Wolfberry-derived zeaxanthin dipalmitate delays retinal degeneration in a mouse model of retinitis pigmentosa through modulating STAT3, CCL2 and MAPK pathways.

Retinitis pigmentosa (RP) is a group of inherited photoreceptor degeneration diseases that causes blindness without effective treatment. The pathogenesis of retinal degeneration involves mainly oxidative stress and inflammatory responses. Zeaxanthin dipalmitate (ZD), a wolfberry-derived carotenoid, has anti-inflammatory and anti-oxidative stress effects. Here we investigated whether these properties of ZD can delay the retinal degeneration in rd10 mice, a model of RP, and explored its underlying mechanism. One shot of ZD or control vehicle was intravitreally injected into rd10 mice on postnatal day 16 (P16). Retinal function and structure of rd10 mice were assessed at P25, when rods degenerate substantially, using a visual behavior test, multi-electrode-array recordings and immunostaining. Retinal pathogenic gene expression and regulation of signaling pathways by ZD were explored using transcriptome sequencing and western blotting. Our results showed that ZD treatment improved the visual behavior of rd10 mice and delayed the degeneration of retinal photoreceptors. It also improved the light responses of photoreceptors, bipolar cells and retinal ganglion cells. The expression of genes that are involved in inflammation, apoptosis and oxidative stress were up-regulated in rd10 mice, and were reduced by ZD. ZD further reduced the activation of two key factors, signal transducer and activator of transcription 3 and chemokine (C-C motif) ligand 2, down-regulated the expression of the inflammatory factor GFAP, and inhibited extracellular signal regulated protein kinases and P38, but not the JNK pathways. In conclusion, ZD delays the degeneration of the rd10 retina both morphologically and functionally. Its anti-inflammatory function is mediated primarily through the signal transducer and activator of transcription 3, chemokine (C-C motif) ligand 2 and MAPK pathways. Thus, ZD may serve as a potential clinical candidate to treat RP.

Prevalence and Influencing Factors on Fatigue of First-line Nurses Combating with COVID-19 in China: A Descriptive Cross-Sectional Study.

Nurses' work-related fatigue has been recognized as a threat to nurse health and patient safety. The aim of this study was to assess the prevalence of fatigue among first-line nurses combating with COVID-19 in Wuhan, China, and to analyze its influencing factors on fatigue. A multi-center, descriptive, cross-sectional design with a convenience sample was used. The statistical population consisted of the first-line nurses in 7 tertiary general hospitals from March 3, 2020 to March 10, 2020 in Wuhan of China. A total of 2667 samples from 2768 contacted participants completed the investgation, with a response rate of 96.35%. Social-demographic questionnaire, work-related questionnaire, Fatigue Scale-14, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Chinese Perceived Stress Scale were used to conduct online survey. The descriptive statistic of nurses' social-demographic characteristics was conducted, and the related variables of work, anxiety, depression, perceived stress and fatigue were analyzed by t-tests, nonparametric test and Pearson's correlation analysis. The significant factors which resulted in nurses' fatigue were further analyzed by multiple linear regression analysis. The median score for the first-line nurses' fatigue in Wuhan was 4 (2, 8). The median score of physical and mental fatigue of them was 3 (1, 6) and 1 (0, 3) respectively. According to the scoring criteria, 35.06% nurses (n=935) of all participants were in the fatigue status, their median score of fatigue was 10 (8, 11), and the median score of physical and mental fatigue of them was 7 (5, 8) and 3 (2, 4) respectively. Multiple linear regression analysis revealed the participants in the risk groups of anxiety, depression and perceived stress had higher scores on physical and mental fatigue and the statistically significant positive correlation was observed between the variables and nurses' fatigue, the frequency of exercise and nurses' fatigue had a statistically significant negative correlation, and average daily working hours had a significantly positive correlation with nurses' fatigue, and the frequency of weekly night shift had a low positive correlation with nurses' fatigue (P<0.01). There was a moderate level of fatigue among the first-line nurses fighting against COVID-19 pandemic in Wuhan, China. Government and health authorities need to formulate and take effective intervention strategies according to the relevant risk factors, and undertake preventive measures aimed at reducing health hazards due to increased work-related fatigue among first-line nurses, and to enhance their health status and provide a safe occupational environment worldwide. Promoting both medical and nursing safety while combating with the pandemic currently is warranted.

GC-MS-based metabolomics research on the anti-hyperlipidaemic activity of Prunella vulgaris L. polysaccharides.

Prunella vulgaris polysaccharides (PVPs) have a variety of biological activities, but the mechanism and extent of their anti-hyperlipidaemic effect remain unclear. In vitro, PVPs had a significant inhibitory effect on angiotensin (Ang II)-induced vascular smooth muscle cell (VSMC) proliferation. A metabolomics approach based on gas chromatography-mass spectrometry (GC-MS) and chemometrics was established in this study to evaluate the anti-hyperlipidaemic activity of PVPs in a high-fat Sprague-Dawley rat model. In vivo, PVPs could significantly reduce the weight gain and the increases in serum total cholesterol (TC), low-density lipoprotein (LDL)-C and non-high-density lipoprotein (HDL)-C levels observed in rats fed a high-fat diet; they could also significantly increase serum GSH-Px activity, reduce the content of MDA and TNF-α and decrease abdominal fat volume in rats. Furthermore, PVPs exerted a repairing effect on morphological and structural damage in liver tissue cells in hyperlipidaemic rats fed a high-fat diet. PVPs improved lipid metabolism disorder in rats. Alanine, threonine, succinic acid, proline, inositol and arachidonic acid levels in the serum were considered potential biomarkers involved in amino acid, glucose, energy and lipid metabolism. Therefore, PVPs may interfere with hyperlipidaemia through anti-lipid peroxidation effects, attenuation of inflammation and regulation of glucose, amino acid, energy and lipid metabolism.

Dysregulated genes targeted by microRNAs and metabolic pathways in bladder cancer revealed by bioinformatics methods.

The present study aimed to identify bladder cancer-associated microRNAs (miRNAs) and target genes, and further analyze the potential molecular mechanisms involved in bladder cancer. The mRNA and miRNA expression profiling dataset GSE40355 was downloaded from the Gene Expression Omnibus database. The Limma package in R was used to identify differential expression levels. The Human microRNA Disease Database was used to identify bladder cancer-associated miRNAs and Target prediction programs were used to screen for miRNA target genes. Enrichment analysis was performed to identify biological functions. The Database for Annotation, Visualization and Integration Discovery was used to perform OMIM_DISEASE analysis, and then protein-protein interaction (PPI) analysis was performed to identify hubs with biological essentiality. ClusterONE plugins in cytoscape were used to screen modules and the InterPro database was used to perform protein domain enrichment analysis. A group of 573 disease dysregulated genes were identified in the present study. Enrichment analysis indicated that the muscle organ development and vascular smooth muscle contraction pathways were significantly enriched in terms of disease dysregulated genes. miRNAs targets (frizzled class receptor 8, EYA transcriptional coactivator and phosphatase 4, sacsin molecular chaperone, calcium voltage-gated channel auxiliary subunit ß2, peptidase inhibitor 15 and catenin α2) were mostly associated with bladder cancer. PPI analysis revealed that calmodulin 1 (CALM1), Jun proto-oncogene, AP-1 transcription factor subunit (JUN) and insulin like growth factor 1 (IGF1) were the important hub nodes. Additionally, protein domain enrichment analysis indicated that the serine/threonine protein kinase active site was enriched in module 1 extracted from the PPI network. Overall, the results suggested that the IGF signaling pathway and RAS/MEK/extracellular signal-regulated kinase transduction signaling may exert vital molecular mechanisms in bladder cancer, and that CALM1, JUN and IGF1 may be used as novel potential therapeutic targets.

Preparations of hyperbranched polymer nano micelles and the pH/redox controlled drug release behaviors.

Hyperbranched polymer nano micelles (NMs) were prepared through a nucleophilic ring opening polymerization between cystamine and polyethylene glycol diglycidyl ether, followed by a reaction of amino groups and dimethyl maleic anhydride. The NMs showed spheric morphologies with hydrodynamic diameters of 106-120nm. Doxorubicin was loaded in the NMs with loading rate as high as 15.38wt%; The NMs possessed negative zeta potentials in aqueous solutions of pH7.4 due to the carboxyl ions on the particle surfaces, but the zeta potentials were converted to positive ones due to the hydrolysis of amide bonds at pH5.0-6.5, leading to the leaving of carboxyl groups and remaining of amino groups. The disulfide bonds in cystamine were designed in the hyperbranched polymer structures of the NMs, and bonds could be broken by a reducing agent l-glutathione (GSH) (10mM), resulting in a targeted drug release. The smart NMs displayed good biodegradability and biocompatibility, and they could be potentially used in drug controlled release field.

Phytochemistry and pharmacological activities of the genus Prunella.

Prunella is a genus of perennial herbaceous plants in the Labiatae family. There are approximately 15 species worldwide, distributed widely in the temperate regions and tropical mountains of Europe and Asia. In the genus Prunella, P. vulgaris is the most studied, following a several thousand-year history as a traditional antipyretic and antidotal Chinese herb. Furthermore, since ancient times, P. vulgaris has been widely used as a cool tea ingredient and consumed as a vegetable. The genus Prunella contains triterpenoids and their saponins, phenolic acids, sterols and associated glycosides, flavonoids, organic acids, volatile oil and saccharides. Modern pharmacological studies have revealed that Prunella possess antiviral, antibacterial, anti-inflammatory, immunoregulatory, anti-oxidative, anti-tumor, antihypertensive and hypoglycemic functions. The active components related to these functions are mainly triterpenoids, phenolic acids, flavonoids and polysaccharides. This review mainly summarizes recent advances in traditional usage, chemical components and pharmacological functions.

[Construction and evaluation of the epidemiological injury criteria based on the combination of 'Hurt' and 'Harm'].

OBJECTIVE: To construct and evaluate the criteria of injury based on the theoretical model that 'Injury' is the combination of 'Hurt' and 'Harm', in order to provide theoretical basis for scientific and rational research on injury in future epidemiological survey. METHODS: The criteria of epidemiological injury was consected by analyzing documents and consulting experts, then Delphi method was used to evaluate its rationality. RESULTS: The epidemiological definition for 'Injury'is the combination of 'Hurt' and 'Harm'. 'Hurt' means the wound in clinical medicine, while 'Harm' means the damage from the views of public health. The active coefficients of two rounds Delphi Method were both 100%. The authority coefficients of two rounds were 0.88 and 0.87, respectively. The coordination coefficients were 0.44 and 0.62 (P<0.05), respectively. After two rounds consulting, all scores of rationality for definition of 'Hurt', definition of 'Harm', 'Injury' being the combination of 'hurt' and 'harm', 'Injury' should be graded, Graded based on the 'Injured' time were above 3, and all values of CV for those index were below 0.25 except Graded based on the 'Injured' time. CONCLUSION: The rationality of Definition of 'Hurt', Definition of 'Harm', 'Injury' being the combination of 'hurt' and 'harm', 'Injury' should be graded and Graded based on the 'Injured' time is good. There is still a certain degree of divergence about Graded based on the 'Injured' time.

[Analysis of different dosage forms of Xiasangju granules on fingerprints and models using high performance liquid chromatography].

To establish the fingerprints of Xiasangju granules (with sugar and non-sugar forms) by HPLC, and provide reference for their identification and effective quality control. High performance liquid chromatography (HPLC) method was used to collect the fingerprints of 20 batches of non-sugar Xiasangju granules and 34 batches of sugar type Xiasangju granules. Their main different components were classified and screened by mode identification methods (principal component analysis, PCA, and orthogonal partial least squares discriminate analysis, OPLS-DA). The principal components were identified by comparing with reference standards. The fingerprints of Xiasangju granules (sugar type and non-sugar type) were established. PCA could not fully classify the two types of granules, while OPLS-DA could obviously classify these two different types of Xiasangju granules. Six components showed greatest difference between two types of granules, including salviaflaside, luteoloside and linarin. The developed mode identification method is helpful to control the overall quality of Xiasangju granules, and it provides an effective approach to quality evaluation.

Surface Charge Convertible and Biodegradable Synthetic Zwitterionic Nanoparticles for Enhancing Cellular Drug Uptake.

To enhance drug cellular uptake, a biodegradable terpolymer is synthesized using taurine, N,N-Bis (acryloyl) cystamine, and dodecylamine as raw materials by Michael addition terpolymerization. The terpolymer is transformed to zwitterionic nanoparticles (NPs) through self-assembly. The surface charge of the NPs is convertible from negative at pH 7.4 to positive at pH 6.5, which endows the NPs' excellent nonfouling feature in bloodstream and effective uptake in tumor cells. The NPs display varied morphologies from solid micelles to polymersomes and nanorods depending on molar ratios of the structural units involved. The NPs can be biodegraded in l-glutathione (GSH) solution due to the split of disulfide bonds in main chains of the terpolymers. The NPs demonstrate good pH/reducing responsiveness in drug delivery and can be potentially used as anticancer drug vehicles for enhancement of cellular uptake of anticancer drug.

[Study on distribution and countermeasures of Oncomelania snails in beach wetlands of Runzhou section of lower reaches of Yangtze River].

OBJECTIVE: To understand the distribution of the river beach wetlands and Oncomelania snails in the lower reaches of the Yangtze River, and explore the countermeasures of snail control. METHODS: The river beach wetlands outside the Yangtze River levee were investigated and classified according to the hierarchical and classification system of wetlands of China. The snail survey was carried out in the beach wetlands of Runzhou section of lower reaches of the Yangtze River from 2004 to 2013. The change trend of snail areas and the densities was analyzed in the wetlands. RESULTS: The river beach of Runzhou section of lower reaches of the Yangtze River belongs to the riverine wetland. There was Oncomelania snail breeding except the permanent water area. At present, there were natural wetlands of 1303.0 hm2, human-made wetlands of 1479.0 hmb2 and wetland function changes of 1059.0 hm2 in the river beach of Runzhou section. There was the snail area of 181.4 hm2 in the natural wetland in 2013. The area of snail control by the molluscicide and environmental modification was 4624.55 hm2 from 2004 to 2013. The decline rates of snail areas and densities were 66.53% and 77.66% respectively. The existing Oncomelania snails were distributed in the natural wetlands. CONCLUSION: The human-made wetland is helpful to snail control. The snail control in the river beach wetlands should attach a great importance to the protection of wetland ecology.

The effects of phytic acid on the Maillard reaction and the formation of acrylamide.

Phytic acid, myo-inositol hexaphosphoric acid, exists in substantial (1-5%) amounts in edible plant seeds. In this study the effects of phytic acid on the Maillard reaction and the formation of acrylamide were investigated. Both phytic acid and phosphate enhanced browning in glucose/ß-alanine system, but phytic acid was less effective than phosphate. Higher pH favoured the catalytic activities for both of them. The influence of the types of sugar and amino acid on the reaction was also examined. Browning was suppressed by the addition of calcium and magnesium ions, but an additive effect was observed for ferrous ions and phytic acid in glucose/ß-alanine solution at pH 8.0. Both phytic acid and phosphate promoted the polymerisation of the reaction intermediates. The kinetics of Maillard reaction was first-ordered reaction in the presence of phytic acid. Phytic acid was less effective than phosphate in the formation of acrylamide. When potato slices were treated with sodium phytate and calcium chloride successively, the formation of acrylamide was greatly suppressed.

A novel fluorescent biosensor for sequence-specific recognition of double-stranded DNA with the platform of graphene oxide.

A fluorescent biosensor for sequence-specific recognition of double-stranded DNA (dsDNA) was developed based upon the DNA hybridization between dye-labeled single-stranded DNA (ssDNA) and double-stranded DNA. The fluorescence of FAM-labeled single-stranded DNA was quenched when it adsorbed on the surface of graphene oxide (GO). Upon addition of the target dsDNA, a homopyrimidine·homopurine part of dsDNA on the Simian virus 40 (SV40) (4424-4440, gp6), hybridization occurred between the dye-labeled DNA and the target dsDNA, which induced the dye-labeled DNA desorbed from the surface of GO, and turned on the fluorescence of the dye. Under the optimum conditions, the enhanced fluorescence intensity was proportional to the concentration of target dsDNA in the range 40.0-260 nM, and the detection limit was found to be 14.3 nM alongside the good sequence selectivity.

An amperometric immunosensor based on an electrochemically pretreated carbon-paraffin electrode for complement III (C3) assay.

An electrochemical immunosensor based on the adsorption of anti-complement III antibody onto an electrochemical pretreated carbon-paraffin electrode has been proposed for the detection of complement III (C(3)). The competitive immunoassay format was adopted with horseradish peroxide-C(3) (HRP-C(3)) as a tracer, 3,3'5,5'-tetramethylbenzidine (TMB) and hydrogen peroxide as the enzyme substrates. In order to measure the amount of HRP-C(3) binding onto the electrode surface, the product of the enzyme catalytic reaction was detected at 100 mV (vs. Ag/AgCl reference electrode). The system was optimized to realize a reliable determination of C(3) in the range of 0.06-10 microg/ml. It exhibits some advantages, such as simplicity of fabrication, rapidity of measurement, and satisfactory sensitivity and reproducibility.

An amperometric immunosensor based on a conducting immunocomposite electrode for the determination of Schistosoma japonicum antigen.

A renewable amperometric immunosensor based on a graphite-paraffin-Schistosoma japonicum antibody (SjAb) biocomposite electrode has been prepared for the detection of Schistosoma japonicum antigen (SjAg). Competitive ELISA was employed involving HRP-SjAg as a tracer and 3,3',5,5'-tetramethylbenzidine (TMB) as a substrate. The product of an enzyme catalytic reaction was detected at +0.1 V (vs. Ag/AgCl reference electrode) for measuring the amount of HRP-labeled SjAg binding to the electrode surface. The assay conditions were optimized, including the amount of SjAb loading in the electrode and HRP-SjAg in the incubation solution, the pH of the measuring solution and the incubation time. The measuring range was 0.5-30 microg/ml under the optimum conditions. Rabbit serum samples of different infection degree were measured, which demonstrated that the immunosensor meets the demands of clinical analysis. It exhibits some advantages, such as simplicity of fabrication, rapidity of measurement, and satisfactory sensitivity and reproducibility.