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The commercial veterinary antibiotic sodium monensinate (MonNa) binds mercury(II) or zinc(II) cations as thiocyanate [Hg(MonNa)2(SCN)2] (1) or isothiocyanate [Zn(MonNa)2(NCS)2] (2) neutral coordination compounds. The structure and physicochemical properties of 1 and 2 were evaluated by the methods of single crystal and/or powder X-ray diffraction, infrared, nuclear magnetic resonance, X-ray photoelectron spectroscopies, and electrospray-mass spectrometry. The primary cores of the two complexes comprise HgS2O2 (1) and ZnN2O2 (2) coordination motifs, respectively, due to the ambidentate binding modes of the SCN–ligands. The directly bound oxygen atoms originate from the carboxylate function of the parent antibiotic. Sodium cations remain in the hydrophilic cavity of monensin and cannot be replaced by the competing divalent metal ions. Zinc(II) binding does not influence the monensin efficacy in the case of Bacillus cereus and Staphylococcus aureus whereas the antimicrobial assay reveals the potential of complex 2 as a therapeutic candidate for the treatment of infections caused by Bacillus subtilis, Kocuria rhizophila, and Staphylococcus saprophyticus.

ABSTRACTInfection with the parasite Toxoplasma gondii leads to production of interferon gamma (IFNγ) that stimulates cells to upregulate defense proteins targeting the parasite for cell intrinsic elimination or growth restriction. Various host defense mechanisms operate at the parasitophorous vacuole (PV) in different human cell types leading to PV disruption, acidification, or membrane envelopment. Ubiquitin and p62 are players in all human host control mechanisms of Toxoplasma, but other unifying proteins have not been identified. Here, we show that p97/valosin-containing protein (VCP), as well as its associated proteins ANKRD13A and UBXD1 control Toxoplasma infection while recruited to the PV in IFNγ-stimulated endothelial cells. Convergent deposition of ANKRD13A, p97/VCP, and UBXD1 onto the same vacuole is dependent on vacuolar ubiquitination and observed within 2 h post-infection. ANKRD13A, p97/VCP, and UBXD1 all drive the acidification mechanism of the vacuole, which is the IFNγ-dependent control pathway of Toxoplasma in endothelial cells. We assessed p97/VCP in Toxoplasma control in various human cells and demonstrate that p97/VCP is a universal IFNγ-dependent host restriction factor targeting the Toxoplasma PV in epithelial (HeLa) and endothelial cells (human umbilical vein endothelial cells), fibroblasts (human foreskin fibroblast), and macrophages (THP1).IMPORTANCEToxoplasma gondii (Tg) is a ubiquitous parasitic pathogen, infecting about one-third of the global population. Tg is controlled in immunocompetent people by mechanisms that are not fully understood. Tg infection drives the production of the inflammatory cytokine interferon gamma (IFNγ), which upregulates intracellular anti-pathogen defense pathways. In this study, we describe host proteins p97/VCP, UBXD1, and ANKRD13A that control Tg at the parasitophorous vacuole (PV) in IFNγ-stimulated endothelial cells. p97/VCP is an ATPase that interacts with a network of cofactors and is active in a wide range of ubiquitin-dependent cellular processes. We demonstrate that PV ubiquitination is a pre-requisite for recruitment of these host defense proteins, and their deposition directs Tg PVs to acidification in endothelial cells. We show that p97/VCP universally targets PVs in human cells and restricts Tg in different human cell types. Overall, these findings reveal new players of intracellular host defense of a vacuolated pathogen.

Two trinuclear oxo-centred iron(III) coordination compounds of monensic and salinomycinic acids (HL) were synthesized and their spectral properties were studied using physicochemical/thermal methods (FT–IR, TG–DTA, TG–MS, EPR, Mössbauer spectroscopy, powder XRD) and elemental analysis. The data suggested the formation of [Fe3(µ3–O)L3(OH)4] and the probable complex structures were modelled using the DFT method. The computed spectral parameters of the optimized constructs were compared to the experimentally measured ones. In each complex, three metal centres were joined together at the axial position by a μ3–O unit to form a {Fe3O}7+ core. The antibiotics monoanions served as bidentate ligands through the carboxylate and hydroxyl groups located at the termini. The carboxylate moieties played a dual role bridging each two metal centres. Hydroxide anions secured the overall neutral character of the coordination species. Mössbauer spectra displayed asymmetric quadrupole doublets that were consistent with the existence of two types of high-spin iron(III) sites with different environments—two Fe[O5] and one Fe[O6] centres. The solid-state EPR studies confirmed the +3 oxidation state of iron with a total spin St = 5/2 per trinuclear cluster. The studied complexes are the first iron(III) coordination compounds of monensin and salinomycin reported so far.

Cold stress-induced analgesia (c-SIA) has been evaluated in male Wistar rats injected with cannabinoid receptors type 1 and a2-adrenergic receptor agonists and antagonists in different combinations before or after stress exposure. The aim of the study was to evaluate whether the endogenous cannabinoid and the adrenergic systems influenced c-SIA, and the patterns of their potential interaction. Exogenous administration of anandamide and Clonidine together, before or after stress exposure, increased c-SIA even with differences in the time of manifestation of the effect, its duration and the degree. The two systems differently contribute to c-SIA pathogenesis and mediation. Administered before stress exposure cannabinoids and the adrenergic system seem to oppose each other: the latter rather potentiates, while cannabinoids suppress c-SIA. Administered after stress exposure, instead, the two systems appear to exert a synergistic effect, and antagonization of each one of them abolishes the analgesic effect.

Social isolation (SI) exerts a harmful effect on brain plasticity even in healthy animals and humans. We reported some new connections between aggressive behavior and SI, and new mechanisms of SI damaging effect on experimental rodents in previous studies. SARS-CoV-2 exhibits neurotropism through its affinity for the ACE2 receptor in endothelial cells found in the brain. The neurotropism in the disease caused by the new coronavirus accords with a wide spectrum of neurological, psychiatric and psychological symptoms. It had been reported that up to almost 43 % of SARS survivors developed long-lasting psychiatric morbidity that persisted at 4 years follow up with main diagnoses in diminishing order of representation: posttraumatic stress disorders, depression, panic disorder, and obsessive-compulsive disorder. Full assessment of the long-term risk of neurological and psychological complications will be greatly needed once the coronavirus pandemic is over. Based on current data and the reported experience with SARS-CoV we hypothesize that the neurobehavioral sequelae of the disease caused by SARS-CoV-2 will necessitate close interaction between emergency medicine and psychological support. The role of social support for the restoration of post-Covid neuropsychological damage is essential because the human being is not only a biological object but also a social subject who needs support from other humans.

The synthesis and characterization of two new water soluble 2,6-bis(imidazolylmethyl)-4-methylphenoxy-containing perylenediimides, PDI-1 and PDI-2, are described. These compounds demonstrate a high fluorescence quantum yield in water and were investigated as potential photosensitizers for generating reactive oxygen species with applications in anticancer activities. The HeLa cell line (VPH18) was used to evaluate their efficacy. Fluorescence microscopy was employed to confirm the successful internalization of PDI-1 and PDI-2, while confocal microscopy revealed the specific locations of both PDIs within the lysosomes and mitochondria. In vitro studies were conducted to evaluate the anticancer activity of PDI-1 and PDI-2. Remarkably, these photosensitizers demonstrated a significant ability to selectively eliminate cancer cells when exposed to a specific light wavelength. The water solubility, high fluorescence quantum yield, and selective cytotoxicity of these PDIs toward cancer cells highlight their potential as effective agents for targeted photodynamic therapy. In conclusion, the findings presented here provide a strong foundation for the future exploration and optimization of PDI-1 and PDI-2 as effective photosensitizers in photodynamic therapy, potentially leading to improved treatment strategies for cancer patients.

The synthesis of orthoferrites of the type La1−xCexFeO3+x/2, x = 0.00, 0.01, 0.03, 0.05, and 0.07, by applying a simple and effective mechanochemical transformation from the constituent oxides is presented. Physicochemical methods such as powder X-ray diffraction (XRD), transmission electron microscopy (TEM), UV–Vis spectroscopy, and Brunauer–Emmett–Teller (BET) adsorption were applied to gain information about the effect of Ce4+ content on the structural, textural, and optical properties of the samples. The catalytic activity of the samples for water decontamination was determined in a photo-Fenton-like activation of persulfate for removal of tetracycline hydrochloride as model pollutant. The presence of persulfate, PDS, considerably increased the removal efficiency under visible light illumination.

The tumor suppressor FBW7 is a substrate adaptor for the E3 ubiquitin ligase complex SKP1-CUL1-F-box (SCF) and itself a target for ubiquitylation. Here, the authors show that TRIP12 mediates branched K11-linked ubiquitylation of FBW7, to regulate its stability and thus abundance of a subset of SCFFBW7 substrates.

Introduction: We present a patient with carcinoma of the tongue with а lymph node and thyroid metastasеs. The squamous cell cancer of the tongue’s 5-year survival rate has not been improved in the last three decades. Most common sites of metastases are the locoregional lymph nodes, followed by distant pulmonary, liver, bone and skin metastasеs. Only ten cases of metastases to the thyroid gland are reported in the literature. Case report: A 79-year old man presented to the University Hospital in Varna, Bulgaria. Two months before admission, he noticed swelling of the tongue and progressive weight loss. The inspection of the oral cavity revealed a lesion on the left margin of the tongue. A biopsy was performed with a histological result of differentiated squamous cell carcinoma of the tongue. A computed tomography scan of the head and neck region discovered a lesion in the right thyroid lobe. 18-fluoro-2-deoxy-glucose-positron emission tomography imaging showed a metabolically active tumor of the tongue with hypermetabolic metastatic cervical lymph nodes and a zone with abnormally elevated fixation of 18F-FDG in the central part of the soft palate. The described thyroid nodule did not have an increased tracer uptake. It was cytologically assessed after fine-needle aspiration biopsy (FNAB) as a metastasis from squamous cell carcinoma of the tongue. Conclusions: Distant metastases from tongue cancer to the thyroid gland are extremely rare and mostly occur in the advanced stages of malignancy.

ZnFe2O4/rGO/g-C3N4 ternary nanocomposite photocatalysts with different ZnFe2O4/g-C3N4 weight ratio (0.5, 0.75, 1) were prepared by a stepwise solvothermal method using ethylene glycol as the solvent. Physicochemical methods such as X-ray diffraction, UV-Vis diffuse reflectance spectroscopy and photoluminescence spectroscopy were applied in order to characterize the composites. The formation of a meso-/macroporous structure with specific surface area between 67 and 77 m2 g‒1 was confirmed by N2 adsorption/desorption. The bandgap of the composites was found to be lower (2.30 eV) than that of g-C3N4 (2.7 eV). In contrast to pure g-C3N4, the composites showed no fluorescence, i.e. no recombination of e‒/h+ took place. All samples, including pure g-C3N4 and ZnFe2O4, were tested for adsorption and photocatalytic degradation of aqueous malachite green model solutions (10‒5 M) under visible light irradiation (λ >400 nm). The results show that the prepared nanocomposites have higher absorption and photocatalytic activity than the pristine g-C3N4 and ZnFe2O4 and can be successfully used for water purification from organic azo-dyes.