It is generally accepted that in comparative constructions, when the clausal element compared is the subject of the matrix clause, the personal pronoun following than can be either nominative which ...is usually used in formal English, where than is considered as a conjunction, or accusative which is usually used in informal English, where than is considered as a preposition. However, the data collected from the COCA corpus indicate that nominative pronouns do not tend to end a comparative construction in either formal or informal English. Based on the fundamentals of Systemic Functional Linguistics, it is improper to consider the accusative form of personal pronouns in comparative constructions as the object of than; rather they are the stressed personal pronouns. It is concluded that in comparative constructions than is always a conjunction, and the personal pronoun following than can be expanded into a finite clause. However, if the nominal group following than has no comparee in the matrix clause, it is not a comparative clause and the than-phrase is a prepositional phrase. It is further concluded that in comparative constructions than is best considered as a paratactic conjunction because comparative constructions cannot be transpositioned with the primary clauses in clause complexes.
•Nominative pronouns do not tend to end a comparative construction.•The accusative forms of personal pronouns following than are the stressed personal pronouns.•In comparative constructions than is a paratactic conjunction.
In our previous study, we found for the first time that temozolomide (TMZ), the first-line chemotherapeutic agent for glioblastoma (GBM), can generate a large amount of reactive oxygen species (ROS) ...under ultrasound irradiation. Sonodynamic therapy (SDT) using TMZ as the sonosensitizer produced more potent antitumor effects than TMZ alone. Here, we further evaluate the effects of TMZ-based SDT on subcellular structures and investigate the immunogenic cell death (ICD)-inducing capability of TMZ-based SDT.
The sonotoxic effects of TMZ were explored in LN229 and GL261 glioma cells. The morphology of endoplasmic reticulum and mitochondria was observed by transmission electron microscopy. The nuclear DNA damage was represented by γ-H2AX staining. Bone marrow-derived dendritic cells (BMDCs) were employed to assess ICD-inducing capability of TMZ-based SDT. A cyclic arginine-glycine-aspartic (c(RGDyC))-modified nanoliposome drug delivery platform was used to improve the tumor targeting of SDT.
TMZ-based SDT had a greater inhibitory effect on glioma cells than TMZ alone. Transmission electron microscopy revealed that TMZ-based SDT caused endoplasmic reticulum dilation and mitochondrial swelling. In addition, endoplasmic reticulum stress response (ERSR), nuclear DNA damage and mitochondrial permeability transition pore (mPTP) opening were promoted in TMZ-based SDT group. Most importantly, we found that TMZ-based SDT could promote the “danger signals” produced by glioma cells and induce the maturation and activation of BMDCs, which was associated with the mitochondrial DNA released into the cytoplasm in glioma cells. In vivo experiments showed that TMZ-based SDT could remodel glioma immune microenvironment and provoke durable and powerful anti-tumor immune responses. What's more, the engineered nanoliposome vector of TMZ conferred SDT tumor targeting, providing an option for safer clinical application of TMZ in combination with SDT in the future.
TMZ-based SDT was capable of triggering ICD in glioma. The discovery of TMZ as a sonosensitizer have shown great promise in the treatment of GBM.
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•Temozolomide (TMZ) can be used as a sonosensitizer for sonodynamic therapy (SDT) in glioma.•TMZ-based SDT disrupted the normal functions of endoplasmic reticulum and mitochondria•TMZ-based SDT was capable of triggering immunogenic cell death (ICD) in glioma.•A c(RGDyC)-modified nanoliposome drug delivery platform improved the tumor targeting of TMZ-based SDT.
Ferroptosis is a new form of regulated cell death caused by the iron-dependent peroxidation of phospholipids and is related to cell metabolism, redox homeostasis and various signalling pathways ...related to cancer. The long noncoding RNA (lncRNA) KB-1460A1.5 acts as a tumour suppressor gene to regulate tumour growth in gliomas, but its molecular network regulatory mechanism is still unclear. In this study, we found that KB-1460A1.5 can induce ferroptosis in glioma and enhance sensitivity to RSL3, a ferroptosis inducer. TMT proteomics and nontargeted metabolomics suggest that KB-1460A1.5 affects polyunsaturated fatty acid metabolic processes. GC‒MS-based medium- and long-chain fatty acid-targeted metabolomics confirmed that upregulation of KB-1460A1.5 decreased the levels of monounsaturated fatty acids (MUFAs), oleic acid (OA) and palmitoleic acid (PO) in glioma cells. The addition of OA and PO restored KB-1460A1.5-induced cellular ferroptosis. Molecularly, KB-1460A1.5 inhibited the mTOR signalling pathway to suppress the expression of downstream sterol regulatory element binding protein 1 (SREBP-1), thereby attenuating the stearoyl-CoA desaturase-1 (SCD1)-mediated desaturation of polyunsaturated fatty acids. Finally, an animal model of subcutaneous glioma confirmed that KB-1460A1.5 could inhibit tumour progression, SREBP1/SCD1 expression, and ferroptosis. In conclusion, increasing the expression level of KB-1460A1.5 in glioma can promote the induction of oxidative stress and ferroptosis in cancer cells through SREBP1/SCD1-mediated adipogenesis, demonstrating therapeutic potential in preclinical models.
Following the criterion of double functionality for identifying grammatical metaphor, this research investigates the diachronic and genre distributions of two of the five types of textual metaphor ...proposed by He et al.: conjunctionalization of conjunctive adverbial groups and prepositionalization of hypotactic conjunction groups. Research based on COHA reveals that: (1) the conjunctionalization of conjunctive adverbial groups agrees with the principle of unidirectional transfer of grammatical metaphor, and during the recent century conjunctive adverbial groups have been experiencing a trend of conjunctionalization; (2) conjunctive prepositions, however, are not directly transferred from hypotactic conjunction groups but are induced by the gerundalization of present participles; and (3) hypotactic conjunction groups will transfer to zero hypotactic conjunction groups, resulting in a new member of textual metaphor. Research based on COCA and BNC shows that both conjunctionalization of conjunctive adverbial groups and prepositionalization of hypotactic conjunction groups tend to occur in informal texts. This confirms the point of view that paratactic clause complexes are favoured in informal genres such as Spoken and Fiction and that simple clauses win out in formal texts due to the wide use of nominalization of verbal groups and verbalization of conjunction groups.
Temozolomide (TMZ) has been determined to be the chemotherapeutic drug with efficacy for glioblastoma (GBM). Thus, potentiating the therapeutic effect of TMZ can undoubtedly yield twice the result ...with half the effort. In this study, we found for the first time that TMZ can produce reactive oxygen species (ROS) under the influence of ultrasound (US). This property allows TMZ-US therapy to have better efficacy in the treatment of GBM. Given that the increasing use of US in central nervous system (CNS) diseases and the importance of TMZ for GBM therapy, our results will facilitate the development of TMZ-associated glioblastoma therapies. Moreover, we found that chemotherapeutic drugs might have the ability to generate ROS under the excitation of US. On a larger scale, our findings may be applicable to a wide range of known drugs.
•TMZ is probably a sonosensitizer that produces ROS under ultrasound irradiation.•TMZ + US showed significant chemotherapeutic sensitivity enhancement and prolonged survival rate compared to TMZ alone.•The combined therapy mainly leads to ROS-mediated necroptosis.
As functional categories, T-TNS and TMOD could both head the structure of an English finite clause. The + TNS,-MOD-featured TTNS serves as a temporal operator to bind the event argument, mapping the ...predicated event to the actual world, whereas the -TNS, + MOD-featured TMOD serves as a modal operator to bind the event argument, linking the predicated event with a possible world. A futurity-denoting English clause is structurally represented as a TNS-defective TMOD P headed either by an overt or a covert TMOD. The infinitival to in futurity clauses could also be viewed as a morphological marker of TMOD. In the case of a null TMOD, the PRE or PAST TNS-feature originating from C passes down to T and morphologically realized either on the overt TMOD or on V, thus the long-standing misconception of 'the present/past tense implying futurity'. The minimalist TMOD P analysis dissolves the purported English future tense, provides a unitary account for various futurity-denoting constructions, and captures the i
Grammatical metaphor in the Hallidayan sense consists of ideational metaphor and interpersonal metaphor. This propels some systemicists to think of the inclusion of textual metaphor into grammatical ...metaphor since the three metafunctions are intertwined, and to carry out research on textual metaphor from different perspectives. However, Halliday has never discussed textual metaphor, only mentioning the textual effects of ideational metaphor. Following the notion of cline, we propose that the relation between the two figures of a sequence can be realized along two lines, one being the unidirectional transfer from the conjunctive adverbial groups through paratactic and hypotactic conjunction groups to preposition groups, the other being that from the conjunctive adverbial groups through paratactic and hypotactic conjunction groups to verbal groups and finally to nominal groups. Based on the double functionality principle, five types of textual metaphor from the perspective of relator are identified: zero conjunctive adverbial groups, conjunctionalization of conjunctive adverbial groups, prepositionalization of conjunction groups, verbalization of conjunction groups and nominalization of conjunctive verbal groups.
The aim of this paper is two-fold: first it examines, based on data from English, Polish, & Hindi, different types of relativization in human language: the standard headed relative, headless ...relative, light-headed relative, & the correlative, with attention to whether the construction has a head & what structural relation there is between its constituents. The paper then identifies & discusses three types of relative constructions in Mandarin Chinese. 28 References. Adapted from the source document
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