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BackgroundHypertension and diabetes can significantly affect the blood flow of the retina and choroid. But there has been no idea about the retinal and choroidal microcirculation of hypertensives associated with diabetes. The objective of the study is to detect the differences in the retinal and choroidal microcirculation of hypertensives, diabetics and hypertensives associated with diabetes by optical coherence tomography angiography (OCTA) and explore their clinical significance.MethodsThis was a cross-sectional and case-control study that 538 older subjects (538 eyes) were enrolled in. There were 187 cases assigned to the hypertensive group, 49 cases to the diabetic group, 129 cases to the hypertensive diabetic group, and 173 cases to the control group. OCTA were used to scan 6*6-mm macula. The related indicators included the thickness and flow density (FD) of each layer of the retina and choroid.ResultsThe retinal superficial FD (SFD) in the hypertensive, diabetic, hypertensive diabetic and control group was 46.4%, 45.3%, 46.4% and 46.4%, respectively. It was significantly lower in the diabetic group than in the other three groups (all P

An incompletely covered CdS/ZnS core/shell is synthesized via a simple hydrothermal method. Due to the defect energy levels introduced by zinc vacancies, the typical type-I heterojunction of CdS/Zn...

Hydroxyapatite nanoparticles (HANPs) have been increasingly regarded and reported due to their potential anti-tumor ability. Previously, we found that the rod-like HANPs had good application potential for cutaneous melanoma (CMM). To satisfy the actual requirements in repairing post-operative skin defects and inhibiting CMM recurrence after tumorectomy, we constructed a novel chitosan/alginate (CS/Alg) hydrogel containing the aforementioned HANPs. The in vitro cell experiments confirmed that activated mitochondrial-dependent apoptosis was tightly related to the anti-tumor ability of HANPs. Specifically, we further discovered several target proteins might be involved in abnormal activating Wnt, proteoglycans in cancer, oxidative phosphorylation and p53 signaling pathways. The in vivo animal experiments demonstrated that the HANPs-loaded CS/Alg hydrogel (CS/Alg/HANPs) had a similar effect on inhibiting tumor growth as HANPs, and CS/Alg hydrogel as well as phosphate buffered saline (PBS) group (control) not showed any effect, proving the key role of HANPs. The immunohistochemical staining demonstrated a tumor inhibition via the mitochondria-mediated apoptosis pathway, consistent with the in vitro evaluation. Moreover, CS/Alg/HANPs exhibited no additional biosafety risk to the functions of major organs. Overall, this CS/Alg/HANPs hydrogel has substantial application potential for treating CMM.

Dahuang Zhechong Pill (DHZCP) is a traditional Chinese medicine prescription used to treat many diseases especially chronic liver disease accompanied by promotion of vascular normalization. In this work, UPLC-Q-TOF-MS/MS analysis was applied to identify the chemical components absorbed in the blood. HIF-1α, VEGF, Ang2 and Tie2 related to vascular normalization were detected to determine the dynamic changes of pharmacodynamic indicators. Then, the spectrum-effect relationship between the UHPLC fingerprint and pharmacodynamic indicators was evaluated dynamically using partial least squares (PLS). As a result, 103 components were identified from rat serum samples, including 56 original compounds and 47 metabolites. According to the PLS, active constituents of DHZCP acting on HIF-1α, VEGF, Ang2 and Tie2 (8, 15, 17 and 20) were found. In subsequent experiments on cells, 7/11 components of HIF-1α/VEGF were found in HepG2 and HUVEC cells, and 11/14/2 components of HIF-1α/VEGF/Tie2. The main pharmacodynamic components of DHZCP in promoting vascular normalization were successfully identified by the spectrum-effect relationship analysis.

Global cerebral ischemia induced by cardiac arrest usually leads to poor neurological outcomes. Numerous studies have focused on ways to prevent ischemic damage in the brain, however clinical therapies are still limited. Our previous studies revealed that delta opioid receptor (DOR) activation with [d-Ala2, d-Leu5] enkephalin (DADLE), a DOR agonist, not only significantly promotes neuronal survival on day 3, but also improves spatial memory deficits on days 5-9 after ischemia. However, the neurological mechanism underlying DADLE-induced cognitive recovery remains unclear. This study first examined the changes in neuronal survival in the CA1 region at the advanced time point (day 7) after ischemia/reperfusion (I/R) injury and found a significant amelioration of damaged CA1 neurons in the rats treated with DADLE (2.5 nmol) when administered at the onset of reperfusion. The structure and function of CA1 neurons on days 3 and 7 post-ischemia showed significant improvements in both the density of the injured dendritic spines and the basic transmission of the impaired CA3-CA1 synapses following DADLE treatment. The molecular changes involved in DADLE-mediated synaptic modulation on days 3 and 7 post-ischemia implied the time-related differential regulation of PKCα-MARCKS on the dendritic spine structure and of BDNF- ERK1/2-synapsin I on synaptic function, in response to ischemic/reperfusion injury as well as to DADLE treatment. Importantly, all the beneficial effects of DADLE on ischemia-induced cellular, synaptic, and molecular deficits were eliminated by the DOR inhibitor naltrindole (2.5 nmol). Taken together, this study suggested that DOR activation-induced protective signaling pathways of PKCα-MARCKS involved in the synaptic morphology and BDNF-ERK-synapsin I in synaptic transmission may be engaged in the cognitive recovery in rats suffering from advanced cerebral ischemia.

Hydrogel is an emerging material widely used in the biological field. The tensile properties of hydrogel mainly depend on its polymer network, but due to the complex microstructure of the network, some properties of the hydrogel have yet to be quantitatively analyzed. In this article, we built a three-dimensional random fiber network to characterize the microstructure of a hydrogel. The fibers were simplified as elastic beams, and the cross-links were regarded as “hinges.” Combined with the macroscopic experimental results, the influence of the change of fiber length and the relationship between the polymer content and the cross-link density were studied. The model was verified by the quasi-static tensile test results of real PVA hydrogel materials with different fiber contents. The results show that the model can well match the tensile stress–strain curve and tensile strength of the PVA hydrogels with different fiber contents. The change in microstructure of the fiber network induces nonlinear behaviors, and although the cross-link number increases with the increase in polymer content, the cross-link density (per unit PVA chain length) of the PVA hydrogel slightly decreases as the content increases.

Lacrimal plug is an effective and widely therapeutic strategy to treat dry eye. However, almost all commercialized plugs are fixed in a certain design and associated with many complications, such as spontaneous plug extrusion, epiphora, and granuloma and cannot be traced in the long-term. Herein, a simple in situ forming hydrogel is developed as a tracer and degradable lacrimal plug to achieve the best match with the irregular lacrimal passages. In this strategy, methacrylate-modified silk fibroin (SFMA) is served as a network, and a self-assembled indocyanine green fluorescence tracer nanoparticle (FTN) is embedded as an indicator to develop the hydrogel plug using visible photo-crosslinking. This SFMA/FTN hydrogel plug has excellent biocompatibility and biodegradability, which can be noninvasively monitored by near-infrared light. In vivo tests based on dry eye rabbits show that the SFMA/FTN hydrogel plug can completely block the lacrimal passages and greatly improve the various clinical indicators of dry eye. These results demonstrate that the SFMA/FTN hydrogel is suitable as an injectable and degradable lacrimal plug with a long-term tracking function. The work offers a new approach to the development of absorbable plugs for the treatment of dry eye.

M1 macrophage accumulation and excessive inflammation are commonly encountered issues in diabetic wounds and can fail in the healing process. Hence, hydrogel dressings with immunoregulatory capacity have great promise in the clinical practice of diabetic wound healing. However, current immunoregulatory hydrogels are always needed for complex interventions and high-cost treatments, such as cytokines and cell therapies. In this study, a novel glycyrrhizic acid (GA)-based hybrid hydrogel dressing with intrinsic immunoregulatory properties is developed to promote rapid diabetic wound healing. This hybrid hydrogel consists of interpenetrating polymer networks composed of inorganic Zn

The number of IoT devices continues to increase, but the security of IoT devices cannot be guaranteed. Many IoT devices are infected with malware, forming huge botnets, which could launch DDoS attacks and cause heavy losses. In recent years, the IoT malware family has a tendency to be centralized on ARM-based IoT devices. The most widely spread families are the Mirai family and Gafgyt family. In this paper, we automatically extract the instruction sequences of these two families' samples and use the instruction sequences as language to describe these samples. We transfer instruction sequences to word vector space by Word2Vec. Then exploiting internal hierarchical structure of functions in malware to construct a hierarchical language model based on transformer-encoder to classify the samples. And the results obtained after visualizing the weights of the model can reflect the correlation of the functions in the sample, which can help the sample analyst find the key function. We use IoT software samples including Mirai samples, Gafgyt samples and benign samples to train our model. In the experiments, our model achieves 99.12% recall rate of malware and 94.67% family classification accuracy rate, which is better than other methods.

Machine reading comprehension, as one of the core tasks of natural language processing, has been a research focus in this field. This paper is mainly aimed at Dureader, a Chinese-oriented multi-document reading comprehension task dataset, and an end-to-end machine reading comprehension model based on neural network is proposed. In this paper, a combination of context-to-question attention and self-attention, and a new fusion method are used to fuse context and attention information. The comparison of experimental results shows that compared with the baseline model, by our methods, BLEU-4 index has been improved by 6% and ROUGE-L index has been improved by 3%.

Lung cancer has always threatened people's health and life. Lung nodules, as early features of lung cancer, have very important clinical significance and research value for the diagnosis of lung cancer. The features captured by the traditional convolutional neural network are limited, in addition, traditional YOLO method has the problems of low accuracy and inaccurate positioning. Aiming at this problem, this paper proposes a new algorithm based on YOLOv3 for detecting lung nodules. The Inception ResBlocks are added to the feature network of YOLOv3, so that the network can extract richer feature information, furthermore, a new bounding box regression loss function is proposed. The loss function GDIoU loss makes the prediction of bounding box regression more accurate and further improves the performance of lung nodule detection. After experimental verification, the AP of this model can reach 83.5%, and the sensitivity can reach 92.6%. The proposed method has a good performance in terms of positioning accuracy and detection rate, and can avoid the problems of false detection and missed detection to a certain extent. It provides a new idea for the detection of lung nodules.

Accumulating evidence showed that cytokines are involved in the development of cancer. IL-13 was showed to induce epithelial-mesenchymal transition and promote metastasis in colorectal cancer, providing a promising therapeutic target for cancer patients. Interestingly, recent studies showed that propofol, one of most common intravenous anesthetic agent, may have antitumor function in different cancer type. However, the impact of propofol on colorectal cancer and IL-13 induced epithelial-mesenchymal transition remains unknown. Herein, we found that propofol can effectively suppress cell proliferation in colorectal cell lines RKO and SW480 cells by using MTT assay. Furthermore, wound healing assay and migration assay demonstrated that propofol has the ability to inhibit epithelial-mesenchymal transition that induced by IL-13 in RKO and SW480 cells. Mechanistically, we found propofol treatment causes up-regulation of miR-361 and miR-135b, that suppress expression of STAT6 and thereafter leads to the inhibition of IL-13/STAT6/ZEB1 signaling pathway. In conclusion, our data for the first time demonstrated that propofol may serve as a novel therapeutic drug for targeting IL-13. The aggressive function of IL-13/STAT6/ZEB1 axis in colorectal cancer was impaired by propofol through miR-361 and miR-135b.

It has been reported that the measurement results by the method of indentation for soft viscoelastic materials are affected apparently by experimental conditions, such as strain rate and indentation depth. In order to enhance the effectiveness of the method of indentation and find optimized loading rates in tests, the Lee–Radok's solution was modified with Hay's correction to describe the indentation response for soft viscoelastic materials, further, a pseudo dissipative work was defined in a normalized indentation loop and its variation against the loading rate was obtained. It is found the pseudo dissipative work exists several maximal values related to the viscous properties of materials, and the corresponding loading rates can be regarded as the optimal loading rates in indentation tests. Based on the theoretical analysis, a new method how to determine the optimized loading rates in indentation was recommended, which was verified by tests of indentation and uniaxial compressive creep for a PVA hydrogel.

BACKGROUND Hailey-Hailey disease (HHD) is a rare autosomal dominant skin condition. The ATP2C1 gene was identified as the defective gene in HHD. To date, 166 pathogenic mutations in ATP2C1 have been observed worldwide. The aim of this study was to identify variations in HHD and summarize the features of the mutations identified in China. MATERIAL AND METHODS We examined 2 familial and 2 sporadic cases of HHD. Genomic DNA polymerase chain reaction and direct sequencing of the ATP2C1 were performed from HHD patients, unaffected family members, and 200 healthy individuals. We also searched the published literature for data about the ATP2C1 gene using PubMed and the Chinese Biological Medicine Database. RESULTS We detected 3 heterozygous mutations, including 2 novel frameshift mutations (c.819insA (273LfsX) and c.1264insTAGATGG (421LfsX)) and 1 recurrent nonsense mutation (c.115C>T (R39X)). To the best of our knowledge, 90 different mutations (including our current results) have been reported in China, all of which occurred in the Chinese Han population. CONCLUSIONS Our data may add to the existing list of ATP2C1 mutations and provide new insight into genetic variants of HHD in China.

Simple Summary Chemotherapeutic agents including cisplatin promote tumor metastasis while inhibiting tumor growth, which still represents a major obstacle for some patients in clinical practices. This study demonstrated that cisplatin induced epithelial-mesenchymal transition and tumor metastasis in lung adenocarcinoma. Further bioinformatic analysis showed that DCBLD2 may play a key role in metastasis after platinum chemotherapy. In terms of mechanism, DCBLD2 stabilized β-catenin through phosphorylation and inactivation of GSK3β, leading to the disintegration of the destruction complex of β-catenin. The accumulated β-catenin transported to the nucleus and promoted the expression of metastasis-related genes. In addition, cisplatin markedly enhanced DCBLD2 (Discoidin, CUB and LCCL domain containing 2) expression via ERK/AP-1 axis. Importantly, DCBLD2-specific siRNAs encapsulated by nanoparticles strikingly inhibited cisplatin-induced metastasis in tumor-bearing mice. Taken together, DCBLD2 mediates cisplatin-induced metastasis and DCBLD2 inhibition is a promising treatment option for preventing chemotherapy-induced metastasis. Abstract Growing evidence suggests that cisplatin and other chemotherapeutic agents promote tumor metastasis while inhibiting tumor growth, which is a critical issue for certain patients in clinical practices. However, the role of chemotherapeutics in promoting tumor metastasis and the molecular mechanism involved are unclear. Here, we investigated the roles of cisplatin in promoting tumor metastasis in lung adenocarcinoma (LUAD). We demonstrated that cisplatin promoted epithelial-mesenchymal transition (EMT), cell motility, and metastasis in vitro and in vivo. The bioinformatic analysis and molecular biology approaches also indicated that DCBLD2 (Discoidin, CUB and LCCL domain containing 2) is a key gene that mediates cisplatin-induced metastasis. DCBLD2 stabilizes β-catenin by phosphorylating GSK3β and transporting accumulated β-catenin to the nucleus to promote the expression of EMT-related transcriptional factors (TFs), ultimately resulting in tumor metastasis. We also identified that cisplatin enhanced DCBLD2 expression by phosphorylating ERK and hence the AP-1-driven transcription of DCBLD2. Furthermore, DCBLD2-specific siRNAs encapsulated by nanocarriers prominently inhibit cisplatin-induced metastasis in vivo. Therefore, DCBLD2 plays a key role in cisplatin-induced metastasis in LUAD and is a potential target for preventing chemotherapy-induced metastasis in vivo.

Novel self-assemble peony-like three-dimensional (3D) copper hydroxyl phosphate (Cu2(OH)PO4) was synthesized on the copper foil by a solution-growth method. The self-aggregate peony-like 3D Cu2(OH)PO4 flowers with the diameter size up to 10–20 μm were composed of hundreds of anisotropic cross-linking petals with several hundred nanometers wide and 110–170 nm thick. After the morphology and structure of these Cu2(OH)PO4 flowers were characterized by transmission electron microscope and scanning electron microscope, the possible growth process of Cu2(OH)PO4 flowers was proposed. The relationship between the shape of Cu2(OH)PO4 nanostructure and photocatalytic activity under visible light irradiation was also investigated. The results indicated that a thin petal and high content of Cu2(OH)PO4 flowers film on the copper substrate proved more convenient for extending their absorption edge to the visible light region, as well as giving a better photocatalytic performance. Keywords: Nanostructured materials, Composite design, Photocatalyst, Energy materials, Copper hydroxyl-phosphate, Nanoflower

For high-water content hydrogels in compression, the water inside of hydrogels contributes to the response of hydrogels to external loads directly, but part of the water is expelled from hydrogels in the meantime to change the volume of the hydrogel and reduce the contribution. In order to consider the contribution of the water in the constitution equation, PVA (polyvinyl alcohol) hydrogels with high-water content were used as examples, and compressive experiments were carried out to measure both the stress-strain relation and the change of the volume in the meantime. By considering the effect of the difference of the contribution of water in different directions of the hydrogel, we deduced a new constitutive equation, which can pretty well depict the stress-strain of hydrogels with different water contents. The results showed that the contribution of water to the total stress increases with the compression strain and even exceed that of the polymer, although the expelled water reduces the contribution at the early loading stage, which well explains the difference of elastic moduli of hydrogels in compression and tension.

Accumulating evidence showed that cytokines are involved in the development of cancer. IL-13 was showed to induce epithelial-mesenchymal transition and promote metastasis in colorectal cancer, providing a promising therapeutic target for cancer patients. Interestingly, recent studies showed that propofol, one of most common intravenous anesthetic agent, may have antitumor function in different cancer type. However, the impact of propofol on colorectal cancer and IL-13 induced epithelial-mesenchymal transition remains unknown. Herein, we found that propofol can effectively suppress cell proliferation in colorectal cell lines RKO and SW480 cells by using MTT assay. Furthermore, wound healing assay and migration assay demonstrated that propofol has the ability to inhibit epithelial-mesenchymal transition that induced by IL-13 in RKO and SW480 cells. Mechanistically, we found propofol treatment causes up-regulation of miR-361 and miR-135b, that suppress expression of STAT6 and thereafter leads to the inhibition of IL-13/STAT6/ZEB1 signaling pathway. In conclusion, our data for the first time demonstrated that propofol may serve as a novel therapeutic drug for targeting IL-13. The aggressive function of IL-13/STAT6/ZEB1 axis in colorectal cancer was impaired by propofol through miR-361 and miR-135b.

As an ultra-soft material (elastic modulus in magnitude of kPa), polyvinyl alcohol (PVA) hydrogels have the potential to substitute articular cartilage, but the measurement of the dynamic stress–strain relations of ultra-soft materials is still challenging. In this paper, a double-striker electromagnetic driving split-Hopkinson pressure bar (SHPB) system was developed, in which all the bars were made of polycarbonate, and the polycarbonate striker was pushed by a metal striker driven electromagnetically to ensure the precise control of impact velocity. With the new SHPB system, well design of the size of hydrogel specimen and rational processing of the signal data, the stress–strain relations of hydrogels with varied PVA contents at different strain rates were measured successfully. Experimental results indicate that PVA hydrogels are a positive strain rate sensitive material with different strain-rate effects at low and high strain rates. Finally, based on the latest quasi-static constitution of the PVA hydrogel, a rate-dependent constitutive equation was recommended, which may well depict the mechanical behaviors of hydrogels with different fiber contents at varied strain rates. It also derives that the contributions of strain rate and fiber content on the mechanical behaviors of the hydrogel are relatively independent.

Objective. Berberine has been used to treat nonalcoholic steatohepatitis (NASH), which has been addressed in many studies. In this study, we investigated the molecular pharmacology mechanisms of berberine using metabolomic techniques.Methods. Sprague-Dawley rats were randomly divided into three groups (10 rats in each group): (i) normal control group; (ii) high-fat diet- (HFD-) induced NASH model group; and (iii) HFD berberine-treated group (i.d. 200 mg/kg). The handling procedure lasted eight weeks. Then, UPLC-Q-TOF/MS techniques coupled with histopathology and biochemical analyses were adopted to explore the mechanisms of berberine on the protective effects against NASH.Key Findings. (i) According to conventional test results, berberine treatment plays a fighting role in HFD-induced NASH due to its beneficial effects against insulin resistance, inflammation, and lipid metabolism. (ii) Based on UPLC-Q-TOF/MS techniques, metabolic profiles that involved sphingomyelin (SM), phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC), 13-hydroperoxy-9, 11-octadecadienoic acid (13-HpODE), eicosatrienoic acid, docosatrienoic acid, and eicosenoic acid could provide potential metabolic biomarkers to address the pharmacological mechanisms of berberine.Conclusions. The parts of molecular pharmacological mechanisms of berberine for NASH treatment are related to the regulation of metabolic disruption involving phospholipid and unsaturated fatty acids in rats with NASH.

Static uniaxial compressive experiments were conducted to study the mechanical behaviors of polyvinyl alcohol (PVA) hydrogels in ambient conditions. It was found that water is expelled during the compression of hydrogels that have high water contents. It means hydrogels may be a mass variable under the compression. In order to depict the mechanical properties intrinsically, a variable mass model with meso-scale cells was proposed to simulate PVA hydrogels. In the model, there are uniform cells with frames of polymer fibers and water, and a virtue membrane designed to wrap up the boundary of the model. The model not only depicts the behaviors of the compressive mechanics and the expelled water, but also explains the nonlinear stress–strain relation of PVA hydrogels and why the hydrogels with high water content demonstrate a modulus considerably lower than the bulk modulus of water.

In this paper, we show a novel method for solving the preimage problem. The most algorithms of dimension reduction are trying to maintain the geometric structures including the local and the global. Usually we assume that the manifolds are local linear. Given the assumption, we can obtain the reconstructing images by calculating the locally optimal linear fits. In the novel pre-image algorithm, firstly we find the k nearest neighbours of test samples in feature space, and then calculate the optimal approximation of test samples by their k nearest neighbours. And we give a simple stability analysis to this nonlinear iterative algorithm. The novel preimage algorithm has been used in the second defect detection of notes' printing. The effect of detection is very obviously in improving detection speed and accuracy.

Dark channel prior algorithm performs excellently in haze removal problem, but it is time consuming. Unlike the computational mathematics based methods, we give image processing ways to accelerate the algorithm. We first use pyramidal method to accelerate the algorithm, but the number of hierarchies could be used is limited, and it will bring roughness and undesired effect. Then the segmentation method is shown in the paper with bad block phenomenon. Additional subjections are used to stitch each segment together. The new algorithm greatly reduces the complexity and allows concurrent computation. By analyzing the Matting Laplacian Matrix, we also give explanation to the phenomena emerged in the experiments.

This paper presents a manifold based kernel optimizing algorithm for KPCA which has recently shown effectiveness for pattern recognition and systematic classification based on extracting nonlinear features. However, their performances largely depend on the kernel function. Current methods simply choose the kernel function empirically or experimentally from a given set of candidates. We use manifold learning to improve the kernel function, which is capable to discover the nonlinear degrees of freedom that underlie complex natural observations. In contrast to previous algorithms for kernel optimization, ours efficiently computes a globally optimal solution that is guaranteed to converge asymptotically to the true structure and extracts the nonlinear features better. Experiments show that the method performed well in the field of pattern recognition.