OSBPL2 compound heterozygous variants cause dyschromatosis, ichthyosis, deafness and atopic disease syndrome.

PURPOSE: In this study, we identified and diagnosed a novel inherited condition called Dyschromatosis, Ichthyosis, Deafness, and Atopic Disease (DIDA) syndrome. We present a series of studies to clarify the pathogenic variants and specific mechanism. METHODS: Exome sequencing and Sanger sequencing was conducted in affected and unaffected family members. A variety of human and cell studies were performed to explore the pathogenic process of keratosis. RESULTS: Our finding indicated that DIDA syndrome was caused by compound heterozygous variants in the oxysterol-binding protein-related protein 2 (OSBPL2) gene. Furthermore, our findings revealed a direct interaction between OSBPL2 and Phosphoinositide phospholipase C-beta-3 (PLCB3), a key player in hyperkeratosis. OSBPL2 effectively inhibits the ubiquitylation of PLCB3, thereby stabilizing PLCB3. Conversely, OSBPL2 variants lead to enhanced ubiquitination and subsequent degradation of PLCB3, leading to epidermal hyperkeratosis, characterized by aberrant proliferation and delayed terminal differentiation of keratinocytes. CONCLUSIONS: Our study not only unveiled the association between OSBPL2 variants and the newly identified DIDA syndrome but also shed light on the underlying mechanism.

Space-confined twin-polymerization enabling homogeneous integration of ultrafine TiO2 nanoparticles into a sulfur-doped carbon matrix for boosting lithium storage.

Homogeneous integration of ultrafine TiO2 nanoparticles into a conductive sulfur-doped carbon skeleton was readily crafted by unusual space-confined twin-polymerization of a titanium-containing single-source coupled monomer and subsequent carbonization, producing a robust hetero-architecture for boosting lithium storage with large reversible capacity, high rate capability, and long-term cycling stability.

Mosaic GJB2 mutations in widespread porokeratotic adnexal ostial nevus: Report of two patients.

Porokeratotic adnexal ostial nevus (PAON) is a rare adnexal hamartoma characterized by keratotic papules following Blaschko's lines, typically located on the unilateral distal extremities. Cutaneous somatic GJB2 mutations have been linked to the pathogenesis of PAON. However, the genetic mechanism underlying bilateral or extended forms, which are less documented, remains unknown. In this study, we presented two cases of PAON with widespread cutaneous lesions and scalp involvement, and demonstrated the presence of GJB2 mosaic mutations in both patients. We further investigated the mosaic frequency in different tissues to gain insights into the mutation events contributing to the phenotype of widespread PAON. Our findings suggest that early postzygotic mutation causing mosaic GJB2 mutations may contribute to the widespread phenotype of PAON, thereby enriching the disease spectrum and mutation profile of PAON.

Microplastic pollution in water environment of typical nature reserves and scenery districts in southern China.

Microplastics were frequently detected in the ocean, freshwater environment and wastewater treatment plants. This study aims to fill up the knowledge gap of microplastic distribution in nature reserves and scenery districts. Microplastic samples were collected, the distribution characteristics were analyzed with a stereoscopic microscope and a Fourier transform infrared spectrometer, and the ecological risks of microplastic pollution were calculated. Microplastics were detected in all the collected water samples and the average abundances of microplastics in the surface water of eleven investigated nature reserves and scenery districts ranged from 542 to 5500 items/m3. The degrees of microplastic pollution of all the surveyed nature reserves and scenery districts were classified as hazard level I. Fiber microplastics represented the largest average proportion (67.4 %) and 91.7 % of the detected microplastics were smaller than 2 mm. Corresponding to the frequent detection of fiber microplastics, cotton was the most abundant (25.5 %) polymer type of the suspected microplastics, followed by polyamide (PA, 20.6 %), polyester (PET, 17.0 %), and cellulose (15.6 %). For the ecological risk of the microplastic polymers, six, two and three nature reserves and scenery districts were defined to be at hazard level I, II and III, respectively. In brief, microplastic pollution occurred in all the surveyed nature reserves/scenery districts and posed different degrees of ecological risks.

Tert-Butylhydroquinone Prevents Oxidative Stress-Mediated Apoptosis and Extracellular Matrix Degradation in Rat Chondrocytes.

Oxidative stress-induced chondrocyte apoptosis and degradation of the extracellular matrix (ECM) play an important role in the progression of osteoarthritis (OA). In addition, tert-butylhydroquinone (TBHQ) is an activator of the nuclear factor erythroid derived-2-related factor 2 (Nrf2). The present study aimed to determine the effectiveness of TBHQ in preventing the apoptosis of chondrocytes and degradation of the extracellular matrix, induced by oxidative stress, in vitro. Therefore, rat chondrocytes were exposed to 20 µM tert-butyl hydroperoxide (TBHP) for 24 h to establish an oxidative damage model, in vitro. Thereafter, cell viability was evaluated using the Cell Counting Kit-8 assay. Moreover, the level of ROS was determined through 2',7'-dichlorofluorescein diacetate staining. The mitochondrial membrane potential of chondrocytes was also measured using JC-1. Furthermore, cell apoptosis was assessed through Annexin V-fluorescein isothiocyanate/propidium iodide staining. The study also performed Western blotting and qPCR to evaluate the expression of extracellular matrix components, matrix catabolic enzymes, and changes in signalling pathways. The results showed that 2.5 and 5 µM of TBHQ reduced the TBHP-induced generation of excessive ROS and improved cell viability. Additionally, 2.5 and 5 µM of TBHQ prevented mitochondrial damage and apoptosis in rat chondrocytes. Treatment with TBHQ also increased the mRNA and protein expression levels of aggrecan and collagen II. However, TBHQ reduced the mRNA and protein expression levels of matrix metalloproteinase 3 (MMP3) and matrix metalloproteinase 13 (MMP13) in rat chondrocytes. In addition, treatment with TBHQ enhanced the protein expression levels of Nrf2, NADPH quinone oxidoreductase 1 (NQO-1), and hemeoxygenase-1 (HO-1) in rat chondrocytes. The current study showed that TBHQ was not only effective in protecting against TBHP-induced oxidative stress but also inhibited the apoptosis of rat chondrocytes and degradation of the ECM by activating the Nrf2 pathway. The results therefore suggest that TBHQ holds potential for use in the treatment of OA.

Numerical Modeling of Earthquake-Damaged Circular Bridge Columns Repaired Using Combination of Near-Surface-Mounted BFRP Bars with External BFRP Sheets Jacketing.

This paper reports the numerical simulation of earthquake-damaged circular columns repaired with the combination of near-surface-mounted (NSM) basalt fiber reinforced polymer (BFRP) bars with external BFRP sheets jacketing at quasi-static loading. The numerical modeling was carried out with the nonlinear OpenSees software platform by using the BeamWithHinges element. In the simulations, the effect of the previous earthquake damage on the behavior of the repaired columns was taken into account, and a simple and effective material damage-accumulation model is proposed to modify the constitutive of materials in the unrepaired regions of the repaired columns. The developed numerical models were validated by comparing their quasi-static findings with those obtained from a previous experimental program, and a good agreement can be observed. Furthermore, the efficiency of the repair technique used in tests is evaluated via the developed numerical model.

Application of constraint-based methods in Staphylococcus aureus metabolic network.

With the remarkable advances in reconstruction of genome-scale metabolic networks, computational methods are increasingly important in investigation of these networks. Since they only need a few available kinetic parameters, constraint-based modeling methods have attracted so much attention in recent years. With the important aid by COBRA Toolbox, Staphylococcus aureus metabolic network (S. aureus_iSB619 model) which contains 619 genes, 571 metabolites and 640 metabolic reactions is studied in the present paper. We investigated (mainly under glucose minimal media condition) the optimal flux distributions, optimal growth rates, dynamic growth, robustness analysis (to PGK and MDH reactions), gene deletion and uniform random sampling (all allowed flux distributions) of the model. The study provided a constraint-based modeling framework of Staphylococcus aureus, and the results could be used in its metabolic engineering and industry microbial research.