Metal organic framework UiO-66 incorporated ultrafiltration membranes for simultaneous natural organic matter and heavy metal ions removal.

In this work, a new type of UiO-66 incorporated polysulfone (PSf) ultrafiltration (UF) membranes was fabricated to enhance antifouling properties and heavy metal ions removal efficiency. The UF membranes incorporating different loadings of the UiO-66 filler were prepared via the classical phase inversion process. These membranes unveiled enhanced hydrophilicity, porosity, water uptake, zeta potential, mechanical strength, permeability, and HA removal ratios due to the incorporation of hydrophilic UiO-66 fillers. Particularly, HA rejection ratios were observed to be approximately 93% for all the modified membranes, which was attributed to electrostatic repulsion interactions between the hydrophilic groups of HA and UiO-66. Moreover, the antifouling abilities of the modified membranes were evaluated and found to be much better with a high flux recovery ratio (FRR) of about 88% when compared to the blank PSf membrane (only around 34%). Moreover, the UiO-66 incorporated membranes were highly-effective in the removal of contaminants like heavy metal ions (Sr2+, Pb2+, Cd2+, and Cr6+) and HA at the same time. Overall, the PSf UF membranes incorporating UiO-66 opened up a new avenue to enhance the membrane hydrophilicity, permeability, antifouling properties as well as heavy metal ions removal abilities.

Cerebral perfusion changes of the basal ganglia and thalami in full-term neonates with hypoxic-ischaemic encephalopathy: a three-dimensional pseudo continuous arterial spin labelling perfusion magnetic resonance imaging study.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the common causes of neurological injury in full-term neonates following perinatal asphyxia. The conventional magnetic resonance technique has low sensitivity in detecting variations in cerebral blood flow in patients with HIE. OBJECTIVE: This article evaluates the clinical diagnostic value of three-dimensional pseudo-continuous arterial spin labelling (3-D pcASL) perfusion magnetic resonance imaging (MRI) for early prediction of neurobehavioral outcomes in full-term neonates with HIE. MATERIALS AND METHODS: All neonates diagnosed with HIE underwent MRI (conventional and 3-D pcASL perfusion MRI). Cerebral blood flow values were measured in the basal ganglia (caudate nuclei, lenticular nuclei), thalami and white matter regions (frontal lobes, corona radiata). After 1-month follow-up, the Neonatal Behavioral Neurological Assessment scores were used to divide patients into favourable outcome group versus adverse outcome group. RESULTS: Twenty-three patients were enrolled in this study. There were no statistical differences between the symmetrical cerebral blood flow values of bilateral basal ganglia, thalami and white matter regions. However, the cerebral blood flow values of grey matter nuclei were higher than the white matter regions. The average value of cerebral blood flow in the basal ganglia and thalami in the adverse outcome group was 37.28±6.42 ml/100 g/min, which is greater than the favourable outcome group (22.55 ± 3.21 ml/100 g/min) (P<0.01). The area under the curve (AUC) of 3-D pcASL perfusion MRI was 0.992 with a cutoff value of 28.75 ml/100 g/min, with a Youden's index of 0.9231. The sensitivity and specificity were 92.3% and 100%, respectively. CONCLUSION: The 3-D pcASL demonstrated higher perfusion alteration in the basal ganglia and thalami of neonatal HIE with adverse outcomes. The 3-D pcASL perfusion MRI has the potential to predict neurobehavioral outcomes of neonates with HIE.

Tissue Transglutaminase Impairs HTR-8/SVneo Trophoblast Cell Invasion via the PI3K/AKT Signaling Pathway.

OBJECTIVES: The pathogenesis of preeclampsia (PE) is associated with impaired trophoblast invasion, which results in placental insufficiency. Our earlier studies demonstrated that tissue transglutaminase (tTG) is highly expressed in human PE serum. However, whether tTG participates in trophoblast invasion remains unclear. The aim of the present study was to determine the role and mechanism of tTG in regulating matrix metalloproteinase (MMP)-2/MMP-9 expression to reduce trophoblast invasiveness in PE. METHODS: HTR-8/SVneo cells were transfected with a lentivirus vector and small interfering RNA targeting tTG. The protein level was detected by Western blotting. Cell proliferation and apoptosis were assessed by MTS and flow cytometry assays, respectively. Cell invasion was investigated by Transwell assay. In addition, the influence of tTG on PI3K and AKT mRNA levels in HTR-8/SVneo cells was evaluated using reverse transcription-quantitative PCR. RESULTS: tTG-overexpression inhibited HTR-8/SVneo cell proliferation and invasion and promoted apoptosis. In addition, upregulation of tTG induced an increase of PI3K and phosphorylated AKT and a decrease of MMP-2 and MMP-9 expression. tTG-knockdown significantly promoted the proliferation and invasion of HTR-8/SVneo cells and inhibited the apoptosis. Furthermore, the PI3K expression level was reduced, and the MMP-2/MMP-9 protein levels were increased. CONCLUSION: Taken together, the present study demonstrated that tTG-overexpression inhibited HTR-8/SVneo cell invasion via reducing the expression of MMP-2 and MMP-9 by activating PI3K/AKT signaling pathway, which may lead to the occurrence or development of PE. The present data provide new insights into modulation of tTG expression as a potential therapeutic target for PE.

Genetic tests aid in counseling of fetuses with cerebellar vermis defects.

OBJECTIVE: To assess the value of chromosome microarray analysis (CMA) and whole exome sequencing (WES) in fetuses with cerebellar vermis defects (CVD). METHODS: From 2013 to 2019, we performed CMA on 43 fetuses with CVD, who were divided into cerebellar vermis hypoplasia (CVH) group and Dandy-Walker malformation (DWM) group according to morphological subtypes. Subsequently, WES was performed on 19 fetuses with normal CMA results to identify diagnostic genetic variants (DGVs). RESULTS: Chromosome aneuploidies and clinically significant copy number variants were identified in 23.3% (10/43) of fetuses, and a significantly higher positive rate was found in fetuses with multiple compared with isolated malformations (36% vs 5.6%, P = .028). STAG2 genes related to Xq25 duplication syndrome was possibly a novel candidate gene for CVD. WES detected eight DGVs in seven genes among the 19 fetuses tested. Autosomal recessive ciliopathies (4/8) caused by TMEM231, CSPP1, and CEP290 mutations, were the most frequent monogenetic diseases, followed by Opitz GBBB syndrome (2/8) caused by MID1 and SPECC1L variants. CONCLUSION: The combined use of CMA and WES has the potential to provide genetic diagnoses in 42% (18/43) of fetal CVD. WES should be offered when CMA results are normal.

A deep-learning model using automated performance metrics and clinical features to predict urinary continence recovery after robot-assisted radical prostatectomy.

OBJECTIVES: To predict urinary continence recovery after robot-assisted radical prostatectomy (RARP) using a deep learning (DL) model, which was then used to evaluate surgeon's historical patient outcomes. SUBJECTS AND METHODS: Robotic surgical automated performance metrics (APMs) during RARP, and patient clinicopathological and continence data were captured prospectively from 100 contemporary RARPs. We used a DL model (DeepSurv) to predict postoperative urinary continence. Model features were ranked based on their importance in prediction. We stratified eight surgeons based on the five top-ranked features. The top four surgeons were categorized in 'Group 1/APMs', while the remaining four were categorized in 'Group 2/APMs'. A separate historical cohort of RARPs (January 2015 to August 2016) performed by these two surgeon groups was then used for comparison. Concordance index (C-index) and mean absolute error (MAE) were used to measure the model's prediction performance. Outcomes of historical cases were compared using the Kruskal-Wallis, chi-squared and Fisher's exact tests. RESULTS: Continence was attained in 79 patients (79%) after a median of 126 days. The DL model achieved a C-index of 0.6 and an MAE of 85.9 in predicting continence. APMs were ranked higher by the model than clinicopathological features. In the historical cohort, patients in Group 1/APMs had superior rates of urinary continence at 3 and 6 months postoperatively (47.5 vs 36.7%, P = 0.034, and 68.3 vs 59.2%, P = 0.047, respectively). CONCLUSION: Using APMs and clinicopathological data, the DeepSurv DL model was able to predict continence after RARP. In this feasibility study, surgeons with more efficient APMs achieved higher continence rates at 3 and 6 months after RARP.

Whole-exome sequencing for prenatal diagnosis of fetuses with congenital anomalies of the kidney and urinary tract.

BACKGROUND: In the absence of cytogenetic abnormality, fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) with/without other structural anomalies show a higher likelihood of monogenic causes; however, defining the underlying pathology can be challenging. Here, we investigate the value of whole-exome sequencing (WES) in fetuses with CAKUT but normal findings upon karyotyping and chromosome microarray analysis. METHODS: WES was performed on DNA from the cord blood of 30 fetuses with unexplained CAKUT with/without other structural anomalies. In the first 23 cases, sequencing was initially performed on fetal DNA only; for the remaining seven cases, the trio of fetus, mother and father was sequenced simultaneously. RESULTS: Of the 30 cases, pathogenic variants were identified in 4 (13%) (UMOD, NEK8, HNF1B and BBS2) and incidental variants in 2 (7%) (HSPD1 and GRIN2B). Furthermore, two of the above four cases had other anomalies in addition to CAKUT. Thus, the detection rate was only 2/22 (9.1%) for isolated CAKUT and 2/8 (25%) for CAKUT with other abnormalities. CONCLUSIONS: Applying WES to the prenatal diagnostic approach in CAKUT fetuses with or without other anomalies allows for an accurate and early etiology-based diagnosis and improved clinical management. To expedite interpretation of the results, trio sequencing should be employed; however, interpretation may nevertheless be compromised by incomplete coverage of all relevant genes.

Selection of antioxidants against ovarian oxidative stress in mouse model.

Oxidative stress (OS) plays an important role in the process of ovarian granulosa cell apoptosis and follicular atresia. The aim of this study was to select antioxidant against OS in ovary tissue. Firstly, we chose the six antioxidants and analyzed the reactive oxygen species (ROS) level in the ovary tissue. The results showed that proanthocyanidins, gallic acid, curcumin, and carotene decrease the ROS level compared with control group. We further demonstrated that both proanthocyanidins and gallic acid increase the antioxidant enzymes activity. Moreover, change in the ROS level was not observed in proanthocyanidins and gallic acid group of brain, liver, spleen, and kidney tissues. Finally, we found that proanthocyanidins and gallic acid inhibit pro-apoptotic genes expression in granulosa cells. Taken together, proanthocyanidins and gallic acid may be the most acceptable and optimal antioxidants specifically against ovarian OS and also may be involved in the inhibition of granulosa cells apoptosis in mouse ovary.

Outcome of isolated enlarged cisterna magna identified in utero: experience at a single medical center in mainland China.

OBJECTIVE: The objective of this study is to explore the effects of prenatal isolated enlarged cisterna magna (IECM) on postnatal development. METHODS: We followed up 123 fetuses with an enlarged cisterna magna (ECM), who were divided into IECM (group 1) and non-IECM (ECM plus other anomalies, group 2) groups, and compared 60 normal infants with normal fetal ultrasound. We assessed infants postnatally using the Gesell Developmental Schedules. Fetal magnetic resonance imaging, karyotyping, and chromosomal microarray analysis test were offered. RESULTS: The developmental quotients of gross motor and adapting abilities were significantly lower in infants with IECM compared with normal infants (80.81 ± 3.44 vs 99.20 ± 4.54 and 98.70 ± 3.27 vs 100.30 ± 5.33, respectively), and the depths ≥15 mm and 13 to 14.90 mm were associated with significantly lower adapting abilities (P < 0.03 and P < 0.05) compared with the normal (97.16 ± 2.17 and 98.21 ± 1.76 vs 100.30 ± 5.33, respectively), while these scores were still within the borderline range, and the other subtests were not significantly different. Furthermore, the group 2 showed a significantly worse performance in the test. CONCLUSIONS: The outcome of children with IECM may be guarded, especially some subtle deficits in adapting and gross motor abilities. In contrast, the developmental quotients of infants with prenatal non-IECM were lower than that those of normal infants. © 2017 John Wiley & Sons, Ltd.

Fatty acid profiling of blood cell membranes by gas chromatography with mass spectrometry.

Fatty acids, which are well-known for their influence on human metabolism and signal transduction, are also a substantial component of cellular membranes and regulate the basic properties and functions of membranes. Owing to their multiple functions, fatty acid profiles of cell membranes are of great interest to those who are studying the relationship between membrane biochemical compositions and functions. A HCl-catalyzed derivation method and a gas chromatography with mass spectrometry analysis method were developed to accurately profile the fatty acids in cell membranes of erythrocytes, leukocytes, and platelets. The detection limits of all 35 fatty acids ranged from 0.58 to 22 ng/mL and the limits of quantitation were between 2.1 and 72 ng/mL. Finally, the established method was used to profile the membrane fatty acids of 44 healthy volunteers from the north and south of China. Results revealed significant differences in the fatty acid profiles from the two regions, particularly those of the erythrocytes. This technique may be applied to cell membrane studies to generate new biological hypotheses concerning fatty acid composition and membrane functions as well as to construct related disease profiles.

Effect of S100A6 over-expression on ß-catenin in endometriosis.

AIM: S100A6 is over-expressed in several human tumors, including pancreatic carcinoma, malignant fibrous histiocytoma, breast, colon, and gastric carcinoma, but little is known about the role of S100A6 in endometriosis. The aim of the present study was to investigate the effect of S100A6 over-expression on ß-catenin in endometrial stromal cells. METHODS: Endometrial stromal cells were transfected with an hS100A6-expressing recombinant lentivirus construct. The expression of ß-catenin was assessed using western blot and reverse transcription-polymerase chain reaction. RESULTS: S100A6 over-expression promoted ß-catenin expression at the RNA and protein levels, in endometrial stromal cells. CONCLUSIONS: S100A6 induces expression of ß-catenin in endometrial stromal cells.

Myocardial hypertrophy: the differentiation of uremic, hypertensive, and hypertrophic cardiomyopathies by cardiac MRI.

OBJECTIVES: To apply cardiac magnetic resonance imaging (CMR) for detailed myocardial characterization in uremic cardiomyopathy (UC), hypertensive cardiomyopathy (HTN), and hypertrophic cardiomyopathy (HCM) aiming to enrich the understanding of UC's etiology and further support the development of therapeutic strategies. METHODS: A total of 152 patients (age: 49.2 ± 9.9 years; 65.8% male) underwent routine CMR from June 2016 to March 2023. Retrospectively, 53 patients with UC, 39 patients with HTN, 30 patients with HCM, and 30 healthy controls were included. Functional analysis, feature tracking of the left ventricle and left atrium, and myocardial T1, T2, and T2* mapping were performed. Statistical analysis included Pearson correlation and ROC analysis to define correlations and discriminators between groups. RESULTS: UC patients demonstrated significantly higher native T1 (p < 0.001 for all) and T2 (p < 0.002 for all) values compared with the other three groups. UC patients revealed higher left atrial reservoir strain rate (p < 0.001 for all) and left atrial conduit strain rate (p < 0.001 for all) absolute values as compared with HTN and HCM patients. A significant correlation between T1 and T2 values in UC patients (r = 0.511, p < 0.001) was found. The combination of T1 values and strain parameters was the best discriminator between UC and HTN patients (AUC = 0.872, 95% CI: 0.801-0.943) and between UC and HCM patients (AUC = 0.840, 95% CI: 0.746-0.934). CONCLUSION: UC reveals distinguishing tissue characteristics as evidenced by T1 and T2 mapping, as well as distinguishing functional strain parameters as compared with other hypertrophic phenotypes such as HTN and HCM. CRITICAL RELEVANCE STATEMENT: The use of CMR imaging in UC patients offers incremental information to elucidate its complex etiology, contributing to ongoing discourse on effective treatment pathways. KEY POINTS: This study investigated uremic, hypertensive, and hypertrophic cardiomyopathies using cardiac MRI. UC patients have higher T1 and T2 values and better preserved cardiac function. Combined strain and T1 values distinguish UC from other cardiomyopathies.

A Comprehensive Survey on Deep Graph Representation Learning.

Graph representation learning aims to effectively encode high-dimensional sparse graph-structured data into low-dimensional dense vectors, which is a fundamental task that has been widely studied in a range of fields, including machine learning and data mining. Classic graph embedding methods follow the basic idea that the embedding vectors of interconnected nodes in the graph can still maintain a relatively close distance, thereby preserving the structural information between the nodes in the graph. However, this is sub-optimal due to: (i) traditional methods have limited model capacity which limits the learning performance; (ii) existing techniques typically rely on unsupervised learning strategies and fail to couple with the latest learning paradigms; (iii) representation learning and downstream tasks are dependent on each other which should be jointly enhanced. With the remarkable success of deep learning, deep graph representation learning has shown great potential and advantages over shallow (traditional) methods, there exist a large number of deep graph representation learning techniques have been proposed in the past decade, especially graph neural networks. In this survey, we conduct a comprehensive survey on current deep graph representation learning algorithms by proposing a new taxonomy of existing state-of-the-art literature. Specifically, we systematically summarize the essential components of graph representation learning and categorize existing approaches by the ways of graph neural network architectures and the most recent advanced learning paradigms. Moreover, this survey also provides the practical and promising applications of deep graph representation learning. Last but not least, we state new perspectives and suggest challenging directions which deserve further investigations in the future.

Few-shot Molecular Property Prediction via Hierarchically Structured Learning on Relation Graphs.

This paper studies few-shot molecular property prediction, which is a fundamental problem in cheminformatics and drug discovery. More recently, graph neural network based model has gradually become the theme of molecular property prediction. However, there is a natural deficiency for existing methods, that is, the scarcity of molecules with desired properties, which makes it hard to build an effective predictive model. In this paper, we propose a novel framework called Hierarchically Structured Learning on Relation Graphs (HSL-RG) for molecular property prediction, which explores the structural semantics of a molecule from both global-level and local-level granularities. Technically, we first leverage graph kernels to construct relation graphs to globally communicate molecular structural knowledge from neighboring molecules and then design self-supervised learning signals of structure optimization to locally learn transformation-invariant representations from molecules themselves. Moreover, we propose a task-adaptive meta-learning algorithm to provide meta knowledge customization for different tasks in few-shot scenarios. Experiments on multiple real-life benchmark datasets show that HSL-RG is superior to existing state-of-the-art approaches.

The Phosphatase Cascade Nem1/Spo7-Pah1 Regulates Fungal Development, Lipid Homeostasis, and Virulence in Botryosphaeria dothidea.

Protein phosphatase complex Nem1/Spo7 plays crucial roles in the regulation of various biological processes in eukaryotes. However, its biological functions in phytopathogenic fungi are not well understood. In this study, genome-wide transcriptional profiling analysis revealed that Nem1 was significantly upregulated during the infection process of Botryosphaeria dothidea, and we identified and characterized the phosphatase complex Nem1/Spo7 and its substrate Pah1 (a phosphatidic acid phosphatase) in B. dothidea. Nem1/Spo7 physically interacted with and dephosphorylated Pah1 to promote triacylglycerol (TAG) and subsequent lipid droplet (LD) synthesis. Moreover, the Nem1/Spo7-dependently dephosphorylated Pah1 functioned as a transcriptional repressor of the key nuclear membrane biosynthesis genes to regulate nuclear membrane morphology. In addition, phenotypic analyses showed that the phosphatase cascade Nem1/Spo7-Pah1 was involved in regulating mycelial growth, asexual development, stress responses, and virulence of B. dothidea. IMPORTANCE Botryosphaeria canker and fruit rot caused by the fungus Botryosphaeria dothidea is one of the most destructive diseases of apple worldwide. Our data indicated that the phosphatase cascade Nem1/Spo7-Pah1 plays important roles in the regulation of fungal growth, development, lipid homeostasis, environmental stress responses, and virulence in B. dothidea. The findings will contribute to the in-depth and comprehensive understanding of Nem1/Spo7-Pah1 in fungi and the development of target-based fungicides for disease management.

ASXL3 gene mutations inhibit cell proliferation and promote cell apoptosis in mouse cardiomyocytes by upregulating lncRNA NONMMUT063967.2.

Congenital heart disease (CHD) is a serious condition with unknown etiology. In a recent study, a compound heterozygous mutation (c.3526C > T [p.Arg1176Trp] and c.4643A > G [p.Asp1548Gly]) in the ASXL3 gene was identified, which is associated with CHD. This mutation was overexpressed in HL-1 mouse cardiomyocyte cells, leading to increased cell apoptosis and decreased cell proliferation. However, whether this effect is mediated by long noncoding RNAs (lncRNAs) is yet to be determined. We identified the differences among lncRNA and mRNA profiles in mouse heart tissues using sequencing to explore this issue. We detected HL-1 cell proliferation and apoptosis through CCK8 and flow cytometry. Fgfr2, lncRNA, and Ras/ERK signaling pathway expressions were evaluated using quantitative real time polymerase chain reaction (qRT-PCR) and western blot (WB) assays. We also conducted functional investigations by silencing lncRNA NONMMUT063967.2. The sequencing revealed significant changes in lncRNA and mRNA profiles, with the expression of lncRNA NONMMUT063967.2 being significantly promoted in the ASXL3 gene mutations group (MT) while the expression of Fgfr2 being downregulated. The in vitro experiments showed that ASXL3 gene mutations inhibited the proliferation of cardiomyocytes and accelerated cell apoptosis by promoting the expression of lncRNAs (NONMMUT063967.2, NONMMUT063918.2, and NONMMUT063891.2), suppressing the formation of FGFR2 transcripts, and inhibiting the Ras/ERK signaling pathway. The decrease in FGFR2 had the same effect on the Ras/ERK signaling pathway, proliferation, and apoptosis in mouse cardiomyocytes as ASXL3 mutations. Further mechanistic studies revealed that suppression of lncRNA NONMMUT063967.2 and overexpression of FGFR2 reversed the effects of the ASXL3 mutations on the Ras/ERK signaling pathway, proliferation, and apoptosis in mouse cardiomyocytes. Therefore, ASXL3 mutation decreases FGFR2 expression by upregulating lncRNA NONMMUT063967.2, inhibiting cell proliferation and promoting cell apoptosis in mouse cardiomyocytes.

Identification of differential microRNAs and messenger RNAs resulting from ASXL transcriptional regulator 3 knockdown during during heart development.

Congenital heart disease (CHD) is the most common birth defect. Although ASXL transcriptional regulator 3 (ASXL3) has been reported to cause hereditary CHD, ASXL3-mediated mechanisms in heart development remain unclear. In this study, we used dimethyl sulfoxide (DMSO) to induce differentiation in P19 cells, observed cell morphology using light microscopy after ASXL3 knockdown, and determined the levels of associated myocardial cell markers using reverse transcription-quantitative polymerase chain reaction and western blotting. Subsequently, we used microRNA sequencing, messenger RNA (mRNA) sequencing, and bioinformatics to initially identify the possible mechanisms through which ASXL3-related microRNAs and mRNAs affect heart development. The results indicated that DMSO induced P19 cell differentiation, which could be inhibited by ASXL3 knockdown. We screened 1214 and 1652 differentially expressed microRNAs and mRNAs, respectively, through ASXL3 knockdown and sequencing; these differentially expressed miRNAs were largely enriched in PI3K-Akt, mitogen-activated protein kinase, and Rap1 signaling pathways. Additionally, 11 miRNAs associated with heart development were selected through a literature review. Our analysis indicated the involvement of mmu-miR-323-3p in P19 cell differentiation through the PI3K-Akt pathway. In conclusion, ASXL3 may be involved in the regulation of heart development. This comprehensive study of differentially expressed microRNAs and mRNAs through ASXL3 knockdown in P19 cells provides new insights that may aid the prevention and treatment of CHD.

Removal of bentazone from micro-polluted water using MIEX resin: kinetics, equilibrium, and mechanism.

The contamination of surface and ground water by bentazone has attracted increasing global concern in recent years. We conducted a detailed investigation using MIEX resin to eliminate bentazone from waters. Batch experiments were carried out to evaluate the effect of process parameters, such as retention time, resin amount, and initial pesticide concentration, on removal efficiency of bentazone. Results showed the sorption process was fast and bentazone could be efficiently removed in 30 minutes. The kinetic process of bentazone sorption on MIEX resin was well described by pseudo second-order model and intraparticle diffusion was the rate controlling step. The MIEX resin possessed the highest sorption capacity of 0.2656 mmol/mL for bentazone according to Langmuir fitting. Bentazone is a hydrophobic ionizable organic compound, and both ionic charge and hydrophobic aromatic structure governed the sorption characteristics on MIEX resin. The different removal efficiencies of ionic and non-ionic pesticides, combined with the charge balance equations of bentazone, SO4(2-), NO3- and Cl-, indicated that removal of bentazone using MIEX resin occurred primarily via ion exchange.

Knockdown of growth factor receptor bound protein 7 suppresses angiogenesis by inhibiting the secretion of vascular endothelial growth factor A in ovarian cancer cells.

Growth factor receptor bound protein 7 (GRB7) plays an important role in regulating the growth and metastasis of ovarian cancer. Angiogenesis is the basis for the growth, invasion, and metastasis of malignant tumors. In the current study, we aimed to determine whether GRB7 plays a role in regulating angiogenesis in ovarian cancer. Immunohistochemistry on tissue microarray showed that GRB7 and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) protein expression were positively correlated in ovarian cancer tissues. GRB7 knockdown suppressed vascular endothelial growth factor A (VEGFA) expression and reduced VEGFA secretion. The effects of GRB7-silenced SKOV-3 cells on human umbilical vein endothelial cells (HUVECs) were evaluated using a transwell cell co-culture model, which showed that knockdown of GRB7 in SKOV-3 cells suppressed HUVEC proliferation, migration, invasion, and tube formation. Moreover, knockdown of GRB7 in SKOV-3 cells downregulated the expression of proteins associated with angiogenesis, including vascular endothelial growth factor receptor-2 (VEGFR2), mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), extracellular signal-regulated kinases 1 and 2 (ERK1/2), notch receptor 1 (NOTCH1), and delta-like canonical Notch ligand 4 (DLL4) in HUVECs. In conclusion, knockdown of GRB7 in ovarian cancer cells is an attractive potential therapeutic target for the suppression of angiogenesis in ovarian cancer. GRB7 may regulate angiogenesis through VEGFA/VEGFR2 signaling and its downstream pathways.

Prenatal diagnosis of submicroscopic chromosomal aberrations in fetuses with congenital cystic adenomatoid malformation by chromosomal microarray analysis.

OBJECTIVES: To explore the copy number variations (CNVs) of fetal congenital cystic adenomatoid malformation (CCAM). METHODS: Fetuses with CCAM were investigated by karyotypes and chromosomal microarray analysis (CMA). The cases were classified as isolated or CCAM with additional structural anomalies. The pregnancy outcome and neonatal prognosis were reported after the follow-up investigation. RESULTS: The karyotypes of 43 fetuses were analyzed and no abnormal karyotype was detected. Thirty-seven cases were further tested using CMA. The CMA identified pathogenic CNVs in three fetuses with a pathogenic detection rate of 8.1%. Well-known microdeletion or microduplication syndromes, including RCAD syndrome, HNPP, and CMT1A were identified, among which HNPP and CMT1A were incidental findings. After excluding two incidental findings, there were no pathogenic CNVs in isolated CCAM. There were no significant differences in pathogenic CNVs between isolated CCAM and CCAM with additional structural anomalies (0%, 0/31 versus 16.7%, 1/6, p=.162). Nearly half of the patients (53.8%, 14/26) underwent surgery after birth with good postoperative recoveries while the remaining half patients were spontaneous regression or asymptomatic. CONCLUSIONS: The results demonstrated the value of CMA in the prenatal diagnosis of CCAM. CCAM associated with other structural defects enhanced the frequency of pathogenic CNVs while isolated CCAM may not be associated with an increase in the prevalence of pathogenic CNVs. CCAMs have an overall good prognosis.

Optimization via game theoretic control.

Using game theoretic control to solve optimization problem is a recently developed promising method. The key technique is to convert a networked system into a potential game, with a pre-assigned criterion as the potential function. An algorithm is designed for updating strategies to reach a Nash equilibrium (i.e. optimal solution).