Comparative GC-MS study of Schizonepeta multifida essential oil from Khakassia Republic shows potentials for nutraceuticals, flavor, and conservation

Schizonepeta multifida (L.) Briq. (Lamiaceae) is among the widely used botanicals in Siberian traditional and modern health and personal care practices, shelf life extension of agricultural produce, antimicrobial, and insect repellent. We investigated the variations or differences in the chemical composition of essential oils in wild accessions harvested from two distinct geographical regions, 'habitat-1' and 'habitat-2', in the Republic of Khakassia, Siberia. The oils were obtained by subjecting the aboveground parts of the plant to hydro-distillation, with subsequent assessment of the chemical composition using GC-FID and GC-MS analyses. The oil composition varied quite a lot according the number of components (61 in samples from 'habitat-1', 45 in sample from 'habitat-2'), the dominant components (pulegone 33.36 %, limonene 20.95 %, cis-beta-ocimene 9.96 % and isomenthone 5.31 % from 'habitat-1', limonene 27.98 %, cis-beta-ocimene 14.42 %, pulegone 14.20 %, beta-myrcene 11.95 %, and terpinolene 6.33 % from 'habitat-2'). In light of the continued overharvesting resulting in genetic erosion, further studies are warranted to establish in-situ and ex-situ conservation strategies of all populations representing different chemotypes/ecotypes and identifying promising genetic lines for sustainable cultivation as a source of renewable raw material for the oil

Sex specificity in innate immunity of insect larvae

The innate immunity of insects has been widely studied. Although the effect of sex on insect immunity has been extensively discussed, differences in immunity between the sexes of larvae insects remain largely unstudied. Studying larval sex differences in immunity may provide valuable information about the mechanisms underlying the insect immune system, which, in turn, can be valuable for the development and improvement of pest management. Here we compared the antibacterial activity in both the midgut tissue and cell-free hemolymph of Lymantria dispar L. (Lepidoptera: Erebidae) females and males at the larval stage without and after a challenge by entomopathogenic bacterium Bacillus thuringiensis Berliner. We also evaluated the sex-specific mortality of L. dispar induced by B. thuringiensis infection. We find that antibacterial activity in the midgut is activated by infection, but only in females. Thus, sex differences in immunity can have important effects even before sexual differentiation at adulthood

326 The anti-TIGIT antibody M6223 induces significant anti-tumor efficacy and immune response via multiple mechanisms of action

BackgroundM6223 is a fully human antagonistic anti-T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) antibody in IgG1 format with Fc-mediated effector function.MethodsThe ability of M6223 to block the interaction of TIGIT with its ligands, CD155 and CD112, and the interaction of TIGIT with CD226 was determined by a flow cytometry-based binding assay. The anti-tumor efficacy, immune profile, and effector function of M6223 were investigated in syngeneic tumor models in huTIGIT knock-in mice. M6223 was either formatted with an effector competent mouse IgG2c constant region (M6223-muIgG2c) or formatted with effector null mouse IgG1-D256A constant region (M6223-muIgG1) as two versions of chimeric antibodies for the in vivo studies.ResultsM6223 dose-dependently blocked the binding of TIGIT to its ligands, including CD155 and CD112, thereby inhibiting a TIGIT-mediated immunosuppressive pathway. In addition, M6223 interrupted the interaction of TIGIT with the costimulatory receptor CD226. By blocking the interactions, the chimeric protein M6223-muIgG2c showed anti-tumor efficacy in multiple tumor models, including an MC38 tumor model (figure 1), and generated tumor antigen-specific long-term protective immunity in immunocompetent huTIGIT knock-in mice. M6223 monotherapy dose-dependently elevated the ratio of CD8+ cytotoxic T cells to regulatory T cells and the ratio of CD226 to TIGIT expression in immune cells in the tumor microenvironment. We also found that M6223 selectively depleted suppressive and exhausted TIGIT+ immune cell subsets and the anti-tumor activity of effector null M6223-muIgG1 was significantly lost (p<0.0001), suggesting that Fc-mediated effector function contributes to M6223 anti-tumor activity. Antibody depletion studies demonstrated that CD8+ T cells and natural killer cells contributed to the anti-tumor activity of M6223 in a complementary manner.Abstract 326 Figure 1M6223-muIgG2c displayed dose-dependent anti-tumor efficacy. M6223-muIgG2c displayed dose-dependent anti-tumor efficacy in an MC38 tumor model in hTIGIT knock-in mice.ConclusionsGiven that TIGIT blockade can inhibit an immunosuppressive pathway as well as remove the suppression on a costimulatory pathway, M6223 has the potential to induce an anti-tumor immune response by three complementary mechanisms: direct blockade of the TIGIT pathway, stimulation of CD226 dimerization/activation, and depletion of TIGIT+ immune subsets by Fc-mediated effector function. Our data demonstrate that these complementary mechanisms orchestrate the anti-tumor activity of M6223. A Phase I, first-in-human clinical trial (NCT04457778) is underway to determine the safety, tolerability, maximum tolerated dose and recommended dose for expansion of M6223 as a single agent (Part 1A) and in combination with bintrafusp alfa (Part 1B) in patients with metastatic or locally advanced solid unresectable tumors.Ethics ApprovalAll animal experiments were performed in accordance with EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA (protocol 17-008, 20-005) and Wuxi AppTec Animal Care and Use Committee (IACUC) guidelines

Interaction of Rhodium with Chloro-Complexes of Palladium at Elevated Temperatures

Синтезированы порошки высокодисперсного родия моно- и полиблочной структуры. Исследованы процессы укрупнения кристаллитов нанодисперсного родия. Методами электронной просвечивающей микроскопии и рентгенофазового анализа детально изучен процесс укрупнения родиевой черни при 130 и 180 °С. Установлено, что в растворах соляной кислоты наблюдается растворение родия (0), связанное с наличием на его поверхности хемосорбированного кислорода. Впервые показана возможность образования твердых родий- палладиевых растворов замещения при протекании реакции цементацииPowders of superfine rhodium with mono- and polyblock structures were obtained. The processes of coarsening of nanodispersed rhodium crystallites were investigated in detail at 130 and 180 °C. In muriatic solutions, dissolution of metal rhodium was found to occur. It was connected with the presence of chemisorbed oxygen at its surface. The possibility of formation of rhodium-palladium substitutional solid solutions on the electrolytic precipitation was firstly establishe

How Teachers-to-Be Acquire Skills To Transfer Civic Values to Primary School Contexts

The paper aims at describing how to train teachers\u2019-to-be to acquire skills necessary to transfer civic values to primary school contexts. It addresses the research questions: what groups of values civic values consist of; what activities might be used to train teachers-to-be to transfer these values to primary school contexts; how pedagogical students should be taught to teach civil values. Case study, pedagogical modeling and pedagogical experiment have been applied in the research. Data have been gathered through interviewing school administration, in-service teachers and teachers-to-be. Model of Teaching Skills Acquisition to Transfer Civic Values to primary school contexts (TSATCVmodel) is described. The research results in enlisting activities to facilitate pedagogical training in civic values teaching on the basis of TSATCV-model; showing educators\u2019 opinions of the teachers\u2019-to-be level of skills in transferring civic values to primary school contexts; describing teachers\u2019-to-be attitudes to their training to transfer civic values in primary school contexts

Behavior of Components of Waste Solutions of Precious Metals Refinery in Autoclave Conditions

В данной работе изучено поведение в гидротермальных условиях компонентов солевых растворов с низким содержанием металлов платиновой группы (< 2 мг/л каждого). Прослежено изменение состава фаз и характеристик осадка в зависимости от параметров гидролитического осаждения соединений железа. Рассмотрены возможности выделения металлов платиновой группы из данных растворовBehavior of components of salt solutions with a low content of platinum grope metals (< 2 mg/l) in hydrothermal conditions was investigated in this work. The changes of the phase composition and the precipitate characteristics were traced depending on the parameters of the hydrolytic precipitation of compounds of iron. Feasibilities of recovery of platinum grope metals from these solutions were discusse

Modulation of Adenovirus Vector Tropism via Incorporation of Polypeptide Ligands into the Fiber Protein

The efficacy of adenovirus (Ad)-based gene therapy might be significantly improved if viral vectors capable of tissue-specific gene delivery could be developed. Previous attempts to genetically modify the tropism of Ad vectors have been only partially successful, largely due to the limited repertoire of ligands that can be incorporated into the Ad capsid. Early studies identified stringent size limitations imposed by the structure of the Ad fiber protein on ligands incorporated into its carboxy terminus and thus limited the range of potential ligand candidates to short peptides. We have previously identified the HI loop of the fiber knob domain as a preferred site for the incorporation of targeting ligands and hypothesized that the structural properties of this loop would allow for the insertion of a wide variety of ligands, including large polypeptide molecules. In the present study we have tested this hypothesis by deriving a family of Ad vectors whose fibers contain polypeptide inserts of incrementally increasing lengths. By assessing the levels of productivity and infectivity and the receptor specificities of the resultant viruses, we show that polypeptide sequences exceeding by 50% the size of the knob domain can be incorporated into the fiber with only marginal negative consequences on these key properties of the vectors. Our study has also revealed a negative correlation between the size of the ligand used for vector modification and the infectivity and yield of the resultant virus, thereby predicting the limits beyond which further enlargement of the fiber knob would not be compatible with the virion's integrity

Modification of Adenovirus Capsid with a Designed Protein Ligand Yields a Gene Vector Targeted to a Major Molecular Marker of Cancer▿

The future of genetic interventions in humans critically depends on the selectivity and efficiency of gene transfer to target tissues. The viral gene vectors explored to date cannot selectively transduce the desired targets. While substantial progress has been made in developing targeting strategies for adenovirus (Ad) vectors, future advances in this direction are severely limited by the shortage of naturally existing molecules available for use as targeting ligands. This shortage is due to fundamental and irresolvable differences at the level of both posttranslational modifications and intracellular trafficking between the Ad structural proteins and those natural proteins that are involved in interactions with the cell surface and could otherwise be considered as potential targeting ligands. We hypothesized that this problem could be resolved by altering the natural tropism of Ad vector through incorporation into its capsid of a rationally designed protein ligand, an affibody, whose structural, functional, and biosynthetic properties make it compatible with the Ad assembly process. We tested this hypothesis by redesigning the receptor-binding Ad protein, the fiber, using affibodies specific for human epidermal growth factor receptor type 2 (Her2), a major molecular marker of human tumors. The biosynthesis and folding of these fiber chimeras were fully compatible with Ad virion formation, and the resultant viral vectors were capable of selective delivery of a dual-function transgene to Her2-expressing cancer cells. By establishing the feasibility of this affibody-based approach to Ad vector targeting, the present study lays the foundation for further development of Ad vector technology toward its clinical use

Interaction of Rhodium with Chloro-Complexes of Palladium at Elevated Temperatures

Синтезированы порошки высокодисперсного родия моно- и полиблочной структуры. Исследованы процессы укрупнения кристаллитов нанодисперсного родия. Методами электронной просвечивающей микроскопии и рентгенофазового анализа детально изучен процесс укрупнения родиевой черни при 130 и 180 °С. Установлено, что в растворах соляной кислоты наблюдается растворение родия (0), связанное с наличием на его поверхности хемосорбированного кислорода. Впервые показана возможность образования твердых родий- палладиевых растворов замещения при протекании реакции цементацииPowders of superfine rhodium with mono- and polyblock structures were obtained. The processes of coarsening of nanodispersed rhodium crystallites were investigated in detail at 130 and 180 °C. In muriatic solutions, dissolution of metal rhodium was found to occur. It was connected with the presence of chemisorbed oxygen at its surface. The possibility of formation of rhodium-palladium substitutional solid solutions on the electrolytic precipitation was firstly establishe

Neurodynamic predictors the effectiveness of cognitive activity of students ensuring healthy lifestyle

The paper presents the results of the assessment of neurodynamic characteristics and correlation of cognitive activity parameters of students with individual neurodynamic characteristics following the criteria of Sustainable Development Goal 3 "Good health and well-being" (SDG 3). The study was conducted in a cohort of female students aged 17-19 (n=111) of the South Ural State Humanitarian Pedagogical University during the inter-sessional period. Diagnostics of neurodynamic characteristics of students was carried out using the hardware and software complex "NS–pSychoTest". Descriptive statistical analysis of data and correlation analysis were carried out in the environment of Statistica v. 7.0. The results of sensorimotor response presented in the article reflect the optimal level of adaptive regulation of the cerebral component of activity in the majority of the surveyed pedagogical university students in the conditions of their educational and professional activities, which is reflected in the relative stability of cerebral processes with average functional mobility and the optimal level of neurophysiological regulation of CNS activity in the conditions of sensory interference of the students of the cohort of the survey. The paper reveals the interrelationships of neurodynamic indicators with various characteristics of cognitive testing, which indicates the success of the development of educational programs