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Background: The high complexity of systemic autoimmune diseases (SADs) has hindered precise management. This study aims to investigate heterogeneity in SADs. Methods: We applied a joint cluster analysis, which jointed multiple correspondence analysis and k-means, to immunomarkers and measured the heterogeneity of clusters by examining differences in immunomarkers and clinical manifestations. The electronic health records of patients who received an antinuclear antibody test and were diagnosed with SADs, namely systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), were retrieved between 2001 and 2016 from hospitals in Taiwan. Results: With distinctive patterns of immunomarkers, a total of 11,923 patients with the three SADs were grouped into six clusters. None of the clusters was composed only of a single SAD, and these clusters demonstrated considerable differences in clinical manifestation. Both patients with SLE and SS had a more dispersed distribution in the six clusters. Among patients with SLE, the occurrence of renal compromise was higher in Clusters 3 and 6 (52% and 51%) than in the other clusters (p < 0.001). Cluster 3 also had a high proportion of patients with discoid lupus (60%) than did Cluster 6 (39%; p < 0.001). Patients with SS in Cluster 3 were the most distinctive because of the high occurrence of immunity disorders (63%) and other and unspecified benign neoplasm (58%) with statistical significance compared with the other clusters (all p < 0.05). Conclusions: The immunomarker-driven clustering method could recognise more clinically relevant subgroups of the SADs and would provide a more precise diagnosis basis. [ABSTRACT FROM AUTHOR]

Notch signaling is a conserved pathway crucial for nervous system development. Disruptions in this pathway are linked to neurodevelopmental disorders, neurodegenerative diseases, and brain tumors. Hairy/E(spl) (HES) genes, major downstream targets of Notch, are commonly used as markers for Notch activation. However, these genes can be activated, inhibited, or function independently of Notch signaling, and their response to Notch disruption varies across tissues and developmental stages. MIB1/Mib1 is an E3 ubiquitin ligase that enables Notch receptor activation by processing ligands like Delta and Serrate. We investigated Notch signaling disruption using the zebrafish Mib1 mutant line, mib1ta52b, focusing on changes in the expression of Hairy/E(spl) (her) genes. Our findings reveal significant variability in her gene expression across different neural cell types, regions, and developmental stages following Notch disruption. This variability questions the reliability of Hairy/E(spl) genes as universal markers for Notch activation, as their response is highly context-dependent. This study highlights the complex and context-specific nature of Notch signaling regulation. It underscores the need for a nuanced approach when using Hairy/E(spl) genes as markers for Notch activity. Additionally, it provides new insights into Mib1's role in Notch signaling, contributing to a better understanding of its involvement in Notch signaling-related disorders. [ABSTRACT FROM AUTHOR]

The template wetting method is a common method used for preparing one‐dimensional polymer nanostructures, which can be widely applied in many fields. Although the template wetting method has generality in controlling the morphology of nanomaterials, it still poses challenges in generating patterned polymer nanoarrays. Here, we present the fabrication of patterned and anti‐patterned azopolymer (PAzo) nanoarrays via the light‐induced nanowetting method. By shining UV lights, the trans‐PAzo converts to cis‐PAzo, causing a reduction of the glass transition temperature (Tg) of the PAzo below room temperature. Consequently, the PAzo polymers can undergo reversible solid–liquid transitions by shining UV and visible lights. When PAzo films are covered with photomasks and anodic aluminum oxide (AAO) templates, followed by shining UV lights, patterned PAzo nanoarrays can be generated. We further apply the concept that cis‐PAzo films can be selectively removed by solvents to generate anti‐patterned PAzo nanoarrays. By covering PAzo films with photomasks and illuminating UV lights, the unmasked areas can be converted to cis‐form, which can then be selectively removed by selected solvents. The patterned PAzo films are then covered with AAO templates, followed by shining UV lights, forming hierarchical anti‐patterned PAzo nanoarrays. [ABSTRACT FROM AUTHOR]

Lumbar ligamentous flavum hematoma (LFH) is a relatively rare pathology, and it is difficult to differentiate it from other cystic lesions. Full-endoscopic spine surgery (FESS), an excellent approach for clear and magnified operative visual field since it allows saline irrigation and minimizes destruction of surrounding tissues, has been applied to the treatment. This study aims to present a case series of patients with lumbar LFH treated by FESS.This case series consists of 17 lumbar LFH cases treated by FESS between May 2018 and November 2021 at a single institution. Patient background and operative data were collected from their medical records. The numerical rating scale (NRS), Oswestry Disability Index (ODI), and European Quality of Life-5 Dimensions (EQ-5D) were recorded preoperatively and postoperatively.Elderly men tend to suffer from lumbar LFH at the L4/5 vertebral level. Discontinuity with facet joint was confirmed under endoscopic visualization in all 17 cases. Blood clots were also observed in all cases under endoscope. The mean operative time was 68.6 min without complication. The patients were discharged at average 1.4 days after FESS with significant improvement of NRS score (P < 0.001). ODI and EQ-5D scores 2-year postoperatively statistically improved (P < 0.001), and there was no recurrence during followup period.The operative outcomes of lumbar LFH treated by FESS were satisfactory. FESS excels not only in the diagnosis but also in the treatment of lumbar LFH.

Central nervous system lesions often cause permanent motility defects in mammals since the injured neurons cannot regenerate. In contrast, lower vertebrates like zebrafish can regenerate lost neurons and restore motor function. This study investigates the efficacy of SC79, a pan-Akt activator, and A674563, a selective Akt1 inhibitor, as potential therapeutic agents for promoting spinal cord recovery post-injury. Spinal cord injury was induced in zebrafish larvae, and the effects of SC79 and A674563 on neuronal and glial regeneration were examined. SC79 promoted neuronal regeneration without affecting glial bridging, while A674563 induced glial bridging but reduced neuronal regeneration. The combination of SC79 and A674563 induced both glial bridging and neuronal regeneration. Optomotor response tests revealed improved motor function recovery with the combined treatment compared to individual treatments. Additionally, these chemical treatments altered the expression of 12 Akt downstream transcriptional target genes, affirming that the combination treatment preferentially regulates spinal cord regeneration through its action on Akt signaling. These findings highlight the complex interplay of Akt signaling pathways in spinal cord regeneration and suggest potential therapeutic strategies for enhancing functional recovery in spinal cord injury patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Traumatic injury to the spinal cord can lead to significant, permanent disability. Mammalian spinal cords are not capable of regeneration; in contrast, adult zebrafish are capable of such regeneration, fully recovering motor function. Understanding the mechanisms underlying zebrafish neuroregeneration may provide useful information regarding endogenous regenerative potential and aid in the development of therapeutic strategies in humans. DELTEX proteins (DTXs) regulate a variety of cellular processes. However, their role in neural regeneration has not been described. We found that zebrafish dtx2 , encoding Deltex E3 ubiquitin ligase 2, is expressed in ependymo-radial glial cells in the adult spinal cord. After spinal cord injury, the heterozygous dtx2 mutant fish motor function recovered quicker than that of the wild-type controls. The mutant fish displayed increased ependymo-radial glial cell proliferation and augmented motor neuron formation. Moreover, her gene expression, downstream of Notch signaling, increased in Dtx2 mutants. Notch signaling inactivation by dominant-negative Rbpj abolished the increased ependymo-radial glia proliferation caused by Dtx2 deficiency. These results indicate that ependymo-radial glial proliferation is induced by Dtx2 deficiency by activating Notch-Rbpj signaling to improve spinal cord regeneration and motor function recovery.

Despite significant advancements, current self-healing materials often suffer from a compromise between mechanical robustness and functional performance, particularly in terms of conductivity and responsiveness to environmental stimuli. Addressing this issue, the research introduces a self-healable and conductive copolymer, poly(ionic liquid-co-acrylic acid) (PIL-co-PAA), synthesized through free radical polymerization, and further optimized by incorporating thermoplastic polyurethane (TPU). This combination leverages the unique properties of each component, especially ion-dipole interactions and hydrogen bonds, resulting in a material that exhibits exceptional self-healing abilities and demonstrates enhanced mechanical properties and electrical conductivity. Moreover, the PIL-co-PAA/TPU films showcase alkaline-responsive behavior, a feature that broadens their applicability in dynamic environments. Through systematic characterization, including thermogravimetric analysis, tensile testing, and electrical properties measurements, the mechanisms behind the improved performance and functionality of these films are elucidated. The conductivities and ultimate tensile strength (σ uts ) of the PIL-co-PAA/TPU films regain 80% under 8 h healing process. To extend the applications for wearable devices, the self-healing properties of commercial cotton fabrics coated with the self-healable PIL-co-PAA are also investigated, demonstrating both self-healing and electrical properties. This study advances the understanding of self-healable conductive polymers and opens new avenues for their application in wearable technology., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)