Porous Se@SiO2 nanospheres alleviate diabetic retinopathy by inhibiting excess lipid peroxidation and inflammation.

BACKGROUND: Lipid peroxidation is a characteristic metabolic manifestation of diabetic retinopathy (DR) that causes inflammation, eventually leading to severe retinal vascular abnormalities. Selenium (Se) can directly or indirectly scavenge intracellular free radicals. Due to the narrow distinction between Se's effective and toxic doses, porous Se@SiO2 nanospheres have been developed to control the release of Se. They exert strong antioxidant and anti-inflammatory effects. METHODS: The effect of anti-lipid peroxidation and anti-inflammatory effects of porous Se@SiO2 nanospheres on diabetic mice were assessed by detecting the level of Malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), decreased reduced/oxidized glutathione (GSH/GSSG) ratio, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL) -1ß of the retina. To further examine the protective effect of porous Se@SiO2 nanospheres on the retinal vasculopathy of diabetic mice, retinal acellular capillary, the expression of tight junction proteins, and blood-retinal barrier destruction was observed. Finally, we validated the GPX4 as the target of porous Se@SiO2 nanospheres via decreased expression of GPX4 and detected the level of MDA, GSH/GSSG, TNF-α, IFN-γ, IL -1ß, wound healing assay, and tube formation in high glucose (HG) cultured Human retinal microvascular endothelial cells (HRMECs). RESULTS: The porous Se@SiO2 nanospheres reduced the level of MDA, TNF-α, IFN-γ, and IL -1ß, while increasing the level of GPX4 and GSH/GSSG in diabetic mice. Therefore, porous Se@SiO2 nanospheres reduced the number of retinal acellular capillaries, depletion of tight junction proteins, and vascular leakage in diabetic mice. Further, we identified GPX4 as the target of porous Se@SiO2 nanospheres as GPX4 inhibition reduced the repression effect of anti-lipid peroxidation, anti-inflammatory, and protective effects of endothelial cell dysfunction of porous Se@SiO2 nanospheres in HG-cultured HRMECs. CONCLUSION: Porous Se@SiO2 nanospheres effectively attenuated retinal vasculopathy in diabetic mice via inhibiting excess lipid peroxidation and inflammation by target GPX4, suggesting their potential as therapeutic agents for DR.

The protective effect of vagus nerve stimulation against myocardial ischemia/reperfusion injury: pooled review from preclinical studies.

Aims: Myocardial ischemia-reperfusion (I/R) injury markedly undermines the protective benefits of revascularization, contributing to ventricular dysfunction and mortality. Due to complex mechanisms, no efficient ways exist to prevent cardiomyocyte reperfusion damage. Vagus nerve stimulation (VNS) appears as a potential therapeutic intervention to alleviate myocardial I/R injury. Hence, this meta-analysis intends to elucidate the potential cellular and molecular mechanisms underpinning the beneficial impact of VNS, along with its prospective clinical implications. Methods and Results: A literature search of MEDLINE, PubMed, Embase, and Cochrane Database yielded 10 articles that satisfied the inclusion criteria. VNS was significantly correlated with a reduced infarct size following myocardial I/R injury [Weighed mean difference (WMD): 25.24, 95% confidence interval (CI): 32.24 to 18.23, p < 0.001] when compared to the control group. Despite high heterogeneity (I2 = 95.3%, p < 0.001), sensitivity and subgroup analyses corroborated the robust efficacy of VNS in limiting infarct expansion. Moreover, meta-regression failed to identify significant influences of pre-specified covariates (i.e., stimulation type or site, VNS duration, condition, and species) on the primary estimates. Notably, VNS considerably impeded ventricular remodeling and cardiac dysfunction, as evidenced by improved left ventricular ejection fraction (LVEF) (WMD: 10.12, 95% CI: 4.28; 15.97, p = 0.001) and end-diastolic pressure (EDP) (WMD: 5.79, 95% CI: 9.84; -1.74, p = 0.005) during the reperfusion phase. Conclusion: VNS offers a protective role against myocardial I/R injury and emerges as a promising therapeutic strategy for future clinical application.

Using the meteorological early warning model to improve the prediction accuracy of water damage geological disasters around pipelines in mountainous areas.

This paper focuses on the threat of water damage geological disasters brought by the complex terrain along the long-distance natural gas pipeline. The role of rainfall factors in the occurrence of such disasters has been fully considered, a meteorological early warning model for water damage geological disasters in mountainous areas based on slope units has been constructed to improve the prediction accuracy of such disasters and timely early warning and forecasting. An actual natural gas pipeline in a typical mountainous area of Zhejiang Province is taken as an example. The hydrology-curvature combined analysis method is chosen to divide the slope units, and the SHALSTAB model is used to fit the slope soil environment to calculate the stability level. Finally, the stability level is coupled with rainfall data to calculate the early warning index for water damage geological disasters in the study area. The results show that compared with the separate SHALSTAB model, the early warning results coupled with rainfall are more effective in predicting water damage geological disasters. The early warning results are compared with the actual disaster points, among the nine actual disaster points, most of the slope units around seven disaster points are in the state of needing early warning, the early warning accuracy rate reaches 77.8 %. The proposed early warning model can carry out targeted deployment in advance according to the divided slope units, and the prediction accuracy of geological disasters induced by heavy rainfall weather is significantly higher and more suitable for the actual location of the disaster point, which can provide a basis for accurate disaster prevention in the research area and areas with similar geological environments.

Automatic Segmentation of Hyperreflective Foci in OCT Images Based on Lightweight DBR Network.

Hyperreflective foci (HF) reflects inflammatory responses for fundus diseases such as diabetic macular edema (DME), retina vein occlusion (RVO), and central serous chorioretinopathy (CSC). Shown as high contrast and reflectivity in optical coherence tomography (OCT) images, automatic segmentation of HF in OCT images is helpful for the prognosis of fundus diseases. Previous traditional methods were time-consuming and required high computing power. Hence, we proposed a lightweight network to segment HF (with a speed of 57 ms per OCT image, at least 150 ms faster than other methods). Our framework consists of two stages: an NLM filter and patch-based split to preprocess images and a lightweight DBR neural network to segment HF automatically. Experimental results from 3000 OCT images of 300 patients (100 DME,100 RVO, and 100 CSC) revealed that our method achieved HF segmentation successfully. The DBR network had the area under curves dice similarity coefficient (DSC) of 83.65%, 76.43%, and 82.20% in segmenting HF in DME, RVO, and CSC on the test cohort respectively. Our DBR network achieves at least 5% higher DSC than previous methods. HF in DME was more easily segmented compared with the other two types. In addition, our DBR network is universally applicable to clinical practice with the ability to segment HF in a wide range of fundus diseases.

Higher-order aberrations and their association with axial elongation in highly myopic children and adolescents.

BACKGROUND: Vision-dependent mechanisms play a role in myopia progression in childhood. Thus, we investigated the distribution of ocular and corneal higher-order aberrations (HOAs) in highly myopic Chinese children and adolescents and the relationship between HOA components and 1-year axial eye growth. METHODS: Baseline cycloplegic ocular and corneal HOAs, axial length (AL), spherical equivalent (SE), astigmatism and interpupillary distance (IPD) were determined for the right eyes of 458 highly myopic (SE ≤-5.0D) subjects. HOAs were compared among baseline age groups (≤12 years, 13-15 years and 16-18 years). Ninety-nine subjects completed the 1-year follow-up. Linear mixed model analyses were applied to determine the association between HOA components, other known confounding variables (age, gender, SE, astigmatism and IPD) and axial growth. A comparison with data from an early study of moderate myopia were conducted. RESULTS: Almost all ocular HOAs and few corneal HOAs exhibited significant differences between different age groups (all p<0.05). After 1 year, only ocular HOA components was significantly negative associated with a longer AL, including secondary horizontal comatic aberration (p=0.019), primary spherical aberration (p<0.001) and spherical HOA (p=0.026). Comparing with the moderate myopia data, the association of comatic aberration with AL growth was only found in high myopia. CONCLUSION: In highly myopic children and adolescents, lower levels of annual ocular secondary horizontal comatic aberration changes, besides spherical aberrations, were associated with axial elongation. This suggests that ocular HOA plays a potential role in refractive development in high myopia.

Individualized Statistical Modeling of Lesions in Fundus Images for Anomaly Detection.

Anomaly detection in fundus images remains challenging due to the fact that fundus images often contain diverse types of lesions with various properties in locations, sizes, shapes, and colors. Current methods achieve anomaly detection mainly through reconstructing or separating the fundus image background from a fundus image under the guidance of a set of normal fundus images. The reconstruction methods, however, ignore the constraint from lesions. The separation methods primarily model the diverse lesions with pixel-based independent and identical distributed (i.i.d.) properties, neglecting the individualized variations of different types of lesions and their structural properties. And hence, these methods may have difficulty to well distinguish lesions from fundus image backgrounds especially with the normal personalized variations (NPV). To address these challenges, we propose a patch-based non-i.i.d. mixture of Gaussian (MoG) to model diverse lesions for adapting to their statistical distribution variations in different fundus images and their patch-like structural properties. Further, we particularly introduce the weighted Schatten p-norm as the metric of low-rank decomposition for enhancing the accuracy of the learned fundus image backgrounds and reducing false-positives caused by NPV. With the individualized modeling of the diverse lesions and the background learning, fundus image backgrounds and NPV are finely learned and subsequently distinguished from diverse lesions, to ultimately improve the anomaly detection. The proposed method is evaluated on two real-world databases and one artificial database, outperforming the state-of-the-art methods.

A simple system for measuring the transmittance curve of x-ray filters at low x-ray energies.

To prevent the x-ray detectors from the interference of optical photons, x-ray filters are widely used in x-ray space missions. As the flux of low energy x-rays would be significantly attenuated by the filters, it is important to derive the transmittance of the filters below 10 keV. In this paper, we present a simple experimental apparatus and data processing method to measure the transmittance curve of x-ray filters in the energy range from 1.6 to 10 keV. The measured spectra were further processed with Geant4 Monte Carlo simulation results and a direct demodulation algorithm. The obtained transmittance is in good accordance with the theoretical calculation and the synchrotron radiation test result, which proves that the proposed system with the algorithm is a reasonable way to characterize the x-ray transmittance performance of filters above 1.6 keV.

Green Tandem [5C + 1C] Cycloaromatization of α-Alkenoyl Ketene Dithioacetals and Nitroethane in Water: Eco-Friendly Synthesis of Ortho-Acylphenols.

For the first time, an eco-friendly and sustainable tandem [5C + 1C] cycloaromatization of α-alkenoyl ketene dithioacetals and nitroethane in water for the efficient synthesis of ortho-acylphenols was reported. In refluxing water, a range of α-alkenoyl ketene dithioacetals and nitroethane smoothly underwent tandem Michael addition/cyclization/aromatization reactions in the presence of 2.0 equivalents of DBU to provide various ortho-acylphenols in excellent yields. The green approach to ortho-acylphenols not only avoided the use of harmful organic solvents, which could result in serious environmental and safety issues, but also exhibited fascinating features such as good substrate scope, excellent yields, simple purification for desired products, ease of scale-up, and reusable aqueous medium.

Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism.

BACKGROUND: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. METHODS: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. RESULTS: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. CONCLUSION: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.

Influence of temperature-salinity-depth structure of the upper-ocean on the frequency shift of Brillouin LiDAR.

Brillouin-based LiDAR is an alternative remote sensing technique for measuring the distribution profiles of temperature, salinity, and sound speed in the upper ocean mixed layer. Its principle is based on the dependence of Brillouin frequency shift on the temperature, salinity, and depth of ocean. Therefore, it is necessary to investigate the effect of various seawater parameters on Brillouin frequency shift for ocean remote sensing by using the Brillouin LiDAR. Here we theoretically and experimentally investigate the influence of temperature, salinity, and pressure (depth) of seawater on Brillouin frequency shift in the upper ocean for the first time. Numerical simulations of the distribution profiles of temperature, salinity, and Brillouin frequency shift in the upper-ocean mixed layers of East China Sea and South China Sea were performed, respectively, by employing the Brillouin equations and the World Ocean Atlas 2018 (WOA18). A special ocean simulation system was designed to carry out the stimulated Brillouin scattering (SBS) experiments for validating the numerical simulations. The results show that the seawater temperature is the most important factor for the Brillouin frequency shift in the upper-ocean mixed layer compared with the salinity and pressure. At the same salinity and pressure, the frequency shift increases by more than 10 MHz for every 1 °C increase in temperature. Also, the differences of Brillouin frequency shift between experimental and theoretical values at the same parameter conditions were analyzed. The experimental results coincide well with the theoretical simulations. This work is essential to future applications of Brillouin LiDAR in remote sensing of the temperature, salinity, or sound velocity profiles of ocean.

A biocompatible theranostic agent based on stable bismuth nanoparticles for X-ray computed tomography/magnetic resonance imaging-guided enhanced chemo/photothermal/chemodynamic therapy for tumours.

Cancer is a leading cause of death worldwide and seriously threatens the health of humans. The current clinical treatments for cancer are not efficient and always lead to significant side effects. Herein, a biocompatible and powerful theranostic agent (Bi@mSiO2@MnO2/DOX) is fabricated using a facile stepwise reaction method. The Bi nanoparticles (NPs) are coated by mesoporous silica to protect the Bi NPs from oxidation, which guarantees the stable photothermal effect of the Bi NPs. When the Bi@mSiO2@MnO2/DOX nanocomposites (NCs) accumulate in the tumour site, hyperthermia is generated by Bi NPs under near-infrared (NIR) light irradiation for photothermal therapy (PTT), and the generated heat triggers the release of DOX for chemotherapy in the tumour. In addition, the MnO2 of the NCs responsively catalyses endogenous H2O2 to generate O2, raising the oxygen level to enhance the effect of chemotherapy in the tumour microenvironment (TME), and consumes glutathione (GSH) to produce Mn2+ for magnetic resonance (MR) imaging. Under acidic TME conditions, H2O2 and Mn2+ also produce toxic hydroxyl radical (·OH) for chemodynamic therapy (CDT). Furthermore, the Bi NPs can also be used as excellent contrast agents for X-ray computed tomography (CT) imaging of tumours with a high CT value (6.865 HU mM-1). The Bi@mSiO2@MnO2/DOX NCs exhibit a powerful theranostic performance for CT/MR imaging-guided enhanced PTT/CDT/chemotherapy, which opens a new prospect to rationally design theranostic agents for tumour imaging.

Novel Peptide NT/K-CRS Derived from Kringle Structure of Neurotrypsin Inhibits Neovascularization In Vitro and In Vivo.

Purpose: To assess the anti-neovascularization effect of a novel peptide NT/K-CRS derived from the kringle domain of neurotrypsin in vitro and in vivo. Methods: Primary human umbilical vein endothelial cells (HUVECs) were treated with vascular endothelial growth factor (VEGF) in advance. Cell migration, lumen formation, and cell proliferation assays were performed to determine the anti-neovascularization effect of NT/K-CRS in HUVECs. TUNEL and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium tests were conducted to evaluate cell viability. Chick chorioallantoic membrane and oxygen-induced retinopathy model were established to assess the anti-angiogenic role of NT/K-CRS in vivo. Results: The in vitro results showed that NT/K-CRS effectively decreased VEGF-induced cell migration and endothelial tube formation, with no significant effect on cell proliferation and cell viability. In addition, NT/K-CRS showed great efficacy in angiogenesis inhibition in chicken embryos. The cytokine release syndrome (CRS) peptide also inhibited retinal neovascularization and improved retinal blood perfusion in oxygen-treated mouse pups through intravitreal injection. Conclusions: NT/K-CRS peptide derived from the kringle domain of neurotrypsin can strongly inhibit neovascularization in vitro and vivo. This novel peptide may become a promising therapeutic agent for neovascular-related ocular diseases.

Novel Peptide NT/K-CFY Derived from Kringle Structure of Neurotrypsin Inhibits Neovascularization.

Purpose: To assess the anti-neovascularization effect of a novel peptide NT/K-CFY derived from the kringle domain of neurotrypsin.Materials and Methods: Cell migration, lumen formation and cell proliferation assays were performed to determine the anti-neovascularization effect of NT/K-CFY in primary human umbilical vein endothelial cells (HUVECs). Chick chorioallantoic membrane (CAM) and oxygen-induced retinopathy (OIR) models were established to assess the anti-angiogenic role of NT/K-CFY in vivo. The retinal expression of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) was examined by western blot and real-time PCR in OIR model.Results: The in vitro results showed that NT/K-CFY effectively and safely decreased VEGF-induced cell migration, cell proliferation and tube formation in HUVECs. In addition, NT/K-CFY showed certain efficacy in angiogenesis inhibition in chicken embryos and oxygen-treated mouse pups. Moreover, the CFY peptide also improved retinal blood perfusion and reversed the abnormal expression of VEGF and PEDF in OIR mouse model.Conclusion: NT/K-CFY peptide strongly inhibits neovascularization in vitro and vivo. This novel peptide may become a promising therapeutic agent for ocular angiogenesis-related diseases.

Protective effects of peptide FK18 against neuro-excitotoxicity in SH-SY5Y cells.

Excitotoxic neuronal injury is associated with numerous acute and chronic neurological disorders, such as Alzheimer's disease and glaucoma. Neuroprotection is a direct and effective therapeutic approach, with small-molecule bioactive peptides displaying certain advantages, including high membrane permeability, low immunogenicity and convenient synthesis and modification. FK18 is a novel peptide derived from basic fibroblast growth factor, which is a protein with neuroprotective effects. The present study aims to evaluate the neuroprotective effect of FK18 against excitotoxic injury. For this purpose, cell viability was determined by the MTS assay, cell apoptosis was assessed by flow cytometry and the TUNEL assay; expression of antiapoptotic proteins Bcl-2, proapoptotic protein Bax and caspase-3 as well as the phosphorylation of Akt and Erk was estimated by western blotting. The results of the present study demonstrated that FK18 effectively increased the viability of, and attenuated glutamate-induced apoptosis of SH-SY5Y cells. In addition, FK18 significantly increased Akt phosphorylation and decreased Erk phosphorylation in SH-SY5Y cells. FK18 also increased the Bcl-2/Bax ratio and decreased the level of cleaved-caspase-3 in SY5Y cells, which was reversed by the Akt pathway inhibitor LY294002, but not by the Erk pathway inhibitor U0126. The findings of the present study suggested that FK18 may be a promising therapeutic agent for the inhibition of neuronal cell death in multiple neurological diseases involving excitotoxicity.

Backward modeling of urinary test reliability for assessing PAH health risks: An approximation solution for naphthalene.

Urine sample tests are one of the most common methods of estimating human exposure to polycyclic aromatic hydrocarbons (PAHs) and assessing population health risks. To evaluate the reliability of the urine test and the impact of other PAH elimination routes on the health risk estimated by this test, we proposed a backward modeling framework integrating other common elimination routes of PAH metabolites to calculate the overall intake rate of the parent PAH based on the levels of corresponding main metabolites in urine. Due to limited biotransformation data, we selected naphthalene as an example to evaluate model performance and collected urine samples from 234 random adults in Shenzhen. The overall intake rates of naphthalene were then simulated and compared to current literature data. The simulated intake rates of naphthalene ranged from 3.70 × 10-3 mg d-1 to 1.95 mg d-1 and followed a lognormal distribution with a median value of 6.51 × 10-2 mg d-1. The results indicated that, if naphthalene exposure occurred only via food for the population of Shenzhen, the literature data fell within the most frequent interval [3.70 × 10-3, 4.45 × 10-2] but were lower than the simulated median value. However, if other exposure routes were considered, the allocation factor-adjusted literature data were close to the simulated median values. In addition, under normal physiological conditions, the simulated results were more sensitive to 1-hydroxynaphthalene (1-OHN) and 2-hydroxynaphthalene (2-OHN) levels in urine than other biometric variables, which is due to the limited load of 1-OHN and 2-OHN in human elimination routes. Furthermore, the suggested safety levels of 1-OHN and 2-OHN in urine to protect 99% of the general population of Shenzhen were 6.40 × 10-6 and 3.75 × 10-5 mg L-1, which could be used as regulatory indicators based on the high reliability of the model.

Boundary Restored Network for Subpleural Pulmonary Lesion Segmentation on Ultrasound Images at Local and Global Scales.

To evaluate the application of machine learning for the detection of subpleural pulmonary lesions (SPLs) in ultrasound (US) scans, we propose a novel boundary-restored network (BRN) for automated SPL segmentation to avoid issues associated with manual SPL segmentation (subjectivity, manual segmentation errors, and high time consumption). In total, 1612 ultrasound slices from 255 patients in which SPLs were visually present were exported. The segmentation performance of the neural network based on the Dice similarity coefficient (DSC), Matthews correlation coefficient (MCC), Jaccard similarity metric (Jaccard), Average Symmetric Surface Distance (ASSD), and Maximum symmetric surface distance (MSSD) was assessed. Our dual-stage boundary-restored network (BRN) outperformed existing segmentation methods (U-Net and a fully convolutional network (FCN)) for the segmentation accuracy parameters including DSC (83.45 ± 16.60%), MCC (0.8330 ± 0.1626), Jaccard (0.7391 ± 0.1770), ASSD (5.68 ± 2.70 mm), and MSSD (15.61 ± 6.07 mm). It also outperformed the original BRN in terms of the DSC by almost 5%. Our results suggest that deep learning algorithms aid fully automated SPL segmentation in patients with SPLs. Further improvement of this technology might improve the specificity of lung cancer screening efforts and could lead to new applications of lung US imaging.

Serum Metabolomics Reveals Personalized Metabolic Patterns for Macular Neovascular Disease Patient Stratification.

The macular neovascular disease is a group disorder with complex pathogenesis of neovascularization for vision impairment and irreversible blindness, posing great challenges to precise diagnosis and management. We prospectively recruited participants with age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), and pathological myopia (PM) and compared with cataract patients without fundus diseases as a control group. The serum metabolome was profiled by gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS) analysis. Multivariate statistical methods as well as data mining were performed for interpretation of macular neovascularization. A total of 446 participants with macular neovascularization and 138 cataract subjects as the control group were enrolled in this study. By employing GC-TOFMS, 131 metabolites were identified and 33 differentiating metabolites were highlighted in patients with macular neovascularization. For differential diagnosis, three panels of specific metabolomics-based biomarkers provided areas under the curve of 0.967, 0.938, and 0.877 in the discovery phase (n = 328) and predictive values of 87.3%, 79%, and 85.7% in the test phase (n = 256). Personalized pathway dysregulation scores measurement using Lilikoi package in R language revealed the pentose phosphate pathway and mitochondrial electron transport chain as the most important pathways in AMD; purine metabolism and glycolysis were identified as the major disturbed pathways in PCV, while the altered thiamine metabolism and purine metabolism may contribute to PM phenotypes. Serum metabolomics are powerful for characterizing metabolic disturbances of the macular neovascular disease. Differences in metabolic pathways may reflect an underlying macular neovascular disease and serve as therapeutic targets for macular neovascular treatment.

Ras-ERK1/2 Signaling Promotes The Development Of Osteosarcoma By Regulating H2BK12ac Through CBP.

BACKGROUND: H2BK12ac is an important histone acetylation pattern of H2B, which has been reported in several cancers. However, whether H2BK12ac joins in Ras-ERK1/2 activation-induced osteosarcoma (OS) cell behaviors remain unclear. The study explored this peradventure and revealed the underlying mechanism. METHODS: MG-63 cells were transfected with pEGFP-N1, pEGFP-RasWT and pEGFP-K-RasG12V/T35S, H2BK12ac and ERK1/2 expression levels were analyzed by Western blot. Effects of H2BK12ac on cell viability, migration, colony formation and cell cycle were investigated by MTT, Transwell, soft-agar colony formation and flow cytometry assays. RT-qPCR and ChIP were performed to study the effect of H2BK12ac and CBP on ERK1/2-downstream gene transcriptions. RESULTS: H2BK12ac was specifically down-regulated by Ras-ERK1/2 activation in MG-63 cells. Down-regulated H2BK12ac participated in regulating cell proliferation and migration of MG-63 cells, meanwhile, affected the transcription of ERK1/2-downstream genes. Additionally, silence of HDAC1 up-regulated H2BK12ac expression, and inhibited the promoting effect of Ras-ERK1/2 on MG-63 cells' proliferation, migration and RNA expression levels of ERK1/2-downstream genes. Further, the degradation of CBP mediated by MDM2 was discovered to be linked to Ras-ERK1/2 activation-induced H2BK12ac down-regulation. CONCLUSION: These findings from the study demonstrated that Ras-ERK1/2 signaling could promote the development of OS via regulating H2BK12ac through MDM2-mediated CBP degradation.

Comparison of Elastic Intramedullary Nails and Locking Compression Plates on Oxidative Stress in Children with Distal Tibial Metaphyseal Fractures.

The aim of this study was to compare the effects of elastic intramedullary nails and locking compression plates on oxidative stress like superoxide dismutase (SOD), total antioxidant capacity (TAC), catalase (CAT), and malondialdehyde (MDA) in children with distal tibial metaphyseal fractures. It was an experimental study carried out from January 2012 to October 2017. Ninety-eight children with distal tibial metaphyseal fractures were randomly divided into group A and group B, 49 cases in each group. Group A was treated with elastic intramedullary nails and group B with locking compression plates. The research showed that operation time of group A was shorter than those of group B (p <0.001), incision complication rate of group A was lower than that of group B (p=0.025), and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score of group A was higher than that of group B (p <0.001) after 12 months of follow-up. On the 7th day after operation, the levels of SOD, TAC and CAT in group A were higher than those in group B (p=0.003, p <0.001, p <0.001, respectively), but level of serum MDA in group A was lower than that in group B (p <0.001). Compared with locking compression plate, elastic intramedullary nail has better short-term effect, less operative time, lower incision complications, and less influence on oxidative stress.

Correlation of retinal layer changes with vision gain in diabetic macular edema during conbercept treatment.

BACKGROUNDS: To assess the changes in individual retinal layer thickness and visual function associated with gains in visual acuity after an intravitreal conbercept injection in the diabetic macular edema (DME) on spectral domain optical coherence tomography (SD-OCT) and microperimetry during 1-year follow-up. METHODS: Retrospective observational study. Twenty patients with clinically significant DME in the study eye were imaged by SD-OCT every 3 months and MP1 microperimeter in the third month while receiving anti-vascular endothelial growth factor (VEGF) (conbercept) treatment. In each patient, seven retinal layers were segmented in 98 scans covering a 6 mm × 6 mm area of the macula at baseline and during 1 year of treatment. An automatic, full-threshold microperimetry of the central field (10° × 10°, 40 stimulated points) with the MP1 microperimeter. Thickness and microperimetry changes were quantitatively measured and evaluated for their correlation with increases in visual acuity. RESULTS: Although thicknesses of the inner nuclear layer (INL) and the outer nuclear layer (ONL) were reduced the most after treatment (p < 0.05), decreases of the ganglion cell layer (GCL) (r = 0.591, p = 0.006) and inner plexiform layer (IPL) (r = 0.663, p = 0.001) in central subfield area was associated with best-corrected visual acuity (BCVA) gain, and had the best estimation of BCVA gain (adjust R2 = 0.544). Mean macular sensitivity in the central subfield was also well correlated with BCVA gain (r = 0.531, p = 0.016). CONCLUSIONS: Neural recovery occurred after the resolution of edema during conbercept treatment, due to the decreases in GCL and IPL associating with gains in vision and improved microperimetry.