hampered by a thermal boundary resistance originating from the discontinuity of the elastic properties. Here, we show that with shrinking dimensions the heat flow from an ultrathin epitaxial film through atomically flat interfaces into a single crystalline substrate is significantly reduced due to violation of Boltzmann equipartition theorem in the angular phonon phase space. For films thinner than the phonons mean free path, we find phonons trapped in the film by total internal reflection, thus suppressing heat transfer. Repopulation of those phonon states, which can escape the film through the interface by transmission and refraction, becomes the bottleneck for cooling. The resulting nonequipartition in the angular phonon phase space slows down the cooling by more than a factor of 2 compared to films governed by phonons diffuse scattering. These allow tailoring of the thermal interface conductance via manipulation of the interface.

Visible-Light-Responsive Self-Assembled Complexes: Improved Photoswitching Properties by Metal Ion Coordination.

A photoswitchable ligand based on azobenzene is self-assembled with palladium(II) ions to form a [Pd2 (E-L)4 ]4+ cage. Irradiation with 470 nm light results in the near-quantitative switching to a monomeric species [Pd(Z-L)2 ]2+ , which can be reversed by irradiation with 405 nm light, or heat. The photoswitching selectivity towards the metastable isomer is significantly improved upon self-assembly, and the thermal half-life is extended from 40 days to 850 days, a promising approach for tuning photoswitching properties.

Quantitative determination of trace phenazopyridine in human urine samples by hyphenation of dispersive solid-phase extraction and liquid-phase microextraction followed by gas chromatography/mass spectrometry analysis.

Magnetic dispersive solid-phase extraction followed by dispersive liquid-liquid microextraction coupled with gas chromatography/mass spectrometry was applied for the quantitative analysis of phenazopyridine in urinary samples. Magnetic dispersive solid-phase extraction was carried out using magnetic graphene oxide nanoparticles modified by poly(thiophene-pyrrole) copolymer. The eluting solvent of this step was used as the disperser solvent for the dispersive liquid-liquid microextraction procedure. To reach the maximum efficiency of the method, effective parameters including sorbent amount, adsorption time, type and volume of disperser and extraction solvents, pH of the sample solution, and ionic strength as well as desorption time, and approach were optimized, separately. Characterization of the synthesized sorbent was studied by utilizing infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray analysis. Calibration curve was linear in the range of 0.5-250 ng/mL (R2  = 0.9988) with limits of detection and quantification of 0.1 and 0.5 ng/mL, respectively. Intra- and interday precisions (RSD%, n = 3) of the method were in the range of 4.6-5.4% and 4.0-5.5%, respectively, at three different concentration levels. Under the optimal condition, this method was successfully applied for the determination of phenazopyridine in human urine samples. The relative recoveries were obtained in the range of 85.0-89.0%.

Spin-column micro-solid phase extraction of chlorophenols using MFU-4l metal-organic framework.

A novel metal-organic framework called MFU-4 l was synthesized from ZnCl2 and 1H-1,2,3-triazolo[4,5-b][4',5'-i])dibenzo[1,4]dioxin. MFU-4 l was characterized and is shown to be a viable sorbent for spin-column micro-solid phase extraction of 4-chlorophenol, 2,3-dichlorophenol, 2,4-dichlorophenol, and 2,4,6-trichlorophenol. Following extraction and elution with methanol, the chlorophenols were quantified by a GC-MS instrument. Various parameters affecting adsorption and desorption were optimized by the one variable at-a-time method. The main feature of the utilized metal-organic framework is its outstanding performance in ultratrace extraction of the target analytes due to the different amino groups existed in the linker structure. Under optimal conditions, the calibration plots are linear in the 0.5-400 µg kg-1 concentration range for water samples, and from 1.0-400 µg kg-1 for soil samples. The respective limits of detection are 0.10 and 0.50 µg kg-1 for water and soil samples, respectively. On top of that, limits of detections are lower than 0.10 and 0.50 µg Kg-1 for water and soil samples, respectively. Inter-day and intra-day relative standard deviations were in the range of 4.4-7.8% for the selected chlorophenols. Preconcentration factors are in the range of 26.3-29.6 for aqueous samples. The method was used to analyze soil and environmental water samples. Graphical abstractSchematic representation of spin-column micro-solid phase extraction of chlorophenols using the MFU-4 l metal-organic framework.

On-line extraction and determination of two herbicides: comparison between two modes of three-phase hollow fiber microextraction.

Two different modes of three-phase hollow fiber liquid-phase microextraction were studied for the extraction of two herbicides, bensulfuron-methyl and linuron. In these two modes, the acceptor phases in the lumen of the hollow fiber were aqueous and organic solvents. The extraction and determination were performed using an automated hollow fiber microextraction instrument followed by high-performance liquid chromatography. For both three-phase hollow fiber liquid-phase microextraction modes, the effect of the main parameters on the extraction efficiency were investigated and optimized by central composite design. Under optimal conditions, both modes showed good linearity and repeatability, but the three-phase hollow fiber liquid-phase microextraction based on two immiscible organic solvents has a better extraction efficiency and figures of merit. The calibration curves for three-phase hollow fiber liquid-phase microextraction with an organic acceptor phase were linear in the range of 0.3-200 and 0.1-150 µg/L and the limits of detection were 0.1 and 0.06 µg/L for bensulfuron-methyl and linuron, respectively. For the conventional three-phase hollow fiber liquid-phase microextraction, the calibration curves were linear in the range of 3.0-250 and 15-400 µg/L and LODs were 1.0 and 5.0 µg/L for bensulfuron-methyl and linuron, respectively. The real sample analysis was carried out by three-phase hollow fiber liquid phase microextraction based on two immiscible organic solvents because of its more favorable characteristics.

Synthesis, analgesic and anti-inflammatory activities of new methyl-imidazolyl-1,3,4-oxadiazoles and 1,2,4-triazoles.

BACKGROUND: Long-term clinical employment of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant side effects including gastrointestinal (GI) lesions and kidney toxicity. In this paper we designed and synthesized new imidazolyl-1,3,4-oxadiazoles and 1,2,4-triazoles by molecular hybridization of previously described anti-inflammatory compounds in the hope of obtaining new safer analgesic and anti-inflammatory agents. METHODS: The target structures were synthesized by preparation of 5-methyl-1H-imidazole-4-carboxylic acid ethyl ester 5. The reaction of hydrazine hydrate with this ester afforded the 5-methyl-1H-imidazole-4-carboxylic acid hydrazide 6 which was converted to target compounds 7-15 according to the known procedures. In silico toxicity risk assessment and drug likeness predictions were done, in order to consider the privileges of the synthesized structures as drug candidates. RESULTS AND DISCUSSION: The analgesic and anti-inflammatory profile of the synthesized compounds were evaluated by writhing and carrageenan induced rat paw edema tests respectively. Compounds 8, 9 and 11-13 and 15 were active analgesic agents and compounds 8, 9 and 11-13 showed significant anti-inflammatory response in comparison with control. Compounds 11 and 13 were screened for their ulcerogenic activities and none of them showed significant ulcerogenic activity. The active Compounds 11 and 12 showed the highest drug likeness and drug score. CONCLUSIONS: The analgesic and anti-inflammatory activities of title compounds were comparable to that of standard drug indomethacin with a safer profile of activity. The results revealed that both of oxadiazole and triazole scaffolds can be determined as pharmacophores. The in silico predictions and pharmacological evaluations showed that compounds 11 and 12 can be chosen as lead for further investigations.

Dynamic configurations of metallic atoms in the liquid state for selective propylene synthesis.

The use of liquid gallium as a solvent for catalytic reactions has enabled access to well-dispersed metal atoms configurations, leading to unique catalytic phenomena, including activation of neighbouring liquid atoms and mobility-induced activity enhancement. To gain mechanistic insights into liquid metal catalysts, here we introduce a GaSn0.029Ni0.023 liquid alloy for selective propylene synthesis from decane. Owing to their mobility, dispersed atoms in a Ga matrix generate configurations where interfacial Sn and Ni atoms allow for critical alignments of reactants and intermediates. Computational modelling, corroborated by experimental analyses, suggests a particular reaction mechanism by which Sn protrudes from the interface and an adjacent Ni, below the interfacial layer, aligns precisely with a decane molecule, facilitating propylene production. We then apply this reaction pathway to canola oil, attaining a propylene selectivity of ~94.5%. Our results offer a mechanistic interpretation of liquid metal catalysts with an eye to potential practical applications of this technology.

Safety of purified Vero cell rabies vaccine manufactured in Pakistan: a comparative analysis of intradermal and intramuscular routes.

BACKGROUND: Rabies vaccines are conventionally given via the intramuscular (IM) route; however, switching the route of administration from IM to intradermal (ID) without affecting efficacy can be advantageous in terms of cost, dosing, and time. Hence, it is indispensable to evaluate its safety along different routes. This study was carried out to ascertain the frequency of adverse drug events (ADEs) and associated factors, as well as to compare safety based on the IM and ID routes. METHODS: A prospective observational study was carried out on 184 individuals with rabies exposure. The vaccination schedules for post-exposure prophylaxis (PEP) included 0.2 milliliter (mL) of purified Vero cell rabies vaccine (PVRV) administered ID at two different sites with 0.1 mL each on days 0, 3, and 7 in first group (3-dose regimen ID) and 0.5 mL administered IM on days 0, 3, 7, 14, and 28 in the second group (5-dose regimen IM). The safety of the vaccines was determined by reviewing ADEs during physical examinations and follow-up. ADEs were characterized by local and systemic effects. RESULTS: Of the total, 99 (53.80%) patients reported ADEs. Those who reported local and systemic ADEs were 80 (43.48%) and 59 (32.06%), respectively, while simultaneous occurrence was reported in 40 (40.40%) patients. The most frequent local ADE (76; 41.30%) reported was pain, followed by erythema (18; 9.78%). Additionally, fever had the highest proportion (25; 13.59%) for systemic effects, followed by headache (15; 8.15%). The patients reported with ADEs by the IM and ID routes were comparable (p >.05). Similarly, both local and systemic effects were also comparable (p >.05). CONCLUSION: Half of the study participants reported ADEs. Almost similar proportions of local and systemic effects were observed. Likewise, the ADEs recorded were comparable for both routes. PVRV carries very low safety concerns with either route for administration.

Liquid Metal Interface for Two-Precursor Autogenous Deposition of Metal Telluride-Tellurium Networks.

Liquid metal-electrolyte can offer electrochemically reducing interfaces for the self-deposition of low-dimensional nanomaterials. We show that implementing such interfaces from multiprecursors is a promising pathway for achieving nanostructured films with combinatory properties and functionalities. Here, we explored the liquid metal-driven interfacial growth of metal tellurides using eutectic gallium-indium (EGaIn) as the liquid metal and the cation pairs Ag+-HTeO2+ and Cu2+-HTeO2+ as the precursors. At the EGaIn-electrolyte interface, the precursors were reduced and self-deposited autogenously to form interconnected nanoparticle networks. The deposited materials consisted of metal telluride and tellurium with their relative abundance depending on the metal ion type (Ag+ and Cu2+) and the metal-to-tellurium ion ratios. When used as electrode modifiers, the synthesized materials increased the electroactive surface area of unmodified electrodes by over 10 times and demonstrated remarkable activity for model electrochemical reactions, including HexRu(III) responses and dopamine sensing. Our work reveals the promising potential of the liquid metal-templated deposition method for synthesizing complex material systems for electrochemical applications.

Single-cell mass spectrometry.

Owing to recent advances in mass spectrometry (MS), tens to hundreds of proteins, lipids, and small molecules can be measured in single cells. The ability to characterize the molecular heterogeneity of individual cells is necessary to define the full assortment of cell subtypes and identify their function. We review single-cell MS including high-throughput, targeted, mass cytometry-based approaches and antibody-free methods for broad profiling of the proteome and metabolome of single cells. The advantages and disadvantages of different methods are discussed, as well as the challenges and opportunities for further improvements in single-cell MS. These methods is being used in biomedicine in several applications including revealing tumor heterogeneity and high-content drug screening.

Comparison of the Accuracy of CBCT Images and Apex Locator in Detection of External Root Resorption with Perforation.

Statement of the Problem: Perforation within external root resorption (ERR) lesions dra-matically affects the prognosis of the involved roots. Failure to diagnose perforation under-mines treatment; therefore, early detection of these lesions is of great importance. The cone-beam computed tomography (CBCT) images and electronic apex locators (EAL) are reliably used to detect root perforations. Purpose: In this in vitro study, we compared the EAL findings with the results obtained by the CBCT images for the detection of perforations within ERR lesions. Materials and Method: This cross sectional study included 160 extracted anterior human teeth. The teeth were categorized into four groups including teeth with intact root, teeth with ERR, teeth with ERR and 0.5 mm perforation, and teeth with ERR with 1 mm perforation. The presence of perforations was compared by CBCT images and root EAL. Results: The sensitivity of CBCT scans in detecting 0.5 mm and 1 mm root perforations was 100% and 97.5%, respectively, while the sensitivity of the EAL was 10% and 27.5% in de-tecting 0.5 mm and 1 mm root perforations, respectively( with the ±0.5mm range of error). For detecting intact and teeth with ERR, the specificity of CBCT scans was 100% and 95%, respectively, and for EAL, it was 100% for both. Poor agreement was found between the two techniques (kappa=-0.025). Conclusion: CBCT scans were more sensitive and specific than EAL scans for detecting perforations in non-obturated root canals in this study.

Do Opioid Addicts Require Higher Doses of Heparin During Percutaneous Coronary Intervention?

BACKGROUND: Patients who undergo percutaneous coronary intervention (PCI) receive anticoagulants, most commonly heparin to prevent thrombotic events during the procedure. Opioid addicts may require higher doses of heparin for PCI. We aimed to compare the effect of heparin on activated clotting time (ACT) between opioid addicts and non-addicts prior to and during PCI. METHODS: This comparative study included 107 patients scheduled for elective PCI, of whom 50 were opioid addicts and 57 non-addicts. Patients' baseline characteristics including age, gender, weight, comorbidities, drug history, and smoking were recorded. Prothrombin time (PT), ýpartial thromboplastin time (PTT), international normalized ratio (INR), and platelet count were measured in venous blood samples collected from all participants. All patients underwent PCI through femoral access. They received 100 IU/kg heparin right at the beginning of the procedure. ACT was measured at 2 and 30 minutes. FINDINGS: Age, gender, weight, and the amount of heparin used were comparable between groups. As for general characteristics, the number of patients with hyperlipidemia was significantly higher in non-addicts (P = 0.031), and cigarette smoking was higher in opioid addicts (P < 0.001). No significant difference was found between the groups regarding PT, PTT, INR, and platelet count (P > 0.050). ACT at 2 and 30 min were significantly lower in opioid addicts (P < 0.001). Taking other variables into account, ACT at 2 min was directly correlated with drug history of aspirin in opioid addicts (P = 0.031) and inversely correlated with cigarette smoking in non-addicts (P = 0.023). CONCLUSION: Opioid addicts may require higher doses of heparin in PCI for the prevention of thrombotic complications compared to non-addicts.

Engineering strategies for enhancing the performance of electrochemical paper-based analytical devices.

Applications of electrochemical detection methods in microfluidic paper-based analytical devices (µPADs) has revolutionized the area of point-of-care (POC) testing towards highly sensitive and selective quantification of various (bio)chemical analytes in a miniaturized, low-coat, rapid, and user-friendly manner. Shortly after the initiation, these relatively new modulations of µPADs, named as electrochemical paper-based analytical devices (ePADs), gained widespread popularity within the POC research community thanks to the inherent advantages of both electrochemical sensing and usage of paper as a suitable substrate for POC testing platforms. Even though general aspects of ePADs such as applications and fabrication techniques, have already been reviewed multiple times in the literature, herein, we intend to provide a critical engineering insight into the area of ePADs by focusing particularly on the practical strategies utilized to enhance their analytical performance (i.e. sensitivity), while maintaining the desired simplicity and efficiency intact. Basically, the discussed strategies are driven by considering the parameters potentially affecting the generated electrochemical signal in the ePADs. Some of these parameters include the type of filter paper, electrode fabrication methods, electrode materials, fluid flow patterns, etc. Besides, the limitations and challenges associated with the development of ePADs are discussed, and further insights and directions for future research in this field are proposed.

Adsorptive removal of Hg2+ from environmental water samples using thioglycerol-intercalated magnetic layered double hydroxides.

Herein, the removal of Hg2+ from environmental water samples was carried out using a novel nanoadsorbent based on magnetite nanoparticles coated by a thioglycerol-intercalated layered double hydroxide. The prepared material was characterized using scanning electron microscopy equipped with an energy dispersive X-ray analyzer and Fourier transform infrared spectrometry. The effective parameters of the removal procedure were identified and optimized through the one-variable-at-a-time method. Under the optimal conditions, the removal characteristics of the synthesized adsorbent including selectivity, distribution coefficient, and loading capacity were calculated in the presence of some interfering ions. The removal efficiency of 94.98% together with the distribution coefficient of 5.00 × 105 mL g-1 and loading capacity of 480.69 mg g-1 showed the considerable capability of this novel adsorbent in the selective removal of Hg2+ from aqueous samples. To evaluate the performance of the synthesized adsorbent in the removal of Hg2+ from environmental water samples, the removal of the desired analyte was carried out using four different real samples. The removal procedures were conducted at the analyte concentration levels of 10.0 and 50.0 mg L-1 for each aqueous sample. The obtained results showed that the removal efficiency was in the range of 91.99-94.97%, which confirmed the high performance of the synthesized adsorbent in the removal of Hg2+ from real samples. Furthermore, the relative standard deviation of as low as 4.18-6.17% showed the acceptable repeatability of this method.

Hollow fiber-based liquid phase microextraction followed by analytical instrumental techniques for quantitative analysis of heavy metal ions and pharmaceuticals.

Hollow-fiber liquid-phase microextraction (HF-LPME) and electromembrane extraction (EME) are miniaturized extraction techniques, and have been coupled with various analytical instruments for trace analysis of heavy metals, drugs and other organic compounds, in recent years. HF-LPME and EME provide high selectivity, efficient sample cleanup and enrichment, and reduce the consumption of organic solvents to a few micro-liters per sample. HF-LPME and EME are compatible with different analytical instruments for chromatography, electrophoresis, atomic spectroscopy, mass spectrometry, and electrochemical detection. HF-LPME and EME have gained significant popularity during the recent years. This review focuses on hollow fiber based techniques (especially HF-LPME and EME) of heavy metals and pharmaceuticals (published 2017 to May 2019), and their combinations with atomic spectroscopy, UV-VIS spectrophotometry, high performance liquid chromatography, gas chromatography, capillary electrophoresis, and voltammetry.

Synthesis and characterization of polyamide-graphene oxide-polypyrrole electrospun nanofibers for spin-column micro solid phase extraction of parabens in milk samples.

In the present study, an electrospun composite of polyamide-graphene oxide-polypyrrole was synthesized. The characterization of the synthesized material was accomplished using field emission scanning electron microscopy (FESEM) and Fourier transform infrared spectroscopy (FT-IR). FESEM images showed uniform and beadles nanofibers. The composite was employed as a novel sorbent for spin-column micro solid phase extraction to determine parabens in milk samples. Addition of graphene oxide and polypyrrole into the polymeric network of polyamide significantly improves the extraction efficiency of the electrospun sorbent due to providing the possibility of various interactions with the target analytes such as hydrogen bonding, hydrophobic and π-π stacking. All effective parameters on the efficiency of both adsorption and desorption steps were optimized. These parameters were pH of sample solution (5.0), sorbent amount (20 mg), type and volume of desorption solvent (200 µL of methanol), number of cycles (7 and 14) and centrifugation speed (600 and 500 rpm) of both adsorption and desorption steps. Under the optimal conditions, the calibration plots were linear within the range of 10-1000, 15-1000, and 20-1000 ng mL-1 for methyl paraben, ethyl paraben and propyl paraben, respectively. Limits of detection were obtained lower than 7.0 ng mL-1 by HPLC-UV. Intra- and inter-assay relative standard deviations were less than 8.6% and 5.8%, respectively. Finally, the method was successfully applied for determination of parabens in some milk samples and good recoveries were obtained within the range of 81.7-97.8%. The results demonstrated good efficiency of the synthesized electrospun composite nanofibers as the packing material for spin-column micro solid phase extraction.

A promising design of microfluidic electromembrane extraction coupled with sensitive colorimetric detection for colorless compounds based on quantum dots fluorescence.

In the present study, a microfluidic platform was exploited for electromembrane extraction. For device integration as a lab-on-a-chip system, the detection step was carried out by a colorimetric method based on fluorescence quenching of quantum dots. The model analyte was transferred under a pulsed applied electrical field across a polypropylene membrane, impregnated with 1-Octanol, into a final aqueous acceptor phase. The obtained acceptor phase was added into a solution containing CdTe quantum dots. Quenching of the quantum dots was tracked by analyzing the main three color components of red, green, and blue in different concentration levels of the analyte. All effective parameters on the extraction efficiency, fluorescence detection, and synthesis of quantum dots were optimized. Under the optimal conditions, the detection was accomplished by three different detection methods including HPLC-UV, spectrofluorometric detection, as well as colorimetry detection via a smartphone. Calibration curves were linear in the range of 2.0-500 µg L-1 for LC-UV, 30-2500 µg L-1 for fluorescence detection, and 2.5-20 µg mL-1 for image analysis. Inter- and intra-assay relative standard deviations were less than 10.1% in all detection modes.