Indirect Action Research Articles

Как учесть мнение населения при промышленном освоении Арктики

The article deals with the issues of taking into account the opinion of the local population when justifying and implementing projects for industrial development of the Arctic. The mechanism and procedures for assessing and taking into account the opinion of the population at all stages of the life cycle of a project for exploration and extraction of minerals from its initiation to completion are proposed by informing the population about the project of planned activities, holding public hearings, ethnological expertise, as well as ethnological audit and ethnosocial monitoring. The model of interaction of stakeholders (mining companies, local authorities and indigenous peoples of the North) is based on the concept of sharing joint benefits from the industrial development of the Arctic, which is based on the cooperation of the parties and corporate social responsibility of business in the area of planned activities. It is proposed to protect the interests of indigenous peoples by signing agreements on the socio-economic development of the territory, creating compensation funds and implementing compensation projects of socio-economic, environmental orientation and projects to preserve the culture and ethnos of indigenous peoples, which are formed on the basis of population surveys. 
 The algorithm of multi-criteria evaluation, ranking and selection of compensation projects, taking into account priorities for various groups of the population, as well as economic regulators for supporting compensation projects, including direct action tools (compensation fund, etc.), and indirect action tools (tax incentives, subsidies to support traditional crafts, etc.) is proposed.

Effect of Local Pressurization on Microstructure and Mechanical Properties of Aluminum Alloy Flywheel Housing with Complex Shape.

In this work, squeeze casting experiments of flywheel housing components with a large wall thickness difference and a complex shape were carried out with AlSi9Mg aluminum alloy. The defects, microstructures, and mechanical properties under different process parameters were investigated. Furthermore, the local pressurization process was applied to the thick-walled positions to force-feed the cast defects. The mechanical properties and microstructures at these positions were analyzed. The results showed that the surface quality of formed components was good and that local pressurization could effectively reduce the shrinkage cavity and shrinkage porosity in thick walls, but the scope and effect of forced feeding were limited. The optimum process parameters were a pouring temperature of 650 °C, a specific pressure of 48 MPa, a mold temperature of 220 °C, a local pressurization of 800 MPa, and pressure delay times of 15 s (side A) and 17 s (side B). The ultimate tensile strength, yield strength, and elongation of the formed component under validation experiments of the optimum process parameters were 201 MPa, 103 MPa, and 5.1%. Meanwhile, the fine grains of primary α-Al were mainly rosette and equiaxed grains, and the average grain size was about 40 μm. The microstructure of the eutectic silicon was acicular and was prone to segregation under pressure. According to profile morphology, the positions after pressurization were divided into a deformation zone, a direct action zone, and an indirect action zone. The coexistence of as-cast and plastic deformation microstructures was observed. The effect of local pressurization mainly involved a change in the solidification process, plastic deformation, and forced feeding.

Department of Pharmacology of the Military Medical Academy in the 21st century: New achievements based on historical traditions (2000–2023)

In the early 2000s at the Department of Pharmacology, active research was launched into the mechanisms of hypoxia, creation of antihypoxic drugs, study of means and technologies for increasing performance, and drugs with immunomodulatory and reparative effects. The mechanisms of hypoxia and life support in extreme conditions have been a traditional area of scientific research of the department. Starting back in the 1960s under the leadership of V. M. Vinogradov, this direction gained development and scientific recognition by the end of the 1990s. During this period, new antihypoxants of direct and indirect actions were created and thoroughly studied, namely, gutimin, bemithyl, amtizol, trimetazidine, and others. Nearly all employees of the department and numerous applicants for academic degrees from among both academic and nonacademic employees participated in the research. The use of approaches and concepts of molecular physiology and pharmacology achieved very interesting and promising results for implementation. An unconditional success in scientific research in this area has been the elucidation of the molecular mechanisms of action of aminothiol-type antihypoxants, which consist in optimizing energy production and energy consumption in cells and the ability of compounds to reduce membrane damage caused by lipid peroxidation and clearly activate antioxidant systems. The second direction was the study of the molecular mechanisms of sustainable adaptation to various factors, which was started by Prof. A. V. Smirnov. Thus, long-term adaptation patterns were established in the body’s adaptation to high-altitude hypoxia, overheating, and heavy repeated loads. The contribution of individual organs to the development of these adaptive phenomena was quantitatively determined. In the experiment, effective schemes for emergency adaptation were developed using “pulse modes” of training influences against the use of pharmacological adaptogens. A significantly more pronounced adaptogenic activity has been established for drugs such as thiobenzimidazole (bemythyl) and trecrezan in comparison with known adaptogens, such as dibazole and eleutherococcus. Based on experimental data, similar schemes for pharmacologically enhanced and accelerated emergency adaptation have been developed and tested on healthy volunteers, particularly to sharp changes in climatic conditions (overheating, hypothermia, and hypoxia) and metabolic cocktails based on the antihypoxant bemityl (B-100, B-200, and B-300). These schemes and pharmacological interventions make it possible, in just a few days, to make the body noticeably adapt to the action of certain climatic factors. The third direction was the creation and study of new pharmacological agents for the correction of the effects of hypoxia, toxic pulmonary edema, and liver and immune system damage based on condensed indole systems and their product transformations. Consequently, indole derivatives (approximately 60 compounds have been synthesized and studied) are low toxic and have antihypoxic, antiedema, hepatoprotective, actoprotective and antiviral activities.

Regulation of Innovative Processes at the Enterprise in a Competitive Environment

Purpose: The objective of the study is to determine the importance of innovation factor in enhancing the competitiveness of enterprises and the necessity of transition of domestic enterprises to an innovative way of development, as well as the regulation of innovation processes in the enterprise in a competitive environment. Design / Methodology / Approach: To achieve the aim of the study, the following scientific methods were used: analysis, synthesis and comparison. Findings: The essence of the regulation of innovation processes at the enterprise in a competitive environment was revealed. It was researched that the revival of investment and business activity in the context of regions had a positive impact on the innovative sphere. All these factors have appreciably improved the innovative environment and provided effective stimulation of the innovative development. Note that foreign and domestic experience has shown that it is the state that has the exclusive role of regulation and stimulation of innovative activity in the enterprise. As it has a powerful influence on innovative process by means of economic methods of direct and indirect action for the purpose of support of competitiveness of innovative production of the enterprises. Originality / Value: The research of motivation of creation of enterprises with foreign investment focused on attraction of advanced technics and technology to the country with such short-term effect as receipt of currency proceeds was further developed. The study showed that enterprises with foreign investment cannot solve the problem of currency deficit in the state, but the creation of conditions for attracting advanced technics and technology to the country is the basis for the implementation of a number of urgent tasks of economic and social development of the country. For this purpose, it is necessary to provide additional benefits to priority basic industries, determining the development of scientific and technological progress in Ukraine and the creation of favorable conditions for the inflow of innovative capital of foreign investors, which will have a positive impact on the development of the Ukrainian economy. Practical Meaning: It is proved that innovation management at Ukrainian enterprises requires formalisation of innovation and investment activity on the basis of production factors and national wealth. Therefore, it is necessary to modernise the methods of assessment of innovation projects, taking into account the latest experience of innovation activity, with the development of basic analytical procedures and determination of the scope of their rational use. Further Research: Development of a mechanism for regulating innovation processes at the enterprise in a competitive environment.

Effect of 20-hydroxyecdysone and its metabolites in the absence or presence of IGF-1 on regulation of skeletal muscle cell growth

Purpose: To investigate the effect of 20-hydroxyecdysone (20E) and its metabolites and their synergistic effect with IGF-1 on regulation of skeletal muscle cell growth.
 Methods: Mouse skeletal muscle cell line (C2C12) was solely treated with 20E and its metabolites (14- deoxy- 20-hydroxyecdysone, poststerone, and 14-deoxypoststerone) at doses of 0.1, 1, and 10 µM or co-treated with IGF-1 (10 ng/ml). Cell viability and proliferative capacity were evaluated using MTT and BrdU incorporation assays, respectively. Myogenic differentiation proteins [embryonic myosin heavy chain (EbMHC) and MHC], androgen receptor (AR), and IGF-1 receptor (IGF-1R) protein expression were investigated using immunocytochemistry.
 Results: Treatments of 20E and its metabolites had no toxicity on skeletal muscle cells or induced AR/IGF-1R expression. In addition, solely treatment of 20E and its metabolites or co-treatment with IGF-1 had no significant effect on cell proliferation and myogenic differentiation capacity. In contrast, IGF-1 treatment alone significantly increased EbMHC expression (p<0.0001), MHC expression (p<0.05), and myotube number (p<0.05).
 Conclusion: These results indicate that 20E and its metabolites have no direct or synergistic effect with IGF-1 on skeletal muscle cell growth. Nevertheless, the pharmacological effects of 20E on skeletal muscle mass and strength in vivo that raises its therapeutic potential may associate with its indirect action.

The BCL2 inhibitor venetoclax mediates anticancer effects through dendritic cell activation.

BCL2 is an apoptosis-inhibitory oncoprotein that also possesses apoptosis-unrelated activities. Pharmacological BCL2 inhibitors have been developed with the scope of driving BCL2-dependent cancer cells into apoptosis, and one BCL2 antagonist, venetoclax, has been clinically approved for the treatment of specific leukemias and lymphomas. Nonetheless, it appears that venetoclax, as well as genetic BCL2 inhibition, can mediate anticancer effects through an indirect action. Such an indirect effect relies on the enhancement of the immunostimulatory function of dendritic cells, hence increasing tumor immunosurveillance. Mechanistically, BCL2 inhibition involves improved antigen presentation by conventional type-1 dendritic cells (cDC1s) due to the activation of an interferon response, leading to a T cell-mediated anticancer immune response that can be further enhanced by PD-1 blockade. These findings support the emerging hypothesis that successful antineoplastic drugs generally mediate their effects indirectly, through the immune system, rather via merely cell-autonomous effects on malignant cells.

A Monte Carlo study on the impact of indirect action on neutron relative biological effectiveness.

Recent Monte Carlo studies have linked the energy-dependent risk of neutron-induced stochastic effects to the relative biological effectiveness (RBE) of neutrons in inflicting difficult-to-repair clusters of lesions in nuclear deoxyribonucleic acid (DNA). However, an investigation on the damaging effects of indirect radiation action is missing from such studies. In this work, we extended our group's existing simulation pipeline by incorporating and validating a model for indirect action. Our updated simulation pipeline was used to study the impact of indirect action and estimate neutron RBE for inflicting clustered lesions in DNA. In our results, although indirect action significantly increased the average yield of DNA damage clusters, our neutron RBE values are lower in magnitude than previous estimates due to model limitations and the greater relative impact of indirect action in lower-linear energy transfer (LET) radiation than in higher-LET radiation.

UFOs shot down: An Extraterrestrial Charade? The last chance before the nuclear Apocalypse

In February 2023, the airspace of two countries in North America and China was the scene of a series of UFO sightings, resulting in the proven shooting down of one of these objects by the United States Air Force. Reportedly, one of the object was identified as a balloon of Chinese origin, while the others remain unknown. With respect to this, the Latin American Academy of Scientific Ufology (LAASU) organized an international meeting to discuss this subject on March 18, 2023 and five professionals from different academic fields were invited to give their points of view. With over 40 years dedicated to Unidentified Flying Objects (UFO) research, Dr. Acosta Navarro, LAASU’s Director, supported the that hypothesis of extraterrestrial manifestation would be the best explanation for the observed UFO phenomena shot down, which could represent a charade or puzzle to be interpreted. The development of this article within LAASU was prioritized by the transcendence and contemporaneity of the phenomenon and was named the "Operation Ray of Zeus". Ten points of argumentation are presented to support this hypothesis. We propose that the downed UFOs could be a consequence of direct or indirect actions by Extraterrestrial Intelligences, which can be interpreted as a charade, intending to raise awareness and reflection about the current critical moment of risk of self-destruction, highlighting our technological limitations and showing our vulnerability.

Determining the effect of drug "Warfarin sodium" on toxicity indicators in an acute experiment

The drug "Warfarin sodium" refers to anticoagulants of indirect action. It contains only one substance - warfarin sodium, the toxicological indicator of which have been studied in many countries. Therefore, the range of indicators for DL50 of warfarin sodium is very large. However, warfarin sodium has not yet been studied in Ukraine, its maximum permissible concentration in the air of the work area has not been established. Significant volumes of production and use of the drug “Warfarin sodium” on the territory of Ukraine necessitate the clarification of its main toxicological indicators and the establishment of the maximum allowable concentration in the air of the working area, which includes several stages. The first of them is the purpose of this work, namely: to establish DL50 upon intragastric administration of the drug "Warfarin sodium" to two species of animals in the conditions of an acute experiment. Experimental animals (60 non-linear white rats and 70 non-linear white mice) were divided into 9 groups. Six groups were injected with the drug "Warfarin sodium" in different doses: the first group (female rats) – 58 mg/kg per animal, the second (also female rats) – 29 mg/kg, the third (male rats) – 323 mg/kg, the fourth (also male rats) – 161.5 mg/kg, the fifth (mice of both sexes) – 374 mg/kg, the sixth (also mice of both sexes) – 187 mg/kg. Three control groups (the first – 6 male rats, the second – 6 female rats, the third – 14 mice) received distilled water. As a result, the mortality rates of experimental animals were obtained, on the basis of which, using the probit analysis method, the toxicity indicator of DL50 was determined: for female rats – 15.85 mg/kg, male rats – 398.11 mg/kg and mice –645.65 mg/kg. The established DL50 for male rats after intragastric administration of the drug "Warfarin sodium" may indicate an increase in their resistance to the drug, and this determines the expediency of periodic repeated acute experiments in order to verify the relevance of previously established DL50 of sodium warfarin. According to DL50 upon intragastric administration to female rats, which are the most sensitive species of animals to it, warfarin sodium belongs to highly hazardous substances.

Cellular lethal damage of 64Cu incorporated in mammalian genome evaluated with Monte Carlo methods.

Targeted Radionuclide Therapy (TRT) with Auger Emitters (AE) is a technique that allows targeting specific sites on tumor cells using radionuclides. The toxicity of AE is critically dependent on its proximity to the DNA. The aim of this study is to quantify the DNA damage and radiotherapeutic potential of the promising AE radionuclide copper-64 (64Cu) incorporated into the DNA of mammalian cells using Monte Carlo track-structure simulations. A mammalian cell nucleus model with a diameter of 9.3 μm available in TOPAS-nBio was used. The cellular nucleus consisted of double-helix DNA geometrical model of 2.3 nm diameter surrounded by a hydration shell with a thickness of 0.16 nm, organized in 46 chromosomes giving a total of 6.08 giga base-pairs (DNA density of 14.4 Mbp/μm3). The cellular nucleus was irradiated with monoenergetic electrons and radiation emissions from several radionuclides including 111In, 125I, 123I, and 99mTc in addition to 64Cu. For monoenergetic electrons, isotropic point sources randomly distributed within the nucleus were modeled. The radionuclides were incorporated in randomly chosen DNA base pairs at two positions near to the central axis of the double-helix DNA model at (1) 0.25 nm off the central axis and (2) at the periphery of the DNA (1.15 nm off the central axis). For all the radionuclides except for 99mTc, the complete physical decay process was explicitly simulated. For 99mTc only total electron spectrum from published data was used. The DNA Double Strand Breaks (DSB) yield per decay from direct and indirect actions were quantified. Results obtained for monoenergetic electrons and radionuclides 111In, 125I, 123I, and 99mTc were compared with measured and calculated data from the literature for verification purposes. The DSB yields per decay incorporated in DNA for 64Cu are first reported in this work. The therapeutic effect of 64Cu (activity that led 37% cell survival after two cell divisions) was determined in terms of the number of atoms incorporated into the nucleus that would lead to the same DSBs that 100 decays of 125I. Simulations were run until a 2% statistical uncertainty (1 standard deviation) was achieved. The behavior of DSBs as a function of the energy for monoenergetic electrons was consistent with published data, the DSBs increased with the energy until it reached a maximum value near 500 eV followed by a continuous decrement. For 64Cu, when incorporated in the genome at evaluated positions (1) and (2), the DSB were 0.171 ± 0.003 and 0.190 ± 0.003 DSB/decay, respectively. The number of initial atoms incorporated into the genome (per cell) for 64Cu that would cause a therapeutic effect was estimated as 3,107 ± 28, that corresponds to an initial activity of 47.1 ± 0.4 × 10-3 Bq. Our results showed that TRT with 64Cu has comparable therapeutic effects in cells as that of TRT with radionuclides currently used in clinical practice.

Updating in the mountains: A sensemaking perspective on ski guiding

For a ski guide, updating on the ever-changing natural conditions and group dynamics is essential to stay safe and provide a good experience for clients. In this paper, we explore how guides update their understanding in the mountains. Our data arise out of a one-season participant ethnography of ski guiding in Norway. The research team had two authors collecting data, one as an “outsider” and another as an “insider”. We find that the work of a ski guide involves a process of monitoring, testing, and projecting. Complementing and challenging the avalanche literature, we find that ski guide decision-making is an embodied updating process rather than a cognitive one that happens at “decision points”. We highlight the implications of these findings both for guides and researchers. Management implications•Continuous updating is critical for adapting to changing conditions and for breaking with set frames of understanding. Therefore, guides should not overly rely on decision aids or fixed decisions.•Guides should listen to their intuition when something “feels off” and be in doubt when something “feels right”.•Clients should acknowledge that they are an active part of the setting and, therefore, influence the outcome with both direct and indirect actions.•Updating relies on the continuous monitoring, testing, and projecting of ecological and social cues. Neither type should be viewed in isolation.

Clinical, Cognitive, and Neurobiological Correlates of Impaired Timing Abilities Associate to Cannabis Use: a Systematic Review

AbstractTime perception received growing interest in psychiatry for its psychopathological implications. Cannabis use can cause a subjective experience of temporal perception alteration and increases the risk of emergence of mental illnesses such as psychotic and mood disorders. In this framework, we systematically reviewed the findings regarding the clinical, cognitive, and neurobiological correlates of time alterations due to cannabis consumption. According to preclinical results, cannabis exerts a dose-dependent time overestimation, associated with motor inhibition and circadian alterations. Clinical results reported that cannabis impair time estimation and time reproduction abilities, causing subjective temporal fragmentation and depersonalization symptoms. The alteration of timing mediated by cannabis use might depend on a dopaminergic indirect action and on structural, functional, and metabolic alterations of the cerebello-thalamo-cortical circuit. Despite the potential interest, however, only few studies explored the link between cannabis-induced alterations of time processing and psychiatric symptoms.

The potential role of <i>Aureobasidium pullulans</i> in the development of foliar symptoms of Esca disease in grapevine

Esca belongs to the group of grapevine trunk diseases - fungal diseases present worldwide in all wine-growing regions. Some aspects of the disease, like the development of external symptoms, have still not been completely discovered and are believed to be affected by several factors, including interactions within the vine microbiome. The examination of the occurrence of the yeast-like fungus Aureobasidium pullulans in the healthy wood of Esca-diseased grapevines via both isolation and qPCR measurements showed a positive correlation between its abundance and the severity of foliar symptoms, suggesting the contribution of this fungus to Esca pathogenesis via an indirect action. In vitro confrontation tests revealed antagonistic interaction between A. pullulans and the Esca pathogen Phaeomoniella chlamydospora. Mutual growth inhibition and the induction of asexual sporogenesis were observed for both fungi without cytotoxic effects. In planta confrontation tests revealed that A. pullulans in combination with P. chlamydospora can lead to severe foliar damage in a strain-dependent manner. This phenomenon could be explained by the altered metabolism of the Esca pathogen in the presence of A. pullulans, or by the cumulative/synergistic effects of the secreted polysaccharides and/or proteins of the two fungi. The present study shows the importance of microbial interactions in the development of plant diseases, highlighting that even a non-pathogenic microorganism can act as a disease-enhancer.

A Geospatial Analysis-Based Method for Railway Route Selection in Marine Glaciers: A Case Study of the Sichuan-Tibet Railway Network

Marine glaciers play a significant role in shaping landforms due to their erosive nature coupled with their surrounding environment. During this process, they pose a natural hazard threat to man-made infrastructure. The dynamic nature of these glaciers poses a particular threat, especially to railway infrastructure constructed in remote areas with glacial activity. Substantial research has been undertaken on the role of threats posed by marine glaciers to railway infrastructure. However, a detailed study of favorable glacier landforms prior to railway construction has yet to be explored. In this study, we propose a geospatial analysis-based method to determine the favorable most landforms shaped by marine glaciers for railway network route selection. This study provides a novel approach by first analyzing the availability of four major favorable landforms shaped by marine glaciers (glacier canyons, valley shoulders, moraine terraces, and ancient dammed lake basins), then proposes a railway route selection method for marine glacier distribution areas involving three steps. First, it is necessary to understand the basic situation of regional glaciers; then, to determine a feasible location for the railway based on judgment of the direct and indirect action areas of glaciers; and finally, through a thematic study of glacial geomorphology, to devise corresponding strategies for using glacial landforms to optimize the railway route. In order to verify the feasibility of the proposed method, it was implemented in the Palong Zangbo watershed of the Sichuan–Tibet railway network. Utilizing the power function method, the glacier basin areas of 22 glacier canyons along the Sichuan–Tibet railway line were identified and the maximum annual average velocity of 75 glaciers over the past ten years was calculated by offset tracking technology. The results indicate that the proposed optimization strategies utilizing glacier canyons for a short and straight route scheme and leveraging moraine terraces for a high-line scheme can provide comprehensive guidance for railway route selection in marine glacial areas.

Insulin Signaling Through the Insulin Receptor Increases Linear Growth Through Effects on Bone and the GH-IGF-1 Axis.

Childhood overnutrition is associated with increased growth and bone mineral density (BMD) vs the opposite for undernutrition. The role of insulin receptor (InsR) signaling in these phenotypes is unclear. Rare disease patients with hyperinsulinemia and impaired InsR function (homozygous [-/-] or heterozygous [+/-] INSR pathogenic variants, type B insulin resistance [TBIR]) model increased InsR signaling, while patients with intact InsR function (congenital generalized lipodystrophy, CGL) model decreased InsR signaling. This work aimed to understand mechanisms whereby InsR signaling influences growth. A cross-sectional comparison was conducted of CGL (N = 23), INSR-/- (N = 13), INSR+/- (N = 17), and TBIR (N = 8) at the National Institutes of Health. Main outcome measures included SD scores (SDS) for height, body mass index, insulin-like growth factor (IGF)-1, and BMD, and IGF binding proteins (IGFBP)-1 and -3. INSR-/- vs CGL had higher insulin (median 266 [222-457] vs 33 [15-55] mcU/mL), higher IGFBP-1 (72 350 [55 571-103 107] vs 6453 [1634-26 674] pg/mL), lower BMI SDS (-0.7 ± 1.1 vs 0.5 ± 0.9), lower height SDS (-1.9[-4.3 to -1.3] vs 1.1 [0.5-2.5]), lower BMD SDS (-1.9 ± 1.4 vs 1.9 ± 0.7), and lower IGFBP-3 (0.37 [0.19-1.05] vs 2.00 [1.45-2.67] μg/mL) (P < .05 for all). INSR +/- were variable. Remission of TBIR lowered insulin and IGFBP-1, and increased IGF-1 and IGFBP-3 (P < .05). Patients with hyperinsulinemia and impaired InsR function exhibit impaired growth and lower BMD, whereas elevated InsR signaling (CGL) causes accelerated growth and higher BMD. These patients demonstrate that insulin action through the InsR stimulates direct anabolic effects in bone and indirect actions through the growth hormone (GH)-IGF-1 axis. TBIR patients exhibit abnormalities in the GH axis that resolve when InsR signaling is restored, supporting a causal relationship between InsR and GH axis signaling.

Metaraminol in reverting hypotension in equine anesthesia with isoflurane and dexmedetomidine: Case report

Systemic hypotension is the most frequent complication of inhalational anesthesia in horses and is directly related to increased post-anesthetic morbidity and mortality. The treatment of hypotension depends on the physiological cause and can be performed with positive chronotropic, inotropic and vasopressor drugs, individually or combined. However, there are few drugs used in horses and the effects of these drugs on cardiovascular support in these animals during anesthesia are poorly described. For this reason, this study aimed to report the action of metaraminol (Aramin®), a vasopressor with direct and indirect action on adrenergic receptors, in the correction of hypotension in a horse submitted to elective orchiectomy, anesthetized with isoflurane and continuous infusion of dexmedetomidine. Cardiovascular changes with different infusion rates of 1, 2 and 4 µg/kg/min are described. Metaraminol reversed hypotension at a rate of 4 µg/kg/min, increasing systolic blood pressure by 93 mmHg, mean blood pressure by 74 mmHg, diastolic blood pressure by 66 mmHg, and reduced cardiac output by 7.1 L/min and heart rate to 32 bpm, in relation to mean arterial pressure of 58 mmHg, cardiac output of 13.4 L/min and heart rate of 36 bpm at the expired rate of 1.3% isoflurane. Furthermore, it improved cardiac contractility at the rate of 2 and 4 µg/kg/min and did not cause arrhythmia at any infusion rates.

Corilagin alleviates liver fibrosis in zebrafish and mice by repressing IDO1-mediated M2 macrophage repolarization

BackgroundLiver fibrosis caused by chronic liver injury, eventually develops into liver cirrhosis and hepatocellular carcinoma. Currently, there are no effective drugs to relieve liver fibrosis due to the lack of molecular pathogenesis characteristics. Former research demonstrates that the hepatic immune microenvironment plays a key role in the pathogenesis of liver fibrosis, thus macrophages are important immune cells in the liver. Our previous study has found that IDO1 plays an important role in the liver immune microenvironment. CRG is a gallic acid tannin found in medicinal plants of many ethnicities that protects against inflammation, tumors and chronic liver disease. However, the mechanism of by which CRG mediates the interaction of IDO1 with macrophages during hepatic immune maturation is not clear. PurposeTo investigate the regulatory mechanism of CRG in liver fibrosis and the intrinsic relationship between IDO1 and macrophage differentiation. MethodsZebrafish, RAW264.7 cells and mice were used in the study. IDO1 overexpression and knockdown cell lines were constructed using lentiviral techniques. ResultsWe discovered that CRG remarkably reduced the AST and ALT serum levels. Histological examination revealed that CRG ameliorates CCL4-induced liver fibrosis and depressed the expression of α-SMA, Lamimin, Collagen-Ι and fibronectin. Besides, we found that CRG promoted increased MerTK expression on partly macrophages. Interestingly, in vitro, we found that CRG suppressed IDO1 expression and regulated macrophage differentiation by upregulating CD86, CD80 and iNOS, while downregulating CD206, CD163, IL-4 and IL-10 expression. Additionally, we found that CRG could inhibit hepatic stellate cell activation by direct or indirect action. ConclusionOur findings suggest that CRG alleviates liver fibrosis by mediating IDO1-mediated M2 macrophage repolarization.

International Terrorism Using Toxic Chemicals as an Element of Hybrid Warfare

Modern terrorism is a complex system that consists of a complex of complementary processes – ideological, criminal, military, political, religious and nationalistic. Chemical terrorism is one of the elements of hybrid warfare – a new technology in the fight for the reorganization of the world at the present stage. The purpose of this article is to consider one of the elements of hybrid wars – chemical terrorism. Sources and informational basis of the research, methodology. In this work, the sources published by the Organization for the Prohibition of Chemical Weapons (OPCW) were used. The publications available through the databases PubMed, Google Scholar, eLibrary, etc. were also studied. Research method – system analysis. The probability of the use of chemical warfare agents and toxic chemicals by terrorists of various ideological orientations as part of a hybrid war strategy has been studied. The discussion of the results. Hybrid military conflicts of a non-classical nature involve the participation of international terrorist organizations in hostilities. The Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on Their Destruction (CWC) does not explicitly prohibit non-state actors from obtaining and using chemical weapons. This situation is very convenient for the states that have signed the CWC and use terrorist organizations as part of the strategy of indirect action. In such cases the information and psychological operations are aimed at the collapse and fragmentation of countries, undermining their ability to resist, discrediting their leaders, and causing a split in the ranks of the allies. This was most clearly shown in the incidents with the use of toxic chemicals in Syria. Conclusion. Working groups under the auspices of the UN and the OPCW, sent to Syria to investigate incidents with the use of sarin, proved unable to conduct objective investigations. They usually ended up on the side of the sponsors of chemical terrorist attacks, despite the evidence of falsification. This, in turn, can lead to serious military conflicts, for which the role of casus belli will be played by false news from the global media. The only mechanism that made it possible to stop such provocations in Syria was a public warning from the Russian side about the place and time of the planned false flag attack. At the same time, such a selective position of the UN and the OPCW can at any moment lead to the loss of the control over chemical weapons in certain regions of the world.

Intrinsic and environmental basis of aging: A narrative review

Longevity has been a topic of interest since the beginnings of humanity, yet its aetiology and precise mechanisms remain to be elucidated. Aging is currently viewed as a physiological phenomenon characterized by the gradual degeneration of organic physiology and morphology due to the passage of time where both external and internal stimuli intervene. The influence of intrinsic factors, such as progressive telomere shortening, genome instability due to mutation buildup, the direct or indirect actions of age-related genes, and marked changes in epigenetic, metabolic, and mitochondrial patterns constitute a big part of its underlying endogenous mechanisms. On the other hand, several psychosocial and demographic factors, such as diet, physical activity, smoking, and drinking habits, may have an even more significant impact on shaping the aging process. Consequentially, implementing dietary and exercise patterns has been proposed as the most viable alternative strategy for attenuating the most typical degenerative aging changes, thus increasing the likelihood of prolonging lifespan and achieving successful aging.

Fire in Savannas and its Impact on Avifauna: Considerations for a Better Environmental Conservation

Savannas are a pyrophytic biome, a biodiversity hotspot, and have global importance, occupying 20% of the Earth's surface. It is a biome that requires burning to maintain its biodiversity and pyrodiversity. It has suffered from altered fire regimes due to the direct and indirect action of factors such as deforestation, agriculture, cattle ranching, and climate change, resulting in habitat loss, degradation, and fragmentation. This fact can impact the avifauna, changing population dynamics and distribution in the landscape. Thus, through a literature search, this study evaluated the influences of fire on avifauna populations in savannas. It was found that fire impacts avifauna directly or indirectly and acts positively or negatively, according to the niche of the species evaluated and its intrinsic characteristics. The observed effect will depend on the fire detection ability, locomotion capacity, species, habit, functional guild, demographic parameters, resource availability, post-disturbance successional evolution, dispersal ability, and the geographic scale of the area affected by the fire. The main impacts observed for this clade are indirect effects, and its most negatively impacted populations are the ratites and those with poor locomotion ability. Despite the many gaps in knowledge about the impact of fire on the population parameters of avifauna, studies that focus on community dynamics indicate that, in general, there are few changes in richness and abundance indices. Thus, a greater understanding of the consequences of fire on birds is necessary to support better the actions of the Integrated Fire Management Program and its expansion throughout the Brazilian territory in search of quality, dynamic, and integrated environmental management.