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Tuberous sclerosis complex (TSC) integrates upstream stimuli and regulates cell growth by controlling the activity of mTORC1. TSC complex functions as a GTPase-activating protein (GAP) towards small GTPase Rheb and inhibits Rheb-mediated activation of mTORC1. Mutations in TSC genes cause tuberous sclerosis. In this study, the near-atomic resolution structure of human TSC complex reveals an arch-shaped architecture, with a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7. This asymmetric complex consists of two interweaved TSC1 coiled-coil and one TBC1D7 that spans over the tail-to-tail TSC2 dimer. The two TSC2 GAP domains are symmetrically cradled within the core module formed by TSC2 dimerization domain and central coiled-coil of TSC1. Structural and biochemical analyses reveal TSC2 GAP-Rheb complimentary interactions and suggest a catalytic mechanism, by which an asparagine thumb (N1643) stabilizes γ-phosphate of GTP and accelerate GTP hydrolysis of Rheb. Our study reveals mechanisms of TSC complex assembly and GAP activity.

Keratoconus (KC), a leading cause of vision impairment, has an unclear aetiology. This study used Mendelian randomization (MR) to explore the causal links between various factors (smoking, asthma, Down syndrome, inflammatory bowel disease, atopic dermatitis, and serum 25-hydroxyvitamin D levels) and KC. A two-sample MR design, grounded in genome-wide association study (GWAS) summary statistics, was adopted using data from FinnGen, UK Biobank, and other GWAS-related articles. The inverse-variance weighted (IVW) method was employed, complemented by the Wald ratio method for factors with only one single-nucleotide polymorphism (SNP). Sensitivity and stability were assessed through Cochrane's Q test, the MR-Egger intercept test, MR-PRESSO outlier test, and the leave-one-out analysis. The IVW results for the ORA (Ocular Response Analyzer) biomechanical parameters indicated significant associations between tobacco smoking (CH: p < 0.001; CRF: p = 0.009) and inflammatory bowel disease (CH: p = 0.032; CRF: p = 0.001) and corneal biomechanics. The Wald ratio method showed tobacco smoking was associated with a lower risk of KC (p = 0.024). Conversely, asthma (p = 0.009), atopic dermatitis (p = 0.012), inflammatory bowel disease (p = 0.017), and serum 25-hydroxyvitamin D levels (p = 0.039) were associated with a higher risk of KC by IVW, and the same applied to Down syndrome (p = 0.004) using the Wald ratio. These results underscore the role of corneal biomechanics as potential mediators in KC risk, warranting further investigation using Corvis ST and Brillouin microscopy. The findings emphasise the importance of timely screening for specific populations in KC prevention and management. [ABSTRACT FROM AUTHOR]

In recent years, there has been a significant focus on bioactive dressings suitable for treating chronic and acute wounds. Electrospinning nanofibers are considered advanced dressing options due to their high porosity and permeability to air and water, effective barrier properties against external pathogens, and excellent resemblance to the extracellular matrix for wound healing and skin regeneration. This article reviews the recent advancements in the application of electrospinning nanofibers for bioactive wound healing. The review begins with an overview of the wound healing process and electrospinning methods. It then explores the advantages and disadvantages of different synthetic and natural polymers used in the preparation of electrospinning wound dressings. The natural polymers discussed in this review include collagen, gelatin, silk fibroin, chitosan, hyaluronic acid, and sodium alginate. Additionally, the review delves into commonly used synthetic polymers like polyvinyl alcohol, polyvinyl chloride, polyethylene lactone, polylactide, and polyurethane for wound dressing applications. Furthermore, the review examines the blending of natural and synthetic polymers to create high‐performance wound dressings. It also explores the incorporation of functional additives, such as antimicrobial agents, growth factors, and natural extracts, into electrospinning nanofibers to expedite wound healing and tissue repair. In conclusion, electrospinning is an emerging technology that provides unique opportunities for designing more effective wound dressings and care products. [ABSTRACT FROM AUTHOR]

As the world's largest reactive carbon reservoir, the ocean plays a critical role in global climate change. Among coastal plant ecosystems, mangroves have the highest carbon storage efficiency and are prone to the impact of anthropogenic activities. In this study, taking the mangrove wetland of Qinglan Bay as an example, we extracted information on mangrove coastal surface change from 1988 to 2020 based on multi-temporal Landsat remote sensing data through field ground surveys and laboratory analysis and used the InVEST model to calculate the spatial and temporal structure of blue carbon in the mangrove area to investigate the effects of mangrove change in an ecological restoration context. The result shows that the overall area of mangrove forests exhibited a decreasing trend from 1988 to 2020, and the area of mangroves decreased from 1559.34 ha to 737.37 ha of which 52.71% was transformed into aquiculture, construction, and farm land. Accordingly, the mangrove carbon sinks from 1988 to 2020 were significantly reduced and the carbon stock decreased at an annual tendency from 1,025,901.71 tons to 712,118.69 tons. With the implementation of mangrove restoration, the decline of mangrove forests has decreased since 2003, promoting the stabilization and enhancement of carbon sinks in the mangrove wetlands of Qinglan Bay. The results of this study provide a technical method to evaluate the carbon sink contribution of mangrove wetland restoration in Hainan Province, a scientific basis and methodological innovation to monitor the carbon sink of mangrove cover change in larger regions of China, a theoretical basis to select criteria for mangrove restoration, and a scientific and systematic management strategy for ecological and mangrove restoration on Hainan Island. [ABSTRACT FROM AUTHOR]