Objective quantification of posterior capsule opacification using swept-source anterior segment optical coherence tomography.

PURPOSE: To objectively quantify posterior capsule opacification (PCO) using swept-source anterior segment optical coherence tomography (SS-ASOCT) in pseudophakic eyes. SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Prospective cross-sectional study. METHODS: One hundred and eighty eyes with PCO (37 multifocal intraocular lenses [MfIOLs] and 143 monofocal intraocular lenses [MoIOLs]) were enrolled. The PCO Irregular Degree (PID), defined to evaluate the surface irregularity of PCO, the average and maximum thickness of PCO (AT-PCO, MT-PCO) were applied to quantify PCO based on SS-ASOCT (CASIA2) images. Corrected distance visual acuity (CDVA), high order aberrations (HOAs), modulation transfer function (MTF) and Strehl ratio were recorded. The associations between SS-ASOCT parameters and visual function parameters were assessed by Spearman's correlation analysis. RESULTS: PID, AT-PCO and MT-PCO showed significant correlations with CDVA, Strehl ratio and HOAs (CDVA: r = 0.702, 0.741, 0.736; Strehl ratio: r = -0.746, -0.719, -0.740; HOAs: r = 0.762, 0.734, 0.752). The correlations of these three parameters with Strehl ratio and HOAs were significantly higher than those of clinical PCO grading with Strehl ratio and HOAs (all P < 0.05). Particularly, PID demonstrated notable correlations with Strehl ratio and HOAs. In addition, patients with MfIOLs presented worse Strehl ratio and HOAs than those with MoIOLs after matching age, PID, AT-PCO and MT-PCO. CONCLUSIONS: This study provides a novel method for objectively quantifying PCO using successive cross-sectional SS-ASOCT images. AT-PCO, MT-PCO and PID are presented as new indicators to document PCO severity, with PID offering a unique perspective by considering the irregularity aspect of PCO.

Nanoparticles for inducing Gaucher disease-like damage in cancer cells.

Nutrient avidity is one of the most distinctive features of tumours. However, nutrient deprivation has yielded limited clinical benefits. In Gaucher disease, an inherited metabolic disorder, cells produce cholesteryl-glucoside which accumulates in lysosomes and causes cell damage. Here we develop a nanoparticle (AbCholB) to emulate natural-lipoprotein-carried cholesterol and initiate Gaucher disease-like damage in cancer cells. AbCholB is composed of a phenylboronic-acid-modified cholesterol (CholB) and albumin. Cancer cells uptake the nanoparticles into lysosomes, where CholB reacts with glucose and generates a cholesteryl-glucoside-like structure that resists degradation and aggregates into microscale crystals, causing Gaucher disease-like damage in a glucose-dependent manner. In addition, the nutrient-sensing function of mTOR is suppressed. It is observed that normal cells escape severe damage due to their inferior ability to compete for nutrients compared with cancer cells. This work provides a bioinspired strategy to selectively impede the metabolic action of cancer cells by taking advantage of their nutrient avidity.

Refractive stability and timing of spectacle prescription following cataract surgery in myopic eyes.

PURPOSE: To investigate the post-operative refractive stabilisation time and provide evidence for the optimal timing of a spectacle prescription in myopic post-cataract surgery patients. METHODS: A total of 116 consecutive myopic cataract patients were recruited from the Zhongshan Ophthalmic Center in this prospective study. Post-operative subjective refraction was assessed after 1 week and 1 month (4-6 weeks), with the interval for the new spectacle acquisition being recorded. Visual Function Index-14 (VF-14) questionnaires were used to assess the vision-related quality of life. RESULTS: There was no significant difference in spherical (p = 0.33), cylindrical (p = 0.65) or spherical equivalent refractions (p = 0.45) obtained 1 week and 1 month post-operatively, indicating that subjects achieved refractive stability within 1 week. In subgroups having differing age and axial lengths, there were also no significant differences between the 1 week and 1 month findings. The spherical equivalent refractive shift between 1 week and 1 month was significantly correlated with the post-operative prediction error (R = 0.35; p < 0.001). Only five (4.3%) out of 116 patients obtained new spectacles 1 week post-surgery. The VF-14 values improved from 85.77 ± 7.24 to 90.45 ± 5.39 after acquiring new spectacles (p < 0.01). CONCLUSIONS: The stabilisation of subjective refraction occurred within 1 week in myopic cataract patients. Shortening the interval before prescribing a new spectacle prescription is recommended for myopic patients following cataract surgery to improve their vision-related quality of life.

Exploration of NPC2 as a Potential Biomarker for Immunotherapy Using RNA-seq and Protein Data - A New Hypothesis.

INTRODUCTION: NPC2 is well known as a player for cholesterol transport. However, the biological role of NPC2 in cancer development and therapy is far from clear. METHODS: Here, we explore the potential role of NPC2 in prognosis and immunotherapy across multiple cancer types by integrating RNA-seq data from TCGA and GTEx, protein data from CPTAC, and multiple web analysis databases. RESULTS: Expression depiction between tumour and normal tissues indicated that NPC2 is overexpressed in the majority of the most common cancer types, including glioblastoma and pancreatic cancer, two cancers mostly difficult to diagnose and treat. CONCLUSION: Cancer stemness in glioblastoma is negatively associated with NPC2 level. NPC2 expression is positively correlated with immune cell infiltration and the expression of several immune checkpoints. IDH1 mutation in GBM is negatively correlated with NPC2 level, while a positive correlation has been found between TP53 mutation and NPC2 expression in pancreatic cancer. NPC2 is also correlated with levels of serum biomarkers used for diagnosis of pancreatic cancer.

A Atractylodes lancea polysaccharide inhibits metastasis of human osteosarcoma U-2 OS cells by blocking sialyl Lewis X (sLex )/E-selectin binding.

In this study, a new water and alkaline-soluble polysaccharide (ALP), with an average molecular weight of 6.63 × 104  Da, was successfully purified from the rhizomes of Atractylodes lancea. GC analysis demonstrated that ALP was a kind of glucan. The effect of the ALP on the interaction between E-selectin and sialyl Lewis X (sLex ) was examined in human osteosarcoma U-2 OS cells. It was obvious that the expression of sLex antigen on the surface of U-2 OS cells was visible under fluorescence microscopy. The addition of ALP (0.5, 1 and 2 mg/mL) resulted in a marked inhibition on the adhesion, migration and invasion of U-2 OS cells to human umbilical vein endothelial cells (HUVECs), which was achieved by the decreased sLex expression on U-2 OS cells. Additionally, the induction of apoptosis can be observed in U-2 OS cells following ALP treatment using TUNEL staining and Annexin V-FITC/PI double-staining analysis on flow cytometry. In conclusion, these results indicated that ALP exerted anti-metastatic activity towards osteosarcoma cells via inhibition of sLex /E-selectin binding, which suggested that ALP could be a potent agent for human osteosarcoma intervention.

Single-Cell Multi-Omics and Its Prospective Application in Cancer Biology.

In recent years, the emergence of single-cell omics technologies, which can profile genomics, transcriptomics, epigenomics, and proteomics, has provided unprecedented insights into characteristics of cancer, enabling higher resolution and accuracy to decipher the cellular and molecular mechanisms relating to tumorigenesis, evolution, metastasis, and immune responses. Single-cell multi-omics technologies, which are developed based on the combination of multiple single-cell mono-omics technologies, can simultaneously analyze RNA expression, single nucleotide polymorphism, epigenetic modification, or protein abundance, enabling the in-depth understanding of gene expression regulatory mechanisms. In this review, the state-of-the-art single-cell multi-omics technologies are summarized and the prospects of their application in cancer biology are discussed.

Simultaneous Profiling of mRNA Transcriptome and DNA Methylome from a Single Cell.

Single-cell transcriptome and single-cell methylome analysis have successfully revealed the heterogeneity in transcriptome and DNA methylome between single cells, and have become powerful tools to understand the dynamics of transcriptome and DNA methylome during the complicated biological processes, such as differentiation and carcinogenesis.Inspired by the success of using these single-cell -omics methods to understand the regulation of a particular "-ome," more interests have been put on elucidating the regulatory relationship among multiple-omics at single-cell resolution. The simultaneous profiling of multiple-omics from the same single cell would provide us the ultimate power to understand the relationship among different "-omes," but this idea is not materialized for decades due to difficulties to assay extremely tiny amount of DNA or RNA in a single cell.To address this technical challenge, we have recently developed a novel method named scMT-seq that can simultaneously profile both DNA methylome and RNA transcriptome from the same cell. This method enabled us to measure, from a single cell, the DNA methylation status of the most informative 0.5-1 million CpG sites and mRNA level of 10,000 genes, of which 3200 genes can be further analyzed with both promoter DNA methylation and RNA transcription. Using the scMT-seq data, we have successfully shown the regulatory relationship between DNA methylation and transcriptional level in a single dorsal root ganglion neuron (Hu et al., Genome Biol 17:88, 2016). We believe the scMT-seq would be a powerful technique to uncover the regulatory mechanism between transcription and DNA methylation, and would be of wide interest beyond the epigenetics community.

The Preliminary Experiences with Three-Dimensional Heads-Up Display Viewing System for Vitreoretinal Surgery under Various Status.

Statement: The current article has not been published elsewhere and has not been submitted simultaneously for publication elsewhere. PURPOSE: To investigate the preliminary use of three-dimensional (3D) heads-up display (HUD) viewing system for vitreoretinal surgery under various status. MATERIALS AND METHODS: Nonrandomized case-control study. Consecutive cases to have vitreoretinal surgery under various status were prospectively recruited. Twenty-five-gauge vitrectomy platform and 3D viewing system were used. Main outcomes included: luminous emittance (lux) of endoillumination pipe, surgical duration, the surgeon and residents' preference and ergonomics. Consecutive patients to have vitreoretinal surgery with the conventional viewing system were recruited as control group following the same inclusion and exclusion criteria and underwent surgeries by the same surgeon with the same microscope and vitrectomy platform. RESULTS: Thirty-one patients (31 eyes; Group Study) and twenty-eight patients (28 eyes; Group Control) were included; without significantly statistical difference in terms of age, gender, main diagnosis, surgical duration, and difficulty rating between both groups (all P > 0.05). Lower endoillumination intensity was needed in Group Study than that in Group Control (10% vs. 35%; 598.7 ± 5.4 vs. 1913.0 ± 12.9 lux, P < 0.001). The surgeon and residents expressed overwhelming preference with the 3D system in both groups. Improved ergonomic was rated in Group Study (4.4 ± 0.8 vs. 3.2 ± 1.0, P < 0.001). Some intraoperative difficulties and discomforts appeared to the surgeon and assistants when using the 3D viewing system. CONCLUSION: Vitreoretinal surgery under various status can be well finished with the HUD platform by novice at the system. Main benefits included lower endoillumination intensity, enhanced users' preference, and improved ergonomics. Some further refinements of the system are expected.

Knockdown of Long Noncoding RNA TUG1 Inhibits the Proliferation and Cellular Invasion of Osteosarcoma Cells by Sponging miR-153.

Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) has been confirmed to be involved in the progression of various cancers; however, its mechanism of action in osteosarcoma has not been well addressed. In our study, TUG1 was overexpressed and miR-153 was downregulated in osteosarcoma tissues and cell lines. A loss-of-function assay showed that TUG1 knockdown suppressed the viability, colony formation, and invasion of osteosarcoma cells in vitro. Moreover, TUG1 was confirmed to be an miR-153 sponge. Ectopic expression of TUG1 reversed the inhibitory effect of miR-153 on the proliferation and invasion of osteosarcoma cells. Further transplantation experiments proved the carcinogenesis of TUG1 in osteosarcoma in vivo. Collectively, our study elucidated that TUG1 contributes to the development of osteosarcoma by sponging miR-153. These findings may provide a novel lncRNA-targeted therapy for patients with osteosarcoma.

Knockdown of Long Non-Coding RNA NEAT1 Inhibits Proliferation and Invasion and Induces Apoptosis of Osteosarcoma by Inhibiting miR-194 Expression.

PURPOSE: Long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has been implicated as an oncogene in the development and progression of osteosarcoma. This study aims to explore the mechanism of NEAT1 in osteosarcoma. MATERIALS AND METHODS: Expressions of NEAT1 and miR-194 in osteosarcoma tissues and cells were detected by quantitative real-time PCR. The effects of NEAT1 knockdown or miR-194 overexpression on cell proliferation, invasion, and apoptosis were determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) assay, transwell invasive assay, and flow cytometry analysis, respectively. Luciferase reporter assay was performed to observe the possible interaction between NEAT1 and miR-194. RESULTS: NEAT1 was upregulated and miR-194 was downregulated in osteosarcoma tissues and cells. Knockdown of NEAT1 or overexpression of miR-194 suppressed proliferation and invasion and induced apoptosis of osteosarcoma cells in vitro. Luciferase reporter assay validated that NEAT1 could interact with miR-194 and negatively modulated its expression. Furthermore, inhibition of miR-194 reversed the suppression of proliferation and invasion and the promotion of apoptosis induced by NEAT1 depletion in osteosarcoma cells. CONCLUSION: Knockdown of NEAT1 suppressed proliferation and invasion and induced apoptosis in osteosarcoma cells by inhibiting miR-194 expression.

MicroRNA-216b/Beclin 1 axis regulates autophagy and apoptosis in human Tenon's capsule fibroblasts upon hydroxycamptothecin exposure.

Proliferation and fibrosis of human Tenon's fibroblasts (HTFs) have significantly challenged the outcome of glaucoma filtration surgery. Hydroxycamptothecin (HCPT) is considered as a potential chemical to overcome this issue as it was previously shown that HCPT inhibited cell proliferation and induced apoptosis in fibroblasts. Here, we further dissected the molecular pathway, through which the HCPT inhibit the proliferation of HTFs. We showed that HCPT induced significant autophagy as well as apoptosis, two self-destructive processes, and down-regulated the expression of miR-216b in HTFs. Overexpression of miR-216b in HTFs suppressed the autophagy and apoptosis induced by HCPT, whereas silence of miR-216b led to effects that were similar to those caused by the treatment with HCPT. Further, we showed that miR-216b could directly target a specific fragment in the 3' untranslated region of Beclin 1 as demonstrated by luciferase assay, and consequently decreased the expression of Beclin 1. Consistently, knocking down Beclin 1 significantly decreased HCPT-triggered autophagy and apoptosis, and increased the viability of HTFs treated with HCPT, thus implicating that Beclin 1 functions as a pro-apoptotic molecule in this circumstance. Altogether, we concluded that miR-216b regulated both autophagy and apoptosis by modulating Beclin 1 in HTFs treated with HCPT. We also demonstrated that HCPT-induced autophagy is one of the agent's anti-proliferative effects.