Associations between corneal curvature and other anterior segment biometrics in young myopic adults.

To investigate the associations between corneal curvature (CC) and other anterior segment biometrics in young myopic adults. In this retrospective multi-center study, 7893 young myopic adults were included. CC and other anterior segment biometrics were measured by Scheimpflug imaging (Pentacam). CC was defined as SimK at central 3 mm area, and other anterior segment biometrics included white-to-white corneal diameter (WTW), central corneal thickness (CCT), corneal volume (CV) at 3 mm, 5 mm, and 7 mm area, anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), anterior corneal eccentricity (ACE) and asphericity (ACAP), posterior corneal eccentricity (PCE) and asphericity (PCAP), anterior chamber depth (ACD), and anterior chamber volume (ACV). Univariate regression analyses were used to assess the associations between CC and other anterior segment biometrics, and multivariate regression analyses were further performed to adjusted for age, gender and spherical equivalent. CC was higher in patients of female gender and higher myopia (all P < 0.05). Eyes in higher CC quartiles had lower WTW, thinner CCT, lower CV at 3 mm and 5 mm, lower ACD, and lower ACV (all P < 0.001), but had larger ACA, larger PCA, less PCE and less PCAP (all P < 0.001), compared to eyes in lower CC quartiles. The trends of CV at 7 mm, ACE and ACAP were inconsistent in different CC quartiles. After adjusting for age, gender and spherical equivalent with multivariate linear regression, CC was positively correlated to CV at 7 mm (ßs = 0.069), ACA (ßs = 0.194), PCA (ßs = 0.187), ACE (ßs = 0.072), PCAP (ßs = 0.087), and ACD (ßs = 0.027) (all P < 0.05), but was negatively correlated to WTW (ßs = - 0.432), CCT (ßs = - 0.087), CV-3 mm (ßs = - 0.066), ACAP (ßs = - 0.043), PCE (ßs = - 0.062), and ACV (ßs = - 0.188) (all P < 0.05). CC was associated with most of the other anterior segment biometrics in young myopic adults. These associations are important for better understanding of the interactions between different anterior segment structures in young myopic patients, and are also useful for the exploration of the pathogenesis of myopia.

Ocular biometrics in eyes with different white-to-white corneal diameter in young myopic adults.

The interactions between white-to-white corneal diameter (WTW) and other ocular biometrics are important for planning of refractive surgery and understanding of ocular structural changes in myopia, but such interactions are rarely investigated in young myopic adults. This is a retrospective study involving 7893 young myopic adults from five centers. WTW and other ocular biometrics were measured by Pentacam. The ocular biometrics included anterior corneal curvature (AK) and posterior corneal curvature (PK), central corneal thickness (CCT) and corneal volume (CV), anterior and corneal eccentricity and asphericity, anterior corneal astigmatism (ACA) and posterior corneal astigmatism, anterior chamber depth (ACD), and anterior chamber volume (ACV). The ocular biometrics were compared among eyes of different WTW quartiles. Multivariate linear regression was used to assess the linear associations between WTW and other ocular biometrics adjusting for age, gender and spherical equivalent. In eyes of different WTW quartiles, other ocular biometrics were also significantly different (all P < 0.05). After adjusting for age, gender and spherical equivalent, WTW was positively correlated to AK (ß = 0.26 to 0.29), ACA (ß = 0.13), anterior corneal asphericity (ß = 0.05), PK (ß = 0.33 to 0.34), posterior corneal asphericity (ß = 0.13), ACD (ß = 0.29), and ACV (ß = 40.69), and was negatively correlated to CCT (ß = - 6.83), CV (ß = - 0.06 to - 0.78), anterior corneal eccentricity (ß = - 0.035), and posterior corneal eccentricity (ß = - 0.14) (all P < 0.001). In conclusion, we found that in young myopic adults, larger WTW was associated with thinner corneal thickness, flatter corneal curvature, more anterior corneal toricity, less corneal eccentricity and asphericity, and broader anterior chamber. Our findings may fill in the gap of literature, and help us better understand how the anterior segment structures interact with the WTW in myopia.

The influence of iris -ciliary angle (ICA) on the vault after implantation of V4c implantable collamer lens: a chain mediation model of ICL haptic related factors.

BACKGROUND: This study aims to identify the relationship between iris -ciliary angle (ICA) and the vault. Additionally, we also seek to investigate the chain mediating effects of the ICL haptic related factors on this relationship. METHODS: The participants were categorized into three groups according to the ICA value as follows: low ICA group (< 35°); moderate ICA group (35°-70°); high ICA group (> 70°). We compared the preoperative ocular characteristics and postoperative examinations among the three groups. Multiple variable stepwise regression was performed to establish the vault prediction formula. The Process V4.0 in SPSS and Hayes's PROCESS model 6 was conducted to further elucidate the mediating effects of the final tip point of ICL haptic and the ICL arc-lens arc on the relationship between the ICA and vault. RESULTS: There was a significant difference in the positions of the ICL haptic among three ICA groups. The regression vault equation was Vault = 679.42-7.26*TCA + 192.30*ACD-196.37*CLR + 73.21* STS(horizontal).A significant negative correlation was found between the ICA and vault (P < 0.01).The chain mediation model revealed that the final tip point of ICL haptic and the ICL arc-Lens arc were sequential mediators between ICA and vault (effect = -1.63, 95% CI = -2.72--0.73). CONCLUSION: The ICA was associated with vault via the mediation effect of the final tip point of the ICL haptic and the ICL arc -lens arc. Assessment of ICL haptic related parameters adds significant information to interpret the vault after surgery.

TRPM8 promotes hepatocellular carcinoma progression by inducing SNORA55 mediated nuclear-mitochondrial communication.

Transient receptor potential melastatin 8 (TRPM8) play crucial roles in solid tumors such as prostate and breast cancers. But the role of TRPM8 in hepatocellular carcinoma (HCC) and its underlying molecular mechanisms remain largely unknown. In this study, the functional roles of TRPM8 in HCC were systematically investigated for the first time. It was found that the expression level of TRPM8 was significantly upregulated in HCC, which was positively correlated with the worse clinicopathological characteristics. Functional studies revealed that pharmacological inhibition or genetic downregulation of TRPM8 ameliorated hepatocarcinogenesis in vitro and in vivo. Mechanistically, the oncogenic role of TRPM8 in HCC was at least partially achieved by affecting mitochondrial function. TRPM8 could modulate the expression of nucleolar relative molecule-small nucleolar RNA, H/ACA box 55 (SNORA55) by inducing transformation of chromatin structure and histone modification type. These data suggest that as a bridge molecule in TRPM8-triggered HCC, SNORA55 can migrate from nucleus to mitochondria and exert oncogenic role by affecting mitochondria function through targeting ATP5A1 and ATP5B. Herein, we uncovered the potent oncogenic role of TRPM8 in HCC by inducing nuclear and mitochondrial dysfunction in a SNORA55 dependent manner, and provided a potential therapeutic target for HCC.

Characteristics and factors associated with the position of the haptic after ICL V4C implantation.

PURPOSE: To assess the position of implantable collamer lens (ICL) haptic after ICL V4C implantation using standardized panoramic ultrasound bimicroscopy (UBM), to analyze its characteristics, associated factors, and the relationship with the clinical vault quantitatively. SETTING: Hankou Aier Eye Hospital, Wuhan, Hubei, China. DESIGN: Cross-sectional study. METHODS: 167 subjects (323 eyes) implanted with ICL V4C who had a 3-month follow-up with UBM examination were included in this study. The relative position of ICL to the adjacent structure and ICL haptic-related parameters (the final tip point of ICL haptic [ftICL haptic], measured from the scleral spur to the final tip of the ICL haptic, the posterior of the ICL to ICL haptic [ICL arc], measured from the posterior surface of the ICL to the ICL haptic plane, and the height of the crystalline lens from the ICL haptic (lens arc), measured from the anterior surface of the crystalline lens to the ICL haptic plane and other parameters), were estimated on the UBM image. Eyes were divided into 3 subgroups according to the ftICL haptic (Group 1: ≤0.5 mm; Group 2: 0.5 to 1.0 mm; and Group 3:≥1.0 mm, respectively), and the factors associated with the ICL haptic-related parameters and their impact on the clinical vault were evaluated. RESULTS: The haptics could be imaged in the ciliary sulcus, on the ciliary body, and under the ciliary body in 629 (48.7%), 525 (40.6%), and 138 (10.7%) eyes, respectively. The ftICL haptic and the summation of ICL arc and lens arc showed a correlation with the clinical vault ( r = -0.34, P = .00; r = 0.87, P = .00). When the ftICL haptic results were divided into 3 groups, the percentage of eyes that exhibited clinical vault >750 µm were lowest in Group 3. Multivariate regression analysis showed spherical equivalent, white-to-white (WTW), anterior chamber volume (ACV) and iris-ciliary angle (ICA); the difference between the implanted ICL size and horizontal sulcus-to-sulcus (ICL size-STS) were associated with the ftICL haptic. The IOP, WTW, ACV, and the ICL size-STS were significantly associated with ICL arc, while the ICA and lens rise were associated with lens arc. CONCLUSIONS: The position of ICL haptic was associated with the clinical vault. Its quantitative evaluation may provide valuable information to help clinicians to select the best ICL size before surgery and understand the formation of clinical vault after surgery.

Radiotherapy Side Effects: Comprehensive Proteomic Study Unraveled Neural Stem Cell Degenerative Differentiation upon Ionizing Radiation.

Cranial radiation therapy is one of the most effective treatments for childhood brain cancers. Despite the ameliorated survival rate of juvenile patients, radiation exposure-induced brain neurogenic region injury could markedly impair patients' cognitive functions and even their quality of life. Determining the mechanism underlying neural stem cells (NSCs) response to irradiation stress is a crucial therapeutic strategy for cognitive impairment. The present study demonstrated that X-ray irradiation arrested NSCs' cell cycle and impacted cell differentiation. To further characterize irradiation-induced molecular alterations in NSCs, two-dimensional high-resolution mass spectrometry-based quantitative proteomics analyses were conducted to explore the mechanism underlying ionizing radiation's influence on stem cell differentiation. We observed that ionizing radiation suppressed intracellular protein transport, neuron projection development, etc., particularly in differentiated cells. Redox proteomics was performed for the quantification of cysteine thiol modifications in order to profile the oxidation-reduction status of proteins in stem cells that underwent ionizing radiation treatment. Via conjoint screening of protein expression abundance and redox status datasets, several significantly expressed and oxidized proteins were identified in differentiating NSCs subjected to X-ray irradiation. Among these proteins, succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial (sdha) and the acyl carrier protein, mitochondrial (Ndufab1) were highly related to neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and Huntington's disease, illustrating the dual-character of NSCs in cell differentiation: following exposure to ionizing radiation, the normal differentiation of NSCs was compromised, and the upregulated oxidized proteins implied a degenerative differentiation trajectory. These findings could be integrated into research on neurodegenerative diseases and future preventive strategies.

Targeted Multifunctional Nanoplatform for Imaging-Guided Precision Diagnosis and Photothermal/Photodynamic Therapy of Orthotopic Hepatocellular Carcinoma.

Background: Effective theranostic of hepatocellular carcinoma (HCC) in an early-stage is imminently demanded to improve its poor prognosis. Combination of the near-infrared (NIR) photoacoustic imaging (PAI) and fluorescence imaging (FLI) can provide high temporospatial resolution, outstanding optical contrast, and deep penetration and thus is promising for accurate and sensitive HCC diagnosis. Methods: A versatile CXCR4-targeted Indocyanine green (ICG)/Platinum (Pt)-doped polydopamine melanin-mimic nanoparticle (designated ICG/Pt@PDA-CXCR4, referred to as IPP-c) is synthesized as an HCC-specific contrast agent for high-resolution precise diagnostic PAI/FLI and optical imaging-guided targeted photothermal therapy (PTT)/photodynamic therapy (PDT) of orthotopic small hepatocellular carcinoma (SHCC). Results: The multifunctional targeted nanoparticle yields superior HCC specificity, high imaging contrast in both PAI and FLI, good stability, reliable biocompatibility, effective singlet oxygen generation and superior photothermal conversion efficiency (PCE, 58.7%) upon 808-nm laser irradiation. The targeting ability of IPP-c was validated in in vitro experiments on selectively killing the CXCR4-overexpressing HCC cells. Moreover, we test the efficient dual-modal optical precision diagnosis properties of IPP-c via in vivo experiments on targeted particle accumulation in an early-stage SHCC mouse model (tumor diameter about 1.2 mm). Then, under the guidance of real-time optical imaging, effective and mini-invasive PTT/PDT of orthotopic SHCCs were demonstrated without damaging adjacent liver tissues or other major organs. Conclusion: This study presented a multifunctional CXCR4-targeted nanoparticle to conduct effective and mini-invasive phototherapeutics of orthotopic SHCCs via the real-time quantitative guidance by optical imaging, which provided a new perception for building a versatile targeted nanoplatform for phototheranostics of early-stage HCC.

Accurate prediction of microvascular invasion occurrence and effective prognostic estimation for patients with hepatocellular carcinoma after radical surgical treatment.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide, with an overall 5-year survival rate of less than 18%, which may be related to tumor microvascular invasion (MVI). This study aimed to compare the clinical prognosis of HCC patients with or without MVI after radical surgical treatment, and further analyze the preoperative risk factors related to MVI to promote the development of a new treatment strategy for HCC. METHODS: According to the postoperative pathological diagnosis of MVI, 160 study patients undergoing radical hepatectomy were divided into an MVI-negative group (n = 68) and an MVI-positive group (n = 92). The clinical outcomes and prognosis were compared between the two groups, and then the parameters were analyzed by multivariate logistic regression to construct an MVI prediction model. Then, the practicability and validity of the model were evaluated, and the clinical prognosis of different MVI risk groups was subsequently compared. RESULT: There were no significant differences between the MVI-negative and MVI-positive groups in clinical baseline, hematological, or imaging data. Additionally, the clinical outcome comparison between the two groups presented no significant differences except for the pathological grading (P = 0.002) and survival and recurrence rates after surgery (P < 0.001). The MVI prediction model, based on preoperative AFP, tumor diameter, and TNM stage, presented superior predictive efficacy (AUC = 0.7997) and good practicability (high H-L goodness of fit, P = 0.231). Compared with the MVI high-risk group, the patients in the MVI low-risk group had a higher survival rate (P = 0.002) and a lower recurrence rate (P = 0.004). CONCLUSION: MVI is an independent risk factor for a poor prognosis after radical resection of HCC. The MVI prediction model, consisting of AFP, tumor diameter, and TNM stage, exhibits superior predictive efficacy and strong clinical practicability for MVI prediction and prognostication, which provides a new therapeutic strategy for the standardized treatment of HCC patients.

Identification of the Immune Subtype of Hepatocellular Carcinoma for the Prediction of Disease-Free Survival Time and Prevention of Recurrence by Integrated Analysis of Bulk- and Single-Cell RNA Sequencing Data.

Background: The main factors affecting the long-term prognosis of hepatocellular carcinoma (HCC) patients undergoing radical surgery are recurrence and metastasis. However, the methods for predicting disease-free survival (DFS) time and preventing postoperative recurrence of HCC are still very limited. Methods: In this study, immune cell abundances in HCC samples were analyzed by single-sample gene set enrichment analysis (ssGSEA), while the prognostic values of immune cells for DFS time prediction were evaluated by the least absolute shrinkage and selection operator (LASSO) and subsequent univariate and multivariate Cox analyses. Next, a risk score was constructed based on the most prognostic immune cells and their corresponding coefficients. Interactions among prognostic immune cells and the specific targets for the prevention of recurrence were further identified by single-cell RNA (scRNA) sequencing data and CellMiner. Results: A novel efficient T cell risk score (TCRS) was constructed based on data from the three most prognostic immune cell types (effector memory CD8 T cells, regulatory T cells and follicular helper T cells) for identifying an immune subtype of HCC patients with longer DFS times and inflammatory immune characteristics. Functional differences between the high- and low-score groups separated by TCRS were clarified, and the cell-cell communication among these immune cells was elucidated. Finally, fifteen hub genes that may be potential therapeutic targets for the prevention of recurrence were identified. Conclusions: We constructed and verified a useful model for the prediction of DFS time of HCC after surgery. In addition, fifteen hub genes were identified as candidates for the prevention of recurrence, and a preliminarily investigation of potential drugs targeting these hub genes was carried out.

High-Efficiency Differentiation of Human Pluripotent Stem Cells to Hematopoietic Stem/Progenitor Cells in Random Positioning Machine Bioreactors.

Human pluripotent stem cells (PSCs) are known to differentiate into almost all the blood lineage cells in vitro and hold a great promise for studying human early hematopoietic development and have a huge potential in the treatment of hematological disorders. Although several methods of hematopoietic stem/progenitor cell (HSPC) differentiation have been developed, the HSPC yields achieved using these strategies are not yet available for clinical application. Recently, bioreactor-based devices and biochemical factors synergistically have been used to induce hematopoietic differentiation and showed a potential role in hematopoiesis. This chapter describes a protocol for using a random positioning machine bioreactor to culture human PSCs and the large-scale production of HPCs. Techniques for characterizing the differentiated cells and assessing the efficiency of hematopoietic differentiation in the bioreactor with immunostaining and flow cytometry are also presented.

Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3ß Pathway and Activating Autophagy in Gastric Cancer.

Objective: Costunolide (Cos) is a sesquiterpene lactone extracted from chicory. Although it possesses anti-tumor effects, the underlying molecular mechanism against gastric cancer cells remains unclear. This study aimed to explore the effect and potential mechanism of Cos on gastric cancer. Methods: The effect of Cos on HGC-27 and SNU-1 proliferation was detected by CCK-8 and clone formation assay. The changes in cell apoptosis were determined using Hoechst 33258 and tunel staining. The morphology of autophagy was analyzed by autophagosomes with the electron microscope and LC3-immunofluorescence with the confocal microscope. The related protein levels of the cell cycle, apoptosis, autophagy and AKT/GSK3ß pathway were determined by Western blot. The anti-tumor activity of Cos was evaluated by subcutaneously xenotransplanting HGC-27 into Balb/c nude mice. The Ki67 and P-AKT levels were examined by immunohistochemistry. Results: Cos significantly inhibited HGC-27 and SNU-1 growth and induced cell cycle arrest in the G2/M phase. Cos activated intrinsic apoptosis and autophagy through promoting cellular reactive oxygen species (ROS) levels and inhibiting the ROS-AKT/GSK3ß signaling pathway. Moreover, preincubating gastric carcinoma cells with 3-methyladenine (3-MA), a cell-autophagy inhibitor, significantly alleviated the effects of Cos in inducing cell apoptosis. Conclusion: Cos induced apoptosis of gastric carcinoma cells via promoting ROS and inhibiting AKT/GSK3ß pathway and activating pro-death cell autophagy, which may be an effective strategy to treat gastric cancer.

Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most commonly diagnosed cancers with a poor prognosis worldwide. Although the treatment of PDAC has made great progress in recent years, the therapeutic effects are still unsatisfactory. Methods. In this study, we identified differentially expressed genes (DEGs) between PDAC and normal pancreatic tissues based on four Gene Expression Omnibus (GEO) datasets (GSE15471, GSE16515, GSE28735 and GSE71729). A protein-protein interaction (PPI) network was established to evaluate the relationship between the DEGs and to screen hub genes. The expression levels of the hub genes were further validated through the Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE and Human Protein Atlas (HPA) databases, as well as the validation GEO dataset GSE62452. Additionally, the prognostic values of the hub genes were evaluated by Kaplan-Meier plotter and the validation GEO dataset GSE62452. Finally, the mechanistic roles of the most remarkable hub genes in PDAC were examined through in vitro experiments. RESULTS: We identified the following nine hub genes by performing an integrated bioinformatics analysis: COL1A1, COL1A2, FN1, ITGA2, KRT19, LCN2, MMP9, MUC1 and VCAN. All of the hub genes were significantly upregulated in PDAC tissues compared with normal pancreatic tissues. Two hub genes (FN1 and ITGA2) were associated with poor overall survival (OS) rates in PDAC patients. Finally, in vitro experiments indicated that FN1 plays vital roles in PDAC cell proliferation, colony formation, apoptosis and the cell cycle. CONCLUSIONS: In summary, we identified two hub genes that are associated with the expression and prognosis of PDAC. The oncogenic role of FN1 in PDAC was first illustrated by performing an integrated bioinformatic analysis and in vitro experiments. Our results provide a fundamental contribution for further research aimed finding novel therapeutic targets for overcoming PDAC.

An Antagonistic Peptide of Gpr1 Ameliorates LPS-Induced Depression through the Hypothalamic-Pituitary-Ovarian Axis.

Depression affects the reproductive axis at the hypothalamus and pituitary levels, which has a significant impact on female fertility. It has been reported that G protein-coupled receptor 1 (Gpr1) mRNA is expressed in both the hypothalamus and ovaries. However, it is unclear whether there is a relationship between Gpr1 and depression, and its role in ovarian function is unknown. Here, the expression of Gpr1 was recorded in the hypothalamus of normal female mice, and co-localized with gonadotrophin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF). We established a depression mouse model to evaluate the antidepressant effect of G5, an antagonistic peptide of Gpr1. The results show that an intraperitoneal injection of G5 improves depressant-like behaviors remarkably, including increased sucrose intake in the sucrose preference test and decreased immobility time in the forced swimming tests. Moreover, G5 treatment increased the release of reproductive hormone and the expression of ovarian gene caused by depression. Together, our findings reveal a link between depression and reproductive diseases through Gpr1 signaling, and suggest antagonistic peptide of Gpr1 as a potential therapeutic application for hormone-modulated depression in women.

Identification of KIF4A as a pan-cancer diagnostic and prognostic biomarker via bioinformatics analysis and validation in osteosarcoma cell lines.

BACKGROUND: Cancer is a disease of abnormal cell proliferation caused by abnormal expression of cancer-related genes. However, it is still difficult to distinguish benign and malignant lesions in many cases. KIF4A has been reported to be associated with a variety of cancer lesions. We aimed to explore whether KIF4A could be used as a biomarker of pan-cancer diagnostic. METHODS: We identified twenty-eight cell cycle-related genes that were overexpressed in no less than ten types of cancer. We determined KIF4A mRNA and protein expression in osteosarcoma (OS) cells. Furthermore, to determine the effect of KIF4A in OS, we silenced KIF4A in OS cells and detected cell viability, colony formation, invasion, migration, apoptosis and cell cycle parameters. RESULTS: KIF4A exhibited upregulated expression in eleven types of cancer. Cell cycle-related genes are extensively overexpressed in various types of cancers. KIF4A overexpression can serve as a diagnostic and prognostic marker in various cancers. Silencing KIF4A inhibited the viability, colony formation, invasion and migration and induced apoptosis and cell cycle arrest of OS cells. Our findings revealed that high expression of KIF4A could serve as a diagnostic and prognostic marker in OS cancers. CONCLUSION: KIF4A could serve as a pan-cancer diagnostic and prognostic marker. KIF4A could be used as a novel therapeutic target for OS.

Simulated Microgravity Potentiates Hematopoietic Differentiation of Human Pluripotent Stem Cells and Supports Formation of 3D Hematopoietic Cluster.

Microgravity has been shown to induces many changes in proliferation, differentiation and growth behavior of stem cells. Little is known about the effect of microgravity on hematopoietic differentiation of pluripotent stem cells (PSCs). In this study, we used the random position machine (RPM) to investigate whether simulated microgravity (SMG) allows the induction of hematopoietic stem/progenitor cell (HSPC) derived from human embryonic stem cells (hESCs) in vitro. The results showed that SMG facilitates hESCs differentiate to HSPC with more efficient induction of CD34+CD31+ hemogenic endothelium progenitors (HEPs) on day 4 and CD34+CD43+ HSPC on day 7, and these cells shows an increased generation of functional hematopoietic cells in colony-forming unit assay when compared with normal gravity (NG) conditions. Additionally, we found that SMG significantly increased the total number of cells on day 4 and day 7 which formed more 3D cell clusters. Transcriptome analysis of cells identified thousands of differentially expressed genes (DEGs) between NG and SMG. DEGs down-regulated were enriched in the axonogenesis, positive regulation of cell adhesion, cell adhesion molecule and axon guidance, while SMG resulted in the up-regulation of genes were functionally associated with DNA replication, cell cycle, PI3K-Akt signaling pathway and tumorigenesis. Interestingly, some key gene terms were enriched in SMG, like hypoxia and ECM receptor interaction. Moreover, HSPC obtained from SMG culture conditions had a robust ability of proliferation in vitro. The proliferated cells also had the ability to form erythroid, granulocyte and monocyte/macrophage colonies, and can be induced to generate macrophages and megakaryocytes. In summary, our data has shown a potent impact of microgravity on hematopoietic differentiation of hPSCs for the first time and reveals an underlying mechanism for the effect of SMG on hematopoiesis development.

A multicenter study of the distribution pattern of posterior corneal astigmatism in Chinese myopic patients having corneal refractive surgery.

Including posterior corneal astigmatism (PCA) into consideration may increase the accuracy of astigmatism correction after corneal refractive surgery. In the present study we aim to investigate the distribution pattern of PCA in a large number of myopic patients from multiple ophthalmic centers. There were 7829 eyes retrospectively included in the study. Pentacam data of the eyes were retrieved from the machine and only results with image quality labelled with 'OK' were included. Distribution of PCA was slightly positively skewed (Skewness = 0.419, Kurtosis = 0.435, KS P < 0.0001). Mean PCA was 0.34 ± 0.14 D (range: 0.00 D-0.99 D). PCA was ≥ 0.25 D in 74.91% of the eyes and was ≥ 0.50 D in 11.61% of the eyes. In 97.55% of the eyes the steep meridian of PCA was vertical (SMV). PCA magnitude was significantly higher in eyes with SMV PCA (P < 0.0001) or high manifest astigmatism (MA, P < 0.0001). There was a significant correlation between anterior corneal astigmatism (ACA) magnitude and PCA magnitude in all of the eyes (r = 0.704, P < 0.0001). There was also a trend of decreasing frequency and magnitude of SMV PCA with aging (both P < 0.0001). In conclusion, PCA is present in myopic patients having corneal refractive surgery and PCA magnitude is increased with higher MA or ACA. Consideration of the impact of PCA on laser astigmatism correction may be necessary.

The Determinant of DNA Repair Pathway Choices in Ionising Radiation-Induced DNA Double-Strand Breaks.

Ionising radiation- (IR-) induced DNA double-strand breaks (DSBs) are considered to be the deleterious DNA lesions that pose a serious threat to genomic stability. The major DNA repair pathways, including classical nonhomologous end joining, homologous recombination, single-strand annealing, and alternative end joining, play critical roles in countering and eliciting IR-induced DSBs to ensure genome integrity. If the IR-induced DNA DSBs are not repaired correctly, the residual or incorrectly repaired DSBs can result in genomic instability that is associated with certain human diseases. Although many efforts have been made in investigating the major mechanisms of IR-induced DNA DSB repair, it is still unclear what determines the choices of IR-induced DNA DSB repair pathways. In this review, we discuss how the mechanisms of IR-induced DSB repair pathway choices can operate in irradiated cells. We first briefly describe the main mechanisms of the major DNA DSB repair pathways and the related key repair proteins. Based on our understanding of the characteristics of IR-induced DNA DSBs and the regulatory mechanisms of DSB repair pathways in irradiated cells and recent advances in this field, We then highlight the main factors and associated challenges to determine the IR-induced DSB repair pathway choices. We conclude that the type and distribution of IR-induced DSBs, chromatin state, DNA-end structure, and DNA-end resection are the main determinants of the choice of the IR-induced DNA DSB repair pathway.

Clinical Prediction of Excessive Vault After Implantable Collamer Lens Implantation Using Ciliary Body Morphology.

PURPOSE: To determine the factors related to the ciliary body that are predictive of outcomes of excessive vault (> 1,000 µm) after Implantable Collamer Lens (ICL V4c; STAAR Surgical) implantation. METHODS: In this retrospective case-control study, 27 eyes of 27 patients who presented with excessive vault (> 1,000 µm) following implantation of an ICL V4c were matched in a 1:2 ratio with those who presented with a normal vault (250 to 1,000 µm) on white-to-white distance, anterior chamber depth, and ICL size. The preoperative biometric parameters and clinical outcomes were compared between the two groups. The relationship between the postoperative vault and various variables was assessed by multiple linear regression analysis. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs for excessive vault. RESULTS: The vault value 1 month postoperatively was associated with preoperative anterior chamber volume, iris-ciliary angle, and crystalline lens rise (P < .05). In the conditional regression logistic analysis, every 1° reduction in iris-ciliary angle was associated with 4% increased odds of vault greater than 1,000 µm (OR = 0.96; 95% CI = 0.93 to 0.99; P < .001) and the anteriorly positioned ciliary body was associated with an increased risk of excessive vault after ICL implantation (OR = 3.57; 95% CI = 1.67 to 7.63; P < .001). In the excessive vault group, 1 eye underwent the ICL extraction and 3 eyes had an ICL exchange for a smaller ICL. After the ICL exchange, the mean value of postoperative vault decreased from 1,525.67 ± 468.22 to 810.33 ± 254.92 µm. CONCLUSIONS: Eyes with an anteriorly positioned ciliary body were associated with a higher rate of excessive vault after ICL implantation, so the size of the ICL may need to be adjusted in these patients. Assessment of ciliary body characteristics adds significant information to the prediction of excessive vault after surgery. [J Refract Surg. 2020;36(6):380-387.].

Clinical observations of iridociliary cysts and their changes after implantable collamer lens implantation in myopic patients.

AIM: To observe the characteristics of iridociliary cysts in myopic patients and evaluate the influences on the position and safety of implantable collamer lens (ICL) after surgery. METHODS: Totally 270 eyes of 135 patients who underwent ICL surgery for the corrections of myopia were included in this study. Preoperative and postoperative morphology of iridociliary cysts were observed in ultrasonic biomicroscopy (UBM) image. RESULTS: A total of 138 iridociliary cysts were found in 88 eyes of 50 patients among 270 eyes of 135 patients before surgery (37%). Twenty-five patients had cysts in one eye (50%) and 25 had cysts in both eyes (50%). The prevalence of iridociliary cysts was negatively correlated with age, but no gender difference (P>0.05). The incidence of iridociliary cysts was much less in eyes with myopia greater than -9.00 D (P<0.05). The diameter of the largest cyst was 1.96 mm and the smallest cyst was 0.24 mm, with a majority within the range of 0.5 to 1.0 mm. Most of the cysts were located in the inferior temporal quadrant. One year after ICL implantation, 51 iridociliary cysts (37%) remained unchanged, 47 cysts (34%) decreased in size, and 40 cysts (29%) disappeared. Most of cysts that changed after surgery were smaller than 1.0 mm (P<0.05) and located in the nasal and temporal sides around the haptics of implantable lens. All the ICL were in their original position. CONCLUSION: Iridociliary cysts are commonly seen in myopic eyes. The cysts have no impact on the safety of ICL surgery. Some cysts may decrease in size or disappear after ICL implantation.

Camellia oil (Camellia oleifera Abel.) attenuates CCl4-induced liver fibrosis via suppressing hepatocyte apoptosis in mice.

Liver fibrosis is a common part of the pathological development of many chronic liver diseases. As liver fibrosis progresses, it may lead to cirrhosis, portal hypertension, liver decompensation, liver tumours, and death. Camellia oil (Camellia oleifera Abel.) is widely used as an edible oil in China. It has a wide range of biological activities and is used as a traditional medicine to treat conditions such as burns and stomach pains. However, whether camellia oil can ameliorate liver fibrosis remains unclear. We constructed a liver fibrosis model induced by carbon tetrachloride (CCl4) and then confirmed the role of camellia oil in liver fibrosis by biochemical examination, histopathological morphology, immunohistochemistry, and western blot analysis. We found that camellia oil ameliorated histopathological lesions, improved liver function and antioxidant capacity, decreased the expression of TGF-ß1 and α-SMA proteins, and downregulated the expression of the pro-apoptotic proteins in CCl4-induced liver fibrosis. Therefore, these results suggest that camellia oil attenuates CCl4-induced liver fibrosis in mice, and its mechanism may function via reduction of hepatocyte apoptosis to inhibit hepatic stellate cell (HSC) activation. Camellia oil may provide a potential new treatment for liver fibrosis as an auxiliary treatment by addition of the edible oil to the daily diet.