Unstable Form Research Articles

Understanding the Meaning of “Aspeset”: Hermeneutical Approaches, Reading Practices and the Departure from Germany in Two Lea Goldberg Novels

Abstract This essay describes the departure from Europe, arguably the theme that unites Lea Goldberg’s three novels, in terms of the German tradition of Hermeneutics. I explore the various hermeneutical approaches in two of the novels, Mikhtavim Minesi’a Meduma and Avedot, and connect their metafictional and metacritical debates to the circumstances of their composition, publication and reception. While Mikhtavim Minesi’a Meduma employs a humanistic and universalist Weltliteratur perspective in order to downplay the emotions of bitter rejection from a beloved cultural home, Avedot contends with hermeneutical and philological questions ranging from authenticity and interpretation to the mystery of artistic creation. Avedot’s plot revolves around the philologist-poet protagonist’s quest for his own pseudo-ancient text, but ultimately raises questions about the spiritual nature of the creative process and whether or not this spiritual baggage can be relayed to an external reader, in political circumstances that accentuate the poet’s sense of alienation. The two novels, with their unstable form, provided Goldberg an opportunity not only to contemplate aesthetic questions, but also to psychologically process the tearing away from the cultural and intellectual legacy of Europe and in particular that of Germany.

Selection of parental pairs when obtaining F1 hybrids of white cabbage with resistance to the tip burn of the inner leaves

Relevance. During the formation of cabbage heads, under certain conditions, white cabbage is damaged by a burn of the top of the inner leaves of the head, which abroad received the stable name “tip burn”. This disorder is interpreted as a physiological or non-infectious disease, the cause of which is a violation of calcium intake. The disease manifests itself inside the cabbage head, resulting from the interaction of environmental stress factors and the predisposed genotype. The most effective way to combat this disorder is to develop highly tolerant hybrids. This is especially true for the south of Russia, where the stress load on plants is maximum.Purpose of the study – to develop a principle for selecting parental pairs for developing hybrids that are resistant to the tip burn of the inner leaves of a cabbage head, and to identify promising hybrids. Materials and methods. In 2021-2022 in FSBSI "Federal Scientific Rice Centre", in the department of vegetable growing, 45 hybrid combinations obtained on the basis of 10 inbred lines were assessed under field conditions for the trait "burn damage to the inner leaves of the cabbage head." An analysis of the combining ability of lines according to Griffin, and an analysis of the inheritance of the trait according to Heiman were carried out. In 2023, a competitive test of promising hybrids was carried out.Results. In both years of research, 5 lines had negatively stable TCA for burn damage: Ten4270, Yas25p, Bs1f, Agr 82, 270Hn111. SCA of lines is more subject to changes from year to year. The effects of SCA in hybrids due to dominance, epistasis and overdominance in individual combinations significantly influence the manifestation of the trait in the direction of decrease or increase. The principle of selecting parental pairs to develop stable hybrids is based on a combination of lines with a negative SCA value; in some cases, it is permissible to include one line with an average SCA and low SCA. Analysis of genetic parameters according to Heiman confirms the prevalence of non-additive inheritance of the lesion; in unstable forms, the disorder is controlled by dominant polygenes and is highly heritable.

Ultra high-performance liquid chromatography tandem mass spectrometry: Development and validation of an analytical method for N2-Ethyl-2’-deoxyguanosine in dried blood spot

In the body, ethanol is metabolized to acetaldehyde by alcohol dehydrogenase and CYP2E1. Acetaldehyde is the main carcinogen that forms DNA adducts, N2-Ethylidene-2'-deoxyguanosine (N2-Ethylidene-dG), which can cause DNA damage and lead to cancer. However, N2-Ethylidene-dG is an unstable form at the nucleoside level and is difficult to measure. So it needs to be reduced using NaBH4 to become N2-Ethyl-2'-deoxyguanosine (N2-Et-dG). This study aims to obtain a selective, sensitive, and validated analytical method to determine N2-Et-dG using ultra-high-performance liquid chromatography-tandem mass spectrometry with allopurinol as the internal standard. The N2-Et-dG analysis was performed using a C18 Acquity® Bridged Ethylene Hybrid column of (1.7 μm, 100 mm × 2.1 mm). The sample matrix used was dried blood spots, and then the DNA sample was extracted using the QIAamp DNA Mini Kit. The optimum analysis conditions were obtained in a combination eluent of 0.1 % acetic acid and methanol (60:40 v/v) with a flow rate of 0.1 mL/min and eluted isocratically for 5 min. Quantification analysis was performed using triple quadrupole mass spectrometry with electrospray ionization in positive mode, with detection at m/z 296.16 > 180.16 for N2-Et-dG and 137.03 > 110.05 for allopurinol, respectively. The validated analytical method follows the 2018 USA Food and Drug Administration guidelines with a linear concentration range of 5–200 ng/mL.

The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers.

If one must prioritize among the vast array of contributing factors to cancer evolution, environmental-stress-mediated chromosome instability (CIN) should easily surpass individual gene mutations. CIN leads to the emergence of genomically unstable life forms, enabling them to grow dominantly within the stable life form of the host. In contrast, stochastic gene mutations play a role in aiding the growth of the cancer population, with their importance depending on the initial emergence of the new system. Furthermore, many specific gene mutations among the many available can perform this function, decreasing the clinical value of any specific gene mutation. Since these unstable life forms can respond to treatment differently than stable ones, cancer often escapes from drug treatment by forming new systems, which leads to problems during the treatment for patients. To understand how diverse factors impact CIN-mediated macroevolution and genome integrity-ensured microevolution, the concept of two-phased cancer evolution is used to reconcile some major characteristics of cancer, such as bioenergetic, unicellular, and multicellular evolution. Specifically, the spiral of life function model is proposed, which integrates major historical evolutionary innovations and conservation with information management. Unlike normal organismal evolution in the microevolutionary phase, where a given species occupies a specific location within the spiral, cancer populations are highly heterogenous at multiple levels, including epigenetic levels. Individual cells occupy different levels and positions within the spiral, leading to supersystems of mixed cellular populations that exhibit both macro and microevolution. This analysis, utilizing karyotype to define the genetic networks of the cellular system and CIN to determine the instability of the system, as well as considering gene mutation and epigenetics as modifiers of the system for information amplification and usage, explores the high evolutionary potential of cancer. It provides a new, unified understanding of cancer as a supersystem, encouraging efforts to leverage the dynamics of CIN to develop improved treatment options. Moreover, it offers a historically contingent model for organismal evolution that reconciles the roles of both evolutionary innovation and conservation through macroevolution and microevolution, respectively.

The Impact of Organic and Chemical Organic Fertilizers on the Efficiency of Cadmium Mobility Reduction by Potassium Hydroxide Modified Biochar

The aim of this study was to investigate the impact of organic and chemical organic fertilizers on the translocation of cadmium in crude oil-contaminated soil treated with potassium hydroxide-modified biochar (KOH-biochar). The soil sample was collected from Chonburi Province. The soil was characterized as moderately acidic sandy loam with relatively low organic matter, medium salinity, medium cation exchange capacity, and high nutrient levels. The concentration of cadmium in the soil fell within the acceptable range for agricultural use. The KOH-biochar exhibited strong alkalinity, a high carbon/nitrogen (C/N) ratio, and an oxygen/carbon (O/C) ratio. Crude oil was slightly acidic, with high organic matter content and low sulfur and cadmium concentrations. The synthetic soil created in this study composed of 5% crude oil, and 100 mg/kg of cadmium. KOH-biochar, organic and chemical organic fertilizers were applied to this synthetic soil. Subsequently, the soil was subjected to extraction with 0.005 M diethylenetriamine pentaacetate (DTPA), and a sequential extraction method was employed to determine six different forms of cadmium in the soil samples. Cadmium concentrations in the extracts were measured using a graphite furnace atomic absorption spectrophotometer. The findings revealed that fertilizers effectively slowed down the movement of cadmium. Fertilizer application led to the transformation of cadmium from unstable forms to more stable forms within the soil. Fertilizer with the highest organic matter content and pH showed the least cadmium mobility. Increased nitrogen and phosphorus content in the fertilizer resulted in slightly higher cadmium mobility within the soil. Conversely, higher potassium content in the fertilizer led to slightly reduced cadmium mobility in the soil.

Combined effect of thermal hydrolysis process and low-temperature pyrolysis on the classification and bioavailability of phosphorus in sewage sludge

Existing phosphorus (P) resources are becoming increasingly scarce, so it is necessary to recover P from potential sources. This paper is based on thermal hydrolysis process (THP) at 140–180 °C, coupled with low-temperature pyrolysis at 300 °C, to study its effect on the recovery and conversion of P from sewage sludge. Most significant change was observed in apatite P, which increased from 3.43 ± 0.48 mg/g in raw sludge to 30.17 ± 1.17 mg/g in biochar (BTHP-180-4-300) during optimal process (THP condition: 180 °C, 4 h; pyrolysis condition: 300 °C). Reactions between phosphates and metal ions became more complete during this combined process. Unstable forms of P were converted into more stable forms, with transformations from Al-P and Fe-P toward Ca-P compounds like Ca3(PO4)2, Ca3Mg3(PO4)4, Ca2P2O7, and Ca(H2PO4)2, making P less degradable and more suitable as slow-release fertilizers. Additionally, P characteristics of actual THP in a sewage treatment plant were similar to those of laboratory THP.

Evaluation of sodium borocaptate (BSH) and boronophenylalanine (BPA) as boron delivery agents for neutron capture therapy (NCT) of cancer: an update and a guide for the future clinical evaluation of new boron delivery agents for NCT.

Boron neutron capture therapy (BNCT) is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron-10, a stable isotope, is irradiated with neutrons of the appropriate energy to produce boron-11 in an unstable form, which undergoes instantaneous nuclear fission to produce high-energy, tumoricidal alpha particles. The primary purpose of this review is to provide an update on the first drug used clinically, sodium borocaptate (BSH), by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug, boronophenylalanine (BPA), which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous melanomas. Subsequently, BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers, specifically brain tumors and recurrent tumors of the head and neck region. The focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high-grade gliomas and their subsequent clinical use to treat patients with high-grade gliomas. First, we will summarize the studies that were carried out in Japan with BSH and subsequently at our own institution, The Ohio State University, and those of several other groups. Second, we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for BNCT. Third, although there have been intense efforts to develop new and better boron delivery agents for BNCT, none of these have yet been evaluated clinically. The present report will provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.

Form, Shape, and Content of an Industrious Unconscious—Becoming with Noisy Storks

ABSTRACT In this response to Hartman and Clough, this issue, I delve into an expanded view of autopoiesis through an unstable form of text – poetic writing – as I further play with indeterminacies. I ponder about a Hartmanian-Cloughian socially engaged psychoanalysis and its affordances to be noisy while harnessing the indeterminacy of infinite (yet always contingent) translations. With these, I further explore their proposal to shatter a dominant information infrastructure along with boundaries of the social and the psychic.

“Omic tools” for investigation creative plant systens

The result of the genotype/environment (G/E) interaction affects the success of the implementation of the genetic program of a plant biological system of any level, from a cell population to a multicellular organism. During this interaction, the plant system absorbs trophic and energy resources, processes and assimilates them. Under normal conditions, signal perception and transduction occurs against the background of homeostasis regulated by the genome. Genetic control is exercised at all stages of growth and development of plant systems via differential gene expression. The activity of metabolism is coordinated by the cooparated action of the ionome, proteome, metabolome, and transcriptome. Direct and cross connections between these aspects of life activity are established and developed constantly and manifest themselves in the form of dynamic phenotypic effects from structural formations and enzyme chains. Disturbanses within the individual stages of metabolism and the disconnection between them reveal differences between stable, sensitive and unstable forms. The obtained information is the basis for experiments to obtain forms with improved characteristics. A range of tasks has been outlined in this direction, and there have already been significant developments. Comparison of the dynamics of the functioning of creative variants of plant systems of any level showed their significant differences from the original forms. Changes in creative systems are determined by the interactions of transgenes with endogenous genes and can manifest themselves in the form of positive/negative/combined characteristics of the new system. Comparative studies of the dynamics of vital activity will provide information about the coordinated process of communication both within the cell and between the tissues of a multicellular organism. The use of various combinations of “omic tools” will facilitate the discovery of new promising candidates among structural and regulatory genes, as well as among promoters. On the other hand, the obtained biological information will be a stimulus for improving the methods and directions of research.

A heterostructured ternary transition metal oxide composite as an efficient electrocatalyst for the hydrogen evolution reaction

A key method for hydrogen production is water electrolysis involving the oxygen and hydrogen evolution reactions. The efficiency of these processes is largely dependent on the use of effective electrode catalysts. Despite the high water-splitting catalytic activity of noble metals such as Pt, Ru, and Ir, their scarcity and costliness pose significant challenges. Although Fe and Fe-based compounds have recently been identified as promising alternative catalysts due to their abundance, affordability, and low toxicity, particularly under the alkaline conditions required for the hydrogen evolution reaction, both can be reduced to unstable forms during the reaction. To address this, the focus of the present study is on developing a ternary transition metal oxide electrocatalyst comprising Ni, Fe, and Co oxides. Thereby, we leveraged the synergistic interactions among them to provide a heterogeneous electrocatalyst for the hydrogen evolution reaction with a sufficiently low overpotential of 45 mV and suitably high Tafel kinetics of 44.99 mV dec−1 and long-term stability. The ternary transition metal oxide electrode showcased superior performance compared to one comprising binary transition metal oxides by achieving a lower overpotential and a better Tafel slope while maintaining catalytic stability even for 100 h at a current density of 1000 mA cm−2. This innovative approach offers a highly efficient alternative catalyst to Fe, which is known to have stability issues for hydrogen production, especially at high current density.

Risk assessment of antimony-arsenic contaminated soil remediated using zero-valent iron at different pH values combined with freeze-thaw cycles.

Soil in mining wastelands is seriously polluted with heavy metals. Zero-valent iron (ZVI) is widely used for remediation of heavy metal-polluted soil because of its excellent adsorption properties; however, the remediation process is affected by complex environmental conditions, such as acid rain and freeze-thaw cycles. In this study, the effects of different pH values and freeze-thaw cycles on remediation of antimony (Sb)- and arsenic (As)-contaminated soil by ZVI were investigated in laboratory simulation experiments. The stability and potential human health risks associated with the remediated soil were evaluated. The results showed that ZVI has a significant stabilizing effect on Sb and As in both acidic and alkaline soils contaminated with dual levels of Sb and As, and the freeze-thaw process in different pH value solution systems further enhances the ability of ZVI to stabilize Sb and As, especially in acidic soils. However, it should be noted that apart from the pH=1.0 solution environment, ZVI's ability to stabilize As is attenuated under other circumstances, potentially leading to leaching of its unstable form and thereby increasing contamination risks. This indicates that the F1 (2% ZVI+pH=1 solution+freeze-thaw cycle) processing exhibits superior effectiveness. After F1 treatment, the bioavailability of Sb and As in both soils also significantly decreased during the gastric and intestinal stages (about 60.00%), the non-carcinogenic and carcinogenic risks of Sb and As in alkaline soils are eliminated for children and adults, with a decrease ranging from 60.00% to 70.00%, while in acidic soil, the non-carcinogenic and carcinogenic risks of As to adults and children is acceptable, but Sb still poses non-carcinogenic risks to children, despite reductions of about 65.00%. These findings demonstrate that soil pH is a crucial factor influencing the efficacy of ZVI in stabilizing Sb and As contaminants during freeze-thaw cycles. This provides a solid theoretical foundation for utilizing ZVI in the remediation of Sb- and As-contaminated soils, emphasizing the significance of considering both pH levels and freeze-thaw conditions to ensure effective and safe treatment.

Ball-milled sepiolite/phosphate rock for simultaneous remediation of cadmium-contaminated farmland and alleviation of phosphorus deficiency symptoms in pepper

Herein, ball-milled combination of sepiolite and phosphate rock was carried out for synergistic passivation of Cd in soil and alleviation of phosphorus deficiency in pepper. The as-prepared BM-Sep2PR1 exhibited extensive pH adaptability and fast uptake for Cd(II) with maximal uptake capacity of 78.67 mg/g. After application of 0.5 % BM-Sep2PR1, the bioavailability of Cd in soil decreased by 58.2 %, and its unstable forms declined by 57.0 % with transformation into residual speciation such as Cd3(PO4)2 and CdnCa5-n(PO4)3OH. Moreover, BM-Sep2PR1 significantly decreased the amount of Cd in pepper shoot (77.8 %) and root (54.8 %), and the bioconcentration factors (soil-root) and translocation factors (root-shoot) were significantly reduced by 54.8 % and 50.8 %, respectively. Notably, the soil available phosphorus, pepper root vitality, and photosynthetic pigment content increased by 202.8 %, 136.4 %, and 58.4 %, respectively, thus significantly alleviating the phosphorus deficiency symptoms of pepper. Additionally, BM-Sep2PR1 improved soil microbial community structure, especially enhanced the abundance of microorganism involved in nutrient cycling and heavy metal resistance. The Cd passivation mechanisms of BM-Sep2PR1 were identified as pore filling, electrostatic attraction, ion exchange, surface complexation, and chemical precipitation. Overall, this study provided a potential strategy for synergetic soil remediation and plant nutrient supplement by using ball-milled functional materials.

"Statues Made of Sugar": Martí, Monuments, and Hemispheric Ventriloquism

Abstract: Monuments speak; they shape citizens' political imaginations. Drawing on an essay by the Cuban intellectual José Martí about Confederate commemoration, I argue that his Confederate solidarities were the result of hemispheric ventriloquism. Widely lauded as an anti-imperial and anti-racist thinker, Martí's hemispheric ventriloquism was driven by: 1) fears of US imperial expansion; 2) a need to rebut critiques of republics as inherently unstable forms of government in light of post-independence civil strife in Latin America; and 3) his hopes for Cuban national unity post-independence. Martí's hemispheric ventriloquism illustrates the dangers of downplaying racist commemoration in the name of liberal pluralism or national unity.

Extraction of alumina from fly ash by pyro-hydro metallurgical routes: A review

Fly ash is a resulting by-product formed due to the burning of pulverized coal on a steam-generating plant. Fly ash mainly contains alumina and silica, hence it can be an excellent secondary source for alumina. Today only 30% of global fly ash can be reused commercially, the remaining was dumped. This causes waste of resources and environmental pollution too. The alumina in the fly ash was in the form mullite phase which is a stable phase so decomposition of this phase is difficult. The mullite phase can be disilicated by calcination, roasting, etc which were pyro-metallurgical routes. Alumina can be extracted as aluminum hydroxide and other unstable forms from fly ash by hydrometallurgical routes. This process requires a huge amount of energy for reaction which is a major drawback of this process. Till now industrial extraction of alumina from fly ash cannot be feasible. Different researchers and scholars did various works to overcome this difficulty. This paper presents a review for extraction of alumina via these routes. It starts with different concepts used in extraction of alumina from fly ash. The middle portion presents the survey of work done by different scholars. The work finally concludes with future possibilties.

Glycerol 3-Phosphate Dehydrogenase: Role of the Protein Conformational Change in Activation of a Readily Reversible Enzyme-Catalyzed Hydride Transfer Reaction.

Kinetic parameters are reported for glycerol 3-phosphate dehydrogenase (GPDH)-catalyzed hydride transfer from the whole substrate glycerol 3-phosphate (G3P) or truncated substrate ethylene glycol (EtG) to NAD, and for activation of the hydride transfer reaction of EtG by phosphite dianion. These kinetic parameters were combined with parameters for enzyme-catalyzed hydride transfer in the microscopic reverse direction to give the reaction equilibrium constants Keq. Hydride transfer from G3P is favored in comparison to EtG because the carbonyl product of the former reaction is stabilized by hyperconjugative electron donation from the -CH2R keto substituent. The kinetic data show that the phosphite dianion provides the same 7.6 ± 0.1 kcal/mol stabilization of the transition states for enzyme-catalyzed reactions in the forward [reduction of NAD by EtG] and reverse [oxidation of NADH by glycolaldehyde] directions. The experimental evidence that supports a role for phosphite dianion in stabilizing the active closed form of the GPDH (EC) relative to the ca. 6 kcal/mol more unstable open form (EO) is summarized.

Abstract 5360: Relief of chromosomal instability-induced cGAS-STING signaling sensitizes STK11-mutant non-small cell lung cancer to immune checkpoint blockade

Abstract Non-small cell lung cancers (NSCLCs) harboring deletions or inactivating mutations in STK11 (encoding LKB1) are associated with poor prognosis and immune evasion, but the underlying mechanisms are poorly understood. Through integrative analyses of >10,000 molecular profiles from public data sources and an additional ~15,000 new patient data profiles, we find identify STK11-deficient NSCLC as an archetypical chromosomally unstable tumor. Using high-content imaging, we show that both human and murine STK11-mutant models have a higher rate of micronuclei and chromosome mis-segregation events, confirming their high degree of chromosomal instability (CIN). We show that CIN-induced tonic activation of the cGAS-STING pathway results in impaired type I interferon expression, thus, turning the physiological function of this pathway on its head. We show that temporary relief of tonic CIN-induced signaling reprogrammed cancer cells towards production of type I interferons. We achieved this through orthogonal routes, including genetic suppression of CIN by overexpression of mitotic centromere-associated kinesin (MCAK), rescue of wild-type STK11 (but not its kinase-dead) allele, genetic deletion or pharmacological inhibition of cGAS. Relief through any of these approaches re-sensitized cells to acute STING agonism with its endogenous ligand (cGAMP) or pharmacological stimulation. Using otherwise isogenic, syngeneic KRAS-mutant Stk11/Lkb1-/- (KL) and KRAS-mutant p53 mutant (KP) murine models, we show that cGAS KO sensitized otherwise highly resistant KL models to immune checkpoint blockade (ICB), while an increase in CIN (through overexpression of dominant-negative MCAK) in KP conferred resistance in this otherwise ICB-sensitive model. In summary, we define STK11-mutant as archetypical chromosomally unstable form of NSCLC, provide mechanistic basis that correlates with poor clinical outcomes, and demonstrate how relief of tonic CIN-induced changes may be therapeutically leveraged. Citation Format: Lindsay A. Caprio, Christy Hong, Amit D. Amin, Somnath Tagore, Mercedes Duran, Meri Rogava, Luke Cai, Leon Ebel, Johannes Melms, Hanina Hibshoosh, Samuel Bakhoum, Benjamin Izar. Relief of chromosomal instability-induced cGAS-STING signaling sensitizes STK11-mutant non-small cell lung cancer to immune checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5360.

Soil amendments alter cadmium distribution and bacterial community structure in paddy soils

Soil amendments play a pivotal role in ensuring the safety of food production by inhibiting the transfer of heavy metal ions from soils to crops. Nevertheless, their impact on soil characteristics and the microbial community and their role in reducing cadmium (Cd) accumulation in rice remain unclear. In this study, pot experiments were conducted to investigate the effects of three soil amendments (mineral, organic, and microbial) on the distribution of Cd speciation, organic components, iron oxides, and microbial community structure. The application of soil amendments resulted in significant reductions in the soil available Cd content (16 %–51 %) and brown rice Cd content (16 %–78 %), facilitating the transformation of Cd from unstable forms (decreasing 10 %–20 %) to stable forms (increasing 77 %–150 %) in the soil. The mineral and organic amendments increased the soil cation exchange capacity (CEC) and plant-derived organic carbon (OC), respectively, leading to reduced Cd accumulation in brown rice, while the microbial amendment enhanced OC complexity and the abundances of Firmicutes and Bacteroidota, contributing to the decreased rice Cd uptake. The synchrotron radiation–based Fourier transform infrared (SR-FTIR) spectroscopy indicated that soil amendments regulated soil Cd species by promoting iron oxides and OC coupling. Moreover, both organic and microbial amendments significantly reduced the diversity and richness of the bacterial communities and altered their compositions and structures, by increasing the relative abundances of Bacteroidota and Firmicutes and decreasing those of Acidobacteria, Actinobacteria, and Myxococcota. Soil microbiome analysis revealed that the increase of Firmicutes and Bacteroidota associated with Cd adsorption and sequestration contributed to the suppression of soil Cd reactivity. These findings offer valuable insights into the potential mechanisms by which soil amendments regulate the speciation and bioavailability of Cd, and improve the bacterial communities, thereby providing guidance for agricultural management practices.

СВЯЗЬ ВОСПАЛИТЕЛЬНЫХ МАРКЕРОВ И ТРЕВОЖНО-ДЕПРЕССИВНЫХ РАССТРОЙСТВ У ПАЦИЕНТОВ С ОСТРЫМ ИНФАРКТОМ МИОКАРДА

Abstract. Introduction. In recent years, the influence of anxiety and depressive disorders on the course of cardiovascular diseases has been increasingly discussed. The main psychosocial risk factors for the development of acute myocardial infarction include depression and anxiety (various anxiety syndromes and disorders). Currently, inflammation is considered as one of the leading links in myocardial infarction pathogenesis, course, and prognosis. Recent studies have linked the development of anxiety and depressive disorders with changes in the proinflammatory cytokine levels. Severity of immunoinflammatory reactions in patients with unstable forms of coronary heart disease is greater than in patients with a stable course of the disease. The aim of our investigation was to study the proinflammatory cytokine levels in patients with myocardial infarction depending on the presence of anxiety and depressive disorders. Materials and Methods. The study included 160 patients, averagely aged 56.2±1.4 years, who were admitted to the hospital with the ST-segment elevation myocardial infarction. The diagnosis of the said disease was set according to the generally accepted diagnostic criteria. In addition to the traditional clinical and instrumental studies, the patients of the groups under study underwent an assessment of the concentrations of inflammatory biomarkers in plasma and psychological tests using anxiety and depression rating scales, such as Zung Depression Scale and Spielberger-Khanin Anxiety Scale. Results and Discussion. Signs of depression were identified in 82 (51.25%) patients with acute myocardial infarction. Symptoms of mild depression were identified in 44 (53.7%) patients, moderate depression in 30 (36.6%) patients, and severe depression in 8 (9.7%) patients. It has been proven that the average depression score increases with the increase in the disease severity. The average score was 49.72+1.68 for personal anxiety in the group and 41.9±1.6 for reactive anxiety. As the class of infarction severity increased, a significant increase in anxiety levels was observed. An increase in the serum concentrations of CRP, IL-1β, IL-6, IL-8, and TNF-α was detected during the development of myocardial infarction, which was statistically significantly associated with the presence of anxiety-depressive disorders and some indicators of myocardial contractile function. Conclusions. Subclinical inflammation is one of the mechanisms of the negative impact of anxiety and depressive disorders on the prognosis for this category of patients. The presence of anxiety and depression symptoms is associated with higher levels of pro-inflammatory markers, i. e., CRP, IL-1β, IL-6, IL-8, and TNF-a. The degree of activation of proinflammatory markers depends on the severity of the myocardial damage signs and on the nature of complications.

Stable Sulforaphane Targets the Early Stages of Osteoclast Formation to Engender a Lasting Functional Blockade of Osteoclastogenesis.

Sulforaphane, the native but unstable form of SFX-01, is an antioxidant that activates the NRF2 and inhibits the NF-KB pathways to achieve its actions. Resolving the mechanism(s) by which SFX-01 serves to control the various osteoclastogenic stages may expose pathways that could be explored for therapeutic use. Here we seek to identify the stage of osteoclastogenesis targeted by SFX-01 and explore whether, like SFN, it exerts its actions via the NRF2 and NF-KB pathways. Osteoclasts generated from the bone marrow (BM) of mice were cultured with SFX-01 at different timepoints to examine each phase of osteoclastogenesis separately. This showed that SFX-01 exerted actions throughout the process of osteoclastogenesis, but had its largest effects in the early osteoclast precursor differentiation stage. Thus, treatment with SFX-01 for the duration of culture, for the initial 3 days differentiation or for as little as the first 24 h was sufficient for effective inhibition. This aligned with data suggesting that SFX-01 reduced DC-STAMP levels, osteoclast nuclear number and modified cytoskeletal architecture. Pharmacological regulation of the NRF2 pathways, via selective inhibitors/activators, supported the anti-osteoclastogenic roles of an SFX-01-mediated by NRF2 activation, as well as the need for tight NF-KB pathway regulation in osteoclast formation/function.

Targeting Oncostatin M Receptor to Attenuate Carotid Artery Plaque Vulnerability in Hypercholesterolemic Microswine.

Atherosclerosis is a chronic inflammatory disease that leads to acute embolism via the formation of atherosclerotic plaques. Plaque formation is first induced by fatty deposition along the arterial intima. Inflammation, bacterial infection, and the released endotoxins can lead to dysfunction and phenotypic changes of vascular smooth muscle cells (VSMCs), advancing the plaque from stable to unstable form and prone to rupture. Stable plaques are characterized by increased VSMCs and less inflammation while vulnerable plaques develop due to chronic inflammation and less VSMCs. Oncostatin M (OSM), an inflammatory cytokine, plays a role in endothelial cells and VSMC proliferation. This effect of OSM could be modulated by p27KIP1, a cyclin-dependent kinase (CDK) inhibitor. However, the role of OSM in plaque vulnerability has not been investigated. To better understand the role of OSM and its downstream signaling including p27KIP1 in plaque vulnerability, we characterized the previously collected carotid arteries from hyperlipidemic Yucatan microswine using hematoxylin and eosin stain, Movat Pentachrome stain, and gene and protein expression of OSM and p27KIP1 using immunostaining and real-time polymerase chain reaction. OSM and p27KIP1 expression in carotid arteries with angioplasty and treatment with either scrambled peptide or LR12, an inhibitor of triggering receptor expressed on myeloid cell (TREM)-1, were compared between the experimental groups and with contralateral carotid artery. The results of this study elucidated the presence of OSM and p27KIP1 in carotid arteries with plaque and their association with arterial plaque and vulnerability. The findings suggest that targeting OSM and p27KIP1 axis regulating VSMC proliferation may have therapeutic significance to stabilize plaque.