Henlea earthworm bioluminescence comprises violet-blue BRET from tryptophan 2-carboxylate to deazaflavin cofactor.

We recently identified the deazaflavin cofactor as a light emitter in novel bioluminescence (BL) system from Siberian earthworms Henlea sp. (Petushkov et al., 2023, Org. Biomol. Chem. 21:415-427). In the present communication we compared in vitro BL spectra in the absence and in the presence of the cofactor and found a wavelength shift from 420 to 476 nm. This violet-blue BRET to deazaflavin cofactor (acceptor of photonless transfer) masks the actual oxyluciferin as an emitter (BRET donor) in the novel BL system. The best candidate for that masked chromophore is tryptophan 2-carboxylate (T2C) found previously as a building block in some natural products isolated from Henlea sp. (Dubinnyi et al., 2020, ChemSelect 5:13155-13159). We synthesized T2C and acetyl-T2C, verified their presence in earthworms by nanoflow-HRMS, explored spectral properties of excitation and emission spectra and found a chain of excitation/emission maxima with a perfect potential for BRET: 300 nm (excitation of T2C) - 420 nm (emission of T2C) - 420 nm (excitation of deazaflavin) - 476 nm (emission of deazaflavin, BL). An array of natural products with T2C chromophore are present in BL earthworms as candidates for novel oxyluciferin. We demonstrated for the Henlea BL that the energy of the excited state of the T2C chromophore is transferred by the Förster mechanism and then emitted by deazaflavin (BRET), similarly to known examples: aequorin-GFP in Aequorea victoria and antenna proteins in bacterial BL systems (lumazine from Photobacterium and yellow fluorescent protein from Vibrio fischeri strain Y1).

Single nucleotide polymorphism rs527236194 of the cytochrome B gene (MT-CYB) is associated with alterations in sperm parameters.

BACKGROUND: The mitochondrial genome is substantially susceptible to mutations and has high polymorphism due to structural features, location, and lack of recombinant variability, as its inheritance is strictly maternal. All of these events can be accompanied by the accumulation of mitochondrial single nucleotide polymorphisms (mtSNPs) in the sperm. The aim of this research was to analyze the influence of mutations in the MT-CYB gene on sperm quality. METHODS AND RESULTS: We conducted a case‒control study to identify mutations in the mitochondrial cytochrome B (MT-CYB) gene in men with asthenoteratozoospermia (89 cases) and oligoasthenoteratozoospermia (65 cases). The comparison group consisted of 164 fertile men. Somatic cell lysis followed by mtDNA extraction was conducted to analyze three mtDNA polymorphisms, rs28357373 (T15629C (Leu295=), rs527236194 (T15784C (p.Pro346=), rs2853506 (A15218G, p.Thr158Ala). Detection and genotyping of polymorphic loci in the MT-CYB gene was performed using the TaqMan allelic discrimination assay. To verify mutations in the MT-CYB gene, automated Sanger DNA sequencing was used. We found that rs527236194 was associated with asthenoteratozoospermia. rs28357373 in the MT-CYB gene did not show any polymorphism in the analyzed groups, which indicates a rare frequency of the TT genotype in our region. Rs28357373 and rs2853506 are not associated with male sperm abnormalities in the Volga-Ural region. CONCLUSION: The association of the rs527236194 polymorphic variant with sperm parameter alterations suggests its role in the pathophysiology of male infertility and requires further investigation in larger samples.

Inter-Rater Reliability of Collateral Status Assessment Based on CT Angiography: A Retrospective Study of Middle Cerebral Artery Ischaemic Stroke.

The importance of assessing the collateral status (CS) in patients with ischaemic stroke (IS) has repeatedly been emphasised in clinical guidelines. Various publications offer qualitative or semiquantitative scales with gradations corresponding to the different extents of the collaterals, visualised mostly on the basis of CTA images. However, information on their inter-rater reliability is limited. Therefore, the aim of this study is to investigate the inter-rater reliability of the scales for collateral assessment. CTA images of 158 patients in the acute period of IS were used in the study. The assessment of CS was performed by two experts using three methodologies: the modified Tan scale, the Miteff scale, and the Rosenthal scale. Cohen's kappa, weighted kappa and Krippendorff's alpha were used as reliability measures. For the modified Tan scale and the Miteff and Rosenthal scales, the weighted kappa values were 0.72, 0.49 and 0.59, respectively. Although the best measure of consistency was found for the modified Tan scale, no statistically significant differences were revealed among the scales. The impact of the CS on the degree of neurological deficit at discharge was shown for the modified Tan and Rosenthal scales. In conclusion, the analysis showed a moderate inter-rater reliability of the three scales, but was not able to distinguish the best one among them.

Conjugated Dienoic Acid Peroxides as Substrates in Chaetopterus Bioluminescence System.

Biochemistry of bioluminescence of the marine parchment tubeworm Chaetopterus has been in research focus for over a century; however, the results obtained by various groups contradict each other. Here, we report the isolation and structural elucidation of three compounds from Chaetomorpha linum algae, which demonstrate bioluminescence activity with Chaetopterus luciferase in the presence of Fe2+ ions. These compounds are derivatives of polyunsaturated fatty acid peroxides. We have also obtained their structural analogues and demonstrated their activity in the bioluminescence reaction, thus confirming the broad substrate specificity of the luciferase.

Cadmium nitrate and DNA methylation in gastropods: comparison between ovotestis and hepatopancreas.

Dietary ingestion is the main route of exposure to hazardous contaminants in land animals. Cadmium, a high-profile toxic metal, affects living systems at different organismal levels, including major storage organs (liver, kidneys), key organs for species survival (gonads), and epigenetic networks regulating gene expression. 5-methylcytosine (5mC) is the most common and best-characterized epigenetic mark among different modified nucleosides in DNA. This important player in methylation-driven gene expression is impacted by cadmium in sentinel terrestrial vertebrates. However, limited information exists regarding its impact on macroinvertebrates, especially land snails commonly used as (eco)toxicological models. We first investigate the methylomic effects of dietary cadmium given as cadmium nitrate on terrestrial mollusks. Mature specimens of the common brown garden snail, Cornu aspersum, were continuously exposed for four weeks to environmentally-relevant cadmium levels. We determined global genomic DNA methylation in hepatopancreas and ovotestis, as well as changes in the methylation status of CG pairs at the 5' region close to the transcription site of gene encoding the Cd-selective metallothionein (Cd-MT). Weight gain/loss, hypometabolism tendency, and survival rates were also assessed. Although this exposure event did not adversely affect survival, gastropods exposed to the highest Cd dose revealed a significant reduction in body weight and a significant increase in hypometabolic behavior. The hepatopancreas, but not the ovotestis, displayed significant hypermethylation, but only for the aforementioned specimens. We also found that the 5' end of the Cd-MT gene was unmethylated in both organs and its methylation status was insensitive to cadmium exposure. Our results are important since they provide scientists, for the first time, with quantitative data on DNA methylation in gastropod ovotestis and refine our understanding of Cd epigenetic effects on terrestrial mollusks.

Novel O-benzylcinnamic acid derivative L26 treats acute lung injury in mice by MD-2.

Acute lung injury (ALI) is an inflammation-mediated respiratory disease that is associated with a high mortality rate. In this study, a series of novel O-benzylcinnamic acid derivatives were designed and synthesized using cinnamic acid as the lead compound. We tested the preliminary anti-inflammatory activity of the compounds by evaluating their effect on inhibiting the activity of alkaline phosphatase (ALP) in Hek-Blue-TLR4 cells, in which compound L26 showed the best activity and 7-fold more active than CIN. ELISA, immunoprecipitation, and molecular docking indicated that L26 targeted MD-2 protein and competed with LPS to bind to MD-2, which resulted in the inhibition of inflammation. In the LPS-induced mouse model of ALI, L26 was found to decrease ALP activity and inflammatory cytokine TNF-α release to reduce lung injury by inhibiting the NF-κB signaling pathway. Acute toxicity experiments showed that high doses of L26 did not cause adverse reactions in mice, and it was safe in vivo. Also, the preliminary pharmacokinetic parameters of L26 were investigated in SD rats (T1/2 = 4.246 h). In summary, L26 exhibited optimal pharmacodynamic and pharmacokinetic characteristics, which suggested that L26 could serve as a potential agent for the development of ALI treatment.

Leaching Stability and Redox Activity of Copper-MFI Zeolites Prepared by Solid-State Transformations: Comparison with Ion-Exchanged and Impregnated Samples.

The catalyst preparation route is well known to affect the copper loading and its electronic state, which influence the properties of the resulting catalyst. Electronic states of copper ions in copper-containing silicalites with the MFI-framework topology obtained by a solid-state transformation S (SST) were studied with using EPR, UV-Vis DR, XRD, H2-TPR and chemical differentiating dissolution. They were compared with Cu-ZSM-5 and Cu-MFI (silicalite) prepared via the ion-exchange and incipient wetness impregnation. SST route was shown to provide the formation of MFI structure and favor clustering of Cu-ions near surface and subsurface of zeolite crystals. The square-planar oxide clusters of Cu2+-ions and the finely dispersed CuO nanoparticles with the size down to 20 nm were revealed in Cu-MFI-SST samples with low (0.5-1.0 wt.%) and high (16 wt.%) Cu-content. The CuO nanoparticles were characterized by energy band gap 1-1.16 eV. The CuO-like clusters were characterized by ligand-to-metal charge transfer band (CTB L → M) at 32,000 cm-1 and contain EPR-visible surface Cu2+-ions. The low Cu-loaded SST-samples had poor redox properties and activity towards different solvents due to decoration of copper-species by silica; whereas CuO nanoparticles were easily removed from the catalyst by HCl. In the ion-exchanged samples over MFI-silicalite and ZSM-5, Cu2+-ions were mainly CuO-like clusters and isolated Cu2+ ions inside MFI channels. Their redox properties and tendency to dissolve in acidic solutions differed from the behavior of SST-series samples.

Discovery of 4-oxo-N-phenyl-1,4-dihydroquinoline-3-carboxamide derivatives as novel anti-inflammatory agents for the treatment of acute lung injury and sepsis.

Acute lung injury (ALI) and sepsis, characterized by systemic inflammatory response syndrome, remain the major causes of death in severe patients. Inhibiting the release of proinflammatory cytokines is considered to be a promising method for the treatment of inflammation-related diseases. In this study, a total of 28 4-oxo-N-phenyl-1,4-dihydroquinoline-3-carboxamide derivatives were designed and synthesized and their anti-inflammatory activities in J774A.1 were evaluated. Among them, derivative 13a was found to significantly inhibit lipopolysaccharide (LPS)-induced expression of the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) on J774A.1, THP-1 and LX-2 cells, and inhibited the activation of the NF-κB pathway. Furthermore, administration of 13ain vivo significantly improved the symptoms in LPS-induced ALI mice, including alleviation of pathological changes in the lung tissue, reduction of pulmonary edema, and inhibition of macrophage infiltration. Moreover, the administration of 13ain vivo significantly promoted survival in LPS-induced sepsis mice. 13a demonstrated favorable pharmacokinetic properties with T1/2 value of 11.8 h and F value of 36.3%. Therefore, this study has identified a novel 4-oxo-N-phenyl-1,4-dihydroquinoline-3-carboxamide derivative, 13a, which is an effective anti-inflammatory agent. The findings have laid a foundation for the further development of agents to treat ALI and sepsis.

Deazaflavin cofactor boosts earthworms Henlea bioluminescence.

The bioluminescence of Siberian earthworms Henlea sp. was found to be enhanced by two low molecular weight activators, termed ActH and ActS, found in the hot extracts. The fluorescence emission maximum of the activators matches the bioluminescence spectrum that peaks at 464 nm. We purified 4.3 and 8.8 micrograms of ActH and ActS from 200 worms and explored them using orbitrap HRMS with deep fragmentation and 1D/2D NMR equipped with cryoprobes. Their chemical structures were ascertained using chemical shift prediction services, structure elucidation software and database searches. ActH was identified as the riboflavin analoge archaeal cofactor F0, namely 7,8-didemethyl-8-hydroxy-5-deazariboflavin. ActS is a novel compound, namely ActH sulfated at the 3' ribityl hydroxyl. We designed and implemented a new four step synthesis strategy forActH that outperformed previous synthetic approaches. The synthetic ActH was identical to the natural one and activated Henlea sp. bioluminescence. The bioluminescence enhancement factor X was measured at different ActH concentrations and the Michaelis constant Km = 0.22 ± 0.01 µM was obtained by nonlinear regression. At an excess of synthetic ActH, the factor X was saturated at Xmax = 33.3 ± 0.5, thus opening an avenue to further characterisation of the Henlea sp. bioluminescence system. ActH did not produce bioluminescence without the luciferin with an as yet unknown chemical structure. We propose that ActH and the novel sulfated deazariboflavin ActS either emit the light of the Henlea sp. bioluminescence and/or accept hydride(s) donor upon luciferin oxidation.

Design, synthesis, and bioactivity evaluation of novel 1-(4-(benzylsulfonyl)-2-nitrophenyl) derivatives as potential anti-inflammatory agents against LPS-induced acute lung injury.

Acute lung injury (ALI) is a devastating disease with a high mortality rate of 30%-40%. There is an unmet clinical need owing to limited treatment strategies and little clinical benefit. The pathology of ALI indicates that reducing the inflammatory response could be a highly desirable strategy to treat ALI. In this study, we designed and synthesized 36 novel 1-(4-(benzylsulfonyl)-2-nitrophenyl) derivatives and evaluated their anti-inflammatory activities by measuring the release of cytokines in lipopolysaccharide (LPS)-challenged J774A.1 cells. Compounds 19, 20, and 39 potently reduced the release of IL-6 and TNF-α in J774A.1 cells. Additionally, 39 improved LPS-induced ALI in vivo and inhibited cytokine production in lung tissues. Furthermore, 39 reduced inflammatory infiltration and downregulated p-p65 levels in lung tissues. Thus, compound 39 could serve as a new lead structure for the development of anti-inflammatory drugs to treat ALI.

Schisandrin B protects against LPS-induced inflammatory lung injury by targeting MyD88.

BACKGROUND: Acute lung injury (ALI) is a challenging clinical syndrome that manifests as an acute inflammatory response. Schisandrin B (Sch B), a bioactive lignan from Schisandra genus plants, has been shown to suppress inflammatory responses and oxidative stress. However, the underlying molecular mechanisms have remained elusive. HYPOTHESIS/PURPOSE: This study performed an in-depth investigation of the anti-inflammatory mechanism of Sch B in macrophages and in an animal model of ALI. METHODS: qPCR array was used to probe the differential effects and potential target of Sch B. ALI was induced by intratracheal administration of LPS in experimental mice with or without Sch B treatment. RESULTS: Our studies show that Sch B differentially modulates inflammatory factor induction by LPS in macrophages by directly binding myeloid differentiation response factor-88 (MyD88), an essential adaptor protein in the toll-like receptor-4 (TLR4) pathway. Sch B spares non-MyD88-pathways downstream of TLR4. Such inhibition suppressed key signaling mediators such as TAK1, MAPKs, and NF-κB, and pro-inflammatory factor induction. Pull down assay using biotinylated-Sch B validate the direct interaction between Sch B and MyD88 in macrophages. Treatment of mice with Sch B prior to LPS challenge reduced inflammatory cell infiltration in lungs, induction of MyD88-pathway signaling proteins, and prevented inflammatory cytokine induction. CONCLUSION: In summary, our studies have identified MyD88 as a direct target of Sch B for its anti-inflammatory activity, and suggest that Sch B may have therapeutic value for acute lung injury and other MyD88-dependent inflammatory diseases.

Heme induces inflammatory injury by directly binding to the complex of myeloid differentiation protein 2 and toll-like receptor 4.

Heme, as an essential component of hemoproteins, is a prosthetic co-factor found in many cells, which is essential for physiologically vital oxygen transport. However, extracellular or circulatory heme is cytotoxic and triggers inflammation. Although the proinflammatory role of heme has been reported to be associated with Toll-like receptor 4 (TLR4) signaling, the exact mechanism remains unknown. Here, we show that heme promotes TLR4 signaling and inflammation via directly physically interacting with TLR4 and its adaptor protein myeloid differentiation protein 2 (MD2). Genetic loss of MD2 ameliorates heme-induced inflammation and inflammatory cytokine production in the spleen of MD2 knockout (MD2-/-) mice. Using mouse macrophage RAW 264.7 cell line, we show that heme induces TLR4 dimerization and MD2/TLR4/MyD88 activation by physically interacting with TLR4 and MD2 in vitro. Genetic loss of MD2 inhibits heme-induced inflammation and MAPK/NF-κB pathway in mouse primary macrophages extracted from MD2-/- mice. Furthermore, pharmacological inhibition of MD2 by L6H9 ameliorates heme-induced inflammation in macrophages. These findings demonstrate that heme causes inflammation by directly binding to MD2/TLR4 complex, leading to activation of TLR4/MAPK/NF-κB signaling pathway and production of downstream effectors of inflammation.

Efficient Inner-to-Outer Wall Energy Transfer in Highly Pure Double-Wall Carbon Nanotubes Revealed by Detailed Spectroscopy.

The coaxial stacking of two single-wall carbon nanotubes (SWCNTs) into a double-wall carbon nanotube (DWCNT), forming a so-called one-dimensional van der Waals structure, leads to synergetic effects that dramatically affect the optical and electronic properties of both layers. In this work, we explore these effects in purified DWCNT samples by combining absorption, wavelength-dependent infrared fluorescence-excitation (PLE), and wavelength-dependent resonant Raman scattering (RRS) spectroscopy. Purified DWCNTs are obtained by careful solubilization that strictly avoids ultrasonication or by electronic-type sorting, both followed by a density gradient ultracentrifugation to remove unwanted SWCNTs that could obscure the DWCNT characterization. Chirality-dependent shifts of the radial breathing mode vibrational frequencies and transition energies of the inner and outer DWCNT walls with respect to their SWCNT analogues are determined by advanced two-dimensional fitting of RRS and PLE data of DWCNT and their reference SWCNT samples. This exhaustive data set verifies that fluorescence from the inner DWCNT walls of well-purified samples is severely quenched through efficient energy transfer from the inner to the outer DWCNT walls. Combined analysis of the PLE and RRS results further reveals that this transfer is dependent on the inner and outer wall chirality, and we identify the specific combinations dominant in our DWCNT samples. These obtained results demonstrate the necessity and value of a combined structural characterization approach including PLE and RRS spectroscopy for bulk DWCNT samples.

Early antithrombotic post-discharge therapy using prophylactic DOAC or dipyridamole improves long-term survival and cardiovascular outcomes in hospitalized COVID-19 survivors.

Introduction: Cardiovascular events are common in COVID-19. While the use of anticoagulation during hospitalization has been established in current guidelines, recommendations regarding antithrombotic therapy in the post-discharge period are conflicting. Methods: To investigate this issue, we conducted a retrospective follow-up (393 ± 87 days) of 1,746 consecutive patients, hospitalized with and surviving COVID-19 pneumonia at a single tertiary medical center between April and December 2020. Survivors received either 30-day post-discharge antithrombotic treatment regime using prophylactic direct oral anticoagulation (DOAC; n = 1,002) or dipyridamole (n = 304), or, no post-discharge antithrombotic treatment (Ctrl; n = 440). All-cause mortality, as well as cardiovascular mortality (CVM) and further cardiovascular outcomes (CVO) resulting in hospitalization due to pulmonary embolism (PE), myocardial infarction (MI) and stroke were investigated during the follow-up period. Results: While no major bleeding events occured during follow-up in the treatment groups, Ctrl showed a high but evenly distributed rate all-cause mortality. All-cause mortality (CVM) was attenuated by prophylactic DOAC (0.6%, P < 0.001) and dipyridamole (0.7%, P < 0.001). This effect was also evident for both therapies after propensity score analyses using weighted binary logistic regression [DOAC: B = -3.33 (0.60), P < 0.001 and dipyridamole: B = -3.04 (0.76), P < 0.001]. While both treatment groups displayed a reduced rate of CVM [DOAC: B = -2.69 (0.74), P < 0.001 and dipyridamole: B = -17.95 (0.37), P < 0.001], the effect in the DOAC group was driven by reduction of both PE [B-3.12 (1.42), P = 0.012] and stroke [B = -3.08 (1.23), P = 0.028]. Dipyridamole significantly reduced rates of PE alone [B = -17.05 (1.01), P < 0.001]. Conclusion: Late cardiovascular events and all-cause mortality were high in the year following hospitalization for COVID-19. Application of prophylactic DOAC or dipyridamole in the early post-discharge period improved mid- and long-term CVO and all-cause mortality in COVID-19 survivors.

PECULIARITIES IN PERFORMING MEDICAL EXAMINATION TO ASSESS THE EXTENT OF ALCOHOL INTOXICATION OF DRIVERS ACCORDING TO THE LEGISLATION OF UKRAINE AND SOME OTHER COUNTRIES.

OBJECTIVE: The aim: This study is aimed at conducting a comprehensive analysis of the Ukrainian legislation regulating the alcohol testing procedure for drivers, investigating the practice of its implementation, reviewing international experience in this field, and elaborating proposals for its improvement. PATIENTS AND METHODS: Materials and methods: During the writing of the article, the current legislation of Ukraine is regulated, which regulates the procedure for medical examination to establish the state of intoxication of drivers, namely the Code of Ukraine on Administrative Offenses. This work meets the requirements of the Declaration of Helsinki. Methodology of the study includes general scientific methods (dialectic method, inductive and deductive approaches), special investigative techniques. CONCLUSION: Conclusions: Our study has underlined the necessity to improve the legal regulation for more effective alcohol testing program for drivers in Ukraine. This implies the elaboration of guideline for alcohol testing procedure and its approval by the Ministry of Health of Ukraine; to specify and legislate maximum permissible indicator values of blood alcohol concentration; to set the list of drugs and other substances through regulation; to adopt administrative responsibility for driving while intoxicated with alcohol (from 0.2 ppm to 1.1), and criminal liability for driving under severe alcoholic intoxication (1.1 ppm and above).

Electroluminescence from Single-Walled Carbon Nanotubes with Quantum Defects.

Individual single-walled carbon nanotubes with covalent sidewall defects have emerged as a class of photon sources whose photoluminescence spectra can be tailored by the carbon nanotube chirality and the attached functional group/molecule. Here we present electroluminescence spectroscopy data from single-tube devices based on (7, 5) carbon nanotubes, functionalized with dichlorobenzene molecules, and wired to graphene electrodes. We observe electrically generated, defect-induced emissions that are controllable by electrostatic gating and strongly red-shifted compared to emissions from pristine nanotubes. The defect-induced emissions are assigned to excitonic and trionic recombination processes by correlating electroluminescence excitation maps with electrical transport and photoluminescence data. At cryogenic conditions, additional gate-dependent emission lines appear, which are assigned to phonon-assisted hot-exciton electroluminescence from quasi-levels. Similar results were obtained with functionalized (6, 5) nanotubes. We also compare functionalized (7, 5) electroluminescence data with photoluminescence of pristine and functionalized (7, 5) nanotubes redox-doped using gold(III) chloride solution. This work shows that electroluminescence excitation is selective toward neutral defect-state configurations with the lowest transition energy, which in combination with gate-control over neutral versus charged defect-state emission leads to high spectral purity.

Correlation of the Imbalance in the Circulating Lymphocyte Subsets With C-Reactive Protein and Cardio-Metabolic Conditions in Patients With COVID-19.

The immune system is severely compromised in patients with COVID-19. The representative group of 43 patients were selected from the cohort of 342 patients with COVID-19 and pneumonia. This group of 43 patients was examined for the levels of C-reactive protein, biomarker of systemic inflammation, and for the subsets of adaptive immune cells. The immunological parameters were correlated with the metabolic parameters and cardiovascular pathology history. We identified that a decrease in the absolute number of T-lymphocytes, T-cytotoxic, T-activated and B-lymphocytes correlated with the higher levels of CRP. The absolute number of T-helpers and the absolute number of double positive T-lymphocytes positively correlated with the levels of iron in serum (Z= 0,310 and Z=0,394). The absolute numbers of T-activated lymphocytes positively correlated with serum levels of LDH (Z = 0,422), ferritin (Z = 0,407) and iron (Z = 0,418). When studying subpopulations of lymphocytes, depending on the combined pathology, we found that the absolute numbers of B-lymphocytes and double positive T-lymphocytes in the peripheral blood were significantly reduced in patients with arterial hypertension (p=0,0074 and p=0,0227, correspondingly). The increased levels of NK cell were found in patients with a history of coronary heart disease (p=0,0108). In addition, we found that deficiencies in the adaptive immune system correlated with the deficiencies in iron metabolism. The cardiovascular pathology upsets the balance in the adaptive and innate immune system in the circulation of patient with severe COVID-19.

The anthropogenic fallout radionuclides in soils of Mount Khuko (the Western Caucasus) and their application for determination of sediment redistribution.

The purposes of this study are to determine the content and origin of anthropogenic fallout radionuclides (FRN) in soils of Mount Khuko, located in the western sector of the Caucasus Mountains and to assess the possibility to use them for evaluation of sediment redistribution for the alpine grasslands,. The field study was carried out in August 2019 near the top of Mount Khuko, located in the western part of the main Caucasus Mountain Ridge. Integral and incremental soil samples were collected from the different morphological units of the studied area. The content of 137Cs and 241Am in soil samples was evaluated using laboratory gamma-spectrometry. A part of samples was selected for Pu isotopes extraction and then alpha-spectrometric analysis. It was established that the 137Cs contamination of soils in the studied area has at least two sources of origin. The first source is the 137Cs bomb-derived fallout after the bomb tests in 1950-60th, which is widespread across the globe. The second source is 137Cs Chernobyl-derived fallout High random variability (Cv = 25-42%) was found within reference sites, located at the undisturbed areas on the local flat interfluves due to high variability of soil characteristics (grain size, density, organic matter content etc.). However minimum spatial variability (range 12,2-14,3 kBq/m2) was identified for the mean value of 137Cs inventories for all 5 reference sites located in the different parts of the studied area. It is difficult to separate individual peaks of the bomb-derived and Chernobyl-derived 137Cs falloutin sediment sinks with low sedimentation rates. Application 239,240Pu as an additional chronological marker allows to identify the origin of above mention peaks in the soils of alpine grasslands and of dry lake bottom.

The role of attraction in the phase diagrams and melting scenarios of generalized 2D Lennard-Jones systems.

Monolayer and two-dimensional (2D) systems exhibit rich phase behavior, compared with 3D systems, in particular, due to the hexatic phase playing a central role in melting scenarios. The attraction range is known to affect critical gas-liquid behavior (liquid-liquid in protein and colloidal systems), but the effect of attraction on melting in 2D systems remains unstudied systematically. Here, we have revealed how the attraction range affects the phase diagrams and melting scenarios in a 2D system. Using molecular dynamics simulations, we have considered the generalized Lennard-Jones system with a fixed repulsion branch and different power indices of attraction from long-range dipolar to short-range sticky-sphere-like. A drop in the attraction range has been found to reduce the temperature of the gas-liquid critical point, bringing it closer to the gas-liquid-solid triple point. At high temperatures, attraction does not affect the melting scenario that proceeds through the cascade of solid-hexatic (Berezinskii-Kosterlitz-Thouless) and hexatic-liquid (first-order) phase transitions. In the case of dipolar attraction, we have observed two triple points inherent in a 2D system: hexatic-liquid-gas and crystal-hexatic-gas, the temperature of the crystal-hexatic-gas triple point is below the hexatic-liquid-gas triple point. This observation may have far-reaching consequences for future studies, since phase diagrams determine possible routes of self-assembly in molecular, protein, and colloidal systems, whereas the attraction range can be adjusted with complex solvents and external electric or magnetic fields. The results obtained may be widely used in condensed matter, chemical physics, materials science, and soft matter.

Myeloid differential protein-2 inhibition improves diabetic cardiomyopathy via p38MAPK inhibition and AMPK pathway activation.

Myeloid differential protein-2 (MD2) has been shown to play a critical role in the progression of diabetic cardiomyopathy (DCM). This study aims to explore the non-inflammatory mechanisms mediated by MD2 in DCM and to test the therapeutic effects of MD2 inhibitor C30 on DCM. Streptozotocin (STZ) was used to construct DCM model in wild-type and MD2 knockout mice. The collected heart samples were subjected to RNA-sequencing assay. Gene set enrichment analysis of the RNA-seq data indicated that MD2 knockout was associated with energy metabolism pathways in diabetic mouse heart. Further data showed that AMPK pathway was impaired under high glucose condition, which was mediated by p38MAPK activation. MD2 knockout or pharmacological inhibitor C30 completely rescued AMPK signaling through p38MAPK inhibition. Importantly, C30 treatment significantly prevented myocardial damage and dysfunction in T1DM mice evidenced by improved cardiac function and reduced cardiomyocyte apoptosis and cardiac fibrosis. Furthermore, the therapeutic effect of C30 on DCM was correlated to p38MAPK inhibition and AMPK pathway activation in vivo and in vitro. In conclusion, MD2 inhibition exhibits therapeutic effects on DCM through p38MAPK inhibition and AMPK activation, which enables MD2 a promising target for DCM treatment by suppressing metaflammation and improving cardiac metabolism.