Starvation insult induces the translocation of high mobility group box 1 to cytosolic compartments in glioma.

High mobility group box 1 (HMGB1) is a highly conserved and ubiquitous nuclear protein in eukaryotic cells. In response to stress, it transfers from the nucleus to the cytoplasm and finally, to the extracellular matrix, participating in inflammation and carcinogenesis. Increased HMGB1 protein levels are frequently associated with the reduced survival of patients with glioma. HMGB1 plays contextual roles depending on its subcellular localization. However, the mechanisms underlying its subcellular localization and secretion remain unclear. In the present study, the subcellular localization and secretion of HMGB1 in starved glioma cells were investigated using immunofluorescence microscopy, enzyme­linked immunosorbent assay, subcellular fractionation, western blotting and immunoelectron microscopy. The results demonstrated that starvation induced HMGB1 translocation from the nucleus to the cytoplasm and finally, to the extracellular milieu in glioma cells. HMGB1 was localized in the mitochondria, endoplasmic reticulum (ER), peroxisomes, autophagosomes, lysosomes, endosomes and the cytoskeleton. Immunoelectron microscopy confirmed that HMGB1 was present within or around cytosolic compartments. Subcellular fractionation further demonstrated that HMGB1 transferred to membrane­bound compartments. In addition, HMGB1 was localized to specific contact areas between the ER and mitochondria, known as mitochondria­associated membranes. On the whole, the results of the present study suggest that starvation induces HMGB1 secretion, which can be inhibited through the suppression of autophagy. Starvation insult induces HMGB1 translocation to the cytosolic compartments of glioma cells, and autophagy may be involved in the extracellular secretion of HMGB1 in starved glioma cells.

Genomic Sequencing as a First-Tier Screening Test and Outcomes of Newborn Screening.

Importance: Newborn screening via biochemical tests is in use worldwide. The availability of genetic sequencing has allowed rapid screening for a substantial number of monogenic disorders. However, the outcomes of this strategy have not been evaluated in a general newborn population. Objective: To evaluate the outcomes of applying gene panel sequencing as a first-tier newborn screening test. Design, Setting, and Participants: This cohort study included newborns who were prospectively recruited from 8 screening centers in China between February 21 and December 31, 2021. Neonates with positive results were followed up before July 5, 2022. Exposures: All participants were concurrently screened using dried blood spots. The screen consisted of biochemical screening tests and a targeted gene panel sequencing test for 128 conditions. The biochemical and genomic tests could both detect 43 of the conditions, whereas the other 85 conditions were screened solely by the gene panel. Main Outcomes and Measures: The primary outcomes were the number of patients detected by gene panel sequencing but undetected by the biochemical test. Results: This study prospectively recruited 29 601 newborns (15 357 [51.2%] male). The mean (SD) gestational age was 39.0 (1.5) weeks, and the mean (SD) birth weight was 3273 (457) g. The gene panel sequencing screened 813 infants (2.7%; 95% CI, 2.6%-2.9%) as positive. By the date of follow-up, 402 infants (1.4%; 95% CI, 1.2%-1.5%) had been diagnosed, indicating the positive predictive value was 50.4% (95% CI, 50.0%-53.9%). The gene panel sequencing identified 59 patients undetected by biochemical tests, including 20 patients affected by biochemically and genetically screened disorders and 39 patients affected by solely genetically screened disorders, which translates into 1 out of every 500 newborns (95% CI, 1/385-1/625) benefiting from the implementation of gene panels as a first-tier screening test. Conclusions and Relevance: In this cohort study, the use of gene panel sequencing in a general newborn population as a first-tier screening test improved the detection capability of traditional screening, providing an evidence-based suggestion that it could be considered as a crucial method for first-tier screening.

Paleoenvironmental changes in the coastal zone of the northwest South China Sea during the last 13 kyr.

Marine sediments in coastal zones serve as valuable archives for understanding the history of silicate chemical weathering and summer monsoon rainfall in source areas, providing insights into terrigenous climate and environmental evolution. In this study, we investigated the grain size, clay minerals, and geochemistry of sediments retrieved from core KZK01 in the coastal zone of the northwest South China Sea during the past 13 thousand years before present (kyr BP). Our findings demonstrated that the illite crystallinity index served as a reliable proxy for assessing the intensity of chemical weathering in the source area. Moreover, it distinctly recorded significant climatic events such as the Younger Dryas and Bond events during the Holocene. The dominant driver of the regional East Asian summer monsoon was identified as summer solar radiation in the Northern Hemisphere at low latitudes. Cold climate events exhibited global consistency, potentially influenced by the presence of ice sheets at high latitudes. Lastly, our records revealed a distinct transition at 9.0 kyr, highlighting significant impacts of the Qiongzhou Strait and sea level rise on regional climate dynamics.

A weighted-sum chaotic sparrow search algorithm for interdisciplinary feature selection and data classification.

In today's data-driven digital culture, there is a critical demand for optimized solutions that essentially reduce operating expenses while attempting to increase productivity. The amount of memory and processing time that can be used to process enormous volumes of data are subject to a number of limitations. This would undoubtedly be more of a problem if a dataset contained redundant and uninteresting information. For instance, many datasets contain a number of non-informative features that primarily deceive a given classification algorithm. In order to tackle this, researchers have been developing a variety of feature selection (FS) techniques that aim to eliminate unnecessary information from the raw datasets before putting them in front of a machine learning (ML) algorithm. Meta-heuristic optimization algorithms are often a solid choice to solve NP-hard problems like FS. In this study, we present a wrapper FS technique based on the sparrow search algorithm (SSA), a type of meta-heuristic. SSA is a swarm intelligence (SI) method that stands out because of its quick convergence and improved stability. SSA does have some drawbacks, like lower swarm diversity and weak exploration ability in late iterations, like the majority of SI algorithms. So, using ten chaotic maps, we try to ameliorate SSA in three ways: (i) the initial swarm generation; (ii) the substitution of two random variables in SSA; and (iii) clamping the sparrows crossing the search range. As a result, we get CSSA, a chaotic form of SSA. Extensive comparisons show CSSA to be superior in terms of swarm diversity and convergence speed in solving various representative functions from the Institute of Electrical and Electronics Engineers (IEEE) Congress on Evolutionary Computation (CEC) benchmark set. Furthermore, experimental analysis of CSSA on eighteen interdisciplinary, multi-scale ML datasets from the University of California Irvine (UCI) data repository, as well as three high-dimensional microarray datasets, demonstrates that CSSA outperforms twelve state-of-the-art algorithms in a classification task based on FS discipline. Finally, a 5%-significance-level statistical post-hoc analysis based on Wilcoxon's signed-rank test, Friedman's rank test, and Nemenyi's test confirms CSSA's significance in terms of overall fitness, classification accuracy, selected feature size, computational time, convergence trace, and stability.

Neuronal p58IPK Protects Retinal Ganglion Cells Independently of Macrophage/Microglia Activation in Ocular Hypertension.

p58IPK is a multifaceted endoplasmic reticulum (ER) chaperone and a regulator of eIF2α kinases involved in a wide range of cellular processes including protein synthesis, ER stress response, and macrophage-mediated inflammation. Systemic deletion of p58IPK leads to age-related loss of retinal ganglion cells (RGC) and exacerbates RGC damage induced by ischemia/reperfusion and increased intraocular pressure (IOP), suggesting a protective role of p58IPK in the retina. However, the mechanisms remain elusive. Herein, we investigated the cellular mechanisms underlying the neuroprotection action of p58IPK using conditional knockout (cKO) mouse lines where p58IPK is deleted in retinal neurons (Chx10-p58IPK cKO) or in myeloid cells (Lyz2-p58IPK cKO). In addition, we overexpressed p58IPK by adeno-associated virus (AAV) in the retina to examine the effect of p58IPK on RGC survival after ocular hypertension (OHT) in wild type (WT) mice. Our results show that overexpression of p58IPK by AAV significantly improved RGC survival after OHT in WT mice, suggesting a protective effect of p58IPK on reducing RGC injury. Conditional knockout of p58IPK in retinal neurons or in myeloid cells did not alter retinal structure or cellular composition. However, a significant reduction in the b wave of light-adapted electroretinogram (ERG) was observed in Chx10-p58IPK cKO mice. Deletion of p58IPK in retinal neurons exacerbates RGC loss at 14 days after OHT. In contrast, deficiency of p58IPK in myeloid cells increased the microglia/macrophage activation but had no effect on RGC loss. We conclude that deletion of p58IPK in macrophages increases their activation, but does not influence RGC survival. These results suggest that the neuroprotective action of p58IPK is mediated by its expression in retinal neurons, but not in macrophages. Therefore, targeting p58IPK specifically in retinal neurons is a promising approach for the treatment of neurodegenerative retinal diseases including glaucoma.

Assessing Heavy Metal Pollution of the Largest Nature Reserve in Tianjin City, China.

Beidagang Wetland (BW) Nature Reserve is centrally situated in Tianjin City, experiencing an extreme industrial development. This study uses index characteristic analysis systems for assessing the individual and combined heavy metal pollution loading in the water during the spring and autumn seasons. By combining the pollution level of single pollutant, a more comprehensive evaluation of water quality in BW was achieved. Water quality was worst during autumn due to high level of Cd and Pb, which indicate the type of anthropogenic activities have a serious effect on heavy metal pollution in BW. In addition, high exchangeable amounts of Cd (> 40%) were found in the sediments of BW, indicating Cd pollution has emerged. There is a need for appropriate abatement actions curbing heavy metal loading and improving water quality of the BW Nature Reserve, thereby ensuring a sustainable management of its ecosystem services.

Macular Morphology in Patients With Diabetic Retinopathy Treated by ILM Peeling: A Propensity Score-Matched Analysis.

BACKGROUND AND OBJECTIVE: To analyze the effects of vitrectomy combined with internal limiting membrane (ILM) peeling in patients with diabetic retinopathy (DR) by propensity score-matched analysis. PATIENTS AND METHODS: Patients with proliferative DR that underwent pars plana vitrectomy were divided into two groups: without or with additional ILM peeling. Propensity score-matched analyses of variables were carried out. Optical coherence tomography (OCT) was conducted at the 6-month follow-up. The primary outcome measures were epiretinal membrane (ERM), intraretinal cystic changes, recurrent macular edema, and blurring of the inner segment/outer segment (IS/OS) margin. RESULTS: There were 41 patients in Group 1 (non-ILM peeling) and 41 patients in Group 2 (ILM peeling). ERM was observed in 11 of 41 eyes (26.8%) in Group 1, and three of 41 eyes (7%) in Group 2 at the 6-month follow-up (P = .019). Intraretinal cystoid changes were observed in 13 eyes of Group 1 and four eyes of Group 2 (P = .014). The median central macular thickness was 250.00 ± 135.09 µm in Group 1 and 235.00 ± 101.55 µm in Group 2 (P = .738). Macular edema was observed in 24 eyes (58.5%) in Group 1 and 19 eyes (46.3%) in Group 2 (P = 0.269). There was no significant difference in foveal dip angle between the groups (P = .820). The IS/OS margin was disrupted in 48.8% and 56.1% of eyes in Groups 1 and 2, respectively, without significant difference. There was also no significant difference in best-corrected visual acuity (BCVA) between two groups before surgery, and there was no significant difference in BCVA between two groups at 6 months after surgery (P = .13). CONCLUSION: The authors' results indicate that vitrectomy combined with ILM peeling can minimize ERM formation and eliminate intraretinal cystoid changes, but the functional recovery is limited. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:420-425.].

Novel Norrie disease gene mutations in Chinese patients with familial exudative vitreoretinopathy.

PURPOSE: This study aims to analyze the Norrie disease gene (NDP) variants in patients with familial exudative vitreoretinopathy (FEVR) and their clinical features. METHODS: Thirty-three Chinese patients (22 familial and 11 simplex) who were diagnosed as FEVR underwent detailed ocular examinations in Beijing Tongren Hospital. Peripheral venous blood was drawn from the patients and their family members for the extraction of genomic DNA. All exons of NDP gene were analyzed by direct sequencing of PCR-amplified DNA fragments. RESULTS: Four novel mutations in NDP gene were identified in four X-linked FEVR families: a C → T transversion, c. 625C → T, in exon 3, resulting in a serine-to-proline change in codon 73 (S73P); a C → G transition, c. 751C → G, in exon 3, resulting in an arginine-to-glycine change in codon 115 (R115G); a T → C transversion of nucleotide 331 at 5'UTR in exon 2 (c.331 T → C); and a C → T transversion of the nucleotide 5 in intron 1 (IVS1 + 5C → T). The mutations were not present in the control group (n = 100). CONCLUSIONS: Our results extend the spectrum of NDP gene mutations. The mutations in the non-coding region of NDP may play a crucial role in the pathogenesis of FEVR.

Fusion of subarachnoid hemorrhage data and computed tomography angiography data is helpful to identify the rupture source in patients with multiple intracranial aneurysms.

Determining the rupture source is imperative in patient with aneurysmal subarachnoid hemorrhage (SAH). About one third of SAH cases with multiple intracranial aneurysms cannot be certain of the rupture source according to the hemorrhage pattern. This study aims to identify of the rupture source in patients with multiple intracranial aneurysms by fusing SAH data and computed tomography angiography (CTA) data. This retrospective study included 52 aneurysmal SAH patients with multiple intracranial aneurysms. In the 52 patients, 36 had definitive hemorrhage patterns on computed tomography imaging. And the other 16 patients had non-definitive hemorrhage patterns, which were bewildered for us to determine the ruptured aneurysms. Fusion of SAH data and CTA data was performed to demonstrate the spatial relationship between the SAH with each aneurysm by using the 3D Slicer software. For the patients with definitive bleed patterns, all of the suspected ruptured aneurysms were confirmed to be accurate according to the surgical records. Interestingly, the suspected rupture sources were correct in 14 of 16 patients with non-definitive hemorrhage patterns. For all 52 patients with multiple intracranial aneurysms, the ruptured aneurysms were identified in 50 cases (96.2%). In conclusion, fusion of SAH data and CTA data can precisely demonstrate the spatial relationship between the SAH with each aneurysm, which is helpful to determine the ruptured aneurysm in patients with multiple intracranial aneurysms.

Glioma cells are resistant to inflammation­induced alterations of mitochondrial dynamics.

Accumulating evidence suggests that inflammation is present in solid tumors. However, it is poorly understood whether inflammation exists in glioma and how it affects the metabolic signature of glioma. By analyzing immunohistochemical data and gene expression data downloaded from bioinformatic datasets, the present study revealed an accumulation of inflammatory cells in glioma, activation of microglia, upregulation of proinflammatory factors (including IL­6, IL­8, hypoxia­inducible factor­1α, STAT3, NF­κB1 and NF­κB2), destruction of mitochondrial structure and altered expression levels of electron transfer chain complexes and metabolic enzymes. By monitoring glioma cells following proinflammatory stimulation, the current study observed a remodeling of their mitochondrial network via mitochondrial fission. More than half of the mitochondria presented ring­shaped or spherical morphologies. Transmission electron microscopic analyses revealed mitochondrial swelling with partial or total cristolysis. Furthermore, proinflammatory stimuli resulted in increased generation of reactive oxygen species, decreased mitochondrial membrane potential and reprogrammed metabolism. The defective mitochondria were not eliminated via mitophagy. However, cell viability was not affected, and apoptosis was decreased in glioma cells after proinflammatory stimuli. Overall, the present findings suggested that inflammation may be present in glioma and that glioma cells may be resistant to inflammation­induced mitochondrial dysfunction.

Real-time segmentation and tracking of excised corneal contour by deep neural networks for DALK surgical navigation.

OBJECTIVE: Corneal disease is one of the main causes of blindness for humans globally nowadays, and deep anterior lamellar keratoplasty (DALK) is a widely applied technique for corneal transplantation. However, the position of stitch points highly influences the success rate of such surgery, which would require accurate control and manipulation of surgical instruments. METHODS: In this paper, we present a deep learning framework for augmented reality (AR) based surgery navigation to guide the suturing in DALK. It can robustly track the excised corneal contour by semantic segmentation and the reconstruction of occlusion. We propose a novel optical flow inpainting network to recover the missing motion caused by occlusion. The occluded regions are detected by weakly supervised segmentation of surgical instruments and reconstructed by key frame warping along the completed optical flow. Then we introduce two types of loss function to adapt the inpainting network in the optical flow space. RESULTS: Our techniques are tested and evaluated by a number of real surgery videos from Shandong Eye Hospital in China. We compare our approaches with other typical methods in the corneal contour segmentation, optical flow inpainting and occlusion regions reconstruction. The tracking accuracy reachs 99.2% in average and PSNR reaches 25.52 for the reconstruction of the occluded frames. CONCLUSION: From the experimental evaluations and user study, both the qualitative and quantitative results indicate that our techniques can achieve accurate detection and tracking of corneal contour under complex disturbance in real-time surgical scenes. Our prototype AR navigation system would be highly useful in clinical practice.

Downregulation of reelin predicts poor prognosis for glioma.

Aim: In the present study, we studied the relationship between RELN and prognosis in glioma. Materials & methods: Expression profiles and methylation data of RELN were obtained from bioinformatic datasets. Correlations between RELN and clinicopathological features and overall survival were respectively assessed using chi-square test and Kaplan-Meier analysis. Results:RELN was downregulated in glioma, and its downregulation correlated well with glioma malignancy and overall survival. Meanwhile, hypermethylation of RELN was significantly correlated with low RELN expression. Additionally, gene set enrichment analysis demonstrated that low expression of RELN correlated with many key cancer pathways, possibly highlighting the importance of RELN in carcinogenesis of brain. Conclusion:RELN may serve as a potential prognostic marker and promising target molecule for new therapy of glioma.

The association between high mobility group box 1 chromatin protein and mitotic chromosomes in glioma cells.

High mobility group box 1 (HMGB1) is an abundant non-histone nuclear protein that functions as a structural protein of chromatin, regulating genome replication and recombination, mRNA transcription and DNA repair. HMGB1 has been implicated in the tumorigenesis of various cancer types, and the upregulation of HMGB1 has been demonstrated in glioma cells. However, the association between HMGB1 and the mitotic chromosomes in glioma remains uncharacterized. In the present study, the sub-cellular localization of HMGB1 in glioma tissues and cells was investigated. In addition, enhanced green fluorescent protein (EGFP)-tagging of the human HMGB1 protein and chromosome spreading were used to investigate the combination of HMGB1 with mitotic chromosomes. The results of the current study indicated that HMGB1 was localized to the nucleus and the cytoplasm, and it was determined to combine with the condensed chromosomes of proliferating cells in paraformaldehyde (PFA)-fixed glioma tissues. However, HMGB1 was also associated with interphase (but not mitotic chromosomes) when fixed with chilled methanol and 5% (v/v) acetic acid or PFA in vitro. Data from live cell imaging and chromosome spreading indicated the association of HMGB1 with mitotic chromosomes in glioma cells. The present results suggest that HMGB1 combines with mitotic chromosomes in glioma cells, and that the use of fixatives may result in the dissociation of the HMGB1-DNA interaction. Therefore, in live specimens and chromosome spreads, EGFP fusion proteins may represent an accurate indicator for the determination of the correct localization and interaction of HMGB1 in glioma cells.

SURGICAL OUTCOMES OF 25-GAUGE PARS PLANA VITRECTOMY USING AIR AS AN INTERNAL TAMPONADE FOR PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To report surgical outcomes of 25-gauge pars plana vitrectomy using air as an internal tamponade for patients with primary rhegmatogenous retinal detachment (RRD). METHODS: A retrospective clinical study of 59 eyes of 59 consecutive patients presented with primary RRD at the Beijing Tongren Eye Center in China. From August 2016 to May 2018, medical records of the patients who underwent 25-gauge pars plana vitrectomy with air tamponade for RRD were reviewed. The main outcome measures were primary and final anatomical success (retinal re-attachment) rates, and postoperative complications. RESULTS: Of the 59 patients, aged 54.47 ± 11.81 years, 31 (52.5%) were men. Vitrectomy was performed 3 to 40 (averaged 16.98 ± 10.17) days after the onset of symptoms, and the mean follow-up period was 12.90 ± 5.92 months (ranging 6.07-26.10 months). Forty-two eyes (71.2%) had RRD with retinal breaks in the superior half of the retina, and the mean number of retinal breaks was 1.75 ± 0.94. Three eyes (5.1%) had RRD with giant retinal tears. Of the 59 eyes, 35 (59.3%) had RRD with inferior quadrants involved. Proliferative vitreoretinopathy (PVR) gradings were C1 in 2 (3.4%) eyes and B or below in 57 (96.6%) eyes. The primary and final anatomical success rates were 94.9% (56/59) and 98.3% (58/59), respectively. Of the three eyes which developed re-detachment of the retina, one eye had postoperative progression of PVR and two eyes were RRD associated with macular hole in high myopia. Postoperative complications included 5 eyes (8.5%) with serous choroidal detachment within 3 days after surgery and 4 eyes (6.8%) with macular epiretinal membrane formation 1 to 8 months after surgery. Secondary cataract surgery was performed in 13 of the 53 phakic eyes (24.5%) during follow-up. CONCLUSION: Small-gauge pars plana vitrectomy with air tamponade may be effective in treating selected cases of relatively simple primary RRD. Additional studies are needed to verify the efficacy of this surgical approach for more complicated cases such as those with giant retinal tears.

Risk Factors of Recurrent Retinal Detachment Following Surgical Treatment for Rhegmatogenous Retinal Detachment: A Retrospective Study.

OBJECTIVE: To identify potential risk factors for recurrent retinal detachment after surgical treatment for rhegmatogenous retinal detachment with choroidal detachment (RRD-CD) in a Chinese population. METHODS: A total of 1212 patients with RRD-CD admitted to Beijing Tongren Hospital from 2004 to 2018 were reviewed retrospectively. The rate of recurrent retinal detachment was calculated, and risk factors were analyzed by logistic regression analysis. RESULTS: The average age of the patients was 48.51 years, 760 patients (62.7%) were male, and 630 patients (52.0%) had right eye disease. The recurrence rate in the same eye was 21.3%. The incidence of recurrence retinal detachment was higher in patients who were male, middle age, and with poor preoperative vision, longer axial length, and scleral buckling. Recurrence usually occurred 3 months after surgery. CONCLUSION: Male, middle age, longer axial length, and scleral buckling could be risk factors for recurrent retinal detachment following surgical treatment in patients with RRD-CD.

Overexpression of high mobility group box 1 (HMGB1) has no correlation with the prognosis in glioma.

Aim: We aimed to characterize the role of HMGB1 overexpression in glioma and to evaluate its use as a biomarker. Materials & methods: We used the gene expression datasets and tissue microarray to assess the expression levels of HMGB1 among gliomas of all grades; We then assessed its correlation with the malignancy and outcome of glioma. Results: The increase in HMGB1 mRNA and protein levels was found in glioma, but there was no correlation between HMGB1 expression and glioma malignancy, and overall survival and vital status of glioma patients. Conclusion: Overexpression of HMGB1 is not associated with the malignancy and outcome in glioma. And it is not the valuable biomarker for the early diagnosis of glioma.

Idiopathic Hypertrophic Pachymeningitis Mimicking Meningioma with Occlusion of Superior Sagittal Sinus: Case Report and Review of Literature.

BACKGROUND: Idiopathic hypertrophic pachymeningitis is a rare inflammatory condition with diffuse thickening of the dura mater, which may cause a compressive effect or vascular compromise. CASE DESCRIPTION: A 40-year-old Chinese man presented with persistent headache for 6 months and a sudden epileptic seizure 2 days ago. Magnetic resonance imaging demonstrated a large (71 × 34 × 27 mm) extra-axial mass at the right frontal convexity with severe edema mimicking meningioma. The lesion and peripheral dura mater showed contrast enhancement. Additionally, the skull near the lesion was eroded. Meningioma was diagnosed, and the patient underwent surgery. During the operation, we found the lesion texture was very tough, and the superior sagittal sinus was occluded. Histopathologic findings revealed a large number of infiltrated lymphocytes with fibrosis and microabscess formation; intracranial idiopathic hypertrophic pachymeningitis was diagnosed. Follow-up magnetic resonance imaging performed 3 months after surgery demonstrated the enhancement was notably alleviated. CONCLUSIONS: Idiopathic hypertrophic pachymeningitis should be part of the differential diagnosis of some cases of meningioma.

LncRNA SNHG20 knockdown suppresses the osteosarcoma tumorigenesis through the mitochondrial apoptosis pathway by miR-139/RUNX2 axis.

Increasing evidence has indicated the important roles of long noncoding RNAs (lncRNAs) in human osteosarcoma tumorigenesis. In present study, we aim to investigate the roles of lncRNA SNHG20 (small nucleolar RNA host gene 20) in osteosarcoma tumorigenesis and explore the in-depth molecular mechanism. Results showed that lncRNA SNHG20 expression was up-regulated in osteosarcoma samples and its high-expression indicated the poor prognosis. Loss-of-functional experiments indicated that SNHG20 knockdown inhibited the proliferation, invasion and induced the apoptosis of osteosarcoma cells in vitro. Specifically, SNHG20 knockdown up-regulated the expression levels of caspase-9, caspase-3 and Bax, indicating that SNHG20 knockdown accelerated the apoptosis of osteosarcoma cells via mitochondrial apoptosis pathway. Bioinformatics analysis revealed that miR-139 both targeted with the 3'-UTR of runt-related transcription factor 2 (RUNX2) and SNHG20, which was verified by luciferase reporter assay and RNA immunoprecipitation (RIP). In conclusion, our data reveals that lncRNA SNHG20/miR-139/RUNX2 axis modulates the osteosarcoma tumorigenesis and apoptosis via mitochondrial apoptosis pathway, providing a novel insight for the pathophysiological process.

Surface-modified PLGA nanoparticles with chitosan for oral delivery of tolbutamide.

The main purpose of present study was to develop novel chitosan-modified polylactic-co-glycolicacid nanoparticles (CS@PLGA NPs) for improving the bio-availability of tolbutamide (TOL). The TOL-loaded CS@PLGA NPs (TOL-CS@PLGA NPs) were fabricated with the solvent evaporation method. The cargo-free CS@PLGA NPs showed a diameter of 228.3±2.5nm monitored with a laser light particlesizer, and the transmission electron microscope (TEM) photographs revealed their "core-shell" structures. The Zeta potential of the original PLGA NPs and the cargo-free CS@PLGA NPs was measured to be -20.2±3.21mV and 24.2±1.1mV, respectively. The changes in Zeta potential indicated the CS chains were coated on the surfaces of the original PLGA NPs. The thermal gravity analysis (TGA) curves suggested that the CS chains improved the thermostability of the original PLGA NPs. The results of cells viability indicated the cargo-free CS@PLGA NPs were nontoxicity. The in vitro release profiles suggested that TOL-CS@PLGA NPs could release TOL in pH 7.4 phosphate buffer solution (PBS) at a sustained manner. Streptozotocin (STZ) was employed to build the diabetic rat models. The physiological changes in the islet ß cells confirmed the obtaining of diabetic rats. After treatment by gavage, the TOL-CS@PLGA NPs showed an excellent hypoglycemic effect. Therefore, the TOL-CS@PLGA NPs had a potential application in oral delivery of TOL.

Association of three single nucleotide polymorphisms at the SIX1-SIX6 locus with primary open angle glaucoma in the Chinese population.

This study investigated the genetic association of three single nucleotide polymorphisms (SNPs; rs10483727, rs33912345, and rs146737847) at the SIX1-SIX6 locus with primary open angle glaucoma (POAG) in the Chinese population. A total of 866 subjects with POAG (685 high-tension glaucoma (HTG) and 181 normal-tension glaucoma (NTG)) and 266 control individuals were included. Significant genetic association was identified for rs10483727 in HTG (P=0.02; odds ratio (OR)=1.31), NTG (P=7.41×10(-6); OR=2.71), and POAG (i.e., HTG and NTG combined; P=0.001; OR=1.44). rs33912345 was also significantly associated with HTG (P=0.008; OR=1.36), NTG(P=2.72×10(-6); OR=2.27), and POAG (P=3.84×10(-4); OR=1.49). The rare SIX6 mutation, rs146737847, was not found in the subjects enrolled in this study. Stratification by patient age identified that both rs10483727 and rs33912345 were significantly associated with NTG in patients aged above 40 years (P=2.08×10(-5); OR=2.28), whereas in patients aged between 20-40 years, rs33912345 was significantly associated with NTG (P=0.017; OR=2.06). In HTG, the genetic associations for both rs10483727 and rs33912345 were significant in patients aged between 20-40 years (P=0.006; OR=1.56) but not in those aged above 40 years (P=0.118, OR=1.21 and P=0.042, OR=1.29, respectively). This study replicated the association of POAG with two SNPs at the SIX1-SIX6 locus and demonstrated that SNPs, rs10483727 and rs33912345, are significantly associated with POAG, especially with NTG in patients aged above 40 years.