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Distressful and negative affective states can be associated with limited self-regulation capacities, while emotion regulation processes (e.g., rumination, negative urgency) might contribute to further depletion of self-control capacities which in turn can lead to diminished control over cannabis use. The mediating functions of rumination (i.e., brooding and reflection), negative urgency (NU) and constructs of cannabis use regulation (i.e., cannabis protective behavioral strategies [CPBS] and cannabis refusal self-efficacy [CRSE]) were examined on the associations between anxious-depressive symptoms and cannabis use outcomes (i.e., frequency, harmful use). The cross-sectional study used a sample of cannabis users showing signs of harmful consumption (N = 750; Males: 70.13% [N = 526]; Age: M = 29.11 [SD = 7.45]). Standardized questionnaires measured anxious-depressive symptoms, rumination, NU, CRSE, CPBS, frequency of cannabis use and harmful cannabis use. A linear regression-based, double-mediation model was performed. Five significant indirect effects were demonstrated in the mediation model. Single-mediation effects were shown between anxious-depressive symptoms and harmful cannabis use via CRSE and via CPBS. Double-mediation effects were presented between anxious-depressive symptoms and harmful cannabis use via reflection and CPBS, via reflection and CRSE, and via NU and CRSE. Emotion and cannabis use regulation pathways explained the associations between anxious-depressive symptoms and harmful cannabis use. The mediation model provided new details on how anxious-depressive symptoms, rumination and NU might lead to harmful cannabis use via regulation of cannabis use. Limited self-regulation capacities and similarities between emotion and cannabis use regulation processes might explain the identified indirect effects. •Emotion and substance use regulation pathways were tested between anxious-depressive symptoms and harmful cannabis use.•Indirect effects were shown via cannabis refusal self-efficacy, and via cannabis protective behavioral strategies.•Double-mediation pathways were shown via reflection and protective behavioral strategies, and refusal self-efficacy.•A double-mediation pathway was shown via negative urgency and cannabis refusal self-efficacy.

Additionally, in March and May, 2014, two incident cases of HIV were detected among PWIDs. Since around 2010, the number of new psychoactive substances (NPS; also known as designer drugs or legal highs) in Europe has almost exponentially increased.2 NPS have overwhelmingly replaced traditional drugs, such as cannabis, amphetamines, and heroin, in Hungary.

This paper reports on the application of experimental optical methods to study vibration of the centrally clamped disc. The natural frequencies and mode shapes with zero rotational speed are analyzed. Influence of rotational velocity to shifting natural frequencies was investigated with optical derotator. To evaluate shifting of natural frequencies run up analysis were measured. In run-up analysis the frequencies of centrally clamped disc considering increased rotational speed are obtained. Obtained waterfall plots show vibration behavior of spinning disc.

In this study, we investigated a novel anti-cancer drug design approach by revisiting diclofenac-based carborane-substituted prodrugs. The redesigned compounds combine the robust carborane scaffold with the oxindole framework, resulting in four carborane-derivatized oxindoles and a unique zwitterionic amidine featuring a nido -cluster. We tested the anti-cancer potential of these prodrugs against murine colon adenocarcinoma (MC38), human colorectal carcinoma (HCT116), and human colorectal adenocarcinoma (HT29). The tests showed that diclofenac and the carborane-substituted oxindoles exhibited no cytotoxicity, the dichlorophenyl-substituted oxindole had moderate anti-cancer activity, while with the amidine this effect was strongly potentiated with activity mapping within low micromolar range. Compound 3 abolished the viability of selected colon cancer cell line MC38 preferentially through strong inhibition of cell division and moderate apoptosis accompanied by ROS/RNS depletion. Our findings suggest that carborane-based prodrugs could be a promising direction for new anti-cancer therapies. Inhibition assays for COX-1 and COX-2 revealed that while diclofenac had strong COX inhibition, the re-engineered carborane compounds demonstrated a varied range of anti-cancer effects, probably owing to both, COX inhibition and COX-independent pathways.

Small-cell lung carcinoma (SCLC) remains one of the most aggressive lung cancers and continues to pose a major challenge for precision oncology. Despite its morphological uniformity, SCLC exhibits marked molecular heterogeneity with recurrent, potentially targetable genomic alterations. Comprehensive profiling is often hindered by limited tissue availability and the need for rapid therapeutic intervention. We performed genomic profiling of 55 primary and metastatic SCLC samples using a 324-gene hybrid-capture next-generation sequencing panel. Consistent with prior reports, nearly all tumors exhibited biallelic and inactivation. Recurrent alterations involved the PI3K/Akt/mTOR pathway (62%), chromatin regulators (42%), and NOTCH signaling genes (15%). mutations were enriched in brain metastases. Frequent copy-number gains affected , , MYC-family genes, and . Two novel recurrent amplifications of potential clinical significance were identified: (33%) and (13%). , a TAM family receptor tyrosine kinase, and , a mitochondrial enzyme involved in succinate metabolism, may contribute to tumor progression and represent emerging therapeutic vulnerabilities. These findings underscore the genomic diversity of SCLC and highlight the potential utility of broad next-generation sequencing in uncovering new molecular targets for precision therapy.

Success of chemotherapy is often hampered by multidrug resistance. One mechanism for drug resistance is the elimination of anticancer drugs through drug transporters, such as breast cancer resistance protein (BCRP; also known as ABCG2), and causes a poor 5‐year survival rate of human patients. Co‐treatment of chemotherapeutics and natural compounds, such as baicalein, is used to prevent chemotherapeutic resistance but is limited by rapid metabolism. Boron‐based clusters as meta‐carborane are very promising phenyl mimetics to increase target affinity; we therefore investigated the replacement of a phenyl ring in baicalein by a meta‐carborane to improve its affinity towards the human ABCG2 efflux transporter. Baicalein strongly inhibited the ABCG2‐mediated efflux and caused a fivefold increase in mitoxantrone cytotoxicity. Whereas the baicalein derivative 5,6,7‐trimethoxyflavone inhibited ABCG2 efflux activity in a concentration of 5 μm without reversing mitoxantrone resistance, its carborane analogue 5,6,7‐trimethoxyborcalein significantly enhanced the inhibitory effects in nanomolar ranges (0.1 μm) and caused a stronger increase in mitoxantrone toxicity reaching similar values as Ko143, a potent ABCG2 inhibitor. Overall, in silico docking and in vitro studies demonstrated that the modification of baicalein with meta‐carborane and three methoxy substituents leads to an enhanced reversal of ABCG2‐mediated drug resistance. Thus, this seems to be a promising basis for the development of efficient ABCG2 inhibitors. Multidrug resistance mediated by the breast cancer resistance protein (BCRP, ABCG2) is challenging in cancer therapy. Therefore, combined use of ABCG2 inhibitors with anticancer agents seems to be useful to overcome drug resistance. Based on baicalein, used in traditional Chinese medicine, we replaced a phenyl group by boran‐based cluster (meta‐carborane) to enhance ABCG2 inhibition and successfully reversed mitoxantrone resistance.

Owing to the involvement of cyclooxygenase-2 (COX-2) in carcinogenesis, COX-2-selective inhibitors are increasingly studied for their potential cytotoxic properties. Moreover, the incorporation of carboranes in structures of established anti-inflammatory drugs can improve the potency and metabolic stability of the inhibitors. Herein, we report the synthesis of carborane-containing derivatives of rofecoxib that display remarkable cytotoxic or cytostatic activity in the micromolar range with excellent selectivity for melanoma and colon cancer cell lines over normal cells. Furthermore, it was shown that the carborane-modified derivatives of rofecoxib showed different modes of action that were dependent on the cell type.

Optimization is a mathematical discipline or tool suitable for minimizing or maximizing a function. It has been largely used in every scientific field to solve problems where it is necessary to find a local or global optimum. In the engineering field of localization, optimization has been adopted too, and in the literature, there are several proposals and applications that have been presented. In the first part of this article, the optimization problem is presented by considering the subject from a purely theoretical point of view and both single objective (SO) optimization and multi-objective (MO) optimization problems are defined. Additionally, it is reported how local and global optimization problems can be tackled differently, and the main characteristics of the related algorithms are outlined. In the second part of the article, extensive research about local and global localization algorithms is reported and some optimization methods for local and global optimum algorithms, such as the Gauss–Newton method, Genetic Algorithm (GA), Particle Swarm Optimization (PSO), Differential Evolution (DE), and so on, are presented; for each of them, the main concept on which the algorithm is based, the mathematical model, and an example of the application proposed in the literature for localization purposes are reported. Among all investigated methods, the metaheuristic algorithms, which do not exploit gradient information, are the most suitable to solve localization problems due to their flexibility and capability in solving non-convex and non-linear optimization functions.

In our research six different mint species (peppermint, spearmint (five different chemotypes), Horse mint, mojito mint, apple mint (two different chemotypes), bergamot mint) have been evaluated by referring to their chemical (essential oil (EO) content and composition) and in vitro biological (antibacterial, antioxidant effect) characteristics. The EO amount of the analyzed mint populations varied between 1.99 and 3.61 mL/100 g d.w. Altogether, 98 volatile compounds have been detected in the oils. Antibacterial effects (inhibition zones, MIC, IC50 and MBC) were evaluated against Escherichia coli, Salmonella enterica, Bacillus cereus and Staphylococcus aureus. The best antibacterial effect was given by a carvacrol–thymol chemotype spearmint population (inhibition zone: 18.00–20.00 mm, MIC: 0.06 v/v%, IC50: 0.01–0.03 v/v%, MBC: 0.06, >2.00 v/v%). The least effective oil in the case of Gram-negative bacteria was bergamot mint (inhibition zone: 7.67–8.67 mm, MIC: 2.00, >2.00 v/v%, IC50: 0.11–0.25 v/v%, MBC: 2.00, >2.00 v/v%), while in the case of Gram-positive bacteria, oils containing dihydrocarvone as the main compound possessed the weakest antibacterial effect (inhibition zone: 9.00–10.00 mm, MIC: 1.00–2.00 v/v%, IC50: 0.22–0.37 v/v%, MBC: >2.00 v/v%). Interestingly, none of the oils could kill B. cereus in the applied concentrations.

Ruthenium-based complexes have received much interest as potential metallodrugs. In this work, four RuII complexes bearing a dicarbollide moiety, a carbonyl ligand, and a phenanthroline-based ligand were synthesized and characterized, including single crystal diffraction analysis of compounds 2, 4, and 5 and an observed side product SP1. Complexes 2–5 are air and moisture stable under ambient conditions. They show excellent solubility in organic solvents, but low solubility in water.