The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases

Reports on bacteria detected in maternal fluids during pregnancy are typically associated with adverse consequences, and whether the female reproductive tract harbours distinct microbial communities beyond the vagina has been a matter of debate. Here we systematically sample the microbiota within the female reproductive tract in 110 women of reproductive age, and examine the nature of colonisation by 16S rRNA gene amplicon sequencing and cultivation. We find distinct microbial communities in cervical canal, uterus, fallopian tubes and peritoneal fluid, differing from that of the vagina. The results reflect a microbiota continuum along the female reproductive tract, indicative of a non-sterile environment. We also identify microbial taxa and potential functions that correlate with the menstrual cycle or are over-represented in subjects with adenomyosis or infertility due to endometriosis. The study provides insight into the nature of the vagino-uterine microbiome, and suggests that surveying the vaginal or cervical microbiota might be useful for detection of common diseases in the upper reproductive tract.Shenzhen Municipal Government of China [JCYJ20160229172757249, JCYJ20150601090833370]; Danish Strategic Research Council [2106-07-0021]; Ole Romer grant from Danish Natural Science Research Council; Solexa project [272-07-0196]SCI(E)ARTICLE

Coordination Chemistry Enables Tunable Crosslinking, Reversible Phase Transition, and 3D Printing of Hydrogels for Biomedical Applications

Hyaluronic acid (HyA) hydrogels are promising in various biomedical applications such as tissue regeneration, drug delivery, cell therapy, and biosensing. Three-dimensional printing (3D printing) can precisely control the structures and properties of the HyA hydrogels, which is highly desirable for many biomedical applications. However, the crosslinking and 3D printing of HyA hydrogels usually require chemical modifications. This may raise toxicity concerns on the hydrogels, especially when regulatory approval is required for the clinical translation of the final products. This dissertation investigated the mechanisms of dynamic coordination and the relationships among the key parameters in controlling the tunable crosslinking, reversible phase transition, and 3D printing of HyA hydrogels for biomedical applications, without blending with other polymers or adding new functional groups. In the first part, tunable crosslinking and reversible phase transition of HyA hydrogels were achieved and demonstrated via dynamic coordination of Fe3+ ions with innate carboxyl groups. The concentrations of Fe3+ and H+ ions and the reaction time determine the coordination state, leading to the low-to-high crosslinking densities and reversible solid-liquid phase transition of HyA hydrogels. In chapters 3 and 4, three different 3D printing approaches for HyA hydrogels were developed, for the first time. Two 3D printing strategies, namely cold-stage and direct-writing methods, were achieved based on the tunable crosslinking and reversible phase transition of the HyA hydrogel. Direct writing of HyA solution in FeCl3 solution was also achieved by decelerating the solidification process of the hydrogel in FeCl3 solution. In chapter 5, the cytocompatibility of HyA hydrogels with different crosslinking densities and 3D-printed HyA constructs was investigated via the direct exposure culture method with bone marrow-derived mesenchymal stem cells (BMSCs). The last part of this dissertation investigated the incorporation of magnetic nanoparticles (MNPs) in the HyA hydrogels in situ. The MNP content and agglomeration in the magnetic hydrogels were tunable by controlling concentrations of Fe3+ and Fe2+ ions. Cell study results indicated that BMSC adhesion density decreased when increasing the MNP content in HyA hydrogels

Research on Defect Recognition of Lithium Battery Pole Piece Based on Deep Learning

In the field of defect recognition, deep learning technology has the advantages of strong generalization and high accuracy compared with mainstream machine learning technology. This paper proposes a deep learning network model, which first processes the self-made 3, 600 data sets, and then sends them to the built convolutional neural network model for training. The final result can effectively identify the three defects of lithium battery pole pieces. The accuracy rate is 92%. Compared with the structure of the AlexNet model, the model proposed in this paper has higher accuracy

DEF6(differentially exprehomolog) exacerbates pathological cardiac hypertrophy via RAC1

Abstract Pathological cardiac hypertrophy involves multiple regulators and several signal transduction pathways. Currently, the mechanisms of it are not well understood. Differentially expressed in FDCP 6 homolog (DEF6) was reported to participate in immunity, bone remodeling, and cancers. The effects of DEF6 on pathological cardiac hypertrophy, however, have not yet been fully characterized. We initially determined the expression profile of DEF6 and found that DEF6 was upregulated in hypertrophic hearts and cardiomyocytes. Our in vivo results revealed that DEF6 deficiency in mice alleviated transverse aortic constriction (TAC)-induced cardiac hypertrophy, fibrosis, dilation and dysfunction of left ventricle. Conversely, cardiomyocyte-specific DEF6-overexpression aggravated the hypertrophic phenotype in mice under chronic pressure overload. Similar to the animal experiments, the in vitro data showed that adenovirus-mediated knockdown of DEF6 remarkably inhibited phenylephrine (PE)-induced cardiomyocyte hypertrophy, whereas DEF6 overexpression exerted the opposite effects. Mechanistically, exploration of the signal pathways showed that the mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2)-extracellular signal-regulated kinase 1/2 (ERK1/2) cascade might be involved in the prohypertrophic effect of DEF6. Coimmunoprecipitation and GST (glutathione S-transferase) pulldown analyses demonstrated that DEF6 can directly interact with small GTPase Ras-related C3 botulinum toxin substrate 1 (Rac1), and the Rac1 activity assay revealed that the activity of Rac1 is altered with DEF6 expression in TAC-cardiac hypertrophy and PE-triggered cardiomyocyte hypertrophy. In the end, western blot and rescue experiments using Rac1 inhibitor NSC23766 and the constitutively active mutant Rac1(G12V) verified the requirement of Rac1 and MEK1/2-ERK1/2 activation for DEF6-mediated pathological cardiac hypertrophy. Our study substantiates that DEF6 acts as a deleterious regulator of cardiac hypertrophy by activating the Rac1 and MEK1/2-ERK1/2 signaling pathways, and suggests that DEF6 may be a potential treatment target for heart failure

Surface Defects Detection and Identification of Lithium Battery Pole Piece Based on Multi-Feature Fusion and PSO-SVM

In order to realize the automatic detection of surface defects of lithium battery pole piece, a method for detection and identification of surface defects of lithium battery pole piece based on multi-feature fusion and PSO-SVM was proposed in this paper. Firstly, image subtraction and contrast adjustment were used to preprocess the defect image to weaken the influence of non-defective areas and enhance the defect features. Then, Canny algorithm and the AND logical operation were used to extract the image of defect area. Next, the texture feature, edge feature, and HOG feature were combined to extract the feature of the defect area image. Finally, the support vector machine (SVM) optimized by particle swarm optimization (PSO) was used to automatically identify and classify defect images. The experimental results show that the proposed method in this paper can effectively detect surface multiple types defects of lithium battery pole piece, and the average recognition rate of defects reaches 98.3%, which is an effective and feasible automatic defect detection and identification method

Photocatalytic Process of Simultaneous Desulfurization and Denitrification of Flue Gas by TiO₂–Polyacrylonitrile Nanofibers

TiO₂ nanoparticles were successfully fabricated on electrospun polyacrylonitrile (PAN) nanofibers via the coupling of electrospinning and hydrothermal pathway. A straightforward photocatalysis oxidation process has been developed for simultaneous desulfurization and denitrification of flue gas using the TiO₂–PAN photocatalyst. Also, the influences of some important operating parameters, such as titanium loading content of catalyst, flue gas humidity, flue gas flow, and inlet flue gas temperature on removal efficiencies of SO₂ and NO were investigated. The results demonstrated that removal efficiencies of 99.3% for SO₂ and 71.2% for NO were attained under the following optimal experiment conditions: titanium loading content, 6.78 At %; gas flow rate, 200 mL/min; flue gas humidity, 5%; inlet flue gas temperature, 40 °C. Furthermore, the presumed reaction mechanism of SO₂ and NO removal using TiO₂–PAN photocatalyst under UV light was proposed

A versatile fabrication strategy of three-dimensional foams for soft and hard tissue engineering

The fabrication strategies of three-dimensional porous biomaterials have been extensively studied and well established in the past decades, yet the biocompatibility and versatility in preparing porous architecture still lacks. Herewith, we present a novel and green fabrication technique of 3D porous foams for both soft and hard engineering. By utilizing the gelatinization and retrogradation property of starches, stabilized porous constructs made of various building blocks from living cells to ceramic particles were created for the first time. In soft tissue engineering applications, 3D cultured tissue foam (CTF) with controlled release property of cells was developed and the foams constituted by osteoblasts, fibroblasts and vascular endothelial cells all exhibited high mechanical stability and preservation of cell viability or functions. More importantly, the CTF achieved sustained self-release of cells controlled by serum (containing amylase) concentration and the released cells also maintained high viability and functions. In the context of hard tissue engineering applications, ceramic/bioglass (BG) foam scaffolds were developed by the similar starch-assisted foaming strategy where the resultant bone scaffolds of hydroxyapatite (HA)/BG and Si33N4/BG possessed>70% porosity with interconnected macropores (sizes 200~400μm) and fine pores (sizes1~10 μm) and superior mechanical properties despite the high porosity. Additionally, in vitro and in vivo evaluations on the biological properties revealed that porous HA/BG foam exhibited desired biocompatibility and osteogenesis. The in vivo study indicated new bone ingrowth after 1 week and significant increases in new bone volume after 2 weeks. In conclusion, the presented foaming strategy provides opportunities for biofabricating CTF with different cells for different target soft tissues and preparing porous ceramic/BG foams with different material components and high strengths—showing great versatility in soft and hard tissue engineering

Carboxymethyl cellulose-alginate interpenetrating hydroxy ethyl methacrylate crosslinked polyvinyl alcohol reinforced hybrid hydrogel templates with improved biological performance for cardiac tissue engineering.

Cardiac tissue engineering is an emerging approach for cardiac regeneration utilizing the inherent healing responses elicited by the surviving heart using biomaterial templates. In this study, we aimed to develop hydrogel scaffolds for cardiac tissue regeneration following myocardial infarction (MI). Two superabsorbent hydrogels, CAHA2A and CAHA2AP, were developed employing interpenetration chemistry. CAHA2A was constituted with alginate, carboxymethyl cellulose, (hydroxyethyl) methacrylate, and acrylic acid, where CAHA2AP was prepared by interpenetrated CAHA2A with polyvinyl alcohol. Both hydrogels displayed superior physiochemical characteristics, as determined by attenuated total reflection infrared spectroscopy spectral analysis, differential scanning calorimetry measurements, tensile testing, contact angle, water profiling, dye release, and conductivity. In vitro degradation of the hydrogels displayed acceptable weight composure and pH changes. Both hydrogels were hemocompatible, and biocompatible as evidenced by direct contact and MTT assays. The hydrogels promoted anterograde and retrograde migration as determined by the z-stack analysis using H9c2 cells grown with both gels. Additionally, the coculture of the hydrogels with swine epicardial adipose tissue cells and cardiac fibroblasts resulted in synchronous growth without any toxicity. Also, both hydrogels facilitated the production of extracellular matrix by the H9c2 cells. Overall, the findings support an appreciable in vitro performance of both hydrogels for cardiac tissue engineering applications