Schwann cells are critical for the proper development and function of the peripheral nervous system (PNS), where they form a collaborative relationship with axons. Past studies highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development. Here, we expand on this, showing that drug-mediated modulation of prohibitins in vitro disrupts myelination and confirming that Schwann cell-specific ablation of prohibitin 2 (Phb2) in vivo results in severe defects in radial sorting and myelination. We show in vivo that Phb2-null Schwann cells cannot effectively proliferate and the transcription factors EGR2 (KROX20), POU3F1 (OCT6), and POU3F2 (BRN2), necessary for proper Schwann cell maturation, are dysregulated. Schwann cell-specific deletion of Jun, a transcription factor associated with negative regulation of myelination, confers partial rescue of the developmental defect seen in mice lacking Schwann cell Phb2. Finally, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on neuronal signals, and thus are potential mediators of PHB2-associated developmental defects. This work develops our understanding of Schwann cell biology, revealing that Phb2 may modulate the timely expression of transcription factors necessary for proper PNS development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell.

Mudstones and shales serve as natural barrier rocks in various geoenergy applications. Although many studies have investigated their mechanical properties, characterizing these parameters at the microscale remains challenging due to their fine-grained nature and susceptibility to microstructural damage introduced during sample preparation. This study aims to investigate the micromechanical properties of clay matrix composite in mudstones by combining high-speed nanoindentation mapping and machine learning data analysis. The nanoindentation approach effectively captured the heterogeneity in high-resolution mechanical property maps. Utilizing machine learning-based k-means clustering, the mechanical characteristics of matrix clay, brittle minerals, as well as measurements on grain boundaries and structural discontinuities (e.g., cracks) were successfully distinguished. The classification results were validated through correlation with broad ion beam-scanning electron microscopy images. The resulting average reduced elastic modulus (E r ) and hardness (H) values for the clay matrix were determined to be 16.2 ± 6.2 and 0.5 ± 0.5 GPa, respectively, showing consistency across different test settings and indenter tips. Furthermore, the sensitivity of indentation measurements to various factors was investigated, revealing limited sensitivity to indentation depth and tip geometry (when comparing Cube corner and Berkovich tip in a small range of indentation depth variations), but decreased stability at lower loading rates. Box counting and bootstrapping methods were applied to assess the representativeness of parameters determined for the clay matrix. A relatively small dataset (indentation number = 60) is needed to achieve representativeness, while the main challenges is to cover a representative mapping area for clay matrix characterization. Overall, this study demonstrates the feasibility of high-speed nanoindentation mapping combined with data analysis for micromechanical characterization of the clay matrix in mudstones, paving the way for efficient analysis of similar fine-grained sedimentary rocks.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40948-024-00864-9.

Schwann cells are critical for the proper development and function of the peripheral nervous system, where they form a mutually beneficial relationship with axons. Past studies have highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development. Here, we expand on this work, showing that drug-mediated modulation of prohibitins in vitro disrupts myelination and confirming that Schwann cell-specific ablation of prohibitin 2 (Phb2) in vivo results in early and severe defects in peripheral nerve development. Using a proteomic approach in vitro, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on the presence of axonal signals. Furthermore, we show in vivo that loss of Phb2 in mouse Schwann cells causes ineffective proliferation and dysregulation of transcription factors EGR2 (KROX20), POU3F1 (OCT6) and POU3F2 (BRN2) that are necessary for proper Schwann cell maturation. Schwann cell-specific deletion of Jun, a transcription factor associated with negative regulation of myelination, confers partial rescue of the development defect seen in mice lacking Schwann cell Phb2. This work develops our understanding of Schwann cell biology, revealing that Phb2 may directly or indirectly modulate the timely expression of transcription factors necessary for proper peripheral nervous system development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell.

UNASSIGNED: As a common chronic inflammatory skin disease, psoriasis seriously affects the physical health and psychological well-being of patients. Various clinical treatments for psoriasis have their own drawbacks, so it is important to find effective and safe drugs. Rehmannioside A (ReA) has anti-inflammatory properties and is the main active ingredient in Fuzhengzhiyanghefuzhiyang decoction (FZHFZY), an herbal compound for the treatment of psoriasis. But no studies have been conducted to determine whether ReA alone can treat psoriasis. Therefore, this study was designed to investigate the effect of ReA in the treatment of psoriasis and its potential mechanism of action.
UNASSIGNED: HaCaT cells were treated with ReA and IL-17A alone for 24 h and 48 h, and the most effective concentrations of ReA and interleukin (IL)-17A were found at 25 μg/mL and 100 ng/mL, respectively. A psoriasis cell model was constructed by stimulating HaCaT cells with IL-17A, followed by intervention with ReA. Cell viability and cell cycle distribution were measured by MTT assay and flow cytometry. The expression levels of keratin family members and chemokines were detected by real-time quantitative PCR (RT-qPCR), the levels of pro-inflammatory cytokines by enzyme-linked immunosorbent assay (ELISA), and key proteins of TRAF6/MAPK signaling pathway by Western blot.
UNASSIGNED: ReA weaken cell viability, down-regulate the expression of keratin family members (KRT6 and KRT17), restore cell cycle distribution to normal distribution, inhibit the release of pro-inflammatory cytokines (IL-6, IL-8 and IL-1β) and lower the expression of chemokines (S100A7, S100A9 and CXCL2) by interfering with the interaction between HaCaT cells and IL-17A. Thus, it exerts an anti-psoriatic effect by reducing the inflammatory response and inhibiting abnormal proliferation of HaCaT cells. Mechanistically, ReA inhibited the TRAF6/MAPK signaling pathway activated by IL-17A stimulation in HaCaT cells.
UNASSIGNED: ReA has in vitro anti-psoriatic effects and may be a new therapeutic agent for psoriasis.

Reactive arthritis is an acute inflammatory aseptic arthritis that is preceded by an infectious process in genetically predisposed individuals. It has been associated with gastrointestinal or genitourinary infection. Reactive arthritis is rare in children. In this review, we present two index cases that need biologic treatment followed by a thorough review of reactive arthritis in children and adolescents with proposed treatment algorithm.

To investigate the absolute wear caused by toothpastes with highly discrepant REA (Relative Enamel Abrasivity) and RDA (Relative Dentin Abrasivity) values on both enamel and dentin: Candida Peppermint (CP; REA: 1; RDA: 42), Colgate Total Original (CTO; REA: 4; RDA: 100), Signal White System (SWS; REA: 8; RDA: 143), and Candida White Diamond (CWD; REA 244; RDA: 12).
Eighty (80) bovine enamel samples and 80 dentin samples were divided into four groups each (n = 20) and investigated after a 6-h brushing procedure (21,600 cycles, 60 cycles/min, load of 2.5 N) with the four toothpastes. The abrasive enamel and dentin wear were registered using a contact profilometer. The median and interquartile range (IQR) of the abrasive enamel and dentin wear were calculated for each group. Pairwise comparisons were conducted using the Wilcoxon signed-rank exact test, and the p-value was adjusted according to Holm (statistical significance set at 0.05).
CWD led to the highest abrasive enamel wear (9.86 μm [5.77]). CTO caused the highest abrasive dentin wear (166.70 μm [69.90]), being statistically significantly higher than the wear for CP (54.20 μm [24.00]) and CWD (17.00 μm [7.80]) (p = 0.00001). The abrasive dentin wear for CWD was statistically significantly lower in comparison to all other groups (p = 0.00001).
Toothpastes with highly discrepant REA and RDA values presented statistically significantly different absolute wear on enamel and dentin. REA and RDA values should both be declared for every toothpaste.

OBJECTIVE: Very little data are known about charcoal toothpastes. The aim of this study was to counteract the missing data by determining the relative dentin abrasivity (RDA) and relative enamel abrasivity (REA) values of charcoal toothpastes.
METHODS: Radioactively charged dentin and enamel samples were randomly divided into groups of eight specimens. Each group was brushed with two of total 12 charcoal toothpaste slurries and with a standard abrasive with a known RDA and REA value. The measured radioactivity in counts per minute within the slurries corresponds to the amount of dentin or enamel abraded. RDA and REA values of the charcoal toothpastes were expressed relative to the known value of the standard slurry.
RESULTS: The RDA and REA values of the charcoal toothpastes have a broad range of 24-166 and 0-14, respectively.
CONCLUSIONS: The RDA and REA values do not differ significantly from previously tested commercially available toothpastes. However, the lack of fluoride compounds in many of the investigated charcoal toothpastes can have a less beneficial effect for the consumers. It is very important to educate patients accordingly.

Preliminary evidence suggests that commonly used genetic tests may be less likely to identify a genetic etiology for ALS-FTD in patients of underrepresented race, ethnicity, and ancestry (REA), as compared to European REA. Patients of underrepresented REA may therefore be less likely to receive accurate and specific genetic counseling information and less likely to have access to gene-targeted therapies currently in clinical trials. We compiled outcome data from 1911 ALS-FTD patients tested at a commercial laboratory over a seven-year period for C9orf72 hexanucleotide repeat expansion (HRE) alone or C9orf72 and multigene sequencing panel testing. We compared the incidence of pathogenic (P), likely pathogenic (LP), and uncertain variants in C9orf72 and other ALS-FTD genes, as well as age at testing, in patients of different REA. The diagnostic rate in patients of European REA (377/1595, 23.64%) was significantly higher than in patients of underrepresented REA (44/316, 13.92%) (p < 0.001). Patients of European REA were more likely to have the C9orf72 HRE (21.3%) than patients of underrepresented REA (10.4%) (p < 0.001). The overall distribution of positive test outcomes in all tested genes was significantly different between the two groups, with relatively more P and LP variants in genes other than C9orf72 identified in patients of underrepresented REA. The incidence of uncertain test outcomes was not significantly different between patients of European and underrepresented REA. Patients with positive test outcomes were more likely to be younger than those with negative or uncertain outcomes. Although C9orf72 HRE assay has been advocated as the first, and in some cases, only genetic test offered to patients with ALS-FTD in the clinical setting, this practice may result in the reduced ascertainment of genetic ALS-FTD in patients of diverse REA.

Peripheral SpA (pSpA) is comprised of ReA, PsA, enteritis-associated arthritis and undifferentiated pSpA (upSpA). ReA and upSpA share T cell oligotypes and metabolomics in serum and SF. We investigated HLA-B27 subtypes and cytokines in serum and SF that were compared between ReA and upSpA.
ReA and upSpA were compared in two cohorts. In cohort I (44 ReA and 56 upSpA), HLA-B27 subtyping was carried out. In cohort II (17 ReA and 21 upSpA), serum and SF cytokines were compared using a multiplex cytokine bead assay (27 cytokines). A total of 28 healthy controls with similar age and sex to cohort II were included for comparison of serum cytokine levels.
In cohort I, HLA-B27 was positive in 81.8% (36/44) of ReA and 85.71% (48/56) of upSpA patients. HLA-B27 typing was successful in 70 patients (30 ReA and 40 uSpA). HLA-B*2705 was the most common, followed by HLA-B*2704 and HLA-B*2707. Frequencies were the same between ReA and upSpA. In cohort II, 14 cytokines were detectable in the serum of patients. The levels of eight cytokines were higher than in the controls. The cytokine levels of ReA and upSpA were similar. Sixteen cytokines were detectable in the SF of patients. There was no statistical difference in the levels between ReA and upSpA. The cytokine profiles in sera and SF were also similar among HLA-B27-positive and negative patients.
ReA and upSpA have similar HLA-B27 subtype associations and similar cytokine profiles. They should be considered as a single entity during studies as well as clinical management.

OBJECTIVE: To investigate whether toothpastes with diamond powder vs those with traditional abrasives abrade dentin and enamel differently and to determine the relative dentin abrasivity (RDA) and relative enamel abrasivity (REA) values of those toothpastes.
METHODS: Dentin and enamel samples of bovine permanent incisors were randomly allocated into groups of eight, brushed with 20 different toothpastes (three of which contained diamond powder) and analysed for their RDA and REA values.
RESULTS: Toothpastes with diamond powder exhibit low RDA values but high REA values. Some RDA values exceeded the ones declared by the manufacturer.
CONCLUSIONS: Diamond powder as an abrasive might have a mild action on dentin, but it is highly abrasive on enamel.