The therapeutic effect of anti-CD19 antibody on DHEA-induced PCOS mice.

Immune dysregulation has been summarized as a critical factor in the occurrence and development of Polycystic ovary syndrome (PCOS), but potential mediators and mechanisms remain unclear. Our previous study showed that CD19+ B cells were involved in the pathogenesis of dehydroepiandrosterone (DHEA)-induced PCOS mice. Here, we studied the therapeutic potential of anti-CD19 antibody (aCD19 Ab) on DHEA-induced PCOS mice. The results showed that aCD19 Ab treatment improved ovarian pathological structure and function of PCOS mice, manifested by an increased number of corpus luteum, a decreased number of cystic follicles and atretic follicles, and regular estrus cycles. The aCD19 Ab treatment reduced the proportion of splenic CD21+ CD23low marginal zone B cells as well as the level of serum IgM and decreased the percentage of peripheral blood and splenic neutrophils. In particular, aCD19 Ab treatment reduced the apoptosis of granulosa cells and macrophage infiltration in ovarian secondary follicles of PCOS mice, as well as the expression of TNF-α in ovarian tissue and serum TNF-α levels. Moreover, we confirmed that TNF-α induced the apoptosis of human ovarian granulosa tumor cell line cells in vitro. Thus, our work demonstrates that aCD19 Ab treatment improves ovarian pathological phenotype and function by reducing local and systemic inflammation in PCOS mice, which may provide a novel insight into PCOS therapy.

Metformin abrogates pathological TNF-α-producing B cells through mTOR-dependent metabolic reprogramming in polycystic ovary syndrome.

B cells contribute to the pathogenesis of polycystic ovary syndrome (PCOS). Clinically, metformin is used to treat PCOS, but it is unclear whether metformin exerts its therapeutic effect by regulating B cells. Here, we showed that the expression level of tumor necrosis factor-alpha (TNF-α) in peripheral blood B cells from PCOS patients was increased. Metformin used in vitro and in vivo was able to reduce the production of TNF-α in B cells from PCOS patients. Administration of metformin improved mouse PCOS phenotypes induced by dehydroepiandrosterone (DHEA) and also inhibited TNF-α expression in splenic B cells. Furthermore, metformin induced metabolic reprogramming of B cells in PCOS patients, including the alteration in mitochondrial morphology, the decrease in mitochondrial membrane potential, Reactive Oxygen Species (ROS) production and glucose uptake. In DHEA-induced mouse PCOS model, metformin altered metabolic intermediates in splenic B cells. Moreover, the inhibition of TNF-α expression and metabolic reprogramming in B cells of PCOS patients and mouse model by metformin were associated with decreased mTOR phosphorylation. Together, TNF-α-producing B cells are involved in the pathogenesis of PCOS, and metformin inhibits mTOR phosphorylation and affects metabolic reprogramming, thereby inhibiting TNF-α expression in B cells, which may be a new mechanism of metformin in the treatment of PCOS.

A self-oriented beacon liquid crystal assay for kanamycin detection with AuNPs signal enhancement.

The authors report a self-oriented beacon liquid crystal (LC) biosensor for kanamycin (Kana) detection with gold nanoparticle (AuNPs) signal enhancement. In this study, an assay was proposed for Kana detection using the aptamer as a self-oriented beacon. Without an additional orientation agent, the Kana aptamer was used as a self-oriented beacon both as an orientation agent for the LCs and as a signal recognition probe for biological molecules. Gold nanoparticles are blended with desired concentrations of the target molecules, which can greatly improve the performance of the biosensor. In the presence of Kana, AuNPs-Kana-aptamer conjugates will form on the sensing interface of the biosensor, which can remarkably destroy the orientated arrangement of the LCs, resulting in changes in the corresponding polarized images of the LCs. The limit of Kana detection is as low as 0.1 pmol L-1. It is important to note that the self-oriented beacons are immobilized on the assembled film of the glass slides for the specific recognition of Kana, simultaneously allowing the homeotropic orientation of the LCs. This study also provides a mechanism for the self-orientation beacon and liquid crystal biosensing.

Action Intention Understanding EEG Signal Classification Based on Improved Discriminative Spatial Patterns.

OBJECTIVE: Action intention understanding EEG signal classification is indispensable for investigating human-computer interactions and intention understanding mechanisms. Numerous investigations on classification tasks extract classification features by using graph theory metrics; however, the classification results are usually not good. METHOD: To effectively implement the task of action intention understanding EEG signal classification, we proposed a new feature extraction method by improving discriminative spatial patterns. RESULTS: The whole frequency band and fusion band achieved satisfactory classification accuracies. Compared with other authors' methods for action intention understanding EEG signal classification, the new method performs more satisfactorily in some aspects. CONCLUSIONS: The new feature extraction method not only effectively avoids complex values when solving the generalized eigenvalue problem but also perfectly realizes appreciable classification accuracies. Fusing the classification features of different frequency bands is a useful strategy for the classification task.

Usnic-Acid-Functionalized Silk Fibroin Composite Scaffolds for Cutaneous Wounds Healing.

Despite the progress in chronic wound treatment, antibacterial cutaneous scaffold with high efficiency in wound healing is still the hot spot in the field. In present study, a functionalized silk fibroin (SF) cutaneous scaffold incorporated with natural medicine usnic acid (UA) is investigated, in which UA is used as an antibacterial and wound-healing reagent. Via electrospinning, UA-SF mixture is fabricated into UA-SF composite scaffold (USCS), which is composed of uniform nanofibers with average diameters of around 360 ± 10 nm. The interwoven nanofibers form mesh structure providing sufficient moisture permeability for scaffold. With methanol treatment, USCS presents improved mechanical properties and stability to protease XIV. In the presence of USCS, the growth rate of both Gram-positive and Gram-negative bacteria, including Staphylococcus aureus, Streptococci pyogenes, Escherichia coli, and Pseudomonas aeruginosa, is significantly inhibited in plate culture and suspension assays. In a cutaneous excisional mouse wound model, USCS presents a significant increase of wound closure rate, compared with pure SF scaffold and commercial dressing, Tegaderm Hydrocolloid 3M . The histological assessments further prove that USCS can enhance re-epithelialization, vascularization, and collagen deposition in wound site to promote the wound-healing process, which indicates the potential application of USCS in chronic wound treatment.

Weighted Brain Network Metrics for Decoding Action Intention Understanding Based on EEG.

Background: Understanding the action intentions of others is important for social and human-robot interactions. Recently, many state-of-the-art approaches have been proposed for decoding action intention understanding. Although these methods have some advantages, it is still necessary to design other tools that can more efficiently classify the action intention understanding signals. New Method: Based on EEG, we first applied phase lag index (PLI) and weighted phase lag index (WPLI) to construct functional connectivity matrices in five frequency bands and 63 micro-time windows, then calculated nine graph metrics from these matrices and subsequently used the network metrics as features to classify different brain signals related to action intention understanding. Results: Compared with the single methods (PLI or WPLI), the combination method (PLI+WPLI) demonstrates some overwhelming victories. Most of the average classification accuracies exceed 70%, and some of them approach 80%. In statistical tests of brain network, many significantly different edges appear in the frontal, occipital, parietal, and temporal regions. Conclusions: Weighted brain networks can effectively retain data information. The integrated method proposed in this study is extremely effective for investigating action intention understanding. Both the mirror neuron and mentalizing systems participate as collaborators in the process of action intention understanding.

Gold nanoparticle-based signal enhancement of an aptasensor for ractopamine using liquid crystal based optical imaging.

The authors report on a method for the determination of ractopamine (RAC) via liquid crystal (LC) optical imaging and gold nanoparticle-induced signal enhancement. The gold nanoparticles (AuNPs) were blended with the desired concentrations of RAC, and this is found to strongly improve the performance of the assay. The RAC aptamers were immobilized on the self-assembled film of a glass slide for specific recognition of RAC. This causes a homeotropic re-orientation of the LCs. Notably, the aptamers need not be immobilized on the nanoparticles like in other methods. The addition of RAC causes the formation of an AuNP-RAC-aptamer conjugate on the sensing interface. This disrupts the orientation of LCs and results in a change of the polarized images of the LCs. The method has a detection limit as low as 1 pM of RAC. Graphical abstract Schematic presentation of a method for the determination of ractopamine (RAC) using liquid crystal (LC) optical imaging and gold nanoparticle-induced signal enhancement. The aptamers need not be immobilized on the nanoparticles like in other methods.

Mesenchymal Stem Cells Alleviate DHEA-Induced Polycystic Ovary Syndrome (PCOS) by Inhibiting Inflammation in Mice.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Chronic inflammation is considered to be the cause of ovarian dysfunction. Increasing evidence in animal studies and in preliminary clinical trials has demonstrated that MSCs possess immunomodulatory effects via their interaction with immune cells. However, their contribution to PCOS remains unclear. In this study, we showed that the administration of hUC-MSCs could efficiently improve the pathological changes of PCOS mice induced by dehydroepiandrosterone (DHEA), including ovarian histopathology and function. Moreover, we found that the administration of MSCs significantly downregulated the expression of proinflammatory factors (TNF-α, IL-1ß, and IFN-γ) and fibrosis-related genes (CTGF) in ovarian and uterus tissues and affected the systemic inflammatory response. The percentage of peripheral neutrophils, M1 macrophages, and B cells was significantly reduced, while M2 macrophages and regulatory T cells (Tregs) were increased in hUC-MSC-treated mice. In the spleen, the percentage of neutrophils, M1 macrophages, IFN-γ +CD19+B cell, IFN-γ +CD4+T cells (Th1), and IL-17+CD4+T cells (Th17) was significantly decreased in hUC-MSC-treated mice. These results suggested that hUC-MSC treatment could alleviate ovarian dysfunction by inhibiting ovarian local and systemic inflammatory responses.

Preparation of DNA-functionalized surfaces for simultaneous homeotropic orientation of liquid crystals and optical recognition of analytes: application to the determination of progesterone.

The work describes a simplified method for the preparation of liquid crystal (LC) bioassay using DNA-based capture molecules and having lower detection limits. The capture DNA probes of the stem-loop structure were immobilized on the surface of a glass slide. A homeotropic orientation of LC molecules can be obtained with the proper surface coverage of capture DNA probes. In the presence of analytes (specifically shown here for the progesterone as a model analyte), the molecular binding between capture DNA probes and progesterone opens the loop of the capture DNA probes. The opened sequence is then amenable to hybridization with a reporter DNA probe that is immobilized on gold nanoparticles. This changes the surface microstructure, disrupts the orientation of LC molecules, and results in an enhanced optical response, expressed as the average grey value of the images. This new kind of surface treatment for simultaneous recognition of target molecules and homeotropic anchoring of LCs reduces the number of preparation steps and makes the process of LC bioassay easier. This method has a detection limit as low as 0.1 pmol·L-1 of progesterone. Graphical abstract Schematic presentation of the liquid crystal-based DNA assay. DMOAP: Dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride; TEA: Triethoxsilylbutyraldehyde; 5CB: 4-cyano-4'-pentylbiphenyl; P4: progesterone.

Detection of sulfadimethoxine using optical images of liquid crystals.

A label-free method for sulfadimethoxine (SDM) detection using an aptamer-based liquid crystal biosensor is developed. The sensor probe is fabricated by immobilizing amine-functionalized aptamers onto the glass slide decorating mixed self-assembled layers of triethoxysilylbutyraldehyde (TEA) and N,N-dimethyl-n-octadecyl-3-aminopropyltrimethoxysilylchloride (DMOAP). Liquid crystals (LCs) are supported on the surface and serve as response elements, which assume the homeotropic alignment and cause a dark optical appearance under crossed polarizers. In the presence of SDM, the formation of SDM-aptamer compounds induces a notable change in the topographical structure of the surface, which disturbs the original homeotropic orientation of LCs and results in a bright optical appearance. A detection limit of 10 µg L-1 is obtained, which is far lower than the maximum residue limit (100 µg L-1 in China). This facile method shows good specificity for SDM detection and may have great potential for detecting other small molecules.

QCM-nanomagnetic beads biosensor for lead ion detection.

As lead poses a serious threat to humans even in small amounts, all kinds of lead detection sensors with high sensitivity and selectivity are being constantly improved and put forward. In this report, a novel, simple and label-free quartz crystal microbalance (QCM) biosensor is proposed for detecting lead ions (Pb2+). The biosensor takes full advantage of the high specificity of GR-5 DNAzyme to Pb2+ and the high sensitivity of QCM. In particular, nanomagnetic beads (NMBs) are used as a novel and effective mean of signal amplification in the biosensor because of their mass and their ability to enhance the inductive effect, which are very beneficial for both higher sensitivity and a lower detection limit. In practice, GR-5 DNAzyme, innovatively combined with NMBs, was modified on the gold electrode of the QCM through gold-sulfur self-assembly. When the electrode was exposed to Pb2+ solution, DNAzyme was severed into two parts at the RNA site (rA), along with the release of NMBs, which caused a great increase in frequency shift of the QCM electrode. Finally, a perfect linear correlation between the logarithm of Pb2+ concentration and the change in frequency was obtained from 1 pM to 50 nM, with a detection limit as low as 0.3 pM. Moreover, the biosensor shows both an average recovery of 97 ± 6% in a drinking water sample and an excellent specificity for Pb2+ compared with other metal ions.

Comprehensive assessment of association between TLR4 gene polymorphisms and cancer risk: a systematic meta-analysis.

Previous studies have explored the association between toll-like receptor 4 (TLR4) polymorphisms and risk of various cancers, but the results remained controversial. To obtain an assessment of the effect of TLR4 polymorphisms (rs4986790, rs4986791 and rs11536889) on cancer risk, fifty-five articles (containing 20107 cases and 28244 controls) were recruited for meta-analysis. Our result indicated that two Single Nucleotide Polymorphisms (SNP) in TLR4 were associated with decreased cancer risk for rs4986791: OR = 0.764, 95% CI: 0.652-0.894, P = 0.001 in allele model; OR = 0.769, 95%CI: 0.650-0.909, P = 0.002 in recessive model; OR = 0.505, 95% CI: 0.352-0.726, P = 0.000 in dominant model; for 11536889: OR = 0.927, 95% CI: 0.872-0.984, P = 0.013 in allele model; OR = 0.926, 95% CI: 0.862-0.944,P = 0.034 in recessive model. In terms of subgroup analyses sorted by ethnicity, only polymorphism of rs4986791 had a significant influence on decrease of cancer risk among both Caucasian and Asian populations. The findings suggested that TLR4 polymorphisms may serve as a genetic risk factor for cancers.

Identification and validation long non-coding RNAs of oral squamous cell carcinoma by bioinformatics method.

Gene markers of oral squamous cell carcinoma (OSCC) have great significance on early diagnosis and treatment of clinical oral cancer. In this study, we used RNA-Seq data from OSCC patients and filtered differentially-expressed long non-coding RNA (lncRNA) to further clarify the molecular mechanism. Firstly, we downloaded datasets of OSCC from National Center for Biotechnology Information(NCBI), which were predicted and analyzed by cufflinks and tophat. Then, differentially expressed lncRNA enrichment was performed with The Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, we verified the gene expression via in vitro assays. Results showed that 52 lncRNAs were significantly differentially expressed compared to those in normal oral tissues, three highly expressed genes (XLOC_002599, XLOC_002634 and XLOC_132858) were verified by RT-PCR, which was consistent with the prediction. XLOC_002634 (GAS5) transcript levels were reduced both in vivo and in vitro assays, which confirmed that the expression of GAS5 was comparatively low in OSCC. Over-expression of GAS5 in cancer cells inhibited cell proliferation. Moreover, the migration and invasion potential of cancer cells were inhibited compared to control groups. All in all, the study indicated that the decrease in GAS5 expression may contribute to OSCC tumor pathogenesis and serve as a potential target for cancer therapy.

Homeotropic orientation behavior of nematic liquid crystals induced by copper ions.

A homeotropic ordering film of nematic liquid crystal (LC) induced by copper ions (Cu(2+)) had been developed. The Cu(ClO4)2 was directly spin-coated on the glass substrate without any other chemical modification. A homeotropic orientation of LC thin-film was generated by the interfacial chemical interaction between nitrile-containing LC and copper ions on the surface. Results showed that an appropriate density of Cu(2+) could shorten the response time of orientation, but a shelf-time was prolonged. The LC film fabrication not only offered a simple process, but also presented a great repeatability to detect organophosphonates (DMMP). This study provided guidance for the design of LC films responding to organic molecules as a biosensor.

[Enhancement and assessment of the fundus image].

A new enhancement method is proposed based on the characteristics of fundus images in this paper. Firstly, top-hat transform is utilized to weaken the background. Secondly, contrast limited adaptive histogram equalization (CLAHE) is performed to improve the uneven illumination. Finally, two-dimensional matched filters are designed to further enhance the contrast between blood vessels and background. The algorithm was tested in DIARETDB0 databases and showed good applicability for both normal and pathological fundus images. A new no-reference image quality assessment method was used to evaluate the enhancement methods objectively. The results demonstrated that the proposed method could effectively weaken the background, increase contrast, enhance details in the fundus images and improve the image quality greatly.

[Study on a new urine analysis core module based on semi-reflection mirror].

A new urine analysis core module based on high performance 32-bit microprocessor and high precision color sensor was presented. A novel optical structure and a specific circuit were applied to improve measurement precision and temperature was used to compensate for results in this core module. The information of urine test peice, such as all original data and color RGB value, reflectivity, semi-quantitative level, etc. can be output. The results showed that the measuring precision was about 95% or above with ideal stability and reliability using this presented core module, which can be conveniently applied in various urine analyzers, and can greatly decrease the cost of urine analyzers in development and production.

A gold nanoparticles enhanced surface plasmon resonance immunosensor for highly sensitive detection of ischemia-modified albumin.

In this study a novel sensitive nanogold particle sensor enhancement based on mixed self-assembled monolayers was explored and used to construct a Surface Plasmon Resonance (SPR) immunosensor to detect Ischemia Modified Albumin (IMA). Compared with a direct binding SPR assay at a limit of detection (LOD) of 100 ng/L, gold nanoparticles (AuNPs) of 10 nm dramatically improved the LOD of IMA to 10 ng/L. Meanwhile, no interfering substance that may lead to false positive results was identified. These results suggested that the SPR biosensor presented superior properties, and provided a simple label-free strategy to increase assay sensitivity for further acute coronary syndrome (ACS) diagnosis.

[Objective evaluation of driving fatigue by using variability of pupil diameter under spontaneous pupillary fluctuation conditions].

Objective evaluation of driver drowsiness is necessary toward suppression of fatigued driving and prevention of traffic accident. We have developed a new method in which we utilized pupillary diameter variability (PDV) under spontaneous pupillary fluctuation conditions. The method consists of three main steps. Firstly, we use a 90s long infrared video of pupillogram infrared-sensitive CCD camera. Secondly, we employed edge detection algorithm based on curvature characteristics of pupil boundary to extract a set of points of visible pupil boundary, and then we adopted these points to fit a circle to obtain the diameter of the pupil in current frame of video. Finally, the values of PDV in 90s long video is calculated. In an experimental pilot study, the values of PDV of two groups were measured. One group rated themselves as alert (12 men), the other group as sleepy (13 men). The results showed that significant differences could be found between the two groups, and the values were 0.06 +/- 0.005 and 0.141 +/- 0.042, respectively. Taking into account of the knowledge that spontaneous pupillary fluctuation is innervated by autonomic nervous system which activity is known to change in parallel with drowsiness and cannot be influenced by subjective motive of people. From the results of the experiments, we concluded that PDV could be used to evaluate driver fatigue objectively.

[Study on the orientation of liquid crystals presented on the glass substrates spin-coated and functionalized with copper ions].

A stable, uniform, easily implemented, LC-based chemical and biological sensor substrate for orientations of liquid crystals (LCs) for a long-term is urgently needed for medical applications of the sensors. We proposed a use of spin-coating of copper perchlorate (Cu(ClO4)2), with five different concentrations(0-100mmol/L), directly on glass slides for fabricating a layer of chemically-sensitive copper ions. Observing the transmitted light with a polarized microscope, we found the luminosity of the light propagated through sensors deposited with copper ions started to weaken gradually after a certain time. The higher was the concentration of copper ions covered on the glass substrates of the sensors, the faster the weakening occurred, and the less time was needed for transmitted light to turn completely dark. But there was no change in luminosity of the transmitted light for the sensors without Cu(ClO4)2 spin-coating even after stored at room temperature (25 degrees C) for a whole day. When the Cu(ClO4)2 deposited sensors were stored within a drying oven at room temperature (25 degrees C) for 2 months, it was found that there vas almost no change in luminosity of the transmitted lights. The results showed that all the thin films of LC on glass slides functionalized with Cu(ClO4)2 could keep homeotropic and stable orientation for a long time; the concentration of Cu (ClO4)2I has an influence on the orientation response speed of LC from planar to perpendicular orientation.