Augmentation of scleral glycolysis promotes myopia through histone lactylation.

Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation (FMT). Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la, and this promoted Notch1 expression. Genetic analyses identified a significant enrichment of two genes encoding glycolytic enzymes, ENO2 and TPI1. Moreover, increasing sugar intake in guinea pigs not only induced myopia but also enhanced the response to myopia induction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleral glycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation.

Dysregulated Arginine Metabolism Is Linked to Retinal Degeneration in Cep250 Knockout Mice.

Purpose: Degeneration of retinal photoreceptors is frequently observed in diverse ciliopathy disorders, and photoreceptor cilium gates the molecular trafficking between the inner and the outer segment (OS). This study aims to generate a homozygous global Cep250 knockout (KO) mouse and study the resulting phenotype. Methods: We used Cep250 KO mice and untargeted metabolomics to uncover potential mechanisms underlying retinal degeneration. Long-term follow-up studies using optical coherence tomography (OCT) and electroretinography (ERG) were performed. Results: OCT and ERG results demonstrated gradual thinning of the outer nuclear layer (ONL) and progressive attenuation of the scotopic ERG responses in Cep250-/- mice. More TUNEL signal was observed in the ONL of these mice. Immunostaining of selected OS proteins revealed mislocalization of these proteins in the ONL of Cep250-/- mice. Interestingly, untargeted metabolomics analysis revealed arginine-related metabolic pathways were altered and enriched in Cep250-/- mice. Mis-localization of a key protein in the arginine metabolism pathway, arginase 1 (ARG1), in the ONL of KO mice further supports this model. Moreover, adeno-associated virus (AAV)-based retinal knockdown of Arg1 led to similar architectural and functional alterations in wild-type retinas. Conclusions: Altogether, these results suggest that dysregulated arginine metabolism contributes to retinal degeneration in Cep250-/- mice. Our findings provide novel insights that increase understanding of retinal degeneration in ciliopathy disorders.

Image-Guided Optical Coherence Tomography to Assess Structural Changes in Rodent Retinas.

Ocular diseases, such as age-related macular degeneration, glaucoma, retinitis pigmentosa, and uveitis, are always accompanied by retinal structural changes. These diseases affecting the fundus always exhibit typical abnormalities in certain cell types in the retina, including photoreceptor cells, retinal ganglion cells, cells in the retinal blood vessels, and cells in the choroidal vascular cells. Noninvasive, highly efficient, and adaptable imaging techniques are required for both clinical practice and basic research. Image-guided optical coherence tomography (OCT) satisfies these requirements because it combines fundus photography and high-resolution OCT, providing an accurate diagnosis of tiny lesions as well as important changes in the retinal architecture. This study details the procedures of data collection and data analysis for image-guided OCT and demonstrates its application in rodent models of choroidal neovascularization (CNV), optic nerve crush (ONC), light-induced retinal degeneration, and experimental autoimmune uveitis (EAU). This technique helps researchers in the eye field to identify rodent retinal structural changes conveniently, reliably, and tractably.

The role of rapid maxillary expansion in pediatric obstructive sleep apnea: Efficacy, mechanism and multidisciplinary collaboration.

This review aims to provide current knowledge about the efficacy, mechanism, and multidisciplinary collaboration of rapid maxillary expansion (RME) treatment in pediatric obstructive sleep apnea (OSA). OSA is a chronic disease characterized by progressively increasing upper airway resistance, with various symptoms and signs. Increasingly the evidence indicates that RME is a non-invasive and effective therapy option for children with OSA. Besides, the therapeutic mechanism of RME includes increasing upper airway volume, reducing nasal resistance, and changing tongue posture. Recent clinical researches and case reports also show that a multidisciplinary approach improves sleep-disordered breathing in children. Applied with adenotonsillectomy, mandibular advancement, continuous positive airway pressure, and comprehensive orthodontic treatment, RME can be more effective in recurrent or residual OSA.

Metabolomic Study of a Rat Model of Retinal Detachment.

Retinal detachment is a serious ocular disease leading to photoreceptor degeneration and vision loss. However, the mechanism of photoreceptor degeneration remains unclear. The aim of this study was to investigate the altered metabolism pathway and physiological changes after retinal detachment. Eight-week-old male SD rats were fed, and the model of retinal detachment was established by injecting hyaluronic acid into the retinal space. The rats were euthanized 3 days after RD, and the retinal tissues were sectioned for analysis. Untargeted lipid chromatography-mass spectrometry lipidomic was performed to analyze the metabolite changes. A total of 90 significant metabolites (34 in anionic and 56 in cationic models) were detected after retinal detachment. The main pathways were (1) histidine metabolism; (2) phenylalanine, tyrosine, and tryptophan biosynthesis; and (3) glycine, serine, and threonine metabolism. The key genes corresponding to each metabolic pathway were verified from the Gene Expression Omnibus (GEO) database of human retinal samples. The results indicated that the production of histamine by histidine decarboxylase from histidine reduced after RD (p < 0.05). Xanthine, hypoxanthine, guanine, and guanosine decreased after RD (p < 0.05). Decreased xanthine and hypoxanthine may reduce the antioxidant ability. The decreased guanosine could not provide enough sources for inosine monophosphate production. Tyrosine is an important neurotransmitter and was significantly reduced after RD (p < 0.05). Citrate was significantly reduced with the increase of ATP-citrate lyase enzyme (ACLY) (p < 0.05). We inferred that lipid oxidation might increase rather than lipid biogenesis. Thus, this study highlighted the main changes of metabolite and physiological process after RD. The results may provide important information for photoreceptor degeneration.

HDAC5, negatively regulated by miR-148a-3p, promotes colon cancer cell migration.

Histone deacetylases (HDACs) are involved in many processes including tumor cell growth and proliferation and regulation of gene expression. To clarify the role of class IIa HDACs in the metastasis of colon adenocarcinoma, we used the class IIa HDAC inhibitor TMP269 and found that it effectively inhibited the migration ability of colon adenocarcinoma cells. Next, we silenced the member of class IIa HDACs and confirmed that the migratory ability of colon adenocarcinoma cells was significantly inhibited by silencing HDAC5 or HDAC7. HDAC5 plays a variety of roles in human cancers. Here, we examined the role of HDAC5 in colon adenocarcinoma. The results indicated that HDAC5 was highly expressed in tumor tissues and negatively correlated with the expression of miR-148a-3p. Moreover, the expression of HDAC5 was correlated with tumor progression. HDAC5 markedly increased the invasion and migration of cancer cells in vitro, an effect that could be inhibited by overexpression of miR-148a-3p. Following an intraperitoneal injection of colon adenocarcinoma cells in athymic nude mice, HDAC5 promoted tumor implant. Together, these findings showed that HDAC5 overexpression in colon adenocarcinoma is consistent with tumor progression and tumor cell migration and the impact of HDAC5 overexpression is reduced by miR-148a-3p.

Dietary ω-3 polyunsaturated fatty acids are protective for myopia.

Myopia is a leading cause of visual impairment and blindness worldwide. However, a safe and accessible approach for myopia control and prevention is currently unavailable. Here, we investigated the therapeutic effect of dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on myopia progression in animal models and on decreases in choroidal blood perfusion (ChBP) caused by near work, a risk factor for myopia in young adults. We demonstrated that daily gavage of ω-3 PUFAs (300 mg docosahexaenoic acid [DHA] plus 60 mg eicosapentaenoic acid [EPA]) significantly attenuated the development of form deprivation myopia in guinea pigs and mice, as well as of lens-induced myopia in guinea pigs. Peribulbar injections of DHA also inhibited myopia progression in form-deprived guinea pigs. The suppression of myopia in guinea pigs was accompanied by inhibition of the "ChBP reduction-scleral hypoxia cascade." Additionally, treatment with DHA or EPA antagonized hypoxia-induced myofibroblast transdifferentiation in cultured human scleral fibroblasts. In human subjects, oral administration of ω-3 PUFAs partially alleviated the near-work-induced decreases in ChBP. Therefore, evidence from these animal and human studies suggests ω-3 PUFAs are potential and readily available candidates for myopia control.

Combination of Trace Metal to Improve Solventogenesis of Clostridium carboxidivorans P7 in Syngas Fermentation.

Higher alcohols such as butanol (C4 alcohol) and hexanol (C6 alcohol) are superior biofuels compared to ethanol. Clostridium carboxidivorans P7 is a typical acetogen capable of producing C4 and C6 alcohols natively. In this study, the composition of trace metals in culture medium was adjusted, and the effects of these adjustments on artificial syngas fermentation by C. carboxidivorans P7 were investigated. Nickel and ferrous ions were essential for growth and metabolite synthesis during syngas fermentation by P7. However, a decreased dose of molybdate improved alcohol fermentation performance by stimulating carbon fixation and solventogenesis. In response to the modified trace metal composition, cells grew to a maximum OD600 nm of 1.6 and accumulated ethanol and butanol to maximum concentrations of 2.0 and 1.0 g/L, respectively, in serum bottles. These yields were ten-fold higher than the yields generated using the original composition of trace metals. Furthermore, 0.5 g/L of hexanol was detected at the end of fermentation. The results from gene expression experiments examining genes related to carbon fixation and organic acid and solvent synthesis pathways revealed a dramatic up-regulation of the Wood-Ljungdahl pathway (WLP) gene cluster, the bcs gene cluster, and a putative CoA transferase and butanol dehydrogenase, thereby indicating that both de novo synthesis and acid re-assimilation contributed to the significantly elevated accumulation of higher alcohols. The bdh35 gene was speculated to be the key target for butanol synthesis during solventogenesis.

Effects of zinc on the production of alcohol by Clostridium carboxidivorans P7 using model syngas.

Renewable energy, including biofuels such as ethanol and butanol from syngas bioconversed by Clostridium carboxidivorans P7, has been drawing extensive attention due to the fossil energy depletion and global eco-environmental issues. Effects of zinc on the growth and metabolites of C. carboxidivorans P7 were investigated with model syngas as the carbon source. The cell concentration was doubled, the ethanol content increased 3.02-fold and the butanol content increased 7.60-fold, the hexanol content increased 44.00-fold in the medium with 280 µM Zn2+, when comparing with those in the control medium [Zn2+, (7 µM)]. Studies of the genes expression involved in the carbon fixation as well as acid and alcohol production in the medium with 280 µM Zn2+ indicated that fdhII was up-regulated on the second day, acs A, fdhII, bdh35 and bdh50 were up-regulated on the third day and bdh35, acsB, fdhI, fdhIII, fdhIV, buk, bdh10, bdh35, bdh40 and bdh50 were up-regulated on the fourth day. The results indicated that the increased Zn2+ content increased the alcohol production through increase in the gene expression of the carbon fixation and alcohol dehydrogenase.

Physiological response of Clostridium ljungdahlii DSM 13528 of ethanol production under different fermentation conditions.

In this study, cell growth, gene expression and ethanol production were monitored under different fermentation conditions. Like its heterotrophical ABE-producing relatives, a switch from acidogenesis to solventogenesis of Clostridium ljungdahlii during the autotrophic fermentation with CO/CO2 could be observed, which occurred surprisingly in the late-log phase rather than in the transition phase. The gene expression profiles indicated that aor1, one of the putative aldehyde oxidoreductases in its genome played a critical role in the formation of ethanol, and its transcription could be induced by external acids. Moreover, a low amount of CaCO3 was proved to have positive influences on the cell density and substrate utilization, followed by an increase of over 40% ethanol and 30% acetate formation.