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In robust parameter design, model parameter uncertainty and quality of experimental data often affect the establishment of response surface models, which in turn affect the acquisition of the optimal operating conditions. This paper proposes a robust multi-response surface modelling and optimisation method based on Bayesian quantile regression, which is a robust regression technique insensitive to outliers, to address the above problems. We first incorporate quantile regression into the Bayesian framework and use Bayes's theorem to obtain posterior inference of model parameters. Then, the Monte Carlo-based expectation maximisation algorithm is used to estimate the model parameters, and the entropy-based overall desirability function is taken asan optimisation objective to obtain the optimal settings. The effectiveness of the proposed method is demonstrated by an additive manufacturing process anda simulation study. Compared with other existing methods, the proposed method can resist the disturbance of outliers, and thus obtain more accurate optimisation results. [ABSTRACT FROM AUTHOR]

In order to compare the influence of different soil types and stratification on water infiltration capacity, two main types of soil in the desert steppe, sierozem (S) and aeolian sandy soil (A), were selected, and infiltration simulation tests were conducted on homogeneous soil and layered soil (layer thickness 5, 10, and 20 cm), respectively. The results show that during the whole experiment, there was a small difference between S5A95 (aeolian sandy soil 95 cm thick was covered with sierozem 5 cm thick) and S10A90 (aeolian sandy soil 90 cm thick was covered with sierozem 10 cm thick) in the wetting front process, infiltration rate and cumulative infiltration, but there was a significant difference between S5A95 and S20A80 (aeolian sandy soil 80 cm thick was covered with sierozem 20 cm thick). In the initial infiltration stage, there was no significant difference between A5S95 (sierozem 95 cm thick was covered with aeolian sandy soil 5 cm thick) and A10S90 (sierozem 90 cm thick was covered with aeolian sandy soil 10 cm thick). However, with the increase of infiltration time, the wetting front process, A5S95, A10S90 and A20S80 had significant differences in terms of wetting front process, infiltration rate and cumulative infiltration. The infiltration capacity of A was significantly higher than that of S. Combined with linear Ä2 value and model parameters, the three infiltration models were comprehensively compared, and the fitting process and results of the general empirical model for the infiltration process of homogeneous soil and layered soil showed good results. Three models were used to simulate the water infiltration process of layered soil with different textures, and the order of the effect is as follows; general empirical model > Kostiakov model > Philip model. Soil type and layer thickness had a great influence on water infiltration process. When sierozem was covered with aeolian sandy soil 20 cm thick, the infiltration capacity was the best. As aeolian sandy soil was covered with sierozem 10 cm thick, the infiltration effect was the worst. Therefore, once coarse graying occurs on the surface of sierozem (the thickness of sand is more than 20 cm) or when the content of fine particles overlying aeolian sandy soil (the thickness of silt and clay soil is more than 10 cm) during ecological restoration is high, the soil hydrological characteristics will change significantly, which may lead to changes in vegetation types and even ecosystem structure. [ABSTRACT FROM AUTHOR]

Introduction: The popular traditional Chinese medicine (TCM) compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) through effects on brain edema, hematoma absorption, and the immune system. This study is to assess whether FYTF-919 is safe and effective as compared to matching placebo treatment in patients with acute ICH. Methods: The ongoing Chinese Herbal medicine in patients with Acute INtracerebral hemorrhage (CHAIN) is a multicenter, prospective, randomized, double-blind placebo-controlled trial of FYTF-919 in patients with acute ICH at 20–30 hospital sites in China. Eligible ICH patients presenting within 48 h after symptom onset are randomly allocated to receive either FYTF-919 (100 mL per day × 28 d, oral) or matching placebo. A sample size of 1,504 patients is estimated to provide 90% power (α 0.05) to detect a ≥20% improvement in average utility-weight scores on the modified Rankin scale (UW-mRS) assessed at 90 days, with 6% non-adherence and 10% lost to follow-up. The primary efficacy outcome is UW-mRS at 90 days. Secondary outcomes include binary measures of the mRS, neurological impairment on the National Institute of Health Stroke Scale, and health-related quality of life on the EuroQol EQ-5D-5L scale at different time points over 6 months of follow-up. The key safety measure is serious adverse events. Conclusion: CHAIN is on schedule to provide reliable evidence over the benefits of a popular herbal TCM for the treatment of acute ICH. [ABSTRACT FROM AUTHOR]

DNA methylation is an essential epigenetic chromatin modification, and its maintenance in mammals requires the protein UHRF1. It is yet unclear if UHRF1 functions solely by stimulating DNA methylation maintenance by DNMT1, or if it has important additional functions. Using degron alleles, we show that UHRF1 depletion causes a much greater loss of DNA methylation than DNMT1 depletion. This is not caused by passive demethylation as UHRF1-depleted cells proliferate more slowly than DNMT1-depleted cells. Instead, bioinformatics, proteomics and genetics experiments establish that UHRF1, besides activating DNMT1, interacts with DNMT3A and DNMT3B and promotes their activity. In addition, we show that UHRF1 antagonizes active DNA demethylation by TET2. Therefore, UHRF1 has non-canonical roles that contribute importantly to DNA methylation homeostasis; these findings have practical implications for epigenetics in health and disease. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the association between serum lactate dehydrogenase (LDH) and the risk of lymph node metastasis (LNM) in the International Federation of Gynecology and Obstetrics (FIGO) 2009 cervical cancer (CC) stages IB1-IIA2. All patient medical records with FIGO 2009 stage IB1-IIA2 CC between January 2012 and January 2022 were analyzed retrospectively. The association between serum LDH and LNM was assessed using uni- and multivariate logistic regression analyses, subgroup analyses and P-splines. The present study included 586 patients, 91 (15.5%) of whom had LNM. Patients with an elevated LDH level were more likely to have a deep stromal invasion, lymph-vascular space invasion, LNM and to be of an older age. Multivariate logistic regression revealed a significant association between LNM and LDH levels. After adjusting for age, FIGO stage, tumor markers and risk factors according to the Sedlis criteria, patients in the highest LDH quartile had an increased risk of LNM compared with those in the lowest LDH quartile (odds ratio, 3.5; 95% CI, 1.57-7.81). Furthermore, P-spline regression revealed a dependence of LNM on LDH. The predictive value of LDH level remained significant in the subgroup analysis. The present study suggested that a higher LDH level was independently associated with CC and LNM, and that LDH level may serve as a potential tumor marker and treatment-related indicator. [ABSTRACT FROM AUTHOR]

Objective: αS1-Casein is more closely associated with milk allergic reaction than other milk protein components. microRNA (miRNA) is a class of small non-coding RNAs that modulate multiple biological progresses by the target gene. However, the post-transcriptional regulation of αS1-casein expression by miRNA in ruminants remains unclear. This study aims to explore the regulatory roles of miR-380-3p on αS1-casein synthesis in goat mammary epithelial cells (GMEC). Methods: αS1-Casein gene and miR-380-3p expression was measured in dairy goat mammary gland by quantitative real-time polymerase chain reaction (qRT-PCR). miR-380-3p overexpression and knockdown were performed by miR-380-3p mimic or inhibitor in GMEC. The effect of miR-380-3p on αS1-casein synthesis was detected by qRT-PCR, western blot, luciferase and chromatin immunoprecipitation assays in GMEC. Results: Compared with middle-lactation period, αS1-casein gene expression is increased, while miR-380-3p expression is decreased during peak-lactation of dairy goats. miR-380-3p reduces αS1-casein abundance by targeting the 3'-untranslated region (3'UTR) of αS1-casein mRNA in GMEC. miR-380-3p enhances β-casein expression and signal transducer and activator of transcription 5a (STAT5a) activity. Moreover, miR-380-3p promotes β-casein abundance through target gene αS1-casein, and activates β-casein transcription by enhancing the binding of STAT5 to β-casein gene promoter region. Conclusion: miR-380-3p decreases αS1-casein expression and increases β-casein expression by targeting αS1-casein in GMEC, which supplies a novel strategy for reducing milk allergic potential and building up milk quality in ruminants. [ABSTRACT FROM AUTHOR]

The effects of dietary supplementation of Clostridium butyricum (CB) on growth performance, serum biochemistry, antioxidant activity, mRNA levels of immune-related genes and resistance to hypoxia stress were studied in largemouth bass. Feed with CB0 (control, 0 CFU/kg), CB1 (4.3×108 CFU/kg), CB2 (7.5×108 CFU/kg), CB3 (1.5×109 CFU/kg) and CB4 (3.2×109 CFU/kg) CB for 56 days, and then a 3 h hypoxic stress experiment was performed. The results showed that dietary CB significantly increased the WGR (weight gain rate), SGR (specific growth rate), PDR (protein deposition rate) and ISI (Intestosomatic index) of largemouth bass (P<0.05). Hepatic GH (growth hormone)/IGF-1 (insulin-like growth factor-1) gene expression was significantly upregulated in the CB3 and CB4 groups compared with the CB0 group (P<0.05), while the FC (feed conversion) was significantly decreased (P<0.05). Serum TP (total protein) and GLU (glucose) levels were significantly higher in the CB4 group than in the CB0 group (P<0.05), while the contents of serum AST (aspartate transaminase), ALT (alanine transaminase), AKP (alkline phosphatase) and UN (urea nitrogen) in CB4 were significantly lower than those in CB0 (P<0.05). T-AOC (total antioxidant capacity), SOD (superoxide dismutase), CAT (catalase), POD (peroxidase) and GSH-Px (glutathione peroxidase) activities were significantly higher in CB3 and CB4 groups than in CB0 group (P<0. 05). The liver MDA (malondialdehyde) content of CB1, CB2, CB3 and CB4 groups was significantly higher than that of CB0 group (P<0. 05). The relative expressions of IL-1β (interleukin 1β), TNF-α (tumor necrosis factor α) and TLR22 (toll-like receptor-22) genes in CB2, CB3 and CB4 groups were significantly lower than those in CB0 group (P<0.05). The relative expression of IL-8 (malondialdehyde) and MyD88 (Myeloid differentiation factor 88) genes in the CB4 group was significantly lower than that in the CB0 group (P<0.05). The liver LZM (lysozyme) content of CB2, CB3 and CB4 groups was significantly higher than that of CB0 group (P<0. 05). The relative expression of IL-10 (interleukin 10) and TGF-β (transforming growth factor β) genes in the CB4 group was significantly higher than that in the CB0 group (P<0.05). Under hypoxic stress for 3 h, the CMR of CB0 group was significantly higher than that of CB1, CB2, CB3 and CB4 groups (P<0.05). Dietary CB can improve the growth performance and resistance to hypoxic stress of largemouth bass by regulating the expression of GH/IGF-1 gene and inflammatory factors and inhibiting TLR22/MyD88 signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical efficacy of thermocoagulation in women with biopsy-confirmed cervical low-grade squamous intraepithelial lesions (LSIL) or less after colposcopy referral. Material and methods: A longitudinal study was performed. Women who were diagnosed with cervical LSIL or chronic cervicitis underwent scheduled follow-up examinations with cytology and human papilloma virus (HPV) genotyping for two years after the initial management with thermocoagulation or observation without treatment. All women underwent scheduled follow-up with combined cytology and HPV test at 6th months, 12th months, and 24th months after the initial management. Both HPV clearance and cytological regression were included in the analysis, with clinical cure defined as normal cytology and negative HPV results. Results: A total of 221 women were included. The histopathological results identified 136 (61.54%) patients with LSIL and 85 (38.46%) with chronic cervicitis. Of these, 113 (51.13%) received thermocoagulation therapy, and 108 (48.87%) chose observation. The 2-year follow-up rate was 91.40%. Women who received thermocoagulation presented a significantly higher probability of cure for two years than those who chose observation (62.86% vs 39.18%, p < 0.001). This preponderance was not observed in the subgroup analysis regarding women with cervical cervicitis (54.17% vs 41.38%, p = 0.277) but was observed in women with LSILs (70.18% vs 38.24%, p < 0.001). Conclusions: Thermocoagulation may be indicated for patients with cervical LSILs as an effective outpatient procedure in clinical practice. [ABSTRACT FROM AUTHOR]

This paper addresses the exponential stability of impulsive systems with both pointwise and distributed delays, where delayed impulses are considered. Based on impulsive control theory, some Lyapunov-based sufficient conditions for exponential stability involving both impulsive perturbation and impulsive control are derived, respectively. Especially, the derived conditions do not impose any restriction on the magnitude relationship between the delay in continuous flow and impulsive delay in the case of impulsive perturbation. It also shows that the delay in continuous flow might have a potential effect on system stability. It may not be reasonable for existing results to assume a common threshold of impulsive strength at every impulse point, such as eδ with δ>0 in the case of impulsive perturbation. Here, based on the proposed concepts of average impulsive estimation and average positive impulsive estimation, impulsive estimation δm can be time-varying, and the information of impulsive delay can be integrated into it to guarantee the effect of impulse. The results of stability analysis are applied to the synchronization of complex networks with mixed delays and impulses. Numerical examples illustrate the efficiency of the derived results. [ABSTRACT FROM AUTHOR]

Organisms from cyanobacteria to humans have evolved a wide array of photoreceptive strategies to detect light. Sunlight avoidance behavior is common in animals without vision or known photosensory genes. While indirect light perception via photothermal conversion is a possible scenario, there is no experimental evidence for this hypothesis. Here, we show a nonvisual and extraocular sunlight detection mechanism by identifying the broad-range thermal receptor 1 (BRTNaC1, temperature range = 33 to 48 °C) in centipede antennae. BRTNaC1, a heat-activated cation-permeable ion channel, is structurally related to members of the epithelial sodium channel family. At the molecular level, heat activation of BRTNaC1 exhibits strong pH dependence controlled by two protonatable sites. Physiologically, temperature-dependent activation of BRTNaC1 upon sunlight exposure comes from a striking photothermal effect on the antennae, where a slightly acidic environment (pH 6.1) of the body fluid leads to the protonation of BRTNaC1 and switches on its high thermal sensitivity. Furthermore, testosterone potently inhibits heat activation of BRTNaC1 and the sunlight avoidance behavior of centipedes. Taken together, our study suggests a sophisticated strategy for nonvisual sunlight detection in myriapods. [ABSTRACT FROM AUTHOR]

Background: Olanzapine (OLZ) is an antipsychotic with a high risk of metabolic syndrome, and its induced metabolic disturbance may be related to the thermogenic function of brown adipose tissue (BAT). Of note is that schizophrenia itself appears to be associated with a higher incidence of metabolic syndrome. However, whether OLZ affects metabolic disorders by regulating BAT function and its mechanism in animal models of schizophrenia have not been reported. Methods: We induced maternal immune activation (MIA) in pregnant rodents by injection of synthetic double-stranded RNA-poly I:C (a virus-like substance), and rats were injected with poly I:C, 10 mg/kg) or saline on day 13 of gestation. Rat offspring received OLZ (1mg/kg, tid) or vehicle from adulthood for 28 days, and body weight and food intake were recorded. Morphological alterations of white adipose tissue (WAT) and BAT were analyzed by HE and oil red staining, and expression of BAT-specific marker proteins/genes was detected by western blot and qRT-PCR. In addition, embryonic stem cells C3H10T1/2 were used to direct differentiation into brown-like adipocytes, and C3H10T1/2 cells were treated with OLZ for the differentiation process. The effects of OLZ on brown-like adipocyte differentiation and activity were analyzed using oil red staining, immunofluorescence and flow cytometry. Results: Compared with the Veh (saline) group, the TG, pWAT weight, adipocyte size and liver weight of the Veh (poly I:C) group were significantly increased, suggesting that the offspring of Poly I:C rats had obvious dyslipidemia and lipid accumulation, which were risk factors for metabolic abnormalities such as obesity. In addition, OLZ treatment resulted in altered WAT and BAT morphology in poly I:C or saline exposed offspring, causing lipid accumulation and weight gain and reducing the expression of the BAT-specific marker molecule UCP1 protein/ gene. At the same time, OLZ inhibited the directional differentiation and mitochondrial activity of C3H10T1/2 brown-like adipocytes. Conclusion: Poly I:C-elicited MIA and OLZ differentially inhibited BAT activity and mitochondrial biogenesis, leading to weight gain in adult rats, a process involving PPAR-γ/UCP1-related thermogenic proteins. [ABSTRACT FROM AUTHOR]

Background: Stroke is a major cause of mortality and long-term physical and cognitive impairment. This study aims to: (1) examine the prevalence of depressive symptoms, disability and pain among Chinese adults with stroke; (2) test the associations of functional limitations and body pain with occurrence of depressive symptoms; (3) investigate gender and urban-rural disparities in these associations. Methods: This study utilized the data from the China Health and Retirement Longitudinal Study in 2018, involving 969 patients with stroke among 17,970 participants aged ≥ 45 years. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression (CES-D) Scale. We performed multivariable logistic regression models to estimate the associations between activities of daily life (ADL), instrumental activities of daily life (IADL) and pain with depressive symptoms. Results: Depressive symptoms were found among 40.2% of stroke patients, with a higher prevalence in females (48.2%) than males (32.7%). Prevalence of ADL limitations, IADL limitations and pain among stroke patients were 39.2, 49.8 and 14.0%, respectively. ADL and IADL limitations and pain were more prevalent among females and residents in rural areas. Multivariable regression analyses showed a significant association between ADL limitation (OR = 1.535, 95% CI = 1.168, 2.018), IADL limitation (OR = 1.666, 95% CI = 1.260, 2.203) and pain (OR = 2.122, 95% CI = 1.466, 3.073) with depressive symptoms. Stratified analyses revealed stronger associations among urban residents. Females had a higher association of ADL and IADL with depressive symptoms but similar in that of pain to themales. The impact of ADL and IADL inmale patients is higher than in females, but the impact of pain on depressive symptoms is higher in female patients. Conclusion: Depressive symptoms are common amongst post-stroke patients in China and are significantly associated with functional disability and physical pain. Our findings have implications for practitioners on the early assessment of pain and depression after stroke. Future research should explore effective intervention measures for physical-mental stroke complications. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the effects of hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), and erythroferrone (ERFE) on hepcidin in patients with chronic kidney disease (CKD) stages 3-5 and renal anemia. Methods: A total of 90 patients with CKD stages 3-5 and renal anemia were selected for the study at the Nephrology Department of Fujian Provincial People's Hospital and divided into three groups, according to CKD stage, while another 30 healthy subjects who underwent a physical examination at the hospital during the same period were selected as the normal group. The serum levels of hepcidin, HIF-1α, HIF-2α, ERFE, and furin were measured using an avidin biotin peroxidase complex enzyme-linked immunosorbent assay to compare the differences between the groups in the related indicators. Results: 1Serum HIF-2α, HIF-1α, ERFE, and furin levels increased gradually in the patients with CKD stages 3-5 (p < 0.05, p < 0.01). 2Simple correlation analysis:Serum hepcidin was positively correlated with HIF-2α, ERFE, and HIF-1α in the CKD patients (p < 0.01). 3Serum hepcidin was positively correlated with HIF-2α, HIF-1α, and ERFE in the CKD patients injected with erythropoietin (EPO) (p < 0.01), while serum hepcidin was positively correlated with HIF-2α and HIF-1α (p < 0.01) in the patients not injected with EPO. 4 Multivariate linear regression analysis showed that HIF-1α, (β = 4.36, p < 0.01), serum ferritin(SF) (β = 0.13, p < 0.01), and HIF-2α (β = 0.66, p < 0.01) were significantly correlated with hepcidin. Conclusion: HIF-1α, HIF-2α, and SF are factors which have an effect on hepcidin in patients with CKD stages 3-5 and renal anemia. The increase of HIF-1α, HIF-2α, and ERFE does not seem to inhibit the increase of hepcidin. [ABSTRACT FROM AUTHOR]

The first filial generation of the cattleyaks demonstrates hybrid vigor; however, the male cattleyaks are infertile and restrict productivity and breeding. The discovery of genes in a segment-specific approach offers valuable information and understanding concerning fertility status, yet the biology of cattleyak epididymis is still progressing. Comparative transcriptome analysis was performed on segment pairs of cattleyak epididymis. The caput versus corpus epididymis provided the highest (57.8%) differentially expressed genes (DEGs), corpus versus cauda (25.1%) followed, whereas caput versus cauda pair (17.1%) had the least DEGs. The expression levels of genes coding EPHB6, TLR1, MUC20, MT3, INHBB, TRPV5, EI24, PAOX, KIF12, DEPDC5, and KRT25, which might have the potentials to regulate the homeostasis, innate immunity, differentiation, motility, transport, and sperm maturation-related function in epididymal cells, were downregulated in the distal segment of epididymis. Top enriched KEGG pathways included mTOR, axon guidance, and taste transduction signaling pathways. EIF4B, EPHB6, and TAS2R42 were enriched in the pathways, respectively. Identifying key, new, and unexplored DEGs among the epididymal segments and further analyzing them could boost cattleyak fertility by maximizing sperm quality from genetically better sires and also facilitate better understanding of the epididymal biology. [ABSTRACT FROM AUTHOR]

The texture of ground-based nephogram is abundant and multiplicity. Many cloud textures are not as clear as artificial textures. A nephogram enhancement algorithm based on Adaptive Fractional Differential is established to extract the natural texture of visible ground-based cloud image. Grunwald-Lentikov (G-L) and Grunwald-Lentikov (R-L) fractional differential operators are applied to the enhancement algorithm of ground-based nephogram. An operator mask based on adaptive differential order is designed. The corresponding mask template is used to process each pixel. The results show that this method can extract image texture and edge details and simplify the process of differential order selection. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma hominis (MH) is an opportunistic pathogen, which often causes funisitis, spontaneous abortion, and low birth weight. However, current laboratory methods are time-consuming, labor-intensive, or require specialized laboratory instruments. Recombinase polymerase amplification (RPA) technology is a rapidly developing field because of the significance for clinical application and commercial value. Few studies have reported the use of RPA to detect MH. In this study, we developed the rapid MH detection assay, which may be potentially used as a sensitive point-of-care testing (POCT) in clinic. Methods: Primers based on the MH 16SrRNA gene and gap gene were explored and screened out. The probe of RPA-LFD was designed based on the optimal primer and confirmed. The reaction conditions of temperature and time for RPA were optimized. The sensitivity and specificity of the analysis were explored. A total of 60 clinical specimens were used to verify the efficiency of the two methods. Results: The optimal reaction conditions were determined as 15 minutes and 39°C. The sensitivity of RPA was 10-6 ng for MH, which is 100,000 times more sensitive than traditional PCR. Moreover, we observed another six non-target reproductive tract common pathogens without amplification products. Furthermore, we found that there was no significant difference between RPA and the cultivation method (p > 0.05). These two methods were in good agreement (Κ = 0.938) when detecting clinical specimens. Conclusions: A new method for sensitive and rapid detection of MH based on RPA was successfully developed, which can be applied in large-scale screening and as a supplementary method to classical methods. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that imaging signs of 'brain frailty' and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED).Methods: Blinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0-2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs.Results: 2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5-14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose.Conclusions: Non-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose. [ABSTRACT FROM AUTHOR]

To adapt to habitat temperature, vertebrates have developed sophisticated physiological and ecological mechanisms through evolution. Transient receptor potential melastatin 8 (TRPM8) serves as the primary sensor for cold. However, how cold activates TRPM8 and how this sensor is tuned for thermal adaptation remain largely unknown. Here we established a molecular framework of how cold is sensed in TRPM8 with a combination of patch-clamp recording, unnatural amino acid imaging, and structural modeling. We first observed that the maximum cold activation of TRPM8 in eight different vertebrates (i.e., African elephant and emperor penguin) with distinct side-chain hydrophobicity (SCH) in the pore domain (PD) is tuned to match their habitat temperature. We further showed that altering SCH for residues in the PD with solventaccessibility changes leads to specific tuning of the cold response in TRPM8. We also observed that knockin mice expressing the penguin's TRPM8 exhibited remarkable tolerance to cold. Together, our findings suggest a paradigm of thermal adaptation in vertebrates, where the evolutionary tuning of the cold activation in the TRPM8 ion channel through altering SCH and solvent accessibility in its PD largely contributes to the setting of the cold-sensitive/tolerant phenotype. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MS) has attracted much attention worldwide for its harmful effects. Although the Cornell product (CP) and Sokolow-Lyon (SL) voltage are independent and strong risk factors of cardiovascular disease, their associations with MS and the relative strength of these associations are unknown. Therefore, we studied these aspects in a community of middle-aged people. Methods: A total of 1112 community residents aged 40–65 years, among which 169 had IDF (2005)–defined MS (MS group) and 943 did not have MS (NMS group), underwent electrocardiography (ECG) at baseline. A questionnaire survey, physical measurements, laboratory biochemical assessments, urine test, ECG, body fat analysis, and abdominal MRI examination were performed subsequently. Fifty-eight participants had developed MS (new-onset MS group) at the follow-up, while 472 residents had not developed MS over the next year (MS-free group). We compared the CP and SL voltage between these two groups. Results: In the overall analysis, CP values were higher in the MS group than in the NMS group (p < 0.05), but SL voltage values were not significantly different (p > 0.05). In the gender-stratified multivariate analysis, CP was significantly different in the male and female populations (p < 0.05), but SL voltage was only different in the male population (p = 0.042). After removing hypertension from MS and NMS groups, there was still significant difference in CP value (< 0.05). Thus, CP showed a more pronounced influence. The new-onset MS group showed significantly higher CP values and the changes in CP values than did the MS-free group at baseline and follow-up (p < 0.05), but the changes in SL values were not significant (p > 0.05). Conclusions: CP values differed significantly between the MS and NMS groups. The new-onset MS group showed higher baseline CP values. Thus, CP is more advantageous than SL voltage in presaging the incidence of MS-related cardiovascular risk. [ABSTRACT FROM AUTHOR]

Nature reserves are key sites for ecotourism. In the context of sustainable development, a great number of ecotourism practices have been carried out in nature reserves around the world. Important ecotourism practices in nature reserves include the establishment of ecotourism certification systems, the development of management mechanisms promoting effective community participation and the development of standards for ecotourism practices. This paper uses questionnaires, a field investigation and interviews to examine the obstacles influencing the sustainable development of ecotourism in nature reserves, taking three nature reserves in Liaoning Province to serve as examples. The study found that there are two kinds of obstacles to the sustainable development of ecotourism in nature reserves. The first group of obstacles all represent common problems in China including: (1) environmental education is ignored; (2) community participation occurs on an ad hoc basis; (3) tourism management is not rigorous; (4) nature reserve administration is in a state of confrontation with local governments and residents. The second group of obstacles consists of specific problems faced by ecotourism in the three nature reserve, each of which has its own natural, social, cultural and economic environment that generate unique difficulties for ecotourism. In order to promote the healthy improvement of nature reserve ecotourism and achieve the goal of sustainable development, the research team puts forward five suggestions, developing correct understanding, striving to meet the reasonable demands of stakeholders, establishing scientific mechanisms, increasing the social responsibility of management departments of nature reserve ecotourism, and providing separate supervision and management. [ABSTRACT FROM AUTHOR]

It is important to extract texture feature from the ground-base cloud image for cloud type automatic detection. In this paper, a new method is presented to capture the contour edge, texture and geometric structure of cloud images by using Contourlet and the power spectrum analysis algorithm. More abundant texture information is extracted. Cloud images can be obtained a multiscale and multidirection decomposition. The coefficient matrix from Contourlet transform of ground nephogram is calculated. The energy, mean and variance characteristics calculated from coefficient matrix are composed of the feature information. The frequency information of the data series from the feature vector values is obtained by the power spectrum analysis. Then Support Vector Machines (SVM) classifier is used to classify according to the frequency information of the trend graph of data series. It is shown that altocumulus and stratus with different texture frequencies can be effectively recognized and further subdivided the types of clouds. [ABSTRACT FROM AUTHOR]

It is known that plant arboviruses infect insect vector cells by endocytosis; however, the cellular receptors that mediate endocytosis have not been well defined. In our recently published work and this study, by clarifying the vertical transmission mechanism of Rice stripe virus (RSV) in Laodelphax striatellus, we provide a novel paradigm for how arboviruses enter insect germ-line cells. Instead of direct interaction with a viral receptor, the virus binds to a secreted ligand protein, hitchhiking the ligand-receptor pathway to achieve cell entry. Vitellogenin (Vg) is an indispensable protein for embryo development that is synthesized extra-ovarially and taken up by germ-line cells through Vg receptor (VgR)-mediated endocytosis. After revealing that RSV invades L. striatellus ovary by a specific molecular interaction with the insect Vg in haemolymph, this study addressed VgR’s function in mediating the RSV invasion of the germarium nurse cells, further confirming the ligand’s receptor-mediated viral cell-invasion mechanism. Understanding the viral ovary-entry pathways in vectors will help to find suitable measures to block the trans-generation transmission of the viruses. [ABSTRACT FROM AUTHOR]

Control of neuronal precursor cell proliferation is essential for normal brain development, and deregulation of this fundamental developmental event contributes to brain diseases. Typically, neuronal precursor cell proliferation extends over long periods of time during brain development. However, how neuronal precursor proliferation is regulated in a temporally specific manner remains to be elucidated. Here, we report that conditional KO of the transcriptional regulator SnoN in cerebellar granule neuron precursors robustly inhibits the proliferation of these cells and promotes their cell cycle exit at later stages of cerebellar development in the postnatal male and female mouse brain. In laser capture microdissection followed by RNA-Seq, designed to profile gene expression specifically in the external granule layer of the cerebellum, we find that SnoN promotes the expression of cell proliferation genes and concomitantly represses differentiation genes in granule neuron precursors in vivo. Remarkably, bioinformatics analyses reveal that SnoN-regulated genes contain binding sites for the transcription factors N-myc and Pax6, which promote the proliferation and differentiation of granule neuron precursors, respectively. Accordingly, we uncover novel physical interactions of SnoN with N-myc and Pax6 in cells. In behavior analyses, conditional KO of SnoN impairs cerebellar-dependent learning in a delayed eye-blink conditioning paradigm, suggesting that SnoN-regulation of granule neuron precursor proliferation bears functional consequences at the organismal level. Our findings define a novel function and mechanism for the major transcriptional regulator SnoN in the control of granule neuron precursor proliferation in the mammalian brain. [ABSTRACT FROM AUTHOR]

Peritoneal fibrosis is a severe complication arising from long-term peritoneal dialysis (PD). Tamoxifen (Tamo) has been clinically proven effective in a series of fibrotic diseases, such as PD-associated encapsulating peritoneal sclerosis (EPS), but the mechanisms underlying Tamoxifen's protective effects are yet to be defined. In the present study, C57BL/6 mice received intraperitoneal injections of either saline, 4.25% high glucose (HG) PD fluid (PDF) or PDF plus Tamoxifen each day for 30 days. Tamoxifen attenuated thickening of the peritoneum, and reversed PDF-induced peritoneal expression of E-cadherin, Vimentin, matrix metalloproteinase 9 (MMP9), Snail, and β-catenin. Mouse peritoneal mesothelial cells (mPMCs) were cultured in 4.25% glucose or 4.25% glucose plus Tamoxifen for 48 h. Tamoxifen inhibited epithelial-to-mesenchymal transition (EMT) as well as phosphorylation of glycogen synthase kinase-3β (GSK-3β), nuclear β-catenin, and Snail induced by exposure to HG. TWS119 reversed the effects of Tamoxifen on β-catenin and Snail expression. In conclusion, Tamoxifen significantly attenuated EMT during peritoneal epithelial fibrosis, in part by inhibiting GSK-3β/β-catenin activation. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the association between cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase inhibitor 2B (CDKN2B) methylation, and coronary heart disease (CHD), and to explore the interaction between methylation status and CHD clinical characteristics in Han Chinese patients. A total of 189 CHD (96 males, 93 females) and 190 well-matched non-CHD controls (96 males, 94 females) were recruited for the study. Methylation-specific polymerase chain reaction technology was used to examine gene promoter methylation status. Comparisons of methylation frequencies between CHD and non-CHD patients were carried out using the Chi-square test. Methylation levels of CDKN2A and CDKN2B genes were not found to be associated with the risk of CHD. However, the mean age of CDKN2A-hypermethylated participants was significantly lower than CDKN2A-unmethylated participants (58.73±5.88 vs. 62.62±5.36 years, adjusted P<0.001). Conversely, the mean age of CDKN2B-hypermethylated participants was significantly higher compared with CDKN2B-unmethylated participants (62.26±5.48 vs. 58.33±7.47 years, adjusted P=0.048). In addition, CDKN2B methylation frequencies were significantly increased in female participants compared with males (99.47 vs. 11.98%, P=0.032). In conclusion, the results indicated that CDKN2A and CDKN2B promoter methylation frequencies were significantly associated with age, and there was a gender dimorphism in CDKN2B methylation. [ABSTRACT FROM AUTHOR]

Aberrant DNA methylation is associated with non-small cell lung cancer (NSCLC), suggesting that gene promoter methylation may be a potential biomarker for the detection or risk prediction of NSCLC. The present study aimed to evaluate the potential usage of angiotensin II receptor type 1 (AGTR1) methylation in two major pathologic subtypes: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Quantitative methylation-specific polymerase chain reaction was used to investigate the effect of AGTR1 promoter methylation in the tumor and the paired adjacent non-tumor tissue samples from 42 patients with LUSC, and 69 with LUAD. The percentage of methylated reference was calculated and presented as the median (interquartile range 25th-75th percentile). The results of the current study revealed that there was significantly increased AGTR1 promoter methylation in the tumor tissues compared with the paired adjacent non-tumor tissue [97.4 (57.22-130.5) vs. 85 (48.25-123); P=0.024]. Furthermore, higher AGTR1 promoter methylation was observed in patients with LUSC compared with LUAD (odds ratio=2.483; 95% confidence interval=1.125-5.480; P=0.023). Significant differences were identified in AGTR1 methylation between non-tumor and the tumor tissues in LUSC [113.5 (68.33-148.73) vs. 93.04 (45.94-140); P=0.008]. In addition, the Cancer Genome Atlas data of 378 patients with LUSC and 477 with LUAD revealed an inverse correlation between gene expression and the methylation status of AGTR1 promoter.. These data suggest that AGTR1 hypermethylation is a promising biomarker to assist in LUSC detection and diagnosis. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced premature ovarian failure (POF) is a severe complication affecting tumor patients at a childbearing age. Mesenchymal stem cells (MSCs) can partially restore the ovarian structure and function damaged by chemotherapy. miR-21 is a microRNA that can regulate cell apoptosis. This study discusses the repair effect and mechanism of MSCs overexpressing miR-21 on chemotherapy-induced POF. Methods: Rat MSCs and granulosa cells (GCs) were isolated in vitro. MSCs were transfected with miR-21 lentiviral vector (LV-miR-21) to obtain MSCs stably expressing miR-21 (miR-21-MSCs). The microenvironment of an ovary receiving chemotherapy was mimicked by adding phosphamide mustard (PM) into the cellular culture medium. The apoptosis rate and the mRNA and protein expression of target genes PTEN and PDCD4 were detected in MSCs. Apoptosis was induced by adding PM into the culture medium for GCs, which were cocultured with miR-21-MSCs. The apoptosis rate and the mRNA and protein expression of PTEN and PDCD4 were detected. The chemotherapy-induced POF model was built into rats by intraperitoneal cyclophosphamide injection. miR-21-MSCs were transplanted into the bilateral ovary. The rats were sacrificed at 15, 30, 45, and 60 days after the last injection. The ovarian weights, follicle count, estrous cycle, and sex hormone levels (estradiol (E2) and follicle-stimulating hormone (FSH)) were detected. Apoptosis of GCs was determined by TUNEL assay. The miR-21 and mRNA and protein expression of PTEN and PDCD4 were determined. Results: The apoptosis decreased in MSCs transfected with miR-21. The mRNA and protein expression of target genes PTEN and PDCD4 was downregulated. GCs cocultured with miR-21-MSCs showed a decreased apoptosis, an upregulation of miR-21, and a downregulation of PTEN and PDCD4. Following the injection of miR-21-MSCs, the ovarian weight and follicle counts increased; E2 levels increased while FSH levels decreased, with less severe apoptosis of GCs. The miR-21 expression in the ovaries was upregulated, while the mRNA expression and protein expression of PTEN and PDCD4 were downregulated. Conclusions: Overexpression of miR-21 in MSCs promoted efficacy against chemotherapy-induced POF and its improvement of the repair effect was related to the inhibition of GC apoptosis by targeting PTEN and PDCD4. [ABSTRACT FROM AUTHOR]

SET and MYND domain containing 3 (SMYD3) is a histone methyltransferase (HMT) and transcription factor, which serves important roles in carcinogenesis. Numerous downstream target genes of SMYD3 have been identified in previous studies. However, the downstream microRNA (miRNA) s regulated by SMYD3 are yet to be elucidated. In the present study, the results of miRNA microarray demonstrated that 30 miRNA expression profiles were upregulated, whilst 24 miRNAs were downregulated by >2.0-fold in the SMYD3-overexpressed MCF-7 breast cancer cells. The HMT activity was demonstrated to be essential for SMYD3-mediated transactivation of miR-200c-3p and the overexpression of miR-200c-3p inhibited the transactivation effects of SMYD3 on myocardin-related transcription factor-A-dependent migration-associated genes. To our best knowledge, the current study is the first to report on the transcriptional regulation of SMYD3 on miRNAs, and miR-200c may be a downstream negative regulator of the SMYD3-mediated pathway in the migration of breast cancer cells. These results may provide a novel theoretical basis to understand the mechanisms underlying the initiation, progression, diagnosis, prevention and therapy of breast cancer. [ABSTRACT FROM AUTHOR]

The aim of the present study was to identify differentially methylated regions (DMRs) in patients with rheumatic heart disease and secondary pulmonary arterial hypertension (RHD-PAH). A genome-wide DNA methylation assay was performed between 6 patients with RHD-PAH and 6 healthy controls using an Illumina Infinium HumanMethylation450 BeadChip kit. The Limma software package was subsequently used to identify significant DMRs. A total of 40 hypomethylated and 64 hypermethylated CpG sites were identified between the RHD-PAH group and the control group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes term and signaling pathway enrichment analyses revealed that the DMRs, mapped to the genes including protein kinase C α, protein kinase AMP-activated non-catalytic subunit γ2, sprouty related EVH1 domain containing 2 and LIF interleukin 6 family cytokine, were significantly enriched in the negative regulation of protein kinase/transferase activity and the positive regulation of protein amino acid phosphorylation/phosphate metabolic process. The identified DMRs may provide novel insights into the pathogenesis of RHD-PAH. [ABSTRACT FROM AUTHOR]

Sporamin, a Kunitz-type trypsin inhibitor (TI) from sweet potato tuberous roots, has demonstrated anti-tumor activity through poorly defined mechanisms. Furthermore, the effects of sporamin on pancreatic cancer have not been explored. Herein, we studied the effects of sporamin on two human pancreatic cancer cell lines, PANC-1 and BxPC-3. Sporamin significantly inhibited the cell viability and proliferation activity and induced apoptosis in PANC-1 and BxPC-3 cells. Consistently, in sporamin-treated PANC-1 and BxPC-3 cells, the anti-apoptotic proteins Bcl-2 and Bcl-XL were downregulated and the pro-apoptotic protein Bax was upregulated. Moreover, nuclear factor kappa B activation and IγBα phosphorylation were inhibited, and total IγBα expression was increased in sporamin-treated PANC-1 and BxPC-3 cells. Thus, our results suggest that the anti-tumor effects of sporamin in pancreatic cancer cells might result partly from induction of apoptosis by downregulating nuclear factor kappa B pathway. [ABSTRACT FROM AUTHOR]

Agarwood (gaharu) is a fragrant resin produced in the heartwood of resinous Gyrinops and Aquilaria species. Artificial agarwood samples were obtained from Aquilaria sinensis (Lour.) Gilg using formic acid (FA) stimulation combined with Fusarium sp. A2 inoculation. The relationship between the expression of chalcone synthase genes (CHS) and dynamic changes in chromone content was explored in resin-deposited parts of the trunks of A. sinensis. CHS gene expression levels were detected by qRT-PCR analysis. The chemical composition of agarwood obtained from the heartwood of A. sinensis before and within 1 year after induction was determined by GC-MS. After induction with FA stimulation combined with F. sp. A2 inoculation, the CHS1 gene showed relatively high expression, whereas the CHS2 gene showed low expression. The relative gene expression level of CHS1 peaked at 12 months, with a 153.1-fold increase, and the dominant period of the CHS2 gene expression was 10 months with a 14.13-fold increase. Moreover, chromones were not detected until after 2 months, and a large proportion of chromone compounds were detected after 4 months. Chromone content increased with time and peaked at 12 months. CHS1 gene expression was significantly correlated with 6-hydroxy-2-(2-phenylethyl)chromone accumulation, and CHS2 gene expression was significantly correlated with 5-hydroxy-6-methoxy-2-(2-phenylethyl)chromone accumulation. CHS gene expression was extremely sensitive to FA stimulation combined with F. sp. A2 inoculation and responded to late-onset injury. CHS genes expression also preceded the chromone accumulation. This work laid the foundation for studies on the mechanism by which genes regulate chromone biosynthesis pathways during the formation of agarwood resin in A. sinensis. [ABSTRACT FROM AUTHOR]

N-myc downstream-regulated gene 4 (NDRG4) has previously been investigated as a possible tumor suppressor. Hypermethylation of tumor suppressor genes contributes to the occurrence and development of certain types of cancer, including acute myeloid leukemia (AML). The current study aimed to assess the contribution of chemotherapy-induced NDRG4 changeable methylation to the development of AML. A total of 30 patients (13 males and 17 females) were involved in the present study. The DNA methylation levels of five C-phosphate-G sites of the NDRG4 gene were measured using bisulfite pyrosequencing techniques. The results indicated significantly reduced gene-body methylation levels of NDRG4 during chemotherapy (prior to chemotherapy: 9.35±4.22%; following chemotherapy: 7.54±3.11%; P=0.030). Further analysis of AML subtypes revealed the methylation reductions were principally contributed by patients with M2 subtype AML (prior to chemotherapy: 9.91±4.76%; following chemotherapy: 5.26±1.16%; P=0.038). A significant association was also observed between the patient age and the altered levels of NDRG4 gene-body methylation in patients with M2 subtype AML (r=0.761; P=0.047), suggesting that reductions in induced-methylation may be age-dependent in patients with M2 subtype AML during chemotherapy. Therefore, age may affect the induced methylation levels of NDRG4 gene-body in patients with AML (particularly patients with M2 subtype AML) during chemotherapy. [ABSTRACT FROM AUTHOR]

The DNA mismatch repair (MMR) gene MutL homolog 1 (MLH1) is critical for the maintenance of genomic integrity. Methylation of the MLH1 gene promoter was identified as a prognostic marker for numerous types of cancer including glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to determine whether MLH1 promoter methylation was associated with survival in male patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin-embedded ESCC tissues were collected from 87 male patients. MLH1 promoter methylation was assessed using the methylation-specific polymerase chain reaction approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate the association between MLH1 promoter methylation and overall survival (OS) in patients with ESCC. Cox regression analysis was used to obtain crude and multivariate hazard ratios (HR), and 95% confidence intervals (CI). The present study revealed that MLH1 promoter methylation was observed in 53/87 (60.9%) of male patients with ESCC. Kaplan-Meier survival analysis demonstrated that MLH1 promoter hypermethylation was significantly associated with poorer prognosis in patients with ESCC (P=0.048). Multivariate survival analysis revealed that MLH1 promoter hypermethylation was an independent predictor of poor OS in male patients with ESCC (HR=1.716; 95% CI=1.008-2.921). Therefore, MLH1 promoter hypermethylation may be a predictor of prognosis in male patients with ESCC. [ABSTRACT FROM AUTHOR]

Advanced technology fosters the growing adoption offlipped classrooms. However, several pitfalls associated with flipped classrooms, especially, lack of students ' engagement in pre-assessment and in-class exercises, warrant educators' special attentions. In this study, we shared our rationales and pedagogical approaches to illustrate how we designed inclass exercises to improve students ' active learning experience through meaningful interaction between instructors and students. While preassessment activities focus on lower-level cognitive activities centered on building knowledge and comprehension, our in-class activities focus on the facilitation of higher-level learning and application. We experimented with using different modes of questions to enhance students ' learning effectiveness. Many students identified in-class exercises as the most prominent factor that contributed to their learning success. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma is a commonly malignant tumor of digestive tract with poor prognosis. Previous studies suggested that forkhead box F2 (FOXF2) could be a candidate gene for assessing and predicting the prognosis of human cancers. However, the relationship between FOXF2 promoter methylation and the prognosis of esophageal squamous cell carcinoma remained unclear. Formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma tissues of 135 esophageal squamous cell carcinoma patients were detected for FOXF2 promoter methylation status by methylation-specific polymerase chain reaction approach. DNA methylation results were evaluated with regard to clinicopathological features and overall survival. Our study confirmed that FOXF2 promoter hypermethylation could independently predict a poorer overall survival of esophageal squamous cell carcinoma patients (p = 0.002), which was consistent with the data mining results of the data from 82 esophageal squamous cell carcinoma patients in The Cancer Genome Atlas datasets (p = 0.036). In addition, no correlation was found between FOXF2 promoter methylation and other clinic pathological parameters (age, gender, differentiation, lymph node metastasis, stage, cutting edge, vascular invasion, smoking behavior, and drinking history). In conclusion, FOXF2 methylation might be a useful prognostic biomarker for esophageal squamous cell carcinoma patients. [ABSTRACT FROM AUTHOR]

Background and Purpose: Limited data exist on health-related quality of life (HRQoL) after intracerebral haemorrhage (ICH). We aimed to determine baseline factors associated with HRQoL among participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2).Methods: The INTERACT studies were randomised controlled trials of early intensive blood pressure (BP) lowering in patients with ICH (<6 hours) and elevated systolic BP (150-220 mm Hg). HRQoL was determined using the European Quality of Life Scale (EQ-5D) at 90 days, completed by patients or proxy responders. Binary logistic regression analyses were performed to identify factors associated with poor overall HRQoL.Results: 2756 patients were included. Demographic, clinical and radiological factors associated with lower EQ-5D utility score were age, randomisation outside of China, antithrombotic use, high baseline National Institutes of Health Stroke Scale (NIHSS) score, larger ICH, presence of intraventricular extension and use of proxy responders. High (≥14) NIHSS score, larger ICH and proxy responders were associated with low scores in all five dimensions of the EQ-5D. The NIHSS score had a strong association with poor HRQoL (p<0.001). Female gender and antithrombotic use were associated with decreased scores in dimensions of pain/discomfort and usual activity, respectively.Conclusions: Poor HRQoL was associated with age, comorbidities, proxy source of assessment, clinical severity and ICH characteristics. The strongest association was with initial clinical severity defined by high NIHSS score.Trial Registration Numbers: NCT00226096 and NCT00716079; Post-results. [ABSTRACT FROM AUTHOR]

Catechol-O-methyltransferase (COMT) gene variation is known to be associated with the risk of acute coronary events. The purpose of the present study was to investigate the contribution of COMT promoter methylation towards the risk of coronary heart disease (CHD). COMT methylation was evaluated in 48 CHD cases and 48 well-matched non-CHD controls using bisulfite pyrosequencing technology. The results demonstrated that CHD cases had a significantly lower level of methylation at COMT CpG3 sites compared with the controls (33.77±5.71 vs. 36.42±5.00%; P=0.018). Further analysis, according to gender, showed that CpG3 methylation was associated with CHD in males (P=0.038) but not in females (P=0.253), suggesting that there is a gender disparity in the association between COMT methylation and CHD. In conclusion, it was determined that COMT CpG3 hypomethylation is associated with an increased risk of CHD in males. [ABSTRACT FROM AUTHOR]