Nonsedating anxiolytics.

Anxiety disorders are the most prevalent psychiatric pathology with substantial cost to society, but the existing treatments are often inadequate. This has rekindled the interest in the GABA-receptor (GABAR) positive allosteric modulator (PAM) compounds, which have a long history in treatment of anxiety beginning with diazepam, chlordiazepoxide, and alprazolam. While the GABAR PAMs possess remarkable anxiolytic efficacy, they have fallen out of favor due to a host of adverse effects including sedation, motor impairment, addictive potential and tolerance development.

Antibacterial and anti-biofilm activities of new fluoroquinolone derivatives coupled with nitrogen-based heterocycles.

We report the design, synthesis, and antimicrobial evaluation of a series of ciprofloxacin (CP) conjugates coupled with nitrogen-containing heterocycles. In vitro screening of these new hybrid compounds (1-13) against a panel of planktonic bacterial strains highlighted thiazolyl homologs 6 and 7 as the most promising candidates for further investigation. These derivatives demonstrated potent growth-inhibitory activity against various standard and clinical isolates, with minimum inhibitory concentrations (MICs) ranging from 0.

1,3-Disubstituted thiourea derivatives: Promising candidates for medicinal applications with enhanced cytotoxic effects on cancer cells.

The distinct chemical structure of thiourea derivatives provides them with an advantage in selectively targeting cancer cells. In our previous study, we selected the most potent compounds, 2 and 8, with 3,4-dichloro- and 3-trifluoromethylphenyl substituents, respectively, across colorectal (SW480 and SW620), prostate (PC3), and leukemia (K-562) cancer cell lines, as well as non-tumor HaCaT cells. Our research has demonstrated their anticancer potential by targeting key molecular pathways involved in cancer progression, including caspase 3/7 activation, NF-κB (Nuclear Factor Kappa-light-chain-enhancer of activated B cells) activation decrease, VEGF (Vascular Endothelial Growth Factor) secretion, ROS (Reactive Oxygen Species) production, and metabolite profile alterations.

Cognitive asymmetry in rats in response to emergent vs. disappearing affordances.

This study examines the effects of novel environmental changes on the behavior of rats in an experimental chamber. We hypothesized that newly discovered opportunities, detected by the animal's cognitive system, would motivate greater investigation of environmental changes than comparable changes that prevent a given behavior. Three experiments differed in the emergence vs.

Characteristics, toxicology and major organ pathology of deaths due to acute alcohol toxicity in Australia, 2011-2022.

Introduction: Acute alcohol toxicity is a significant component of alcohol-related mortality. The study aimed to: (i) determine the circumstances of death and characteristics of fatal alcohol toxicity cases, 2011-2022; (ii) determine their toxicological profile and major autopsy findings; and (iii) determine trends in population mortality rates.

Methods: Retrospective study of acute alcohol toxicity deaths in Australia, 2011-2022, retrieved from the National Coronial Information System.

Nanostructure and thermal characteristics of silica/human serum albumin systems based on a modified nanosilica entero-vulnerosorbent.

Entero-vulnerosorbents based on geometrically modified (GM) (mechanical treatment at different times, = 1, 4, and 7 h) fumed nanosilica A300 (NS) and protein molecules (human serum albumin/GM-nanosilica systems) were characterized with a focus on their surface, morphology, topography, and thermal properties. Microscopic, spectroscopic, and analytical techniques, including atomic force microscopy (AFM), optical profilometry (OP), high-resolution transmission electron microscopy (HRTEM), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), and elemental analysis (CHN), were used. The differentiation in the surface morphology, micro-nanoroughness, surface chemistry, thermal properties of the silica support, and protein/nanosilica systems were found.

Multiplexed Surface Electrode Arrays Based on Metal Oxide Thin-Film Electronics for High-Resolution Cortical Mapping.

Electrode grids are used in neuroscience research and clinical practice to record electrical activity from the surface of the brain. However, existing passive electrocorticography (ECoG) technologies are unable to offer both high spatial resolution and wide cortical coverage, while ensuring a compact acquisition system. The electrode count and density are restricted by the fact that each electrode must be individually wired.

Physicochemical, structural, and adsorption characteristics of DMSPS--DVB nanopolymers.

The aim of this work is the synthesis and characterization of the series of S,S'-thiodi-4,1-phenylene bis(thio-methacrylate)--divinylbenzene (DMSPS--DVB) nanomaterials. The series of new nanopolymers including three mixed systems with different ratios of DMSPS and DVB components, DMSPS--DVB = 1:1, DMSPS--DVB = 1:2, and DMSPS--DVB = 1:3, was synthesized in the polymerization reaction. The research task is to investigate the influence of the reaction mixture composition on morphological, textural, and structural properties of final nanosystems including size, shape, and agglomeration effect.

Proapoptotic effects of halogenated bis-phenylthiourea derivatives in cancer cells.

New halogenated thiourea derivatives were synthesized via the reaction of substituted phenylisothiocyanates with aromatic amines. Their cytotoxic activity was examined in in vitro studies against solid tumors (SW480, SW620, PC3), a hematological malignance (K-562), and normal keratinocytes (HaCaT). Most of the compounds were more effective against SW480 (1a, 3a, 3b, 5j), K-562 (2b, 3a, 4a), or PC3 (5d) cells than cisplatin, with favorable selectivity.

Reactivity to pseudorandom environmental patterns in woodlice: Effects of hydric deprivation and light exposure.

Exploratory activity is an essential component of animal behavior, including among invertebrate species. This study examined the effects of hydric deprivation and their possible modulation by light exposure on locomotion and rearing-up behavior in two woodlice species, Porcellio scaber (Latreille 1804) and Armadillidium vulgare (Latreille 1804). It was also an attempt to replicate previous findings on the stimulation of these behaviors in P.

Conformational degrees of freedom and stability of splay-bend ordering in the limit of a very strong planar anchoring.

We study the self-organization in a monolayer (a two-dimensional system) of flexible planar trimer particles. The molecules are made up of two mesogenic units linked by a spacer, all of which are modeled as hard needles of the same length. Each molecule can dynamically adopt two conformational states: an achiral bent-shaped (cis-) and a chiral zigzag (trans-) one.

Interaction of Bis-(sodium-sulfopropyl)-Disulfide and Polyethylene Glycol on the Copper Electrodeposited Layer by Time-of-Flight Secondary-Ion Mass Spectrometry.

The interactions of the functional additives SPS (bis-(sodium-sulfopropyl)-disulfide) and polyethylene glycol (PEG) in the presence of chloride ions were studied by time-of-flight secondary-ion mass spectrometry (TOF-SIMS) in combination with cyclic voltammetry measurements (CV). The PEG, thiolate, and chloride surface coverages were estimated and discussed in terms of their electrochemical suppressing/accelerating abilities. The conformational influence of both the gauche/trans thiolate molecules, as well as around C-C and C-O of PEG, on the electrochemical properties were discussed.

Anticancer activity and metabolic alteration in colon and prostate cancer cells by novel moxifloxacin conjugates with fatty acids.

The positive and pro-economic trend in the management of cancer treatment is the search for the antineoplastic potential of known, widely used and safe drugs with a different clinical purpose. A good candidate seems to be moxifloxacin with broad-spectrum antibacterial activity, which as the member of the fourth generation fluoroquinolone is known to affect not only bacterial but also eukaryotic DNA topoisomerases, however at high concentration. Due to the fact that the modification of parent drug with lipid component can improve anticancer potential by increasing of bioavailability, selectivity, and cytotoxic efficiency, we evaluated the mechanisms of cytotoxic activity of novel moxifloxacin conjugates with fatty acids and verified metabolic profile in SW480, SW620 and PC3 cell lines.

Synthesis, Structural Characterization and Biological Activity Evaluation of Novel Cu(II) Complexes with 3-(trifluoromethyl)phenylthiourea Derivatives.

Copper complexes with 1,3-disubstituted thiourea derivatives, all containing 3-(trifluoromethyl)phenyl tail and 1-alkyl/halogen-phenyl substituent, were synthesized. The experimental spectroscopic studies and theoretical calculation revealed that two ligands coordinate to Cu(II) in a bidentate fashion via thiocarbonyl S and deprotonated N atoms of thiourea moiety. Such monomers are characteristic of alkylphenylthiourea complexes, whereas the formation of a sandwich-type dimer is observed for halogeno derivatives.

Rat's response to a novelty and increased complexity of the environment resulting from the introduction of movable vs. stationary objects in the free exploration test.

Most animals, including rats, show a preference for more complex environments. This is demonstrated particularly well when complexity increases due to the addition of new elements to the environment. The aim of the study was to investigate the reaction to novelty, understood as a change in environmental properties that involve both changes in complexity and controllability.

Rates, characteristics and toxicology of cocaine-related deaths in Australia, 2000-2021.

Aims: To (i) assess the population mortality rates of cocaine-related deaths in Australia, 2000 to 2021; (ii) determine the circumstances of death and case characteristics; and (iii) determine their toxicological profile.

Design: Retrospective study of cocaine-related deaths in Australia, 2000 to 2021, retrieved from the National Coronial Information System.

Setting: Australia-wide.

Decrease in the rewarding value of spatial novelty due to the contamination of the stimulus field with light - Evidence from a free exploration test involving rats.

It has been shown that rearranging the spatial properties of a familiar environment consistently elicits a positive response in rats directed toward the source of novelty. Previous studies have been conducted under red light or darkness. The purpose of this study was to test the effect of rearranging the spatial properties of a familiar environment in conjunction with a change in lighting conditions.

Influence of excessive sucrose consumption on exploratory behaviour in rats - Possible implications for the brain reward system.

Due to the low cost of production and the strong evolutionary preference for sweet taste in humans, sugar is added to many food products. This leads to often involuntary overconsumption of high amounts of sugar. Yet, growing evidence indicates that high-sugar diets impact brain function and impair cognitive ability.

Effect of geometric modification of fumed nanoscale silica for medical applications on adsorption of human serum albumin: Physicochemical and surface properties.

The influence of the geometric modification (GM) of fumed nanoscale silica A300 (NS) on the adsorption capacity of human serum albumin (HSA) as well as the physicochemical and textural properties of the protein/nanosilica system was analyzed. An effective medical enterosorbent based on fumed nanosilica was designed and produced in the Chuiko Institute of Surface Chemistry, National Academy of Sciences of Ukraine. To design an effective nanomaterial for biomedical applications as a wound-healing material, the adsorption, physicochemical and surface properties of the initial nanosilica (NS), nanosilica after geometric modification (GM-nanosilica), and HSA/nanosilica biocomposites were characterized.

The New Face of a Well-Known Antibiotic: A Review of the Anticancer Activity of Enoxacin and Its Derivatives.

Enoxacin as a second-generation synthetic quinolone is known for its antibacterial action; however, in recent years there have been studies focusing on its anticancer potential. Interestingly, it turns out that compared to other fluoroquinolones, enoxacin exhibits uncommon cytotoxic properties. Besides its influence on apoptosis, the cell cycle and cell growth, it exhibits a regulatory action on microRNA biogenesis.

The Effect of Conjugation of Ciprofloxacin and Moxifloxacin with Fatty Acids on Their Antibacterial and Anticancer Activity.

Novel conjugates (CP) of moxifloxacin (MXF) with fatty acids (-) were synthesized with good yields utilizing amides chemistry. They exhibit a more pronounced cytotoxic potential than the parent drug. They were the most effective for prostate cancer cells with an IC below 5 µM for respective conjugates with sorbic (), oleic (), 6-heptenoic (), linoleic (), caprylic (), and stearic () acids.