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• MrgprD+ neurons in the TG densely innervate the nasal mucosa, unlike sparsely innervating TrkB+ neurons. • The MrgprD+ neurons specifically target Sp5C's outer edge, while the TrkB+ neurons innervate Sp5 subregions. • The Sp5 and Sol neurons with TG inputs project to the VPM, VPL, Po, ZI, mRt, ml, SC, DC, PAG, and PBN. The trigeminal ganglion (TG) comprises primary sensory neurons responsible for orofacial sensations, subsequently projecting to the trigeminal nuclei in the brainstem. However, the circuit basis of nasal mechanosensation is not well characterized. Here we elucidate the anatomical organization of both peripheral and central projections of the TG. We found that the non-peptidergic nociceptor, MAS-related G protein-coupled receptor member D positive (MrgprD + ) neurons in the TG densely innervate the nasal mucosa, whereas the low-threshold mechanoreceptors subtypes rarely innervate the nasal mucosa. We also identified the central projection pattern of the mechanosensory neurons in TG. The tyrosine kinase receptor C positive (TrkC + ) neurons, tyrosine kinase receptor B positive (TrkB + ) and tyrosine hydroxylase positive (TH + ) neurons project to multiple subregions of brainstem trigeminal complex and solitary nucleus. In contrast, the MrgprD + neurons only densely project to outer edge of Sp5C. In addition, we further determined the ascending pathway of the TG neurons. Taken together, our study demonstrates the peripheral and central projection pattern of mechanosensory neurons in the TG, which provides a basis for the future functional studies. [ABSTRACT FROM AUTHOR]

This study investigates the distinctive social behaviors observed in individuals with Rett syndrome (RTT), characterized by the loss of spoken language, impaired eye gaze communication, gait abnormalities, and sleep issues. The research aims to identify social profiles in RTT and explore their correlation with sleep, sleep-disordered breathing (SDB), and daytime sleepiness. Standard overnight sleep macrostructure and respiratory parameters were assessed. Extracting 25 social-related items and one for daytime sleepiness from the Rett Syndrome Behavioral Questionnaire, factor analysis was applied to establish latent social profiles. These profiles were then correlated with sleep parameters. The nonparametric Mann-Whitney U test compared social profiles based on the presence of SDB (defined by an apnea-hypopnea index greater than one per hour) and daytime sleepiness. The study involved 12 female subjects with confirmed RTT diagnoses and MECP2 mutations, aged 8.54 ± 5.30 years. The Rett Syndrome Behavioral Questionnaire revealed a total average score of 25.83 ± 12.34, indicating varying degrees of social impairments. Comprising 25 social-related items, factor analysis yielded four social profiles: "interactive motricity," "mood change," "anxiety/agitation," and "gazing." Longer sleep onset latency correlated with increased socio-behavioral impairments, particularly in interactive motricity reduction. Conversely, higher rapid eye movement sleep was associated with fewer interactive socio-motor behaviors. No significant differences in social profiles were found concerning the presence of SDB or daytime sleepiness. The findings suggest four distinct social profiles in RTT individuals, hinting at shared disrupted circuits between sensorimotor functioning and sleep-related neuronal pathways. Despite the absence of differences in SDB or daytime sleepiness, the study highlights the relationship between sleep parameters, such as sleep onset latency and rapid eye movement sleep, and socio-behavioral outcomes in RTT with MECP2 mutations. [ABSTRACT FROM AUTHOR]

Interferon-tau (IFNT), a pregnancy recognition signal in ruminants, promotes the establishment of endometrial receptivity by inducing the expression of interferon-stimulated genes (ISGs) via the Janus kinase/signal transducer and activator of transcription (JAK/STATs) signaling pathway. However, the precise mechanisms remain largely unknown. Ubiquitin-specific protease 18 (USP18) acts specifically on the ISGylation modification system to exert deubiquitination and participates in the regulation of the type I IFN signaling pathway. The purpose of this study was to determine the role and mechanism of USP18 on endometrial receptivity in goat. USP18 was mainly localized in the uterine luminal and glandular epithelium, and its expression levels were significantly increased from days 5–18 of early pregnancy. Progesterone (P 4), estradiol (E 2), and IFNT significantly stimulated USP18 expression in goat endometrial epithelial cells (gEECs) cultured in vitro. Meanwhile, the markers of endometrial receptivity HOXA11, ITGB1, ITGB3, and ITGB5 were significantly upregulated after USP18 overexpression in gEECs. However, USP18 interference significantly inhibited the expression of HOXA10, ITGB1, ITGB3, and ITGB5 in gEECs. In addition, both the phosphorylation levels of STAT1 and the expression of ISGylation-modified proteins were significantly increased after USP18 silencing in gEECs. Furthermore, pretreatment with the STAT1 inhibitor Fludara markedly restored the effect of USP18 interference in gEECs. In summary, USP18 may play an important role in promoting goat endometrial receptivity by regulating the JAK/STAT1 pathway and ISGylation. • USP18 was mainly localized in the uterine luminal and glandular epithelium, and its expression levels were significantly increased from days 5–18 of early pregnancy. • The markers of endometrial receptivity HOXA11, ITGB1, ITGB3, and ITGB5 were significantly upregulated after USP18 overexpression in gEECs. • Both the phosphorylation levels of STAT1 and the expression of ISGylation-modified proteins were significantly increased after USP18 silencing in gEECs. [ABSTRACT FROM AUTHOR]

Renal fibrosis and loss of kidney function are key characteristics of chronic kidney disease (CKD). To address the lack of effective treatments, multifunctional layer-by-layer (LbL) assembled polymeric gene-carrier nanoparticles (PCHS-NP) are prepared to realize preferential accumulation and retention within renal glomerular cells, thereby effectively leveraging cortically localized structures for the synthesis and paracrine secretion of the antifibrotic growth factor, bone morphogenetic protein-7 (BMP7). PCHS-NP had stable homogenous morphologies, kidney-targeting functionality, antioxidative effects, and high transfection efficiency. In unilateral ureteral obstruction (UUO)-induced renal fibrosis, a single systemic injection of PCHS-NP prevents tubular atrophy and interstitial fibrosis, and the resultant tissue microenvironment is more conducive to tubular regeneration driven by the upregulation of proliferative SOX9-expressing tubular cells. In longer-term folic acid (FA)-induced renal fibrosis, we show that early, late, and repeat systemic injections restore kidney health and function. This study indicates that PCHS-NP accomplish a promising therapeutic option for the treatment of CKD. [Display omitted] • Layer-by-layer assembled nanoparticles were highly homogenous and stable. • Triserine decorations facilitated kidney uptake whilst reducing liver uptake. • Traceable Cy5-loaded nanoparticles revealed renal glomerular cell accumulation. • Elevated paracrine BMP7 production was realized after one systemic injection. • Antioxidative and antifibrotic effects were conducive for renal regeneration. [ABSTRACT FROM AUTHOR]