Preparation and structural characterization of chitosan­sodium alginate nanocapsules and their effects on the stability and antioxidant activity of blueberry anthocyanins.

This study prepared a nanocapsule (NPs) from chitosan (CS) and sodium alginate (ALG) and used them to enhance the stability of blueberry anthocyanins (BA) The optimal NPs was obtained at pH value of 3.25, BA concentration of 0.5 mg/mL and mixing ratio of CS to ALG of 1:1 (W/W). Further, the formation of composite NPs was confirmed by a series of characterization methods. The CS-BA-ALG NPs appeared spherical, smooth, and evenly distributed when observed under an optical microscope and transmission Electron Microscope. The X-ray Diffractometer and Fourier Transform Infrared spectroscopy data proved that electrostatic interaction and hydrogen bonding are dominant forces to form NPs. Thermogravimetric analysis and differential scanning calorimetry results demonstrated that the CS-BA-ALG NPs system significantly improved the thermal stability of anthocyanins. In addition, it was also proved that CS-BA-ALG NPs showed high antioxidant capacity and protection capacity.

Evaluating the Stroke Risk of Patients using Machine Learning: A New Perspective from Sichuan and Chongqing.

Stroke is the leading cause of death and disability among people in China, and it leads to heavy burdens for patients, their families and society. An accurate prediction of the risk of stroke has important implications for early intervention and treatment. In light of recent advances in machine learning, the application of this technique in stroke prediction has achieved plentiful promising results. To detect the relationship between potential factors and the risk of stroke and examine which machine learning method significantly can enhance the prediction accuracy of stroke. We employed six machine learning methods including logistic regression, naive Bayes, decision tree, random forest, K-nearest neighbor and support vector machine, to model and predict the risk of stroke. Participants were 233 patients from Sichuan and Chongqing. Four indicators (accuracy, precision, recall and F1 metric) were examined to evaluate the predictive performance of the different models. The empirical results indicate that random forest yields the best accuracy, recall and F1 in predicting the risk of stroke, with an accuracy of .7548, precision of .7805, recall of .7619 and F1 of .7711. Additionally, the findings show that age, cerebral infarction, PM 8 (an anti-atrial fibrillation drug), and drinking are independent risk factors for stroke. Further studies should adopt a broader assortment of machine learning methods to analyze the risk of stroke, by which better accuracy can be expected. In particular, RF can successfully enhance the forecasting accuracy for stroke.

Gum arabic as a sole wall material for constructing nanoparticle to enhance the stability and bioavailability of curcumin.

In this study, a kind of nanoparticle prepared using gum arabic as a sole wall material for loading curcumin was obtained. The properties and digestive characteristics of the curcumin-loaded nanoparticle were determined. Results showed that the maximum loading amount of the nanoparticle was 0.51 µg/mg with an approximately 500 nm size. The Fourier transform infrared (FTIR) spectrum showed that the complexation was mainly related to the -C[bond, double bond]O, -CH, and -C-O-C- groups. The curcumin-loaded nanoparticle exhibited good stability under highly concentrated salinity stress, and the stability of the curcumin loaded in nanoparticles was significantly higher than that of free curcumin under ultraviolet radiation. The curcumin loaded in nanoparticle was released mainly in the intestinal digestion stage, and the release process was sensitive to the pH changes rather than protease. In conclusion, these nanoparticles can be a potential nanocarrier for enhancing the stability of curcumin which can be applied in the salt-containing food system.

D-α-tocopherol polyethylene glycol 1000 succinate-based microemulsion delivery system: Stability enhancement of physicochemical properties of luteolin.

In the present study, D-α-Tocopherol polyethylene glycol 1000 succinate-based self-microemulsifying drug delivery systems (TPGS-SMEDDS) were introduced to enhance the solubility and stability of luteolin. The ternary phase diagrams were constructed to obtain the maximum area of microemulsion and suitable formulations of TPGS-SMEDDS. The particle size distribution and polydispersity index of selected TPGS-SMEDDS were analyzed to be less than 100 nm and 0.4, respectively. The thermodynamic stability results suggested that the TPGS-SMEDDS was stable during the heat-cool and freeze-thaw cycle. Moreover, the TPGS-SMEDDS exhibited excellent encapsulation capacity (51.21 ± 4.39 to 85.71 ± 2.40%) and loading efficiency (61.46 ± 5.27 to 102.86 ± 2.88 mg/g) to luteolin. In addition, the TPGS-SMEDDS showed an admirable vitro release ability with a ratio of more than 88.40 ± 1.14% for luteolin in 24 h. Therefore, TPGS-based SMEDDS might provide an effective role for the oral administration of luteolin and holds promise as a potential delivery for poorly soluble bioactive compounds.

Ultrasound-assisted free radical modification on the structural and functional properties of ovalbumin-epigallocatechin gallate (EGCG) conjugates.

The influence of ultrasound-assisted free radical modification on the structure and functional properties of ovalbumin-epigallocatechin gallate (OVA-EGCG) conjugates was investigated by experimental measurements and computer simulations. Compared with the traditional free radical condition, the ultrasonic-assisted processing significantly increased the conjugating efficiency of OVA and EGCG and shortened the conjugating from 24 h to 1 h without affecting the equivalent amount of EGCG conjugating. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis and multi-spectroscopy analysis (Fourier transform infrared spectroscopy, intrinsic fluorescence spectroscopy, and UV spectroscopy) indicated that the covalent conjugates could be formed between OVA and EGCG. And modification in the conformation of OVA was induced by EGCG. Furthermore, molecular docking results demonstrated the possession of high-affinity EGCG binding location on OVA, supporting and clarifying the experimental results. In addition, the functional properties of OVA including emulsification (emulsifying activity and emulsion stability) and antioxidant properties (DPPH scavenging capacity and ABTS scavenging capacity) were significantly improved after conjugation with EGCG, especially in ultrasound-assisted conditions. Overall, OVA-EGCG conjugates produced by ultrasound-assisted free radical treatment could be applied as a potential emulsifier and antioxidant, thereby expanding the application of OVA as a dual-functional ingredient.

Effects of blackberry polysaccharide on the quality improvement of boiled chicken breast.

Blackberry polysaccharide was isolated from blackberry powder with 70% ethanol. The crude polysaccharide was composed of 95.44% glucose, 2.01% arabinose, 1.81% galactose and 0.74% glucuronic acid. Chicken breast meat was only marinated with different concentrations of the isolated blackberry polysaccharide (1 g/kg, 3 g/kg) for 24 h at a ratio of material to liquid of 1:3, and boiled at 80℃ for 1 h. The differences in texture, water distribution and volatile flavor components among different groups （adding 0,1,3 g/kg blackberry polysaccharide) were investigated. The results showed that the addition of blackberry polysaccharide could significantly improve the hardness of chicken breast, the transformation of free water to bound water, the overall flavor characteristics of the control group and the addition of different concentrations of blackberry polysaccharide were significantly different, and the concentration of volatile flavor substances in boiled chicken breast was reduced.

Heart rate estimation from color video sequences with high SNR.

We propose an absorption intensity heartbeat modulation-averaged shifted histogram (AIHM-ASH) method for estimating human heart rate (HR) using color videos of lip image sequences. When heartbeat occurs, AIHM is generated. Based on the AIHM, HR signals can be demodulated by computing the instantaneous HR modulation depth that presents the relative red blood cell (RBC) concentration from the green channel image of the RGB color video. In addition, the ASH algorithm further suppresses the background tissue and vein signals, and increases the signal-to-noise ratio (SNR). The experimental results for flow phantoms, chicken embryos, and human lips validated the proposed method's optimal estimation conditions and effectiveness, where the accuracy and root mean square error (RMSE) were 99.23% and 0.8 bpm, respectively. The proposed HR estimation method has significant potential to advance health monitoring and disease prevention via conventional color video cameras installed in public places.

Enhancement of bioavailability and bioactivity of diet-derived flavonoids by application of nanotechnology: a review.

Flavonoids, which are a class of polyphenols widely existing in food and medicine, have enormous pharmacological effects. The functional properties of flavonoids are mainly distributed to their anti-oxidative, anticancer, and anti-inflammatoryeffects, etc. However, flavonoids' low bioavailability limits their clinical application, which is closely related to their intestinal absorption and metabolism. In addition, because of the short residence time of oral bioactive molecules in the stomach, low permeability and low solubility in the gastrointestinal tract, flavonoids are easy to be decomposed by the external environment and gastrointestinal tract after digestion. To tackle these obstacles, technological approaches like microencapsulation have been developed and applied for the formulation of flavonoid-enriched food products. In the light of these scientific advances, the objective of this review is to establish the structural requirements of flavonoids for appreciable anticancer, anti-inflammatory, and antioxidant effects, and elucidate a comprehensive mechanism that can explain their activity. Furthermore, the novelty in application of nanotechnology for the safe delivery of flavonoids in food matrices is discussed. After a literature on the flavonoids and their health attributes, the encapsulation methods and the coating materials are presented.

Hypertension Status Moderated the Relationship between the Hippocampal Subregion of the Left GC-ML-DG and Cognitive Performance in Subjective Cognitive Decline.

Background: To investigate the relationship between hypertension status, hippocampus/hippocampal subregion structural alteration, and cognitive performance in subjective cognitive decline (SCD). Methods: All participants were divided into two groups according to blood pressure status: SCD without hypertension and SCD with hypertension. The cognitive assessments and T1-MPRAGE brain MRI were performed to measure the cognitive function and the volume of the hippocampus and hippocampal subregions. Association and mediating/moderating effects were analyzed between the volume of hippocampus/hippocampal subregions and cognitive scores. Results: Compared to the SCD without hypertension, we found (1) increased reaction time (RT) of the Go/No go test, compatible test, and divided attention visual task and (2) decreased volume of the left whole hippocampal/left subiculum/left CA1/left presubiculum/left parasubiculum/left molecular layer HP/left GC-ML-DG/left HATA in SCD with hypertension. There was a significant negative association between the volume of the left GC-ML-DG and Go/No go test RT in SCD without hypertension. A significant moderating effect of hypertension status on the relationship between the volume of the left GC-ML-DG and Go/No go test RT was found. Conclusion: The results suggested that hypertension status affects inhibitory control function and visual divided attention which may be related to the reduction of hippocampus/hippocampal subregion volume in SCD. Limitations. The study has several limitations. First, this study does not include a healthy control group. In further studies, healthy controls may need to assess the interaction between hypertension status and disease status on cognitive function. Second, we defined the hypertension status using with or without hypertension disease. More detailed parameters of hypertension status need to be further studied. Third, our study was a small number of participants/single-center and cross-sectional study, which may hinder its generalization. A large-sample/multicenter, longitudinal study is helpful to comprehensively understand the relationship between hypertension status and cognitive function in SCD patients.

Effects on Adherence to a Mobile App-Based Self-management Digital Therapeutics Among Patients With Coronary Heart Disease: Pilot Randomized Controlled Trial.

BACKGROUND: The adherence to secondary prevention treatment in patients with coronary heart disease (CHD) is low. Digital therapeutics (DTx) refers to an emerging branch of medicine that delivers medical interventions directly to patients using evidence-based, clinically evaluated, technology-based software algorithms or apps to facilitate disease management, which may be an efficient tool to optimize adherence. OBJECTIVE: This paper aims to investigate the effect of mobile app-based self-management DTx on long-term use of secondary prevention medications in patients with CHD in China. METHODS: This pilot study was a parallel-designed, open-labeled, single-center, randomized controlled trial. Hospitalized patients with CHD admitted to Peking University First Hospital between April 2016 and June 2017 were randomized before discharge on a 1:1 ratio. The intervention group received regular follow-up combined with DTx, which is a self-management mobile app already installed on an Android 5 (Mi Pad 1, Xiaomi Corporation) tablet. Structured data from the hospital informatics system were integrated automatically, and medication, lifestyle intervention plan, follow-up protocol, and patient education materials were also provided according to the diagnosis. Participants could use DTx for self-management at home. The control group was under conventional hospital-based follow-up care. Patients were followed up for 1 year, and the primary end point was the percentage of all guideline-recommended medications at 12 months. The secondary end points included the percentage adhered to standard secondary prevention medications at 6 months, the control rate of lipid profile, and blood pressure at 6 months and 1 year. RESULTS: Among 300 randomized patients with CHD, 290 (96.7%) were included in the final analysis, including 49.3% (143/290) and 50.7% (147/290) of patients from the intervention and control groups, respectively. Baseline characteristics were similar between the 2 groups. There was a statistically significant improvement in the percentage of all guideline-recommended medications at 12 months in the intervention group compared with the control group (relative risk [RR] 1.34, 95% CI 1.12-1.61; P=.001), and there was no interaction with baseline characteristics. The intervention group had a significantly higher proportion of patients achieving blood pressure under control (systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg) and low-density lipoprotein cholesterol <1.8 mmol/L (RR 1.45, 95% CI 1.22-1.72; P<.001 and RR 1.40, 95% CI 1.11-1.75; P=.004, respectively) at 12 months. Furthermore, on logistic regression, the intervention group had a lower risk of withdrawing from guideline-recommended medications (odds ratio 0.46, 95% CI 0.27-0.78; P=.004). CONCLUSIONS: Among patients with CHD, using a mobile app-based self-management DTx in addition to traditional care resulted in a significant improvement in guideline-recommended medication adherence at 12 months. The results of the trial will be applicable to primary care centers, especially in rural areas with less medical resources. TRIAL REGISTRATION: ClinicalTrials.gov NCT03565978; https://clinicaltrials.gov/ct2/show/NCT03565978.

Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.

Ovalbumin (OVA) is a high nutritious protein, but the poor emulsibility limited its application. The present study glycosylated OVA with dextran (Dex) by controlled wetheating (60-90 °C for 3 h). Temperature was an inductive factor for glycosylation degree (DG and browning intensity), and higher temperature could accelerate the reaction. Variations in molecular structure of OVA were analyzed by SDS-PAGE, FTIR, fluorescence spectroscopy and UV spectroscopy, which verified successes in the generation of glycoconjugate with more flexible structure. Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature. Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA. Thus, controlled glycosylation reaction is an available method to improve the emulsifying properties of OVA.

Structural characteristics and emulsifying properties of myofibrillar protein-dextran conjugates induced by ultrasound Maillard reaction.

In this study, we investigated the effect of the ultrasound-assisted Maillard reaction on the structural and emulsifying properties of myofibrillar protein (MP) and dextran (DX) conjugates with different molecular weights (40, 70 and 150 kDa). Compared with classical heating, mild and moderate ultrasound-assisted methods (100-200 W) could accelerate the later stage of the Maillard reaction, which increased the degree of graft (DG) and the content of advanced Maillard reaction products (MPRs). Structural analysis revealed conjugates obtained by Maillard reaction induced the loss of ordered secondary structures (α-helix, ß-sheets) and red-shift of maximum emission wavelength of intrinsic fluorescence spectrum. The conjugate containing 40 kDa DX exhibited higher extent of Maillard reaction compared to those containing 70 kDa and 150 kDa DX under various treating methods. Moreover, the ultrasound-assisted Maillard reaction could effectively improve the emulsifying behaviors. 100 W ultrasound-induced conjugates grafted by 70 kDa DX produced the smallest emulsion size with optimum storage stability. Confocal laser scanning microscopy and analytical centrifugal analyzer further confirmed MP grafted by 70 kDa DX with the assistance of 100 W ultrasound field could produce the smallest and most homogeneous MP-base emulsion with no flocculation. Our study demonstrated that mild ultrasound treatment resulted in well-controlled Maillard reaction, and the related glycoconjugate grafted with 70 kDa DX showed the greatest improvements in emulsifying ability and stability. These findings provided a theoretical foundation for the development of emulsion-based foods with excellent characteristics.

Effect of two-step microwave heating on the gelation properties of golden threadfin bream (Nemipterus virgatus) myosin.

The effects of different microwave heating (MH) methods on gelation properties of golden threadfin bream myosin and related mechanism were investigated in this study. Compared with conventional heating and one-step MH methods, myosin gel developed by 100 W coupled with 300 W MH method (MH100 + MH300) had stronger gel strength (p < 0.05) with more immobilized water (p < 0.05). Raman analysis suggested that this two-step method promoted the suitable unfolding of myosin before aggregation formation, and contributed to stabilizing the ordered secondary structure. Confocal laser scanning microscopy images revealed that 100 W microwave followed by 300 W MH produced a compact networked structure with small cavities and a thick cross-linked gel wall. Furthermore, from a perspective of molecular forces, the improvement of gelation properties by the MH100 + MH300 method were mainly involved in the enhancement of regular hydrophobic interaction and stabilization of weak protein-water hydrogenbonds.

Echinacoside­induced nitric oxide production in endothelial cells: Roles of androgen receptor and the PI3K­Akt pathway.

Echinacoside (ECH) is a natural compound with an endothelium­dependent vasodilatory effect. Nitric oxide (NO) is an important vasorelaxant released from endothelial cells. In order to examine the molecular mechanism of ECH­induced NO production in endothelial cells, the present study investigated the involvement of androgen receptor (AR) and the phosphatidylinositol 3­kinase (PI3K)/protein kinase B (Akt) pathway in the phosphorylation of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVECs). Using the fluorescent probe DAF­FM, the production of NO was found to be significantly increased, and eNOS was phosphorylated at Ser1177 in a concentration­â€‹dependent manner under 0.01­10 µM ECH treatment in HUVECs. In addition, NO production and eNOS phosphorylation induced by ECH were diminished when pretreated with the AR antagonist nilutamide, or when transfected with AR small interfering RNAs. Furthermore, the ECH­induced phosphorylation of the Akt at Ser473 was abrogated by 5 µM wortmannin (a PI3K inhibitor). These data indicated that ECH stimulated NO production via the AR­dependent activation of eNOS in HUVECs, and that the PI3K/Akt pathway may be involved in eNOS phosphorylation induced by ECH.

1H NMR spectroscopy-based metabolic profiling of Ophiocordyceps sinensis and Cordyceps militaris in water-boiled and 50% ethanol-soaked extracts.

Ophiocordyceps sinensis, a well-known Chinese complementary herb, is a rare and valuable therapeutic resource. Cordyceps militaris (C. militaris) is a commonly used substitute for O. sinensis. A metabolomic-based approach for exploring the similarities and differences in the metabolites of O. sinensis and C. militaris in water-boiled and 50% ethanol-soaked extracts is of great significance. To distinguish between the global metabolite profiles of O. sinensis and C. militaris extracts obtained from either the water-boiled or 50% ethanol-soaked methods, we investigated the herb samples using 1HNMR-based metabolic fingerprints combined with multivariate statistical analysis. This study revealed that a total of 52 primary metabolites were identified and quantified from O. sinensis and C. militaris samples. Forty-three (83% of 52) metabolites were detectable in both O. sinensis and C. militaris. According to the variable importance in projection (VIP) value and p-value from the Mann-Whitney test, 7 metabolites (alanine, aspartate, glutamate, mannitol, ornithine, serine, and trehalose) differed between O. sinensis and C. militaris. Arginine, glucose, putrescine, pyroglutamate, betaine, O-phosphocholine, and xylose differed significantly between the water-boiled and 50% ethanol-soaked methods used to prepare the herb extracts. This study demonstrated that water-boiled extraction was a much faster method (30 min. vs 360 days) that resulted in a 30% higher number of extracted metabolites (compared to 50% for the ethanol-soaked method) for both O. sinensis and C. militaris.

Effects of microwave-vacuum pre-treatment with different power levels on the structural and emulsifying properties of lotus seed protein isolates.

The present study investigated the changes in structural and emulsifying properties of lotus seed protein isolates (LSPIs) under different microwave-vacuum (MV) treatments. A decrease of fluorescence peak intensity with blue-shift of the fluorescence emission maximum indicated that MV treatment induced unfolding of LSPIs so that more hydrophobic residues were exposed. Raman spectra showed that the ordered secondary structures (α-helix, ß-sheet) gradually converted into ß-turns and random coils during 50-150 W MV treatment. Particle size distribution and atomic force microscope revealed that the amounts of small subunits increased when the LSPIs were modified by 50-100 W MV treatment. Emulsions prepared by 100-W-MV-LSPIs exhibited the optimal emulsifying ability with the smallest oil droplet sizes. Confocal laser scanning microscopy and analytical centrifugal analyzer further proved 50-100 W MV-treatment enhanced the flocculation and creaming stability. Our findings provide a certain theoretical foundation to apply MV technology for developing desirable LSPIs-stabilized emulsions.

Microbial dynamics and flavor formation during the traditional brewing of Monascus vinegar.

Monascus vinegar is one of the most famous and popular Chinese vinegars. The present study identified 60 volatile compounds, 23 amino acids, and seven organic acids during the traditional brewing of Monascus vinegar. Acetic acid, alanine, alcohols, esters, lactic acid, and valine were the predominant metabolic compounds found during the fermentation process. Komagataeibacter medellinensis, Lactobacillus acetotolerans, Saccharomycopsis fibuligera, Sterigmatomyces halophilus, and Yarrowia lipolytica were the dominant microorganisms during the traditional brewing of Monascus vinegar. Furthermore, based on Spearman's correlation analysis, K. medellinensis showed a positive correlation with acetic acid, acetoin, benzaldehyde, phenethyl acetate, 4-ethylphenol, proline, threonine, and isoleucine. Saccharomyces cerevisiae was positively associated with the production of acetoin, benzeneacetaldehyde, 2,3,5-trimethylpyrazine, proline, threonine, and isoleucine. Bacillus velezensis and Yarrowia lipolytica were positively correlated with esters and alcohols, implying that these microorganisms might make a significant contribution to the flavor of vinegar. These findings demonstrated that some microorganisms may play important roles in improving the aromatic quality of Monascus vinegar.

Perceptions and Acceptance of mHealth in Patients With Cardiovascular Diseases: A Cross-Sectional Study.

BACKGROUND: Mobile health (mHealth)-a method of assisting long-term care in patients with chronic cardiovascular diseases (CVDs)-is gaining popularity in China, mainly owing to the large number of patients and limited clinical resources. Patients of different ages have varying needs for CVD management. However, evidence regarding how age influences Chinese CVD patients' use and perceptions of mHealth is limited. OBJECTIVE: This study aimed to explore age-related differences among Chinese patients with CVD regarding their use and perceptions of mHealth and to determine the factors that influence this population's willingness to use mHealth technologies. METHODS: We conducted a cross-sectional study of patients with chronic CVDs in a tertiary hospital in Beijing using a new questionnaire designed by the investigators. Participants were sourced using nonproportional quota-sampling methods, being recruited consecutively in each sampling category (age 18-49, 50-64, 65-74, and ≥75 years, with at least 25 men and 25 women in each age group). The survey consisted of 5 parts, including sociodemographic profile and medical history; current disease management situation; self-evaluation of disease management; current usage of mobile and internet technology (IT); and willingness to use an mHealth solution to perform disease self-management. Responses were compared among the 4 age groups as well as between patients who were willing to use mHealth solutions and those who were not. Multivariate logistic regression model was used to identify predictors of willingness to use mHealth for self-management. RESULTS: Overall, 231 patients (124 men) completed the questionnaire; of these, 53 were aged 18-49 years, 66 were aged 50-64 years, 54 were aged 65-74 years, and 58 were aged ≥75 years. Patients in the older cohorts visited hospitals more often than did those in the younger cohorts (P<.001), and they also showed lower technology skills regarding the use of mobile or internet devices (P<.001) and searched for health-related information on the internet less often (P<.001). In addition, 68.0% (157/231) of the patients showed interest in using mHealth solution to manage their disease; of these, 40.8% (64/157) were aged 65 years. Patients who were more willing to use mHealth solution to manage their diseases were younger (P<.001), more educated (P<.001), still working (P=.001), possessed higher skill regarding mobile or internet device use (P<.001), and more frequently searched for health information on the internet (P<.001). Finally, multivariate logistic regression showed that IT skill was the single indicator (P=.003) of willingness to use mHealth, not age. CONCLUSIONS: Although age is associated with the use of mobile or internet devices, the sole indicator of mHealth use for self-management was participants' IT skills. Education regarding the use of mobile devices and development of easy-to-use software might improve the acceptance of mHealth solutions among older patient populations.

Profile of Ophiocordyceps sinensis transcriptome and differentially expressed genes in three different mycelia, sclerotium and fruiting body developmental stages.

Ophiocordyceps sinensis, a Chinese complementary and alternative medicine (CAM), is an entomopathogenic, fungus, parasitizing larvae of the moth genus Thitarodes. It has three stages of the life cycle, i.e., the anamorph mycelia prior to infection (Cm_Os), the mycelia sclerotium forming in the caterpillar (Te_Ca), and the fruiting bodies or stromata (Te_St). Characterization of the O. sinensis transcriptome among these stages could provide a better understanding of the underlying biology processes. Transcriptomics of the O. sinensis asexual mycelia and hyphae in deceased caterpillars and perithecial stroma was assessed by using Illumina HiSeq™ 2000 technology. A total of 14,922 unigenes were identified and categorized into 46 sub-categories under three gene ontology categories ("biological process", "cellular component", and "molecular function"). Of these genes, 5520 were differentially expressed among the libraries of these three groups of samples (P < 0.05), and 391 genes occurred in all three groups. Compared to the anamorph stage, there were 3049 differentially expressed genes (DEGs) in the teleomorph stage, but only 1023 DEGs occurred within the teleomorph groups (Te_St vs. Te_Ca). Collectively, this study provides a novel resource to further investigate O. sinensis and their three different development stages.

Suramin interacts with the positively charged region surrounding the 5-fold axis of the EV-A71 capsid and inhibits multiple enterovirus A.

Suramin was previously shown to bind to the EV-A71 capsid through its naphthalenetrisulfonic acid groups, thereby reducing virus-cell binding and inhibiting viral replication. Here, we identify VP1-145 as the critical amino acid that accounts for the differential sensitivity of EVA-71 viruses to suramin. A single Q or G to E substitution at VP1-145 results in an approximately 30-fold shift of IC50 or IC90 values reproducing the inhibition profile observed with field isolates expressing either the 145Q or E mutation. Our data support the conclusion that suramin binds to the positively charged region surrounding the 5-fold axis of the capsid and consequently blocks the virus attachment and entry into host cells. In order to assess the antiviral-spectrum of suramin, we analyzed 18 representative enteroviruses: A (n = 7), B (n = 5), C (n = 5) and D (n = 1). We show that suramin potency is restricted to enterovirus A species. Clinical development of suramin is further supported by pharmacokinetic data demonstrating bioactive plasma levels after a single dose intramuscular administration in macaques. Altogether, our findings support the clinical development of suramin as a novel entry inhibitor for the treatment of enterovirus A infections.