Reduced Retinal Vascular Density and Skeleton Length in Amblyopia.

Purpose: This study aimed to investigate the possible relationship between retinal vascular abnormalities and amblyopia by analyzing vascular structures of fundus images. Methods: In this observational study, retinal fundus images were collected from 36 patients with unilateral amblyopia, 33 patients with bilateral amblyopia, and 36 healthy control volunteers. We developed a customized training algorithm based on U-Net to digitalize the vasculature in the fundus images to quantify vascular density (area and fractal dimension), skeleton length, and number of bifurcation points. For statistical comparisons, this study divided participants into two groups. The amblyopic eyes and the fellow eyes of patients with unilateral amblyopia formed the paired group, while bilateral amblyopic patients and healthy controls formed the independent group. Results: In the paired group, the vascular area (P = 0.007), vascular fractal dimension (P = 0.007), and vascular skeleton length (P = 0.002) of the amblyopic eyes were significantly smaller than those of the fellow eyes. In the independent group, significant decreases in the vascular fractal dimension (P = 0.006) and skeleton length (P = 0.048) were observed in bilateral amblyopia compared to control. The vascular area was also significantly correlated with best-corrected visual acuity in amblyopic eyes. Conclusions: This study demonstrated that retinal vascular density and skeleton length in amblyopic eyes were significantly smaller compared to control, indicating an association between the changes in retinal vascular features and the state of amblyopia. Translational Relevance: Our algorithm presents amblyopic retinal vascular changes that are more biologically interpretable for both clinicians and researchers.

General room-temperature Suzuki-Miyaura polymerization for organic electronics.

π-Conjugated polymers (CPs) have broad applications in high-performance optoelectronics, energy storage, sensors and biomedicine. However, developing green and efficient methods to precisely synthesize alternating CP structures on a large scale remains challenging and critical for their industrialization. Here a room-temperature, scalable and homogeneous Suzuki-Miyaura-type polymerization reaction is developed with broad generality validated for 24 CPs including donor-donor, donor-acceptor and acceptor-acceptor connectivities, yielding device-quality polymers with high molecular masses. Furthermore, the polymerization protocol significantly reduces homocoupling structural defects, yielding more structurally regular and higher-performance electronic materials and optoelectronic devices than conventional thermally activated polymerizations. Experimental and theoretical studies reveal that a borate transmetalation process plays a key role in suppressing protodeboronation, which is critical for large-scale structural regularity. Thus, these results provide a general polymerization tool for the scalable production of device-quality CPs with alternating structural regularity.

Advances in the anti-tumor potential of hederagenin and its analogs.

Hederagenin is a pentacyclic triterpenoid that is widely distributed as the main pharmaceutical ingredient in various medicinal plants. Similarly as other pentacyclic triterpenoids, hederagenin has various pharmacological effects such as anti-tumor, anti-inflammatory, anti-depressant, and anti-viral activities. In particular, the anti-tumor activity of hederagenin indicates its potential for development into highly effective chemotherapeutic agents. Studies revealed that hederagenin effectively suppresses the growth of various tumor cell lines in vitro and interacts with several molecular targets that play essential roles in various cellular signaling pathways. The compound suppresses transformation, inhibits proliferation, and induces apoptosis in tumor cells. In this review, we highlight research progress on the source, pharmacokinetics, pharmacological activity, and mechanism of action of hederagenin and the anti-tumor activity of its analogs by integrating and analyzing relevant domestic and international studies and providing a basis for their further development and application.

Characterization of a chlorine resistant and hydrophilic TiO2/calcium alginate hydrogel filtration membrane used for protein purification maintaining protein structure.

The development of membranes for protein purification has stringent requirement of disinfection resistance, low protein adsorption and anti-fouling, without changing protein structure. In this study, hydrophilic titanium dioxide (TiO2)/calcium alginate (TiO2/CaAlg) hydrogel membranes were prepared by a simple ionic cross-linking method. The effects of the porogenic agent polyethylene glycol (PEG) concentration, the molecular weight of PEG, and the concentration of TiO2 on the filtration properties were systematically investigated. The TiO2/CaAlg membrane exhibited excellent bovine serum albumin (BSA) rejection and anti-fouling properties. The mechanical properties and surface energy of the TiO2/CaAlg membrane were significantly improved. The chemical bonding mechanism of TiO2 and NaAlg was investigated by molecular dynamic simulation. The TiO2/CaAlg membrane had good chlorine resistance and could be disinfected or cleaned with sodium hypochlorite. The TiO2/CaAlg hydrogel membrane loaded with polyhydroxybutyrate (PHB) nanofibers maintained high flux (136.7 L/m2h) and high BSA rejection (98.0 %) at 0.1 MPa. The results of circular dichroism and synchronous fluorescence indicated that the secondary structure of BSA was maintained after membrane separation. This study provides one method for the preparation of green and environmentally friendly membrane for protein purification.

Room Temperature Anhydrous Suzuki-Miyaura Polymerization Enabled by C-S Bond Activation.

The Suzuki-Miyaura cross-coupling is one of the most important and powerful methods for constructing C-C bonds. However, the protodeboronation of arylboronic acids hinder the development of Suzuki-Miyaura coupling in the precise synthesis of conjugated polymers (CPs). Here, an anhydrous room temperature Suzuki-Miyaura cross-coupling reaction between (hetero)aryl boronic esters and aryl sulfides was explored, of which universality was exemplified by thirty small molecules and twelve CPs. Meanwhile, the mechanistic studies involving with capturing four coordinated borate intermediate revealed the direct transmetalation of boronic esters in the absence of H2 O suppressing the protodeboronation. Additionally, the room temperature reaction significantly reduced the homocoupling defects and enhanced the optoelectronic properties of the CPs. In all, this work provides a green protocol to synthesize alternating CPs.

Enhanced Readout from Spatial Interference Fringes in a Point-Source Cold Atom Inertial Sensor.

When the initial size of an atom cloud in a cold atom interferometer is negligible compared to its size after free expansion, the interferometer is approximated to a point-source interferometer and is sensitive to rotational movements by introducing an additional phase shear in the interference sequence. This sensitivity on rotation enables a vertical atom-fountain interferometer to measure angular velocity in addition to gravitational acceleration, which it is conventionally used to measure. The accuracy and precision of the angular velocity measurement depends on proper extraction of frequency and phase from spatial interference patterns detected via the imaging of the atom cloud, which is usually affected by various systematic biases and noise. To improve the measurement, a pre-fitting process based on principal component analysis is applied to the recorded raw images. The contrast of interference patterns are enhanced by 7-12 dB when the processing is present, which leads to an enhancement in the precision of angular velocity measurements from 6.3 µrad/s to 3.3 µrad/s. This technique is applicable in various instruments that involve precise extraction of frequency and phase from a spatial interference pattern.

Spatial filtering of Zeeman sub-states in an atomic fountain.

In an atomic fountain, atoms in motion can be spatially separated into discrete Zeeman sub-states by magnetically induced Stern-Gerlach effect. With resonant light pulses acting as a shutter, specific states are selected for subsequent experiments. Such separation-selection process in atomic optics is the analogue of a spatial filter in physical optics which selects and purifies the modes of light. This technique is demonstrated by injecting a pulsed current in a circular coil around a vertical atomic fountain, separating the pre-cooled Rubidium atoms by a distance of centimeters in between, and filtering each single sub-state with block pulses. The filtered atoms after the process is highly purified in the desired sub-state. The apparatus of the atomic spatial filter is adaptable in atomic optics and can be integrated into the high-vacuum chamber of an atomic fountain.

Metabolomics and Network Pharmacology-Based Investigation into the Mechanisms Underlying the Therapeutic Effect of a New Chinese Traditional Medicine (Cui Nai Ling) on Bromocriptine-Induced Hypogalactia.

As a traditional veterinary medicine to promote lactation, Cui Nai Ling (CNL) can not only increase milk supply and promote health but also improve the overall physiological function and immunity of the animals. In order to further improve CNL's effect on lactation, we have previously made a new CNL (NCNL) by adding Tetrapanacis Medulla and replacing Vaccariae Semen with fried Vaccariae Semen in CNL. We have demonstrated that the lactation-promoting effect of NCNL is better than that of CNL. However, the underlying mechanisms by which NCNL promotes lactation are unclear. In this study, we performed metabolomics, network pharmacology, and pharmacodynamic studies to explore the underlying mechanisms by which NCNL promotes lactation in rats with bromocriptine-induced hypogalactia. The results showed that NCNL significantly improved the loss of appetite in female adult rats and the weight loss of pups caused by the disorder of lactation. Biochemical analysis showed that NCNL could regulate the levels of PRL, T4, E2, Ca, UREA, GLU, ALT, AST, TCHO, and TG in serum. The pathological results showed that NCNL could promote lactation and increase the mammary gland index by improving breast acinar tissue morphology in rats with hypogalactia. Network pharmacology studies showed that NCNL promotes lactation through P13K-Akt, insulin resistance, and prolactin signaling pathways, among which the most frequently affected pathway was the P13K-Akt signaling pathway. Metabolomics studies showed that NCNL can significantly upregulate phenylalanine, tyrosine, and tryptophan biosynthesis and tyrosine metabolism pathways and downregulate cysteine and methionine metabolism pathways. NCNL can significantly increase the serum prolactin concentration, improve the glucose and lipid metabolism disorders, and regulate PI3K-Akt, insulin resistance, and prolactin pathways to affect the amino acids' metabolism in the mammary gland and ultimately exert its therapeutic effect on bromocriptine-induced postpartum hypogalactia. These findings revealed the effect and application value of NCNL on animals with postpartum hypogalactia.

EmDL: Extracting miRNA-Drug Interactions from Literature.

The microRNAs (miRNAs), regulators of post-transcriptional processes, have been found to affect the efficacy of drugs by regulating the biological processes in which the target proteins of drugs may be involved. For example, some drugs develop resistance when certain miRNAs are overexpressed. Therefore, identifying miRNAs that affect drug effects can help understand the mechanisms of drug actions and design more efficient drugs. Although some computational approaches have been developed to predict miRNA-drug associations, such associations rarely provide explicit information about which miRNAs and how they affect drug efficacy. On the other hand, there are rich information about which miRNAs affect the efficacy of which drugs in the literature. In this paper, we present a novel text mining approach, named as EmDL (Extracting miRNA-Drug interactions from Literature), to extract the relationships of miRNAs affecting drug efficacy from literature. Benchmarking on the drug-miRNA interactions manually extracted from MEDLINE and PubMed Central, EmDL outperforms traditional text mining approaches as well as other popular methods for predicting drug-miRNA associations. Specifically, EmDL can effectively identify the sentences that describe the relationships of miRNAs affecting drug effects. The drug-miRNA interactome presented here can help understand how miRNAs affect drug effects and provide insights into the mechanisms of drug actions. In addition, with the information about drug-miRNA interactions, more effective drugs or combinatorial strategies can be designed in the future. The data used here can be accessed at http://mtd.comp-sysbio.org/.

Altered spontaneous calcium signaling of in situ chondrocytes in human osteoarthritic cartilage.

Intracellular calcium ([Ca2+]i) signaling is an essential universal secondary messenger in articular chondrocytes. However, little is known about its spatiotemporal features in the context of osteoarthritis (OA). Herein, by examining the cartilage samples collected from patients undergoing knee arthroscopic surgery, we investigated the spatiotemporal features of spontaneous [Ca2+]i signaling in in situ chondrocytes at different OA stages. Our data showed zonal dependent spontaneous [Ca2+]i signaling in healthy cartilage samples under 4 mM calcium environment. This signal was significantly attenuated in healthy cartilage samples but increased in early-degenerated cartilage when cultured in 0 mM calcium environment. No significant difference was found in [Ca2+]i intensity oscillation in chondrocytes located in middle zones among ICRS 1-3 samples under both 4 and 0 mM calcium environments. However, the correlation was found in deep zone chondrocytes incubated in 4 mM calcium environment. In addition, increased protein abundance of Cav3.3 T-type voltage dependent calcium channel and Nfatc2 activity were observed in early-degenerated cartilage samples. The present study exhibited OA severity dependent spatiotemporal features of spontaneous [Ca2+]i oscillations of in situ chondrocytes, which might reflect the zonal specific role of chondrocytes during OA progression and provide new insight in articular cartilage degradation during OA progression.

GEAR: A database of Genomic Elements Associated with drug Resistance.

Drug resistance is becoming a serious problem that leads to the failure of standard treatments, which is generally developed because of genetic mutations of certain molecules. Here, we present GEAR (A database of Genomic Elements Associated with drug Resistance) that aims to provide comprehensive information about genomic elements (including genes, single-nucleotide polymorphisms and microRNAs) that are responsible for drug resistance. Right now, GEAR contains 1631 associations between 201 human drugs and 758 genes, 106 associations between 29 human drugs and 66 miRNAs, and 44 associations between 17 human drugs and 22 SNPs. These relationships are firstly extracted from primary literature with text mining and then manually curated. The drug resistome deposited in GEAR provides insights into the genetic factors underlying drug resistance. In addition, new indications and potential drug combinations can be identified based on the resistome. The GEAR database can be freely accessed through http://gear.comp-sysbio.org.

[Indirect coculture of human infrapatellar fat pad-derived stem cells with osteoarthritic chondrocytes induces their chondrogenesis].

Objective: To promote phenotype recovery of osteoarthritic articular chondrocytes( OACs) and induce chondrogenic differentiation of infrapatellar fat pad-derived stem cells( IPFPSCs) by indirectly coculturing these two types of cells. Methods: The OACs and IPFPSCs were isolated and cultured in vitro. This experiment included single IPFPSCs group,single OACs group,and coculture group. After cells were cultured in vitro with chondrogenic medium for 21 days,the chondrocyte phenotypes were determined by HE staining( cell morphology),Alcian blue staining( glycosaminoglycan content) and immunofluorescence cytochemistry( collagen 1,collagen 2,collagen 3,aggrecan,SOX9). Results: In coculture group,the OACs aggregated into microspheres,and the IPFPSCs were oval in shape. In single culture groups,the OACs were less aggregated and the spheres were smaller; and the IPFPSCs were spindle in shape. HE staining showed that,in the coculture group,the nuclei of OACs spheres were dark,and the IPFPSCs were rich in cytoplasm; while in single culture groups,the nuclei of OAC spheres were less dark,and the IPFPSCs were less stained compared with the coculture group. Alcian blue staining indicated that glycosaminoglycan content was higher in the coculture group than in single culture groups. Immunofluorescent staining showed that the intensity of chondrogenic markers( collagen 2,aggrecan,and SOX9)was stronger,while the intensity of collagen 1 and collagen 10 was weaker in the coculture group as compared with single culture groups. Conclusion: The indirect coculture of IPFPSCs with OACs can contribute to the phenotype recovery of OACs and induce the chondrogenic differentiation of IPFPSCs.

[Research on Diagnosis Algorithm of Parkinson's Disease Based on Speech Sample Multi-edit and Random Forest].

Parkinson's disease(PD)diagnosis based on speech data has been proved to be an effective way in recent years.There are still some problems on preprocessing samples,ensemble learning,and so on.The problems can further cause misleading of classifiers,unsatisfactory classification accuracy and stability.This paper proposed a new diagnosis algorithm of PD by combining multi-edit sample selection method and random forest.At the end of it,this paper presents a group of experiments carried out with the newest public datasets.Experimental results showed that this proposed algorithm realized the classification of the samples and the subjects of PD.Furthermore,it achieved average classification accuracy of 100% and obtained improvement of up to 29.44% compared to those provided by the subjects.This paper proposes a new speech diagnosis algorithm for PD based on instance selection;and the method algorithm has a higher and more stable classification accuracy,compared with the other algorithms.

[Study on single-walled carbon nanotube thin film photoelectric device].

The single-walled carbon nanotube film photoelectric device was invented, and it can generate net photocurrent under bias voltage when it is illuminated by the laser. The influences of bias voltage, laser power and illuminating position on the net photocurrent were investigated. The experimental results showed that when the center of the film was illuminated, the photocurrent increased with the applied bias, but tended to saturate as the laser power increased. As the voltage and the laser power reached 0. 2 V and 22. 7 mW respectively, the photocurrent reached 0. 24 µA. When the voltage was removed, the photocurrent varied with the laser illuminating position on the film and its value was distributed symmetrically about the center of the device. The photocurrent reached maximum and almost zero respectively when the laser illuminated on two ends and the center of the film. Analysis proposes that the net photocurrent can be generated due to internal photoelectric effect when the device is under voltage and the laser illuminates on the center of the film. It can be also generated due to photo-thermoelectric effect when the device is under no voltage and the laser illuminates on the film, and the relation between the net photocurrent and the illuminating position was derived according to the nature of thermoelectric power of single-walled carbon nanotubes with the established temperature model, which coincides with experimental result. Two effects are the reasons for the generation and variety of the net photocurrent and they superimpose to form the result of the net photocurrent when the device is under general conditions of voltage and laser illuminating position. The device has potential applications in the areas of photovoltaic device and optical sensor for its characteristic.

Study on modification of single-walled carbon nanotubes on the surface of monocrystalline silicon solar cells.

Modification of single-walled carbon nanotubes (SWNTs) on the surface of monocrystalline silicon solar cells was investigated. The modification was realized by dropping a well-distributed mixture of SWNTs and ethanol with different dosages on the surface of monocrystalline silicon solar cells in the same effective area. The experimental results showed that the increasing rates of conversion efficiency, short-circuit current, and fill factor were 4.37%, 2.18%, and 2.11%, respectively; the open circuit voltage and series resistance decreased by 0.11% and 9.37% compared with the bare solar cell without an antireflection (AR) layer, when the modification reached the best state by dropping a 0.5 mL mixture solution with a concentration of 0.08 g/L. With the energy-band diagrams of the heterojunction and p-n junction, the principles of the modification of SWNTs on monocrystalline silicon solar cells and the reasons for the change of electrical parameters were analyzed theoretically. Through experiments and theoretical analyses, the modification of SWNTs on solar cells is a potential and effective way to improve the performance of solar cells.