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1.
J Phys Chem B ; 128(16): 3972-3980, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38624173

RESUMO

Complex molten chloride salt mixtures of uranium, magnesium, and sodium are top candidates for promising nuclear energy technologies to produce electricity based on molten salt reactors. From a local structural perspective, LaCl3 is similar to UCl3 and hence a good proxy to study these complex salt mixtures. As fission products, lanthanide salts and their mixtures are also very important in their own right. This article describes from an experimental and theory perspective how very different the structural roles of MgCl2 and NaCl are in mixtures with LaCl3. We find that, whereas MgCl2 becomes an integral part of multivalent ionic networks, NaCl separates them. In a recent article (J. Am. Chem. Soc. 2022, 144, 21751-21762) we have called the disruptive behavior of NaCl "the spacer salt effect". Because of the heterogeneous nature of these salt mixtures, there are multiple structural motifs in the melt, each with its particular free energetics. Our work identifies and quantifies these; it also elucidates the mechanisms through which Cl- ions exchange between Mg2+-rich and La3+-rich environments.

2.
Prog Neurobiol ; 235: 102600, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38548126

RESUMO

Animal models of human neurological disorders provide valuable experimental tools which enable us to study various aspects of disorder pathogeneses, ranging from structural abnormalities and disrupted metabolism and signaling to motor and mental deficits, and allow us to test novel therapies in preclinical studies. To be valid, these animal models should recapitulate complex pathological features at the molecular, cellular, tissue, and behavioral levels as closely as possible to those observed in human subjects. Pathological states resembling known human neurological disorders can be induced in animal species by toxins, genetic factors, lesioning, or exposure to extreme conditions. In recent years, novel animal models recapitulating neuropathologies in humans have been introduced. These animal models are based on synthetic biology approaches: opto- and chemogenetics. In this paper, we review recent opto- and chemogenetics-based animal models of human neurological disorders. These models allow for the creation of pathological states by disrupting specific processes at the cellular level. The artificial pathological states mimic a range of human neurological disorders, such as aging-related dementia, Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, epilepsy, and ataxias. Opto- and chemogenetics provide new opportunities unavailable with other animal models of human neurological disorders. These techniques enable researchers to induce neuropathological states varying in severity and ranging from acute to chronic. We also discuss future directions for the development and application of synthetic biology approaches for modeling neurological disorders.


Assuntos
Epilepsia , Doença de Parkinson , Animais , Humanos , Optogenética/métodos , Modelos Animais , Neuropatologia
3.
BMC Pediatr ; 24(1): 200, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515059

RESUMO

BACKGROUND: The results of disparate clinical studies indicate abnormally frequent cases of certain microorganisms in children with autism spectrum disorders (ASD). However, these data require clarification and systematization. The study aims to study the structure of the microbial profile in children with ASD and genetic folate cycle deficiency (GFCD) and consider differences in diagnostic approaches for identifying microorganisms of different types. METHODS: The study analyzed medical data from 240 children (187 boys and 63 girls) with GFCD aged 2 to 9 years. The children had clinical manifestations of ASD (the study group, SG). The control group (CG) included 53 clinically healthy children (37 boys and 16 girls) of the same age but without GFCD. Both groups of children were tested on active herpetic infections (HSV-1/2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8), ТТV, Streptococcus pyogenes, Candida albicans, Borrelia burgdorferi, Mycoplasma pneumoniae, Chlamydia pneumoniae, Yersinia enterocolitica, Toxoplasma gondii, congenital CMV neuroinfection and postnatal HSV-1/2 encephalitis. The testing used diagnostic methods specified in PubMed-indexed studies. RESULTS: In the SG, TTV was found in 196 children (82%), HHV-7 - in 172 (72%), HHV-6 - in 162 (68%), EBV - in 153 (64%), Streptococcus pyogenes - in 127 (53%), Candida albicans - in 116 (48%), Borrelia - in 107 (45%), Mycoplasma pneumoniae - in 94 (39%), Chlamydia pneumoniae - in 85 (35%), Yersinia entеrocolitica - in 71 (30%), Toxoplasma gondii - in 54 (23%), congenital CMV neuroinfection - in 26 (11%), and postnatal HSV-1/2 encephalitis - in 11 children (5% of cases) (p < p0.05; Z < Z0.05). In the SG, there was a higher microbial load in older children (p < p0.05; Z < Z0.05). No gender differences were found. CONCLUSIONS: The study described and characterized a specific abnormal microbial spectrum with a predominance of viral opportunistic agents in children with ASD associated with GFCD.


Assuntos
Transtorno do Espectro Autista , Infecções por Citomegalovirus , Encefalite , Infecções por Herpesviridae , Herpesvirus Humano 6 , Masculino , Criança , Feminino , Humanos , Infecções por Herpesviridae/diagnóstico , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/diagnóstico , Herpesvirus Humano 6/genética , Ácido Fólico
4.
Mol Neurobiol ; 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37995077

RESUMO

A delicate balance between quiescence and division of the radial glia-like stem cells (RGLs) ensures continuation of adult hippocampal neurogenesis (AHN) over the lifespan. Transient or persistent perturbations of this balance due to a brain pathology, drug administration, or therapy can lead to unfavorable long-term outcomes such as premature depletion of the RGLs, decreased AHN, and cognitive deficit. Memantine, a drug used for alleviating the symptoms of Alzheimer's disease, and electroconvulsive seizure (ECS), a procedure used for treating drug-resistant major depression or bipolar disorder, are known strong AHN inducers; they were earlier demonstrated to increase numbers of dividing RGLs. Here, we demonstrated that 1-month stimulation of quiescent RGLs by either memantine or ECS leads to premature exhaustion of their pool and altered AHN at later stages of life and that aging of the brain modulates the ability of the quiescent RGLs to be recruited into the cell cycle by these AHN inducers. Our findings support the aging-related divergence of functional features of quiescent RGLs and have a number of implications for the practical assessment of drugs and treatments with respect to their action on quiescent RGLs at different stages of life in animal preclinical studies.

5.
ACS Appl Mater Interfaces ; 15(10): 13772-13782, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36877214

RESUMO

Understanding the mechanisms leading to the degradation of alloys in molten salts at elevated temperatures is significant for developing several key energy generation and storage technologies, including concentrated solar and next-generation nuclear power plants. Specifically, the fundamental mechanisms of different types of corrosion leading to various morphological evolution characteristics for changing reaction conditions between the molten salt and alloy remain unclear. In this work, the three-dimensional (3D) morphological evolution of Ni-20Cr in KCl-MgCl2 is studied at 600 °C by combining in situ synchrotron X-ray and electron microscopy techniques. By further comparing different morphology evolution characteristics in the temperature range of 500-800 °C, the relative rates between diffusion and reaction at the salt-metal interface lead to different morphological evolution pathways, including intergranular corrosion and percolation dealloying. In this work, the temperature-dependent mechanisms of the interactions between metals and molten salts are discussed, providing insights for predicting molten salt corrosion in real-world applications.

6.
Redox Biol ; 60: 102604, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36640726

RESUMO

Oxidative stress, a state of disrupted redox signaling, reactive oxygen species (ROS) overproduction, and oxidative cell damage, accompanies numerous brain pathologies, including aging-related dementia and Alzheimer's disease, the most common neurodegenerative disorder of the elderly population. However, a causative role of neuronal oxidative stress in the development of aging-related cognitive decline and neurodegeneration remains elusive because of the lack of approaches for modeling isolated oxidative injury in the brain. Here, we present a chemogenetic approach based on the yeast flavoprotein d-amino acid oxidase (DAAO) for the generation of intraneuronal hydrogen peroxide (H2O2). To validate this chemogenetic tool, DAAO and HyPer7, an ultrasensitive genetically encoded H2O2 biosensor, were targeted to neurons. Changes in the fluorescence of HyPer7 upon treatment of neurons expressing DAAO with d-norvaline (D-Nva), a DAAO substrate, confirmed chemogenetically induced production of intraneuornal H2O2. Then, using the verified chemogenetic tool, we emulated isolated intraneuronal oxidative stress in acute brain slices and, using electrophysiological recordings, revealed that it does not alter basal synaptic transmission and the probability of neurotransmitter release from presynaptic terminals but reduces long-term potentiation (LTP). Moreover, treating neurons expressing DAAO with D-Nva via the patch pipette also decreases LTP. This observation indicates that isolated oxidative stress affects synaptic plasticity at single cell level. Our results broaden the toolset for studying normal redox regulation in the brain and elucidating the role of oxidative stress to the pathogenesis of cognitive aging and the early stages of aging-related neurodegenerative diseases. The proposed approach is useful for identification of early markers of neuronal oxidative stress and may be used in screens of potential antioxidants effective against neuronal oxidative injury.


Assuntos
Peróxido de Hidrogênio , Estresse Oxidativo , Humanos , Idoso , Peróxido de Hidrogênio/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Antioxidantes/farmacologia , Plasticidade Neuronal/fisiologia
7.
J Am Chem Soc ; 144(47): 21751-21762, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36379028

RESUMO

Lanthanides are important fission products in molten salt reactors, and understanding their structure and that of their mixtures is relevant to many scientific and technological problems including the recovery and separation of rare earth elements using molten salt electrolysis. The literature on molten salts and specifically on LaCl3 and LaCl3-NaCl mixtures is often fragmented, with different experiments and simulations coinciding in their explanation for certain structural results but contradicting or questioning for others. Given the very practical importance that actinide and lanthanide salts have for energy applications, it is imperative to arrive at a clear unified picture of their local and intermediate-range structure in the neat molten state and when mixed with other salts. This article aims to unequivocally answer a set of specific questions: is it correct to think of long-lived octahedral coordination structures for La3+? What is the nature as a function of temperature of networks and intermediate-range order particularly upon dilution of the trivalent ion salt? Is the so-called scattering first sharp diffraction peak (FSDP) for neat LaCl3 truly indicative of intermediate-range order? If so, why is there a new lower-q peak when mixed with NaCl? Are X-ray scattering and Raman spectroscopy results fully consistent and easily described by simulation results? We will show that answers to these questions require that we abandon the idea of a most prominent coordination state for M3+ ions and instead think of multiple competing coordination states in exchange due to significant thermal energy in the molten state.


Assuntos
Elementos da Série dos Lantanídeos , Sais , Sais/química , Cloreto de Sódio , Íons/química , Temperatura
8.
Virusdisease ; 33(2): 155-165, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35991701

RESUMO

The purpose of this study is to diagnose herpesvirus infections in refractory atypical trigeminal neuralgia, to assess pathogenetic links, and to explore the efficacy of antiviral treatment. In a prospective controlled study, 95 patients with trigeminal neuralgia received antiviral therapy (valacyclovir + alpha2b-interferon) (experimental group, EG). Other patients refused to receive treatment (control group 1 (CG1), n = 31). Control group 2 (CG2) included 32 healthy individuals of the same age and sex. Herpesvirus infection was diagnosed in blood leukocytes by PCR (Biocom, Russian Federation). Serum concentrations of IgM, IgA and IgG to HSV-1/2, VZV (ELISA, Vector-Best, Russian Federation) were determined. Reactivation of herpesvirus infections was observed in the EG in 87% of cases. The heterogeneity of herpesvirus-associated damage of trigeminal nerves and anatomically related areas of the central nervous system (CNS) has been demonstrated. The treatment applied was effective for herpesvirus infection (77%) and pain (61%) and ineffective for immunity correction (26% of cases). Atypical refractory trigeminal neuralgia is associated with herpesvirus infections that reactivate due to minor immunodeficiencies. Antiviral treatment suppresses herpesviruses and reduces the intensity of pain. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-022-00769-9.

9.
Immunology ; 167(3): 443-450, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35866691

RESUMO

The purpose of the present study is to evaluate the efficacy of combination immunotherapy with Propes and Inflamafertin in GDFC adults with natural killer (NK) and/or natural killer T-lymphocyte (NKT) cell deficiency. This single-centre, retrospective, controlled, non-randomized clinical trial analysed medical records of 212 adult GDFC patients aged 19-50 years (study group [SG]). SG received Propes at a dose of 2 ml intramuscularly every other day at night for three consecutive months and Inflamafertin at a dose of 2 ml IM every other day at night for three consecutive months in rotation with Propes. The control group involved 34 patients with GDFC who followed the same age and gender distribution pattern but did not receive immunotherapy. The number of NK cells reached the lower limit of normal in 95 out of 131 patients (72% of cases) with baseline deficiency of these lymphocytes. The average number of NK cells in the blood of SG patients almost doubled during the 3-month course of immunotherapy (P ˂ 0.05; Z ˂ Z0.05 ). However, it almost returned to initial levels 2 months following the discontinuation of the immunotherapeutic agents (P ˃ 0.05; Z ˃ Z0.05 ). Combination immunotherapy with Propes and Inflamafertin is an effective strategy for the treatment of immunodeficiency caused by GDFC in adult patients.


Assuntos
Células T Matadoras Naturais , Adulto , Ácido Fólico , Humanos , Imunoterapia , Células Matadoras Naturais , Estudos Retrospectivos
10.
J Phys Chem Lett ; 13(25): 5956-5962, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35735362

RESUMO

Molten inorganic salts are attracting resurgent attention because of their unique physicochemical properties, making them promising media for next-generation concentrating solar power systems and molten salt reactors. The dynamics of these highly disordered ionic media is largely studied by theoretical simulations, while the robust experimental techniques capable of observing local dynamics are not well-developed. To provide fundamental insights into the atomic-scale transport properties of molten salts, we report the real-space dynamics of molten magnesium chloride at high temperatures employing the Van Hove correlation function obtained by inelastic neutron scattering. Our results directly depict the distance-dependent dynamics of a molten salt on the picosecond time scale. This study demonstrates the capability of the developed approach to describe the locally correlated- and self-dynamics in molten salts, significantly improving our understanding of the interplay between microscopic structural parameters and their dynamics that ultimately control physical properties of condensed matter in extreme environments.

11.
Microbiol Immunol ; 66(4): 193-199, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35102619

RESUMO

This study aimed to compare the efficacy of valaciclovir, valganciclovir, and artesunate in treating chronic reactivated human herpesvirus type 6 (HHV-6) and human herpesvirus type 7 (HHV-7) infection associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). From 255 patients (192 cases) with reactivated HHV-6 and HHV-7 infections (confirmed based on blood leukocyte PCR), valaciclovir, valganciclovir, or artesunate was administered at a dose of 3000, 900, and 100 mg/day, respectively, for 3 months (study group). The control group consisted of similar patients with ME/CFS (n = 63) not taking any antiviral drugs. The significance of differences was evaluated by Student's t-test and the nonparametric criterion-the number of Z-signs. Negative PCR results in patients with HHV-6 and HHV-7 treated with valaciclovir was achieved in 26% and 23% (first month), 34%, and 28% (second month), 37% and 34% of cases (third month), respectively (P < 0.05; Z < Z0.05 ). The same results with valganciclovir were obtained in 35% and 33% (first month), 44% and 39% (second month), 48% and 45% of cases (third month), but with artesunate in 44% and 41% (first month), 57% and 53% (second month), 68% and 63% of cases (third month), respectively (P < 0.05; Z < Z0.05 ). Artesunate is more effective than valganciclovir and valacyclovir in patients with ME/CFS with reactivated HHV-6 and HHV-7 infections.


Assuntos
Síndrome de Fadiga Crônica , Herpesvirus Humano 6 , Herpesvirus Humano 7 , Artesunato , Humanos , Valaciclovir/uso terapêutico , Valganciclovir/uso terapêutico
12.
Histochem Cell Biol ; 157(2): 239-250, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34757474

RESUMO

Detection of synthetic thymidine analogues after their incorporation into replicating DNA during the S-phase of the cell cycle is a widely exploited methodology for evaluating proliferative activity, tracing dividing and post-mitotic cells, and determining cell-cycle parameters both in vitro and in vivo. To produce valid quantitative readouts for in vivo experiments with single intraperitoneal delivery of a particular nucleotide, it is necessary to determine the time interval during which a synthetic thymidine analogue can be incorporated into newly synthesized DNA, and the time by which the nucleotide is cleared from the blood serum. To date, using a variety of methods, only the bioavailability time of tritiated thymidine and 5-bromo-2'-deoxyuridine (BrdU) have been evaluated. Recent advances in double- and triple-S-phase labeling using 5-iodo-2'-deoxyuridine (IdU), 5-chloro-2'-deoxyuridine (CldU), and 5-ethynyl-2'-deoxyuridine (EdU) have raised the question of the bioavailability time of these modified nucleotides. Here, we examined their labeling kinetics in vivo and evaluated label clearance from blood serum after single intraperitoneal delivery to mice at doses equimolar to the saturation dose of BrdU (150 mg/kg). We found that under these conditions, all the examined thymidine analogues exhibit similar labeling kinetics and clearance rates from the blood serum. Our results indicate that all thymidine analogues delivered at the indicated doses have similar bioavailability times (approximately 1 h). Our findings are significant for the practical use of multiple S-phase labeling with any combinations of BrdU, IdU, CldU, and EdU and for obtaining valid labeling readouts.


Assuntos
Bromodesoxiuridina/metabolismo , Desoxiuridina/análogos & derivados , Glibureto/análogos & derivados , Timidina/metabolismo , Animais , Disponibilidade Biológica , Bromodesoxiuridina/administração & dosagem , Bromodesoxiuridina/sangue , Giro Denteado/metabolismo , Desoxiuridina/administração & dosagem , Desoxiuridina/sangue , Desoxiuridina/metabolismo , Glibureto/administração & dosagem , Glibureto/sangue , Glibureto/metabolismo , Injeções Intraperitoneais , Cinética , Camundongos , Camundongos Endogâmicos C57BL , Timidina/administração & dosagem , Timidina/análogos & derivados
13.
ChemSusChem ; 15(2): e202102136, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-34862754

RESUMO

Development of efficient carbon capture-and-release technologies with minimal energy input is a long-term challenge in mitigating CO2 emissions, especially via CO2 chemisorption driven by engineered chemical bond construction. Herein, taking advantage of the structural diversity of ionic liquids (ILs) in tuning their physical and chemical properties, precise reaction energy regulation of CO2 chemisorption was demonstrated deploying metal-ion-amino-based ionic liquids (MAILs) as absorbents. The coordination ability of different metal sites (Cu, Zn, Co, Ni, and Mg) to amines was harnessed to achieve fine-tuning on stability constants of the metal ion-amine complexes, acting as the corresponding cations in the construction of diverse ILs coupled with CO2 -philic anions. The as-afforded MAILs exhibited efficient and controllable CO2 release behavior with great reduction in energy input and minimal sacrifice on CO2 uptake capacity. This coordination-regulated approach offers new prospects for the development of ILs-based systems and beyond towards energy-efficient carbon capture technologies.


Assuntos
Líquidos Iônicos , Aminas , Ânions , Carbono , Dióxido de Carbono
14.
J Biol Chem ; 297(5): 101345, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34717955

RESUMO

Detection of thymidine analogues after their incorporation into replicating DNA represents a powerful tool for the study of cellular DNA synthesis, progression through the cell cycle, cell proliferation kinetics, chronology of cell division, and cell fate determination. Recent advances in the concurrent detection of multiple such analogues offer new avenues for the investigation of unknown features of these vital cellular processes. Combined with quantitative analysis, temporal discrimination of multiple labels enables elucidation of various aspects of stem cell life cycle in situ, such as division modes, differentiation, maintenance, and elimination. Data obtained from such experiments are critically important for creating descriptive models of tissue histogenesis and renewal in embryonic development and adult life. Despite the wide use of thymidine analogues in stem cell research, there are a number of caveats to consider for obtaining valid and reliable labeling results when marking replicating DNA with nucleotide analogues. Therefore, in this review, we describe critical points regarding dosage, delivery, and detection of nucleotide analogues in the context of single and multiple labeling, outline labeling schemes based on pulse-chase, cumulative and multilabel marking of replicating DNA for revealing stem cell proliferative behaviors, and determining cell cycle parameters, and discuss preconditions and pitfalls in conducting such experiments. The information presented in our review is important for rational design of experiments on tracking dividing stem cells by marking replicating DNA with thymidine analogues.


Assuntos
Ciclo Celular , Autorrenovação Celular , Rastreamento de Células , Replicação do DNA , Células-Tronco , Timidina , Animais , Humanos , Células-Tronco/citologia , Células-Tronco/metabolismo , Timidina/análogos & derivados , Timidina/química , Timidina/farmacologia
15.
Angew Chem Int Ed Engl ; 60(49): 25688-25694, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34582075

RESUMO

Perfluorinated covalent triazine frameworks (F-CTFs) have shown unique features and attractive performance in separation and catalysis. However, state-of-the-art F-CTFs synthesized via the ZnCl2 -promoted procedure have quite low fluorine contents due to C-F bond cleavage induced by chloride (a Lewis base) and the harsh conditions deployed (400-700 °C). Fabricating F-CTFs with high fluorine contents (>30 wt %) remains challenging. Herein, we present a low-temperature ionothermal approach (275 °C) to prepare F-CTFs, which is achieved via polymerization of tetrafluoroterephthalonitrile (TFPN) over the Lewis superacids, e.g., zinc triflimide [Zn(NTf2 )2 ] without side reactions. With low catalyst loading (equimolar), F-CTFs are afforded with high fluorine content (31 wt %), surface area up to 367 m2 g-1 , and micropores around 1.1 nm. The highly hydrophobic F-CTF-1 exhibits good capability to boost electroreduction of CO2 to CO, with faradaic efficiency of 95.7 % at -0.8 V and high current density (-141 mA cm-2 ) surpassing most of the metal-free electrocatalysts.

16.
Chem Sci ; 12(23): 8026-8035, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34194692

RESUMO

Enhancing the solar energy storage and power delivery afforded by emerging molten salt-based technologies requires a fundamental understanding of the complex interplay between structure and dynamics of the ions in the high-temperature media. Here we report results from a comprehensive study integrating synchrotron X-ray scattering experiments, ab initio molecular dynamics simulations and rate theory concepts to investigate the behavior of dilute Cr3+ metal ions in a molten KCl-MgCl2 salt. Our analysis of experimental results assisted by a hybrid transition state-Marcus theory model reveals unexpected clustering of chromium species leading to the formation of persistent octahedral Cr-Cr dimers in the high-temperature low Cr3+ concentration melt. Furthermore, our integrated approach shows that dynamical processes in the molten salt system are primarily governed by the charge density of the constituent ions, with Cr3+ exhibiting the slowest short-time dynamics. These findings challenge several assumptions regarding specific ionic interactions and transport in molten salts, where aggregation of dilute species is not statistically expected, particularly at high temperature.

17.
Nat Commun ; 12(1): 3441, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108466

RESUMO

Three-dimensional bicontinuous porous materials formed by dealloying contribute significantly to various applications including catalysis, sensor development and energy storage. This work studies a method of molten salt dealloying via real-time in situ synchrotron three-dimensional X-ray nano-tomography. Quantification of morphological parameters determined that long-range diffusion is the rate-determining step for the dealloying process. The subsequent coarsening rate was primarily surface diffusion controlled, with Rayleigh instability leading to ligament pinch-off and creating isolated bubbles in ligaments, while bulk diffusion leads to a slight densification. Chemical environments characterized by X-ray absorption near edge structure spectroscopic imaging show that molten salt dealloying prevents surface oxidation of the metal. In this work, gaining a fundamental mechanistic understanding of the molten salt dealloying process in forming porous structures provides a nontoxic, tunable dealloying technique and has important implications for molten salt corrosion processes, which is one of the major challenges in molten salt reactors and concentrated solar power plants.

18.
J Phys Chem B ; 125(22): 5971-5982, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34037400

RESUMO

In this work, we resolve a long-standing issue concerning the local structure of molten MgCl2 by employing a multimodal approach, including X-ray scattering and Raman spectroscopy, along with the theoretical modeling of the experimental spectra based on ab initio molecular dynamics (AIMD) simulations utilizing several density functional theory (DFT) methods. We demonstrate the reliability of AIMD simulations in achieving excellent agreement between the experimental and simulated spectra for MgCl2 and 50 mol % MgCl2 + 50 mol % KCl, and ZnCl2, thus allowing structural insights not directly available from experiment alone. A thorough computational analysis using five DFT methods provides a convergent view that octahedrally coordinated magnesium in pure MgCl2 upon melting preferentially coordinates with five chloride anions to form distorted square pyramidal polyhedra that are connected via corners and to a lesser degree via edges. This is contrasted with the results for ZnCl2, which does not change its tetrahedral coordination on melting. Although the five-coordinate MgCl53- complex was not considered in the early literature, together with an increasing tendency to form a tetrahedrally coordinated complex with decreasing the MgCl2 content in the mixture with alkali metal chloride systems, current work reconciles the results of most previous seemingly contradictory experimental studies.

19.
Glycobiology ; 31(8): 959-974, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-33978736

RESUMO

Elevated plasma levels of hyaluronic acid (HA) is a disease marker in liver pathology and other inflammatory disorders. Inhibition of HA synthesis with coumarin 4-methylumbelliferone (4MU) has a beneficial effect in animal models of fibrosis, inflammation, cancer and metabolic syndrome. 4MU is an active compound of approved choleretic drug hymecromone with low bioavailability and a broad spectrum of action. New, more specific and efficient inhibitors of hyaluronan synthases (HAS) are required. We have tested several newly synthesized coumarin compounds and commercial chitin synthesis inhibitors to inhibit HA production in cell culture assay. Coumarin derivative compound VII (10'-methyl-6'-phenyl-3'H-spiro[piperidine-4,2'-pyrano[3,2-g]chromene]-4',8'-dione) demonstrated inhibition of HA secretion by NIH3T3 cells with the half-maximal inhibitory concentration (IC50) = 1.69 ± 0.75 µΜ superior to 4MU (IC50 = 8.68 ± 1.6 µΜ). Inhibitors of chitin synthesis, etoxazole, buprofezin, triflumuron, reduced HA deposition with IC50 of 4.21 ± 3.82 µΜ, 1.24 ± 0.87 µΜ and 1.48 ± 1.44 µΜ, respectively. Etoxazole reduced HA production and prevented collagen fibre formation in the CCl4 liver fibrosis model in mice similar to 4MU. Bioinformatics analysis revealed homology between chitin synthases and HAS enzymes, particularly in the pore-forming domain, containing the proposed site for etoxazole binding.


Assuntos
Ácido Hialurônico , Himecromona , Animais , Quitina , Hialuronan Sintases/metabolismo , Ácido Hialurônico/metabolismo , Himecromona/farmacologia , Camundongos , Células NIH 3T3
20.
Int J Mol Sci ; 21(21)2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33142884

RESUMO

Redox reactions are of high fundamental and practical interest since they are involved in both normal physiology and the pathogenesis of various diseases. However, this area of research has always been a relatively problematic field in the context of analytical approaches, mostly because of the unstable nature of the compounds that are measured. Genetically encoded sensors allow for the registration of highly reactive molecules in real-time mode and, therefore, they began a new era in redox biology. Their strongest points manifest most brightly in in vivo experiments and pave the way for the non-invasive investigation of biochemical pathways that proceed in organisms from different systematic groups. In the first part of the review, we briefly describe the redox sensors that were used in vivo as well as summarize the model systems to which they were applied. Next, we thoroughly discuss the biological results obtained in these studies in regard to animals, plants, as well as unicellular eukaryotes and prokaryotes. We hope that this work reflects the amazing power of this technology and can serve as a useful guide for biologists and chemists who work in the field of redox processes.


Assuntos
Técnicas Biossensoriais/métodos , Proteínas Luminescentes/genética , Imagem Molecular/métodos , Animais , Glutationa/metabolismo , Humanos , Proteínas Luminescentes/metabolismo , Oxirredução , Espécies Reativas de Oxigênio/metabolismo
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