A novel targeted co-delivery nanosystem for enhanced ovarian cancer treatment via multidrug resistance reversion and mTOR-mediated signaling pathway

Background Multidrug resistance (MDR) is the main challenge of successful chemotherapy for ovarian cancer patients, with 50% to 75% of ovarian cancer patients eventually relapsed due to it. One of the effective strategies for treating MDR and improving therapeutic efficiency of ovarian cancer is to use nanotechnology-based targeted drug delivery systems. In this study, a novel nano targeted co-delivery system modified by hyaluronic acid (HA) was developed by using gold nanorods coated with functionalized mesoporous silica nanoparticles (HA-PTX/let-7a-GNR@MSN) for combined delivery of hydrophobic chemotherapy drug Paclitaxel (PTX) and lethal-7a (let-7a), a microRNA (miR), to overcome MDR in ovarian cancer. Furthermore, we also analyzed the molecular mechanism of this nanotherapeutic system in the treatment of ovarian cancer. Results HA-modified nanocomplexes can specifically bind to the CD44 receptor, which is highly expressed in SKOV3/SKOV3TR cells, achieving effective cell uptake and 150% enhancement of tumor site permeability. The nanosystem realized the stable combination and protective transportation of PTX and miRs. Analysis of drug-resistant SKOV3TR cells and an SKOV3TR xenograft model in BALB/c-nude mice showed significant downregulation of P-glycoprotein in heterogeneous tumor sites, PTX release, and subsequent induction of apoptosis. More importantly, this nanosystem could synergistically inhibit the growth of ovarian tumors. Further studies suggest that mTOR-mediated signaling pathways play an important role in reversing drug resistance and inducing apoptosis. Conclusions To sum up, these data provide a model for overcoming PTX resistance in ovarian cancer. Graphical Abstract

Variant-synonymous varieties of generally used phrases in the works of M. Rudenko (lexical, morphological and phonetic)

The article analyzes the variant-synonymous varieties of commonly used phrases used by M. Rudenko in his works, determines their functional load in the structure of the literary text. The subject of consideration are modified units that form variant or synonymous pairs with codified forms. In prose works, the author often uses variants of commonly used codified phraseological units or their synonyms. In the scientific literature, unfortunately, there are no clear criteria for distinguishing between variants and synonyms of phrases. Therefore, following V. Uzhchenko, we use the terms variant-synonymous pair (pair of phrases that are in synonymous relations or are considered as variants) or variant-synonymous type of phraseological unit (a type of commonly used expression that is its variant or synonym). The emergence of these units of the phraseological system is mainly due to the substitution of one structural component of the expression to another. Most often in a stable combination of words the verb is replaced (there are 19 such phrases), less often the noun (15 units). Adjectives or verbs, pronouns can also be replaced. Rudenko skillfully uses also known methods of creative comprehension of phraseology in the fabric of a work of art. First of all, he resorted to expanding the component composition of a stable combination of words, so that the newly introduced author’s words complicate the traditional formula of phraseology, while enhancing their expressiveness. By actualizing the statement, the author reduces the component composition of the phrase, because a short version of the phraseology involves knowledge of a more complete form and thus intrigues the reader. The general meaning of the whole image of the phrase is often conveyed by the author descriptively, which creates a new expression. Rudenko rarely introduces formal variants, but in artistic texts we find morphological and phonetic variants of commonly used phrases.

Genomic Characterization of Escherichia coli Isolates Belonging to a New Hybrid aEPEC/ExPEC Pathotype O153:H10-A-ST10 eae-beta1 Occurred in Meat, Poultry, Wildlife and Human Diarrheagenic Samples

Different surveillance studies (2005–2015) in northwest Spain revealed the presence of eae-positive isolates of Escherichia coli O153:H10 in meat for human consumption, poultry farm, wildlife and human diarrheagenic samples. The aim of this study was to explore the genetic and genomic relatedness between human and animal/meat isolates, as well as the mechanism of its persistence. We also wanted to know whether it was a geographically restricted lineage, or whether it was also reported elsewhere. Conventional typing showed that 32 isolates were O153:H10-A-ST10 fimH54, fimAvMT78, traT and eae-beta1. Amongst these, 21 were CTX-M-32 or SHV-12 producers. The PFGE XbaI-macrorestriction comparison showed high similarity (>85%). The plasmidome analysis revealed a stable combination of IncF (F2:A-:B-), IncI1 (STunknown) and IncX1 plasmid types, together with non-conjugative Col-like plasmids. The core genome investigation based on the cgMLST scheme from EnteroBase proved close relatedness between isolates of human and animal origin. Our results demonstrate that a hybrid MDR aEPEC/ExPEC of the clonal group O153:H10-A-ST10 (CH11-54) is circulating in our region within different hosts, including wildlife. It seems implicated in human diarrhea via meat transmission, and in the spreading of ESBL genes (mainly of CTX-M-32 type). We found genomic evidence of a related hybrid aEPEC/ExPEC in at least one other country.

Genomic Characterization of ESBL-producing Escherichia coli Isolates Belonging to a Hybrid aEPEC/ExPEC Pathotype O153:H10-A-ST10 eae-beta1 Occurred in Human Diarrheagenic Isolates, Meat, Poultry and Wildlife

Different surveillance studies (2005-2015) on the presence of ESBL-producing E. coli in the northwest Spain revealed that eae-positive isolates of serotype O153:H10 were periodically detected in meat (of beef, chicken and pork), and also implicated in human diarrhea. This study aimed: i) to characterize the degree of relatedness between human and animal isolates; ii) to know if this was a geographically restricted or disseminated genetic lineage. Thirty-two isolates were conventionally typified as O153:H10-A-ST10 fimH54, fimAvMT78, traT and eae-beta1, being 21 of those CTX-M-32 or SHV-12 producers. PFGE comparison of their macrorestriction profiles showed high similarity (>85%). The plasmidome analysis revealed a stable combination of IncF (F2:A-:B-), IncI1 (STunknown) and IncX1 plasmid types, together with non-conjugative Col-like. Besides, the core genome investigation based on the cgMLST scheme from Enterobase, proved close relatedness between isolates of human and animal origin. Our results demonstrate that a hybrid MDR aEPEC/ExPEC of clonal group O153:H10-A-ST10 (CH11-54) would be playing a successful role in spreading ESBLs (CTX-M-32) in our region within different hosts, including wildlife. It would be potentially implicated in human diarrhea via food (meat) transmission. Importantly, we proved genomic evidence of a related hybrid aEPEC/ExPEC in other countries.

Phrasemics of Mykola Rudenko’s poetic works

The article presents a general description of the phrasemicon of M. Rudenko, used in the poetry of the artist, clarifies its function and pragmatic intentions of the author. The subject of consideration were the poetic works of the artist, placed in the collection of Mykola Rudenko „Poetry” (Kyiv, 1991). The research introduces a descriptive method of studying linguistic phenomena with its procedures of semantic-stylistic and contextual-interpretive analysis. Phrases used in the poetic works of M. Rudenko complement and clarify the metaphorically expressed idea. It is no coincidence that the leading role in the poetic texts of the artist belongs to the figurative and expressive phraseology, which often includes metaphorical units. In his poems, the writer opens up greater opportunities for the realization of his creative ideas. Therefore, in addition to these stable combinations of words, the author uses constant comparisons, euphemisms, hyperboles. The thematic grouping of poetic works allows us to identify stable combinations of words used by the master of the word to depict the image of the author, his opponent. Therefore, we can talk about the phraseological portrait of the Ukrainian people in the poetry of M. Rudenko, his native land, as well as the lyrical hero and his opponent. With the help of phrases the poet figuratively reproduces the attitude of different groups of the population to the language, determines the place of the native language in the life of the Ukrainian people. Using various ways of stylistic use and contextual transformation of phraseological units (creation of semantic oppositions, use of antonymous opposition, semantic renewal), the poet often modifies them in order to give the expression a certain connotation, strengthen the expressiveness of the phrase, update its semantic nuances. This is served by the methods of expanding the component composition of a stable combination of words, permutation of components, introduction of a phrase into a new context, lexical replacement of one component by another. Using the image, which became the basis of common phraseology, the author often forms a stable combination of words.

Stable word combinations сomprehensive dictionary as a source base for translation lexicographical works

In Russian, Ukrainian, and Polish lexicographical work, all the preconditions for organizing a comprehensive stable word combinations dictionary have been formed. The these works registers in each Slavic linguistic school will have to be formed by various units of different types, which are characterized by the semantic integrity. First of all, it is planned to include word equivalents, phraseological units, terminological combinations, proverbs, sayings. The formed dictionaries will reflect the language processes dynamics because a significant part of their register units have a transitional status of existence, as a result of which this work will be useful for theoretical linguistics. However, first of all, the need of compiling this dictionary is caused by practical activities. In Russian, Ukrainian, and Polish basic monolingual dictionaries stable word combinations are presented quite fully, but the approaches to their organization are mostly understandable only to specialists. Users of these works have significant difficulties in finding any stable combination. This activity is somewhat facilitated by specialized dictionaries of various units, but even in this case, the user requires some linguistic training. Being organized according to a certain concept, a stable combinations comprehensive dictionary will greatly facilitate the user's search, especially translation activities, which are greatly complicated by the lack of dictionary registers for differently formed units. This is true for the translation from one Slavic language to another, as well as similar actions in the field of Slavic-Germanic and, of course, Slavic-Romance languages etc. In the proposed work it is proved that the compiled complex stable word combinations dictionaries in each separate Slavic language will become an important source for improvement of already created paper and on-line translation dictionaries.

On the History of Early Musical Groups: Instrumental Consorts in England at the Turn of the 16th—17th Centuries

Appealing to the stated topic is relevant because of the desire to concretize the knowledge of little-known in Russian musicology instrumental consorts (musical groups), as well as to expand the existing understanding of the court culture of Renaissance England and its musical and sound appearance. The main center of English consorts development was the Royal court of the Tudors — Henry VIII and his daughter Elizabeth I. Their heyday was at the peak of the “Golden Age” of English culture. Based on the results of scienti­fic research by Western scientists and visual and verbal sources available for study, the article outlines the milestones in the history of the main types of instrumental consort in England — the whole consort, consisting of instruments of the same family, and the broken consort, today often identified with the mixed consort, which connects heterogeneous instruments. The article notes that the early history of the recorder consort in England was closely connected with creative activities of the family of Venetian musicians Bassano. Extremely popular in musical circles of England, the consort of viol was originally formed thanks to Flemish and, somewhat later, Italian musicians. As for the mixed consort, which united performers of the viols da gamba and da braccio, lute, bandore, cistre and recorder, it started to be called “English” because of the stable combination of certain musical instruments. Analysis of consort music anthologies of the 16th—17th centuries made it possible to identify individual genre and musical-style reference points in musical groups’ repertoire, in which musicians improved the principles of instrumental polyphony and the stile concertante, topical in the Modern Period.

A Syro-Turkic Poem on Divine Economy Ascribed to Khāmīs

The text being discussed is found in many manuscripts of the Divan (collection of poems) of an East Syriac poet Khāmīs bar Qardāḥē (late 13th century). The edition demonstrates the discrepancies in rendering glosses in the Turkish stanzas, in contrast to a relative unity of readings in the Syriac ones. To explain these discrepancies, the following pages discuss the lack of consistency in the Turkic Garshuni tradition. In addition, the poem is one of the earliest texts of this group. It should be dated to the period close to the life of Khāmīs, but was not necessarily composed by this poet, since it is absent from the earliest surviving copies. All the Syriac stanzas use quatrains in a 7-7-8-8 meter. Each of them has its own internal rhyme that follows a constant scheme, i.e. in every first, second and and fourth lines of each verse (ааха). In the Turkic stanzas, the verses have an irregular meter that varies from eight to ten syllables. In the Turkic translation of the Syriac original, one finds many syriacisms, such as bar Maryam (the Son of Mary), a stable combination used in the texts. Such a broad use of borrowings, both in vocabulary and syntax, is common for translated religious texts, especially liturgical ones, in which the proximity to the original might have a great importance.

Chemoselective reduction of aldehydes via a combination of NaBH4 and acetylacetone

A bench-stable combination of NaBH4–acetylacetone was developed for the efficient chemoselective reduction of aldehydes in the presence of ketones.