Exogenous Sources Research Articles

Haloboration of o‐Alkynyl Phenols Generates Halogenated Bicyclic‐Boronates**

AbstractBenzoxaborinines are intermediates en‐route to bicyclic boronates that are important active pharmaceutical ingredients (APIs). Herein, the haloboration of o‐alkynyl‐phenols using BX3 (X=Cl or Br) is disclosed as a route to form C4‐X‐benzoxaborinines with good functional group tolerance. Computational studies indicated that there are two similar in barrier mechanisms: (i) double alkyne haloboration followed by retro‐haloboration; (ii) concerted trans‐haloboration involving an exogenous chloride source. The C4‐halide in these benzoxaborinines is useful, with a one‐pot haloboration‐Negishi cross coupling protocol effective to form benzoxaborinines with an alkyl or an aryl at C4. Therefore this method is a useful addition to the toolbox for synthesising bicyclic‐boronates that are attracting increasing attention as APIs.

Haloboration of o-Alkynyl Phenols Generates Halogenated Bicyclic-Boronates.

Benzoxaborinines are intermediates en-route to bicyclic boronates that are important active pharmaceutical ingredients (APIs). Herein, the haloboration of o-alkynyl-phenols using BX3 (X=Cl or Br) is disclosed as a route to form C4-X-benzoxaborinines with good functional group tolerance. Computational studies indicated that there are two similar in barrier mechanisms: (i) double alkyne haloboration followed by retro-haloboration; (ii) concerted trans-haloboration involving an exogenous chloride source. The C4-halide in these benzoxaborinines is useful, with a one-pot haloboration-Negishi cross coupling protocol effective to form benzoxaborinines with an alkyl or an aryl at C4. Therefore this method is a useful addition to the toolbox for synthesising bicyclic-boronates that are attracting increasing attention as APIs.

Metabolic flexibility during a trophic transition reveals the phenotypic plasticity of greater duckweed (Spirodela polyrhiza 7498).

The greater duckweed (Spirodela polyrhiza 7498) exhibits trophic diversity (photoautotrophic, heterotrophic, photoheterotrophic, and mixotrophic growth) depending on the availability of exogenous organic carbon sources and light. Here, we show that the ability to transition between various trophic growth conditions is an advantageous trait, providing great phenotypic plasticity and metabolic flexibility in S. polyrhiza 7498. By comparing S. polyrhiza 7498 growth characteristics, metabolic acclimation, and cellular ultrastructure across these trophic modes, we show that mixotrophy decreases photosynthetic performance and relieves the CO2 limitation of photosynthesis by enhancing the CO2 supply through the active respiration pathway. Proteomic and metabolomic analyses corroborated that S. polyrhiza 7498 increases its intracellular CO2 and decreases reactive oxygen species under mixotrophic and heterotrophic conditions, which substantially suppressed the wasteful photorespiration and oxidative-damage pathways. As a consequence, mixotrophy resulted in a higher biomass yield than the sum of photoautotrophy and heterotrophy. Our work provides a basis for using trophic transitions in S. polyrhiza 7498 for the enhanced accumulation of value-added products.

Recent advances in the role of endogenous hydrogen sulphide in cancer cells.

Hydrogen sulphide (H2 S) is a gaseous neurotransmitter that can be self-synthesized by living organisms. With the deepening of research, the pathophysiological mechanisms of endogenous H2 S in cancer have been increasingly elucidated: (1) promote angiogenesis, (2) stimulate cell bioenergetics, (3) promote migration and proliferation thereby invasion, (4) inhibit apoptosis and (5) activate abnormal cell cycle. However, the increasing H2 S levels via exogenous sources show the opposite trend. This phenomenon can be explained by the bell-shaped pharmacological model of H2 S, that is, the production of endogenous (low concentration) H2 S promotes tumour growth while the exogenous (high concentration) H2 S inhibits tumour growth. Here, we review the impact of endogenous H2 S synthesis and metabolism on tumour progression, summarize the mechanism of action of H2 S in tumour growth, and discuss the possibility of H2 S as a potential target for tumour treatment.

SIRT7 orchestrates melanoma progression by simultaneously promoting cell survival and immune evasion via UPR activation

Melanoma is the most lethal type of skin cancer, originating from the malignant transformation of melanocyte. While the development of targeted therapy and immunotherapy has gained revolutionary advances in potentiating the therapeutic effect, the prognosis of patients with melanoma is still suboptimal. During tumor progression, melanoma frequently encounters stress from both endogenous and exogenous sources in tumor microenvironment. SIRT7 is a nuclear-localized deacetylase of which the activity is highly dependent on intracellular nicotinamide adenine dinucleotide (NAD+), with versatile biological functions in maintaining cell homeostasis. Nevertheless, whether SIRT7 regulates tumor cell biology and tumor immunology in melanoma under stressful tumor microenvironment remains elusive. Herein, we reported that SIRT7 orchestrates melanoma progression by simultaneously promoting tumor cell survival and immune evasion via the activation of unfolded protein response. We first identified that SIRT7 expression was the most significantly increased one in sirtuins family upon stress. Then, we proved that the deficiency of SIRT7 potentiated tumor cell death under stress in vitro and suppressed melanoma growth in vivo. Mechanistically, SIRT7 selectively activated the IRE1α-XBP1 axis to potentiate the pro-survival ERK signal pathway and the secretion of tumor-promoting cytokines. SIRT7 directly de-acetylated SMAD4 to antagonize the TGF-β-SMAD4 signal, which relieved the transcriptional repression on IRE1α and induced the activation of the IRE1α-XBP1 axis. Moreover, SIRT7 up-regulation eradicated anti-tumor immunity by promoting PD-L1 expression via the IRE1α-XBP1 axis. Additionally, the synergized therapeutic effect of SIRT7 suppression and anti-PD-1 immune checkpoint blockade was also investigated. Taken together, SIRT7 can be employed as a promising target to restrain tumor growth and increase the effect of melanoma immunotherapy.

Growing underground: Development of thermogenesis in pups of the fossorial rodent Ctenomys talarum

In mammals, during the pup’s development and adult life, integrated requirements of all activities of the individual must conform to a sustained rate of metabolism. Thus, partitioning the available energy according to short-term priorities at a specific moment allows animals to survive and optimize long-term reproductive success. In altricial rodents, thermal balance is a key factor for survival. When no exogenous source of heat is present, altricial pups rapidly lose heat, reaching ambient temperature (Ta). Fossorial rodents showed a strong dependence on burrows, where Ta remains relatively stable within narrow ranges. Pups of the fossorial rodent Ctenomys talarum are altricial, making them an excellent model to evaluate the development of thermogenic capacity. In this study, the ontogeny of the thermogenic capacity of pups of C. talarum was evaluated. Using respirometry techniques, non-shivering thermogenesis (NST), total thermogenic capacity (cold-induced maximum metabolic rate, MMR), and resting metabolic rate (RMR) in pups until post-weaning age (day 60) were analyzed. No NST was present in pups until day 60 despite the presence of molecular markers for NST in brown adipose tissue deposits, which became functional in adults. Although pups are altricial at birth, they maintain their thermal balance behaviorally during lactation. Total thermogenic capacity became fixed at an early age, indicating an improvement in shivering thermogenesis (ST) efficiency after day 10, which might be related to the development of musculature related to digging. Before the aboveground dispersal period (~day 60), pups gradually reached adult Tb by improving ST and thermal isolation, allowing them to confront climatic fluctuations on the surface.

Impact of the Yellow River capture on the paleoenvironmental changes of Hongze Lake, China

The Yellow River (YR) capture of the Huai River had a profound effect on the landscape evolution, ecology, and social development in China, disrupting the evolution of some vital shallow floodplain lakes. Because of the absence of lacustrine sediment provenance analysis, previous studies were inadequate in distinguishing the influence of YR capture on paleoenvironmental changes in these lakes, especially on landscape evolution, redox conditions, lake level changes, and organic productivity. The current study aims to use X-ray fluorescence-core scanning (XRF-CS) and multivariate statistics on a 9.8 m sediment core from Hongze Lake (HZL), China, to analyze the impact of the YR capture on the lake's paleoenvironmental changes and the sediment provenance simultaneously. High-resolution images, magnetic susceptibility, and XRF-based multi-element data were obtained using a GEOTEK Multi-Sensor Core Logger. The calcium (Ca) content indicates the presence of YR sediment in HZL, given the high Ca content in YR sediment and the identification of mainly exogenous sources of Ca in HZL. The high values of Ca indicate that 48.7% of the sediment in the center of HZL is related to the YR's incursion. Periods of higher Ca content coincide with periods of higher oxygenation levels of the lake (as indicated by the ratio of manganese to titanium) and lower organic content in the lake sediment (as indicated by the ratio of incoherent to coherent scatter). These analyses reveal that the YR's capture of HZL significantly increased the lake's oxygen level. Furthermore, the decrease in the organic content of sediment tends to be the result of the accelerated deposition caused by the YR. The decrease in Ca content coincides with an increase in lake levels (as indicated by magnetic susceptibility). Thus, it can be inferred that the embankment on the eastern side of HZL, built to increase lake storage, has reduced the incursion frequency of the YR.

Day-ahead aircraft routing with data-driven primary delay predictions

Flight delays are major sources of disruptions in airline operations. To mitigate them, day-ahead aircraft routing aims to create flight sequences that can absorb delays and minimize their propagation. However, flight delays are unknown ahead of operations; moreover, predicting delays is complicated by the fact that historical data encompass both primary delays (arising from exogenous sources) and propagated delays (arising from cascading effects in an airline’s network). This paper thus develops predictive and prescriptive analytics models to forecast primary delays and to optimize day-ahead aircraft routing toward delay mitigation. We develop a quantile regression model to reconstruct primary delays from historical data, and an ensemble machine learning model to predict them based on flight-level features, environmental features, and traffic features—estimated via a queuing model of airport operations. Then, we formulate deterministic and stochastic optimization models to support day-ahead aircraft routing. Using real-world data from Vueling Airlines, we evaluate the models out of sample against real-world counterfactuals. Results show that our predictive model achieves a mean absolute error of 7–8 minutes and that our prescriptive models can reduce delay costs by 3–5%. This paper shows the benefits of predictive and prescriptive analytics to enhance the robustness of airline operations by (i) creating shorter aircraft rotations, and (ii) strategically allocating schedule slack to avoid the propagation of long delays in later phases of the day. This research led to the deployment of the models in collaboration with the Vueling data science unit.

Proteins and their functionalization for finding therapeutic avenues in cancer: Current status and future prospective.

Despite the remarkable advancement in the health care sector, cancer remains the second most fatal disease globally. The existing conventional cancer treatments primarily include chemotherapy, which has been associated with little to severe side effects, and radiotherapy, which is usually expensive. To overcome these problems, target-specific nanocarriers have been explored for delivering chemo drugs. However, recent reports on using a few proteins having anticancer activity and further use of them as drug carriers have generated tremendous attention for furthering the research towards cancer therapy. Biomolecules, especially proteins, have emerged as suitable alternatives in cancer treatment due to multiple favourable properties including biocompatibility, biodegradability, and structural flexibility for easy surface functionalization. Several in vitro and in vivo studies have reported that various proteins derived from animal, plant, and bacterial species, demonstrated strong cytotoxic and antiproliferative properties against malignant cells in native and their different structural conformations. Moreover, surface tunable properties of these proteins help to bind a range of anticancer drugs and target ligands, thus making them efficient delivery agents in cancer therapy. Here, we discuss various proteins obtained from common exogenous sources and how they transform into effective anticancer agents. We also comprehensively discuss the tumor-killing mechanisms of different dietary proteins such as bovine α-lactalbumin, hen egg-white lysozyme, and their conjugates. We also articulate how protein nanostructures can be used as carriers for delivering cancer drugs and theranostics, and strategies to be adopted for improving their in vivo delivery and targeting. We further discuss the FDA-approved protein-based anticancer formulations along with those in different phases of clinical trials.

Abstract P593: Urinary Nitrate Was Not Associated With Prevalence of Dyslipidemia Among Adults in the National Health and Nutrition Examination Survey, 2009-2016

Introduction: Exogenous dietary sources of nitrate (green leafy vegetables) and endogenous oxidation of nitric oxide are potential sources of urinary nitrate. While nitrate exposure elicits a profound impact on vascular health and higher levels of urinary nitrate correlate with reduced blood pressure, less is known about its association with blood cholesterol. Hypothesis: Higher urinary nitrate levels are inversely related to dyslipidemia prevalence. Methods: Cross-sectional 2009-2016 National Health and Nutrition Examination Survey (NHANES) was used to identify participants aged ≥20 years. Participants were categorized into four quartiles based on urinary nitrate levels (ng/mL) - Q1: ≤26,300; Q2: 26,300-45,800; Q3: 45,800-72,200; Q4: >72,200. Primary analysis was survey-weighted logistic regression modeling to estimate the association of urinary nitrate with dyslipidemia prevalence (defined as self-report, total cholesterol [TC] ≥200 mg/dL, high-density lipoprotein cholesterol [HDL-C] <40 mg/dL for men or <50 mg/dL for women, low-density lipoprotein cholesterol [LDL-C] ≥100 mg/dL, triglycerides [TG] ≥150 mg/dL, or non-HDL-C ≥130 mg/dL). The model was adjusted for age, sex, race/ethnicity, smoking status, income level, hypertension, and diabetes. Secondary analysis included comparison of TC, HDL-C, LDL-C, TG, and non-HDL-C stratified by urinary nitrate quartiles. Survey-weighted ANCOVA, adjusted for the same co-variates, was performed at a significance level of 0.05; if significance level was met, post-hoc multiple comparison test using the Dunnett-Hsu method was performed, with Q1 as the reference. Results: Across the 8-year NHANES survey, 3,099 participants (74.7% aged <60 years, 50.5% women, and 65.6% non-Hispanic white) were included in the study. Hypertension and diabetes prevalence were 24.5% and 9.3%, respectively. Urinary nitrate was not significantly associated with hypercholesterolemia prevalence (Q2 vs. Q1, OR 0.87 [95% CI, 0.62-1.23]; Q3 vs. Q1, OR 1.09 [95% CI, 0.71-1.68]; Q4 vs. Q1, OR 0.89 [95% CI, 0.59-1.37]). No statistically significant trends in TC, HDL-C, LDL-C, TG, or non-HDL-C were observed with urinary nitrate quartiles. Conclusion: Higher urinary nitrate excretion, a marker of nitrate exposure and elevated nitrate levels, was not associated the prevalence of dyslipidemia. Therefore, while a healthy diet may lead to changes in cholesterol, such changes may be independent of dietary nitrate intake.

Multi-residue analysis of certain lanolin nipple care products for trace contaminants

BackgroundTopical lanolin is commonly used on nipples to aid breastfeeding success. The raw material undergoes refinement to remove contaminants such as pesticides, which may accumulate from exogenous environmental sources. The level of refinement influences final lanolin purity. For use in nipple creams, a lanolin which complies with a published monograph (either USP or Ph. Eur.) is desirable to ensure a non-toxic product with neutral taste and smell, and low allergenicity.MethodsThe aim of this study was to determine the residual trace pesticide levels and quantify the Free Lanolin Alcohols (FLA) levels in two commercially available lanolin products (HPA LANOLIN (Lansinoh Laboratories Inc.); PURELAN (Medela AG)) and two lanolin ingredients (PHARMALAN PH EU-SO-(RB) and CORONA-8 SO-(RB) (Croda, Goole, UK)) using established validated methods. Test samples were subjected to Gas-Chromatographic and Liquid-Chromatographic analysis to quantify and identify a panel of 178 pesticide residues. FLA levels and the presence of oxidative metabolites were also determined.ResultsThe purity of the lanolin ingredients was consistent with expectations based on their level of refinement; lanolin in compliance with the Ph. Eur. monograph demonstrated the highest level of purity. Differences were seen between the lanolin nipple creams tested, in terms of FLA levels and pesticide residue levels. Specifically, the HPA LANOLIN contained an extremely low level of FLA (0.61%), which was fourfold less than in the PURELAN (2.76%). Additionally, the HPA LANOLIN did not contain any detectable pesticide residues. The PURELAN was found to contain a number of pesticide residues, however the detected levels were low and within the permitted limits and so despite their presence, the PURELAN was still compliant with the relevant monographs.ConclusionsThis data reinforces that the purity of monograph compliant Lanolin makes it suitable for use on the nipples of breastfeeding mothers. A higher level of refinement leads to a reduction in pesticide contaminants also reduces FLA levels in the final material, minimizing the risk of allergenicity.

The Role of Microbiota-Derived Vitamins in Immune Homeostasis and Enhancing Cancer Immunotherapy.

Not all cancer patients who receive immunotherapy respond positively and emerging evidence suggests that the gut microbiota may be linked to treatment efficacy. Though mechanisms of microbial contributions to the immune response have been postulated, one likely function is the supply of basic co-factors to the host including selected vitamins. Bacteria, fungi, and plants can produce their own vitamins, whereas humans primarily obtain vitamins from exogenous sources, yet despite the significance of microbial-derived vitamins as crucial immune system modulators, the microbiota is an overlooked source of these nutrients in humans. Microbial-derived vitamins are often shared by gut bacteria, stabilizing bioenergetic pathways amongst microbial communities. Compositional changes in gut microbiota can affect metabolic pathways that alter immune function. Similarly, the immune system plays a pivotal role in maintaining the gut microbiota, which parenthetically affects vitamin biosynthesis. Here we elucidate the immune-interactive mechanisms underlying the effects of these microbially derived vitamins and how they can potentially enhance the activity of immunotherapies in cancer.

Increase in chlorophyll-a concentration in Lake Taihu from 1984 to 2021 based on Landsat observations

Lake Taihu, located in a densely populated and highly industrialized area in eastern China, has experienced dramatic changes in water quality since the reform and opening-up in the 1980s. Landsat data can be used to trace water quality changes over approximately 40 years. However, chlorophyll-a (Chla) estimation, which characterizes the trophic status, has not been thoroughly explored (especially in turbid water using wide bandwidth Landsat) due to the interference of suspended particulate matter (SPM) to Chla. In this study, we used Landsat TM/OLI for turbid water Chla inversion and to analyze the spatiotemporal variation of Chla in Lake Taihu for 38 years and its influencing factors. An optical classification algorithm based on Rrs(green)/Rrs(red) was used to exclude highly turbid waters dominated by SPM; Chla was estimated only in waters with low SPM. We constructed an exponential estimation model based on Rrs(NIR)/Rrs(red), and verified the accuracy of the model using the measured Chla synchronized with satellite data. The model was applied to Landsat images to calculate the Chla concentration in Lake Taihu during 1984–2021, and its spatiotemporal distribution patterns were further analyzed. Spatially, the Chla concentrations in the western and northern regions of Lake Taihu were higher than those in other regions, probably because these areas are estuaries with large exogenous pollutant discharge and more nutrients are imported from exogenous sources. Chla showed an overall significant upward trend from 1984 to 2021 probably because of temperature rise, wind speed reduction, and nutrient increase. The results of the spatial and temporal variation of Chla and the influencing factors in this study provide supporting data for eutrophication monitoring and management in Lake Taihu. The proposed Chla estimation method can be extended to assess the spatial and temporal distribution of eutrophication in other inland waters with similar optical properties.

Islamist terrorism and the status of women

We investigate the effect of Islamist terrorist activity on women's legal position in society, using data for 171 countries between 1970 and 2016. To identify causal effects, we exploit the prevalence of Islamist terrorism in neighboring countries as an exogenous source of variation, arguing that regional terrorism affects local terrorism through contagion effects. We show that increased activity by Islamist terrorist groups is linked to lower legal status of women. By contrast, we find that neither Islam per se nor other types of terrorism have comparable effects. This reinforces the notion that Islamist terrorism is singularly interested and effective in weakening women's rights. Our results are consistent with a rational-economic model of terrorism, where Islamist terrorists purposefully use violence to maximize political utility, while governments make concessions that constrain the role of women because the costs of compliance are lower than the harm from continued Islamist terrorism.

The plurality of social pedagogy

This contribution is dedicated to plurality in social pedagogy. The author argues that plurality has several sources. Exogenous sources of plurality include non-unified semantics or different educational paradigms, concepts, approaches, didactic principles and educational practices. Plurality is reflected in different learning environments, in teaching styles or teaching management. Taxonomies, social roles, characteristics and competences of those who are subjects or objects of social pedagogy are also plural. The lack of a universal value system and the heterogeneity of people’s thinking also contributes to the plurality in pedagogy. Endogenous sources of plurality include motives and student aspirations.

RAD51 filament formation, dynamics, and regulation.

DNA damage can arise through various mechanisms such as exogenous sources (UV radiation) or endogenous sources (replication fork collapse). Damaged DNA poses a significant risk to the cell, as unrepaired damage can lead to mutations, gross chromosomal rearrangements, or even cell death. RAD51 is a highly conserved recombinase which serves crucial functions in the cell through its role in DNA damage repair (homologous recombination, HR) and in replication fork protection. In HR, RAD51 (with the help of mediators and paralogs) forms a nucleoprotein filament on the single-stranded DNA produced via resection of a double-stranded break. This nucleoprotein filament then invades the homologous sequence which will serve as a template for accurate repair of the damaged DNA. The mechanism by which the RAD51 nucleoprotein filament protects the replication fork is poorly understood. Slight deviations towards either a more or a less stable RAD51 filament may cause aberrant recombination, and/or failure to protect DNA replication forks by changing the filament assembly, stability and/or dynamics. Using a combination of single-molecule and bulk biochemical assays, this study examines filament dynamics of RAD51 in varying contexts: different physiological conditions, varying mutated residues, and with and without small molecule inhibitors known to alter RAD51 function. We use dual-optical tweezers combined with confocal microscopy to examine RAD51 filament formation in real time, with a microfluidic chip set up that allows for introduction of varying conditions for the same single DNA molecule. Following characterization of filament formation at the single-molecule level, DNA strand exchange assays are used to determine how variations on filament assembly and stability alter the primary recombinase function of RAD51. We show here that alterations to RAD51 filament formation, stability, or dynamics can alter the critical recombinase function of RAD51.

Biotin pathway in novel Fodinibius salsisoli sp. nov., isolated from hypersaline soils and reclassification of the genus Aliifodinibius as Fodinibius.

Hypersaline soils are extreme environments that have received little attention until the last few years. Their halophilic prokaryotic population seems to be more diverse than those of well-known aquatic systems. Among those inhabitants, representatives of the family Balneolaceae (phylum Balneolota) have been described to be abundant, but very few members have been isolated and characterized to date. This family comprises the genera Aliifodinibius and Fodinibius along with four others. A novel strain, designated 1BSP15-2V2T, has been isolated from hypersaline soils located in the Odiel Saltmarshes Natural Area (Southwest Spain), which appears to represent a new species related to the genus Aliifodinibius. However, comparative genomic analyses of members of the family Balneolaceae have revealed that the genera Aliifodinibius and Fodinibius belong to a single genus, hence we propose the reclassification of the species of the genus Aliifodinibius into the genus Fodinibius, which was first described. The novel strain is thus described as Fodinibius salsisoli sp. nov., with 1BSP15-2V2T (=CCM 9117T = CECT 30246T) as the designated type strain. This species and other closely related ones show abundant genomic recruitment within 80-90% identity range when searched against several hypersaline soil metagenomic databases investigated. This might suggest that there are still uncultured, yet abundant closely related representatives to this family present in these environments. In-depth in-silico analysis of the metabolism of Fodinibius showed that the biotin biosynthesis pathway was present in the genomes of strain 1BSP15-2V2T and other species of the family Balneolaceae, which could entail major implications in their community role providing this vitamin to other organisms that depend on an exogenous source of this nutrient.

The role of lysosomes in lipid homeostasis.

Lipids function as the major building blocks of cellular membranes, as signaling molecules and as energy stores for metabolism. These important functions require a precise regulation of lipid biosynthesis, transport, turnover and storage. Lipids are exchanged among organelles through a sophisticated network of vesicular and non-vesicular transport routes. Lysosomes, as the main catabolic organelle, are at the center of this network and have recently evolved as one of the master-regulators of cellular lipid metabolism. Lipids from both endogenous and exogenous sources can be processed, sensed and sorted in and out of the lysosome. In this review, we focus on the role of the lysosome in lipid catabolism, transport and signaling. We highlight recent discoveries on the transport of lipids out of the lysosomal lumen and their exchange with other organelles via membrane contact sites. We also discuss the direct role of lysosomal lipids in the TORC1 signaling pathway, a regulator of cellular metabolism. Finally, we address lysosomal biogenesis, its role in the sorting of lipid metabolic enzymes and the dysregulation of these processes in disease.

INDIVIDUAL FACTORS OF STRESSOGENESIS OF THE LEGAL MENTALITY OF THE UKRAINIAN ETHNOS IN THE CONTEXT OF DOMESTIC STATE-FORMATION: SOCIAL-PHILOSOPHY ANALISE

In 2013-2022, the Ukrainian ethnic group faced numerous external and internal challenges, which were largely the result of its previous historical development and profound transformations in the public consciousness.These changes, in turn, have become a natural reaction to a number of historical processes and phenomena that have taken place in the territory of the people from ancient times to the present. In this article, the author aims to analyze some factors of stress genesis of the ethnic legal mentality of the Ukrainian ethnic group and show their impact on the content of its behavioral stereotypes. The methodology of this study is comprehensive and is based on socio-philosophical and philosophical and legal analysis of behavioral attitudes of Ukrainians in the field of legal understanding.Results. In the course of analyzing the scientific works of a number of researchers, we found that during its historical existence, the Ukrainian ethnic group has experienced a number of events, phenomena and processes of objective reality, which led to the transformation of the content of its behavioral stereotypes. Factors of stress genesis can be divided into endogenous and exogenous. Exogenous sources of Ukrainian ethnopsychologists include, for example, continuous invasions of various aggressors (Tatar, Polish, Russian, German) and various attempts to acculturate Ukrainians.According to them, endogenous factors include various migration processes that have generated marginality and betrayal by Ukrainian leaders of their people. In the future, the established guidelines play or may play a destructive role in the process of nationbuilding.Conclusions. We found that the stress genesis of domestic political and legal can be defined as the process of creating political and legal mentality of the Ukrainian ethnos under the influence of events, phenomena, processes of its sociohistorical development, as well as factors of geographical location and environmental conditions. community and, as a consequence, cause transformations in the content of its guidelines. In addition, the border situation of Ukrainian lands, long statelessness of the ethnic group, serfdom in the homeland and other factors of socio-historical development of the national ethnic group have led to the emergence or deepening in the people’s consciousness such destructive stereotypes as anarchism, legal nihilism, freedom “, absenteeism and civic passivity, deep corruption traditions and nepotism, low status of state property, etc.

Mass Spectrometry Analysis of DNA and Protein Adducts as Biomarkers in Human Exposure to Cigarette Smoking: Acrolein as an Example.

Acrolein is a major component in cigarette smoke and a product of endogenous lipid peroxidation. It is difficult to distinguish human exposure to acrolein from exogenous sources versus endogenous causes, as components in cigarette smoke can stimulate lipid peroxidation in vivo. Therefore, analysis of acrolein-induced DNA and protein adducts by the highly accurate, sensitive, and specific mass spectrometry-based methods is vital to estimate the degree of damage by this IARC Group 2A carcinogen. This Perspective reviews the analyses of acrolein-induced DNA and protein adducts in humans by mass spectrometry focusing on samples accessible for biomonitoring, including DNA from leukocytes and oral cells and abundant proteins from blood, i.e., hemoglobin and serum albumin.