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To study the role and mechanism of aquaporin-8 (AQP8) in placental vascular development in gestational diabetes mellitus (GDM), hematoxylin–eosin staining and immunohistochemistry were utilized to analyze the histopathological changes in placentas in GDM patients. Transwell, CCK-8, and tube formation assays were performed to examine cell migration, proliferation, and tube formation. AQP8, vascular cell adhesion molecule 1 (VCAM-1), tumor necrosis factor alpha (TNF)-α, and vascular endothelial growth factor (VEGF)-A expression levels were investigated. Relative to the control group, the placentas in the GDM group showed morphological changes, the number of microvessels in the placental villi arterioles was significantly higher, and the area of microvessels in the arterioles of placental villi was significantly lower. The expression levels of VCAM-1, TNF-α, VEGF-A, and AQP8 in the GDM placentas and human umbilical vein endothelial cells (HUVECs) stimulated by high glucose were significantly higher than those in the control group, and AQP8 was located in placental endothelial cells. Overexpression of glucose and AQP8 inhibited tube formation, migration, and proliferation in HUVECs. High glucose levels can induce dysfunction in vascular endothelial cells and lead to pathological changes in the placental vascular structure in GDM. AQP8 overexpression in placental GDM can inhibit endothelial cell behavior, cause endothelial cell dysfunction, and further participate in the occurrence and development of GDM placental vascular lesions.

Hyperhimatins A-P (1-16), sixteen new bicyclic polyprenylated acylphloroglucinols (BPAPs), were isolated and identified from Hypericum himalaicum. The planner structures of hyperhimatins A-P were confirmed via extensive NMR and careful HRESIMS data analysis. The absolute configurations of the new compounds were mainly determined by electronic circular dichroism (ECD) calculation, NMR calculation, and the circular dichroism data of the in situ formed [Rhsub2/sub(OCOCFsub3/sub)sub4/sub] complexes. All compounds were assessed for the glucose transporter 4 (GLUT-4) translocation and expression enhancing effects in L6 myotubes. Compounds 1-16 could promote the GLUT-4 expression by the range of 1.95-6.04 folds, and accelerate the GLUT-4 fusion with the plasma membrane ranged from 53.56% to 76.97% at a consistence of 30 μg/mL, among compound 10 displayed the strongest GLUT-4 translocation effect.

Transplantation of allogeneic adult spinal cord tissues (aSCTs) to replace the injured spinal cord, serves as a promising strategy in complete spinal cord injury (SCI) repair. However, in addition to allograft immune rejection, damage-associated molecular pattern (DAMP)-mediated inflammatory microenvironments greatly impair the survival and function of transplants. In this study, we aimed to regulate the immune microenvironment after aSCT implantation by developing a functional hybrid gelatin and hyaluronic acid hydrogel (F-G/H) modified with cationic polymers and anti-inflammatory cytokines that can gelatinize at both ends of the aSCT to glue the grafts for perfect matching at defects. The F-G/H hydrogel exhibited the capacities of DAMP scavenging, sustainably released anti-inflammatory cytokines, and reduced lymphocyte accumulation, thereby modulating the immune response and enhancing the survival and function of aSCTs. When the hydrogel was used in combination with a systemic immunosuppressive drug treatment, the locomotor functions of SCI rats were significantly improved after aSCTs and F-G/H transplantation. This biomaterial-based immunomodulatory strategy may provide the potential for spinal cord graft replacement for treating SCI. STATEMENT OF SIGNIFICANCE: In this study, we aimed to regulate the immune microenvironment by developing a functional hybrid gelatin and hyaluronic acid hydrogel (F-G/H) modified with cationic polymers and anti-inflammatory cytokines that can gelatinize at both ends of the aSCT to glue the grafts for perfect matching at defects. We found that with the treatment of F-G/H hydrogel, the aSCT survival and function was significantly improved, as a result of reducing recruitment and activation of immune cells through TLR- and ST-2- related signaling. With the combination of immunosuppressive drug treatment, the locomotor functions of SCI rats were significantly improved after aSCTs and F-G/H transplantation. Findings from this work suggest the potential application of the F-G/H as a biomaterial-based immunoregulatory strategy for improving the therapeutic efficiency of the transplanted spinal cord graft for spinal cord injury repair.

This study aims to investigate underlying mechanisms of gestational diabetes mellitus (GDM). In this work, the GSE70493 dataset from GDM and control samples was acquired from Gene Expression Omnibus (GEO) database. Afterward, differentially expressed genes (DEGs) were screened between GDM and control samples. Subsequently, functional enrichment analysis and protein-protein interaction (PPI) network analysis of these DEGs were carried out. Furthermore, significant sub-modules were identified, and the functional analysis was also performed. Finally, we undertook a quantitative real-time polymerase chain reaction (qRT-PCR) with the purpose of confirming several key genes in GDM development. There were totally 528 up-regulated and 684 down-regulated DEGs between GDM and healthy samples. The functional analyses suggested that the above genes were dramatically enriched in type 1 diabetes mellitus (T1DM) process and immune-related pathways. Moreover, PPI analysis revealed that several members of human leukocyte antigen (HLA) superfamily, including down-regulated HLA-DQA1, HLA-DRB1, HLA-DPA1, and HLA-DQB1 served as hub genes. In addition, six significant sub-clusters were extracted and functional analysis suggested that these four genes in sub-module 1 were also associated with immune and T1DM-related pathways. Finally, they were also confirmed by qRT-PCR array. Besides, the four members of HLA superfamily might be implicated with molecular mechanisms of GDM, contributing to a deeper understanding of GDM development.

Nowadays, with the increasing number of surveillance cameras, human behavior detection is of importance for public security. Detection of fight behavior using video surveillance is an essential and challenging research field. We propose a multiview fight detection method based on statistical characteristics of the optical flow and random forest. Cyberphysical systems for monitoring can obtain timely and accurate information from this method. Two novel descriptors named Motion Direction Inconsistency (MoDI) and Weighted Motion Direction Inconsistency (WMoDI) are defined to improve the performance of existing methods for videos with different shooting views and solve the misjudgment on nonfight, such as running and talking. First, YOLO V3 algorithm is applied to mark the motion areas, and then, the optical flow is computed to extract descriptors. Finally, Random Forest is used for classification based on statistical characteristics of descriptors. The evaluation results on CASIA dataset demonstrate that the proposed method can improve the accuracy and reduce the rate of missing alarm and false alarm for the detection, and it is very robust against videos with different shooting views.

Yiling Lu,1,* Weichun Tang,2,3,* Xiaoyu Wang,1 Xinyi Kang,1 Jun You,1 Liping Chen1 1Department of Obstetrics and Gynecology, Nantong First People’s Hospital, Nantong, Jiangsu, 226001, People’s Republic of China; 2NHC Key Laboratory of Antibody Technique, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China; 3Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liping ChenDepartment of Gynecology and Obstetrics, Nantong First People’s Hospital, Nantong, Jiangsu, 226001, People’s Republic of ChinaEmail 42770899@qq.comBackground: Endometrial cancer (EC) is a multifactorial disease, and its progression may be driven by abnormal genetic methylation. To clarify the underlying molecular mechanisms and sensitive biomarkers for EC, this study used an integrated bioinformatic analysis to explore the methylation-driven genes of EC.Methods: The mRNA expression data, methylation data and corresponding clinical information of EC samples were downloaded from The Cancer Genome Atlas (TCGA) database. MethylMix algorithm was used to screen out methylation-driven genes in EC. Functional and pathway enrichment analysis and the protein–protein interaction (PPI) analysis were conducted to demonstrate the functions and interactions between these genes. Then, prognosis-related methylated genes were screened out by using univariate and multivariate Cox analyses, and a prognostic risk assessment model for EC was constructed. The methylation sites and expression profiles of candidate genes were further investigated.Results: A total of 127 methylated genes were identified in EC. Four genes (RP11-968O1.5, DCAF12L1, MSX1 and ALS2CR11) were selected as candidate genes to construct a reliable prognostic risk model. The univariate and multivariate Cox proportional hazards regression analyses showed that the risk score based on four genes was an independent prognostic indicator for OS among EC patients. A nomogram was established and the calibration plot analysis indicated the good performance and clinical utility of the nomogram. In addition, the methylation and expression of MSX1 and DCAF12L1 were significantly associated with EC survival rate. The joint ROC analysis revealed that the AUC of DCAF12L1-MSX1 was 0.867, which suggested both have a good EC-diagnosing efficiency. We then coped DCAF12L1 and MSX1 with GESA analysis, finding both were mainly associated with the KRAS signaling pathway.Conclusion: This bioinformatic study combs the methylated genes involved in EC development for the first time, finding that MSX1 and DCAF12L1 could serve as EC prognostic markers and drug targets.Keywords: endometrial cancer, methylation-driven genes, integrated bioinformatic analysis, prognosis, biomarkers

Lysosomes are one of the major centers for regulating cargo degradation and protein quality control. Transcription factor EB (TFEB)-promoted lysosome biogenesis enhances lysosome-mediated degradation and alleviates neurodegenerative diseases, but the mechanisms underlying TFEB modification and activation are still poorly understood. Here, we report essential roles of TFEB acetylation in TFEB nuclear translocation and lysosome biogenesis, which are independent of TFEB dephosphorylation. By screening small molecules, we find that Trichostatin A (TSA), the pan-inhibitor of histone deacetylases (HDACs), promotes nuclear translocation of TFEB. TSA enhances the staining of cells by LysoTracker Red and increases the expression of lysosomal and autophagic genes. We identify four novel acetylated lysine residues in TFEB, which are important for TFEB nuclear translocation and lysosome biogenesis. We show that TFEB acetylation is regulated by HDACs (HDAC5, HDAC6, and HDAC9) and lysine acetyltransferases (KATs), including ELP3, CREBBP, and HAT1. During TSA-induced cytosol-to-nucleus translocation of TFEB, acetylation is independent of TFEB dephosphorylation, since the mTORC1- or GSK3β-related phosphorylation sites on TFEB are still phosphorylated. Administration of TSA to APP/PS1 mice increases the expression of lysosomal and autophagic genes in mouse brains and also improves memory. Accordingly, the β-amyloid plaque burden is decreased. These results show that the acetylation of TFEB, as a novel mechanism of TFEB activation, promotes lysosome biogenesis and alleviates the pathogenesis of Alzheimer's disease. Our results also suggest that HDAC inhibition can promote lysosome biogenesis, and this may be a potential therapeutic approach for the treatment of neurodegenerative diseases and disorders related to HDAC hyperactivation.

Fetal growth restriction (FGR) is a common obstetric disease, which is harmful to the pregnant women and fetuses. It has many influencing factors, but the specific etiology is not clear. MiRNA plays an important role in the fetal growth and development. In this article, we use TaqMan Low-Density Array to screen and analyze the differently expressed miRNAs in FGR-affected placenta (n = 40) and the normal placenta (n = 40). A total of 139 abnormally expressed miRNAs in the FGR-affected placenta were identified, and miR-1227-3p was the most highly downregulated miRNA. Importantly, miR-1227-3p may promote the proliferation in HTR-8/SVneo cells, while inhibited the apoptosis of HTR-8/SVneo cells. DAVID was used to analyze the pathway enrichment of target genes of miR-1227-3p to predict its mechanism of action. Furthermore, the putative targets of miR-1227-3p were predicted using the TargetScan, PicTar, DIANA LAB, and miRWalk database. The potential expression of target genes of miR-1227-3p, including PRKAB2, AKT1, PIK3R3, and MKNK1 were significantly increased in FGR-affected placenta. Taken together, miR-1227-3p may participate in the development of FGR via regulating trophoblast cell proliferation and apoptosis by targeting genes involved in the insulin pathway. MiR-1227-3p may have a potential clinical value in the prevention and treatment of FGR, we need to study further to prove its value in the future.

This aim of this meta-analysis was to evaluate the association between risk of childhood type 1 diabetes and maternal 25-hydroxyvitamin D [25(OH)D] levels during pregnancy. A literature search on databases including PubMed and Embase was conducted up to December 2018. The pooled odds radio weighted mean difference (WMD) and the corresponding 95% confidence intervals (CIs) were calculated using the RevMan 5.3 software. A total of 4 studies were included in this meta-analysis. The overall analysis indicated that the maternal 25(OH)D levels during pregnancy was significantly associated with the risk of type 1 diabetes in offspring (WMD=-2.54, 95% CI=-4.65 to -0.44, p=0.02). The subgroup analyses showed that sample for detection vitamin D (serum/plasma) may not a factor influencing the results of this meta-analysis. However, gestational trimester may be a factor affecting the results. The results showed that no significant association was observed between risk of type 1 diabetes in offspring and 25(OH)D level during first or second gestational trimester (p>0.05). Lower maternal 25(OH)D levels during pregnancy is associated with higher risk of type 1 diabetes in offspring. Gestational trimester may be a factor influencing the results of this meta-analysis.

Urban greenery is essential to the living environment of humans. Objectively assessing the rationality of the spatial distribution of green space resources will contribute to regional greening plans, thereby reducing social injustice. However, it is difficult to propose a reasonable greening policy aimed at the coordinated development of an urban agglomeration due to a lack of baseline information. This study investigated the changes in spatial fairness of the greenery surrounding residents in Guangdong-Hong Kong-Macao Greater Bay by examining time-series remote sensing images from 1997 to 2017. With the substitution of impervious, artificial surfaces for universal areas of human activities, we quantified the amount of surrounding greenery from the perspective of human activities at the pixel level by utilizing a nested buffer. The Gini coefficient was further calculated for each city to quantify the spatial fairness of the surrounding greenery to people. The results indicated that areas with less greenery surrounding them decreased during 1997 and 2017 in Guangdong-Hong Kong-Macao Greater Bay. The spatial fairness did not tend to increase with the improvements in the overall greening level. The spatial fairness of 4 cities had an increasing trend, and the Gini coefficients of 5 cities were still over 0.6 in 2017. We further proposed different greening policy suggestions for different cities based on the amount of greenery surrounding people and the trend in fairness. The results and the conclusion of this research will help to improve future regional greening policies and to reduce environmental injustice.

The exchange processes between the Maryland Coastal Bays system (MCBs) and their adjacent coastal ocean were simulated using a three-dimensional unstructured-grid based hydrodynamic model, which was validated by observed data including water level, current velocity and salinity. Idealized experiments were then carried out to investigate the impact of wind forcing on water exchange and salt flux. Through these experiments, the exchanges between the MCBs and coastal ocean were investigated at two inlets (Ocean City Inlet and Chincoteague Inlet). Given that winds and tides are two key external forces known to impact estuarine dynamics, the effect of each individual force on the exchange processes was studied to evaluate the corresponding influence on the inlet dynamics. It was found that wind forcing significantly impacts the inlet dynamics: the effect of wind directions on exchange processes under strong wind speeds is substantial; for example, northwesterly winds push flux to the southern part of the bays, while southwesterly winds pile up flux towards northern Chincoteague Bay. The effect of wind forcing on the exchange dynamics becomes stronger with the augmentation of its speed. Meanwhile, tidal forcing is the major driver of exchange dynamics at weak wind speeds (e.g., 3 m/s), and its effect on exchange process gradually weakens with stronger wind speeds (e.g., 7 m/s, 15 m/s). In addition, sensitivity tests elucidated that closing either inlet results in a significant impact on the water elevation, current velocity and salinity nearby the relevant cut-off inlet areas.