A weighted non-negative matrix factorization approach to predict potential associations between drug and disease.

BACKGROUND: Associations of drugs with diseases provide important information for expediting drug development. Due to the number of known drug-disease associations is still insufficient, and considering that inferring associations between them through traditional in vitro experiments is time-consuming and costly. Therefore, more accurate and reliable computational methods urgent need to be developed to predict potential associations of drugs with diseases. METHODS: In this study, we present the model called weighted graph regularized collaborative non-negative matrix factorization for drug-disease association prediction (WNMFDDA). More specifically, we first calculated the drug similarity and disease similarity based on the chemical structures of drugs and medical description information of diseases, respectively. Then, to extend the model to work for new drugs and diseases, weighted [Formula: see text] nearest neighbor was used as a preprocessing step to reconstruct the interaction score profiles of drugs with diseases. Finally, a graph regularized non-negative matrix factorization model was used to identify potential associations between drug and disease. RESULTS: During the cross-validation process, WNMFDDA achieved the AUC values of 0.939 and 0.952 on Fdataset and Cdataset under ten-fold cross validation, respectively, which outperforms other competing prediction methods. Moreover, case studies for several drugs and diseases were carried out to further verify the predictive performance of WNMFDDA. As a result, 13(Doxorubicin), 13(Amiodarone), 12(Obesity) and 12(Asthma) of the top 15 corresponding candidate diseases or drugs were confirmed by existing databases. CONCLUSIONS: The experimental results adequately demonstrated that WNMFDDA is a very effective method for drug-disease association prediction. We believe that WNMFDDA is helpful for relevant biomedical researchers in follow-up studies.

A subthermionic tunnel field-effect transistor with an atomically thin channel.

The fast growth of information technology has been sustained by continuous scaling down of the silicon-based metal-oxide field-effect transistor. However, such technology faces two major challenges to further scaling. First, the device electrostatics (the ability of the transistor's gate electrode to control its channel potential) are degraded when the channel length is decreased, using conventional bulk materials such as silicon as the channel. Recently, two-dimensional semiconducting materials have emerged as promising candidates to replace silicon, as they can maintain excellent device electrostatics even at much reduced channel lengths. The second, more severe, challenge is that the supply voltage can no longer be scaled down by the same factor as the transistor dimensions because of the fundamental thermionic limitation of the steepness of turn-on characteristics, or subthreshold swing. To enable scaling to continue without a power penalty, a different transistor mechanism is required to obtain subthermionic subthreshold swing, such as band-to-band tunnelling. Here we demonstrate band-to-band tunnel field-effect transistors (tunnel-FETs), based on a two-dimensional semiconductor, that exhibit steep turn-on; subthreshold swing is a minimum of 3.9 millivolts per decade and an average of 31.1 millivolts per decade for four decades of drain current at room temperature. By using highly doped germanium as the source and atomically thin molybdenum disulfide as the channel, a vertical heterostructure is built with excellent electrostatics, a strain-free heterointerface, a low tunnelling barrier, and a large tunnelling area. Our atomically thin and layered semiconducting-channel tunnel-FET (ATLAS-TFET) is the only planar architecture tunnel-FET to achieve subthermionic subthreshold swing over four decades of drain current, as recommended in ref. 17, and is also the only tunnel-FET (in any architecture) to achieve this at a low power-supply voltage of 0.1 volts. Our device is at present the thinnest-channel subthermionic transistor, and has the potential to open up new avenues for ultra-dense and low-power integrated circuits, as well as for ultra-sensitive biosensors and gas sensors.

Spectral Reconstruction Using an Iteratively Reweighted Regulated Model from Two Illumination Camera Responses.

An improved spectral reflectance estimation method was developed to transform captured RGB images to spectral reflectance. The novelty of our method is an iteratively reweighted regulated model that combines polynomial expansion signals, which was developed for spectral reflectance estimation, and a cross-polarized imaging system, which is used to eliminate glare and specular highlights. Two RGB images are captured under two illumination conditions. The method was tested using ColorChecker charts. The results demonstrate that the proposed method could make a significant improvement of the accuracy in both spectral and colorimetric: it can achieve 23.8% improved accuracy in mean CIEDE2000 color difference, while it achieves 24.6% improved accuracy in RMS error compared with classic regularized least squares (RLS) method. The proposed method is sufficiently accurate in predicting the spectral properties and their performance within an acceptable range, i.e., typical customer tolerance of less than 3 DE units in the graphic arts industry.

Urine metabolomics study of Bushen Huoxue Prescription on diabetic retinopathy rats by UPLC-Q-exactive Orbitrap-MS.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes and remains one of the leading causes of blindness worldwide. Previous studies have shown that Bushen Huoxue Prescription (BP) possesses an effect on preventing and treating DR, but the mechanisms of action are not entirely clear. In order to clarify the mechanisms, the pharmacodynamical assessments of BP were investigated. Combining the pharmacodynamical studies, it was found that BP could inhibit high expression of VEGF and HIF-1α, indicating significant therapeutic effects on DR. In order to further investigate the mechanism of BP in treating DR, a urine metabolomics method based on ultrahigh-performance liquid chromatography coupled with Q-exactive quadrupole-electrostatic field Orbitrap mass spectrometry was established to observe the metabolic variations in DR rats and investigate the therapeutic effect of BP on DR. As a result, nine potential biomarkers associated with DR were found. The metabolic pathways related to these compounds were explored, and the results showed that these biomarkers were mainly associated with gut microbial metabolism, lipid metabolism and tryptophan metabolism. The results for the pharmacodynamics and metabolomics provided a theoretical basis for clarifying the mechanism of BP in the treatment of DR.

Heterologous Expression of CLIBASIA_03915/CLIBASIA_04250 by Tobacco Mosaic Virus Resulted in Phloem Necrosis in the Senescent Leaves of Nicotiana benthamiana.

Huanglongbing (HLB), also known as citrus greening, is the most notorious citrus disease worldwide. Candidatus Liberibacter asiaticus (CaLas) is a phloem-restricted bacterium associated with HLB. Because there is no mutant library available, the pathogenesis of CaLas is obscure. In this study, we employed tobacco mosaic virus (TMV) to express two mature secretion proteins CLIBASIA_03915 (m03915) and CLIBASIA_04250 (m04250) in Nicotiana benthamiana (N. benthamiana). Phloem necrosis was observed in the senescent leaves of N. benthamiana that expressed the two low molecular weight proteins, while no phloem necrosis was observed in the plants that expressed the control, green fluorescent protein (GFP). Additionally, no phloem necrosis was observed in the senescent leaves of N. benthamiana that expressed the null mutation of m03915 and frameshifting m04250. The subcellular localizations of m03915 and m04250 were determined by fusion with GFP using confocal microscopy. The subcellular localization of m03915 was found to be as free GFP without a nuclear localization sequence (NLS). However, m04250 did have an NLS. Yeast two-hybrid (Y2H) was carried out to probe the citrus proteins interacting with m03915 and m04250. Six citrus proteins were found to interact with m03915. The identified proteins were involved in the metabolism of compounds, transcription, response to abiotic stress, ubiquitin-mediated protein degradation, etc. The prey of m04250 was involved in the processing of specific pre-mRNAs. Identification of new virulence factors of CaLas will give insight into the pathogenesis of CaLas, and therefore, it will eventually help develop the HLB-resistant citrus.

Intercalation Doped Multilayer-Graphene-Nanoribbons for Next-Generation Interconnects.

Copper-based interconnects employed in a wide range of integrated circuit (IC) products are fast approaching a dead-end due to their increasing resistivity and diminishing current carrying capacity with scaling, which severely degrades both performance and reliability. Here we demonstrate chemical vapor deposition-synthesized and intercalation-doped multilayer-graphene-nanoribbons (ML-GNRs) with better performance (more than 20% improvement in estimated delay per unit length), 25%/72% energy efficiency improvement at local/global level, and superior reliability w.r.t. Cu for the first time, for dimensions (down to 20 nm width and thickness of 12 nm) suitable for IC interconnects. This is achieved through a combination of GNR interconnect design optimization, high-quality ML-GNR synthesis with precisely controlled number of layers, and effective FeCl3 intercalation doping. We also demonstrate that our intercalation doping is stable at room temperature and that the doped ML-GNRs exhibit a unique width-dependent doping effect due to increasingly efficient FeCl3 diffusion in scaled ML-GNRs, thereby indicating that our doped ML-GNRs will outperform Cu even for sub-20 nm widths. Finally, reliability assessment conducted under accelerated stress conditions (temperature and current density) established that highly scaled intercalated ML-GNRs can carry over 2 × 108 A/cm2 of current densities, whereas Cu interconnects suffer from immediate breakdown under the same stress conditions and thereby addresses the key criterion of current carrying capacity necessary for an alternative interconnect material. Our comprehensive demonstration of highly reliable intercalation-doped ML-GNRs paves the way for graphene as the next-generation interconnect material for a variety of semiconductor technologies and applications.

Functionalization of transition metal dichalcogenides with metallic nanoparticles: implications for doping and gas-sensing.

Transition metal dichalcogenides (TMDs), belonging to the class of two-dimensional (2D) layered materials, have instigated a lot of interest in diverse application fields due to their unique electrical, mechanical, magnetic, and optical properties. Tuning the electrical properties of TMDs through charge transfer or doping is necessary for various optoelectronic applications. This paper presents the experimental investigation of the doping effect on TMDs, mainly focusing on molybdenum disulfide (MoS2), by metallic nanoparticles (NPs), exploring noble metals such as silver (Ag), palladium (Pd), and platinum (Pt) as well as the low workfunction metals such as scandium (Sc) and yttrium (Y) for the first time. The dependence of the doping behavior of MoS2 on the metal workfunction is demonstrated and it is shown that Pt nanoparticles can lead to as large as 137 V shift in threshold voltage of a back-gated monolayered MoS2 FET. Variation of the MoS2 FET transfer curves with the increase in the dose of NPs as well as the effect of the number of MoS2 layers on the doping characteristics are also discussed for the first time. Moreover, the doping effect on WSe2 is studied with the first demonstration of p-type doping using Pt NPs. Apart from doping, the use of metallic NP functionalized TMDs for gas sensing application is also demonstrated.

[Effect of Bushen Huoxue Compound on Retinal Müller Cells in High Glucose or AGEs Conditions].

OBJECTIVE: To explore the effect of Bushen Huoxue Compound (BHC) on lactate dehydrogenase (LDH) leakage, expressions of vascular endothelial growth factor (VEGF) and VEGF mRNA in retinal Muller cells under high glucose condition or advanced glycosylation end products (AGEs) condition by using serum pharmacological method. METHODS: The retinal Müller cells of 5-7 days post-natal Sprague Dawley (SD) rats were cultured with modified enzyme-digestion method. Purified retinal Muller cells were cultured in normal conditions, high glucose condition (50 mmol/L) or AGEs (50 mg/L and 100 mg/L) conditions, and BHC-containing serum was added to culture medium. The LDH leakage and VEGF expressions were measured by enzyme-linked immunosorbent assay (ELISA). In addition, the relative expression of VEGF mRNA was tested by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Compared with the normal control group, expressions of VEGF and VEGF mRNA were significantly increased in the high glucose group, the low dose AGEs group and the high dose AGEs group (all P < 0.01). The LDH leakage was obviously increased in the high dose AGEs group, when compared with the normal control group and the high glucose group (P < 0.01). The LDH leakage, expressions of VEGF and VEGF mRNA were obviously decreased by BHC-containing serum both in high glucose and AGEs conditions (P < 0.05, P < 0.01). BHC-containing serum had no significant effect on the LDH leakage and expressions of VEGF and VEGF mRNA in normal conditions (P > 0.05). CONCLUSIONS: AGEs intervention could obviously lower the stability of Müller cell membrane. Up-regulated expressions of VEGF and VEGF mRNA in cultured Müller cells could be induced by AGEs or high glucose. BHC-containing serum could stabilize the stability of Müller cell membrane, inhibit the transcription of VEGF mRNA and decrease the protein expression of VEGF, which might be one of important mechanisms for preventing and treating diabetic retinopathy.

Treatment of diabetic retinopathy with herbs for tonifying kidney and activating blood circulation: A review of pharmacological studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes. Chinese medicine believes that kidney deficiency and blood stasis are significant pathogenesis of DR. A characteristic therapeutic approach for this pathogenesis is the kidney-tonifying and blood-activating method. By literature retrieval from several databases, we methodically summarized the commonly used kidney-tonifying and blood-activating herbs for treating DR, including Lycii Fructus, Rehmanniane Radix Praeparata, and Corni Fructus with the function of nourishing kidney; Salvia Miltiorrhizae Radix et Rhizoma with the function of enhancing blood circulation; Rehmanniae Radix with the function of nourishing kidney yin; and Astragali Radix with the function of tonifying qi. It has been demonstrated that these Chinese herbs described above, by tonifying the kidney and activating blood circulation, significantly improve the course of DR. AIM OF THE STUDY: Through literature research, to gain a thorough comprehension of the pathogenesis of DR. Simultaneously, through the traditional application analysis, modern pharmacology research and network pharmacology analysis of kidney-tonifying and blood-activating herbs, to review the effectiveness and advantages of kidney-tonifying and blood-activating herbs in treating DR comprehensively. MATERIALS AND METHODS: PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang Data were used to filter the most popular herbs for tonifying kidney and activating blood in the treatment of DR. The search terms were "diabetic retinopathy" and "tonifying kidney and activating blood". Mostly from 2000 to 2023. Network pharmacology was applied to examine the key active components and forecast the mechanisms of kidney-tonifying and blood-activating herbs in the treatment of DR. RESULTS: Kidney deficiency and blood stasis are the pathogenesis of DR, and the pathogenesis is linked to oxidative stress, inflammation, hypoxia, and hyperglycemia. Scientific data and network pharmacology analysis have demonstrated the benefit of tonifying kidney and activating blood herbs in treating DR through several channels, multiple components, and multiple targets. CONCLUSIONS: This review first presents useful information for subsequent research into the material foundation and pharmacodynamics of herbs for tonifying kidney and activating blood, and offers fresh insights into the treatment of DR.

Exploring the mechanism of Bushen Huoxue prescription in the treatment of early diabetic retinal edema from the perspective of inner blood-retinal barrier injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus, diabetes belongs to the category of "emaciation-thirst disease" in traditional Chinese medicine (TCM). Bushen Huoxue Prescription (BHP) is composed of traditional Chinese materia medica, which has therapeutic effects on DR and early diabetic retinal edema (EDRE). However, the therapeutic mechanism is unclear. AIM OF THE STUDY: Exploring the mechanism of BHP against EDRE. METHODS: Feeding Sprague Dawley (SD) rats a high-fat, high-sugar diet as well as providing intraperitoneal injections of streptozotocin (STZ) to promote inner blood-retinal barrier (iBRB) damage that can trigger EDRE, evaluating the therapeutic effect of BHP by the level of expressiveness of TJ proteins (ZO-1,Occludin) of the iBRB and the leakage of rhodamine B isothiocyanate (RITC) in the retina. The combination of network pharmacology and metabolomics was employed to study the mechanism of BHP in preventing of EDRE, then four proteins which were closely to the damage of iBRB were chosen for the validation by employing Western Blot (WB). RESULTS: Research of network pharmacology had shown that BHP had efficacy against EDRE by regulating targets such as AKT1, ALB, TNF, PPARG, etc, its potential pathways mainly involving signaling pathways such as HIF-1. In untargeted metabolomics analysis of serum, 15 differential metabolites were identified, with the metabolic pathways focusing on ketone body metabolism and synthesis, sphingolipid metabolism and phenylalanine metabolism. The conclusions of metabolomics and network pharmacology revealed that BHP can treat EDRE by alleviating hypoxia and oxidative stress and exerting protection of the iBRB. Finally, BHP's protection behavior of the iBRB was validated by WB experiments. CONCLUSION: Through integrating pharmacodynamics, network pharmacology and metabolomics, BHP was discovered to have a crucial function in EDRE therapy by preserving the integrity of iBRB. This comprehensive strategy also provided a reasonable way to reveal the multi-components, multi-targets, multi-pathways mechanism of TCM.

Choroidal vascularity index in different types of central serous chorioretinopathy: A meta-analysis.

PURPOSE: To evaluate the choroidal vascularity index (CVI) in different types of central serous chorioretinopathy (CSC), healthy control eyes, and fellow eyes. METHODS: Relevant studies published up to January 2023 were identified by searching multiple databases, including PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI). Studies investigating the difference in CVI between CSC and control eyes were included. Data from these studies were analyzed using Stata (version 17) software. Weighted mean difference (WMD) and 95% confidence interval (95%CI) were calculated for the CVI in CSC eyes, control eyes, and fellow eyes. RESULTS: The meta-analysis included 15 studies, with 213 acute CSC eyes, 153 chronic CSC eyes, 92 uncategorized CSC eyes, 40 resolved CSC eyes, 409 eyes of normal healthy controls, and 318 fellow eyes. The result revealed that CVI was higher in acute CSC eyes (WMD = 5.40, 95%CI = 2.36-8.44, P = 0.001) compared to control eyes. Also, CVI in chronic CSC eyes was higher than in control eyes (WMD = 1.26, 95%CI = 0.03-2.49, p = 0.046). The fellow eyes of acute CSC had a higher CVI when compared to control eyes (WMD = 2.53, 95%CI = 0.78-4.28, p = 0.005). There was no significant difference in CVI between acute and chronic CSC eyes (WMD = 0.75, 95%CI = -0.31-1.82, P = 0.167). In the sub-analysis based on the area selected for CVI calculation, the WMDs in the whole image subgroups were lower than the main analysis for the comparisons of fellow eyes of acute CSC and control eyes, acute CSC eyes and control eyes, and acute CSC eyes and fellow eyes. In the macular area subgroups, the WMDs were higher than in the whole image subgroups, suggesting a potential regional variation of CVI in CSC eyes. CONCLUSIONS: The results demonstrated that CVI is increased in CSC eyes and fellow eyes of acute CSC. There is no significant difference in CVI between acute and chronic CSC eyes. The area selected for CVI calculation can influence the outcome, which requires further clinical research to clarify.

Globally Adaptive Neural Network Tracking for Uncertain Output-Feedback Systems.

This article investigates the problem of global neural network (NN) tracking control for uncertain nonlinear systems in output feedback form under disturbances with unknown bounds. Compared with the existing NN control method, the differences of the proposed scheme are as follows. The designed actual controller consists of an NN controller working in the approximate domain and a robust controller working outside the approximate domain, in addition, a new smooth switching function is designed to achieve the smooth switching between the two controllers, in order to ensure the globally uniformly ultimately bounded of all closed-loop signals. The Lyapunov analysis method is used to strictly prove the global stability under the combined action of unmeasured states and system uncertainties, and the output tracking error is guaranteed to converge to an arbitrarily small neighborhood through a reasonable selection of design parameters. A numerical example and a practical example were put forward to verify the effectiveness of the control strategy.

Integrated serum pharmacochemistry and serum pharmacology to investigate the active components and mechanism of Bushen Huoxue Prescription in the treatment of diabetic retinopathy.

This study aimed to investigate the active components of Bushen Huoxue Prescriptions (BHP), and further clarify the mechanism by the integration of serum pharmacochemistry and serum pharmacology based on spectrum-effect relationship in vivo. In this paper, the components absorbed into serum were analyzed by ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap-high resolution mass spectrometry (UPLC-Q-Exactive Orbitrap-HRMS). And Müller cells were chosen as target cells to further investigate the mechanism. After cell purification, the well-grown cells were identified by Hematoxylin-eosin staining (HE) staining and immunofluorescence assay, such as glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). The logarithmic phase cells were divided into normal group, model group and 12 BHP groups. The hyperglycemic and hypoxic model was induced by 50 mmol/L glucose and 1 mmol/L sodium disulfite. Enzyme-linked immunesorbnent assay (ELISA) was used to detect the expressions of five factors closely related to DR, named vascular endothelial growth factor (VEGF), hypoxia-inducible factor1-alpha (HIF-1α), protein kinase C-ß (PKC-ß), angiopoietin-2 (ANG-2) and transforming growth factor-ß (TGF-ß). Finally, the spectrum-effect relationship was investigated to screen the active components of BHP by partial least squares regression (PLSR). The results showed that 83 metabolic components, containing 30 prototypes and 53 metabolites were found in BHP serum. 12 characteristic common peaks were chosen to establish spectrum-effect relationship. Significantly, all the 12 BHP serum exhibited stronger inhibition on the expression of VEGF, PKC-ß, and ANG-2, and the expression of VEGF, PKC-ß, ANG-2 was chosen to establish the spectrum-effect relationship in vivo. The results of PLSR revealed that the content of methylation and sulfuration of caffeic acid, dehydroxylation and sulfation of Danshensu, daidzein, O-demethylangolanolin, cryptotanshinone, tanshinone IIA and protopanaxatriol were inversely correlated with VEGF expression of Müller cells; the areas of dihydrocaffeic acid, methylation and sulfuration of caffeic acid, dehydroxylation and sulfation of Danshensu, daidzein, cryptotanshinone, tanshinone IIA were negative correlation with the expression of PKC-ß; while the coefficient of hydroxytyrosol sulfation, R-equol, O-demethylangolanolin, dihydrotanshinone IIA, hydrated cryptotanshinone, protopanaxatriol showed negative correlation with the expression of ANG-2. The above results indicated that cryptotanshinone, tanshinone IIA, daidzein and protopanaxatriol need be focused in our future research. In addition, this research idea provides feasible ways to investigate and determine pharmacodyamic material basis and screen the Q-markers of TCM and its formulas.

Case report: A case of Acute Macular Neuroretinopathy secondary to Influenza A virus during Long COVID.

Ocular abnormalities have been reported in association with viral infections, including Long COVID, a debilitating illness caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This report presents a case of a female patient diagnosed with Acute Macular Neuroretinopathy (AMN) following an Influenza A virus infection during Long COVID who experienced severe inflammation symptoms and ocular complications. We hypothesize that the rare occurrence of AMN in this patient could be associated with the immune storm secondary to the viral infection during Long COVID.

Bibliometric and visual analysis of diabetes mellitus and pyroptosis from 2011 to 2022.

OBJECTIVE: To visualize and analyze the published literature on diabetes mellitus and pyroptosis based on a bibliometric approach, so as to provide a comprehensive picture of the hot research directions and dynamic progress in this field. METHODS: This study was based on the web of science core collection database to conduct a comprehensive search of the published literature in the field of diabetes mellitus and Pyroptosis from January 1985 to August 2022, including the published research literature in this field, as well as a visual analysis of the number of citations, year of publication, journal, author, research institution, country, and research topic. RESULTS: A total of 139 literature on research related to diabetes mellitus and cellular scorch from 2011 to 2022 were retrieved, with a total of 3009 citations and a maximum of 255 citations for a single article, which had a first author Schmid-Burgk, JL The first author of this article is from Germany; among 20 publishing countries, China leads with 100 articles; among 222 publishing institutions, Harbin Medical University leads with 18 articles and 184 citations; among 980 authors, Chen, X from China tops the list of high-impact authors with 5 articles and 29 citations. Among the 98 journals, "CELL DEATH DISEASE" ranked first in both volume and high-impact journals with 4 articles and 29 citations. Among 349 keywords, "pyroptosis" ranked first with a cumulative frequency of 65 times. The cluster analysis was divided into three categories, chronic complications of diabetes mellitus and pyroptosis (67 articles), diabetes mellitus and pyroptosis (60 articles), and diabetes mellitus combined with other diseases and pyroptosis (12 articles), and the number of articles related to diabetes mellitus and its chronic complications increased rapidly from 2019, among which, diabetic cardiomyopathy (27 articles) had the highest number of articles. CONCLUSIONS: Based on a comprehensive analysis of published literature in the field of diabetes mellitus and pyroptosis from 2011 to 2022, this study achieved a visual analysis of studies with significant and outstanding contributions to the field, thus framing a picture showing the development and changes in the field. At the same time, this study provides research information and direction for clinicians and investigators to conduct diabetes mellitus and pyroptosis-related research in the future.

Combining non-negative matrix factorization with graph Laplacian regularization for predicting drug-miRNA associations based on multi-source information fusion.

Increasing evidences suggest that miRNAs play a key role in the occurrence and progression of many complex human diseases. Therefore, targeting dysregulated miRNAs with small molecule drugs in the clinical has become a new treatment. Nevertheless, it is high cost and time-consuming for identifying miRNAs-targeted with drugs by biological experiments. Thus, more reliable computational method for identification associations of drugs with miRNAs urgently need to be developed. In this study, we proposed an efficient method, called GNMFDMA, to predict potential associations of drug with miRNA by combining graph Laplacian regularization with non-negative matrix factorization. We first calculated the overall similarity matrices of drugs and miRNAs according to the collected different biological information. Subsequently, the new drug-miRNA association adjacency matrix was reformulated based on the K nearest neighbor profiles so as to put right the false negative associations. Finally, graph Laplacian regularization collaborative non-negative matrix factorization was used to calculate the association scores of drugs with miRNAs. In the cross validation, GNMFDMA obtains AUC of 0.9193, which outperformed the existing methods. In addition, case studies on three common drugs (i.e., 5-Aza-CdR, 5-FU and Gemcitabine), 30, 31 and 34 of the top-50 associations inferred by GNMFDMA were verified. These results reveal that GNMFDMA is a reliable and efficient computational approach for identifying the potential drug-miRNA associations.

Encapsulation of Silicon Nano Powders via Electrospinning as Lithium Ion Battery Anode Materials.

Silicon-containing polyester from tetramethoxysilane, ethylene glycol, and o-Phthalic anhydride were used as encapsulating materials for silicon nano powders (SiNP) via electrospinning, with Polyacrylonitrile (PAN) as spinning additives. In the correct quantities, SiNP could be well encapsulated in nano fibers (200-400 nm) using scanning electron microscopy (SEM). The encapsulating materials were then carbonized to a Si-O-C material at 755 °C (Si@C-SiNF-5 and Si@C-SiNF-10, with different SiNP content). Fiber structure and SiNP crystalline structure were reserved even after high-temperature treatment, as SEM and X-ray diffraction (XRD) verified. When used as lithium ion battery (LIB) anode materials, the cycling stability of SiNPs increased after encapsulation. The capacity of SiNPs decreased to ~10 mAh/g within 30 cycles, while those from Si@C-SiNF-5 and Si@C-SiNF-10 remained over 500 mAh/g at the 30th cycle. We also found that adequate SiNP content is necessary for good encapsulation and better cycling stability. In the anode from Si@C-SiNF-10 in which SiNPs were not well encapsulated, fibers were broken and pulverized as SEM confirmed; thus, its cycling stability is poorer than that from Si@C-SiNF-5.

Exploring the quality markers and mechanism of Bushen Huoxue Prescription in prevention and treatment of diabetic retinopathy based on Chinmedomics strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicines have complex chemical composition; therefore, revealing the effective substances of Chinese herbal medicine becomes a prerequisite for scientific elucidation of the mechanism of action of Bushen Huoxue Prescription (BHP) against diabetic retinopathy (DR) and the development of new drugs. AIM OF THE STUDY: The Chinmedomics technique was used to evaluate the pharmacodynamic ingredients and mechanism of action of BHP against DR rats. MATERIALS AND METHODS: The overall physiological condition of the rats, including body weight, blood glucose, inflammatory factor levels, histological staining, and urine metabolic profile were examined to evaluate the model and its effects. The chemical composition of BHP in vivo and ex vivo was fully analyzed utilizing UPLC-Q-Exactive Orbitrap MS in conjunction with TCM serum pharmacochemistry. Finally, correlation analysis between biomarkers, and serum migration components was used to identify Quality markers (Q-markers) that were significantly associated with effectiveness. RESULTS: The UPLC-Q-Exactive Orbitrap MS platform was used to identify a total of 29 chemicals in serum, 17 of which were highly linked with effectiveness and can be potentially employed as pharmacodynamic substances for BHP against DR. In addition, 14 biomarkers related to galactose metabolism, starch and sucrose metabolism, pantothenate and CoA biosynthesis, glycine, serine, and threonine metabolism were identified. These pathways reveal that DR may be inextricably linked to levels of oxidative stress and inflammation in the organism. Finally, five active ingredients were identified as potential Q-markers of BHP against DR, namely ajugol, protocatechuic acid, tanshinone IIA, panaxatriol and puerarin. CONCLUSION: This study successfully clarified the efficacy and Q-markers of BHP through the Chinmedomics strategy, which is of great significance in determining the quality standards of BHP.

Combining K Nearest Neighbor With Nonnegative Matrix Factorization for Predicting Circrna-Disease Associations.

Accumulating evidences show that circular RNAs (circRNAs) play an important role in regulating gene expression, and involve in many complex human diseases. Identifying associations of circRNA with disease helps to understand the pathogenesis, treatment and diagnosis of complex diseases. Since inferring circRNA-disease associations by biological experiments is costly and time-consuming, there is an urgently need to develop a computational model to identify the association between them. In this paper, we proposed a novel method named KNN-NMF, which combines K nearest neighbors with nonnegative matrix factorization to infer associations between circRNA and disease (KNN-NMF). Frist, we compute the Gaussian Interaction Profile (GIP) kernel similarity of circRNA and disease, the semantic similarity of disease, respectively. Then, the circRNA-disease new interaction profiles are established using weight K nearest neighbors to reduce the false negative association impact on prediction performance. Finally, Nonnegative Matrix Factorization is implemented to predict associations of circRNA with disease. The experiment results indicate that the prediction performance of KNN-NMF outperforms the competing methods under five-fold cross-validation. Moreover, case studies of two common diseases further show that KNN-NMF can identify potential circRNA-disease associations effectively.

[Effects of electromagnetic pulse exposure on the permeability of inner blood-retinal barrier model in vitro].

OBJECTIVE: To establish the inner blood-retinal barrier (BRB) model in vitro by co-culturing RF/6A cells and C6 cells and to investigate the effects of EMP (200 kV/m, 200 pulses) exposure on the permeability of the inner BRB model in vitro. METHODS: RF/6A cells and C6 cells were co-cultured on transwell, and the characteristic of the inner BRB model was assessed by detecting transendothelial electrical resistance (TEER) and the permeability of horseradish peroxidase (HRP). The co-cultured model was exposed or sham exposed to the EMP (200 kV/m 200 pulses) for 0.5, 3, 6, 12, 24 h in vitro, then TEER and the permeability of HRP were measured for studying the effects of EMP on the permeability of inner BRB model in vitro. RESULTS: TEER value (145 Ωcm(2)) of the co-culturing inner BRB model significantly increased, as compared to that of RF/6A cells alone model (P < 0.05) on the 6th day after inoculation. There was significant difference of permeability of HRP between the co-culturing inner BRB model and RF/6A cells alone model (P < 0.05). The ability of inhibiting large molecular materials in the co-culturing inner BRB model enhanced. The TEER value decreased and the permeability of HRP increased as compared to the sham group at 0.5, 3, 6 h after the exposure. CONCLUSION: The inner BRB model by co-culturing RF/6A cells and C6 cells in vitro is efficient and suitable to study the alterations of the restricted permeability function of the inner BRB. EMP (200 kV/m for 200 pulses) could induce the enhanced permeability of the inner BRB model in vitro.