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Continental marginal seas are key reservoirs of anthropogenic pollutants. Understanding the physical processes controlling the air–sea exchange dynamics of polychlorinated biphenyls (PCBs) in the continental margin seas is crucial to constrain the contribution of PCBs from land and rivers to the ocean; however, the transport and fate of PCBs, and their controlling factors of air–sea exchange in the continental marginal seas still remain poorly understood. Here, we collected atmospheric and surface water samples from the Yellow Sea (YS) and East China Sea (ECS) in summer 2018 and winter 2019, and examined the PCB concentrations. The PCB air–sea gas exchange fluxes showed higher net volatilization in winter, largely due to southward movement of the strengthened Yellow Sea Coastal Current and Yangtze River Diluted Water with high PCB concentrations. Both the dissolved PCB concentrations in seawater and wind speed were the primary factors influencing the PCB air–sea exchange fluxes in winter. By contrast, weak PCB volatilization fluxes occurred when the Taiwan Warm Current with low PCB concentrations dominated in the ECS in summer. In comparison, the accumulation and release of some PCB homologues caused by a green tide in the coastal YS could lead to increased volatilization flux in summer. Our results suggest the transfer of air–sea exchange dynamics of PCBs from a water concentration‐dominated pattern to an environmental parameter‐controlled one due to their decreased land‐based input, and highlight the impact of water mass‐triggered changes (environmental parameters and algal blooms) on the air–sea exchange behavior of PCBs in the continental marginal sea. Plain Language Summary: Polychlorinated biphenyls (PCBs) are a kind of persistent organic pollutants, harmful to the physical health and marine ecology. Seawater acts as a reservoir for PCBs. PCBs in surface seawater could be released to the atmosphere. We found that ocean current greatly impacts the volatilization flux of PCBs from seawater to the atmosphere. The seasonal variation of ocean current in the East China Marginal Seas (ECMS) are complex. In winter, strong coastal currents and rivers brought a bulk of PCBs to the ECMS and contributed to a strong PCB volatilization flux; while in summer, clean ocean current dominated the ECMS and thus caused less PCB volatilization. The green tide could lead to a significant PCB volatilization due to degradation of microorganisms. This work highlights the importance of ocean currents and microorganism in seawater on the air–sea exchange dynamics of PCBs in the continental marginal sea. Key Points: Seasonal transport of ocean currents determined the dynamics of polychlorinated biphenyls (PCBs) air–sea exchange in the continental marginEnvironmental parameters are more important for the dynamics of PCB air–sea exchange over the remote sea areas than over the coastal watersDechlorination process could lead to significant volatilization flux of tetra‐CB [ABSTRACT FROM AUTHOR]

Abstract: This study is to examine the attitudes of students towards the case studies based on mobile messaging in a pharmacotherapy introduction class. Case studies were divided into 4 groups, with 30 pharmacy students each group. Each group was required to share pharmaceutical care plans on WeChat by posting messages. A post‐activity survey was conducted: Over 70% of the students agreed that mobile messaging‐based case studies (MMBC) helped developing skills and knowledge and stimulating additional research and readings. Over 60% of the students felt that MMBC helped understanding others' viewpoints and sharing their experience and knowledge. More than half of the students agreed that MMBC was more convenient than traditional and internet‐based case study. Less than 30% of the students agreed that the interaction with other students was good. The findings reflect the MMBC studies' popularity with students. Recommendations to use MMBC studies include (a) balance the merits, such as expressing opinions clearly and concisely, allowing for collaborative learning, with the drawbacks: distraction and the low quality of interactions; (b) use small groups for case discussion; (c) design a collaborative schedule dividing the discussion into different sections. [ABSTRACT FROM AUTHOR]

Modern environmental and climatological studies produce multiple outcomes at high spatial resolutions. Multivariate spatial modeling is an established means to quantify cross-correlation among outcomes. However, existing models typically suffer from poor computational efficiency and lack the flexibility to simultaneously estimate auto- and cross-covariance structures. In this article, we undertake a novel construction of covariance by utilizing spectral convolution and by imposing an inverted Wishart prior on the cross-correlation structure. The cross-correlation structure with this functional inverted Wishart prior flexibly accommodates not only positive but also weak or negative associations among outcomes while preserving spatial resolution. Furthermore, the proposed model is computationally efficient and produces easily interpretable results, including the individual autocovariances and full cross-correlation matrices, as well as a partial cross-correlation matrix reflecting the outcome correlation after excluding the effects caused by spatial convolution. The model is examined using simulated data sets under different scenarios. It is also applied to the data from the North American Regional Climate Change Assessment Program, examining long-term associations between surface outcomes for air temperature, pressure, humidity, and radiation, on the land area of the North American West Coast. Results and predictive performance are compared with findings from approaches using convolution only or coregionalization. [ABSTRACT FROM AUTHOR]

Background Gut microbial community, which may influence our mood, can be shaped by modulating the gut ecosystem through dietary strategies. Understanding the gut-brain correlationship in healthy people is important for maintenance of mental health and prevention of mental illnesses. Methods A case study on the correlation between gut microbial alternation and mood swing of healthy adults was conducted in a closed human life support system during a 105-day experiment. Gut microbial community structures were analyzed using high-throughput sequencing every 2 weeks. A profile of mood states questionnaire was used to record the mood swings. Correlation between gut microbes and mood were identified with partial least squares discrimination analysis. Key Results Microbial community structures in the three healthy adults were strongly correlated with mood states. Bacterial genera Roseburia, Phascolarctobacterium, Lachnospira, and Prevotella had potential positive correlation with positive mood, while genera Faecalibacterium, Bifidobacterium, Bacteroides, Parabacteroides, and Anaerostipes were correlated with negative mood. Among which, Faecalibacterium spp. had the highest abundance, and showed a significant negative correlation with mood. Conclusions & Inferences Our results indicated that the composition of microbial community could play a role in emotional change in mentally physically healthy adults. [ABSTRACT FROM AUTHOR]

In this study, we aimed to investigate whether progesterone-induced acrosome reaction ( AR) rate could be an indicator for fertilisation rate in vitro. Twenty-six couples with unexplained infertility and undergoing in vitro fertilisation ( IVF) treatment were involved. On the oocytes retrieval day after routine IVF, residual sperm samples were collected to receive progesterone induction (progesterone group) or not (control group). AR rate was calculated and fertilisation rate was recorded. The correlation between progesterone-induced AR and fertilisation rate and between sperm normal morphology and 3 PN (tripronuclear) were analysed using the Spearman correlation analysis. The AR rate of progesterone group was statistically higher than that of the control group (15.6 ± 5.88% versus 9.66 ± 5.771%, P < 0.05), but not significantly correlated with fertilisation rate ( r = −0.053, P > 0.01) or rate of high-quality embryo development ( r = −0.055, P > 0.01). Normal sperm morphology also showed no significant correlation with the amount of 3 PN zygotes ( r = 0.029, P > 0.01), rate of 3 PN zygotes production ( r = 0.20, P > 0.01), rate of 3 PN embryo development ( r = −0.406, P > 0.01), fertilisation rate ( r = −0.148, P > 0.01) or progesterone-induced AR rate ( r = 0.214, P > 0.01). Progesterone can induce AR in vitro significantly; however, the progesterone-induced AR may not be used to indicate fertilisation rate. [ABSTRACT FROM AUTHOR]

An abstract of the article "Clinical value of fetal echocardiography in diagnosis of fetal cardiac structural abnormalities" by Y. Guo and colleagues is presented.

Objective/hypothesis: Adenoviral interleukin-2 (AdV-IL-2) gene therapy has previously not proven effective in treating established murine oral cancer. We hypothesize that the intratumoral level of IL-2 expression is a major limiting factor in treatment outcome.Methods: A microscopic disease and established oral cancer murine model was used to test this hypothesis. IL-2 gene transfer was performed with a recombinant adenovirus vector.Results: Tumor cells were transduced in vitro with AdV-IL-2 and subsequently implanted into the floor of the mouth in C3H/HeJ mice. IL-2 expression in vitro ranged from 990 to 1,050 pg/10(6) tumor cells. This microscopic disease treatment resulted in either complete tumor regression or a dramatic decrease in tumor progression. Cytolytic T-cell (CTL) assays demonstrated a predominance of CD8-specific, T-cell-mediated tumor killing. Reducing IL-2 expression by half with a mixture of 1:1 transduced to nontransduced tumor cells eliminated the antitumor effect and decreased the CTL response. These findings support the presence of a critical "threshold" of IL-2 expression. Adenovirus repurification and amplification allowed isolation of a twofold-higher-titer AdV-IL-2 vector. Treatment of established tumors with the higher-titer AdV-IL-2 at a new maximal dose of 1.4 x 10(9) plaque-forming units (pfu) increased in vivo IL-2 expression to 1,127 pg/10(6) cells and generated a significant antitumor response. Complete regression of established tumors, however, could not be achieved, and we noted a decrease in IL-2 expression well below the threshold at 1 week after treatment. Upon repeat maximal AdV-IL-2 injection in vivo, a greater antitumor effect and increased CTL response was seen, but also, 28% of the animals died of IL-2 toxicity.Conclusion: Although limited by expression and toxicity as a single-treatment strategy for established tumors, AdV-IL-2 gene therapy should be considered a potential component of combination therapy strategies. [ABSTRACT FROM AUTHOR]

An effective "suicide gene" therapy strategy in experimental studies has been the use of the herpes simplex virus thymidine kinase gene (HSV-tk) to sensitize tumors to the cytotoxic effects of ganciclovir administration. Previous studies using this model have focused on utilizing maximal viral titers and high levels of ganciclovir that are not compatible with human dosing. Because of the high ganciclovir doses and the maximal viral titers, this strategy has limited application to actual clinical scenarios. In the following studies the authors investigate tumor regression in an oral squamous cell carcinoma animal model as a function of variable adenoviral titers and more physiologic ganciclovir dosing. Using adenoviral titers ranging from 1 x 10(8) to 2 x 10(9) plaque forming units (pfu) to treat oral tumors, they found no statistical difference in tumor regression among the different viral doses, despite differences in mitotic activity. Each treatment group, however, demonstrated a significant effect on tumor regression when compared with controls. Furthermore, the authors were able to reduce the level of ganciclovir administration to 10 mg/kg twice daily from established levels of 100 to 150 mg/kg twice daily while maintaining significant tumor responses to the HSV-tk therapy. Mean survival of animals treated with this lower ganciclovir dose was significantly higher than in controls and was equal to established means based on previous studies using higher ganciclovir doses. The optimization of this suicide gene therapy strategy is imperative in order to minimize theoretical and known viral and ganciclovir toxicities while establishing a foundation upon which to design appropriate and effective clinical trials. [ABSTRACT FROM AUTHOR]

Background and purpose Recent studies found that microembolic signals ( MESs) could be detected by transcranial Doppler in patients with moyamoya disease. However, the clinical significance of MESs in moyamoya disease remains unclear. Our aim was to investigate whether the MESs could predict cerebral ischaemic events in patients with moyamoya disease. Methods Fifty-four consecutive patients with moyamoya disease were recruited. MESs were monitored by transcranial Doppler for 30 min in the bilateral middle cerebral arteries of each patient on admission. Patients were followed up for 1 year. The primary end-point was cerebral ischaemic events including stroke and transient ischaemic attack ( TIA). Results MESs were detected in 11 (20.4%) patients, with a frequency of 11 (10.2%) in 108 hemispheres. Logistic regression analysis revealed that previous ischaemic events within 3 months were associated with the presence of MESs (odds ratio 4.41, 95% CI 1.11-17.59). During a median follow-up of 384 days, 14 (13.0%) hemispheres had ischaemic events (seven strokes and seven TIAs). Cox regression showed that the hazard ratio for the risk of new ischaemic stroke and TIA in the hemispheres with MESs was 6.84 (95% CI 1.82-25.66) compared with those without, and 10.61 (95% CI 1.66-67.70) for ischaemic stroke alone, after controlling for age, sex, presence of ischaemic events at baseline, Suzuki stages and revascularization surgery. Conclusions In patients with moyamoya disease, the presence of MESs is associated with recent ischaemic symptoms and independently predicts cerebral ischaemic events. MES detection may be of potential clinical value in the management of patients with moyamoya disease. [ABSTRACT FROM AUTHOR]

Silicon (Si) can increase plant defence systems against abiotic and biotic stress, but there is little information on UV-B radiation stress alleviation by Si for field crops. Using soybean ( Glycine max (L.) Mell) seedlings, we determined how Si may mediate UV-B radiation stress by studying changes in biomass, physiological attributes and antioxidants' activities. The seedlings were raised with 0, 1.70 and 2.55 m of Si in the growth chamber under ambient, ambient +2.7 kJ mday and ambient +5.4 kJ mday of UV-B radiation. As expected, plants suffered severe growth limitations under UV-B radiation, but Si alleviated these limitations through improvements in leaf area (LA) and root-to-shoot ratio (R/S). The UV-B radiation stress reduced the LA by 73.9-94.7%, total dry weight (TDW) by 11.8-36.6% and R/S by 9.2-30.2% but induced the activities of soluble protein by 18.4-21.0%, catalase (CAT) by 22.7-54.2%, superoxide dismutase (SOD) by 31.9-63.1%, and peroxidases (POD) by as much as 162.9-381.6%. Further confirmation of stress alleviations by Si was noted from reductions in these stress signals (antioxidant activities) under UV-B radiation: CAT decreased significantly by 78.3-79.4%, SOD by 5.3-7.2% and POD by 49.9-61.9% in silicon-treated UV-B stressed soybean. [ABSTRACT FROM AUTHOR]

Coronatine (COR) is a new plant growth regulator that mimics the biological activities of methyl jasmonate. We determined whether COR enhanced chilling tolerance of cucumber ( Cucumis sativus L. cv. Jinchun 4) seedlings and if such tolerance was correlated with changes in the activity of antioxidant enzymes. COR was applied to seedlings at two-leaf stage at 0 (Control), 0.1, 1, 10, and 100 nm. Seedlings were then subjected to chilling stress at 5 ± 1 °C for 4 days. Seedlings treated with COR showed significant higher tolerance to chilling stress and the optimal concentration was 1–10 nm. Compared with control, the chilling injury index (CII) of the seedlings treated with COR at 1 and 10 nm was decreased by 44.9 % and 24.5 %, respectively, while the membrane chilling stability (MCS) expressed as the change of relative conductance was increased by 37.2 % and 17.0 %, respectively. The malondialdehyde (MDA) content in leaves treated with COR at 1 nm was decreased by 39.7 %, and the O2− production rate and H2O2 content reduced by 28.6 % and 8.5 %, respectively. Treatment with COR at 1 nm increased the activities of superoxide dismutase (SOD) in leaves by 34.4 %, catalase (CAT) by 58.7 % and ascorbate peroxidase (APX) by 23.0 % under low temperature. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities were also significantly improved by 28.9 % and 21.3 % following treatment with COR at 1 and 10 nm, respectively. The overall results suggest that COR enhanced chilling tolerance in cucumber seedlings by improving the antioxidative defence system. [ABSTRACT FROM AUTHOR]

We explored the effects of recombinant A-box (rA-box), a specific blockade for endogenous high mobility group box 1 (HMGB1) protein, on acute lung inflammation induced by lipopolysaccharide (LPS) in vivo. Acute lung injury (ALI) was produced successfully by intratracheal administration of LPS (10 μg/mouse) in male BALB/ c mice. rA-box (0.3, 0.6 mg/mouse, i.p.) was administered 30 min prior to or 2 h after LPS exposure. Bronchoalveolar lavage fluid (BALF) was obtained to measure chemokines, proinflammatory cytokines, total cell counts and proteins at the indicated time points. It was found that rA-box caused a significant reduction in the total cells and neutrophils in BALF, a significant reduction in the W/D ratio and protein leakage at 24 h after LPS challenge. In addition, rA-box was also believed to have downregulated the expression of LPS-induced chemokines (keratinocyte-derived chemokine) and proinflammatory cytokines, including early mediator TNF-a and late mediator HMGB1. These findings confirm the significant protection of rA-box against LPS-induced ALI, and the effect mechanism of rA-box was associated with decreasing the expression of chemokines and proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Although some tissue-specific cis-acting elements have been identified, the molecular mechanisms of tissue-specific gene expression remain elusive. Here, we report the identification by a yeast one-hybrid screen of five proteins, Os10g31330/glycine-rich, Os01g10400/metallothionein-like, Os05g51180/nucleic acid-binding, Os05g37930/unknown and Os01g01689/phosphatidylinositol kinase that bound to either the positive or negative tissue-specific cis elements of a rice promoter from the green tissue-specific D54O gene. These proteins are localised in the nucleus and the genes encoding them are differentially expressed in different tissues, further suggesting their putative roles in regulating gene expression. These results suggest that the green tissue-specific expression of the D54O gene may be regulated by the interaction of multiple proteins with cis elements in the promoter region. [ABSTRACT FROM AUTHOR]

We studied the effects of coronatine (COR), a structural and functional analogue of jasmonates, on the drought tolerance of two rice cultivars, Handao 297 (a drought-tolerant upland rice) and Yuefu (a drought-sensitive lowland rice). Seedlings were treated with COR at the three-leaved stage at 0.01 and 0.1 μm for 24 h, followed by imposition of water deficit induced with 20 % polyethylene glycol (PEG). Water stress reduced the biomass of both cultivars and increased leaf lipid peroxidation and solute leakage. Pre-treatment with COR significantly increased the activities of superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase in leaf tissues of water-stressed Handao 297 (0.01 μm) and Yuefu (0.1 μm) seedlings. COR supplement also increased the accumulation of 44 and 32 kDa polypeptides in water-stressed Handao 297 (0.01 and 0.1 μm) and Yuefu (0.1 μm) and significantly induced the expression of 29 kDa polypeptide in Handao 297. The results suggest that COR might alleviate drought stress by activating antioxidant enzymes and inducing proteins, thereby preventing membrane peroxidation and denaturation of bio-molecules. Thus, membrane permeability decreased substantially by 24–27 % in Handao 297, and 22–29 % in Yuefu. The optimal concentrations conferring drought resistance were 0.01 for the upland rice and 0.1 μm for the lowland cultivar. [ABSTRACT FROM AUTHOR]

Chemical regulation using plant growth regulators has proved to be potentially beneficial in water-saving agriculture. This experiment was conducted with winter wheat ( Triticum aestivum L. cv. ‘Jingdong 6’) to study the effect of chemical regulation on alleviation of water deficit stress during the grain filling stage. Uniconazole, a plant growth regulator, was foliar sprayed at 85 % (adequate irrigation) and 60 % (deficit irrigation) field capacity. Results showed that the distribution of 3H-H2O in roots and flag leaf, characteristics of vascular bundle in primary roots and internode below spike, roots activity, transpiration rate and stomatal conductance of flag leaf were negatively affected by deficit irrigation after flowering. Foliar spraying at the early jointing stage with 13.5 gha−1 uniconazole was able to relieve and compensate for the harmful effects of deficit irrigation. Both the area of vascular bundle in primary roots and internode below the ear were increased by uniconazole, while root viability and their ability to absorb and transport water were increased. In the flag leaf, stomatal conductance was reduced to maintain the transpiration rate and water use efficiency (WUE) measured for a single wheat plant was higher. Uniconazole increased WUE by 25.0 % under adequate and 22 % under deficit irrigations. Under adequate irrigations, the 14C-assimilates export rate from flag leaf in 12 h (E12h) was increased by 65 % and 36 % in early and late filling stages, while under deficit irrigations, the E12h of uniconazole-treated plants exceeded that of control plants by 5 % and 34 % respectively. Physiological damages caused by water deficiency during the grain filling stage of wheat was alleviated by foliar spraying with uniconazole. [ABSTRACT FROM AUTHOR]

The objective was to study soil water conservation and physiological growth of wheat ( Triticum aestivum L.) using composted cattle manure applied either as mulch or incorporated with soil at 20 Mg ha−1. Haruhikari, a relatively drought-sensitive and Hongmangmai, a relatively drought-tolerant wheat, were the cultivars studied under both adequate and deficit irrigation. Fourteen weeks after sowing (WAS), the number of tillers and leaves was significantly reduced by 19 % and 30 % respectively under deficit irrigation and Hongmangmai produced slightly (10 %) more tillers than Haruhikari. Unlike mulching, the incorporation of manure had favourable effects on plants in terms of shoot dry mass (SDM) by 36 % and number of tillers and leaves by 40 %. Haruhikari produced substantially (29 %) greater root mass under adequate irrigation but Hongmangmai produced slightly (2.7 %) more roots and responded much better to manure use whether under adequate or deficit irrigation. As a result, Hongmangmai suffered less severe reductions in tillers and biomass under water stress. In comparison, the mulched manure treatment saved 15 % and 64 % respectively more water than the control and the treatment incorporating manure, but this advantage in water-saving did not translate to superior plant growth. Leaf water potential (ψl) under adequate irrigation significantly exceeded that under deficit irrigation by 27 % and the ψ l of Haruhikari exceeded that of Hongmangmai by 15 %. However, Hongmangmai may be considered more tolerant of dehydration since it maintained much higher net photosynthetic rates (PN) even with a lower leaf water potential. The reduction in the PN and intracellular carbon dioxide concentration (Ci) of the cultivars under deficit irrigation was on account of decreasing stomatal conductance (gs) and transpiration rate but on average, the gs of Hongmangmai significantly exceeded that of Haruhikari by as much as 0.53 under adequate irrigation and 0.22 under deficit irrigation. In conclusion, we suggest that the drought tolerance of Hongmangmai was related to its superior root growth and greater ability than Haruhikari, to efficiently utilize incorporated manure for growth under water stress. [ABSTRACT FROM AUTHOR]

Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) activities are modulated in a manner that reflects the secretory demand on β cells to integrate long- and short-term nutrient sensing information. Our studies have focused on the mechanisms of ERK1/2 activation in β cells and on the actions of ERK1/2 that regulate β cell function. Insulin and growth factors regulate ERK1/2 in β cells in a largely calcium-independent manner. Nutrients and anticipatory hormones, in contrast, activate ERK1/2 in a calcium-dependent manner in these cells. We are exploring the key intermediates in these distinct activation pathways and find that calcineurin is essential for the nutrient pathway but is not essential for the growth factor pathway. Using reporter assays, heterologous reconstitution, electrophoretic mobility shift assays, Northern analysis, Q-PCR and chromatin immunoprecipitation, we have examined several genes that are regulated by ERK1/2, primarily the insulin gene and the apoptotic factor C/EBP-homologous protein (CHOP)-10 (GADD153/DDIT-3), a bZIP protein. ERK1/2-sensitive transcriptional regulators common to these two genes are C/EBP-β and MafA. The insulin promoter is both positively and negatively regulated by glucose and other nutrients. Exposure to glucose for minutes to hours causes an increase in the rate of insulin gene transcription. In contrast, exposure to elevated glucose for 48 h or more results in inhibition of the insulin gene promoter. Both of these processes depend on ERK1/2 activity. Expression of CHOP is induced by stresses including nutrient deprivation and endoplasmic reticulum stress. CHOP gene expression, especially that regulated by nutrients, is also ERK1/2-dependent in β cells, These studies support the hypothesis that the genes regulated by ERK1/2 and the mechanisms employed are key to maintaining normal β cell function. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of the γ-secretase inhibitors (GSIs) on the growth of human tongue carcinoma cells and to provide the molecular mechanism for potential application of GSIs in the treatment of tongue carcinoma. Materials and methods: Human tongue carcinoma Tca8113 cells were cultured with the GSI L-685 458. Cell growth was determined by the methylthiazole tetrazolium method. Cell cycle and apoptosis were analyzed by flow cytometry and/or confocal microscopy. RT-PCR and Western blot were employed to determine the intracellular expression levels. Nuclear factor kappa B (NF- κB) activation was examined by electrophoretic mobility shift assay. Results: L-685,458 dose-dependently inhibited the growth of human tongue carcinoma Tca8113 cells by inducing G0–G1 cell cycle arrest and apoptosis. The mRNA and protein levels of Hairy/Enhancer of Split-1, a target of Notch activation, were decreased dose-dependently by L-685,458. Furthermore, L-685,458 down-regulated cyclin D1, B-cell lymphocytic-leukemia proto-oncogene 2 and c-Myc expressions, which are regulated by the transcription factor NF- κB. Coincident with this observation, L-685,458 induced a dose-dependent reduction of constitutive NF- κB activation in Tca8113 cells. Conclusions: The GSI L-685,458 may have a therapeutic value for the treatment of human tongue carcinoma. Moreover, the effects of L-685,458 in tumor inhibition may act partially via the modulation of Notch and NF- κB. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of the gamma-secretase inhibitors (GSIs) on the growth of human tongue carcinoma cells and to provide the molecular mechanism for potential application of GSIs in the treatment of tongue carcinoma. Materials and methods: Human tongue carcinoma Tca8113 cells were cultured with the GSI L-685 458. Cell growth was determined by the methylthiazole tetrazolium method. Cell cycle and apoptosis were analyzed by flow cytometry and/or confocal microscopy. RT-PCR and Western blot were employed to determine the intracellular expression levels. Nuclear factor kappa B (NF-kappaB) activation was examined by electrophoretic mobility shift assay. Results: L-685,458 dose-dependently inhibited the growth of human tongue carcinoma Tca8113 cells by inducing G0-G1 cell cycle arrest and apoptosis. The mRNA and protein levels of Hairy/Enhancer of Split-1, a target of Notch activation, were decreased dose-dependently by L-685,458. Furthermore, L-685,458 down-regulated cyclin D1, B-cell lymphocytic-leukemia proto-oncogene 2 and c-Myc expressions, which are regulated by the transcription factor NF-kappaB. Coincident with this observation, L-685,458 induced a dose-dependent reduction of constitutive NF-kappaB activation in Tca8113 cells. Conclusions: The GSI L-685,458 may have a therapeutic value for the treatment of human tongue carcinoma. Moreover, the effects of L-685,458 in tumor inhibition may act partially via the modulation of Notch and NF-kappaB. [ABSTRACT FROM AUTHOR]

Background Highly pathogenic avian influenza H5N1 virus has caused increasing human infection in Eurasia since 2004. So far, H5N1 human infection has been associated with over 50% mortality that is partly because of delay of diagnosis and treatment. Objectives and methods Here, we report that an H5N1 influenza virus infected a 31-year-old patient in Shenzhen in June 2006. To identify the possible source of the infection, the human isolate and other H5N1 influenza viruses obtained from poultry and wild birds in southern China during the same period of time were characterized. Results Genetic and antigenic analyses revealed that the human H5N1 influenza virus, Shenzhen/406H/06, is of purely avian origin and is most closely related to viruses detected in poultry and wild birds in Hong Kong in early 2006. Conclusions The findings of the present study suggest that the continued endemicity of H5N1 influenza virus in the poultry in southern China increases the chance for introduction of the virus to humans. This highlights the importance of continued surveillance of poultry and wild birds for determining the source for human H5N1 infection. [ABSTRACT FROM AUTHOR]

Depletion of the protective ozone layer in the atmosphere leads to increasing UV-B radiation on the earth's surface with potential effects on the response of plants to different stresses. Abutilon theophrasti, Amaranthus retroflexus, Digitaria sanguinalis and Chloris virgata are common weeds encountered in most arable fields in China. The effectiveness of herbicides used in controlling these weeds needs to be evaluated with increased UV-B radiation. Seedlings of these four weeds were therefore grown under ambient and elevated UV-B radiation to compare the efficacy of paraquat, a commonly used contact herbicide. Irrespective of species sensitivity to radiation, the elevated UV-B radiation decreased the effectiveness of paraquat. Net photosynthesis rate was adversely affected except for D. sanguinalis, while the chlorophyll content was significantly reduced in A. retroflexus and C. virgata. UV-B treatment increased the leaf surface wax and decreased the absorption of 14C-paraquat in A. theophrasti, D. sanguinalis and C. virgata. These results suggest that the response of weeds to paraquat or the use of the herbicide may be affected by increased UV-B radiation, to the extent that larger doses may be required to achieve desired effects. This may have damaging consequences for the environment. [ABSTRACT FROM AUTHOR]

To study the echocardiographic characteristics and pregnancy outcomes of fetal coronary artery compensatory dilatation, and to explore the clinical value of echocardiography in diagnosis of coronary artery compensatory dilatation (CACD). The CDFI and B-flow techniques of fetal echocardiography can diagnose coronary artery dilatation in prenatal. CACD can be induced by increased coronary blood perfusion in cases of fetal growth restriction, anemia, cerebrovascular diseases, and decompensation of cerebral protective effect. [Extracted from the article]

16-17 July 2010, International AIDS Society's Workshop 'Towards a Cure': HIV Reservoirs and Strategies to Control Them, Vienna, Austria [ABSTRACT FROM AUTHOR]

An abstract of the article "Application value of fetal echocardiography in diagnosing of congenital vascular ring," by Y. Guo and colleagues is presented.

An abstract of the article "Clinical value of transvaginal real-time three-dimensional hysterosalpingo-contrast sonography in the evaluation of tubal patency" by Y. Guo and colleagues is presented.

Background: Peanut allergy is among the most severe and common food allergies. The diagnosis has a significant impact on the quality of life for patients and their families. An effective management approach depends on accurate, safe, and easily implementable diagnostic methods. We previously developed a cell-based assay using Hoxb8 mast cells (Hoxb8 MCs) aimed at improving clinical allergy diagnosis. In this study, we assessed its diagnostic performance by measuring blinded sera from a prospectively enrolled and pre-validated peanut allergy cohort., Methods: Hoxb8 MCs were passively sensitized with sera from peanut-allergic and peanut tolerant children and adolescents (n = 112). Degranulation of Hoxb8 MCs was quantified upon stimulation with dose-titrated peanut extract by means of flow cytometry, using CD107a as activation marker. The results from the Hoxb8 mast cell activation test (Hoxb8 MAT) were compared to established diagnostic assays such as the skin prick test (SPT), specific IgE (sIgE) levels, and the basophil activation test (BAT). Additionally, serum samples from BAT nonresponders were assessed with the Hoxb8 MAT., Results: Hoxb8 MAT displayed a robust dose-dependent activation to peanut extract, with a cutoff value of ≤5.2% CD107a positive cells. The diagnostic accuracy was highest at allergen concentrations ≥100 ng/mL, with an area under the receiver operating characteristic curve (AUROC) of 0.97, 93% sensitivity, and 96% specificity, outperforming traditional SPT and sIgE tests. When compared to BAT, Hoxb8 MAT exhibited comparable diagnostic efficacy. Moreover, sera from BAT nonresponders were accurately classified into allergics and nonallergics by the Hoxb8 MAT., Conclusions: The Hoxb8 MAT demonstrated a very good diagnostic precision in patients prospectively assessed for peanut allergy comparable to the fresh whole blood-based BAT. Additionally, it demonstrated its value for accurate classification of BAT nonresponders into allergic and nonallergic individuals. Further investigations into its utility in the routine clinical setting are warranted., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: This study investigated the long-term clinical and angiographic outcomes of encephaloduroarteriosynangiosis treatment for symptomatic intracranial atherosclerotic arterial steno-occlusive disease to further evaluate the potential therapeutic role of encephaloduroarteriosynangiosis in this population., Methods and Results: A total of 152 adult patients with symptomatic intracranial atherosclerotic arterial steno-occlusive disease who were treated with encephaloduroarteriosynangiosis and intensive medical management across 3 tertiary centers in China between January 2011 and September 2019 were retrospectively included. The primary outcomes were defined as postoperative cerebrovascular events, including ischemic and hemorrhagic stroke. The postoperative neovascularization was analyzed qualitatively and quantitatively by using angiography. Clinical, radiological, and long-term follow-up data were analyzed using Cox regression, logistic regression, and linear regression analyses. Primary outcome rates were 3.2% (5/152) within 30 days, 6.6% (10/152) within 2 years, 9.2% (14/152) within 5 years, and 11.1% (17/152) during a median 9.13 years follow-up. Initial infarction symptoms were positively associated with recurrent ischemic stroke. Additionally, posterior circulation involvement and coexisting cardiac disease indicated poorer neurological status, whereas encephaloduroarteriosynangiosis neovascularization efficacy was negatively associated with older age and vascular risk factors but positively associated with posterior circulation involvement., Conclusions: Encephaloduroarteriosynangiosis plus intensive medical management appears efficacious and safe for symptomatic intracranial atherosclerotic arterial steno-occlusive disease, with low perioperative risk and favorable long-term results. Further prospective trials are needed to verify its efficacy and determine the optimal patient selection criteria.

Background: The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion., Methods and Results: We analyzed the association between qualifying event-the latest ischemic event (transient ischemic attack [TIA] or stroke)-and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P =0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P =0.86) or stroke (6.7% versus 8.9%, P =0.55)., Conclusions: Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

Background: There is limited evidence on the associations of dietary factors and patterns with risk of later-onset ulcerative colitis (UC) in Chinese adults., Aims: To investigate the associations of dietary factors and patterns with risk of later-onset UC in Chinese., Methods: The prospective China Kadoorie Biobank cohort study recruited 512,726 participants aged 30-79. Dietary habits were assessed using food frequency questionnaires. Dietary patterns were derived by factor analysis with a principal component method. Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: During a median follow-up of 12.1 years, 312 cases of newly diagnosed UC were documented (median age of diagnosis 60.1 years). Egg consumption was associated with higher risk of UC (HR for daily vs. never or rarely: 2.29 [95% CI: 1.26-4.16]), while spicy food consumption was inversely associated with risk of UC (HR: 0.63 [0.45-0.88]). The traditional northern dietary pattern, characterised by high intake of wheat and low intake of rice, was associated with higher risk of UC (HR for highest vs. lowest quartile of score: 2.79 [1.93-4.05]). The modern dietary pattern, characterised by high intake of animal-origin foods and fruits, was associated with higher risk of UC (HR: 2.48 [1.63-3.78]). Population attributable fraction was 13.04% (7.71%-19.11%) for daily/almost daily consumption of eggs and 9.87% (1.94%-18.22%) for never/rarely consumption of spicy food., Conclusions: The findings highlight the importance of evaluating dietary factors and patterns in the primary prevention of later-onset UC in Chinese adults., (© 2024 John Wiley & Sons Ltd.)

Introduction: Brain arteriovenous malformation (bAVM) might have a higher risk of rupture after partial embolization, and previous studies have shown that some metrics of vascular stability are related to bAVM rupture risk., Objective: To analyze vascular stability of bAVM in patients after partial embolization., Methods: Twenty-four patients who underwent partial embolization were classified into the short-term, medium-term, and long-term groups, according to the time interval between partial embolization and surgery. The control group consisted of 9 bAVM patients who underwent surgery alone. Hemodynamic changes after partial embolization were measured by angiogram. The inflammatory infiltrates and cell-cell junctions were evaluated by MMP-9 and VE-cadherin. At the protein level, the proliferative and apoptotic events of bAVMs were analyzed by immunohistochemical staining of VEGFA, eNOS, and caspase-3. Finally, neovascularity and apoptotic cells were assessed by CD31 staining and TUNEL staining., Results: Immediately after partial embolization, the blood flow velocity of most bAVMs increased. The quantity of MMP-9 in the medium-term group was the highest, and VE-cadherin in the medium-term group was the lowest. The expression levels of VEGFA, eNOS, and neovascularity were highest in the medium-term group. Similarly, the expression level of caspase-3 and the number of apoptotic cells were highest in the medium-term group., Conclusion: The biomarkers for bAVM vascular stability were most abnormal between 1 and 28 days after partial embolization., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Schistosomiasis is a tropical parasitic disease that damages the liver and poses a serious threat to human health. Macrophages play a key role in the development of liver granulomas and fibrosis by undergoing polarization from M1 to M2 type during schistosomiasis. Therefore, regulating macrophage polarization is important for controlling pathological changes that occur during this disease. Triggering receptor expressed on myeloid cells 2 (TREM2) expressed on the surface of macrophages, dendritic cells and other immune cells has been shown to play a role in inhibiting inflammatory responses and regulating M2 macrophage polarization, however its role in macrophage polarization in schistosomiasis has not been investigated. In this study, we confirmed that TREM2 expression was upregulated in the livers and peritoneal macrophages of mice infected with Schistosoma japonicum. Moreover, the TREM2 expression trend correlated with the expression of M2 macrophage polarization-related molecules in the liver tissues of S. japonicum-infected mice. Using Trem2 -/- mice, we also showed that Trem2 deletion inhibited Arg1 and Ym1 expression in liver tissues. Trem2 deletion also increased the number of F4/80 + CD86+ cells in peritoneal macrophages of infected mice. In summary, our study suggests that TREM2 may be involved in M2 macrophage polarization during schistosomiasis., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Problem: T-cells are key players in fighting the coronavirus disease 2019 (COVID-19). The checkpoint molecule B7-H4, a member of the B7 family, can inhibit T-cell activation and proliferation by inhibiting NF-kb expression. We aimed to elucidate the immunological role of soluble B7-H4 (sB7-H4) and B7-H4 in pregnant women suffered from an acute Sars-Cov2 infection., Methods: Expression levels of sB7-H4 and cytokines were detected by enzyme linked immunosorbent assay. B7-H4 and cytokines mRNA expression was analyzed by qPCR, and B7-H4 and NF-κb (p65) protein levels were investigated by western blot and immunofluorescence staining in placenta chorionic villous and decidual basalis tissues of COVID-19 affected women and healthy controls., Results: Fibrinoid necrosis in the periphery of placental villi was increased in the COVID-19-affected patients. sB7-H4 protein in maternal and cord blood serum and IL-6/IL-10 were increased while leukocytes were decreased during SARS-CoV-2 infection. Serum sB7-H4 level was increased according to the severity of SARS-Cov-2 infection. Cytokines (IL-6, IL-18, IL-1β, TNF-α), B7-H4 mRNA and protein in the decidual basalis tissues of COVID-19-infected pregnant women were significantly increased compared to healthy controls. IL-18 and IL-1β were significantly increased in the placenta chorionic villous samples of COVID-19 affected patients, while NF-κb (p65) expression was decreased., Conclusions: The expression of the immunological marker sB7-H4 correlated with the severity of COVID-19 disease in pregnant women. sB7-H4 and B7-H4 can be used to monitor the progression of COVID-19 infection during pregnancy, and for evaluating of the maternal immune status., (© 2022 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Cancer stem cells (CSCs), a group of tumour cells with stem cell characteristics, have the ability of self-renewal, multi-lineage differentiation and tumour formation. Since CSCs are resistant to conventional radiotherapy and chemotherapy, their existence may be one of the root causes of cancer treatment failure and tumour progression. The elimination of CSCs may be effective for eventual tumour eradication. Because of the good therapeutic effects without major histocompatibility complex (MHC) restriction and the unique characteristics of CSCs, chimeric antigen receptor T-cell (CAR-T) therapy is expected to be an important method to eliminate CSCs. In this review, we have discussed the feasibility of CSCs-targeted CAR-T therapy for cancer treatment, summarized current research and clinical trials of targeting CSCs with CAR-T cells and forecasted the challenges and future direction from the perspectives of toxicity, persistence and potency, trafficking, infiltration, immunosuppressive tumour microenvironment, and tumour heterogeneity., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: B7-H4, a checkpoint molecule of the B7 family, regulates a broad spectrum such as T-cell activation, cytokine secretion, tumour progression, and invasion capacities. Our previous data revealed that soluble B7-H4 (sB7-H4) blood serum levels are elevated in women at high risk for the hypertensive pregnancy disorder preeclampsia (PE) in the first trimester, as well as in patients with confirmed early/late-onset PE., Aim: We here aim to investigate the expression pattern of B7-H4 in placental tissues of PE and HELLP Syndrome versus control group., Methods: B7-H4 protein expression and localization were investigated by immunoblotting and co-immunohistochemistry in placental chorionic villous and decidual basalis tissues., Results: B7-H4 protein was prominently expressed at the cell membrane, in the cytoplasm of the syncytiotrophoblast (STB) and interstitial extravillous trophoblast (EVT). B7-H4 protein levels in placental chorionic villous tissue were significantly higher in women with early-onset/late-onset PE and HELLP, while it was decreased in decidual basalis tissues of early-onset PE and HELLP compared with controls., Conclusion: B7-H4 was inversely expressed in placental chorionic villous and decidual basalis tissues of PE and HELLP patients. The increase in B7-H4 in the STB in PE and HELLP may lead to excessive apical expression and release of soluble B7-H4 in the maternal circulation. In contrast, the decrease in B7-H4 in decidual basalis tissues could be related to the decrease in invasion ability of the EVT in PE. Thus, the current results strongly suggest that B7-H4 is involved in the pathogenesis of PE and HELLP., (© 2021 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Background: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed., Objective: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies., Methods: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63 + basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparison to extract and marker allergen-specific IgE., Results: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) in a sub-analysis in sensitized patients undergoing OFC., Conclusions: Basophil activation test can predict allergic clinical status to peanut and tree nuts in multi-nut-sensitized children and may reduce the need for high-risk OFCs in patients., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Multiplex tests allow for measurement of allergen-specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta-analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen-specific IgE to peanut/tree nut allergens from three IgE test platforms., Methods: Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high-risk, pre-school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL-chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra-test correlations between PR-10 and nsLTP allergens were assessed., Results: Using two regression methods, we demonstrated the ability to model allergen-specific relationships with acceptable measures of fit (r 2  = 94%-56%) for peanut and tree nut sIgE testing at the extract and molecular-level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9., Conclusion: Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta-analysis., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Duration of surgical general anaesthesia is associated with severe brain injury and neurological deficits. The specific mechanisms underlying post-general anaesthesia brain injury, however, still remain to be elucidated. Herein, we explore the role of microRNA-214 (miR-214) in the occurrence of brain injury after general anaesthesia and its underlying mechanism. Hippocampal tissues and neurons were isolated from rats exposed to 2% sevoflurane. TUNEL stains reflect hippocampal neuron apoptosis. Cultured hippocampal neurons stained with JC-1 and MitoTracker dyes were imaged by fluorescence microscope to visualize changes of mitochondrial membrane potential and mitochondrial fusion. Mitochondrial function was evaluated. Mitofusin 2 (Mfn2) binding to miR-214 or pyruvate kinase M2 (Pkm2) was confirmed by co-immunoprecipitation, immunofluorescence, dual luciferase reporter gene and RNA immunoprecipitation assays. After exposure to 2% sevoflurane, up-regulated miR-214 expression and impaired interaction between Mfn2 and Pkm2 were found in rat hippocampal tissues. Rats exposed to 2% sevoflurane also experienced neuronal injury, mitochondrial defects and deficits in the brain-derived neurotrophic factor (Bdnf) signalling. miR-214 was shown to target Mfn2 by impairing its binding with Pkm2. Inhibiting miR-214 expression using its specific inhibitor improved mitochondrial membrane potential, enhanced mitochondrial fusion, maintained mitochondrial function, restored interaction between Mfn2 and Pkm2, and activated the Bdnf signalling in cultured hippocampal neurons. Adenovirus infection of miR-214 inhibitor reduced neuron apoptosis and maintained mitochondrial function in the hippocampus of rats exposed to 2% sevoflurane. Taken together, the study demonstrates inhibition of miR-214 is cerebral protective against brain injury following general anaesthesia., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background Heterozygous mutation in BMP (bone morphogenetic protein) receptor 2 is rare, but BMP cascade suppression is common in congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH); however, the underling mechanism of BMP cascade suppression independent of BMP receptor 2 mutation is unknown. Methods and Results Pulmonary hypertensive status observed in CHD-PAH was surgically reproduced in rats. Gremlin-1 expression was increased, but BMP cascade was suppressed, in lungs from CHD-PAH patients and shunted rats, whereas shunt correction retarded these trends in rats. Immunostaining demonstrated increased gremlin-1 was mainly in the endothelium and media of remodeled pulmonary arteries. However, mechanical stretch time- and amplitude-dependently stimulated gremlin-1 secretion and suppressed BMP cascade in distal pulmonary arterial smooth muscle cells from healthy rats. Under static condition, gremlin-1 significantly promoted the proliferation and inhibited the apoptosis of distal pulmonary arterial smooth muscle cells from healthy rats via BMP cascade. Furthermore, plasma gremlin-1 closely correlated with hemodynamic parameters in CHD-PAH patients and shunted rats. Conclusions Serving as an endogenous antagonist of BMP cascade, the increase of gremlin-1 in CHD-PAH may present a reasonable mechanism explanation for BMP cascade suppression independent of BMP receptor 2 mutation.

Background: There have been few comprehensive scale studies on the non-motor symptoms (NMS) of patients with essential tremor (ET) with head tremor (ETh) and those with ET without head tremor (ETol). We aimed to explore the motor symptoms and NMS of these two subgroups., Methods: We enrolled 199 patients with ET (125, ETol; 74 ETh) and 132 healthy controls. We evaluated motor symptoms using the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) and NMS using the Non-Motor Symptom Scale (NMSS). We compared NMSS scores and the prevalence of each NMS between the patient subgroups. Finally, we conducted a logistic regression analysis of the correlation between head tremor and NMS severity, as well as other determinants., Results: There were no significant between-subgroup differences in demographic characteristics. Further, they presented similar tremor clinical manifestation; however, the ETh subgroup showed a higher prevalence of rest tremor, feeling of sadness, forgetting things or events, and swallowing difficulty, as well as TRS scores, compared with the ETol subgroup. Both patient subgroups showed high scores and prevalence (>50%) in difficulty falling asleep. Logistic regression analysis indicated age as a tremor severity determinant; further, head tremor and tremor severity were NMS determinants., Conclusion: Both patient subgroups presented various NMS including sleep disturbances, cognitive deficits, and affective disorders. The ETh subgroup showed a high prevalence of certain NMS aspects including memory and affective disorder; further, they had aggravated NMS. ET with both upper limb tremor and head tremor may be regarded as a more severe clinical subtype., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Previous studies have found significant differences in clinical characteristics between pediatric and adult moyamoya disease (MMD) patients, but few studies have focused on the factors underlying these differences. We aimed to investigate the differences in leptomeningeal collateral (LMC) status between pediatric and adult MMD patients and to analyze the effects of LMCs on clinical characteristics and therapeutic prognosis., Methods: We retrospectively analyzed 214 MMD patients from January 2014 to January 2016. Clinical characteristics and LMC status were compared between the pediatric and adult patients. LMC status was graded as good or poor depending on the retrograde flow from the posterior cerebral artery (PCA) on digital subtraction angiography (DSA)., Results: A total of 83 pediatric and 131 adult (1:1.6) MMD patients were analyzed. Pediatric patients were more likely to experience a transient ischemic attack (81%), whereas adult patients were more likely to experience infarction (51%). Regarding the different MMD stages (the early, medium, and advanced stages corresponded to Suzuki stages 1-2, 3-4, and 5-6, respectively), the prevalence of good LMC status was higher for pediatric patients than for adult patients in the early stage (P = 0.047) and the medium stage (P = 0.001), but there were no differences between these patient groups in the advanced stage (P = 0.547). Worse postoperative angiographic outcomes (P = 0.017) were found in adult patients than in pediatric patients in the medium stage. Poor LMC status had strong correlations with infarction (P < 0.001 and P = 0.017) and poor postoperative outcomes (P = 0.003 and P = 0.043) in both pediatric and adult patients., Conclusions: Pediatric MMD patients have greater patency and a greater ability to establish good LMC status than adult patients, and poor LMC status has a strong correlation with severe clinical symptoms and poor postoperative outcomes. LMC status may be an important factor in the differences in clinical characteristics and prognosis between pediatric and adult MMD patients., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

The balance between bone formation and bone resorption is closely related to bone homeostasis. Osteoclasts, originating from the monocyte/macrophage lineage, are the only cell type possessing bone resorption ability. Osteoclast overactivity is thought to be the major reason underlying osteoclast-related osteolytic problems, such as Paget's disease, aseptic loosening of prostheses and inflammatory osteolysis; therefore, disruption of osteoclastogenesis is considered a crucial treatment option for these issues. WKYMVm, a synthetic peptide, which is a potent FPR2 agonist, exerts an immunoregulatory effect. This peptide inhibits the production of inflammatory cytokines, such as (IL)-1β and TNF-α, thus regulating inflammation. However, there are only few reports on the role of WKYMVm and FPR2 in osteoclast cytology. In the current study, we found that WKYMVm negatively regulates RANKL- and lipopolysaccharide (LPS)-induced osteoclast differentiation and maturation in vitro and alleviates LPS-induced osteolysis in animal models. WKYMVm down-regulated the expression of osteoclast marker genes and resorption activity. Furthermore, WKYMVm inhibited osteoclastogenesis directly through reducing the phosphorylation of STAT3 and NF-kB and indirectly through the CD9/gp130/STAT3 pathway. In conclusion, our findings demonstrated the potential medicinal value of WKYMVm for the treatment of inflammatory osteolysis., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Aim: Proteins mainly expressed in normal lungs and significantly changed in lungs exposed to systemic-to-pulmonary shunts might be promising targets for pulmonary arterial hypertension induced by congenital heart diseases (PAH/CHD). This study aimed to investigate the potential role of differential screening-selected gene aberrative in neuroblastoma (DAN) in PAH/CHD., Methods: PAH was surgically induced by the combined surgery (right pulmonary artery ligation and left cervical systemic-to-pulmonary shunt) in Sprague-Dawley (SD) rats. Exogenous DAN was supplemented by osmotic minipumps., Results: Firstly, DAN was significantly decreased in patients with severe PAH/CHD and negatively correlated with pulmonary hemodynamic indices derived from right cardiac catheterization. Secondly, pulmonary hypertensive status and apparent pulmonary vasculopathies of PAH/CHD were surgically reproduced in SD rats. Real time-PCR and Western blot analysis revealed that DAN mRNA and protein levels decreased in lungs exposed to systemic-to-pulmonary shunts, and immunofluorescence staining found that DAN was highly expressed in pulmonary arteries of normal lungs but seldom detected in severely remodelling pulmonary arteries, furthermore, plasma levels of DAN in shunted-rats manifested a time-depended decrease and negatively correlated with pulmonary hemodynamic indices. Thirdly, DAN specially reversed the anti-proliferative and pro-apoptotic effects of bone morphogenetic protein 2/4 (BMP2/4) on pulmonary arterial smooth muscle cells via BMP2/4-BMPR2-Smad1/5/8-Id1 signalling pathway. Furthermore, continuous supplementation of exogenous DAN protein increased the extent of shunt-associated PAH., Conclusion: Compensatory decrease of DAN in hypertensive lungs may retard the deterioration of shunt-associated PAH, at least in part, by antagonizing BMP signalling pathway. Furthermore, DAN might be a potential biomarker for PAH/CHD., (© 2019 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Background The goal of this study is to report the characteristics and long-term clinical outcomes of patients with spontaneous coronary artery dissection (SCAD) and to identify factors associated with recurrent SCAD . Methods and Results This is a retrospective cohort study that included patients who underwent coronary angiography for evaluation of acute myocardial infarction between 2006 and 2016. Among 26 598 patients hospitalized with a principal diagnosis of acute myocardial infarction, 208 (0.78%) were diagnosed with SCAD . Patients with SCAD were younger (49.0±11.6 versus 65.6±12.2 years) and more likely to be women (88.9% versus 31.6%). Atherosclerotic risk factors, such as hypertension, hyperlipidemia, obesity, and diabetes mellitus, were less prevalent. Median follow-up was 4.7 years. Mortality was lower in patients with SCAD (1-year mortality: 2.4% versus 8.8%; P<0.001). After using propensity score matching to control for differences in age, sex, and comorbidities, the difference in mortality was no longer present, suggesting that lower mortality in patients with SCAD is attributed primarily to their baseline characteristics. Recurrent SCAD occurred in 22 patients (10.6%). Multivariate Cox regression modeling showed concomitant fibromuscular dysplasia (hazard ratio, 5.1; 95% CI , 1.6-15.8; P=0.005) and migraine headaches (hazard ratio, 3.4; 95% CI , 1.4-8.4; P=0.008) to be associated with increased risk of recurrent SCAD . Conclusions Among patients with acute myocardial infarction, patients with SCAD have a lower risk of mortality, which is attributed primarily to their younger age, female sex, and low prevalence of atherosclerotic risk factors. Risk of recurrent SCAD persists years after the initial presentation. Patients with fibromuscular dysplasia and migraine are at higher risk for recurrent SCAD .

This investigation was conducted to elucidate whether atractylenolide II could reverse the role of lncRNA XIST/miR-30a-5p/ROR1 axis in modulating chemosensitivity of colorectal cancer cells. We totally collected 294 pairs of colorectal cancer tissues and adjacent normal tissues and also purchased colorectal cancer cell lines and human embryonic kidney cell line. 5-fluorouracil, cisplatin, mitomycin and adriamycin were designated as the chemotherapies for colorectal cell lines, and atractylenolides were arranged as the Chinese drug. The expressions of XIST, miR-30a-5p and ROR1 were quantified with aid of qRT-PCR or Western blot, and luciferase reporter gene assay was implemented to determine the relationships among XIST, miR-30a-5p and ROR1. Our results demonstrated that XIST and ROR1 expressions were dramatically up-regulated, yet miR-30a-5p expression was down-regulated within colorectal cancer tissues (P < 0.05). The overexpressed XIST and ROR1, as well as under-expressed miR-30a-5p, were inclined to promote viability and proliferation of colorectal cells under the influence of chemo drugs (P < 0.05). In addition, XIST could directly target miR-30a-5p, and ROR1 acted as the targeted molecule of miR-30a-5p. Interestingly, atractylenolides not only switched the expressions of XIST, miR-30a-5p and ROR1 within colorectal cancer cells but also significantly intensified the chemosensitivity of colorectal cancer cells (P < 0.05). Finally, atractylenolide II was discovered to slow down the viability and proliferation of colorectal cancer cells (P < 0.05). In conclusion, the XIST/miR-30a-5p/ROR1 axis could be deemed as pivotal markers underlying colorectal cancer, and administration of atractylenolide II might improve the chemotherapeutic efficacy for colorectal cancer., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)