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Hydrogels are attractive materials for drug delivery applications due to biocompatible, porous structure with the possibility to load and deliver drugs in a controllable manner. In this paper, poly(methacrylic acid) (PMAA) hydrogels are described, which are synthesized by free-radical polymerization, using poly(ethylene glycol) diacrylate (PEGDA) as a crosslinker. Influence of the PEGDA content on hydrogel properties was investigated and compared to commonly used crosslinker - N,N’-methylenebisacrylamide (MBA). The increasing concentration of crosslinkers led to a higher degree of crosslinking, which was demonstrated by a higher degree of conversion, lower swelling capacity, and improved thermal stability and mechanical properties. Also, the PEGDA-crosslinked hydrogels demonstrated a higher degree of crosslinking than the corresponding MBA-crosslinked hydrogels. Potential application of the synthesized hydrogels for controlled drug delivery was investigated by using two model drugs - oxaprozin and ciprofloxacin. In vitro drug release tests indicated that the interactions between drug, polymer and medium have a key influence on the drug release behavior, rather than the swelling rate. Drug release tests in simulated gastrointestinal conditions indicated that PEGDA-crosslinked PMAA hydrogels are suitable for colon-targeted delivery of oxaprozin.

The influence of different hydroxides, applied to activate carbon black, on the electrochemical properties of activated carbon was investigated. The carbon material was prepared by hydrothermal treatment of sucrose and afterwards thermally activated using KOH, NaOH and LiOH. The electrochemical properties of the obtained samples were examined by cyclic voltammetry and electrochemical impedance spectroscopy and correlated to their physicochemical properties. All samples showed characteristic capacitor-like behaviour. The highest specific capacitance was obtained for the KOH-treated sample, while the increase in capacitance follows the sequence of the growth of ionic radius of a metal from an alkali which is used for activation. It was found that the dependence on the type of hydroxide is due to differences in the radii of a metal. The alkalies of larger radii of metal generated make pores wider and consequently the structure of a porous layer become more accessible to the charge transfer of capacitive response.

The contemporary phase of marketing development emphasizes the increasingly important role of economic entities as an integral part of society and a catalyst for positive changes. Researchers mainly focus their attention on large companies and sectors that significantly impact the local community and society. In that sense, this article addresses the Serbian banking sector. The authors analyzed the corporate social responsibility activities of 24 banks and their reporting practices. The analysis included a study of the content of publicly available documents and reports and news published on banks' websites and Facebook profiles. In addition, the authors explored stakeholders' perceptions of socially responsible banking activities. A survey of 30 banks stakeholder representatives showed: what are the critical issues in local communities; what are the respondents' attitudes about banks and the way they operate in Serbia; to what extent have stakeholders noticed the social marketing activities of commercial banks; what is the attitude of stakeholders regarding the issue of rewarding banks for socially responsible behavior. After reviewing and discussing the main findings, the authors provide key recommendations and possible directions for further research.

The cytotoxicity of amorphous calcium phosphate (ACP) and chitosan lactate (ChOL) multifunctional and hybrid composite coatings on MRC-5 human lung fibroblast cell line was elucidated. ACP/TiO2 and ACP/TiO2/ /ChOL were deposited onto Ti by a novel in situ anodization/anaphoretic process at constant voltage. Cytotoxicity tests showed that there was no significant decrease in the survival of healthy MRC-5 cells exposed to composite samples without chitosan lactate, while there was an increase in the number of viable cells in the sample containing ChOL. These findings show that there was improved cell proliferation, differentiation and cell viability in the ChOL-containing sample, which makes ACP/TiO2/ChOL coating a good candidate for applications in medicine and stomatology.

The contemporary phase of marketing development emphasizes the increasingly important role of economic entities as an integral part of society and a catalyst for positive changes. Researchers mainly focus their attention on large companies and sectors that significantly impact the local community and society. In that sense, this article addresses the Serbian banking sector. The authors analyzed the corporate social responsibility activities of 24 banks and their reporting practices. The analysis included a study of the content of publicly available documents and reports and news published on banks' websites and Facebook profiles. In addition, the authors explored stakeholders' perceptions of socially responsible banking activities. A survey of 30 banks stakeholder representatives showed: what are the critical issues in local communities; what are the respondents' attitudes about banks and the way they operate in Serbia; to what extent have stakeholders noticed the social marketing activities of commercial banks; what is the attitude of stakeholders regarding the issue of rewarding banks for socially responsible behavior. After reviewing and discussing the main findings, the authors provide key recommendations and possible directions for further research.

Mimicking the extraordinary performances of natural materials presents an attractive, but challenging approach in the synthesis of advanced functional materials. In the field of separation techniques, the design of a low-cost, regenerative, environmentally friendly sorbent and the utilization of most of its active centers to remove the targeted pollutant are everyday challenges. The combination of casein and poly(sodium methacrylate) (PMANa) in the form of a soft polymer network is proposed as a promising sorbent for the removal of Ni2+ from wastewater. Such a combination and an applied synthetic route form hybrid materials with better sorption properties than both their components alone. SEM and TEM show that caseinate micelles are dissociated and the more exposed protein structure is stabilized by the PMANa network and able to form various stable complexes. The achieved sorption capacity (224 mg g−1) is among the highest reported in the literature. The very high removal efficiency in the wide range of the initial Ni2+ concentrations (0.05–200 ppm) and easy and complete regeneration without decrease in sorption capacities make these low-cost materials highly sensitive sorbents attractive for use under real conditions where it is necessary to avoid environmental risks and provide the recovery and reuse of the metal. [ABSTRACT FROM AUTHOR]

The optimization of the anodization process of Ti substrate for in situ synthesis of hydroxyapatite/titanium oxide composite coatings on titanium substrate was accomplished. The anodization was performed under 30, 60 and 90 V cell voltage, and the morphology of treated surface, as well as linear and surface roughness, were analysed by field emission-scanning electron microscopy, atomic force microscopy and roughness tester. It was shown by linear and surface roughness analyses that titanium anodized under 60 V has the highest roughness, whereas at 90 V the flattening of the surface occurs. As the highest surface roughness results emerged at 60 V, the novel process of composite anHAp/TiO2 coating synthesis, which comprises simultaneous processes of TiO2 formation and HAp deposition, as well as HAp impregnation within TiO2 surface layer, was performed at this voltage. Ti substrate surface was completely covered by composite coating, with no visible cracks. The adhesion quantified according to ASTM D3359-02 standard is considerably improved with respect to the coatings obtained by cathaphoretic processes, with no need of subsequent sintering. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. ON172060]

Supercapacitors are the best choice when there is a need to deliver high power to the consumer or to store energy. Hybrid supercapacitors with their beneficial characteristics can somewhat overcome the basic lack of batteries, that is the low power density, and when supercapacitors are combined with batteries, the current maximum power can be increased and the lifetime extended. The number of research studies on development of new materials and construction technologies for supercapacitors has been increasing steadily in recent years. As a result, production of commercial devices and their applications are constantly growing, with improved product properties. Here we present the current state of development of supercapacitors as highly promising energy storage systems by an overview of operation principles, main components and various electrode materials and electrolytes, as well as description of different modes of production. A special attention was paid to the need of a good match of the active material and electrolytes, in order to achieve high capacity of the device. The electrode/electrolyte phase optimization is the key to maximizing characteristics of a supercapacitor, especially the capacitance. In selecting the materials, requirements of the final application must be considered, such as the specific energy and power, energy and power density, and service life-time. In addition to material selection, design and optimization of the cell configuration provide new opportunities for development of hybrid battery/supercapacitor systems. Demand for such systems will increase in future, when using a battery or a supercapacitor alone will not be able to meet specific needs, such as the energy density, number of charge and discharge cycles or voltage. Finally, equally important as the development of materials and cells, are the electrode production technology and the cell construction, which need to be optimized in order to improve supercapacitor properties. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 172060: Nov pristup dizajniranju materijala za konverziju i skladištenje energije, kao i bilateralnog projekta Srbija Hrvatska: Superkondenzatori visoke snage zasnovani na grafen/pseudokapacitivnim materijalima]

Goals. The goal of this study was a development of biocompatible composite hydrogels, structurally similar to native bone tissue, by incorporation of ~60 wt % of calcium hydroxyapatite (HA) into a matrix of hydrogels. Also, a possibility to control swelling kinetic and equilibrium swelling degree (SDeq) of hydrogels, by altering the degree of neutralization of the precursor (DN) was examined. Methods. Composite hydrogels, based on HA and poly(methacrylic acid) (PMAA), were synthesized by free-radical polymerization with different DN. Theoretical content of HA in synthesized composites was 60 wt %. Composites were synthesized by methods of dynamic mechanical analysis and scanning electron microscopy. SDeq and swelling kinetic were examined in distilled water and simulated body fluid. Results. Morphological observations revealed uniform distribution and strong bond of spherical HA particles within the polymer matrix. Swelling analyses demonstrated that SDeq is directly proportional to DN, while rheological examinations indicated inverse proportion between DN and storage modulus, but due to the HA particles inclusion, mechanical properties of composites were significantly better compared to monophasic PMAA hydrogels. Significance. Simple method of synthesis of composite hydrogels with high content of filler nanoparticles is presented. Incorporation of HA nanoparticles significantly improved mechanical properties of hydrogels, while at the same time was demonstrated a possibility to control swelling kinetic by influencing the DN.

For the preparation of RuO2 coatings on Ti substrate, the RuO2 was synthesized in acidic aqueous medium by simple one-step low temperature-controlled microwave (MW) irradiation. The physical composition of synthesized solid phase was analysed through particle size distribution (PSD), whereas the coating was investigated for its capacitive response and activity in oxygen evolution reaction (OER). The oxide phase was found highly polydisperse, with overlapped fractions within rather narrow particle size range and clear tendency toward agglomeration. The smallest particles and their best resolved fractions were synthesized at the temperature just above the boiling point of the reaction medium, and quite below the chloride-to-oxide conversion temperature. Consequently, the highest OER activity was registered for RuO2/Ti anodes prepared from this sample, with strong indication of different oxide structure, with respect to the electrodes prepared from samples synthesized at higher temperatures. However, the coatings from high temperature samples have considerably higher capacitance than those synthesized at lower temperatures. These findings can be rather correlated to the MW temperature-dependent oxide structure than to different morphology analysed through PSD.

The aim of this work was to examine the possibility of modification of commercial denture base materials with itaconic acid esters, in order to obtain material with less toxicity and higher biocompatibility. Despite their relatively higher price compared to methacrylates, itaconic acid and itaconates are materials of choice for environmentally friendly applications, because they are not produced from petrochemical sources, but from plants. Commercial system based on poly(methyl methacrylate) was modified using ditetrahydrofurfuryl itaconate (DTHFI), wherein the ratio of DTHFI was varied from 2.5 to 10% by weight. Copolymerization was confirmed using FTIR spectroscopy, while SEM analysis showed the absence of micro defects and pores in the structure. The effect of the itaconate content on the absorption of fluids, the residual monomer content, thermal, dynamic-mechanical and mechanical properties (hardness, toughness, stress and elongation at break) was investigated. It was found that the addition of DTHFI significantly reduced the amount of residual methyl methacrylate, what made these materials less toxic. It was shown that the increase in DTHFI content gave materials with decreased glass transition temperature, as well as with decreased storage modulus, ultimate tensile strength and impact fracture resistance, however mechanical properties were in the rang prescribed by ADA standards, and can be used in practice. The deterioration of mechanical properties was therefore worth losing in order to gain lesser toxicity of the leached monomer. [Projekat Ministarstva nauke Republike Srbije, br. 172062: Synthesis and characterization of novel functional polymers and polymeric nanomaterials]

Porous electrochemical supercapacitive materials, as an important type of new-generation energy storage devices, require a detailed analysis and knowledge of their capacitive performances upon different charging/discharging regimes. The investigation of the responses to dynamic perturbations of typical representatives, noble metal oxides, carbonaceous materials and RuO2-impregnated carbon blacks, by electrochemical impedance spectroscopy (EIS) is presented. This presentation follows a brief description of supercapacitive behavior and origin of pseudocapacitive response of noble metal oxides. For all investigated materials, the electrical charging/discharging equivalent of the EIS response was found to obey the transmission line model envisaged as so-called „resistor/capacitor (RC) ladder“. The ladder features are correlated to material physicochemical properties, its composition and the composition of the electrolyte. Fitting of the EIS data of different supercapacitive materials to appropriate RC ladders enables the in-depth profiling of the capacitance and pore resistance of their porous thin-layers and finally the complete revelation of capacitive energy storage issues. [Projekat Ministarstva nauke Republike Srbije, br. 172060]

The use of polymeric adsorbents for the removal of azo dyes from solution has been reviewed. Adsorption techniques are widely used to remove certain classes of pollutants from waters, especially those which are not easily biodegradable. The removal of azo dyes as pollutants from wastewaters of textile, paper, printing, leather, pharmaceutical and other industries has been addressed by the researchers. The wider use of already available adsorbents is restricted due to their high costs which lead to investigation and development of new materials that can be cheaper, eficient and easy regenerated. The aim of this article is to present to the readers the widespread investigations in recent years of synthetic and natural polymers as adsorbents and potential replacement of conventional adsorbents. This review presents only the data obtained using raw, hydrogel, grafted and crosslinked forms of synthetic and nature based polymers, and the discussion is limited to these polymer-based materials and their adsorption properties. [Projekat Ministarstva nauke Republike Srbije, br. 43009 i br. 172062.]

The results of an investigation of the capacitive characteristics of sol-gel-processed titanium- and carbon-supported electrochemically active noble metal oxides, as representatives of porous electrode materials, are presented in the lecture. The capacitive properties of these materials were correlated to their composition, the preparation conditions of the oxides and coatings, the properties of the carbon support and to the composition of the electrolyte. The results of the electrochemical test methods, cyclic voltammetry and electrochemical impedance spectroscopy, were employed to resolve the possible physical structures of the mentioned porous materials, which are governed by the controlled conditions of the preparation of the oxide by the sol-gel process.

The properties of activated titanium anodes, RuO2-TiO2/Ti and RuO2--TiO2-IrO2/Ti, prepared from oxide sols by the sol-gel procedure, are reviewed. RuO2 and TiO2 sols were synthesized by forced hydrolysis of the corresponding chlorides in acid medium. The morphology of the prepared sols was investigated by transmission electron microscopy. The chemical composition of the RuO2 sol was determined by X-ray diffraction and thermogravimetric analysis. The loss of electrocatalytic activity of a RuO2-TiO2/Ti anode during an accelerated stability test was investigated by examination of the changes in the electrochemical characteristics in the potential region of the chlorine and oxygen evolution reaction, as well as on the open circuit potential. These electrochemical characteristics were investigated by cyclic voltammetry, electrochemical impedance spectroscopy and polarization measurements. The changes in electrochemical characteristics of the anode prepared by the sol-gel procedure were compared to the changes registered for an anode prepared by the traditional thermal decomposition of metal chlorides. The comparison indicated that the main cause for the activity loss of the sol-gel prepared anode was the electrochemical dissolution of RuO2, while in the case of thermally prepared anode the loss was mainly caused by the formation of an insulating TiO2 layer in the coating/Ti substrate interphase. The results of an accelerated stability test on RuO2-TiO2/Ti and RuO2--TiO2-IrO2/Ti anodes showed that the ternary coating is considerably more stable than the binary one, which is the consequence of the greater stability of IrO2 in comparison to RuO2.

The electrochemical characteristics of a mixture of Pt-black and WC powders and its catalytic activity for methanol and formic acid oxidation were investigated in acid solution. XRD and AFM measurements revealed that the WC powder employed for the investigation was a single-phase material consisting of crystallites/spherical particles of average size of about 50 nm, which were agglomerated into much larger particles. Cyclic voltammetry showed that the WC underwent electrochemical oxidation, producing tungstate species. In the case of the mixed Pt + WC powders, the tungstate species were deposited on the Pt as a thin film of hydrous tungsten oxide. Enhanced hydrogen intercalation in the hydrous tungsten oxide was observed and it was proposed to be promoted in mixed powders by the presence of hydrogen adatoms on bare Pt sites. The determination of Pt surface area in the Pt + WC layer by stripping of underpotentially deposited Cu revealed that the entire Pt surface was accessible for underpotential deposition of Cu. Investigation of the electrochemical oxidation of methanol and formic acid on Pt + WC and pure Pt layers did not indicate electrocatalytic promotion due to the presence of WC.

The photoelectrochemical properties of a sol-gel prepared titanium oxide coating applied onto a Ti substrate were investigated. The oxide coating was formed from an inorganic sol thermally treated in air at 350°C. The coating consisted of agglomerates of narrow size distribution around 100 nm. The photoelectrochemical characteristics were evaluated by investigating the changes in the open circuit potential, current transients and impedance characteristics of a Ti/TiO2 electrode upon illumination by UV light in H2SO4 solution and in the oxidation of benzyl alcohol. The electrode was found to be active for photoelectrochemical reactions in the investigated solutions.

The characteristics of a ternary oxide coating, on titanium, which consisted of TiO2, RuO2 and IrO2 in the molar ratio 0.6:0.3:0.1, calculated on the metal atom, were investigated for potential application for cathodic protection in a seawater environment. The oxide coatings on titanium were prepared by the sol-gel procedure from a mixture of inorganic oxide sols, which were obtained by forced hydrolysis of metal chlorides. The morphology of the coating was examined by scanning electron microscopy. The electrochemical properties of activated titanium anodes were investigated by cyclic voltammetry and polarization measurements in a H2SO4- and NaCl-containing electrolyte, as well as in seawater sampled on the Adriatic coast in Tivat, Montenegro. The anode stability during operation in seawater was investigated by the galvanostatic accelerated corrosion stability test. The morphology and electrochemical characteristics of the ternary coating are compared to that of a sol-gel-prepared binary Ti0.6Ru0.4O2 coating. The activity of the ternary coating was similar to that of the binary Ti0.6Ru0.4O2 coating in the investigated solutions. However, the stability in seawater is found to be considerably greater for the ternary coating.

Titanium anodes with an active RuO2 coating of two different thicknesses were prepared from the oxide suspended in ethanol ("ink" method), while the oxide itself was synthesized by the hydrolysis of ruthenium ethoxide in an ethanolic solution (alkoxide route). The morphology of prepared oxide was examined by scanning electron microscopy. The electrochemical properties of the prepared Ti/RuO2 anodes, involving their cyclic voltammetric behavior in H2SO4 and NaCl solutions, activity in the chlorine and oxygen evolution reaction, impedance behavior in H2SO4, and stability during electrolysis in dilute chloride solutions, were investigated. The performances of the anodes are compared to those of a Ti/RuO2 anode prepared by the sol-gel procedure from an oxide sol obtained by the forced hydrolysis of ruthenium chloride in acid solution. The anodes prepared via the alkoxide route showed a higher capacitance and activity for the chlorine evolution reaction than the anode prepared by the inorganic sol-gel procedure. The results of the stability test showed that the utilization of the coating active material is better when the anodes were prepared via the alkoxide route than via the inorganic sol-gel procedure, particularly for anodes with a smaller mass of coating. The different rates of loss of activity indicate a degradation mechanism for the anodes prepared via the alkoxide route in which electrochemical dissolution of RuO2 from the coating surface prevails over the growth of an insulating TiO2 layer in the coating/Ti substrate interphase. The effect of RuO2 dissolution from the coating surface increases with increasing coating mass.

In order to understand the role of TiO2 in the deactivation mechanism of an active RuO2–TiO2 coating, an additional TiO2 layer was introduced in the support coating interphase of regular Ti//[RuO2–TiO2 anode in one case and on the surface of the coating in the other. The electrochemical behavior of these, with TiO2 enriched, anodes was compared with the behavior of anodes with regular RuO2–TiO2 coatings, which were subjected to an accelerated stability test. A high-frequency semicircle in the complex plane plot obtained by electrochemical impedance spectroscopy, for a regular RuO2–TiO2 coating corresponds to TiO2 enrichment in the coating as a consequence of anode corrosion. In the case of the coatings with additional TiO2 layers, a high-frequency semicircle was not observed. The additional TiO2 layers increase the coating overall resistance and influence the coating impedance behavior at low frequencies. Similar equivalent electrical circuits were used to analyze the impedance behavior of coatings having an additional TiO2 layer at different position within RuO2–TiO2 coating.

The influence of different parameters (forced hydrolysis duration in the preparation of sols, alcohol addition in the sol mixture for application, as well as sol/alcohol mixture ageing time) on the morphology and electrochemical properties of RuO2-TiO2 coatings obtained by the sol-gel procedure is presented. The oxide sols were sharacterized by spectroscopic and microscopic methods (X-ray diffraction, TEM, etc). The morphology of the obtained coatings was examined by scanning tunneling microscopy, while the electrochemical properties were investigated by cyclic voltammetry polarization measurements, electrochemical impedance spectroscopy and the accelerated stability test. The greatest real surface area was obtained for coatings with the smallest RuO2 particles and largest TiO2 particles. Alcohol addition caused enlargement of the oxide grains and, consequently, a decrease in the real surface area. The same effects of oxide grain size were registered on electrochemically active surface area. The electrocatalytic activity of the obtained anodes for the chlorine evolution reaction increased with growth of the TiO2 particles, but depended on the RuO2 particle size to a small degree. The corrosion stability of the anode coatings consisting of the smallest RuO2 particles and largest TiO2 particles whis the greatest in the electrolysis of a sodium-chloride solution.

The influence of the addition of methanol, ethanol, 1-propanol and 2-propanol to the dispersing medium of amixture of RuO2 and TiO2 sols on the electrochemically active surface area for proton exchange, as well as on the electrocatalytic activity for the chlorine evolution reaction (CER) of RuO2-TiO2/Ti electrode obtained by sol-gel procedure was investigated. The electrochemically active surface area was examined by cyclic voltammetry, while the analysis of the activity for the CER was performed by polarization measurements. The stability of the obtained anode coatings was also checked by an accelerated stability test. The anode properties depend on the number of C atoms in the alcohol molecule, as well as on the elapsed time between the preparation of the sols/alcohol mixture and its application onto the titanium support. The addition of alcohol increased the activity of the anodes for the CER, compared to those prepared without the addition, but their stability was smaller.

We developed a focused series of original phenyl-glycinamide derivatives which showed potent activity across in vivo mouse seizure models, namely, maximal electroshock (MES) and 6 Hz (using both 32 and 44 mA current intensities) seizure models. Following intraperitoneal ( i.p .) administration, compound ( R )-32 , which was identified as a lead molecule, demonstrated potent protection against all seizure models with ED 50 values of 73.9 mg/kg (MES test), 18.8 mg/kg (6 Hz, 32 mA test), and 26.5 mg/kg (6 Hz, 44 mA test). Furthermore, ( R )-32 demonstrated efficacy in both the PTZ-induced kindling paradigm and the iv PTZ seizure threshold test. The expression of neurotrophic factors, such as mature brain-derived neurotrophic factor (mBDNF) and nerve growth factor (NGF), in the hippocampus and/or cortex of mice, and the levels of glutamate and GABA were normalized after PTZ-induced kindling by ( R )-32 . Importantly, besides antiseizure activity, ( R ) -32 demonstrated potent antinociceptive efficacy in formalin-induced pain, capsaicin-induced pain, as well as oxaliplatin- and streptozotocin-induced peripheral neuropathy in mice ( i.p .). No influence on muscular strength and body temperature in mice was observed. Pharmacokinetic studies and in vitro ADME-Tox data ( i.e. , high metabolic stability in human liver microsomes, a weak influence on CYPs, no hepatotoxicity, satisfactory passive transport, etc. ) proved favorable drug-like properties of ( R ) -32 . Thermal stability of ( R )- 32 shown in thermogravimetry and differential scanning calorimetry gives the opportunity to develop innovative oral solid dosage forms loaded with this compound. The in vitro binding and functional assays indicated its multimodal mechanism of action. ( R ) -32 , beyond TRPV1 antagonism, inhibited calcium and sodium currents at a concentration of 10 μM. Therefore, the data obtained in the current studies justify a more detailed preclinical development of ( R ) -32 for epilepsy and pain indications.

Hydrogels endure various dynamic stresses, demanding robust mechanical properties. Despite significant advancements, matching hydrogels' strength to biological tissues and plastics is often challenging without applying potentially harmful crosslinkers. Using hydrogen bonds as sacrificial bonds offers a promising strategy to produce tough, versatile hydrogels for biomedical and industrial applications. Poly(methacrylic acid) (PMA)/gelatin hydrogels were synthesized by thermally induced free-radical polymerization and crosslinked only by physical bonds, without adding any chemical crosslinker. The addition of gelatin increased the formation of hydrophobic domains in the structure of the hydrogels, which acted as permanent crosslinking points. The increase in PMA and gelatin contents generally led to a lower equilibrium water content (WC), higher thermal stability and better mechanical properties. The values of tensile strength and toughness reached up to 1.44 ± 0.17 MPa and 4.91 ± 0.51 MJ m -3 , respectively, while the compressive modulus and strength reached up to 0.75 ± 0.06 MPa and 24.81 ± 5.85 MPa, respectively, with the WC being higher than 50 wt.%. The obtained values for compressive mechanical properties are comparable with super-strong hydrogels reported in the literature. In addition, hydrogels exhibited excellent fatigue resistance and biocompatibility, as well as great shape memory properties, which make them prominent candidates for a wide range of biomedical applications.

This manuscript systematically assesses three different glycerides (tripalmitin, glyceryl monostearate, and a blend of mono-, di- and triesters of palmitic and stearic acids (Geleol™)) as potential gelator structuring agents of medium-chain triglyceride oil to form an oleogel-based injectable long-acting local anesthetic formulation for postoperative pain management. Drug release testing, oil-binding capacity, injection forces, x-ray diffraction, differential scanning calorimetry, and rheological testing were serially performed to characterize the functional properties of each oleogel. After benchtop assessment, the superior bupivacaine-loaded oleogel formulation was compared to bupivacaine HCl, liposomal bupivacaine, and bupivacaine-loaded medium-chain triglyceride oil in a rat sciatic nerve block model to assess in vivo long-acting local anesthetic performance. In vitro drug release kinetics were similar for all formulations, indicating that drug release rate is primarily dependent on the drug's affinity to the base oil. Glyceryl monostearate-based formulations had superior shelf-life and thermal stability. The glyceryl monostearate oleogel formulation was selected for in vivo evaluation. It was found to have a significantly longer duration of anesthetic effect than liposomal bupivacaine and was able to provide anesthesia twice as long as the equipotent bupivacaine-loaded medium-chain triglyceride oil, indicating that the increased viscosity of the oleogel provided enhanced controlled release over the drug-loaded oil alone., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brett Davis, Susan Wojtalewicz, Sierra Erickson, Jonathon Vizmeg, Jack Shuckra, Keelah Barger, Andrew Cleveland, Jordan Davis, Stefan Niederauer, Michael Beeman, Jayant Agarwal, Caleb Lade report financial support was provided by Rebel Medicine Inc. Brett Davis, Susan Wojtalewicz, Sierra Erickson, Jonathon Vizmeg, Jack Shuckra, Keelah Barger, Andrew Cleveland, Jordan Davis, Stefan Niederauer, Michael Beeman, Jayant Agarwal, Caleb Lade reports a relationship with Rebel Medicine Inc that includes: board membership, employment, and/or equity or stocks. Cameron Metcalf, Karen Wilcox, and Vanja Panic have no conflicting interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Thermogenesis by uncoupling protein 1 (UCP1) is one of the primary mechanisms by which brown adipose tissue (BAT) increases energy expenditure. UCP1 resides in the inner mitochondrial membrane (IMM), where it dissipates membrane potential independent of adenosine triphosphate (ATP) synthase. Here, we provide evidence that phosphatidylethanolamine (PE) modulates UCP1-dependent proton conductance across the IMM to modulate thermogenesis. Mitochondrial lipidomic analyses revealed PE as a signature molecule whose abundance bidirectionally responds to changes in thermogenic burden. Reduction in mitochondrial PE by deletion of phosphatidylserine decarboxylase (PSD) made mice cold intolerant and insensitive to β3 adrenergic receptor agonist-induced increase in whole-body oxygen consumption. High-resolution respirometry and fluorometry of BAT mitochondria showed that loss of mitochondrial PE specifically lowers UCP1-dependent respiration without compromising electron transfer efficiency or ATP synthesis. These findings were confirmed by a reduction in UCP1 proton current in PE-deficient mitoplasts. Thus, PE performs a previously unknown role as a temperature-responsive rheostat that regulates UCP1-dependent thermogenesis.

Brown adipose tissue (BAT) is composed of thermogenic cells that convert chemical energy into heat to maintain a constant body temperature and counteract metabolic disease. The metabolic adaptations required for thermogenesis are not fully understood. Here, we explore how steady state levels of metabolic intermediates are altered in brown adipose tissue in response to cold exposure. Transcriptome and metabolome analysis revealed changes in pathways involved in amino acid, glucose, and TCA cycle metabolism. Using isotopic labeling experiments, we found that activated brown adipocytes increased labeling of pyruvate and TCA cycle intermediates from U 13 C-glucose. Although glucose oxidation has been implicated as being essential for thermogenesis, its requirement for efficient thermogenesis has not been directly tested. We show that mitochondrial pyruvate uptake is essential for optimal thermogenesis, as conditional deletion of Mpc1 in brown adipocytes leads to impaired cold adaptation. Isotopic labeling experiments using U 13 C-glucose showed that loss of MPC1 led to impaired labeling of TCA cycle intermediates. Loss of MPC1 in BAT increased 3-hydroxybutyrate levels in blood and BAT in response to the cold, suggesting that ketogenesis provides an alternative fuel source to compensate. Collectively, these studies highlight that complete glucose oxidation is essential for optimal brown fat thermogenesis., Competing Interests: VP, SP, JB, TT, JV, SL, JS, GG, CB, Tv, WH, SS, JC, GD, JR, CV No competing interests declared, (© 2020, Panic et al.)

Although metabolic adaptations have been demonstrated to be essential for tumor cell proliferation, the metabolic underpinnings of tumor initiation are poorly understood. We found that the earliest stages of colorectal cancer (CRC) initiation are marked by a glycolytic metabolic signature, including downregulation of the mitochondrial pyruvate carrier (MPC), which couples glycolysis and glucose oxidation through mitochondrial pyruvate import. Genetic studies in Drosophila suggest that this downregulation is required because hyperplasia caused by loss of the Apc or Notch tumor suppressors in intestinal stem cells can be completely blocked by MPC overexpression. Moreover, in two distinct CRC mouse models, loss of Mpc1 prior to a tumorigenic stimulus doubled the frequency of adenoma formation and produced higher grade tumors. MPC loss was associated with a glycolytic metabolic phenotype and increased expression of stem cell markers. These data suggest that changes in cellular pyruvate metabolism are necessary and sufficient to promote cancer initiation., Competing Interests: Declaration of Interests The University of Utah has filed a patent related to the mitochondrial pyruvate carrier, of which J.R. and C.S.T. are listed as co-inventors. All other authors declare no competing interests., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Adipocyte differentiation is controlled by multiple signaling pathways. To identify new adipogenic factors, C3H10T1/2 adipocytes were treated with previously known antiadipogenic phytochemicals (resveratrol, butein, sulfuretin, and fisetin) for 24 hours. Commonly regulated genes were then identified by transcriptional profiling analysis. Three genes (chemokine (C-X-C motif) ligand 1 [ Cxcl1], heme oxygenase 1 [ Hmox1], and PHD (plant homeo domain) finger protein 16 [ Phf16]) were upregulated while two genes (G0/G1 switch gene 2 [ G0s2] and patatin-like phospholipase domain containing 3 [ Pnpla3]) were downregulated by these four antiadipogenic compounds. Tissue expression profiles showed that the G0s2 and Pnpla3 expressions were highly specific to adipose depots while the other three induced genes were ubiquitously expressed with significantly higher expression in adipose tissues. While Cxcl1 expression was decreased, expressions of the other four genes were significantly increased during adipogenic differentiation of C3H10T1/2 cells. Small interfering RNA-mediated knockdown including Phf16 and Pnpla3 indicated that these genes might play regulatory roles in lipid accumulation and adipocyte differentiation. Specifically, the silencing of two newly identified adipogenic genes, Phf16 or Pnpla3, suppressed lipid accumulation and expression of adipocyte markers in both 3T3-L1 and C3H10T1/2 cells. Taken together, these data showed previously uncovered roles of Phf16 and Pnpla3 in adipogenesis, highlighting the potential of using phytochemicals for further investigation of adipocyte biology., (© 2018 Wiley Periodicals, Inc.)

Identifying regulatory mechanisms that influence inflammation in metabolic tissues is critical for developing novel metabolic disease treatments. Here, we investigated the role of microRNA-146a (miR-146a) during diet-induced obesity in mice. miR-146a is reduced in obese and type 2 diabetic patients and our results reveal that miR-146a-/- mice fed a high-fat diet (HFD) have exaggerated weight gain, increased adiposity, hepatosteatosis, and dysregulated blood glucose levels compared to wild-type controls. Pro-inflammatory genes and NF-κB activation increase in miR-146a-/- mice, indicating a role for this miRNA in regulating inflammatory pathways. RNA-sequencing of adipose tissue macrophages demonstrated a role for miR-146a in regulating both inflammation and cellular metabolism, including the mTOR pathway, during obesity. Further, we demonstrate that miR-146a regulates inflammation, cellular respiration and glycolysis in macrophages through a mechanism involving its direct target Traf6. Finally, we found that administration of rapamycin, an inhibitor of mTOR, was able to rescue the obesity phenotype in miR-146a-/- mice. Altogether, our study provides evidence that miR-146a represses inflammation and diet-induced obesity and regulates metabolic processes at the cellular and organismal levels, demonstrating how the combination of diet and miRNA genetics influences obesity and diabetic phenotypes., Competing Interests: The authors have declared that no competing interests exist.

Stimulation of white adipose tissue (WAT) browning is considered as a potential approach to treat obesity and metabolic diseases. Our previous studies have shown that phytochemical butein can stimulate WAT browning through induction of Prdm4 in adipocytes. Here, we investigated the effects of butein on diet-induced obesity and its underlying molecular mechanism. Treatment with butein prevented weight gains and improved metabolic profiles in diet-induced obese mice. Butein treatment groups also displayed higher body temperature, increased energy expenditure, and enhanced expression of thermogenic genes in adipose tissue. Butein also suppressed body weight gains and improved glucose and insulin tolerance in mice housed at thermoneutrality (30 °C). These effects were associated with adipose-selective induction of Prdm4, suggesting the role of Prdm4 in butein-mediated anti-obese effects. To directly assess the in vivo role of Prdm4, we generated aP2-Prdm4 transgenic mouse lines overexpressing Prdm4 in adipose tissues. Adipose-specific transgenic expression of Prdm4 recapitulated the butein's actions in stimulating energy expenditure, cold tolerance, and thermogenic gene expression, resulting in prevention of obesity and improvement of metabolism. Mechanistically, direct inhibition of PI3Kα activity followed by selective suppression of its downstream Akt1 mirrored butein's effect on Ucp1 expression and oxygen consumption. In addition, effects of butein were completely abolished in Akt1 KO mouse embryonic fibroblasts. Together, these studies demonstrate the role of butein in obesity and metabolic diseases, further highlighting that adipose PI3Kα-Akt1-Prdm4 axis is a regulator of energy expenditure.

Selective inhibition of α-helix-mediated protein-protein interactions (PPIs) with small organic molecules provides great potential for the discovery of chemical probes and therapeutic agents. Protein Data Bank data mining using the HippDB database indicated that (1) the side chains of hydrophobic projecting hot spots at positions i, i + 3, and i + 7 of an α-helix had few orientations when interacting with the second protein and (2) the hot spot pockets of PPI complexes had different sizes, shapes, and chemical groups when interacting with the same hydrophobic projecting hot spots of α-helix. On the basis of these observations, a small organic molecule, 4'-fluoro-N-phenyl-[1,1'-biphenyl]-3-carboxamide, was designed as a generic scaffold that itself directly mimics the binding mode of the side chains of hydrophobic projecting hot spots at positions i, i + 3, and i + 7 of an α-helix. Convenient decoration of this generic scaffold led to the selective disruption of α-helix-mediated PPIs. A series of small-molecule inhibitors selective for β-catenin/B-cell lymphoma 9 (BCL9) over β-catenin/cadherin PPIs was designed and synthesized. The binding mode of new inhibitors was characterized by site-directed mutagenesis and structure-activity relationship studies. This new class of inhibitors can selectively disrupt β-catenin/BCL9 over β-catenin/cadherin PPIs, suppress the transactivation of canonical Wnt signaling, downregulate the expression of Wnt target genes, and inhibit the growth of Wnt/β-catenin-dependent cancer cells.