Search

Nano-silica (SiO2) has been widely used to fill rubbers (crosslinked) and usual polyolefin elastomers (POEs). SiO2 filled POE with crystalline structure can also be crosslinked. Crystallization, structure, and mechanical properties of crosslinked POE/SiO2 composites can be affected by SiO2. In this paper, crosslinked POE/SiO2 composites were obtained through two different methods: dynamic crosslinking in molten state and static crosslinking. For the non-crosslinked and static crosslinked composites, SiO2 had a more significant effect on the nucleation in non-crosslinked POE than in static crosslinked POE. For the dynamic crosslinked composite, SiO2 and crosslinking points hindered the mobility of POE chains and suppressed the POE crystallization, resulting in smaller and fewer crystals. Dynamic mechanical analysis showed that the SiO2 and POE were compatible, as evidenced by the lower tan(δ) value in SiO2-filled samples. The latter was more consistent with the higher tensile strength and elongation at break for the non-crosslinked and static crosslinked composites than for the non-filled samples. However, the dynamic crosslinked composite exhibited the worst elongation at break, resulting from the lowest number of crystals and shortened molecular chains due to the shearing that occurred during crosslinking process. The SiO2 had no observable effect on the permanent deformation of samples.

Osteoporosis is a worldwide disease that seriously affects the quality of life and survival rate of the elderly. The detection of bone biomarkers will provide supplementary information on bone mineral density, contributing to the accurate diagnosis of osteoporosis and better health care for prevention. This study aimed to investigate the efficacy of oxidative stress markers—8-oxo-7,8-dihydroguanine (8-oxoGsn) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGsn) in the assessment of osteoporosis. We conducted a cross-sectional study among menopausal women with a mean (standard deviation) age of 62.967 (7.798) years old (n = 151). Participants were recruited for the bone mineral density (BMD) assessment, blood and urinary samples. Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine and 8-oxo-7,8-dihydro-guanine concentrations were measured by ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). The urinary 8-oxoGsn/Cre value differed significantly between normal and osteoporotic participants (p < 0.001), while the 8-oxodGsn/Cre value did not (p = 0.720). Even after adjusting for the age and body mass index, the BMD was still associated with urinary 8-oxoGsn/Cre value. ROC analysis showed that 8-oxoGsn has a strong diagnostic value for osteoporosis (AUC = 0.744). The results show for the first time that 8-oxoGsn may be a biomarker for the future diagnosis of osteoporosis in women.

Background: Cytochrome P450 (P450) is the largest family of enzymatic proteins in the human liver, and its features have been studied in physiology, medicine, biotechnology, and phytoremediation. Objective: The aim of this study was to assess the catalytic activities of 28 human CYP3A4 alleles by using dronedarone as a probe drug in vitro, including 7 novel alleles recently found in the Han Chinese population. Methods: We expressed 28 CYP3A4 alleles in insect microsomes and incubated them with 1-100 μM of dronedarone at 37 °C for 40 minutes to obtain the metabolites of N-debutyl-dronedarone. Results: Compared with the wild type of CYP3A4, the 27 defective alleles can be classified into four categories. Three alleles had no detectable enzyme activity leading to a lack of kinetic parameters of N-debutyl-dronedarone; the other three alleles slightly despaired when it comes to intrinsic clearance values compared with the features of the wild type. Sixteen alleles exhibited 35.91%~79.70% relative values (in comparison to the wild-type) and could be defined as the “moderate decrease group”. The rest of the alleles showed a considerable decrease in intrinsic clearance values, ranging from 11.88%~23.34%. Therefore they were classified as a “significantly decreased group”. More specifically, 18 CYP3A4 alleles exhibited a substrate inhibition trend toward dronedarone when the concentration rises to 20 μM. Conclusion: The outcomes of this novel study on the metabolism of dronedarone by CYP3A4 alleles can be used as experimental data support for the individualized use of this modern drug.

To assess associations between infants with macrosomia and placental expression levels of lipid activated/transport-related factors and umbilical cord blood lipid concentrations in healthy pregnancy. We conducted a case-control study of 38 macrosomic neonates (MS group) and 39 normal-birth-weight newborns (NC group) in a healthy pregnancy. Cord blood lipid levels were measured by automatic biochemical analyzer, mRNA and protein expression levels of placental lipid activated/transport-related factors were determined by real-time polymerase chain reaction and western blot, respectively. Compared with NC group, cord blood total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and non-esterified fatty acid (NEFA) concentrations were decreased in the MS group. The mRNA and protein expression levels of placental peroxisome proliferator-activated receptors (PPARα, PPARγ), plasma membrane fatty acid-binding protein (FABPpm), and fatty acid translocase (FAT/CD36) were significantly higher in the MS group than the NC group. And there was a weak positive correlation between the expression of PPARγ, FABP4, and FABP3 mRNA in the placenta and the HDLC (rs = 0.439; P = 0.005), NEFA (rs = 0.342; P = 0.041), and TG (rs = 0.349; P = 0.034) levels in the cord blood in the MS group, respectively. After multivariate adjustment, the logistic regression analysis showed that high placental PPARα (adjusted odds ratio [AOR] = 3.022; 95% confidence interval [CI] 1.032-8.853) and FAT/CD36 (AOR=2.989; 95%CI 1.029-8.679) and low LDLC concentration in the cord blood (AOR=0.246; 95%CI 0.080-0.759) increased the risk of macrosomia. The increased PPARα and FAT/CD36 expression levels may influence the occurrence of fetal macrosomia through regulating placental lipid transport.

The dynamic crosslinking method has been widely used to prepare rubber/plastic blends with thermoplastic properties, and the rubber phase is crosslinked in these blends. Both polyolefin elastomer (POE) and ethylene-propylene-diene monomer rubber (EPDM) can be crosslinked, which is different from usual dynamic crosslinking components. In this paper, dynamic crosslinked POE/EPDM blends were prepared. For POE/EPDM blends without dynamic crosslinking, EPDM can play a nucleation role, leading to POE crystallizing at a higher temperature. After dynamic crosslinking, the crosslinking points hinder the mobility of POE chains, resulting in smaller crystals, but having too many crosslinking points suppresses POE crystallization. Synchrotron radiation studies show that phase separation occurs and phase regions form in non-crosslinked blends. After crosslinking, crosslinking points connecting EPDM and part of POE chains, enabling more POE to enter the EPDM phase and thus weakening phase separation, indicates that dynamic crosslinking improves the compatibility of POE/EPDM, also evidenced by a lower β conversion temperature and higher α conversion temperature than neat POE from dynamic mechanical analysis. Moreover, crosslinking networks hinder the crystal fragmentation during stretching and provide higher strength, resulting in 8.3% higher tensile strength of a 10 wt% EPDM blend than neat POE and almost the same elongation at break. Though excessive crosslinking points offer higher strength, they weaken the elongation at break.

Background: CYP2C19 is an important member of the cytochrome P450 enzyme superfamily. We recently identified 31CYP2C19 alleles in the Han Chinese population; studying the effects of CYP2C19 on drug metabolism can help reduce adverse drug reactions and therapeutic failure. Aim: The aim of this study was to assess the catalytic activities of 31 allelic isoforms and their effects on the metabolism of clomipramine in vitro. Methods: The wild-type and 30 CYP2C19 variants were expressed in insect cells, and each variant was characterized using clomipramine as the substrate. Reactions were performed at 37°C with 5–150 μmol/L substrate for 30 min. By using ultra-high-performance liquid chromatography-mass spectrometry to detect the products, the kinetic parameters Km, Vmax, and intrinsic clearance (Vmax/Km) of N-desmethyl clomipramine were determined. Results: Among the CYP2C19 variants tested, CYP2C19*29, L16F, and T130M showed extremely increased intrinsic clearance of clomipramine, CYP2C19*3C, and N277K showed similar intrinsic clearance (Vmax/Km) values with CYP2C19*1, while the intrinsic clearance values of other variants were significantly decreased (from 0.65% to 63.28%). In addition, CYP2C19*3 and 35FS could not be detected because they have no detectable enzyme activity. Conclusions: As the first report of 31 CYP2C19 alleles for clomipramine metabolism, our study could provide corresponding reference for clomipramine for further studies in vivo and offer valuable information relevant to the personalized medicine for CYP2C19-metabolized drug.

Increased systemic RNA oxidative damage and diagnostic value of RNA oxidative metabolites during Shigella flexneri-induced intestinal infection

More and more evidence support the concept that RNA oxidation plays a substantial role in the progress of multiple diseases; however, only a few studies have reported RNA oxidation caused by microbial pathogens. Urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn), which are broadly used as indicators of oxidative damage of RNA and DNA, were analyzed in this study to determine which can be used as a biomarker of infection in challenged with Vibrio parahaemolyticus (V. parahaemolyticus). In this work, 24 specific-pathogen-free (SPF) male SD rats were randomly divided into two groups: an infection group and a phosphate-buffered saline (PBS) control group. Our results proved that 8-oxo-Gsn rather than 8-oxo-dGsn was significantly increased after challenged with V. parahaemolyticus in urine and tissue samples of SD rats compared with the PBS control group. Simultaneously, white blood cells (WBCs) counts, intestinal inflammation and inflammatory factors (including CRP, IL-6, IL-1β, TNF-α, IL-10, and IL-17A) were also increased sharply. Which has more clinical value is that the trend of urinary 8-oxo-Gsn was consistent with WBCs, intestinal inflammation and all kinds of inflammatory factors. More importantly is that urinary 8-oxo-Gsn of infection group was positively correlated with WBCs and various inflammatory cytokines. In a word, our results demonstrated that as a systemic RNA oxidation biomarker, we hope 8-oxo-Gsn can be used as a biomarker of the severity of microbial pathogens infection, rather than a specific biomarker of microbial pathogens infection.

Due to the low permeability of tight reservoirs, throats play a significant role in controlling fluid flow. Although many studies have been conducted to investigate fluid flow in throats in the microscale domain, comparatively fewer works have been devoted to study the effect of adsorption boundary layer (ABL) in throats based on the digital rock method. By considering an ABL, we investigate its effects on fluid flow. We build digital rock model based on computed tomography technology. Then, microscopic pore structures are extracted with watershed segmentation and pore geometries are meshed through Delaunay triangulation approach. Finally, using the meshed digital simulation model and finite element method, we investigate the effects of viscosity and thickness of ABL on microscale flow. Our results demonstrate that viscosity and thickness of ABL are major factors that significantly hinder fluid flow in throats.

Background: PRP injection was proved to promote the health condition of individuals with mild to moderate Carpal Tunnel Syndrome （CTS）. However, carpal tunnel release (CTR) was still an important treatment for individuals with moderate, as well as severe CTS.Methods: To explore whether adjuvant PRP treatment would improve the prognosis while using CTR, we included 82 patients in this study. Preoperative and postoperative visual analog scale (VAS), Boston carpal tunnel syndrome questionnaire-symptom severity scale (BCTQ-SSS), Boston carpal tunnel syndrome questionnaire-functional status scale (BCTQ-FSS), and grip strength was used to examine the patient's symptoms and function.Results: CTR combined with PRP treatment improved the VAS (1.9±0.5 versus 1.4±0.4, PConclusions: The use of PRP does not affect long-term prognosis while increasing the surgery cost. To conclude, PRP as an adjuvant treatment of CTR has limited effect. Considering the additional financial burden on patients, CTR combined with PRP should be cautious in CTS treatment.

Leukemia is a broad term for blood cell cancer. Leukemia is divided into acute or chronic, depending on cell differentiation. Leukemia patients are prone to adverse reactions during chemotherapy, such as anxiety, depression, and even suicide, affecting prognosis. As a nursing model developed by three well-known cognitive psychologists, empathetic nursing with mindfulness cognitive therapy (ENMCT) can effectively reduce anxiety and depression and improve the quality of life in patients with chronic disease.To explore the effect of ENMCT on cancer-induced fatigue, hope level, and negative emotions in patients with long-term leukemia chemotherapy.A total of 103 patients with long-term leukemia chemotherapy diagnosed and treated in our hospital from July 2017 to October 2019 were enrolled and randomly assigned to observation and control groups using the random number table approach. Fifty-one patients in the control group received routine nursing, while 52 patients in the observation group received empathic nursing with mindfulness cognitive therapy. After three months of nursing care, cancer-induced fatigue was measured with the Piper Fatigue Scale (PFS), hope level with the Herth Hope Index (HHI), and negative emotion with the Hamilton Anxiety Scale (HAMA)/Hamilton Depression Scale (HAMD). Self-management (Chinese Strategies Used by People to Promote Health) was also recorded.The observation group's total scores in behavior, cognition, emotion, feeling, and PFS were lower than the control group after the intervention (Empathetic nursing with cognitive mindfulness therapy is beneficial in improving cancer-related fatigue, negative emotions, expectation level, and self-management ability in patients with long-term leukemia chemotherapy.

Zinc ions (Zn2+) act as a transcription factor in eukaryotic cells for mediating protein-protein interactions in human healthy. The simple and sensitive detection of Zn2+ is the crucial mission in analytical field. This work demonstrated a novel and fast Zn2+ detection strategy based on “signal on” mode with electrochemiluminescence (ECL) luminophore, in which singlet oxygen was generated via electrocatalytic reduction of zinc proto-porphyrin IX grafted onto Pd nanocubes (ZnPPIX-Pd NCs). In protocol, Pd NCs were synthetized under hydrothermal conditions and aminated through thermal oxidative polymerization of 3-aminopropyltriethoxysilane (APTES), followed by further linking with PPIX via amide reaction. The resulting PPIX-Pd NCs effectively captured Zn2+ in chelation and monitored by Fourier transform infrared (FTIR) spectroscopy and ultraviolet-visible (UV-vis) absorption spectroscopy. By virtue of the metal resonance responses of Pd NCs, an intense monochromic, potential shuffling and enhanced ECL irradiation shows up for the hybrid nanocomposite with H2O2 as the coreactant. To this end, an ultrasensitive method based on the nanocomposite with a “signal-on” model was developed for Zn2+ detection with a low detection limit down to 0.38 nM (based on a S/N= 3), excellent precision and high stability. The ECL strategy reveals the potential application in molecular diagnosis and offers a new avenue for bioassay of structural Zn(II) proteins and zinc finger-binding nucleotides.

Olmutinib (Olita™) is an oral third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) which is used to treat non-small cell lung cancer (NSCLC). A simple, rapid, and sensitive method based on ultra-performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) has been developed for the determination of olmutinib. Sample preparation was performed following simple one-step protein precipitation with acetonitrile. Olmutinib and internal standard (dasatinib) were separated on an Eclipse Plus C18 RRHD (2.1 × 50 mm, 1.8 μm) column. The mobile phase consisted of acetonitrile–0.1% formic acid in water with gradient elution. A total run time of 1.7 min was achieved. Detection was performed on a positive-ion electrospray ionization mass spectrometer in multiple reaction monitoring (MRM) mode, using transitions of m/z 487.2 → 402.1 for olmutinib and m/z 488.2 → 401 for dasatinib (IS), respectively. The calibration curve (R2 = 0.999) was linear over the range of 1–500 ng/mL. ...

Electrochemiluminescence (ECL) has attracted significant interest because of its superior properties and potential applications in bioanalysis, and therefore many luminescent nanomaterials have been developed. Herein, well-defined Pd nanocones (Pd NCs) were facilely obtained by a one-pot hydrothermal method with poly- l -lysine (PLL) as a green protecting ligand, which were mainly characterized by transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Then, the as-obtained Pd NCs were first explored as an anodic ECL emitter, where tripropylamine (TPA) worked as the coreactant to boost the ECL emission. The possible ECL mechanism of Pd NCs/TPA system was extensively explored by ECL and electrochemical techniques. Briefly, the ECL emission underwent the oxidation-reduction route, in which both Pd NCs and TPA were initially oxidized, and then the oxidized TPA lost an proton to form reducing agent (TPA·) strongly reacted with the oxidized Pd NCs generating Pd NCs* for the emission. Furthermore, using dopamine (DA) as an ECL quencher, an ultrasensitive sensor was constructed for DA detection. The fabricated ECL sensor shows high sensitivity and selectivity, good stability, and wide linear range with the low detection limit of 0.46 pM. It offers a new avenue to exploit ECL illuminant and enriches the ECL emission theory.

BackgroundThe discovery of biomarkers has become an attractive field in studying autoimmune diseases. For example, in the study of systemic lupus erythematosus (SLE), various biomarkers such as genes and miRNAs have been identified for the diagnosis of SLE and its organ involvement. ResultsThe expression data of gene microarray GSE50772 was downloaded from the GEO, and 257 differentially expressed genes (DEGs) were obtained by using limma plug-in for R software. The tissue-specific gene expression analyses were performed in BioGPS database. Then, a protein-protein interaction (PPI) network was constructed with STRING and visualized in Cytoscape. Whereafter, top twenty hub genes derived from the PPI network, could basically differentiate the SLE samples from the non-SLE samples, were ascertained through CytoHubba. What is noticeable is that the five novel hub genes ( ORM1, SLPI, OLFM4, TCN1 and CRISP3) and a related miRNA (hsa-let-7e-5p) may be considered as candidate biomarkers of SLE. ConclusionsFive genes (ORM1, SLPI, OLFM4, TCN1 and CRISP3) and a miRNA(hsa-let-7e-5p) in this discovery-driven study may become potential biomarkers for diagnosing SLE and assessing its organ damage, and they also will provide valuable information on the pathogenesis of SLE.

BACKGROUND Shigella flexneri (S. flexneri) is a major pathogen causing acute intestinal infection, but the systematic oxidative damage incurred during the course of infection has not been investigated. AIM To investigate the incurred systemic RNA oxidative damage and the diagnostic value of RNA oxidative metabolites during S. flexneri-induced intestinal infection. METHODS In this study, a Sprague-Dawley rat model of acute intestinal infection was established by oral gavage with S. flexneri strains. The changes in white blood cells (WBCs) and cytokine levels in blood and the inflammatory response in the colon were investigated. We also detected the RNA and DNA oxidation in urine and tissues. RESULTS S. flexneri infection induced an increase in WBCs, C-reactive protein, interleukin (IL)-6, IL-10, IL-1β, IL-4, IL-17a, IL-10, and tumor necrosis factor α (TNF-α) in blood. Of note, a significant increase in urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn), an important marker of total RNA oxidation, was detected after intestinal infection (P = 0.03). The urinary 8-oxo-Gsn level returned to the baseline level after recovery from infection. In addition, the results of a correlation analysis showed that urinary 8-oxo-Gsn was positively correlated with the WBC count and the cytokines IL-6, TNF-α, IL-10, IL-1β, and IL-17α. Further detection of the oxidation in different tissues showed that S. flexneri infection induced RNA oxidative damage in the colon, ileum, liver, spleen, and brain. CONCLUSION Acute infection induced by S. flexneri causes increased RNA oxidative damage in various tissues (liver, spleen, and brain) and an increase of 8-oxo-Gsn, a urinary metabolite. Urinary 8-oxo-Gsn may be useful as a biomarker for evaluating the severity and prognosis of infection.

Background: Macrosomia is a serious public health problem worldwide, the underlying etiology and mechanism of macrosomia born to healthy mothers are still unclear. Abnormal lipid transport during pregnancy exerts potential and adverse impacts on fetus, our study aimed to assess associations between macrosomia and placental expression levels of lipid transport-related genes and umbilical cord blood lipid concentrations in healthy pregnancy.Methods: We conducted a case-control study of 38 macrosomia and 39 normal-birth-weight newborns in healthy pregnancy. Cord blood lipid levels were measured by automatic biochemical analyzer, mRNA and protein expression levels of placental lipid transport-related factors were determined by real-time polymerase chain reaction and western blot, respectively. Results: The single factor analysis showed that placental mRNA and protein expression levels of PPARα, PPARγ, FABPpm, LXRα, FABP3, FABP4 and FAT/CD36 were significantly higher and cord blood total cholesterol, low-density lipoprotein cholesterol, and non-esterified fatty acid (NEFA) concentrations were significantly lower in macrosomia group. Further analysis found that placental PPARγ, FABP4 and FABP3 mRNA expression levels were positively correlated with high-density lipoprotein cholesterol, NEFA and triglycerides concentrations in macrosomia cord blood, respectively. After multivariate adjustment, the logistic regression analysis showed that high placental PPARα (AOR=3.022; 95%CI:1.032-8.853) and FAT/CD36 (AOR=2.989; 95%CI:1.029-8.679) expression increased the risk of delivering macrosomia. Conclusions: The increase of PPARα and FAT/CD36 mRNA expression levels is associated with the occurrence of macrosomia, suggesting that they may be important regulators during placental lipid transport in macrosomia.

To investigate the occurrence, distribution, and potential risks of pharmaceuticals and personal care products (PPCPs) in the South costal area of China, a total of 20 PPCPs in water and aquatic organisms (fish, crab, and shellfish), obtained from 7 coastal rivers of the Chaoshan area, were determined using solid-phase extraction (SPE) and high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The results showed that up to 16 to 18 kinds of PPCPs could be detected in the rivers and aquatic organisms of the Chaoshan area, and the concentrations of PPCPs in the rivers and organisms ranged from 0.30-2223 ng ·L

Organophosphate esters (OPEs) are widely used flame retardants that are frequently released into the environment, causing potential harm to humans and ecosystems. Tibet is located on the Tibetan Plateau, known as the “roof of the world”, but the occurrence of OPEs in Tibet remains unclear. This is the first report of the occurrence, potential sources and risks of 12 OPEs in water, soil, sediment and snow from Xainza, a typical town at high elevation in Tibet (average elevation = 4700 m). Ten OPEs were observed, with ∑OPE concentrations of 46.45–1744.73 ng/L in surface water, 29.74–73.85 ng/g in soil, and 13.30–32.23 ng/g in sediment. Moreover, the mean ∑OPE concentration in snow was 413.90 ng/L. Tris (2-chloroethyl) phosphate (TCEP) and tris (2-chloroisopropyl) phosphate (TCPP) were the main OPEs in surface water and snow, while 2-ethylhexyl diphenyl phosphate (EHDPP) was dominant in soil and sediment. Local human activities and long-distance atmospheric transport may be the main sources of OPEs in Xainza. The assessment of ecological risk indicated that EHDPP in soil poses potential risk. The occurrence of OPEs in Xainza showed that more attention should be paid to persistent organic pollutants in high-elevation regions.

In view of the problem that time delay always existing in wide area power system can cause severe effects on the operation performance of the whole system, this paper studies the stability of the wide area power system with interval time-varying delays. Firstly, the model of wide area power system with interval time-varying delay is established, based on that, a new augmented vector and new Lyapunov-Krasoskii functional (LKF) are constructed. Then, the delay-partitioning approach, Wirtinger integral inequality, free-matrix-based inequality and convex combination approach are used to estimate the derivative of the functional, and as a result, a less conservative stability criterion for the delayed power system is obtained. Finally, numerical simulations of the typical second-order system, the single machine system and two-area four-generator power system are given to illustrate that the proposed method in this paper expands the stability margin of the system effectively.

Ischemic injury in the heart is associated with death of cardiomyocytes and even after decades of research there is no appropriate therapeutic intervention to treat ischemic injury. The microRNA miR-34a is known to be induced in cardiomyocytes following ischemic injury. Another hallmark of ischemic injury is impaired glycolysis. The objective of the current study was to investigate the effects of short- and long-term exposure to hypoxia on miR-34a expression on apoptosis and regulation of key glycolysis metabolic enzymes. Both repeated short-term (30 min) burst of hypoxia with intermittent reoxygenation (30 min) as well as long-term (4 h) exposure to hypoxia followed by 6 h of reoxygenation robustly induced miR-34a levels. Hypoxia induced changes in cardiac permeability and localization of the channel protein connexin 34 as well as induced apoptosis as evident by levels of cleaved-caspase 3/7 and impaired cell proliferation. Hypoxia was also associated with decreased expression of key glycolytic enzymes hexokinase-1, hexokinase-2, glucose-6-phosphate-isomerase, and pyruvate dehydrogenase kinase 1. Attenuation of hypoxia-induced miR-34a by anti-miR-34a antagomir, but not a control antagomir, decreased miR-34a levels to those observed under normoxia and also inhibited apoptosis, potentially by rescuing expression of the key glycolytic enzymes. Cumulatively, our results establish that therapeutic targeting of miR-34a via antagomir might be a potent therapeutic mechanism to treat ischemic injury in the heart.

The aim of this study was to explore the independent prognostic factors related to postoperative recurrence‐free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. According to histological type, patients with benign PTBs were classified as a low‐risk group, while borderline and malignant PTBs were classified as a high‐risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups, and a nomogram was generated to predict recurrence‐free survival at 1, 3, and 5 years. Among the 404 patients, 168 (41.6%) patients had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty‐five patients experienced postoperative local recurrence, including six benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low‐risk group, while the surgical approach and tumor border were independent prognostic factors for RFS in the high‐risk group, and patients receiving simple excision with an infiltrative tumor border had a higher recurrence rate. A nomogram developed based on clinicopathologic features and surgical approaches could predict recurrence‐free survival at 1, 3, and 5 years. For high‐risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, degree of stromal cell hyperplasia, and atypia can be applied for patient counseling and clinical management. The efficacy of adjuvant radiotherapy remains uncertain.

Qigong is a gentle exercise that promotes health and well-being. This study evaluated the acute physiological and psychological effects of one session of qigong exercise in older practitioners. A total of 45 participants (mean age, 65.14 years) were recruited. Meridian electrical conductance, State-Trait Anxiety Inventory (STAI), heart rate variability (HRV), and Short Form 36 (SF-36) were evaluated and compared before and after one session of qigong exercise. The results revealed that the electrical conductance of all meridians, except spleen and bladder meridians, increased significantly (p<0.05). Compared with baseline values, upper to lower body ratio and sympathetic/vagal index were significantly improved and closer to 1 (p=0.011 and p=0.007, resp.). STAI-S and STAI-T scores decreased significantly (p<0.001 and p=0.001, resp.). The RR interval of HRV decreased significantly (p=0.035), a significant positive correlation was observed between kidney meridian electrical conductance and SF-36 physical scores (r=0.74, p=0.018), and a positive correlation was observed between pericardium meridian electrical conductance and SF-36 mental scores (r=0.50, p=0.06). In conclusion, one session of qigong exercise increased meridian electrical conductance, reduced anxiety, and improved body and autonomic nervous system balance. These findings provide scientific evidence for acute physiological and psychological effects of qigong exercise in older practitioners.

The difference in compatibility at the molecular level can lead to a change of microphase separation structure of thermoplastic polyurethanes blend systems, which will improve their thermal and mechanical properties. In this study, TDI-polyester based TPU was blended with MDI-polyether-based TPU and MDI-polyester based TPU, with different ratios. In the blend system, the obvious reduction of the melting temperature of the high-temperature TDI-polyester based TPU component indicates its hard segments can be mutually integrated with the other component. For TDI-polyester based TPU/MDI-polyether based TPU blends, their similar hard segment ratio and similar chemical structure of the soft segment give the molecular chains of the two components better compatibility. The aggregation structure of the two kinds of chains can rearrange at the molecular level which makes the hard domains mutually integrate to form a new phase separation structure with larger phase region distance. As a result, the yield strength of this blend increased by almost 143% when the elongation at break was only reduced by 12%. In contrast, the other group of blends still partly maintain their respective micro domains, forming a weak interface and leading to a decreased of elongation at break.

with the development of space exploration, the resolution of optical system is required to be higher and higher. According to the Rayleigh criterion, the resolution of the optical system is directly proportional to the aperture. However, due to the influence of processing capacity and size of the rocket fairing, it is difficult to achieve one single large aperture. Therefore, the scheme of using small size segmented-mirror to achieve one large aperture becomes an effective form. Because location difference between the deployment and the ideal position, the imaging quality will be affected, and cannot be imaged in serious case. For the analysis of influence of the position error on the imaging quality, the traditional method is to analyze on the optical transfer function and Strehl ratio in theory, ignoring the influence of various aberrations that cannot be corrected by the optical system itself. In this paper, the segmented-mirror primary mirror system model is established to analyze the influence of the position error and the real influence of the various aberrations of the system, so as to complete the analysis of the influence more comprehensively. Through the analysis of different position errors, we can get the final wave-front aberration and Strehl ratio of the system under the influence of position error, which can be used as a reference for the analysis of position error influence of segmented-mirror primary mirror form and sparse aperture form of large aperture optical system in the future.

A structure of suppressing stray light of space-based infrared optical system was designed. In order to reduce the internal radiation, reflective baffles and traditional baffles were designed. The system of reflective baffles described here consist of vanes whose outward facing surfaces are ellipsoids and whose backward facing surfaces are hyperboloids of one sheet. Software tracepro was also used to build the system model and simulate analysis of the system. According to the simulated dates, the PST curve was drawn. The results indicate that stray light off axis was well suppressed. Thermal radiation of the system respectively at different temperature were also simulated. When the temperature was down below 115 K, the illumination of target that gets to imager is an order of magnitude higher than the internal thermal radiation that gets to imager. The results indicate that thermal radiation was also well suppressed.

Background/objective The term macrosomia is used to describe neonates with a birth weight of 4000 g or more. Macrosomia is a potential risk factor for obesity and metabolic syndromes in postnatal and adult life, yet little is known about its associations with metabolic difference in the early age. We performed metabolic profiling of umbilical cord blood to discover differential metabolites of macrosomia. Methods We conducted a case-control study of full-term singletons with normal maternal glucose tolerance [50 cases (macrosomia, birth weight ⩾4000 g); 50 controls (normal weight, birth weight 2500-3999 g)]. Metabolites in umbilical cord blood were detected using an untargeted metabolomic approach based on gas chromatography/mass spectrometry. We performed logistic regression to evaluate the associations between metabolites and macrosomia. We also performed pathway analysis based on KEGG and MBRole. Results Compared with controls, the macrosomia cases had a greater male proportion, gestational age, paternal body mass index (BMI) and maternal pre-pregnancy BMI. Forty-two metabolites differed between the cases and controls. After multivariable adjustment, 2-methylfumarate [adjusted odds ratio (AOR)=1.232, 95% confidence interval (CI): 1.102-1.376], uracil (AOR=38.494, 95% CI: 5.635-262.951), elaidic acid (AOR=0.834, 95% CI: 0.761-0.915), ribose (AOR=0.089, 95% CI: 0.021-0.378), lactulose (AOR=0.815, 95% CI: 0.743-0.894) and 4-aminobutyric acid (AOR=0.835, 95% CI: 0.764-0.912) remained significantly associated with macrosomia. Pyrimidine metabolism and pentose and glucuronate interconversions were the two top-ranking pathways enriched with those metabolites (-log P-value=3.49 and 2.47, respectively). Conclusion Levels of 2-methylfumarate, uracil, ribose, elaidic acid, lactulose and 4-aminobutyric acid were associated with the incidence of macrosomia. The alteration of pathways involving those factors might be linked with the incidence of macrosomia and relevant metabolic syndromes later in life, and further studies are needed to confirm it and verify the mechanisms.

Good application of metal-organic frameworks (MOFs) on uranium adsorption has attracted increasing attention recently. MIL-53(Al)-AO, synthesized by introducing amidoxime groups to MIL-53(Al)-NH2 aimed to adsorb U(VI), was characterized by scanning electron microscopy, X-ray diffraction, thermogravimetric analysis and fourier transformed infrared spectroscopy. The sorption capacity of MIL-53(Al)-AO for U(VI) in aqueous solutions has been enhanced to 2.36 times compared with MIL-53(Al)-NH2 at pH 6.0 under the same conditions according to the experimental results, possibly due to the strong chelation of amidoxime. Effects of contact time, pH, interfering ions, and U(VI) concentration on the sorption of U(VI) for MIL-53(Al)-AO were also investigated. The sorption was strongly dependent on pH and independent of coexist ions. Result of this study shows that the MIL-53(Al)-AO was a kind of potential material to enrich U(VI) from aqueous solutions, and amidoxime could be introduced to MOFs sorbent by transforming the grafted amino groups on MIL-53(Al)-NH2.

To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. This case–control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital’s database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P

Background: Cardiovascular diseases (CVDs) are serious public health issues and the burden of CVDs is at alarmingly high level in China. The aim of the current study was to estimate the prevalence of CVDs and modifiable risk factors, and explore the association of risk factors, risk factor clustering with CVDs among Nanjing adults from eastern China. Methods: A population-based cross-sectional survey was conducted by a stratified clustered sampling between June and November 2011. A representative sample of 40,896 residents aged over 18 years was interviewed by face-to-face questionnaire survey, anthropometric measurements and laboratory examinations. The prevalence of CVDs including coronary heart disease (CHD) and stroke was determined according to a participant’s self-report. Multivariable logistic regression models were used to estimate the relationship between relevant risk factors, their clustering and CVDs. Results: The weighted prevalence of self-reported in the entire population was 1.1% for CHD; and 1.4% for stroke. The weighted prevalence of hypertension, diabetes, dyslipidemia, overweight or obesity, and current smoking was 25.0%, 6.7%, 29.6%, 35.9% and 24.5%, respectively. In multivariable-adjusted models, higher levels of body mass index, systolic blood pressure and fasting plasma glucose could be associated with increased risks of CHD and stroke, whereas higher level of high-density lipoprotein cholesterol could be related to lower risks of CHD. Hypertension, diabetes and dyslipidemia were likely to be positively associated with self-reported CVDs regardless of genders in multivariable logistic regression models. Participants with CVDs had significant higher proportion of at least two of CVD risk factors than their counterparts without CVDs. Compared to those having no risk factor; adults with one, two, three or more CVD risk factors had possibly gradually increased risks of CHD and stroke in both genders. Conclusion: Higher regional prevalence of CVDs was likely to be synergistic effects of risk factors aggregation. Therefore, multifactorial intervention strategies based on associated risk factors may be available for prevention and control of CVDs in Chinese population. Keywords: Cardiovascular diseases, Risk Factors, Prevalence, Coronary heart disease, Stroke, China

Primary liver cancer accounts for the third most deadly type of malignant tumor globally, and approximately 80% of the cases are hepatocellular carcinoma (HCC), which highly relies on the activity of hypoxia responsive pathways to bolster its metastatic behaviors. MicroRNA-29a (MIR29A) has been shown to exert a hepatoprotective effect on hepatocellular damage and liver fibrosis induced by cholestasis and diet stress, while its clinical and biological role on the activity hypoxia responsive genes including LOX, LOXL2, and VEGFA remains unclear. TCGA datasets were retrieved to confirm the differential expression and prognostic significance of all genes in the HCC and normal tissue. The Gene Expression Omnibus (GEO) dataset was used to corroborate the differential expression and diagnostic value of MIR29A. The bioinformatic identification were conducted to examine the interaction of MIR29A with LOX, LOXL2, and VEGFA. The suppressive activity of MIR29A on LOX, LOXL2, and VEGF was verified by qPCR, immunoblotting, and luciferase. The effect of overexpression of MIR29A-3p mimics in vitro on apoptosis markers (caspase-9, -3, and poly (ADP-ribose) polymerase (PARP)), cell viability and wound healing performance were examined using immunoblot and a WST-1 assay and a wound healing assay, respectively. The HCC tissue presented low expression of MIR29A, yet high expression of LOX, LOXL2, and VEGFA as compared to normal control. Serum MIR29A of HCC patients showed decreased levels as compared to that of normal control, with an area under curve (AUC) of 0.751 of a receiver operating characteristic (ROC) curve. Low expression of MIR29A and high expression of LOX, LOXL2, and VEGFA indicated poor overall survival (OS). MIR29A-3p was shown to target the 3′UTR of LOX, LOXL2, and VEGFA. Overexpression of MIR29A-3p mimic in HepG2 cells led to downregulated gene and protein expression levels of LOX, LOXL2, and VEGFA, wherein luciferase reporter assay confirmed that MIR29A-3p exerts the inhibitory activity via directly binding to the 3′UTR of LOX and VEGFA. Furthermore, overexpression of MIR29A-3p mimic induced the activity of caspase-9 and -3 and PARP, while it inhibited the cell viability and wound healing performance. Collectively, this study provides novel insight into a clinical-applicable panel consisting of MIR29, LOX, LOXL2, and VEGFA and demonstrates an anti-HCC effect of MIR29A via comprehensively suppressing the expression of LOX, LOXL2, and VEGFA, paving the way to a prospective theragnostic approach for HCC.

Background: A retrospective analysis of diagnoses was performed in patients with phyllodes tumors of the breast (PTB) who received preoperative core needle biopsy (CNB) and had breast surgery at Fudan University Shanghai Cancer Center from January 1, 2002 to April 1, 2013. The resulting data allowed us to compare the accordance between CNB and excision diagnoses of PTB patients and evaluate the accuracy of CNB in preoperative diagnosis. Methods: Data from 128 patients with PTB who had undergone preoperative CNB and breast surgery were retrospectively analyzed. We reviewed the medical history, clinical follow-up data, and CNB diagnostic data. A diagnostic test was used to evaluate the sensitivity and specificity of CNB in diagnosing benign, borderline, and malignant phyllodes tumors. Results: The accuracy of CNB for diagnosing PTB was 13.3% (17/128). Of the remaining patients, 98 (75.5% of the PTB patients) were diagnosed with fibroadenoma or fibroepithelial lesions. The sensitivity of CNB at diagnosing benign, borderline, and malignant phyllodes tumors were 4.9% (2/41), 4.2% (3/71), and 25.0% (4/16), respectively, whereas the corresponding specificity were 92.0%, 98.2%, and 100%, respectively. Some clinical features, such as large tumor size, rapid growth, or surgical history of fibroadenomas, were indicative of an increased possibility of PTB. Conclusions: CNB provides a pathological basis for the preoperative diagnosis of PTB, but it has a poor accuracy and offers limited guidance for surgical decisions. Considering CNB along with multiple histologic features may improve the ability to accurately diagnose PTB. An integrated assessment using CNBs in combination with clinical data and imaging features is suggested as a reliable strategy to assist PTB diagnosis.

Jiayang He,1 Ping Fang,2 Xiang Zheng,2 Chenchen Wang,2 Tenghui Liu,2 Bowen Zhang,2 Jian Wen,2 Ren-ai Xu3 1Department of Pharmacy, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China; 2Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang, China; 3Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Aim: The aim of this study was to study the effect of celecoxib on agomelatine metabolism in vitro and in vivo. Methods: Ten healthy male Sprague–Dawley rats were randomly divided into 2 groups: Group A (control group) and Group B (30 mg/kg celecoxib). Then a single dose of 20 mg/kg agomelatine was administered orally 30 min after administration of celecoxib. In an in vitro study, celecoxib with a series of concentrations was added to an incubation mixture containing recombinant human CYP2C9, human or rat liver microsomes to determine the half-maximal inhibitory concentration on the metabolism of agomelatine. Moreover, a mechanism study was performed to determine the inhibitory effect of celecoxib on CYP2C9. Results: The results showed that a single dose of 30 mg/kg celecoxib significantly increased the area under the concentration-time curve and maximum concentration of agomelatine. In addition, celecoxib inhibited the metabolism of agomelatine in the in vitro studies, which was determined to be by a competitive mechanism on CYP2C9. Those results indicated that celecoxib has an inhibitory effect on the metabolism of agomelatine both in vivo and in vitro. Conclusion: Thus, more attention should be paid when celecoxib is administered combined with agomelatine. Keywords: agomelatine, liver microsomes, pharmacokinetics, celecoxib, CYP2C9

1. Cytochrome P450 3A4 (CYP3A4) is an important member of the cytochrome P450 enzyme superfamily, with 33 allelic variants reported previously. Genetic polymorphisms of CYP3A4 can produce a significant effect on the efficacy and safety of some drugs, so the purpose of this study was to clarify the catalytic characteristics of 22 CYP3A4 allelic isoforms, including 6 novel variants in Han Chinese population, on the oxidative metabolism of amiodarone in vitro. 2. Wild-type CYP3A4*1 and other variants expressed by insect cells system were incubated respectively with 10-500 μM substrate for 40 min at 37 °C and terminated at -80 °C immediately. Then these samples were treated as required and detected with ultra-performance liquid chromatography-tandem mass spectrometry used to analyze its major metabolite desethylamiodarone. 3. Among the 21 CYP3A4 variants, compared with the wild-type, the intrinsic clearance values (Vmax/Km) of two variants were apparently decreased (11.07 and 2.67% relative clearance) while twelve variants revealed markedly increased values (155.20∼435.96%), and the remaining of seven variants exhibited no significant changes in enzyme activity. 4. This is the first time report describing all these infrequent alleles for amiodarone metabolism, which can provide fundamental data for further clinical studies on CYP3A4 alleles.