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Symbiotic microorganisms may provide their hosts with abilities critical to their occupation of microhabitats. Gut (intestinal) bacterial communities aid animals to digest substrates that are either innutritious or toxic, as well as support their development and physiology. The role of microbial communities associated with sibling species in the hosts’ adaptation remains largely unexplored. In this study, we examined the composition and plasticity of the bacteriomes in two sibling intertidal gastropod species, Littorina fabalis and L. obtusata, which are sympatric but differ in microhabitats. We applied 16S rRNA gene metabarcoding and shotgun sequencing to describe associated microbial communities and their spatial and temporal variation. A significant drop in the intestinal bacteriome diversity was revealed during the cold season, which may reflect temperature-related metabolic shifts and changes in snail behavior. Importantly, there were significant interspecies differences in the gut bacteriome composition in summer but not in autumn. The genera Vibrio, Aliivibrio, Moritella and Planktotalea were found to be predominantly associated with L. fabalis, while Granulosicoccus, Octadecabacter, Colwellia, Pseudomonas, Pseudoalteromonas and Maribacter were found to be mostly associated with L. obtusata. Based on these preferential associations, we analyzed the metabolic pathways’ enrichment. We hypothesized that the L. obtusata gut bacteriome contributes to decomposing algae and detoxifying polyphenols produced by fucoids. Thus, differences in the sets of associated bacteria may equip their closely phylogenetically related hosts with a unique ability to occupy specific micro-niches.

Azacarbazoles have attracted significant interest due to their valuable properties, such as anti-pathogenic and antitumor activity. In this study, a series of structurally related tricyclic benzo[4,5]- and tertacyclic naphtho[2′,1′:4,5]imidazo[1,2-c]pyrimidinone derivatives with one or two positively charged tethers were synthesized and evaluated for anti-proliferative activity. Lead tetracyclic derivative 5b with two amino-bearing arms inhibited the metabolic activity of A549 lung adenocarcinoma cells with a CC50 value of 3.6 μM, with remarkable selectivity (SI = 17.3) over VA13 immortalized fibroblasts. Cell-cycle assays revealed that 5b triggers G2/M arrest without signs of apoptosis. A study of its interaction with various DNA G4s and duplexes followed by dual luciferase and intercalator displacement assays suggests that intercalation, rather than the modulation of G4-regulated oncogene expression, might contribute to the observed activity. Finally, a water-soluble salt of 5b was shown to cause no acute toxic effects, changes in mice behavior, or any decrease in body weight after a 72 h treatment at concentrations up to 20 mg/kg. Thus, 5b is a promising candidate for studies in vivo; however, further investigations are needed to elucidate its molecular target(s).

Assessment of glycoconjugate expression on cell membranes using the lectin histochemistry technique may be a feasible approach for evaluating the functional state of the cell. The aim of this study was to evaluate carbohydrate determinants of rat stomach mucosa cell membranes under the conditions of COX-1/-2 blockage­ with indomethacin and pretreatment with the tripeptide H-Glu-Asp-Gly-OH. Male Wistar rats were divided into 3 groups (n = 6 per group): 1st group (control) received vehicle; 2nd – indomethacin (35 mg/kg); 3rd – H-Glu-Asp-Gly-OH (10 µg) 30 min before indomethacin. Rats were sacrificed 24 hours later. Gastric mucosa (GM) carbohydrate determinants were studied by lectin-peroxidase technique. The lectins panel included α-fucose- (LABA), syalo- (WGA, SNA), mannose- (Con A, LCA) and galactose-specific (HPA, PNA, SBA) lectins. Intensity of lectin-receptor reaction was scored: 0 – no reaction; 1 – weak; 2 – mild; and 3 – strong reaction. COX-1/2 blockage caused GM lesions, attenuated by H-Glu-Asp-Gly-OH. WGA and SNA showed the highest affinity to GM. Indomethacin decreased SNA-labeling of epitheliocytes and mucocytes and LABA-labeling of chief cells. H-Glu-Asp-Gly-OH reversed the glycosylation changes, caused by COX-1/COX-2 blockage only in regards to labeling of chief cells with LABA, epitheliocytes and mucocytes with LCA, mucocytes with SNA. Predominantly H-Glu-Asp-Gly-OH under COX-1/COX-2 blockage had an effect opposite to indomethacin alone but glycosylation changes under these conditions differed significantly also from the control. COX-1/COX-2 blockage causes alteration of glycosylation processes in rat GM, mainly reduction of NeuNAc(α2-6)DGal and α-Fuc content. H-Glu-Asp-Gly-OH under the conditions of COX-1/COX-2 blockage leads to more profound changes in GM lectin-binding pattern compared to the independent effect of indomethacin and to control.

Nanoparticle-based chemotherapy is considered to be an effective approach to cancer diagnostics and therapy in modern biomedicine. However, efficient tumor targeting remains a great challenge due to the lack of specificity, selectivity, and high dosage of chemotherapeutic drugs required. A two-step targeted drug delivery strategy (DDS), involving cancer cell pre-targeting, first with a first nontoxic module and subsequent targeting with a second complementary toxic module, is a solution for decreasing doses for administration and lowering systemic toxicity. To prove two-step DDS efficiency, we performed a direct comparison of one-step and two-step DDS based on chemotherapy loaded PLGA nanoparticles and barnase*barstar interface. Namely, we developed and thoroughly characterized the two-step targeting strategy of HER2-overexpressing cancer cells. The first targeting block consists of anti-HER2 scaffold polypeptide DARPin9_29 fused with barstar. Barstar exhibits an extremely effective binding to ribonuclease barnase with Kaff = 1014 M−1, thus making the barnase*barstar protein pair one of the strongest known protein*protein complexes. A therapeutic PLGA-based nanocarrier coupled to barnase was used as a second targeting block. The PLGA nanoparticles were loaded with diagnostic dye, Nile Blue, and a chemotherapeutic drug, doxorubicin. We showed that the two-step DDS increases the performance of chemotherapy-loaded nanocarriers: IC50 of doxorubicin delivered via two-step DDS was more than 100 times lower than that for one-step DDS: IC50 = 43 ± 3 nM for two-step DDS vs. IC50 = 4972 ± 1965 nM for one-step DDS. The obtained results demonstrate the significant efficiency of two-step DDS over the classical one-step one. We believe that the obtained data will significantly change the direction of research in developing targeted anti-cancer drugs and promote the creation of new generation cancer treatment strategies.

The extreme aggressiveness and lethality of many cancer types appeal to the problem of the development of new-generation treatment strategies based on smart materials with a mechanism of action that differs from standard treatment approaches. The targeted delivery of nanoparticles to specific cancer cell receptors is believed to be such a strategy; however, there are no targeted nano-drugs that have successfully completed clinical trials to date. To meet the challenge, we designed an alternative way to eliminate tumors in vivo. Here, we show for the first time that the targeting of lectin-equipped polymer nanoparticles to the glycosylation profile of cancer cells, followed by photodynamic therapy (PDT), is a promising strategy for the treatment of aggressive tumors. We synthesized polymer nanoparticles loaded with magnetite and a PDT agent, IR775 dye (mPLGA/IR775). The magnetite incorporation into the PLGA particle structure allows for the quantitative tracking of their accumulation in different organs and the performing of magnetic-assisted delivery, while IR775 makes fluorescent in vivo bioimaging as well as light-induced PDT possible, thus realizing the theranostics concept. To equip PLGA nanoparticles with targeting modality, the particles were conjugated with lectins of different origins, and the flow cytometry screening revealed that the most effective candidate for breast cancer cell labeling is ConA, a lectin from Canavalia ensiformis. In vivo experiments showed that after i.v. administration, mPLGA/IR775–ConA nanoparticles efficiently accumulated in the allograft tumors under the external magnetic field; produced a bright fluorescent signal for in vivo bioimaging; and led to 100% tumor growth inhibition after the single session of PDT, even for large solid tumors of more than 200 mm3 in BALB/c mice. The obtained results indicate that the mPLGA/IR775 nanostructure has great potential to become a highly effective oncotheranostic agent.

Hybrid multimodal nanoparticles, applicable simultaneously to the noninvasive imaging and therapeutic treatment, are highly demanded for clinical use. Here, Fe-Au core-satellite nanoparticles prepared by the method of pulsed laser ablation in liquids were evaluated as dual magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents and as sensitizers for laser-induced hyperthermia of cancer cells. The biocompatibility of Fe-Au nanoparticles was improved by coating with polyacrylic acid, which provided excellent colloidal stability of nanoparticles with highly negative ζ-potential in water (−38 ± 7 mV) and retained hydrodynamic size (88 ± 20 nm) in a physiological environment. The ferromagnetic iron cores offered great contrast in MRI images with r2 = 11.8 ± 0.8 mM−1 s−1 (at 1 T), while Au satellites showed X-ray attenuation in CT. The intravenous injection of nanoparticles enabled clear tumor border visualization in mice. Plasmonic peak in the Fe-Au hybrids had a tail in the near-infrared region (NIR), allowing them to cause hyperthermia under 808 nm laser exposure. Under NIR irradiation Fe-Au particles provided 24.1 °C/W heating and an IC50 value below 32 µg/mL for three different cancer cell lines. Taken together, these results show that laser synthesized Fe-Au core-satellite nanoparticles are excellent theranostic agents with multimodal imaging and photothermal capabilities.

Galvanochemical treatment efficiency for the galvanic waste purification is estimated. Results of the model laboratory experiment have shown high (over 99%) degree of water purification from heavy metal ions and a number of anions.

The development of non-invasive photothermal therapy (PTT) methods utilizing nanoparticles as sensitizers is one of the most promising directions in modern oncology. Nanoparticles loaded with photothermal dyes are capable of delivering a sufficient amount of a therapeutic substance and releasing it with the desired kinetics in vivo. However, the effectiveness of oncotherapy methods, including PTT, is often limited due to poor penetration of sensitizers into the tumor, especially into solid tumors of epithelial origin characterized by tight cellular junctions. In this work, we synthesized 200 nm nanoparticles from the biocompatible copolymer of lactic and glycolic acid, PLGA, loaded with magnesium phthalocyanine, PLGA/Pht-Mg. The PLGA/Pht-Mg particles under the irradiation with NIR light (808 nm), heat the surrounding solution by 40 °C. The effectiveness of using such particles for cancer cells elimination was demonstrated in 2D culture in vitro and in our original 3D model with multicellular spheroids possessing tight cell contacts. It was shown that the mean inhibitory concentration of such nanoparticles upon light irradiation for 15 min worsens by more than an order of magnitude: IC50 increases from 3 µg/mL for 2D culture vs. 117 µg/mL for 3D culture. However, when using the JO-4 intercellular junction opener protein, which causes a short epithelial–mesenchymal transition and transiently opens intercellular junctions in epithelial cells, the efficiency of nanoparticles in 3D culture was comparable or even outperforming that for 2D (IC50 = 1.9 µg/mL with JO-4). Synergy in the co-administration of PTT nanosensitizers and JO-4 protein was found to retain in vivo using orthotopic tumors of BALB/c mice: we demonstrated that the efficiency in the delivery of such nanoparticles to the tumor is 2.5 times increased when PLGA/Pht-Mg nanoparticles are administered together with JO-4. Thus the targeting the tumor cell junctions can significantly increase the performance of PTT nanosensitizers.

An 8-week growth trial was conducted to determine the sensitivity of white sturgeon (Acipenser transmontanus) to the toxicological effects of elevated dietary selenium (Se). Juvenile white sturgeon were fed diets supplemented with Se in the form Of L-selenomethionine (SeMet), resulting in dietary concentrations of 0.4, 9.6, 20.5, 41.7, 89.8, and 191.1 mu g Se/g diet on a dry weight basis. Effects of dietary SeMet on survival, swimming activity, growth, whole-body proximate composition, tissue Se concentrations, and histopathology were determined. Sturgeon survival among treatment groups did not differ significantly with a mean survival rate of 99 +/- 0.43% across all groups. A significant decrease (p < 0.05) in swimming activity and growth rate was observed in sturgeon fed at or above 41.7 mu g Se/g diet. Dietary SeMet concentrations were negatively correlated with whole-body protein and lipid content, but positively correlated with ash and moisture content. Selenium accumulated. in the kidney, muscle, liver, gill, and plasma tissues in a dose-dependent manner. Histopathological alterations in the liver and kidney were observed in sturgeon fed above 20.5 mu g Se/g diet. The threshold dietary Se toxicity concentration for white sturgeon was estimated to lie between 10 and 20 jig Se/g diet based on the histopathological alterations in the kidney. Research examining the consequences of elevated dietary Se concentrations on more sensitive life stages and the interactive effects of Se with other chemical or physical stressors are needed in order to determine if dietary threshold should be lowered to minimize the potential impacts of Se on white sturgeon in the San Francisco Bay-Delta. (c) 2006 Elsevier B.V. All rights reserved.

The effect of enhanced permeability and retention is often not sufficient for highly effective cancer therapy with nanoparticles, and the development of active targeted drug delivery systems based on nanoparticles is probably the main direction of modern cancer medicine. To meet the challenge, we developed polymer PLGA nanoparticles loaded with fluorescent photosensitive xanthene dye, Rose Bengal, and decorated with HER2-recognizing artificial scaffold protein, affibody ZHER2:342. The obtained 170 nm PLGA nanoparticles possess both fluorescent and photosensitive properties. Namely, under irradiation with the green light of 540 nm nanoparticles, they produced reactive oxygen species leading to cancer cell death. The chemical conjugation of PLGA with anti-HER2 affibody resulted in the selective binding of nanoparticles only to HER2-overexpressing cancer cells. HER2 is a receptor tyrosine kinase that belongs to the EGFR/ERbB family and is overexpressed in 30% of breast cancers, thus serving as a clinically relevant oncomarker. However, the standard targeting molecules such as full-size antibodies possess serious drawbacks, such as high immunogenicity and the need for mammalian cell production. We believe that the developed affibody-decorated targeted photosensitive PLGA nanoparticles will provide new solutions for ongoing problems in cancer diagnostics and treatment, as well in cancer theranostics.

The situation in the Russian real estate market can be significantly aggravated in the context of the crisis caused by the pandemic COVID-19. To understand how soon the Russian residential real estate market will be able to adapt to the new realities, it is necessary to give a forecast of the main trends that will occur in this sector in the post-viral era. The impact on the residential real estate market of the crisis caused by the widespread introduction of the quarantine regime and other restrictive measures in the framework of countering the pandemic of viral infection, the declaration of public health emergencies has not been investigated in the international and domestic literature. Since the current crisis is caused by the shock of demand and the shock of supply, which allows us to talk about it as a financial crisis with massive bankruptcy of both legal entities and individuals, the authors in their study relied on scientific works, the subject of which were the development of the real estate market in the context of the economic crisis. The main results of the study include: highlighting the characteristics of the residential real estate market that developed on the eve of the outbreak of the crisis; in conditions of shock period; its restoration and possible directions for the development of the residential real estate market in the near and medium term. In order to predict the situation in the domestic residential real estate market, a model of housing affordability ratio was applied (taking into account mortgage support). The findings of a study of the situation in the residential real estate market allowed the authors to propose a number of measures that need to be taken at the level of state authorities in the context of the "pandemic effect."

The article is devoted to the issues of heterogeneity in the development of the infrastructure environment of macro-regional economic systems (federal districts) and their regions. An assessment of the state and effectiveness of the infrastructure environment in macro-regions and regions of the Russian Federation is made, it is concluded that interregional heterogeneity in the provision of physical infrastructure and its state affects the functioning and development of both regional economic systems and the economic system of the state as a whole. It is emphasized that the priority of state policy in the development of the infrastructure environment of regions - leaders leads to the migration of labor to these regions, increases the burden on their budgets, further enhances asymmetric regional development, and contributes to the growth of social tension in regions with an insufficient and degrading infrastructure environment. The article presents data on per capita financing for the development of infrastructure of leading regions and outsider regions, the level of infrastructure development in the regional context. The authors propose to use such promising mechanisms as bonds and infrastructure crowdfunding to finance the development of infrastructure of leading regions.

Azacarbazoles have attracted significant interest due to their valuable properties, such as anti-pathogenic and antitumor activity. In this study, a series of structurally related tricyclic benzo[4,5]- and tertacyclic naphtho[2′,1′:4,5]imidazo[1,2-c]pyrimidinone derivatives with one or two positively charged tethers were synthesized and evaluated for anti-proliferative activity. Lead tetracyclic derivative 5b with two amino-bearing arms inhibited the metabolic activity of A549 lung adenocarcinoma cells with a CC50 value of 3.6 μM, with remarkable selectivity (SI = 17.3) over VA13 immortalized fibroblasts. Cell-cycle assays revealed that 5b triggers G2/M arrest without signs of apoptosis. A study of its interaction with various DNA G4s and duplexes followed by dual luciferase and intercalator displacement assays suggests that intercalation, rather than the modulation of G4-regulated oncogene expression, might contribute to the observed activity. Finally, a water-soluble salt of 5b was shown to cause no acute toxic effects, changes in mice behavior, or any decrease in body weight after a 72 h treatment at concentrations up to 20 mg/kg. Thus, 5b is a promising candidate for studies in vivo; however, further investigations are needed to elucidate its molecular target(s). [ABSTRACT FROM AUTHOR]

The interaction of SnCl4 with benzoyl-(salicyloyl) hydrazones of benz-(HBb, 2-OHHBb) and p-dimetilaminobenz- (HBdb, 2-OH-HBdb) aldehydes in acetonitrile have been studied. It has been shown, that with HBb the initial hydrazone(1) and with other hydrazones have been isolated complexes [SnCl4(2-OH-HBb)]⋅1,5CH3CN (2), [SnCl4(Bdb⋅H)] (3), [SnCl4(2-OH-Bdb⋅H)] (4), the composition and structure of which is determined by methods of elemental analysis, conductivity measurements (in nitrobenzene), as well as methods of thermogravimetry, electronic and IR spectroscopy. It has been shown, that in (2-4) is implemented bidentate O(C = O/CO), N(CH = N) coordination of ligand with the stabilization of both the ketone (OC = O, 2), and enolic (OC-O, 3, 4) forms. In 3, 4 the negative charge is located on the coordination site of tin is compensated due to protonation of the tertiary nitrogen atom of aldehyde fragment.

Oncotheranostic nanoagents are powerful artificial tools that significantly outperform traditional antitumor therapies. Among the wide variety of nanoagents, poly-(lactic-co-glycolic acid) (PLGA) nanoparticles have proven to be one of the most successful candidates for translation into clinical practice. Here, we present PLGA nanoparticles for HER2-targeted diagnostic and photodynamic therapy with proven efficacy in vivo. Namely, we developed an oncotheranostic platform that is based on PLGA nanoparticles and possesses red/green light dual-activated diagnostic/therapeutic properties for HER2-targeted photodynamic therapy of aggressive breast cancer. PLGA nanoparticles were loaded with a red light-activated dye Nile Blue with pronounced solvatochromic properties for diagnostic applications and with a green light-activated photodynamic sensitizer Rose Bengal for photodynamic therapy. Targeted delivery was ensured by the noncovalent decoration of nanoparticles with anti-HER2 antibodies, which can be readily adapted for large-scale biotechnological production. In vitro and in vivo studies proved the effectiveness of red light-mediated HER2-specific imaging and green light-induced cytotoxicity of anti-HER2 PLGA. Interestingly, these particles fluoresced only after cellular internalization, which minimizes background signals inside the organism, thus facilitating real-time diagnostics. The particles allowed efficient and selective visualization of the HER2-positive primary tumor node and metastases spread and led to complete remission in BALB/c Nu/Nu mice with the HER2-positive xenografts after a single session of photodynamic therapy. [ABSTRACT FROM AUTHOR]