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After three years of polarimetric monitoring of blazars, the RoboPol project has uncovered several key characteristics of polarimetric rotations in the optical for these most variable sources. The most important of these is that polarization properties of the synchrotron emission in the optical appear to be directly linked with gamma-ray activity. In this paper, we discuss the evidence for this connection, as well as the broader features of polarimetric behavior in blazars that are key in making progress with theoretical modeling of blazar emission.

2-Amino-4H-chromene derivatives possess anticancer property proved on different in vivo and in vitro models of malignancies such breast, nasopharyngeal, bladder, ovary carcinomas, astrocytoma, and osteosarcoma. We assumed it might be effective to apply one of the derivatives as promising approach to lung carcinoma treatment. to evaluate how novel 4-aryl substituted 2-amino-4H-chromene derivative AX-554 impacts tumor growth and progression, as well as possible mechanisms for anticancer effect development on in vivo patient-derived heterotopic xenograft model of lung carcinoma in mice. This was an experimental in vivo study. 40 nu/nu BALB/c female mice were randomly allocated into four equal groups: Intact, control, reference, and main group. Animals of three latter groups were ingrafted with human-derived lung adenocarcinoma. Antitumor and antimetastatic action of AX-554 novel aminochromone derivative as a substance were studied. Mice survival was registered. Kinase of anaplastic lymphoma (ALK), tubulin Beta-3 (TUBB3), and c-mesenchymal-epithelial transition (MET) concentrations in the prime tumor nodes homogenates were determined by quantitative enzyme-linked immunosorbent assay. Dannet's parametric criterion and the nonparametric exact Fisher test were used. The normality of the distribution was determined using ANOVA. The survival curve was analyzed using Gehan's criterion with the Yates's correction. Aminochromone derivative possesses an inhibitory effect on human lung adenocarcinoma transplanted into nu/nu BALB/c female mice, as well as significant antimetastatic activity. About 50 mg/kg/day AX-554 intragastric course increases animals' life expectancy of more than 3.3 times when compared with the control and induces remission in 60% of cases. The anticancer effect of the derivative is due to anti-ALK-mediated activation of tumor cells apoptosis and suppression TUBB3-dependent cell proliferation.

Significant progress in the installation of renewable energy requires the improvement of energy production and storage technologies. Hydrogen energy storage systems based on reversible metal hydride materials can be used as an energy backup system. Metal hydride hydrogen storage systems are distinguished by a high degree of safety of their use, since hydrogen is stored in a solid phase, a high volumetric density of stored hydrogen, and the possibility of long-term storage without losses. A distinctive feature of metal hydride materials is the reversible and selective absorption and release of high-purity hydrogen. This paper presents experimental studies of LaNi 5 -based metal hydride materials with a useful hydrogen capacity of 1.0–1.3 wt.% H 2 with equilibrium pressures of 0.025 - 0.05 MPa and 0.1 - 1.2 MPa at moderate temperatures of 295 - 353 K for the hydrogen purification systems and hydrogen long-term storage systems, respectively. The applicability of metal hydride technologies for renewable energy sources as energy storage systems in the form of hydrogen is also shown.

The goal of this study was to assess how PD-L1 expression in tissue specimens of patients with main molecular subtypes of NMIBC (luminal, basal and double-negative p53-mutant) associates with relapsed-free survival in dependence on the tumor grade and prior treatment of primary bladder cancer. PD-L1 expressions on the membrane of neoplastic and CD8+ immune cells were assessed in tumor specimens (n = 240) of primary and relapsed luminal, basal and double-negative p53-mutant NMIBC. Association between relapse-free survival and PD-L1 expression was estimated for high- and low-grade relapsed NMIBC according to previous treatment and their molecular profile, using the Kaplan–Meier method, and assessed by using the log-rank test. Potential confounders were adjusted by Cox regression models. In a group of patients who underwent only TUR without intravesical therapy, there were significant differences in relapse time between high- and low-grade tumors in basal and luminal molecular subtypes; for basal relapsed carcinoma, RFS was shorter in cases where tumors were less malignant. Both intravesical mitomycin and Bacillus Calmette–Guerin (BCG) therapy significantly extended the time of recurrence of low-grade luminal and basal bladder malignancies with no intergroup differences in double-negative NMIBC. PD-L1 expression status was associated with RFS for luminal relapsed NMIBCs in the group without previous frontline intervention, and with RFS in the group of patients with luminal relapsed bladder cancer previously utilized BCG. Obtained results may be considered as a promising approach for further clinical implementation.

Background: bladder cancer is one of the most common urinary tract malignancies. Establishment of robust predictors of disease progression and outcome is important for personalizing treatment of non-muscular invasive bladder carcinoma (NMIBC). In this study we evaluated association of PD-L1 expression with other prognostic biomarkers, such as expression of miRNA-145 and miRNA-200a, FGFR3 gene expression, and mutation status in tissue specimens of the luminal subtype of newly diagnosed high and low grade NMIBC. Methods: twenty patients with primary luminal NMIBC were enrolled in the study. Tumor grade and risk level were determined in accordance with European Organization for Research and Treatment of Cancer (EORTC) guidelines and World Health Organization (WHO) classification. Neoplasm molecular subtype and PD-L1 expression level were assessed by immunohistochemistry. We used real-time PCR to evaluate the expression of microRNAs and FGFR3. We detected FGFR3 hotspot mutations in codons 248 and 249 by Sanger sequencing. Results: high grade primary luminal NMIBC showed comparatively higher expression of PD-L1 and microRNA-145 than a low grade tumor, whereas the latter had a higher FGFR3 expression and hotspot mutation rate. The tumor grade (HR = 571.72 [11.03–2.96] p = 0.002), PD-L1 expression (HR = 2.33 [0.92–1.92] p = 0.012), and FGFR3 expression (HR = 0.08 [0.17–0.42] p = 0.003) were associated with relapse-free survival. Conclusions: tumor grade in association with PD-L1 and FGFR3 expression can be considered as a complex predictor for primary luminal NMIBC progression.

Background: The main goal of our study was to explore the wound-healing property of a novel cerium-containing N-acethyl-6-aminohexanoate acid compound and determine key molecular targets of the compound mode of action in diabetic animals. Methods: Cerium N-acetyl-6-aminohexanoate (laboratory name LHT-8-17) as a 10 mg/mL aquatic spray was used as wound experimental topical therapy. LHT-8-17 toxicity was assessed in human skin epidermal cell culture using (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A linear wound was reproduced in 18 outbred white rats with streptozotocin-induced (60 mg/kg i.p.) diabetes; planar cutaneous defect was modelled in 60 C57Bl6 mice with streptozotocin-induced (200 mg/kg i.p.) diabetes and 90 diabetic db/db mice. Firmness of the forming scar was assessed mechanically. Skin defect covering was histologically evaluated on days 5, 10, 15, and 20. Tissue TNF-α, IL-1β and IL-10 levels were determined by quantitative ELISA. Oxidative stress activity was detected by Fe-induced chemiluminescence. Ki-67 expression and CD34 cell positivity were assessed using immunohistochemistry. FGFR3 gene expression was detected by real-time PCR. LHT-8-17 anti-microbial potency was assessed in wound tissues contaminated by MRSA. Results: LHT-8-17 4 mg twice daily accelerated linear and planar wound healing in animals with type 1 and type 2 diabetes. The formulated topical application depressed tissue TNF-α, IL-1β, and oxidative reaction activity along with sustaining both the IL-10 concentration and antioxidant capacity. LHT-8-17 induced Ki-67 positivity of fibroblasts and pro-keratinocytes, upregulated FGFR3 gene expression, and increased tissue vascularization. The formulation possessed anti-microbial properties. Conclusions: The obtained results allow us to consider the formulation as a promising pharmacological agent for diabetic wound topical treatment.

Background: Establishment of heterotopic patient-derived xenografts of primary and relapsed non-muscular invasive bladder cancer (NMIBC) to explore the biological property of PD-L1 signaling that may impact bladder tumor growth in humanized animals. Methods: Tumor cells of luminal, basal, and p53 subtypes of primary and relapsed NMIBC were engrafted to irradiated (3.5 Gy) NOG/SCID female mice along with intraperitoneal transplantation of human lymphocytes (5 × 107 cells/mouse); a role of PD-L1 signaling pathway inhibition for bladder cancer growth was assessed in humanized animals that carried PD-L1-expressing main molecular subtypes of bladder carcinoma patient-derived xenografts (PDX) and provided with selective anti-PD-L1 treatment. We used two-tailed Student’s t test to explore differences between main and control subgroups. Significance of intergroup comparison was measured with one-way ANOVA followed by the Tukey’s or Newman–Keul’s criterion. Survival curves were analyzed with the Gehan’s criterion with the Yate’s correction. The Spearman’s correlation was used to assess the link between CD8+ expression and sPD-L1 serum level. Differences were considered statistically significant at p < 0.05. Results: Heterotopic primary and relapsed luminal, basal, and p53 subtypes of NMIBC PDXs were established. More than 25% of counted tumor cells of all PDX specimens expressed PD-L1, so the tumors were ranged as PD-L1 positive. Anti-PD-L1 intervention increased survival of the animals that carried both primary and relapsed luminal noninvasive, muscular invasive, and relapsed luminal bladder cancer xenografts. There was significant retardation of tumor volume duplication time in aforementioned subgroups correlated with PD-L1 expression. Bad response of p53 mutant subtypes of NMIBC on specific anti-PD-L1 treatment may be associated with low CD8+ cells representation into the tumors tissue. Conclusions: Established PD-L1-positive NMIBC PDXs differently replied on anti-PD-L1 treatment due to both NMIBC molecular subtype and tumor T-suppressors population. The results may have major implications for further clinical investigations.

This paper presents the experimental results of the system integration of a fuel cell (FC), an electrolyzer and a metal hydride hydrogen storage and purification system. A pilot scale experimental power installation H2Smart with an electric power of 1 kW is developed, and the results of its operation in different regimes are presented. The problems of hydrogen desorption for the supply of FC and hydrogen sorption from the electrolyzer at the start are shown. Possible solutions of this problem are proposed.

Background. To evaluate acute toxicity and local anaesthetic activity of a formulation containing a novel dimethylacetamide derivative, antioxidant, and vasoconstrictor in rats with chronic periodontitis. Methods. Novel anaesthetic dimethylacetamide-containing formulation LHT-15-32 was studied as 2% water solution. Its acute intravenous and subcutaneous toxicity was determined in mice. Pain sensitivity threshold of the upper second molar was determined in rats with experimental periodontitis. Oxidative stress activity and total antioxidant capacity were determined in rats’ gingival mucosa by induced chemiluminescence. Local changes were evaluated in periodontal tissue by morphological examination. Tissue IL-1β, IL-10, and TNF-α concentration was quantitatively assessed by an enzyme-linked immunosorbent assay. LHT-15-31 Na-blocking activity was studied on isolated neurons of Limnaea stagnalis’ parapharyngeal ganglion. Isolated sciatic nerve of Rana radibunda was perfused with different concentrations of LHT-15-32 to assess its conductivity. Statistical analysis was used, and continuous variables were presented as mean ± square deviation. The normality of distribution was determined using ANOVA. Newman–Keuls parametric criterion was used for intergroup comparison. LD50 indexes were calculated by probit analysis. Results. LHT-15-32 acute intravenous and subcutaneous toxicity was lower than that of its active substance. The formulation by infraorbital administration induced deep dental anaesthesia which lasted over 70 min and activated the local antioxidant defense system and decreased IL-1β level in gingival tissue. LHT-15-32 triggered tissue reparation around the impacted upper molar in rats assessed five days after administration. At 10−6 to 10−3 M concentration, LHT-15-32 inhibited sciatic nerve conductivity and blocked Na+ channels of isolated neurons in a dose-dependent manner. Conclusions. The formulation may be considered as an effective and safe approach to anaesthetize upper molars with periodontitis.

We analyze the broadband activity of the flat spectrum radio quasar PKS 1222+216 from 2008 to 2015 using multi-frequency monitoring which involves γ-ray data from the Fermi Large Area Telescope, total intensity and linear polarization observations from different optical telescopes in R band, and imaging of the inner jet structure with the Very Long Baseline Array (VLBA) at 43 GHz. During the observations, the source showed several dramatic flares at γ rays and optical bands, with the rising branch of a γ-ray flare accompanied by a rapid rotation of the polarization position angle (EVPA), a fast increase of the degree of polarization in the optical band, brightening of the VLBI core, and appearance of a new superluminal component in the parsec-scale jet. The rapid variability of the optical linear polarization may be explained by a strong turbulence in the jet plasma. We find a correlation between the γ rays, optical R band, and 43 GHz variability on a long-term scale (months and years), and a good general alignment between EVPAs in R band and at 43 GHz, while the correlation between short-term variations (days and weeks) is weaker. Synchronous activity across the bands supports the idea that the emission regions responsible for the γ-ray and optical flares are co-spatial and located in the vicinity of the mm-wave core of the parsec-scale jet. However, these connections do not completely explain the challenging behaviour of PKS 1222+216, since there are some γ-ray flares which are not accompanied by jet events, and vice versa. We need a continuation of multi-frequency monitoring along with high resolution imaging of the parsec-scale jet to understand in detail the origin of high energy emission in blazars.