Search

Four new glycosides of polyhydroxysteroids, ceramasterosides A, B, D, and E (1–4), and two previously known compounds, ceramasteroside C1 (5) and attenuatoside B-I (6), were isolated from an extract of a deep-sea sea star species, the orange cookie star Ceramaster patagonicus. The structures of 1–4 were elucidated by the extensive NMR and ESIMS methods. Steroid monoglycosides 1 and 2 had a common 3β,6α,8,15β,16β-pentahydroxysteroid nucleus and a C–29 oxidized stigmastane side chain and differed from each other only in monosaccharide residues. Ceramasteroside A (1) contained 3-O-methyl-4-O-sulfated β-D-xylopyranose, while ceramasteroside B (2) had 3-O-methyl-4-O-sulfated β-D-glucopyranose, recorded from starfish-derived steroid glycosides for the first time. Their biological activity was studied using a model of lipopolysaccharide-induced (LPS) inflammation in a SIM-A9 murine microglial cell line. During the LPS-induced activation of microglial cells, 1, 3, and 5, at a non-toxic concentration of 1 µM, showed the highest efficiency in reducing the production of intracellular NO, while 4 proved to be most efficient in reducing the extracellular nitrite production. All the test compounds reduced the LPS-induced malondialdehyde (MDA) production. The in vitro experiments have demonstrated, for the first time, the antioxidant activity of the compounds under study.

Background: Drosophila melanogaster provides a powerful platform to study the physiology and genetics of aging, i.e., the mechanisms underpinnings healthy aging, age-associated disorders, and acceleration of the aging process under adverse environmental conditions. Here, we tested the responses of daily rhythms to age-accelerated factors in two wild-type laboratory-adapted strains, Canton-S and Harwich. Methods: On the example of the 24 h patterns of locomotor activity and sleep, we documented the responses of these two strains to such factors as aging, high temperature, carbohydrate diet, and diet with different doses of caffeine-benzoate sodium. Results: The strains demonstrated differential responses to these factors. Moreover, compared to Canton-S, Harwich showed a reduced locomotor activity, larger amount of sleep, faster rate of development, smaller body weight, lower concentrations of main sugars, lower fecundity, and shorter lifespan. Conclusions: It might be recommended to use at least two strains, one with a relatively fast and another with a relatively slow aging process, for the experimental elaboration of relationships between genes, environment, behavior, physiology, and health.

Despite great advances in the treatment of oncological diseases, the development of medical technologies to prevent or reduce complications of therapy, in particular, those associated with surgery and the introduction of antibiotics, remains relevant. The aim of this study is to evaluate the effectiveness of the use of autoprobiotics based on indigenous non-pathogenic strains of Enterococcus faecium and Enterococcus hirae as a personalized functional food product (PFFP) in the complex therapy of colorectal cancer (CRC) in the early postoperative period. A total of 36 patients diagnosed with CRC were enrolled in the study. Study group A comprised 24 CRC patients who received autoprobiotic therapy in the early postoperative period, while the control group C included 12 CRC patients without autoprobiotic therapy. Prior to surgery and between days 14 and 16 post-surgery, comprehensive evaluations were conducted on all patients, encompassing the following: stool and gastroenterological complaints analysis, examination of the gut microbiota (bacteriological study, quantitative polymerase chain reaction, metagenome analysis), and analysis of interleukins in the serum. Results: The use of autoprobiotics led to a decrease in dyspeptic complaints after surgery. It was also associated with the absence of postoperative complications, did not cause any side effects, and led to a decrease in the level of pro-inflammatory cytokines (IL-6 and IL-18) in the blood serum. The use of autoprobiotics led to positive changes in the structure of escherichia and enterococci populations, the elimination of Parvomonas micra and Fusobacterium nucleatum, and a decrease in the quantitative content of Clostridium perfringens and Akkermansia muciniphila. Metagenomic analysis (16S rRNA) revealed an increase in alpha diversity. Conclusion: The introduction of autoprobiotics in the postoperative period is a highly effective and safe approach in the complex treatment of CRC. Future studies will allow the discovery of additional fine mechanisms of autoprobiotic therapy and its impact on the digestive, immune, endocrine, and neural systems.

New imidazolidine-2,4,5-triones with norabietic, nordehydroabietic, and adamantane substituents were synthesized by reacting oxalyl chloride and the corresponding ureas, providing good yields. Bioisosteric replacement of the ureide group with a parabanic acid fragment made it possible to increase the solubility of compounds and conduct biological studies. The compounds inhibit the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 in submicromolar concentrations. Cytotoxic concentrations were also studied on the glioblastoma cell line SNB19.

Background: Activity plays a very important role in keeping bodies strong and healthy, slowing senescence, and decreasing morbidity and mortality. Drosophila models of evolution under various selective pressures can be used to examine whether increased activity and decreased sleep duration are associated with the adaptation of this nonhuman species to longer or harder lives. Methods: For several years, descendants of wild flies were reared in a laboratory without and with selection pressure. To maintain the “salt” and “starch” strains, flies from the wild population (called “control”) were reared on two adverse food substrates. The “long-lived” strain was maintained through artificial selection for late reproduction. The 24 h patterns of locomotor activity and sleep in flies from the selected and unselected strains (902 flies in total) were studied in constant darkness for at least, 5 days. Results: Compared to the control flies, flies from the selected strains demonstrated enhanced locomotor activity and reduced sleep duration. The most profound increase in locomotor activity was observed in flies from the starch (short-lived) strain. Additionally, the selection changed the 24 h patterns of locomotor activity and sleep. For instance, the morning and evening peaks of locomotor activity were advanced and delayed, respectively, in flies from the long-lived strain. Conclusion: Flies become more active and sleep less in response to various selection pressures. These beneficial changes in trait values might be relevant to trade-offs among fitness-related traits, such as body weight, fecundity, and longevity.

Deoxycholic acid derivatives containing various heterocyclic functional groups at C-3 on the steroid scaffold were designed and synthesized as promising dual tyrosyl-DNA phosphodiesterase 1 and 2 (TDP1 and TDP2) inhibitors, which are potential targets to potentiate topoisomerase poison antitumor therapy. The methyl esters of DCA derivatives with benzothiazole or benzimidazole moieties at C-3 demonstrated promising inhibitory activity in vitro against TDP1 with IC50 values in the submicromolar range. Furthermore, methyl esters 4d–e, as well as their acid counterparts 3d–e, inhibited the phosphodiesterase activity of both TDP1 and TDP2. The combinations of compounds 3d–e and 4d–e with low-toxic concentrations of antitumor drugs topotecan and etoposide showed significantly greater cytotoxicity than the compounds alone. The docking of the derivatives into the binding sites of TDP1 and TDP2 predicted plausible binding modes of the DCA derivatives.

In this study formal derivation of mode coupling equations in underwater acoustics is revisited. This derivation is based on the method of multiple scales from which modal expansion of the field emerges, and the vectorized WKBJ equation for the coefficients in this expansion are obtained in an automatic way. Asymptotic analysis accomplished in this work also establishes a connection between coupled mode parabolic equations in three-dimensional case and the generalized WKBJ solution that emerges as its two-dimensional counterpart. Despite the fact that similar mode coupling equations can be found in literature, in our study a new systematic and formalized approach to their derivation is proposed. A theorem that guarantees asymptotic conservation of the energy flux in the considered two-dimensional waveguide is also proven.

The purpose of this work was a comparative metabolomic study of extracts of from Siberian breeds of the Solanum tuberosum L.: Tuleevsky, Kuznechanka, Memory of Antoshkina, Tomichka, Hybrid 15/F-2-13, Hybrid 22103-10, Hybrid 17-5/6-11, and Sinilga from the collection of Siberian Federal Scientific Centre of Agrobiotechnology of the Russian Academy of Sciences. HPLC was used in combination with ion trap to identify target analytes in extracts of tuber part of a potato. The results showed the presence of 87 target analytes corresponding to S. tuberosum. In addition to the reported metabolites, a number of metabolites were newly annotated in S. tuberosum. There were essential amino acid L-Tryptophan, L-glutamate, L-lysine, Nordenine; flavones Ampelopsin; Chrysoeriol, Diosmetin, Diosmin, Myricetin; flavanones Naringenin and Eriodictyol-7-O-glucoside; dihydrochalcone Phlorizin; oligomeric proanthocyanidin (Epi)afzelechin-(epi)afzelechin; Shikimic acid; Hydroxyphenyllactic acid; Fraxidin; Myristoleic acid; flavan-3-ols Epicatechin, Gallocatechin, Gibberellic acid, etc.

The structure and diversity of microbial communities developing in the combined gradient of temperature (44–19 °C), as well as concentration of oxygen (0–10 mg/L) and hydrogen sulfide (33–0.7 mg/L), were studied in the thermal sulfide spring on the coast of Northern Lake Baikal. The predominance of bacteria participating in sulfur and nitrogen cycles and significant changes in the composition of microbial communities were noted at changing physicochemical conditions. Thiovirga sp. (sulfur-oxidizing bacteria, up to 37%) and Azonexus sp. (nitrogen-fixing bacteria, up to 43%) were dominant at high temperatures and concentrations of hydrogen sulfide in two hydrotherms. In addition, a significant contribution of the Rhodocyclaceae family (up to 51%) which is involved in the denitrification processes, and Acetoanaerobium sp. (up to 20%) fixing carbon oxide were found in the spring water. In the stream, mainly oxygenic cyanobacteria (up to 56%) developed at a temperature of 33 °C, in the presence of hydrogen sulfide and oxygen. In addition, sulfur bacteria of the genus Thiothrix (up to 48%) found in epibiotic communities of benthic animals of Lake Baikal were present here. Thiothrix sp. formed massive fouling in the zone of mixing lake and thermal waters with a significant contribution of hydrogen-oxidizing bacteria of the genus Hydrogenophaga (up to 22.5%). As well as chemolitho- and phototrophic bacteria, chemoorganotrophs (phyla Firmicutes, Chloroflexi, Desulfobacterota, Nitrospirota, Fibrobacterota, etc.) have been identified in all communities. The chemical parameters of water in spring and coastal zones indicate a significant change in the composition of thermal waters occurring with the participation of diverse microbial communities that contribute to the assimilation of inorganic components of mineral thermal waters.

The use of cancer chemotherapy sensitizers is a promising approach to induce the effect of clinically used anticancer treatments. One of the interesting targets is Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), a DNA-repair enzyme, that may prevent the action of clinical Topoisomerase 1 (Top1) inhibitors, such as topotecan (Tpc). Tdp1 eliminates covalent Top1-DNA (Top1c) complexes that appear under the action of topotecan and determines the cytotoxic effect of this drug. We hypothesize that Tdp1 inhibition would sensitize cells towards the effect of Tpc. Herein, we report the synthesis and study of lipophilic derivatives of purine nucleosides that efficiently suppress Tdp1 activity, with IC50 values in the 0.3–22.0 μM range. We also showed that this compound class can enhance DNA damage induced by topotecan in vitro by Comet assay on human cell lines HeLa and potentiate the antitumor effect of topotecan in vivo on a mice ascitic Krebs-2 carcinoma model. Thereby, this type of compound may be useful to develop drugs, that sensitize the effect of topotecan and reduce the required dose and, as a result, side effects.

In this research, we present a detailed comparative analysis of the bioactive substances of soybean varieties k-11538 (Russia), k-11559 (Russia), k-569 (China), k-5367 (China), k-5373 (China), k-5586 (Sweden), and Primorskaya-86 (Russia) using an LSM 800 confocal laser microscope and an amaZon ion trap SL mass spectrometer. Laser microscopy made it possible to clarify in detail the spatial arrangement of the polyphenolic content of soybeans. Our results revealed that the phenolics of soybean are spatially located mainly in the seed coat and the outer layer of the cotyledon. High-performance liquid chromatography (HPLC) was used in combination with an amaZon SL BRUKER DALTONIKS ion trap (tandem mass spectrometry) to identify target analytes in soybean extracts. The results of initial studies revealed the presence of 63 compounds, and 45 of the target analytes were identified as polyphenolic compounds.

Three new ceramides (1–3) and three new cerebrosides (4, 8, and 9), along with three previously known cerebrosides (ophidiocerebrosides C (5), D (6), and CE-3-2 (7)), were isolated from a deep-sea starfish species, the orange cookie starfish Ceramaster patagonicus. The structures of 1−4, 8, and 9 were determined by the NMR and ESIMS techniques and also through chemical transformations. Ceramides 1–3 contain iso-C21 or C23 Δ9-phytosphingosine as a long-chain base and have C16 or C17 (2R)-2-hydroxy-fatty acids of the normal type. Cerebroside 4 contains C22 Δ9-sphingosine anteiso-type as a long-chain base and (2R)-2-hydroxyheptadecanoic acid of the normal type, while compounds 8 and 9 contain saturated C-17 phytosphingosine anteiso-type as a long-chain base and differ from each other in the length of the polymethylene chain of (2R)-2-hydroxy-fatty acids of the normal type: C23 in 8 and C24 in 9. All the new cerebrosides (4, 8, and 9) have β-D-glucopyranose as a monosaccharide residue. The composition of neutral sphingolipids from C. patagonicus was described for the first time. The investigated compounds 1–3, 5–7, and 9 exhibit slight to moderate cytotoxic activity against human cancer cells (HT-29, SK-MEL-28, and MDA-MB-231) and normal embryonic kidney cells HEK293. Compounds 2, 5, and 6 at a concentration of 20 µM inhibit colony formation of MDA-MB-231 cells by 68%, 54%, and 68%, respectively. The colony-inhibiting activity of compounds 2, 5, and 6 is comparable to the effect of doxorubicin, which reduces the number of colonies by 70% at the same concentration.

Rosa rugosa Thumb., Rosa davurica Pall., and Rosa acicularis Lindl. contain a large number of target analytes which are bioactive compounds. High performance liquid chromatography (HPLC), in combination with the ion trap (tandem mass spectrometry), was used to identify target analytes in MeOH extracts of R. rugosa, R. davurica, and R. acicularis, originating from the Russian Far East, Trans-Baikal Region, and Western Siberia. The results of initial studies revealed the presence of 146 compounds, of which 115 were identified for the first time in the genus Rosa (family Rosaceae). The newly identified metabolites belonged to 18 classes, including 14 phenolic acids and their conjugates, 18 flavones, 7 flavonols, 2 flavan-3-ols, 2 flavanones, 3 stilbenes, 2 coumarins, 2 lignans, 9 anthocyanins, 3 tannins, 8 terpenoids, 3 sceletium alkaloids, 4 fatty acids, 2 sterols, 2 carotenoids, 3 oxylipins, 3 amino acids, 5 carboxylic acids, etc. The proven richness of the bioactive components of targeted extracts of R. rugosa, R. davurica, and R. acicularis invites extensive biotechnological and pharmaceutical research, which can make a significant contribution both in the field of functional and enriched nutrition, and in the field of cosmetology and pharmacy.

The research presents a comparative metabolomic study of extracts of Vigna unguiculata seed samples from the collection of the N.I. Vavilov All-Russian Institute of Plant Genetic Resources. Analyzed samples related to different areas of use in agricultural production, belonging to different cultivar groups sesquipedalis (vegetable accessions) and unguiculata (grain accessions). Metabolome analysis was performed by liquid chromatography combined with ion trap mass spectrometry. Substances were localized in seeds using confocal and laser microscopy. As a result, 49 bioactive compounds were identified: flavonols, flavones, flavan-3-ols, anthocyanidin, phenolic acids, amino acids, monocarboxylic acids, aminobenzoic acids, fatty acids, lignans, carotenoid, sapogenins, steroids, etc. Steroidal alkaloids were identified in V. unguiculata seeds for the first time. The seed coat (palisade epidermis and parenchyma) is the richest in phenolic compounds. Comparison of seeds of varieties of different directions of use in terms of the number of bioactive substances identified revealed a significant superiority of vegetable accessions over grain ones in this indicator, 36 compounds were found in samples from cultivar group sesquipedalis, and 24 in unguiculata. The greatest variety of bioactive compounds was found in the vegetable accession k-640 from China.

Three types of Zostera marina L. collection were extracted using the supercritical CO2-extraction method. For the purposes of supercritical CO2-extraction, old seagrass ejection on the surf edge, fresh seagrass ejection on the surf edge and seagrass collected in water were used. Several experimental conditions were investigated in the pressure range 50–350 bar, with the used volume of co-solvent ethanol in the amount of 1% in the liquid phase at a temperature in the range of 31–70 °C. The most effective extraction conditions are: pressure 250 Bar and temperature 60 °C for Z. marina collected in sea water. Z. marina contain various phenolic compounds and sulfated polyphenols with valuable biological activity. Tandem mass-spectrometry (HPLC-ESI–ion trap) was applied to detect target analytes. 77 different biologically active components have been identified in Z. marina supercritical CO2-extracts. 38 polyphenols were identified for the first time in Z. marina.

Inhibiting tyrosyl-DNA phosphodiesterase 1 (TDP1) is a promising strategy for increasing the effectiveness of existing antitumor therapy since it can remove the DNA lesions caused by anticancer drugs, which form covalent complexes with topoisomerase 1 (TOP1). Here, new adamantane–monoterpene conjugates with a 1,2,4-triazole or 1,3,4-thiadiazole linker core were synthesized, where (+)-and (−)-campholenic and (+)-camphor derivatives were used as monoterpene fragments. The campholenic derivatives 14a–14b and 15a–b showed activity against TDP1 at a low micromolar range with IC50 ~5–6 μM, whereas camphor-containing compounds 16 and 17 were ineffective. Surprisingly, all the compounds synthesized demonstrated a clear synergy with topotecan, a TOP1 poison, regardless of their ability to inhibit TDP1. These findings imply that different pathways of enhancing topotecan toxicity other than the inhibition of TDP1 can be realized.

Inhibition of human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1) by different chiral lipophilic nucleoside derivatives was studied. New Tdp1 inhibitors were found in the series of the studied compounds with IC50 = 2.7–6.7 μM. It was shown that D-lipophilic nucleoside derivatives manifested higher inhibition activity than their L-analogs, and configuration of the carbohydrate moiety can influence the mechanism of Tdp1 inhibition.

Dracocephalum palmatum S. and Dracocephalum ruyschiana L. contain a large number of target analytes, which are biologically active compounds. High performance liquid chromatography (HPLC) in combination with an ion trap (tandem mass spectrometry) was used to identify target analytes in extracts of D. palmatum S. and D. ruyschiana L. originating from Yakutia. The results of initial studies revealed the presence of 114 compounds, of which 92 were identified for the first time in the genus Dracocephalum. New identified metabolites belonged to 17 classes, including 16 phenolic acids and their conjugates, 18 flavones, 5 flavonols, 2 flavan-3-ols, 1 flavanone, 2 stilbenes, 10 anthocyanins, 1 condensed tannin, 2 lignans, 6 carotenoids, 3 oxylipins, 2 amino acids, 3 sceletium alkaloids, 3 carboxylic acids, 8 fatty acids, 1 sterol, and 3 terpenes, along with 6 miscellaneous compounds. It was shown that extracts of D. palmatum are richer in the spectrum of polyphenolic compounds compared with extracts of D. ruyschiana, according to a study of the presence of these compounds in extracts, based on the results of mass spectrometric studies.

Desirable changes in the biochemical composition of food plants is a key outcome of breeding strategies. The subsequent localization of nutritional phytochemicals in plant tissues gives important information regarding the extent of their synthesis across a tissue. We performed a detailed metabolomic analysis of phytochemical substances of grains from Zea mays L. (var. Pioneer) by tandem mass spectrometry and localization by confocal microscopy. We found that anthocyanins are located mainly in the aleurone layer of the grain. High-performance liquid chromatography in combination with ion trap tandem mass spectrometry revealed the presence of 56 compounds, including 30 polyphenols. This method allows for effective and rapid analysis of anthocyanins by plotting their distribution in seeds and grains of different plants. This approach will permit a more efficient screening of phenotypic varieties during food plant breeding.

This paper presents a methodology for classifying train passages into different types with a weigh-in-motion (WIM) system to allow the calibration of railway fatigue load models and identify individual vehicles from the measurements for the continuous calibration of railway WIM stations from in-service trains. The quality assurance of the measured responses is demonstrated using statistical methods. This paper discusses the measurement station, the method used for processing the raw data, the algorithm used to identify the train types and vehicles automatically, and the limits of the obtained load spectra. The measurement errors are demonstrated to be satisfying for use in fatigue load model calibration. Furthermore, this paper proposes actions for accurately obtaining the actual traffic conditions and describes the future work required in this area.

The fruit fly Drosophila melanogaster is a classic research object in genetics and systems biology. In the genetic analysis of flies, a routine task is to determine the offspring size and gender ratio in their populations. Currently, these estimates are made manually, which is a very time-consuming process. The counting and gender determination of flies can be automated by using image analysis with deep learning neural networks on mobile devices. We proposed an algorithm based on the YOLOv4-tiny network to identify Drosophila flies and determine their gender based on the protocol of taking pictures of insects on a white sheet of paper with a cell phone camera. Three strategies with different types of augmentation were used to train the network. The best performance (F1 = 0.838) was achieved using synthetic images with mosaic generation. Females gender determination is worse than that one of males. Among the factors that most strongly influencing the accuracy of fly gender recognition, the fly’s position on the paper was the most important. Increased light intensity and higher quality of the device cameras have a positive effect on the recognition accuracy. We implement our method in the FlyCounter Android app for mobile devices, which performs all the image processing steps using the device processors only. The time that the YOLOv4-tiny algorithm takes to process one image is less than 4 s.

A series of deoxycholic acid (DCA) amides containing benzyl ether groups on the steroid core were tested against the tyrosyl-DNA phosphodiesterase 1 (TDP1) and 2 (TDP2) enzymes. In addition, 1,2,4- and 1,3,4-oxadiazole derivatives were synthesized to study the linker influence between a para-bromophenyl moiety and the steroid scaffold. The DCA derivatives demonstrated promising inhibitory activity against TDP1 with IC50 in the submicromolar range. Furthermore, the amides and the 1,3,4-oxadiazole derivatives inhibited the TDP2 enzyme but at substantially higher concentration. Tryptamide 5 and para-bromoanilide 8 derivatives containing benzyloxy substituent at the C-3 position and non-substituted hydroxy group at C-12 on the DCA scaffold inhibited both TDP1 and TDP2 as well as enhanced the cytotoxicity of topotecan in non-toxic concentration in vitro. According to molecular modeling, ligand 5 is anchored into the catalytic pocket of TDP1 by one hydrogen bond to the backbone of Gly458 as well as by π–π stacking between the indolyl rings of the ligand and Tyr590, resulting in excellent activity. It can therefore be concluded that these derivatives contribute to the development of specific TDP1 and TDP2 inhibitors for adjuvant therapy against cancer in combination with topoisomerase poisons.

Mounting evidence implicates microRNAs (miRNAs) in the pathology of schizophrenia. These small noncoding RNAs bind to mRNAs containing complementary sequences and promote their degradation and/or inhibit protein synthesis. A single miRNA may have hundreds of targets, and miRNA targets are overrepresented among schizophrenia-risk genes. Although schizophrenia is a neurodevelopmental disorder, symptoms usually do not appear until adolescence, and most patients do not receive a schizophrenia diagnosis until late adolescence or early adulthood. However, few studies have examined miRNAs during this critical period. First, we examine evidence that the miRNA pathway is dynamic throughout adolescence and adulthood and that miRNAs regulate processes critical to late neurodevelopment that are aberrant in patients with schizophrenia. Next, we examine evidence implicating miRNAs in the conversion to psychosis, including a schizophrenia-associated single nucleotide polymorphism in MIR137HG that is among the strongest known predictors of age of onset in patients with schizophrenia. Finally, we examine how hemizygosity for DGCR8, which encodes an obligate component of the complex that synthesizes miRNA precursors, may contribute to the onset of psychosis in patients with 22q11.2 microdeletions and how animal models of this disorder can help us understand the many roles of miRNAs in the onset of schizophrenia.

Vehicle emission particles (VEPs) represent a significant part of air pollution in urban areas. However, the toxicity of this category of particles in different aquatic organisms is still unexplored. This work aimed to extend the understanding of the toxicity of the vehicle exhaust particles in two species of marine diatomic microalgae, the planktonic crustacean Artemia salina, and the sea urchin Strongylocentrotus intermedius. These aquatic species were applied for the first time in the risk assessment of VEPs. Our results demonstrated that the samples obtained from diesel-powered vehicles completely prevented egg fertilization of the sea urchin S. intermedius and caused pronounced membrane depolarization in the cells of both tested microalgae species at concentrations between 10 and 100 mg/L. The sample with the highest proportion of submicron particles and the highest content of polycyclic aromatic hydrocarbons (PAHs) had the highest growth rate inhibition in both microalgae species and caused high toxicity to the crustacean. The toxicity level of the other samples varied among the species. We can conclude that metal content and the difference in the concentrations of PAHs by itself did not directly reflect the toxic level of VEPs, but the combination of both a high number of submicron particles and high PAH concentrations had the highest toxic effect on all the tested species.

Extraction process of Cucumaria frondosa japonica Semper, 1868, which are subspecies of Cucumaria frondosa (Gunnerus, 1767), were studied. It was shown that supercritical carbon dioxide extraction of holothuria was more effective than conventional solvent extraction. Step-by-step extraction with carbon dioxide followed by supercritical extraction with the addition of a co-solvent of ethanol can almost double the yields of extracts of triterpene glycosides, styrenes and carotenoids. Moreover, the fraction of triterpene glycosides practically does not contain colored impurities, in contrast to traditional ethanol extraction. The obtained extracts by HPLC in combination with tandem mass spectrometry (HPLC-MS/MS) identified 15 triterpene glycosides, 18 styrene compounds and 14 carotenoids. Supercritical extraction made it possible to obtain extracts with yields superior to conventional hexane and alcohol extracts. Moreover, such an approach with the use of supercritical fluid extraction (SFE) and subsequent profiling of metabolites can help with the study of holothuria species that are not as well studied.

The colored grain of wheat (Triticum aestivum L.) contains a large number of polyphenolic compounds that are biologically active ingredients. The purpose of this work was a comparative metabolomic study of extracts from anthocyaninless (control), blue, and deep purple (referred to here as black) grains of seven genetically related wheat lines developed for the grain anthocyanin pigmentation trait. To identify target analytes in ethanol extracts, high-performance liquid chromatography was used in combination with Bruker Daltonics ion trap mass spectrometry. The results showed the presence of 125 biologically active compounds of a phenolic (85) and nonphenolic (40) nature in the grains of T. aestivum (seven lines). Among them, a number of phenolic compounds affiliated with anthocyanins, coumarins, dihydrochalcones, flavan-3-ols, flavanone, flavones, flavonols, hydroxybenzoic acids, hydroxycinnamic acids, isoflavone, lignans, other phenolic acids, stilbenes, and nonphenolic compounds affiliated with alkaloids, carboxylic acids, carotenoids, diterpenoids, essential amino acids, triterpenoids, sterols, nonessential amino acids, phytohormones, purines, and thromboxane receptor antagonists were found in T. aestivum grains for the first time. A comparative analysis of the diversity of the compounds revealed that the lines do not differ from each other in the proportion of phenolic (53.3% to 70.3% of the total number of identified compounds) and nonphenolic compounds (46.7% to 29.7%), but diversity of the compounds was significantly lower in grains of the control line. Even though the lines are genetically closely related and possess similar chemical profiles, some line-specific individual compounds were identified that constitute unique chemical fingerprints and allow to distinguish each line from the six others. Finally, the influence of the genotype on the chemical profiles of the wheat grains is discussed.

Numerous sound propagation models in underwater acoustics are based on the representation of a sound field in the form of a decomposition over normal modes. In the framework of such models, the calculation of the field in a range-dependent waveguide (as well as in the case of 3D problems) requires the computation of normal modes for every point within the area of interest (that is, for each pair of horizontal coordinates x,y). This procedure is often responsible for the lion’s share of total computational cost of the field simulation. In this study, we present formulae for perturbation of eigenvalues and eigenfunctions of normal modes under the water depth variations in a shallow-water waveguide. These formulae can reduce the total number of mode computation instances required for a field calculation by a factor of 5–10. We also discuss how these formulae can be used in a combination with a wide-angle mode parabolic equation. The accuracy of such combined model is validated in a series of numerical examples.

Usnic acid (UA) is a secondary metabolite of lichens that exhibits a wide range of biological activities. Previously, we found that UA derivatives are effective inhibitors of tyrosyl-DNA phosphodiesterase 1 (TDP1). It can remove covalent complex DNA-topoisomerase 1 (TOP1) stabilized by the TOP1 inhibitor topotecan, neutralizing the effect of the drugs. TDP1 removes damage at the 3′ end of DNA caused by other anticancer agents. Thus, TDP1 is a promising therapeutic target for the development of drug combinations with topotecan, as well as other drugs for cancer treatment. Ten new UA enamino derivatives with variation in the terpene fragment and substituent of the UA backbone were synthesized and tested as TDP1 inhibitors. Four compounds, 11a-d, had IC50 values in the 0.23–0.40 μM range. Molecular modelling showed that 11a-d, with relatively short aliphatic chains, fit to the important binding domains. The intrinsic cytotoxicity of 11a-d was tested on two human cell lines. The compounds had low cytotoxicity with CC50 ≥ 60 μM for both cell lines. 11a and 11c had high inhibition efficacy and low cytotoxicity, and they enhanced topotecan’s cytotoxicity in cancerous HeLa cells but reduced it in the non-cancerous HEK293A cells. This “protective” effect from topotecan on non-cancerous cells requires further investigation.

This work represents a comparative metabolomic study of extracts of wild grapes obtained from six different places in the Primorsky and Khabarovsk territories (Far East Russia) and extracts of grapes obtained from the collection of N.I. Vavilov All-Russian Institute of Plant Genetic Resources (St. Petersburg). The metabolome analysis was performed by liquid chromatography in combination with ion trap mass spectrometry. The results showed the presence of 118 compounds in ethanolic extracts of V. amurensis grapes. In addition, several metabolites were newly annotated in V. amurensis. The highest diversity of phenolic compounds was identified in the samples of the V. amurensis grape collected in the vicinity of Vyazemsky (Khabarovsk Territory) and the floodplain of the Arsenyevka River (Primorsky Territory), compared to the other wild samples and cultural grapes obtained in the collection of N.I. Vavilov All-Russian Institute of Plant Genetic Resources.

In this paper, a series of novel abietyl and dehydroabietyl ureas, thioureas, amides, and thioamides bearing adamantane moieties were designed, synthesized, and evaluated for their inhibitory activities against tyrosil-DNA-phosphodiesterase 1 (TDP1). The synthesized compounds were able to inhibit TDP1 at micromolar concentrations (0.19–2.3 µM) and demonstrated low cytotoxicity in the T98G glioma cell line. The effect of the terpene fragment, the linker structure, and the adamantane residue on the biological properties of the new compounds was investigated. Based on molecular docking results, we suppose that adamantane derivatives of resin acids bind to the TDP1 covalent intermediate, forming a hydrogen bond with Ser463 and hydrophobic contacts with the Phe259 and Trp590 residues and the oligonucleotide fragment of the substrate.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising target for anticancer therapy due to its ability to counter the effects topoisomerase 1 (Top1) poison, such as topotecan, thus, decreasing their efficacy. Compounds containing adamantane and monoterpenoid residues connected via 1,2,4-triazole or 1,3,4-thiadiazole linkers were synthesized and tested against Tdp1. All the derivatives exhibited inhibition at low micromolar or nanomolar concentrations with the most potent inhibitors having IC50 values in the 0.35–0.57 µM range. The cytotoxicity was determined in the HeLa, HCT-116 and SW837 cancer cell lines; moderate CC50 (µM) values were seen from the mid-teens to no effect at 100 µM. Furthermore, citral derivative 20c, α-pinene-derived compounds 20f, 20g and 25c, and the citronellic acid derivative 25b were found to have a sensitizing effect in conjunction with topotecan in the HeLa cervical cancer and colon adenocarcinoma HCT-116 cell lines. The ligands are predicted to bind in the catalytic pocket of Tdp1 and have favorable physicochemical properties for further development as a potential adjunct therapy with Top1 poisons.

Humans and fruit flies demonstrate similarity in sleep-wake behavior, e.g., in the pattern of sleep disturbances caused by an exposure to high temperature. Although research has provided evidence for a clear connection between sleeping problems and infertility in women, very little is known regarding the mechanisms underlying this connection. Studies of dysgenic crosses of fruit flies revealed that an exposure to elevated temperature induces sterility in female intra-specific hybrids exclusively in one of two cross directions (progeny of Canton-S females crossed with Harwich males). Given the complexity and limitations of human studies, this fruit flies’ model of temperature-sensitive sterility might be used for testing whether the effects of high temperature on fertility and on 24-h sleep pattern are inter-related. To document this pattern, 315 hybrids were kept for at least five days in constant darkness at 20 °C and 29 °C. No evidence was found for a causal link between sterility and sleep disturbance. However, a diminished thermal responsiveness of sleep was shown by females with temperature-induced sterility, while significant responses to high temperature were still observed in fertile females obtained by crossing in the opposite direction (i.e., Canton-S males with Harwich females) and in fertile males from either cross.

A new type of berberine derivatives was obtained by the reaction of berberrubine with aliphatic sulfonyl chlorides. The new polycyclic compounds have a sultone ring condensed to C and D rings of a protoberberine core. The reaction conditions were developed to facilitate the formation of sultones with high yields without by-product formation. Thus, it was shown that the order of addition of reagents affects the composition of the reaction products: when sulfochlorides are added to berberrubine, their corresponding 9-O-sulfonates are predominantly formed; when berberrubine is added to pre-generated sulfenes, sultones are the only products. The reaction was shown to proceed stereo-selectively and the cycle configuration was confirmed by 2D NMR spectroscopy. The inhibitory activity of the synthesized sultones and their 12-brominated analogs against the DNA-repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1), an important target for a potential antitumor therapy, was studied. All derivatives were active in the micromolar and submicromolar range, in contrast to the acyclic analogs and 9-O-sulfonates, which were inactive. The significance of the sultone cycle and bromine substituent in binding with the enzyme was confirmed using molecular modeling. The active inhibitors are mostly non-toxic to the HeLa cancer cell line, and several ligands show synergy with topotecan, a topoisomerase 1 poison in clinical use. Thus, novel berberine derivatives can be considered as candidates for adjuvant therapy against cancer.