An esterase-responsive ibuprofen nano-micelle pre-modified embryo derived nucleus pulposus progenitor cells promote the regeneration of intervertebral disc degeneration

Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration(IDD).Current limitations of stem cells include with their insufficient cell source,poor proliferation capacity,low nucleus pulposus(NP)-specific differentiation potential,and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation.To address these challenges,embryo-derived long-term expandable nucleus pulposus progenitor cells(NPPCs)and esterase-responsive ibuprofen nano-micelles(PEG-PIB)were prepared for synergistic transplantation.In this study,we propose a biomaterial pre-modification cell strategy;the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis.The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro;their further synergistic transplantation yielded effective functional recovery,histological regeneration,and inhibition of pyroptosis during IDD regeneration.Herein,we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.

Headedness in Yorǘhbá： An Examination of the Deviant Value of Determiner Phrase

The issue of ＂headedness＂ is a product of Chomsky＇s （1988） notion of UG （Universal Grammar） that led to the development of a framework known as P＆P （Principles and Parameters） theory. It is this theory we have adopted for our analysis in this paper. The purpose of this paper is to examine the inconsistency in the value of Head Parameter with reference to the value of DP （determiner phrase） in Yorfib^i. As a native speaker of Yorfib~, the author has adopted an introspective method of data collection and used the intuitive knowledge of other native speakers of the language for necessary clarifications. Despite the fact that English and Yorfib~ are both head-initial, the structure of the NPs （noun phrases） in English shows that the head noun is always pre-modified, making the NP ＂head-final＂--a violation of the value of Head Parameter in the language. This necessitated the need for Abney＇s （1987） DP hypothesis; in which the determiner heads its own phrase, thereby making a NP in English head-initial. This solves the problem of Head Parameter in English. However, since nouns in Yor/lb^i are post-modified, adopting ＂DP-analysis＂ will automatically produce head-final--a violation of the value of Head Parameter in the language. Given the inconsistency in the specification of head-complement order among the noun phrases in English and Yorfib~, this paper proposes to set a parameter for SVO （Subject-Verb-Object） languages with pre-modification （like English） to adopt ＂DP-analysis＂, and those with post-modification （like Yorfib^t） to adopt ＂NP-analysis＂. This will ensure ＂head-initial＂ value for the two categories of SVO languages