Animal modeling for myopia.

Background: Myopia is one of the most common eye diseases globally, and has become an increasingly serious health concern among adolescents. Understanding the factors contributing to the onset of myopia and the strategies to slow its progression is critical to reducing its prevalence. Main text: Animal models are key to understanding of the etiology of human diseases. Various experimental animal models have been developed to mimic human myopia, including chickens, rhesus monkeys, marmosets, mice, tree shrews, guinea pigs and zebrafish. Studies using these animal models have provided evidences and perspectives on the regulation of eye growth and refractive development. This review summarizes the characteristics of these models, the induction methods, common indicators of myopia in animal models, and recent findings on the pathogenic mechanism of myopia. Conclusions: Investigations using experimental animal models have provided valuable information and insights into the pathogenic mechanisms of human myopia and its treatment strategies.

A modified hyaluronic acid hydrogel with strong bacterial capture and killing capabilities for drug-resistant bacteria-infected diabetic wound healing.

Management of diabetic wounds becomes increasingly challenging as bacterial infections intensify the inflammation. Employing polysaccharide hydrogels with inherent antibacterial qualities can significantly reduce the need for antibiotics to manage infections in diabetic wounds. The typical approach to achieving antibacterial outcomes with hydrogels relies on the penetration of bacteria into their porous architecture. Such penetration not only takes time but can also prolong inflammation, thus impeding the healing of wounds. Hence, the quick capture and eradication of bacteria are essential for optimizing the hydrogel's antibacterial performance. Herein, we introduce a multifunctional polysaccharide hydrogel dressing-designated as HAQ-created for managing bacterial infections in diabetic wounds. This dressing is based on hyaluronic acid, which is modified with methacrylic anhydride, and special functional groups are added to the modified hyaluronic acid matrix: phenylboronic acid for capturing bacteria and quaternary ammonium chitosan for bacterial destruction. As expected, the HAQ system exhibits robust antibacterial effectiveness against both methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa in vitro and in vivo. Consequently, HAQ stands as a promising hydrogel dressing with intrinsic antibacterial capabilities and offers significant potential for managing diabetic wounds infected by drug-resistant bacteria.

Geographic variation in leaf traits and palatability of a native plant invader during domestic expansion.

Like alien plant invasion, range expansion of native plants may threaten biodiversity and economies, rendering them native invaders. Variation in abiotic and biotic conditions across a large geographic scale greatly affects variation in traits and interactions with herbivores of native plant invaders, which is an interesting yet mostly unexplored issue. We used a common garden experiment to compare defensive/nutritional traits and palatability to generalist herbivores of 20 native (23.64° N-30.18° N) and introduced range (31.58° N-36.87° N) populations of Reynoutria japonica, which is a native invader following range expansion in China. We analyzed the relationships among herbivore pressure, climate, plant chloroplast haplotypes, leaf traits, and herbivore performance. Of the 16 variables tested, we observed range differences in 11 variables and latitudinal clines in nine variables. In general, herbivores performed better on the introduced plants than on the native plants, and better on the high-latitude plants than on the low-latitude plants within the introduced populations. Three key traits (leaf thickness, specific leaf area, and carbon-to-nitrogen [C:N] ratio) determined palatability to herbivores and were significantly associated with temperature and/or precipitation of plant provenance as well as with plant haplotypes but not with herbivore pressure. Our results revealed a causal sequence from plant-range-based environmental forces and genetic context to plant quality and palatability to herbivores in R. japonica. These findings suggest a post-introduction evolution of R. japonica, which may partly explain the colonization success of this important native, but invasive plant.

Fibroblast growth factor 21 improves insulin sensitivity by modulating the bile acid-gut microbiota axis in type â ¡ diabetic mice.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is an important regulator of glycolipid metabolism. However, whether the gut microbiota is related to the anti-diabetic and obesity effects of FGF21 remains unclear. METHODS: Our research used KO/KO db/db male mice and streptozotocin (STZ)-induced to simulate the construction of two type II diabetic mellitus (T2DM) models, and detected impaired glucose tolerance in the model by using the ipGTT and ITT assays, and collected feces from the model mice for sequencing of the intestinal flora and the content of short-chain fatty acids. H＆E staining was used to detect changes in intestinal tissue, the serum levels of LPS and GLP-1 were detected by ELISA. RESULTS: In this study, we found that FGF21 significantly improved insulin sensitivity, attenuated intestinal lesions, and decreased serum lipopolysaccharide (LPS) concentrations in T2DM mice. Moreover, FGF21 reshaped the gut microbiota and altered their metabolic pathways in T2DM mice, promoting the production of short-chain fatty acids (SCFAs) and the secretion of glucagon-like peptide 1 (GLP-1). Fecal transplantation experiments further confirmed that feces from FGF21-treated diabetic mice demonstrated similar effects as FGF21 in terms of anti-diabetic activity and regulation of gut microbiota dysbiosis. Additionally, the antibiotic depletion of gut microbiota abolished the beneficial effects of FGF21, including increased GLP-1 secretion and fecal SCFA concentration. Additionally, the FGF21 effects of ameliorating intestinal damage and suppressing plasma LPS secretion were suppressed. All these findings suggest that FGF21 prevents intestinal lesions by modifying the gut microbiota composition. Furthermore, FGF21 affected bile acid synthesis by inhibiting CYP7A1, the key enzyme of bile acid synthesis. CONCLUSSION: Therefore, FGF21 enriched beneficial bacteria by preventing bile acid synthesis and stimulating the secretion of the intestinal hormone GLP-1 via the increased production of gut microbiota metabolites, thereby exerting its anti-diabetic effects.

Photothermal-enhanced in situ supramolecular hydrogel promotes bacteria-infected wound healing in diabetes.

Bacterial infection can impede the healing of chronic wounds, particularly diabetic wounds. The high-sugar environment of diabetic wounds creates a favorable condition for bacterial growth, posing a challenge to wound healing. In clinical treatment, the irregular shape of the wound and the poor mechanical properties of traditional gel adjuvants make them susceptible to mechanical shear and compression, leading to morphological changes and fractures, and difficult to adapt to irregular wounds. Traditional gel adjuvants are prepared in advance, while in situ gel is formed at the site of administration after drug delivery in a liquid state, which can better fit the shape of the wound. Therefore, this study developed an in situ HA/GCA/Fe2+-GOx gel using a photothermal-enhanced Fenton reaction to promote the generation of hydroxyl radicals (·OH). The generation of ·OH has an antibacterial effect while promoting the formation of the gel, achieving a dual effect. The addition of double-bonded adamantane (Ada) interacts with the host-guest effect of graphene oxide and the double-bond polymerization of HAMA gel, making the entire gel system more complete. At the same time, the storage modulus (G') of the gel increased from 130 to 330 Pa, enhancing the mechanical properties of the gel. This enables the gel to have better injectability and self-healing effects. The addition of GOx can consume glucose at the wound site, providing a good microenvironment for the repair of diabetic wounds. The gel has good biocompatibility and in a diabetic rat wound model infected with S. aureus, it can effectively kill bacteria at the wound site and promote wound repair. Meanwhile, the inflammation of wounds treated with HA/GCA/Fe2+-GOx + NIR was lighter compared to untreated wounds. Therefore, this study provides a promising strategy for treating bacterial-infected diabetic wounds.

Arrays of Bowl-Shaped Janus Particle Film with Structured Colors.

Structural colors generated via total internal reflection (TIR) using nanostructure-free micro-concave shapes have garnered increasing attention. However, the application of large micro-concave structures for structural coloration remains limited. Herein, a flexibly tunable structural color film fabricated by casting polydimethylsiloxane (PDMS) on an array of large poly(glycidyl methacrylate) (PGMA) bowl-shaped particles is reported. The resultant film exhibits tunable red to green structural colors with changing observation angles. Moreover, the color can be further tailored by altering the shape of the film itself. The incorporation of the PDMS layer not only facilitates a shift in the locus of TIR from the bottom surface to the top concave surface of the particles, thereby enabling the generation of structural color, but also confers enhanced flexibility to the film. Further decoration with silver nanoparticles imparts antimicrobial properties, yielding a novel antimicrobial coating material with structural colors. The simple and cost-effective strategy for the production of structural color films provides potential applications in antimicrobial coatings, enabling accessible and customizable structural coloration using big-size micro-concave particles.

Bioactive glass 1393 promotes angiogenesis and accelerates wound healing through ROS/P53/MMP9 signaling pathway.

Compared to bioactive glass 45S5, bioactive glass 1393 has shown greater potential in activating tissue cells and promoting angiogenesis for bone repair. Nevertheless, the effect of bioactive glass 1393 in the context of wound healing remains extensively unexplored, and its mechanism in wound healing remains unclear. Considering that angiogenesis is a critical stage in wound healing, we hypothesize that bioactive glass 1393 may facilitate wound healing through the stimulation of angiogenesis. To validate this hypothesis and further explore the mechanisms underlying its pro-angiogenic effects, we investigated the impact of bioactive glass 1393 on wound healing angiogenesis through both in vivo and in vitro studies. The research demonstrated that bioactive glass 1393 accelerated wound healing by promoting the formation of granulation, deposition of collagen, and angiogenesis. The results of Western blot analysis and immunofluorescence staining revealed that bioactive glass 1393 up-regulated the expression of angiogenesis-related factors. Additionally, bioactive glass 1393 inhibited the expression of ROS and P53 to promote angiogenesis. Furthermore, bioactive glass 1393 stimulated angiogenesis through the P53 signaling pathway, as evidenced by P53 activation assays. Collectively, these findings indicate that bioactive glass 1393 accelerates wound healing by promoting angiogenesis via the ROS/P53/MMP9 signaling pathway.

The TRIM21-FOXD1-BCL-2 axis underlies hyperglycaemic cell death and diabetic tissue damage.

Chronic hyperglycaemia is a devastating factor that causes diabetes-induced damage to the retina and kidney. However, the precise mechanism by which hyperglycaemia drives apoptotic cell death is incompletely known. Herein, we found that FOXD1, a FOX family transcription factor specifically expressed in the retina and kidney, regulated the transcription of BCL-2, a master regulator of cell survival. Intriguingly, the protein level of FOXD1, which responded negatively to hyperglycaemic conditions, was controlled by the TRIM21-mediated K48-linked polyubiquitination and subsequent proteasomal degradation. The TRIM21-FOXD1-BCL-2 signalling axis was notably active during diabetes-induced damage to murine retinal and renal tissues. Furthermore, we found that tartary buckwheat flavonoids effectively reversed the downregulation of FOXD1 protein expression and thus restored BCL-2 expression and facilitated the survival of retinal and renal tissues. In summary, we identified a transcription factor responsible for BCL-2 expression, a signalling axis (TRM21-FOXD1-BCL-2) underlying hyperglycaemia-triggered apoptosis, and a potential treatment for deleterious diabetic complications.

Genetic and epigenetic regulators of retinal Müller glial cell reprogramming.

Background: Retinal diseases characterized with irreversible loss of retinal nerve cells, such as optic atrophy and retinal degeneration, are the main causes of blindness. Current treatments for these diseases are very limited. An emerging treatment strategy is to induce the reprogramming of Müller glial cells to generate new retinal nerve cells, which could potentially restore vision. Main text: Müller glial cells are the predominant glial cells in retinae and play multiple roles to maintain retinal homeostasis. In lower vertebrates, such as in zebrafish, Müller glial cells can undergo cell reprogramming to regenerate new retinal neurons in response to various damage factors, while in mammals, this ability is limited. Interestingly, with proper treatments, Müller glial cells can display the potential for regeneration of retinal neurons in mammalian retinae. Recent studies have revealed that dozens of genetic and epigenetic regulators play a vital role in inducing the reprogramming of Müller glial cells in vivo. This review summarizes these critical regulators for Müller glial cell reprogramming and highlights their differences between zebrafish and mammals. Conclusions: A number of factors have been identified as the important regulators in Müller glial cell reprogramming. The early response of Müller glial cells upon acute retinal injury, such as the regulation in the exit from quiescent state, the initiation of reactive gliosis, and the re-entry of cell cycle of Müller glial cells, displays significant difference between mouse and zebrafish, which may be mediated by the diverse regulation of Notch and TGFß (transforming growth factor-ß) isoforms and different chromatin accessibility.

cGAS-STING signaling in cell death: Mechanisms of action and implications in pathologies.

Cyclic GMP-AMP synthase (cGAS) monitors dsDNA in the cytosol in response to pathogenic invasion or tissue injury, initiating cGAS-STING signaling cascades that regulate various cellular physiologies, including IFN /cytokine production, autophagy, protein synthesis, metabolism, senescence, and distinct types of cell death. cGAS-STING signaling is crucial for host defense and tissue homeostasis; however, its dysfunction frequently leads to infectious, autoimmune, inflammatory, degenerative, and cancerous diseases. Our knowledge regarding the relationships between cGAS-STING signaling and cell death is rapidly evolving, highlighting their essential roles in pathogenesis and disease progression. Nevertheless, the direct control of cell death by cGAS-STING signaling, rather than IFN/NF-κB-mediated transcriptional regulation, remains relatively unexplored. This review examines the mechanistic interplays between cGAS-STING cascades and apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagic/lysosomal cell death. We will also discuss their pathological implications in human diseases, particularly in autoimmunity, cancer, and organ injury scenarios. We hope that this summary will stimulate discussion for further exploration of the complex life-or-death responses to cellular damage mediated by cGAS-STING signaling.