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Diabetic macular edema (DME) is the main cause of visual impairment in diabetic patients. Early detection of DME will significantly reduce the risk of vision loss for the patients. According to the clinical DME grading standard, the positional relationship between Hard Exudates (HEs) and macular center is an important basis for DME grading. Accurate DME grading is thus predicated on properly locating the macular center and segmenting HEs. HEI-MED and E-ophtha EX data sets were tested by the proposed DME grading method, reaching an average accuracy of 94.4% and 87%, respectively. The proposed method was also tested by comparison against other commonly used methods as per its potential to assist doctors in initially screening DME; it was found to not only improve the efficiency of DME detection, but also to save Optical Coherence Tomography medical resources over the other methods tested.

Oral lichen planus (OLP) is an inflammatory disease. It is believed that infection and immune dysfunction play a key role in its pathogenesis, but the specific mechanism of action remains unclear. The 16s rRNA high-throughput sequencing technique was used to analyze the microbial flora structure in the saliva of OLP patients and healthy controls. The relative abundance of Derxia, Haemophilus, and Pseudomonas in the saliva of the OLP group was lower than that of the healthy control group, but there was no significant difference in the overall structure of the microbial population. In addition, we measured the protein expression levels of toll-like receptor 4 (TLR4) and nuclear factor-kappab p65 (NF-κB p65) in the tissues of OLP patients, and found that there was a significant increase and positive correlation between them (r = 0.907, P = 0.034). The expression levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the OLP group were consistent with those of NF-κB p65. Therefore, we believe that changes in the composition ratio of microbialflora break the original balance state of flora, promote the occurrence of immune inflammatory reaction, and then lead to the generation or aggravation of OLP disease. This discovery provides new ideas for further research on OLP initiation and immune regulation mechanism.

Canine distemper virus (CDV) causes a highly contagious disease in a wide range of carnivores. The hemagglutinin (H) protein of viruses shows the highest variability and plays an important role in modulation of viral antigenicity, virulence, and receptor recognition. Since 2012, canine distemper (CD) outbreaks in fur-bearing animals (minks, foxes, raccoon dogs) caused by CDV variants with I542N and Y549H substitutions in the H protein have been frequently reported in China. To characterize the molecular evolutionary dynamics and epidemiological dynamics of CDV, 235 H gene sequences of CDV wild-type strains collected from 22 countries between 1975 and 2015, including 44 strains predominant in fur-bearing animals in China, were analyzed. The phylogenetic relationships and evolutionary rates of the CDV strains were determined by Bayesian phylogenetics. The CDV strains clustered into distinct geographic genotypes, irrespective of the species of isolation. All the variant strains formed a distinct monophyletic cluster and belonged to the F sub-genotype within the Asia-1 genotype-currently the predominant sub-genotype in fur-bearing animals in China. Evolutionary analysis suggested that the variant strains originated in 2006. Furthermore, the selection pressure analysis revealed that the Y549H substitution was under positive selection pressure for adaptation toward the fur-bearing animals. The residue at position 549 also showed structural interaction with the V domain of the mink signaling lymphocyte-activation molecule (SLAM) receptor based on the homology modeling of the H-SLAM complex. Our results suggested that the Y549H substitution contributed to the molecular adaptation of CDV variants in the fur-bearing animals during the viral evolutionary phase in China.

Hemorrhage is one of the early symptoms of diabetic retinopathy, so accurate detection of hemorrhage has important significance in building automatic screening system of diabetic retinopathy. In this paper, a method based on two dimensional (2D) Gaussian fitting and human visual characteristics is proposed. Firstly, brightness correction and contrast limited adaptive histogram equalization are used to preprocess original color fundus image. Secondly, candidate hemorrhages are extracted based on background estimation and watershed segmentation. Thirdly, 2D Gaussian fitting and human visual characteristics are used to extract visual features of candidate hemorrhages. Finally, hemorrhages are obtained from candidate hemorrhages based on visual features. The proposed method is evaluated on 219 fundus images of DIARETDB database. Experimental results show that overall average sensitivity, specificity and accuracy for hemorrhage in image level are 100%, 82% and 95.42% respectively, and overall average sensitivity and positive predictive value for hemorrhage in lesion level are 94.01% and 90.30% respectively. The results show that this method can realize automatic detection of hemorrhages in fundus image with high accuracy.

The Signal lymphatic activation molecule (SLAM, also known as CD150) as the cellular receptor of canine distemper virus (CDV) plays an important role in the virus-host interaction. However, it is still unknown whether amino acid differences in the SLAM variable (V) region affect the formation of syncytia. Here, using raccoon dog SLAM (rSLAM) and mink SLAM (mSLAM), we performed SLAM-V homologous modeling, site-directed mutagenesis, and surface expression analysis, as well as a cell fusion assay, to study the interaction between SLAM and CDV. More specifically, our investigation focused on two amino acid residues (74 and 129) of SLAM, previously predicted to play a relevant role in receptor-ligand interaction. Our results indicated that only residues at position 60, 74, and 129 were different between rSLAM and mSLAM among the 29 amino acids that might interact with CDV H, and residues 74 and 129 were located in the interface region interacting with CDV H. The amino acid substitution at the positions of 74 have a significant effect on the expression of mSLAM. The SLAM-V74I mutation in mink significantly improved the cell fusion efficiency of CDV. In contrast, the SLAM-I74V mutation in the raccoon dog significantly decreased cell fusion efficiency. We conclude that residue 74 of SLAM plays an important role during the the formation of syncytia. Only when implementing CDV infection analysis, the rSLAM-Q129R can significantly decreased the mean number of syncytia, but the mSLAM-R129Q can't. Additionally, residue 60 show variability between rSLAM and mSLAM. We believe that our study makes a significant contribution to the literature because we provide molecular data, partially accounting for the differences in host membrane and virus interaction laying the foundation for further molecular work.

PDK1 (3-Phosphoinositide dependent protein kinase-1) is a member in the PI3K (phosphatidylinositol 3 kinase) pathway and is implicated in neurodevelopmental disease with microcephaly. Although the role of PDK1 in neurogenesis has been broadly studied, it remains unknown how PDK1 may regulate oligogenesis in the central nervous system (CNS). To address this question, we generated oligodendrocyte (OL) lineage cells specific PDK1 conditional knockout (cKO) mice. We find that PDK1 cKOs display abnormal white matter (WM), massive loss of mature OLs and severe defect in myelination in the CNS. In contrast, these mutants exhibit normal neuronal development and unchanged apoptosis in the CNS. We demonstrate that deletion of PDK1 severely impairs OL differentiation. We show that genetic or pharmacological inhibition of PDK1 causes deficit in the mammalian target of rapamycin (mTor) signaling and down-regulation of Sox10. Together, these results highlight a critical role of PDK1 in OL differentiation during postnatal CNS development.

Pudendal nerve block (PNB) is one of the common anesthesia methods, which has been widely applied in postoperative analgesia of hemorrhoids in recent years. To analyze the effectiveness and safety of PNB on postoperative analgesia of hemorrhoids, we conducted a systematic review of 7 randomized controlled trials (RCT) searched from PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), the China Network Knowledge Infrastructure (CNKI), the Wan Fang Database and Chinese Biomedicine (CBM), which were published before 7th September, 2020, and involved a total of 560 participants. We evaluated the function of PNB in improving outcomes of postoperative analgesia of hemorrhoids. Visual analogue scale (VAS) scores on postoperative 6, 12, 24, 48 h and the first time of defecation were enhanced by the application of PNB. The incidence of urinary retention, the need for analgesics [odds ratio (OR), 0.11; 95% CI, 0.04-0.37; P=0.0003] and the incidence of side effects (OR, 0.12; 95% CI, 0.04-0.39; P=0.004) in patients receiving PNB were lower than those of controls. In addition, there was no significant difference in the incidence of bleeding between groups. PNB could effectively relieve postoperative pain of hemorrhoids and reduce complications without increasing the incidence of side effects. Our results still need to be confirmed by high-quality, multi-center clinical studies.

Cracks within concrete accelerate the ingress of chloride ions, causing acceleration of the degradation of the mechanical performance of reinforced-concrete (RC) structures. The effects of cracks should therefore be considered in the durability design of RC structures. However, the available test observations show large discrepancies regarding the quantitative effect of cracks on chloride diffusivity in concrete, and the corresponding developed empirical formulas have some limitations. In the present study, a unified quantitative relation between the chloride diffusion coefficient in cracks and crack width was developed. The parameters in the proposed formula have their own physical meanings, and the corresponding curve of the formula is smooth without an inflection point. The rationality and accuracy of the developed simplified formula were verified through comparisons with test data. Furthermore, chloride diffusivity in cracked concrete was studied and simulated based on the developed simplified formula, and the effects of crack width and crack depth were examined. The simulation results indicate that chloride diffusivity in cracked concrete is significantly affected by both crack width and crack depth. Moreover, the chloride diffusion behaviour in higher strength concrete with lower porosity is much more sensitive to cracks than normal- and lower strength concretes.

Objective To investigate the expression levels of membrane-anchored complement regulatory proteins (mCRPs), CD46, CD55 and CD59 in oral lichen planus (OLP), and evaluate the activation status of complement. Design Thirty-seven cases of OLP patients (20 non-erosive OLP and 17 erosive OLP) and twenty healthy controls were recruited in this study. The proteins and mRNA expression levels of CD46, CD55 and CD59 in OLP tissues were detected by western blotting and RT-qPCR respectively, and the expression levels of complement C3 and sC5b-9 in OLP patients’ saliva were detected by ELISA to evaluate the activation status of complement. In addition, mucosa tissues of another 3 non-erosive OLP patients and another 3 healthy controls were collected, and the epithelial layer of two groups were separated to culture primary keratinocytes in vitro. Immunofluorescence was used to further detect the expression of mCRPs at the cellular level. Results The levels of CD46, CD55 and CD59 in OLP tissues and cells were significantly decreased compared with those of the healthy control group, and the level of complement C3 in the patients’ saliva was significantly decreased, while the level of sC5b-9 was increased. Conclusions These results suggest that the reduced expression of mCRPs keeps the complement system in a continuously active state, which may be the reason of the persistent local immune inflammatory state in OLP. This study aimed to provide new insights for the etiology and therapy of OLP.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors with high incidence, rapid progress, and high mortality. There are still some defects in the treatments of OSCC, which seriously affect the quality of patients’ life. Therefore, it is urgent to find a safer and more effective treatment for OSCC. Low molecular weight fucoidan (LMWF) has various biological activities, such as antitumor, anti-inflammatory, and antithrombotic, and has no obvious side effects, but the effect of LMWF on OSCC has not been reported. In this study, the effects of LMWF on dysplastic oral keratinocyte (DOK) and OSCC cells SCC-9 and SCC-25 were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, TUNEL, colony formation, and wound healing assay, and the expression levels of Notch-1 and Jagged-1 treated with LMWF were detected by RT-qPCR. The results showed that LMWF could inhibit the proliferation and migration of DOK and SCC-9, and promote apoptosis. Low molecular weight fucoidan upregulated the expression of Notch-1 and Jagged-1 in DOK and SCC-9 cells. It indicated that LMWF might promote the apoptosis of DOK and SCC-9 by upregulating the Notch signal pathway, thereby inhibiting cell proliferation and playing an antitumor role. It provided theoretical basis to develop LMWF as a novel therapeutic drug for oral cancer.

A non-mydriasis optical system for binocular fundus camera has been designed in this paper. It can capture two images of the same fundus retinal region from different angles at the same time, and can be used to achieve three-dimensional reconstruction of fundus. It is composed of imaging system and illumination system. In imaging system, Gullstrand Le Grand eye model is used to simulate normal human eye, and Schematic eye model is used to test the influence of ametropia in human eye on imaging quality. Annular aperture and black dot board are added into illumination system, so that the illumination system can eliminate stray light produced by corneal-reflected light and omentoscopic lens. Simulation results show that MTF of each visual field at the cut-off frequency of 90lp/mm is greater than 0.2, system distortion value is -2.7%, field curvature is less than 0.1 mm, radius of Airy disc is 3.25um. This system has a strong ability of chromatic aberration correction and focusing, and can image clearly for human fundus in which the range of diopters is from -10 D to +6 D(1 D = 1 m

The extensive environmental adaptability of the genus Paenibacillus is related to the enormous diversity of its gene repertoires. Paenibacillus sp. SSG-1 has previously been reported, and its agar-degradation trait has attracted our attention. Here, the genome sequence of Paenibacillus sp. SSG-1, together with 76 previously sequenced strains, was comparatively studied. The results show that the pan-genome of Paenibacillus is open and indicate that the current taxonomy of this genus is incorrect. The incessant flux of gene repertoires resulting from the processes of gain and loss largely contributed to the difference in genomic content and genome size in Paenibacillus. Furthermore, a large number of genes gained are associated with carbohydrate transport and metabolism. It indicates that the evolution of glycometabolism is a key factor for the environmental adaptability of Paenibacillus species. Interestingly, through horizontal gene transfer, Paenibacillus sp. SSG-1 acquired an approximately 150 kb DNA fragment and shows an agar-degrading characteristic distinct from most other non-marine bacteria. This region may be transported in bacteria as a complete unit responsible for agar degradation. Taken together, these results provide insights into the evolutionary pattern of Paenibacillus and have implications for studies on the taxonomy and functional genomics of this genus.

The fat sand rats (Psammomys obesus) can easily induce obesity and acquire type 2 diabetes mellitus when they are fed with high-carbohydrate diets. P. obesus is often used as an animal model for st...

A series of N,N’-disubstituted-2-nitroethene-1,1-diamine and N,N’-disubstituted- N’’-cyanoguanidine derivatives were prepared and evaluated for in vivo analgesic activity. The blood brain barrier (BBB) VolSurf model was used to predict the BBB permeation profiles of our synthesized compounds. Some compounds show both remarkable analgesic activity and good BBB permeation profiles, and these compounds might be developed for treatment of opioid tolerance and dependence.