Uncovering the Role of Hydroxycinnamoyl Transferase in Boosting Chlorogenic Acid Accumulation in Carthamus tinctorius Cells under Methyl Jasmonate Elicitation.

Chlorogenic acids (CGAs) are bioactive compounds widely used in the food, pharmaceutical, and cosmetic industries. Carthamus tinctorius is an important economic crop, and its suspension cells are rich in CGAs. However, little is known about the biosynthesis and regulation of CGAs in Carthamus tinctorius cells. This study first elucidated the regulatory mechanism of CGA biosynthesis in methyl jasmonate (MeJA)-treated Carthamus tinctorius cells and the role of the MeJA-responsive hydroxycinnamoyl transferase (HCT) gene in enhancing their CGA accumulation. Firstly, temporal changes in intracellular metabolites showed that MeJA increased the intracellular CGA content up to 1.61-fold to 100.23 mg·g-1. Meanwhile, 31 primary metabolites showed significant differences, with 6 precursors related to increasing CGA biosynthesis. Secondly, the transcriptome data revealed 3637 new genes previously unannotated in the Carthamus tinctorius genome and 3653 differentially expressed genes. The genes involved in the plant signaling pathway and the biosynthesis of CGAs and their precursors showed a general up-regulation, especially the HCT gene family, which ultimately promoted CGA biosynthesis. Thirdly, the expression of a newly annotated and MeJA-responsive HCT gene (CtHCT, CtNewGene_3476) was demonstrated to be positively correlated with CGA accumulation in the cells, and transient overexpression of CtHCT enhanced CGA accumulation in tobacco. Finally, in vitro catalysis kinetics and molecular docking simulations revealed the ability and mechanism of the CtHCT protein to bind to various substrates and catalyze the formation of four hydroxycinnamic esters, including CGAs. These findings strengthened our understanding of the regulatory mechanism of CGA biosynthesis, thereby providing theoretical support for the efficient production of CGAs.

Regulatory mechanisms of dopamine metabolism in a marine Meyerozyma guilliermondii GXDK6 under NaCl stress as revealed by integrative multi-omics analysis.

Dopamine can be used to treat depression, myocardial infarction, and other diseases. However, few reports are available on the de novo microbial synthesis of dopamine from low-cost substrate. In this study, integrated omics technology was used to explore the dopamine metabolism of a novel marine multi-stress-tolerant aromatic yeast Meyerozyma guilliermondii GXDK6. GXDK6 was found to have the ability to biosynthesize dopamine when using glucose as the substrate. 14 key genes for the biosynthesis of dopamine were identified by whole genome-wide analysis. Transcriptomic and proteomic data showed that the expression levels of gene AAT2 encoding aspartate aminotransferase (regulating dopamine anabolism) were upregulated, while gene AO-I encoding copper amine oxidase (involved in dopamine catabolism) were downregulated under 10 % NaCl stress compared with non-NaCl stress, thereby contributing to biosynthesis of dopamine. Further, the amount of dopamine under 10 % NaCl stress was 2.51-fold higher than that of zero NaCl, which was consistent with the multi-omics results. Real-time fluorescence quantitative PCR (RT-qPCR) and high-performance liquid chromatography (HPLC) results confirmed the metabolic model of dopamine. Furthermore, by overexpressing AAT2, AST enzyme activity was increased by 24.89 %, the expression of genes related to dopamine metabolism was enhanced, and dopamine production was increased by 56.36 % in recombinant GXDK6AAT2. In conclusion, Meyerozyma guilliermondii GXDK6 could utilize low-cost carbon source to synthesize dopamine, and NaCl stress promoted the biosynthesis of dopamine.

Salt stress perception and metabolic regulation network analysis of a marine probiotic Meyerozyma guilliermondii GXDK6.

Introduction: Extremely salt-tolerant microorganisms play an important role in the development of functional metabolites or drug molecules. Methods: In this work, the salt stress perception and metabolic regulation network of a marine probiotic Meyerozyma guilliermondii GXDK6 were investigated using integrative omics technology. Results: Results indicated that GXDK6 could accept the salt stress signals from signal transduction proteins (e.g., phosphorelay intermediate protein YPD1), thereby contributing to regulating the differential expression of its relevant genes (e.g., CTT1, SOD) and proteins (e.g., catalase, superoxide dismutase) in response to salt stress, and increasing the salt-tolerant viability of GXDK6. Omics data also suggested that the transcription (e.g., SMD2), translation (e.g., MRPL1), and protein synthesis and processing (e.g., inner membrane protein OXA1) of upregulated RNAs may contribute to increasing the salt-tolerant survivability of GXDK6 by improving protein transport activity (e.g., Small nuclear ribonucleoprotein Sm D2), anti-apoptotic ability (e.g., 54S ribosomal protein L1), and antioxidant activity (e.g., superoxide dismutase). Moreover, up to 65.9% of the differentially expressed genes/proteins could stimulate GXDK6 to biosynthesize many salt tolerant-related metabolites (e.g., ß-alanine, D-mannose) and drug molecules (e.g., deoxyspergualin, calcitriol), and were involved in the metabolic regulation of GXDK6 under high NaCl stress. Discussion: This study provided new insights into the exploration of novel functional products and/or drugs from extremely salt-tolerant microorganisms.Graphical Abstract.

Effect of Interfacial Interaction on the Demolding Deformation of Injection Molded Microfluidic Chips.

During the demolding process, the interfacial interaction between the polymer and the metal mold insert will lead to the deformation of the micro-structure, which will directly affect the molding quality and performance of injection molded microfluidic chips. In this study, the demolding quality of micro-channels and micro-mixing structures of polycarbonate (PC), polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC), and polystyrene (PS) microfluidic chips for heavy metal detection were investigated by molding experiments. The experimental results showed that the structures of microfluidic chips could be completely replicated. However, tensile deformation and fracture defects were observed at the edges of the micro-structures after demolding. Compared to the Ni mold insert, the calculation of the relative deviation percentages showed that the width of the micro-channel became larger and the depth became smaller, while the dimensions of the micro-mixing structure changes in the opposite direction. Subsequently, a molecular dynamics (MD) simulation model of polymer/nickel (Ni) mold insert for injection molding was established. The changes of adhesion work, demolding resistance and potential energy during demolding were analyzed. The simulation results showed that the polymer structures had some deformations such as necking, molecular chain stretching and voids under the action of adhesion work and demolding resistance. The difference in the contact area with the mold insert directly brought different interfacial interactions. In addition, the potential energy change of the polymer system could be used to quantitatively characterize the demolding deformation of the structure. Overall, the MD method is able to effectively explain the internal mechanisms of interfacial interactions, leading to the demolding deformation of polymer structures from the molecular/atomic scale.

Investigation of multi-timescale processing phenomena in femtosecond laser drilling of zirconia ceramics.

Femtosecond lasers have been applied to machining of zirconia (ZrO2) ceramics because of their ultrashort pulse duration and high peak power. However, an unclear understanding of the ultrafast laser-material interaction mechanisms limits the achievement of precision processing. In this study, a pump-probe imaging method comprising a focusing probe beam integrated with a high-speed camera was developed to directly observe and quantitatively evaluate the multi-timescale transient processing phenomena, including electron excitation, shockwave propagation, plasma evolution, and hole formation, occurring on the picosecond to second timescales, inside a ZrO2 sample. The variation mechanism in the shapes, lifetimes, and dimensions of these phenomena and their impacts on the drilling performance under different laser parameters were explored. The clear imaging and investigation of the above phenomena contribute to revealing the ultrafast laser-material interaction mechanisms and precision processing in the laser-drilling of zirconia ceramics.

Temporal-spatial characteristics of filament induced by a femtosecond laser pulse in transparent dielectrics.

The evolution mechanism of femtosecond laser-induced filaments has been widely investigated owing to its application prospects in microprocessing. However, the material dependence of the excitation, stability, and decay of filaments is not well understood despite the importance of their precise utilization. In this study, the spatiotemporal evolution of filaments induced by a single femtosecond laser pulse in sapphire and silica glass was investigated using time-resolved pump-probe shadowgraphy on femtosecond and picosecond timescales. The results revealed that the evolution was significantly different in the two typically transparent dielectrics in terms of the electronic plasma dynamics and filament lifetimes. This difference can be attributed to the self-trapped excitons (STEs) in silica glass. Furthermore, the filament dependence on pump energy and focal position was experimentally analyzed. Divergent filaments were observed when the focal position was near the surface because of the effect of the excited plasma on beam propagation. Moreover, the evolution of filament length in the two materials was discussed. This study contributes to the applications of filaments in precise processing.

Copper Tolerance Mechanism of the Novel Marine Multi-Stress Tolerant Yeast Meyerozyma guilliermondii GXDK6 as Revealed by Integrated Omics Analysis.

Various agricultural products used in food fermentation are polluted by heavy metals, especially copper, which seriously endangers human health. Methods to remove copper with microbial strategies have gained interests. A novel Meyerozyma guilliermondii GXDK6 could survive independently under high stress of copper (1400 ppm). The copper tolerance mechanism of GXDK6 was revealed by integrated omics in this work. Whole-genome analysis showed that nine genes (i.e., CCC2, CTR3, FRE2, GGT, GST, CAT, SOD2, PXMP4, and HSP82) were related to GXDK6 copper tolerance. Copper stress elevated glutathione metabolism-related gene expression, glutathione content, and glutathione sulfur transferase activity, suggesting enhanced copper conjugation and detoxification in cells. The inhibited copper uptake by Ctr3 and enhanced copper efflux by Ccc2 contributed to the decrease in intracellular copper concentration. The improved expression of antioxidant enzyme genes (PXMP4, SOD2, and CAT), accompanied by the enhanced activities of antioxidant enzymes (peroxidase, superoxide dismutase, and catalase), decreased copper-induced reactive oxygen species production, protein carbonylation, lipid peroxidation, and cell death. The metabolite D-mannose against harsh stress conditions was beneficial to improving copper tolerance. This study contributed to understanding the copper tolerance mechanism of M. guilliermondii and its application in removing copper during fermentation.

Breast Mass Detection in Mammography Based on Image Template Matching and CNN.

In recent years, computer vision technology has been widely used in the field of medical image processing. However, there is still a big gap between the existing breast mass detection methods and the real-world application due to the limited detection accuracy. It is known that humans locate the regions of interest quickly and further identify whether these regions are the targets we found. In breast cancer diagnosis, we locate all the potential regions of breast mass by glancing at the mammographic image from top to bottom and from left to right, then further identify whether these regions are a breast mass. Inspired by the process of human detection of breast mass, we proposed a novel breast mass detection method to detect breast mass on a mammographic image by stimulating the process of human detection. The proposed method preprocesses the mammographic image via the mathematical morphology method and locates the suspected regions of breast mass by the image template matching method. Then, it obtains the regions of breast mass by classifying these suspected regions into breast mass and background categories using a convolutional neural network (CNN). The bounding box of breast mass obtained by the mathematical morphology method and image template matching method are roughly due to the mathematical morphology method, which transforms all of the brighter regions into approximate circular areas. For regression of a breast mass bounding box, the optimal solution should be searched in the feasible region and the Particle Swarm Optimization (PSO) is suitable for solving the problem of searching the optimal solution within a certain range. Therefore, we refine the bounding box of breast mass by the PSO algorithm. The proposed breast mass detection method and the compared detection methods were evaluated on the open database Digital Database for Screening Mammography (DDSM). The experimental results demonstrate that the proposed method is superior to all of the compared detection methods in detection performance.

First report of fruit blight caused by Alternaria alternata on sesame in Northeast China.

Sesame (Sesamum indicum L.) is an important oilseed crop in China and it is also used in food and health products. In August of 2019, a blight sesame fruit was observed in a field of Liaoyang city, Liaoning province of China. Initial disease symptoms consisted of brown or dark brown spots on fruit. With time, lesions coalesced and the whole fruit turned dark brown or black. Most of the diseased fruit had thin and small, deformed, necrotic, hardened cracked epidermal lesions. Lesions were also produced on stem and petioles leading to leaf abscission. The disease results in premature fruit death, and in turn, considerable yield losses. To determine the causal agent, symptomatic fruit with developing lesions were collected, and surface sterilized in 2% NaClO for 3 min, rinsed three times in distilled water, and plated onto PDA medium. After incubation at 25°C for 5 days, a dark olivaceous fungus with abundant, branched, brown to black, and septate hyphae was consistently isolated. Twenty single spores were separated with an inoculation needle under stereomicroscope. The conidia were in chains, brown, obclavate, ovoid or ellipsoid, with 1-6 transverse septa and 0-4 longitudinal or oblique septa 12.5 to 45 × 6.5 to 14.5 µm in size. Conidiophores were septate, light brown to olive brown, measuring 22-60 µm × 2-4 µm. The morphological characteristics of the 20 isolates all matched the description of Alternaria alternata (Simmons, 2007). The internal transcribed spacer (ITS) region of rDNA of 15 isolates was amplified using primers ITS1/ITS4 (White et al. 1990) and EF1-728F/EF1-986R (Carbone et al. 1999) and sequenced. Identical sequences were obtained and the sequence of the isolate ZMHG12 was submitted to GenBank (Accession no. MW418181 and MW700316). BLAST analysis of the sequences of the isolates of ZMHG12 showed 100% to A. alternata (KP739875 and LC132712). In pathogenicity tests, a conidial suspension (2.5 × 105 conidia per ml) was prepared from 7 days-old cultures of isolate ZMHG12 grown on PDA at 25°C. Fruit of 10 two-month-old potted sesame plants (Variety "Liaozhi 8") were sprayed with the conidia suspension until runoff. Another 10 plants sprayed with distilled water to served as non-inoculated controls. All plants were maintained for 48 h in a humid chamber with a temperature of 25°C to 26°C, and then moved to a greenhouse. Ten days after inoculation, all fruit of inoculated plants exhibited symptoms similar to those observed in the field and non-inoculated control plants remained symptomless. The experiment was repeated twice with similar results. A. alternata has been reported as a pathogen caused leaf blight disease of sesame in Pakistan (Nayyar et al. 2017). To our knowledge, this is the first report of A.alternata causing fruit blight of sesame in China. To date, we have observed the disease on sesames in fields of Fuxin, Chaoyang and Tieling city in Liaoning Province, and Tongliao city in Inner Mongolia of China, and it has become an important disease in sesame production of China. References : Simmons E. G. 2007. Alternaria: An identification manual. CBS Fungal Biodiversity Center, Utrecht, Netherlands. White T. J., et al. 1990. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego. Carbone I., et al. 1999. Mycologia, 91: 553-556. Nayyar, B. G., et al. 2017. Plant Pathology Journal, 33 (6): 543-553.

Whole genome sequencing and metabolomics analyses reveal the biosynthesis of nerol in a multi-stress-tolerant Meyerozyma guilliermondii GXDK6.

BACKGROUND: Nerol (C10H18O), an acyclic monoterpene, naturally presents in plant essential oils, and is used widely in food, cosmetics and pharmaceuticals as the valuable fragrance. Meanwhile, chemical synthesis is the only strategy for large-scale production of nerol, and the disadvantages of chemical synthesis greatly limit the production and its application. These defects drive the interests of researchers shift to the production of nerol by eco-friendly methods known as biosynthesis methods. However, the main technical bottleneck restricting the biosynthesis of nerol is the lacking of corresponding natural aroma-producing microorganisms. RESULTS: In this study, a novel multi-stress-tolerant probiotics Meyerozyma guilliermondii GXDK6 with aroma-producing properties was identified by whole genome sequencing and metabolomics technology. GXDK6 showed a broad pH tolerance in the range of 2.5-10.0. The species also showed salt tolerance with up to 12% NaCl and up to 18% of KCl or MgCl2. GXDK6 exhibited heavy-metal Mn2+ tolerance of up to 5494 ppm. GXDK6 could also ferment with a total of 21 kinds of single organic matter as the carbon source, and produce abundant aromatic metabolites. Results from the gas chromatography-mass spectrometry indicated the production of 8-14 types of aromatic metabolites (isopentanol, nerol, geraniol, phenylethanol, isobutanol, etc.) when GXDK6 was fermented up to 72 h with glucose, sucrose, fructose, or xylose as the single carbon source. Among them, nerol was found to be a novel aromatic metabolite from GXDK6 fermentation, and its biosynthesis mechanism had also been further revealed. CONCLUSION: A novel aroma-producing M. guilliermondii GXDK6 was identified successfully by whole genome sequencing and metabolomics technology. GXDK6 showed high multi-stress-tolerant properties with acid-base, salty, and heavy-metal environments. The aroma-producing mechanism of nerol in GXDK6 had also been revealed. These findings indicated the aroma-producing M. guilliermondii GXDK6 with multi-stress-tolerant properties has great potential value in the fermentation industry.

Multi-Omics Analysis of Lipid Metabolism for a Marine Probiotic Meyerozyma guilliermondii GXDK6 Under High NaCl Stress.

Investigating microbial lipid regulation contributes to understanding the lipid-dependent signal transduction process of cells and helps to improve the sensitivity of microorganisms to environmental factors by interfering with lipid metabolism, thus beneficial for constructing advanced cell factories of novel molecular drugs. Integrated omics technology was used to systematically reveal the lipid metabolism mechanism of a marine Meyerozyma guilliermondii GXDK6 under high NaCl stress and test the sensitivity of GXDK6 to antibiotics when its lipid metabolism transformed. The omics data showed that when GXDK6 perceived 10% NaCl stress, the expression of AYR1 and NADPH-dependent 1-acyldihydroxyacetone phosphate reductase was inhibited, which weaken the budding and proliferation of cell membranes. This finding was further validated by decreased 64.39% of OD600 under 10% NaCl stress when compared with salt-free stress. In addition, salt stress promoted a large intracellular accumulation of glycerol, which was also verified by exogenous addition of glycerol. Moreover, NaCl stress remarkably inhibited the expression of drug target proteins (such as lanosterol 14-alpha demethylase), thereby increasing sensitivity to fluconazole. This study provided new insights into the molecular mechanism involved in the regulation of lipid metabolism in Meyerozyma guilliermondii strain and contributed to developing new methods to improve the effectiveness of killing fungi with lower antibiotics.

Consensus guided incomplete multi-view spectral clustering.

Incomplete multi-view clustering which aims to solve the difficult clustering challenge on incomplete multi-view data collected from diverse domains with missing views has drawn considerable attention in recent years. In this paper, we propose a novel method, called consensus guided incomplete multi-view spectral clustering (CGIMVSC), to address the incomplete clustering problem. Specifically, CGIMVSC seeks to explore the local information within every single-view and the semantic consistent information shared by all views in a unified framework simultaneously, where the local structure is adaptively obtained from the incomplete data rather than pre-constructed via a k-nearest neighbor approach in the existing methods. Considering the semantic consistency of multiple views, CGIMVSC introduces a co-regularization constraint to minimize the disagreement between the common representation and the individual representations with respect to different views, such that all views will obtain a consensus clustering result. Experimental comparisons with some state-of-the-art methods on seven datasets validate the effectiveness of the proposed method on incomplete multi-view clustering.

LncRNA NLIPMT Inhibits Tumorigenesis in Esophageal Squamous-Cell Carcinomas by Regulating miR-320/Survivin Axis.

BACKGROUND: LncRNA has been widely investigated for decades and plays critical roles in the progression of cancer. However, lncRNA NLIPMT, as a novel non-coding RNA, only was studied in breast cancer. This study aimed to explore the role of NLIPMT in esophageal squamous-cell carcinomas (ESCC). MATERIALS AND METHODS: NLIPMT, miR320 and survivin mRNA in ESCC tissues (or non-tumor tissue) were detected by qRT-PCR. Dual-luciferase reporter assay was performed to assess the relationship between miR-320 and survivin. In ESCC cell lines KYSE510 and ECA109, miR-320 mimic and expression vectors carrying NLIPMT and survivin were used. Cell cycle, apoptosis, proliferation and migration were detected by flow cytometry, CCK-8, transwell assay, respectively. NIPMT, miR-320 and survivin expression were measured by qRT-PCR and Western blotting. RESULTS: NLIPMT was downregulated in ESCC and predicted poor survival of ESCC patients. NLIPMT was positively correlated with miR-320 and negatively correlated with survivin in ESCC tumor tissues. Dual-luciferase reporter assay showed that miR-320 directly regulated survivin. qRT-PCR and Western blotting showed that NLIPMT promoted miR-320 expression and inhibited survivin expression via up-regulating miR-320. Moreover, both NLIPMT and miR-320 overexpression inhibited cell proliferation and migration and promoted cell cycle arrest and apoptosis in ESCC cells, while their effects were abolished by survivin overexpression. CONCLUSION: We demonstrate that NLIPMT inhibits cell proliferation and migration and promotes cell cycle arrest and apoptosis in ESCC cells by regulating the miR-320/survivin axis. NLIPMT may be a novel prognosis biomarker in ESCC patients.

Transgenic expression of human C19MC miRNAs impacts placental morphogenesis.

INTRODUCTION: The chromosome 19 miRNA cluster (C19MC) encodes a large family of microRNAs (miRNAs) that are abundantly expressed in the placenta of higher primates and also in certain cancers. In the placenta, miRNAs from this cluster account for nearly 40% of all miRNAs present in trophoblasts. However, the function of these miRNAs in the placenta remains poorly understood. Recent observations reveal a role for these miRNAs in cell migration, and suggest that they are involved in the development and function of the human placenta. Here, we examine the placenta in transgenic mice expressing the human C19MC miRNAs. METHODS: We produced transgenic mice using pronuclear microinjection of a bacterial artificial chromosome plasmid carrying the entire human C19MC locus and derived a homozygous line using crossbreeding. We performed morphological characterization and profiled gene expression changes in the placentas of the transgenic mice. RESULTS: C19MC transgenic mice delivered on time with no gross malformations. The placentas of transgenic mice expressed C19MC miRNAs and were larger than wild type placentas. Histologically, we found that the transgenic placenta exhibited projections of spongiotrophoblasts that penetrated deep into the labyrinth. Gene expression analysis revealed alterations in the expression of several genes involved in cell migration, with evidence of enhanced cell proliferation. DISCUSSION: Mice that were humanized for transgenically overexpressed C19MC miRNAs exhibit enlarged placentas with aberrant delineation of cell layers. The observed phenotype and the related gene expression changes suggest disrupted migration of placental cell subpopulations.

The Overexpression of Kinesin Superfamily Protein 2A (KIF2A) was Associated with the Proliferation and Prognosis of Esophageal Squamous Cell Carcinoma.

AIM: Kinesin family member 2A (KIF2A) is a member of the kinesin-13 superfamily protein. KIF2A played a role in the development of many tumors. However, the role of KIF2A in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to investigate the role of KIF2A in ESCC. METHODS: We used bioinformatics analysis to study the expression levels and prognosis of KIF2A in ESCC and normal tissues. We also used our own samples to verify the results by immunohistochemistry. Then, the biological functions of KIF2A in ESCC was studied by cell experiments and animal experiments. RESULTS: Both the TCGA database and our samples showed that KIF2A was relatively highly expressed in ESCC tissues and was significantly associated with disease-free survival (P =0.037) in TCGA database. Colony formation assay, CCK8 and Western blotting results showed that knockdown of KIF2A can significantly reduce colony forming ability and proliferation ability. The results of animal experiments showed that knocking down KIF2A can significantly reduce the tumor volume of mice. CONCLUSION: KIF2A might be used as a prognostic factor for ESCC, and knockdown of KIF2A could inhibit ESCC proliferation in vitro and in vivo, respectively. KIF2A could serve as a potential prognostic biomarker and therapeutic target for future ESCC.

Positive Influence of Stroke Health Manager on Risk Factors Control and Medication Adherence After Ischemic Stroke.

Background: From 2017, the Stroke Health Manager Training Project was carried out by the Chinese Government to strengthen health management and follow-up intervention after ischemic stroke. The aim of this study was to investigate whether after the intervention of the stroke health manager, the control of blood pressure, low-density lipoprotein cholesterol (LDL-C), glucose level, and the use of secondary prevention medications improved 3 months after discharge from our center following ischemic stroke. Methods: The study used a history-controlled approach. Patients who received stroke health manager intervention from May 1, 2018, to March 31, 2019, were considered as the intervention group; those from May 1, 2017, to April 30, 2018, were enrolled as the control group. Stroke health manager intervention included health education, discharge advice, online WeChat public group follow-up, and clinical consultation. Results: In total, 642 patients with ischemic stroke were enrolled in this study (277 in the control group, 365 in the intervention group). At 3 months, the blood pressure, LDL-C and glucose control in the intervention group were better than in the control group (all P < 0.05). At the same time, the overall persistence for secondary prevention medications at 3 months after discharge increased from 201/277 (72.56%) to 303/365 (83.01%, P = 0.001). The persistence for patients taking antiplatelet, hypoglycemic and statins were significantly higher in the intervention group (P < 0.05). Conclusions: Stroke health manager intervention improved the control of blood pressure, LDL-C, glucose levels and the persistence for secondary prevention medications 3 months after discharge.

Effects of Nursing Quality Improvement on Thrombolytic Therapy for Acute Ischemic Stroke.

Background and purpose: Intravenous thrombolytic therapy significantly improves the outcomes of acute ischemic stroke patients in a time-dependent manner. The aim of this study was to investigate whether continuous nursing quality improvement in stroke nurses has a positive effect on reducing the time to thrombolysis in acute ischemic stroke. Methods: The implementation of nursing quality improvement measures includes establishing full-time stroke nurses, pre-notification by emergency medical services (EMS), stroke team notification protocols, rapid triage, publicity and education, etc. Using a history-controlled approach, we analyzed acute ischemic stroke patients with intravenous thrombolysis during a pre-intervention period (April 1, 2015-July 31, 2016), trial period (August 1, 2016-October 31, 2016), and post-intervention period (November 1, 2016-September 30, 2017). This was done in accordance with the implementation of nursing quality improvement measures, including the general characteristics of the three groups, the time of each step in the process of thrombolysis, and the prognosis. Results: After the implementation of nursing quality improvement measures, the median door-to-needle time (DNT) was shortened from 73 min (interquartile range [IQR] 62-92 min) to 49 min (IQR 40-54 min; p < 0.001) in the post-intervention period. The median onset-to-needle time (ONT) was reduced from 193 min (IQR 155-240 min) to 167 min (IQR 125-227 min; p < 0.001). The proportion of patients with DNT ≤ 60 min increased from 23.94% (51/213) to 86.36% (190/220; p < 0.001) while the proportion of patients with DNT ≤ 40 min increased from 3.29% (7/213) to 25.00% (55/220; p < 0.001). The median time for door-to-laboratory results was decreased from 68 min to 56 min (p < 0.001). There was no significant difference in the fatality rate, 90-day modified Rankin score, length of stay or hospitalization expenses between the three groups of patients (p> 0.05). Conclusions: Implementation of nursing quality improvement measures in stroke nurses is an important factor in shortening the time of medication in patients with thrombolytic therapy, reducing the delay of intravenous thrombolysis in the hospital and helping to expedite presenting patients' arrival to the hospital post-stroke.

The Accumulation of Key Stroke Risk Factors and Its Association With the Characteristics of Subjects: A Population Based Cross Sectional Study.

Background: Evidence has shown that the greater the accumulation of risk factors for stroke, the greater the risk of stroke. Early intervention in the accumulation of risk factors for stroke can effectively reduce the incidence of stroke. The study aimed to investigate the distribution of the number of certain risk factors for stroke (hypertension, hyperlipidemia, overweight and obesity, and diabetes) and to explore the cause of the accumulation of certain stroke risk factors. Methods: A total of 4,052 participants aged 40 years or older were selected by the multistage stratified cluster sampling method in Dehui City in Jilin province, China. Descriptive data analyses were conducted. Multiple regression analyses were used to explore the adjusted association between the accumulation of key stroke risk factors and subjects' lifestyle and demographic characteristics. Results: Overall, 84.1% of the participants in this study had one or more of the four certain risk factors for stroke. The odds ratios (ORs) and 95% confidence intervals (CIs) of having ≥1, ≥2, and ≥3 key stroke risk factors were 1.627 (1.258, 2.103), 1.446 (1.209, 1.728), and 1.394 (1.164, 1.670), respectively, for males compared to females. Similarly, the ORs and 95% CIs of having ≥1, ≥2, and ≥3 key stroke risk factors were 1.227 (1.009, 1.492), 1.256 (1.096, 1.442), and 1.450 (1.262, 1.667), respectively, for partially salty diets compared to normal diets. Compared to people who did not exercise regularly, the ORs and 95% CIs of having ≥1, ≥2, and ≥3 key stroke risk factors were 0.693 (0.544, 0.883), 0.800 (0.679, 0.944), and 0.775 (0.659, 0.913), respectively, for people who regularly exercised. Compared to people who without a family history of cerebrovascular diseases, the ORs and 95% CIs were 1.418 (1.162, 1.732), 1.327 (1.154, 1.525), and 1.209 (1.050, 1.393), for people who with it. Conclusions: Male, partially salty diets, and family history of cerebrovascular diseases were risk factors for the accumulation of certain stroke risk factors while regular physical exercise was a protective factor.

MicroRNA-423 promotes proliferation, migration and invasion and induces chemoresistance of endometrial cancer cells.

Altered microRNA expression serves essential roles in tumorigenesis and progression in endometrial cancer. In the present study the effect of miR-423 on proliferation, chemosensitivity, migration and invasion of endometrial cancer cells was examined. A WST-1 assay was used to examine the proliferation of HEC-1B and Ishikawa endometrial cancer cells with either upregulation or downregulation of miR-423, with or without cisplatin treatment. The migration and invasion of HEC-1B and Ishikawa endometrial cancer cells were examined via Transwell migration and Matrigel invasion assays. Protein expression levels, including B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein, E- and N-cadherin, snail, vimentin, phosphatase and tensin homolog (PTEN) and protein kinase B (AKT) were examined by western blotting. A caspase-Glo3/7 assay was carried out to evaluate the effect of miR-423 on cisplatin-induced apoptosis in HEC-1B and Ishikawa endometrial cancer cells. Overexpression of miR-423 enhanced the proliferation, and increased migration and invasion in endometrial cancer cells. miR-423 also decreased the sensitivity of endometrial cancer cells following cisplatin treatment. miR-423 inhibited cisplatin-induced apoptosis in endometrial cancer cells by regulation of caspase 3/7 and Bcl-2 expression. Furthermore, the E-cadherin expression was significantly decreased, and the expression of N-cadherin, snail and Vimentin were increased in both HEC-1B cells and Ishikawa cells following overexpression of miR-423. Conversely, downregulation of miR-423 increased the expression of E-cadherin and decreased the expression of N-cadherin, snail and Vimentin. Further experiments demonstrated that the expression levels of PTEN and phosphorylated-AKT in HEC-1B and Ishikawa endometrial cancer cells was decreased and increased, respectively, following aberrant expression of miR-423. miR-423 displayed an important role in tumorigenesis and progression in endometrial cancer cells, and may therefore be used as a potential biomarker to predict chemotherapy response and prognosis in endometrial cancer.

Antioxidant Melatonin: Potential Functions in Improving Cerebral Autoregulation After Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a subtype of stroke with high mortality and morbidity. Impaired cerebral autoregulation following SAH has been reported owing to effects on sympathetic control, endothelial function, myogenic response, and cerebral metabolism. Impaired cerebral autoregulation is associated with early brain injury, cerebral vasospasm/delayed cerebral ischemia, and SAH prognosis. However, few drugs have been reported to improve cerebral autoregulation after SAH. Melatonin is a powerful antioxidant that is effective (easily crosses the blood brain barrier) and safe (tolerated in large doses without toxicity). Theoretically, melatonin may impact the control mechanisms of cerebral autoregulation via antioxidative effects, protection of endothelial cell integrity, suppression of sympathetic nerve activity, increase in nitric oxide bioavailability, mediation of the myogenic response, and amelioration of hypoxemia. Furthermore, melatonin may have a comprehensive effect on cerebral autoregulation. This review discusses the potential effects of melatonin on cerebral autoregulation following SAH, in terms of the association between pharmacological activities and the mechanisms of cerebral autoregulation.