Formulation and preclinical evaluation of 99mTc–gemcitabine as a novel radiopharmaceutical for solid tumor imaging

The aim of this study is the formulation of a new radiopharmaceutical for imaging solid tumor bearing. Gemcitabine is a nucleoside analogue used as chemotherapeutic agent. Gemcitabine was formulated and radiolabeled with one of the most important diagnostic radioactive isotopes (technetium-99m) to be investigated in solid tumor imaging. The labeling parameters such as gemcitabine amount, stannous chloride amount, pH of the reaction mixture, and reaction time were optimized. ^99mTc–gemcitabine was prepared at pH 9 with a maximum labeling yield of 96 ± 0.3 % without any notable decomposition at room temperature over a period of 8 h. The preclinical evaluation and biodistribution in solid tumor bearing mice showed that ^99mTc–gemcitabine had solid tumor selectivity, preclinical high biological accumulation in tumor cells and high retention. Tumor/normal muscle (T/NT) ratios increased with time showing high T/NT ratio (T/NT = 4.9 ± 0.27 at 120 min post injection) and high Tumor/Blood ratio (3.4 ± 0.06), suggesting ^99mTc–gemcitabine as a novel solid tumor imaging agent.     

Mixed-ligand metal complexes containing an ONS Schiff base and imidazole/benzimidazole ligands: synthesis,characterization, crystallography and biological activity

Salicylaldehyde-4-methylthiosemicarbazone (H₂MTSali) has been prepared via the condensation reaction of 4-methyl-3-thiosemicarbazide and salicylaldehyde. Four new mixed-ligand copper(II) and nickel(II) complexes with a general formula [M(MTSali)L] (M = Cu²⁺ or Ni²⁺; L = co-ligand) were synthesized, where L is either imidazole (im) or benzimidazole (bzim). The Schiff base and its mixed-ligand complexes were characterized by IR and UV/Vis spectroscopy, and the complexes by molar conductivity and magnetic susceptibility measurements. The spectroscopic data indicated that the Schiff base behaves as a tridentate ONS donor ligand coordinating via the phenoxide-oxygen, azomethine-nitrogen, and thiolate-sulphur atoms. Magnetic data indicate a square planar environment for the nickel(II) complexes while molar conductance values indicate that the metal complexes are essentially non-electrolytes in DMSO solution. X-ray crystallography shows Cu(MTSali)bzim (1) and Ni(MTSali)bzim (3) to be isostructural, with the metal(II) ions being coordinated by a N₂OS donor set that defines an approximate square planar geometry; in both cases, the benzimidazole is splayed with respect to the coordination plane. The copper(II) complexes were active against MDA-MB-231 and MCF-7 breast cancer cell lines, more so than H₂MTSali, whereas the nickel(II) complexes were inactive.     

Thymoquinone Loaded Topical Nanoemulgel for Wound Healing: Formulation Design and In-Vivo Evaluation

Thymoquinone is a natural bioactive with significant therapeutic activity against multiple ailments including wound healing. The poor aqueous solubility and low skin permeability limit its therapeutic efficacy. The present investigation aimed to improve the biopharmaceutical attributes of thymoquinone to enhance its topical efficacy in wound healing. A nanoemulsion-based hydrogel system was designed and characterized as a nanotechnology-mediated drug delivery approach to improve the therapeutic efficacy of thymoquinone, utilizing a high-energy emulsification technique. The black seed oil, as a natural home of thymoquinone, was utilized to improve the drug loading capacity of the developed nanoemulsion system and reduced the oil droplet size to <100 nm through ultrasonication. The influence of formulation composition, and the ultrasonication process conditions, were investigated on the mean globule size and polydispersity index of the generated nanoemulsion. Irrespective of surfactant/co-surfactant ratio and % concentration of surfactant/co-surfactant mixture, the ultrasonication time had a significant (p < 0.05) influence on the mean droplet size and polydispersity index of the generated nanoemulsion. The developed nanoemulgel system of thymoquinone demonstrated the pseudoplastic behavior with thixotropic properties, and this behavior is desirable for topical application. The nanoemulgel system of thymoquinone exhibited significant enhancement (p < 0.05) in skin penetrability and deposition characteristics after topical administration compared to the conventional hydrogel system. The developed nanoemulgel system of thymoquinone exhibited quicker and early healing in wounded Wistar rats compared to the conventional hydrogel of thymoquinone, while showing comparable healing efficacy with respect to marketed silver sulfadiazine (1%) cream. Furthermore, histopathology analysis of animals treated with a developed formulation system demonstrated the formation of the thick epidermal layer, papillary dermis along with the presence of extensive and organized collagen fibers in newly healed tissues. The outcome of this investigation signifies that topical delivery of thymoquinone through nanoemulgel system is a promising candidate which accelerates the process of wound healing in preclinical study.     

Thermal shock problem in a homogeneous isotropic hollow cylinder with energy dissipation

In this work, we constructed the equations of generalized thermoelasticity of a homogeneous isotropic hollow cylinder. The formulation is applied in the context of the Green and Naghdi theory of types II and III. The material of the cylinder is assumed to be homogeneous isotropic both mechanically and thermally. The problem has been solved numerically using a finite-element method. Numerical results for the temperature distribution, displacement, radial stress, and hoop stress are represented graphically. Comparisons are made with the results predicted by the types II and III. The results obtained in this paper can be used to design various homogeneous thermoelastic elements under thermal load to meet special engineering requirements.     

Porous silicon bandgap broadening at natural oxidation

Emission and excitation photoluminescence spectra of porous silicon thin layers have been investigated at natural oxidation. The shift of both types of spectra to high-energy region with time has been shown. Analysis of excitation spectra points out the indirect behavior of electron transitions responsible for visible photoluminescence, which remains unaltered at natural oxidation. The value of optical bandgap is estimated in each case. It is shown that the optical bandgap broadens during oxidation due to size reduction of silicon nanocrystallites.     

Some Transformations of Mono-and Dichloro(diethoxyphosphoryl)acetaldehydes

Addition of ethanol and diethyl phosphonate to the carbonyl group of 2,2-dichloro-2-(diethoxyphosphoryl)-acetaldehyde has been studied, and the corresponding α-chloro ether, acetal, and phosphorylated metrifonate have been obtained. α,α-Dichloro-α-phosphoryl carbonyl compounds have been found to undergo haloform cleavage by the action of bases. Perkow reaction of mono- and dichloro(diethoxyphosphoryl)acetaldehydes with triethyl phosphite afforded diethyl 2-(diethoxyphosphoryl)ethenyl phosphates.     

Stabilization of Highly Efficient and Stable Phase‐Pure FAPbI3 Perovskite Solar Cells by Molecularly Tailored 2D‐Overlayers

As a result of their attractive optoelectronic properties, metal halide APbI₃ perovskites employing formamidinium (FA⁺) as the A cation are the focus of research. The superior chemical and thermal stability of FA⁺ cations makes α‐FAPbI₃ more suitable for solar‐cell applications than methylammonium lead iodide (MAPbI₃). However, its spontaneous conversion into the yellow non‐perovskite phase (δ‐FAPbI₃) under ambient conditions poses a serious challenge for practical applications. Herein, we report on the stabilization of the desired α‐FAPbI₃ perovskite phase by protecting it with a two‐dimensional (2D) IBA₂FAPb₂I₇ (IBA=iso‐butylammonium overlayer, formed via stepwise annealing. The α‐FAPbI₃/IBA₂FAPb₂I₇ based perovskite solar cell (PSC) reached a high power conversion efficiency (PCE) of close to 23 %. In addition, it showed excellent operational stability, retaining around 85 % of its initial efficiency under severe combined heat and light stress, that is, simultaneous exposure with maximum power tracking to full simulated sunlight at 80 °C over 500 h.     

Differential Ion Mobility Separations in up to 100 % Helium Using Microchips

The performance of differential IMS (FAIMS) analyzers is much enhanced by gases comprising He, especially He/N₂ mixtures. However, electrical breakdown has limited the He fraction to ~50 %–75 %, depending on the field strength. By the Paschen law, the threshold field for breakdown increases at shorter distances. This allows FAIMS using chips with microscopic channels to utilize much stronger field intensities (E) than “full-size” analyzers with wider gaps. Here we show that those chips can employ higher He fractions up to 100 %. Use of He-rich gases improves the resolution and resolution/sensitivity balance substantially, although less than for full-size analyzers. The optimum He fraction is ~80 %, in line with first-principles theory. Hence, one can now measure the dependences of ion mobility on E in pure He, where ion-molecule cross section calculations are much more tractable than in other gases that form deeper and more complex interaction potentials. This capability may facilitate quantitative modeling of high-field ion mobility behavior and, thus, FAIMS separation properties, which would enable a priori extraction of structural information about the ions.

Detecting and Removing Data Artifacts in Hadamard Transform Ion Mobility-Mass Spectrometry Measurements

Applying Hadamard transform multiplexing to ion mobility separations (IMS) can significantly improve the signal-to-noise ratio and throughput for IMS coupled mass spectrometry (MS) measurements by increasing the ion utilization efficiency. However, it has been determined that fluctuations in ion intensity as well as spatial shifts in the multiplexed data lower the signal-to-noise ratios and appear as noise in downstream processing of the data. To address this problem, we have developed a novel algorithm that discovers and eliminates data artifacts. The algorithm employs an analytical approach to identify and remove artifacts from the data, decreasing the likelihood of false identifications in subsequent data processing. Following application of the algorithm, IMS-MS measurement sensitivity is greatly increased and artifacts that previously limited the utility of applying the Hadamard transform to IMS are avoided. Figure

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Effect of bromide salts on the acid hydrolysis of anti-bacterial hydrophilic Schiff base amino acid iron(II) complexes

Salt effects on the kinetics of acid hydrolysis of some novel hydrophilic iron(II) complexes have been investigated in aqueous medium. The ligands are derived from the condensation of amino acids (glycine, L-alanine, L-leucine, L-isoleucine, DL-methionine, DL-serine or L-phenylalanine) and sodium 2-hydroxybenzaldehyde-5-sulfonate. The reaction was studied under conditions of pseudo first order kinetics. The general rate equation was suggested as follows: rate = k _obs[complex], where k _obs = k ₂[H⁺]. The reaction rate decreases with an increase of the salt concentration.