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101.
采用渗硼烧结法合成了一种新型TiBN粉体材料,它兼有陶瓷性和金属性,电阻率为2.6×10-3Ω·cm。以TiBN和TiN为增强相,采用粉末冶金法制备了Cu/TiBN和Cu/TiN电接触材料,系统的研究了不同含量TiBN和TiN的电接触材料的微观结构和物理性能。结果表明,与TiN相比,TiBN增强相能明显改善Cu基电接触材料的导电性能、抗氧化性能、硬度和抗电弧侵蚀性能。当含量为5wt.%时,Cu/TiBN电接触材料的抗电弧侵蚀能力最好,重量损失仅为1.5mg。电弧侵蚀时,在Cu/TiBN表面生成TixOy、B2O3和N2等产物,这些产物能明显改善Cu/TiBN电接触材料的抗电弧侵蚀能力。新开发的Cu/TiBN电接触材料具有优异的物理性能和抗电弧侵蚀性能,在电接触行业中拥有广阔的应用前景。 相似文献
102.
Ekaterina M. Dvorianinova Nadezhda L. Bolsheva Elena N. Pushkova Tatiana A. Rozhmina Alexander A. Zhuchenko Roman O. Novakovskiy Liubov V. Povkhova Elizaveta A. Sigova Daiana A. Zhernova Elena V. Borkhert Dmitry N. Kaluzhny Nataliya V. Melnikova Alexey A. Dmitriev 《International journal of molecular sciences》2022,23(21)
High-quality genome sequences help to elucidate the genetic basis of numerous biological processes and track species evolution. For flax (Linum usitatissimum L.)—a multifunctional crop, high-quality assemblies from Oxford Nanopore Technologies (ONT) data were unavailable, largely due to the difficulty of isolating pure high-molecular-weight DNA. This article proposes a scheme for gaining a contiguous L. usitatissimum assembly using Nanopore data. We developed a protocol for flax nuclei isolation with subsequent DNA extraction, which allows obtaining about 5 μg of pure high-molecular-weight DNA from 0.5 g of leaves. Such an amount of material can be collected even from a single plant and yields more than 30 Gb of ONT data in two MinION runs. We performed a comparative analysis of different genome assemblers and polishers on the gained data and obtained the final 447.1-Mb assembly of L. usitatissimum line 3896 genome using the Canu—Racon (two iterations)—Medaka combination. The genome comprised 1695 contigs and had an N50 of 6.2 Mb and a completeness of 93.8% of BUSCOs from eudicots_odb10. Our study highlights the impact of the chosen genome construction strategy on the resulting assembly parameters and its eligibility for future genomic studies. 相似文献
103.
Sergey O. Bachurin Elena F. Shevtsova Galina F. Makhaeva Alexey Yu. Aksinenko Vladimir V. Grigoriev Tatiana V. Goreva Tatiana A. Epishina Nadezhda V. Kovaleva Natalia P. Boltneva Sofya V. Lushchekina Elena V. Rudakova Darya V. Vinogradova Pavel N. Shevtsov Elena A. Pushkareva Ludmila G. Dubova Tatiana P. Serkova Ivan M. Veselov Vladimir P. Fisenko Rudy J. Richardson 《International journal of molecular sciences》2022,23(22)
The development of multi-target-directed ligands (MTDLs) would provide effective therapy of neurodegenerative diseases (ND) with complex and nonclear pathogenesis. A promising method to create such potential drugs is combining neuroactive pharmacophoric groups acting on different biotargets involved in the pathogenesis of ND. We developed a synthetic algorithm for the conjugation of indole derivatives and methylene blue (MB), which are pharmacophoric ligands that act on the key stages of pathogenesis. We synthesized hybrid structures and performed a comprehensive screening for a specific set of biotargets participating in the pathogenesis of ND (i.e., cholinesterases, NMDA receptor, mitochondria, and microtubules assembly). The results of the screening study enabled us to find two lead compounds (4h and 4i) which effectively inhibited cholinesterases and bound to the AChE PAS, possessed antioxidant activity, and stimulated the assembly of microtubules. One of them (4i) exhibited activity as a ligand for the ifenprodil-specific site of the NMDA receptor. In addition, this lead compound was able to bypass the inhibition of complex I and prevent calcium-induced mitochondrial depolarization, suggesting a neuroprotective property that was confirmed using a cellular calcium overload model of neurodegeneration. Thus, these new MB-cycloalkaneindole conjugates constitute a promising class of compounds for the development of multitarget neuroprotective drugs which simultaneously act on several targets, thereby providing cognitive stimulating, neuroprotective, and disease-modifying effects. 相似文献
104.
Leonel Pekarek Basilio De la Torre-Escuredo Oscar Fraile-Martinez Cielo García-Montero Miguel A. Saez David Cobo-Prieto Luis G. Guijarro Jose V. Saz Patricia De Castro-Martinez Diego Torres-Carranza Tatiana Pekarek Ana Clara Carrera Melchor Alvarez-Mon Miguel A. Ortega 《International journal of molecular sciences》2022,23(23)
Osteosarcoma represents a rare cause of cancer in the general population, accounting for <1% of malignant neoplasms globally. Nonetheless, it represents the main cause of malignant bone neoplasm in children, adolescents and young adults under 20 years of age. It also presents another peak of incidence in people over 50 years of age and is associated with rheumatic diseases. Numerous environmental risk factors, such as bone diseases, genetics and a history of previous neoplasms, have been widely described in the literature, which allows monitoring a certain group of patients. Diagnosis requires numerous imaging tests that make it possible to stratify both the local involvement of the disease and its distant spread, which ominously determines the prognosis. Thanks to various clinical trials, the usefulness of different chemotherapy regimens, radiotherapy and surgical techniques with radical intent has now been demonstrated; these represent improvements in both prognosis and therapeutic approaches. Osteosarcoma patients should be evaluated in reference centres by multidisciplinary committees with extensive experience in proper management. Although numerous genetic and rheumatological diseases and risk factors have been described, the use of serological, genetic or other biomarkers has been limited in clinical practice compared to other neoplasms. This limits both the initial follow-up of these patients and screening in populations at risk. In addition, we cannot forget that the diagnosis is mainly based on the direct biopsy of the lesion and imaging tests, which illustrates the need to study new diagnostic alternatives. Therefore, the purpose of this study is to review the natural history of the disease and describe the main biomarkers, explaining their clinical uses, prognosis and limitations. 相似文献
105.
Luping Pang Stijn Lenders Evgenii M. Osipov Stephen D. Weeks Jef Rozenski Tatiana Piller Davie Cappoen Sergei V. Strelkov Arthur Van Aerschot 《International journal of molecular sciences》2022,23(23)
Mycothiol (MSH), the major cellular thiol in Mycobacterium tuberculosis (Mtb), plays an essential role in the resistance of Mtb to various antibiotics and oxidative stresses. MshC catalyzes the ATP-dependent ligation of 1-O-(2-amino-2-deoxy-α-d-glucopyranosyl)-d-myo-inositol (GlcN-Ins) with l-cysteine (l-Cys) to form l-Cys-GlcN-Ins, the penultimate step in MSH biosynthesis. The inhibition of MshC is lethal to Mtb. In the present study, five new cysteinyl-sulfonamides were synthesized, and their binding affinity with MshC was evaluated using a thermal shift assay. Two of them bind the target with EC50 values of 219 and 231 µM. Crystal structures of full-length MshC in complex with these two compounds showed that they were bound in the catalytic site of MshC, inducing dramatic conformational changes of the catalytic site compared to the apo form. In particular, the observed closure of the KMSKS loop was not detected in the published cysteinyl-sulfamoyl adenosine-bound structure, the latter likely due to trypsin treatment. Despite the confirmed binding to MshC, the compounds did not suppress Mtb culture growth, which might be explained by the lack of adequate cellular uptake. Taken together, these novel cysteinyl-sulfonamide MshC inhibitors and newly reported full-length apo and ligand-bound MshC structures provide a promising starting point for the further development of novel anti-tubercular drugs targeting MshC. 相似文献
106.
Kristina A. Sharlo Irina D. Lvova Svetlana P. Belova Ksenia A. Zaripova Boris S. Shenkman Tatiana L. Nemirovskaya 《International journal of molecular sciences》2023,24(1)
Muscle unloading leads to signaling alterations that cause muscle atrophy and weakness. The cellular energy sensor AMPK can regulate myofiber-type shift, calcium-dependent signaling and ubiquitin-proteasome system markers. We hypothesized that the prevention of p-AMPK downregulation during the first week of muscle unloading would impede atrophy development and the slow-to-fast shift of soleus muscle fibers, and the aim of the study was to test this hypothesis. Thirty-two male Wistar rats were randomly assigned to four groups: placebo control (C), control rats treated with metformin (C + M), 7 days of hindlimb suspension (HS) + placebo (7HS), and 7 days of HS + metformin administration (7HS + M). In the soleus of the 7HS rats, we detected a slow-to-fast fiber-type shift as well as a significant downregulation of MEF-2D and p300 in the nuclei. In the 7HS group, we also found decreases in p-ACC (AMPK target) protein level and in the expression of E3 ubiquitin ligases and p-CaMK II protein level vs. the C group. The 7-day metformin treatment for soleus muscle unloading (1) prevented slow-to-fast fiber-type shift; (2) counteracted changes in the p-ACC protein level; (3) hindered changes in the nuclear protein level of the slow myosin expression activators MEF-2D and p300, but did not affect NFATc1 signaling; and (4) attenuated the unloading-induced upregulation of MuRF-1, atrogin-1, ubiquitin and myostatin mRNA expression, but did not prevent soleus muscle atrophy. Thus, metformin treatment during muscle disuse could be useful to prevent the decrease in the percentage of slow-type fatigue-resistant muscle fibers. 相似文献
107.
Maria S. Gavrish Mark D. Urazov Tatiana A. Mishchenko Victoria D. Turubanova Ekaterina A. Epifanova Victoria G. Krut Alexey A. Babaev Maria V. Vedunova Elena V. Mitroshina 《International journal of molecular sciences》2022,23(17)
Currently, the role of the neurotrophic factors BDNF and GDNF in maintaining the brain’s resistance to the damaging effects of hypoxia and functional recovery of neural networks after exposure to damaging factors are actively studied. The assessment of the effect of an increase in the level of these neurotrophic factors in brain tissues using genetic engineering methods on the resistance of laboratory animals to hypoxia may pave the way for the future clinical use of neurotrophic factors BDNF and GDNF in the treatment of hypoxic damage. This study aimed to evaluate the antihypoxic and neuroprotective properties of BDNF and GDNF expression level increase using adeno-associated viral vectors in modeling hypoxia in vivo. To achieve overexpression of neurotrophic factors in the central nervous system’s cells, viral constructs were injected into the brain ventricles of newborn male C57Bl6 (P0) mice. Acute hypobaric hypoxia was modeled on the 30th day after the injection of viral vectors. Survival, cognitive, and mnestic functions in the late post-hypoxic period were tested. Evaluation of growth and weight characteristics and the neurological status of animals showed that the overexpression of neurotrophic factors does not affect the development of mice. It was found that the use of adeno-associated viral vectors increased the survival rate of male mice under hypoxic conditions. The present study indicates that the neurotrophic factors’ overexpression, induced by the specially developed viral constructs carrying the BDNF and GDNF genes, is a prospective neuroprotection method, increasing the survival rate of animals after hypoxic injury. 相似文献
108.
Marek Skrzypski Pawe A. Koodziejski Ewa Pruszyska-Oszmaek Tatiana Wojciechowicz Paulina Janicka Magorzata Krek Emilian Maek Mathias Z. Strowski Krzysztof W. Nowak 《International journal of molecular sciences》2022,23(17)
Adropin is a peptide hormone encoded by Energy Homeostasis Associated gene. Adropin modulates energy homeostasis and metabolism of lipids and carbohydrates. There is growing evidence demonstrating that adropin enhances insulin sensitivity and lowers hyperlipidemia in obese mice. The aim of this study was to investigate the effects of daily administration of adropin for four weeks in mice with experimentally induced type 2 diabetes (T2D). Adropin improved glucose control without modulating insulin sensitivity. Adropin reduced body weight, size of adipocytes, blood levels of triacylglycerol and cholesterol in T2D mice. T2D mice treated with adropin had lower liver mass, reduced hepatic content of triacylglycerol and cholesterol. Furthermore, adropin attenuated elevated blood levels of hepatic enzymes (ALT, AST, GGT and ALP) in T2D mice. In T2D mice, adropin increased the circulating adiponectin level. Adropin had no effects on circulating insulin and glucagon levels and did not alter pancreatic islets morphology. These results suggest that adropin improves glucose control, lipid metabolism and liver functions in T2D. In conjunction with reduced lipid content in hepatocytes, these results render adropin as an interesting candidate in therapy of T2D. 相似文献
109.
Olga Shchagina Valeriy Fedotov Tatiana Markova Olga Shatokhina Oksana Ryzhkova Tatiana Fedotova Aleksander Polyakov 《International journal of molecular sciences》2022,23(17)
Palmoplantar keratoderma is a clinically polymorphic disorder with a heterogeneous etiology characterized by marked hyperkeratotic lesions on the surface of palms and soles. Hereditary forms of palmoplantar keratoderma usually have autosomal dominant inheritance and are caused by mutations in dozens of genes, most of which belong to the keratin family. We carried out clinical and molecular genetic analysis of the affected and healthy members of four families with autosomal dominant palmoplantar keratoderma. In three out of four family cases of autosomal dominant palmoplantar keratoderma, the following molecular genetic causes were established: in two families—previously non-described missense mutations in the AQP5 gene (): c.369C>G (p.(Asn123Lys)) and c.103T>G (p.(Trp35Gly)); in one family—a described splice site mutation in the KRT9 gene ( NM_001651.4): c.31T>G. In one family, the possible cause of palmoplantar keratoderma was detected—a variant in the KRT1 gene ( NM_000226.4): c.931G>A (p.(Glu311Lys)). NM_006121.4相似文献
110.
Vladimir Burmistrov Christophe Morisseau Denis A. Babkov Tatiana Golubeva Dmitry Pitushkin Elena V. Sokolova Vladimir Vasipov Yaroslav Kuznetsov Sergey V. Bazhenov Uliana S. Novoyatlova Nikolay A. Bondarev Ilya V. Manukhov Victoria Osipova Nadezhda Berberova Alexander A. Spasov Gennady M. Butov Bruce D. Hammock 《International journal of molecular sciences》2022,23(18)
The inhibitory potency of the series of inhibitors of the soluble epoxide hydrolase (sEH) based on the selenourea moiety and containing adamantane and aromatic lipophilic groups ranges from 34.3 nM to 1.2 μM. The most active compound 5d possesses aliphatic spacers between the selenourea group and lipophilic fragments. Synthesized compounds were tested against the LPS-induced activation of primary murine macrophages. The most prominent anti-inflammatory activity, defined as a suppression of nitric oxide synthesis by LPS-stimulated macrophages, was demonstrated for compounds 4a and 5b. The cytotoxicity of the obtained substances was studied using human neuroblastoma and fibroblast cell cultures. Using these cell assays, the cytotoxic concentration for 4a was 4.7–18.4 times higher than the effective anti-inflammatory concentration. The genotoxicity and the ability to induce oxidative stress was studied using bacterial lux-biosensors. Substance 4a does not exhibit genotoxic properties, but it can cause oxidative stress at concentrations above 50 µM. Put together, the data showed the efficacy and safety of compound 4a. 相似文献