Protective effects of sodium butyrate on fluorosis in rats by regulating bone homeostasis and serum metabolism.

Fluorosis due to high fluoride levels in drinking water profoundly affects the development of human skeletal and dental structures. Sodium butyrate (NaB) has been found to regulate overall bone mass and prevent pathological bone loss. However, the mechanism of NaB action on fluorosis remains unclear. In this study, a rat model of fluorosis induced by 100 mg/L sodium fluoride was used to investigate the impact of NaB on bone homeostasis and serum metabolomics. It was found that NaB significantly reduced the levels of bone resorption markers CTX-Ⅰ and TRACP-5B in fluorosis rats. Moreover, NaB increased calcium and magnesium levels in bone, while decreasing phosphorus levels. In addition, NaB improved various bone microstructure parameters, including bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone separation (Tb. SP), and structural model index (SMI) in the femur. Notably, NaB intervention also enhanced the antioxidant capacity of plasma in fluorosis rats. Furthermore, a comprehensive analysis of serum metabolomics by LC-MS revealed a significant reversal trend of seven biomarkers after the intervention of NaB. Finally, pathway enrichment analysis based on differential metabolites indicated that NaB exerted protective effects on fluorosis by modulating arginine and proline metabolic pathways. These findings suggest that NaB has a beneficial effect on fluorosis and can regulate bone homeostasis by ameliorating metabolic disorders.

Long-term Prognosis of Vision Loss Caused by Facial Hyaluronic Acid Injections and the Potential Approaches to Address This Catastrophic Event.

BACKGROUND: Vision loss is a serious complication of hyaluronic acid (HA) filler injections, and long-term observations regarding the prognosis, particularly with angiography, are rare. OBJECTIVES: This study aimed to investigate the long-term prognosis and living status of patients with visual defects due to HA filler injections. METHODS: Nine patients with vision loss caused by HA filler injections and receiving different treatments were included and followed up for 2 to 6 years after their accident. Follow-ups, including outpatient ophthalmologic examinations, were performed. RESULTS: In the follow-up observation, all patients had reintegrated into society and work. The prognosis was similar for all hyaluronidase treatments, including retrobulbar injections and superselective ophthalmic artery thrombolysis. The facial appearance was not remarkably affected, and only 3 patients reported slight scarring. Ptosis disappeared in all the patients, and slight strabismus was found in 5 patients. However, vision improvement was very limited, even in the patients whose occluded retinal central artery received reperfusion. CONCLUSIONS: This long-term follow-up showed that the patients with vision loss caused by HA filler injections could reintegrate into society after treatment. Although the embolization of the retinal central artery led to reperfusion, vision was not restored, which further demonstrated the difficulty of recovering vision with the current treatment and the importance of prophylaxis. Autohydrolysis of HA by incorporating hyaluronidase-containing stimuli-responsive nanoparticles and a dual-pipe syringe are potential future approaches to address this catastrophic event.

Meta-Analysis of the Comprehensive Efficacy of Intraocular Lens Implantation in Glaucoma Patients.

This study is aimed at investigating the efficacy of intraocular lens (IOL) implantation in patients suffering from glaucoma through meta-analysis of the previously published research. For this purpose, different literature databases were searched for identification of clinical studies published between January 2000 and January 2022 on evaluating IOL's efficacy in treating glaucoma. RevMan 5.3 was used to conduct a meta-analysis of the pertinent data. The central anterior chamber depth (ACD), corneal endothelial cell counts, best-corrected visual acuity (BCVA), intraocular pressure (IOP), anti-glaucoma medications (AGM), and axial length (AL) changes were compared, and the incidence of postoperative complications was thoroughly evaluated. The Cochran chi-square test was used to examine the heterogeneity of the evaluation results. According to the inclusion and exclusion criteria, 20 studies included 948 glaucomatous eyes. IOP was significantly lower than before treatment (MD = 8.64, 95 CI: 5.75-11.53; Z = 5.86, P < 0.0001), while ACD increased significantly (MD = -1.38, 95 percent CI: -1.74-1.02; Z = 7.49, P < 0.0001). The corneal endothelial cell counts were homogeneous (MD = 225.08, 95% CI: -64.17 to -514.33; Z = 1.53, P = 0.20). AGM utilisation decreased (MD = 1.43, 95% CI: 0.752.12, Z = 4.09, P < 0.0001). AL decreased significantly (MD = 0.31; 95% CI: 0.09-0.54; Z = 2.71; P = 0.007). The incidence of complications remained insignificant after IOL treatment (OR = 1.05, 95% CI: 0.42 to 2.60; Z = 0.10, P = 0.92; P = 0.92). These findings indicate that IOL treatment can significantly reduce intraocular pressure, glaucoma drug use, and aqueous level (AL) in glaucoma patients while increasing the depth of the central anterior chamber. This study offers a theoretical foundation for selecting glaucoma treatment methods.

Scleral HIF-1α is a prominent regulatory candidate for genetic and environmental interactions in human myopia pathogenesis.

BACKGROUND: Myopia is a good model for understanding the interaction between genetics and environmental stimuli. Here we dissect the biological processes affecting myopia progression. METHODS: Human Genetic Analyses: (1) gene set analysis (GSA) of new genome wide association study (GWAS) data for 593 individuals with high myopia (refraction ≤ -6 diopters [D]); (2) over-representation analysis (ORA) of 196 genes with de novo mutations, identified by whole genome sequencing of 45 high-myopia trio families, and (3) ORA of 284 previously reported myopia risk genes. Contributions of the enriched signaling pathways in mediating the genetic and environmental interactions during myopia development were investigated in vivo and in vitro. RESULTS: All three genetic analyses showed significant enrichment of four KEGG signaling pathways, including amphetamine addiction, extracellular matrix (ECM) receptor interaction, neuroactive ligand-receptor interaction, and regulation of actin cytoskeleton pathways. In individuals with extremely high myopia (refraction ≤ -10 D), the GSA of GWAS data revealed significant enrichment of the HIF-1α signaling pathway. Using human scleral fibroblasts, silencing the key nodal genes within protein-protein interaction networks for the enriched pathways antagonized the hypoxia-induced increase in myofibroblast transdifferentiation. In mice, scleral HIF-1α downregulation led to hyperopia, whereas upregulation resulted in myopia. In human subjects, near work, a risk factor for myopia, significantly decreased choroidal blood perfusion, which might cause scleral hypoxia. INTERPRETATION: Our study implicated the HIF-1α signaling pathway in promoting human myopia through mediating interactions between genetic and environmental factors. FUNDING: National Natural Science Foundation of China grants; Natural Science Foundation of Zhejiang Province.

Gaussian mixture model-hidden Markov model based nonlinear equalizer for optical fiber transmission.

The demand for high speed data transmission has increased rapidly over the past few years, leading to the development of the data center concept. As is known, nonlinear effects in optical fiber transmission systems are becoming significant with the development of transmission speed. Since it is difficult for conventional DSP algorithms to accurately capture these nonlinear distortions, many machine learning-based equalizers have been proposed. However, previous corresponding experiments mainly focused on achieving low BER while the computational complexity is much greater. In this paper, we propose a Gaussian mixture model (GMM)-hidden Markov model (HMM) based nonlinear equalizer, which utilizes the received signals' statistical characteristics as the priori information to reduce the computational complexity. The BER performance of the GMM-HMM based equalizer has been evaluated in a PAM-4 modulated VCSEL-MMF optical interconnect link, which shows an excellent capability of mitigating nonlinear distortions. In addition, the computational complexity of GMM-HMM based equalizer is about 73% lower than that of recurrent neural networks (RNN) based methods with similar BER performance.

Scleral hypoxia is a target for myopia control.

Worldwide, myopia is the leading cause of visual impairment. It results from inappropriate extension of the ocular axis and concomitant declines in scleral strength and thickness caused by extracellular matrix (ECM) remodeling. However, the identities of the initiators and signaling pathways that induce scleral ECM remodeling in myopia are unknown. Here, we used single-cell RNA-sequencing to identify pathways activated in the sclera during myopia development. We found that the hypoxia-signaling, the eIF2-signaling, and mTOR-signaling pathways were activated in murine myopic sclera. Consistent with the role of hypoxic pathways in mouse model of myopia, nearly one third of human myopia risk genes from the genome-wide association study and linkage analyses interact with genes in the hypoxia-inducible factor-1α (HIF-1α)-signaling pathway. Furthermore, experimental myopia selectively induced HIF-1α up-regulation in the myopic sclera of both mice and guinea pigs. Additionally, hypoxia exposure (5% O2) promoted myofibroblast transdifferentiation with down-regulation of type I collagen in human scleral fibroblasts. Importantly, the antihypoxia drugs salidroside and formononetin down-regulated HIF-1α expression as well as the phosphorylation levels of eIF2α and mTOR, slowing experimental myopia progression without affecting normal ocular growth in guinea pigs. Furthermore, eIF2α phosphorylation inhibition suppressed experimental myopia, whereas mTOR phosphorylation induced myopia in normal mice. Collectively, these findings defined an essential role of hypoxia in scleral ECM remodeling and myopia development, suggesting a therapeutic approach to control myopia by ameliorating hypoxia.

Cause and Effect Relationship between Changes in Scleral Matrix Metallopeptidase-2 Expression and Myopia Development in Mice.

Myopia is a serious sight-compromising condition in which decreases in scleral biomechanical strength are associated with protease up-regulation resulting in thinning of its collagenous framework and changes in the extracellular matrix composition. Matrix metallopeptidase (MMP)-2 is one of the known proteases mediating these alterations. To determine whether MMP-2 up-regulation precedes myopia development, the direct effects of gain and loss in Mmp2 gene function were evaluated on refractive development and form deprivation myopia in mice. Four weeks after injecting an adeno-associated virus serotype 8 packaged Mmp2 overexpression vector (AAV8-Mmp2), scleral MMP-2 up-regulation was accompanied by significant myopia in a normal visual environment. In contrast, AAV8 packaging with shRNA targeting Mmp2 inhibited rises in MMP-2 expression induced by form deprivation by 54% and reduced myopia development by 23% compared with eyes injected with an irrelevant scrambled sequence. Because opposing changes in MMP-2 protein expression levels had corresponding effects on myopia progression, up-regulation of this protease contributes to inducing this condition. This notion of a cause-and-effect relationship between MMP-2 up-regulation and myopia development is supported by showing that form-deprived myopia development was attenuated by 27% in fibroblast-specific Mmp2 deletion (S100a4creMmp2fl/fl) mice relative to Cre-negative littermates (Mmp2fl/fl). Therefore, MMP-2 is a potential drug target for inhibiting myopia progression.

The economic impact of SARS in Beijing, China.

OBJECTIVE: To document the impact of the severe acute respiratory syndrome (SARS) outbreak in Beijing on indicators of social and economic activity. METHODS: Associations between time series of daily and monthly SARS cases and deaths and volume of public train, airplane and cargo transport, tourism, household consumption patterns and gross domestic product growth in Beijing were investigated using the cross-correlation function. RESULTS: Significant correlation coefficients were found for all indicators except wholesale accounts and expenditures on necessities, with the most significant correlations occurring with a delay of 1 day to 1 month. CONCLUSIONS: Especially leisure activities, local and international transport and tourism were affected by SARS particularly in May 2003. Much of this consumption was merely postponed; but irrecoverable losses to the tourist sector alone were estimated at about US$ 1.4 bn, or 300 times the cost of treatment for SARS cases in Beijing.