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The optimization of job shop scheduling is pivotal for improving overall production efficiency within a workshop. In demand-driven personalized production modes, achieving a balance between workshop resources and the diverse demands of customers presents a challenge in scheduling. Additionally, considering the self-interested behaviors of agents, this study focuses on tackling the problem of multi-agent job shop scheduling with private information. Multiple consumer agents and one job shop agent are considered, all of which are self-interested and have private information. To address this problem, a two-stage decentralized algorithm rooted in the genetic algorithm is developed to achieve a consensus schedule. The algorithm allows agents to evolve independently and concurrently, aiming to satisfy individual requirements. To prevent becoming trapped in a local optimum, the search space is broadened through crossover between agents and agent-based block insertion. Non-dominated sorting and grey relational analysis are applied to generate the final solution with high social welfare. The proposed algorithm is compared using a centralized approach and two state-of-the-art decentralized approaches in computational experiments involving 734 problem instances. The results validate that the proposed algorithm generates non-dominated solutions with strong convergence and uniformity. Moreover, the final solution produced by the developed algorithm outperforms those of the decentralized approaches. These advantages are more pronounced in larger-scale problem instances with more agents. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) have been studied for damaged liver repair; however, the conclusions drawn regarding their homing capacity to the injured liver are conflicting. Besides, the relative utility and synergistic effects of these two cell types on the injured liver remain unclear. Methodology/Principal Findings: MSCs, HSCs and the combination of both cells were obtained from the bone marrow of male mice expressing enhanced green fluorescent protein(EGFP)and injected into the female mice with or without liver fibrosis. The distribution of the stem cells, survival rates, liver function, hepatocyte regeneration, growth factors and cytokines of the recipient mice were analyzed. We found that the liver content of the EGFP-donor cells was significantly higher in the MSCs group than in the HSCs or MSCs+HSCs group. The survival rate for the MSCs group was significantly higher than that of the HSCs or MSCs+HSCs group; all surpassed the control group. After MSC-transplantation, the injured livers were maximally restored, with less collagen than the controls. The fibrotic areas had decreased to a lesser extent in the mice transplanted with HSCs or MSCs+HSCs. Compared with mice in the HSCs group, the mice that received MSCs had better improved liver function. MSCs exhibited more remarkable paracrine effects and immunomodulatory properties on hepatic stellate cells and native hepatocytes in the treatment of the liver pathology. Synergistic actions of MSCs and HSCs were most likely not observed because the stem cells in liver were detected mostly as single cells, and single MSCs are insufficient to provide a beneficial niche for HSCs. Conclusions/Significance: MSCs exhibited a greater homing capability for the injured liver and modulated fibrosis and inflammation more effectively than did HSCs. Synergistic effects of MSCs and HSCs were not observed in liver injury. [ABSTRACT FROM AUTHOR]

The petrochemical as well as zircon U-Pb and Lu-Hf isotopic studies of granulite facies metamorphic rock from the Ta0xi Group in eastern Nanling Range, Central Cathaysia indicate that its protolith is the sedimentary rock with low maturation index. The clastic materials are mostly from middle Neoproterozoic (∼736 Ma) granitoid rocks with minor Neoarchaean and Paleoproterozoic rocks. The timing of this Neoproterozoic magmatism is in agreement with the second period of magmatism widespread surrounding the Yangtze Block. Hf isotopic data indicate that the Neoproterozoic granitoids resulted from the recycled Paleoproterozoic mantle-derived crustal materials. The sedimentary rock was deposited in Late Neoproterozoic Era, and carried into low crust in Early Paleozoic. The partial melting of the meta-sedimentary rock took place at about 480 Ma and subsequently granulite facies metamorphism occurred at ca. 443 Ma. The zircons forming during this time interval (Early Paleozoic) show large Hf isotope variations, and their ϵHf(t) values increase from -13.2 to +2.36 with decreasing age, suggesting the injection of mantle-derived materials during partial melting and metamorphism processes in the Early Paleozoic. Calculation results show that this metamorphic rock, if evolved to Mesozoic, has similar isotopic composition to the nearby Mesozoic high Si peraluminous granites, implying that this kind of granulite facies metamorphic rock is probably the source material of some Mesozoic peraluminous granitoids in eastern Nanling Range. [ABSTRACT FROM AUTHOR]

Background. This study was designed to identify the potassium-channel opener pinacidil as a cardioplegic agent vs hyperkalemic cardioplegia in terms of its efficacy in immature cardioprotection.Methods. By a Langendorff model, 21 hearts of 21- to 28-day-old New Zealand rabbits underwent 90 min of global hypothermic (15°C) ischemia protected with a different single dose of hypothermic (4°C) cardioplegia (pinacidil [50 μmol/l], St. Thomas’ solution combined with pinacidil [50 μmol/l], and St. Thomas’ solution). The percent recovery of the cardiac function, creatine kinase release, and cellular ultrastructure were compared.Results. Pinacidil (50 μmol/l) provided significantly the best postreperfused percentage recovery of the function than the other groups; pinacidil cardioplegia showed a significant reduction of creatine kinase release in the coronary flow compared with the other groups; St. Thomas’ solution combined with pinacidil showed the highest release. Percentage recovery of the coronary flow, water contents, and ultrastructural changes were similar between the groups.Conclusions. Pinacidil provided better protection during ischemia-reperfusion in the immature rabbit heart than St. Thomas’ solution, whereas pinacidil combined with St. Thomas’ solution showed the worst protective effects in immature hearts. [Copyright &y& Elsevier]

Introduction: Recurrence after microwave ablation (MWA) has not been extensively studied. We aimed to investigate the patterns, treatments, and survival of patients with hepatocellular carcinoma (HCC) who experienced early and late recurrence after MWA. Methods: This retrospective study included patients with HCC recurrence after MWA as the initial treatment from January 2008 to December 2021. Recurrence patterns, treatments, and outcomes between patients with early and late HCC recurrence were compared. Prognostic factors of post-recurrence survival (PRS) were identified by multivariable Cox regression analyses. Results: Among 222 patients, 128 developed early recurrence (≤2 years after MWA) and 94 had late recurrence (>2 years). Majority of the recurrent HCC were intrahepatic-only recurrence, within the Milan criteria, and received potentially curative treatment. No significant differences in the recurrence patterns, vascular invasion, tumor staging, post-recurrence treatments, or median PRS (35.0 vs. 33.0 months, p = 0.523) were identified between patients with early and late recurrence. Multivariable analyses suggested that multiple tumor number (hazard ratio [HR]: 1.54; 95% CI: 1.03–2.30, p = 0.038), extrahepatic recurrence (HR: 2.14, 95% CI: 1.16–3.92, p = 0.015), vascular invasion (HR: 2.37, 95% CI: 1.18–4.76, p = 0.038), and higher ALBI grade (HR: 2.18, 95% CI: 1.54–3.08, p < 0.001) were independent risk factors of worse PRS, while curative treatment after recurrence (HR: 0.59, 95% CI: 0.38–0.92, p = 0.020) was associated with better PRS. Conclusions: No differences in recurrence patterns, post-recurrence treatments, or PRS were found between HCC patients with early and late recurrence following MWA. Tumor burden and patients' liver function reserve should be considered to decide the optimal post-recurrence treatment after MWA. [ABSTRACT FROM AUTHOR]

Looks at some of the factors which limit the development of volcanic crust, while highlighting various types of volcanic crust which can be found. Factors which influence the composition of the crust; Details on some of the crust materials.

Warfarin is the most often anticoagulant choice for preventable thromboembolism. Notably, vitamin K plays a vital role in the process of warfarin's anticoagulant effect. Therefore, we presume NPC1L1, a key transporter of vitamin K (VK) intestinal absorption, may modulate the anticoagulant effect of warfarin. Studies have shown that NPC1L1(‐762T>C, rs2073548) and p53 (P72R, rs1042522) variations are implicated in influencing NPC1L1 expression. This study aimed to assess the association between these two variants and warfarin stable dose (WSD). A two‐stage extreme phenotype design was used to explore the influence of these two variants (rs2073548, rs1042522) on WSD variance in 655 Chinese patients undergoing heart valve replacement surgery. NPC1L1 rs2073548, p53 rs1042522, VKORC1 rs9923231 and CYP2C9*1/*3 polymorphisms were genotyped by polymerase chain reaction‐restriction fragment polymorphism (PCR‐RFLP) or Sanger sequencing, respectively. WSD was identified when target monitoring international normalized ratio (INR) value at 2.0‐3.0. In the discovery phase, NPC1L1 rs2073548 A allele carriers occupied a significantly higher rate in the low dose group (P =.019). However, in the validation group, warfarin dosage in patients with the rs2073548 AA, AG and GG genotypes were 2.91 ± 0.97 mg/day, 3.02 ± 1.00 mg/day and 3.00 ± 1.06 mg/day, respectively. Multiple linear regression analysis results suggested that CYP2C9*3 and VKORC1 rs9923231, but not NPC1L1 rs2073548, were independent predictors of WSD in Chinese heart valve replacement (HVR) surgical patients. [ABSTRACT FROM AUTHOR]

Background: Stem cell transplantation shows great potential to improve the long-term survival of cirrhosis patients. However, therapeutic effects may not be homogeneous across the whole study population. This study constructed an easy-to-use nomogram to improve prognostic prediction and aid in treatment decision making for cirrhotic patients. Methods: From August 2005 to April 2019, 315 patients with decompensated cirrhosis receiving autologous peripheral blood stem cell (PBSC) transplantation were enrolled in this study. They were randomly classified into training (2/3) and validation (1/3) groups. A predictive model was developed using Cox proportional hazard models and subsequently validated. The predictive performance of the model was evaluated and also compared with other prognostic models. Results: Age, creatinine, neutrophil-to-lymphocyte ratio, and Child–Turcotte–Pugh class were included in the nomogram as prognostic variables. The nomogram showed high discrimination power concerning the area under receiver operating characteristic curves (3/5-year AUC: 0.742/0.698) and good consistency suggested by calibration plots. Patients could be accurately stratified into poor- and good-outcome groups regarding liver-transplantation free survival after receiving PBSC therapy (P < 0.001). Compared with poor-outcome group, the liver function of patients listed for liver transplantation in the good-outcome group was significantly improved (P < 0.001). Besides, our nomogram achieved a higher C-index (0.685, 95% CI 0.633–0.738) and better clinical utility compared with other conventional prognostic models. Conclusions: The proposed nomogram facilitated an accurate prognostic prediction for patients with decompensated cirrhosis receiving PBSC transplantation. Moreover, it also held the promise to stratify patients in clinical trials or practice to implement optimal treatment regimens for individuals. [ABSTRACT FROM AUTHOR]

Epigenetic modification occurring in RNA has become the hotspot of the field. N6-methyladenosine (m6A) methylation is the most abundant RNA internal modification mainly occurring at the consensus motif DR (m6A) CH (D = A/G/U, R = A/G, H = A/C/U) in the 3'-UTR particularly the region near stop codons. The life cycle of m6A methylation includes "writers," "erasers," and "readers", which are responsible for the addition, removal, and recognition of m6A, respectively. m6A modification has been reported changing RNA secondary structure or modulating the stability, localization, transport, and translation of mRNAs to play crucial roles in various physiological and pathological conditions. Liver, as the largest metabolic and digestive organ, modulates vital physiological functions, and its dysfunction gives rise to the occurrence of various diseases. Despite the advanced intervening measures, mortality due to liver diseases is continuously high. Recent studies have explored the roles of m6A RNA methylation in the pathogenesis of liver diseases, providing new insights for studying the molecular mechanism of liver diseases. In the review, we extensively summarize the life cycle of m6A methylation, as well as its function and relevant mechanisms in liver fibrosis (LF), nonalcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatitis virus infection, and hepatocellular carcinoma (HCC), and eventually we explore the potential of m6A as a treatment option for these liver diseases. [ABSTRACT FROM AUTHOR]

Anomaly event detection in crowd scenes is extremely important; however, the majority of existing studies merely use hand-crafted features to detect anomalies. In this study, a novel unsupervised deep learning framework is proposed to detect anomaly events in crowded scenes. Specifically, low-level visual features, energy features, and motion map features are simultaneously extracted based on spatiotemporal energy measurements. Three convolutional restricted Boltzmann machines are trained to model the mid-level feature representation of normal patterns. Then a multimodal fusion scheme is utilized to learn the deep representation of crowd patterns. Based on the learned deep representation, a one-class support vector machine model is used to detect anomaly events. The proposed method is evaluated using two available public datasets and compared with state-of-the-art methods. The experimental results show its competitive performance for anomaly event detection in video surveillance. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cell (MSC) therapy has been shown to be a promising option for liver fibrosis treatment. However, critical factors affecting the efficacy of MSC therapy for liver fibrosis remain unknown. Follistatin-like 1 (FSTL1), a TGF-β-induced matricellular protein, is documented as an intrinsic regulator of proliferation and differentiation in MSCs. In the present study, we characterized the potential role of FSTL1 in MSC-based anti-fibrotic therapy and further elucidated the mechanisms underlying its action. Methods: Human umbilical cord-derived MSCs were characterized by flow cytometry. FSTL1low MSCs were achieved by FSTL1 siRNA. Migration capacity was evaluated by wound-healing and transwell assay. A murine liver fibrotic model was created by carbon tetrachloride (CCl4) injection, while control MSCs or FSTL1low MSC were transplanted via intravenous injection 12 weeks post CCl4 injection. Histopathology, liver function, fibrosis degree, and inflammation were analysed thereafter. Inflammatory cell infiltration was evaluated by flow cytometry after hepatic nonparenchymal cell isolation. An MSC-macrophage co-culture system was constructed to further confirm the role of FSTL1 in the immunosuppressive capacity of MSCs. RNA sequencing was used to screen target genes of FSTL1. Results: FSTL1low MSCs had comparable gene expression for surface markers to wildtype but limited differentiation and migration capacity. FSTL1low MSCs failed to alleviate CCl4-induced hepatic fibrosis in a mouse model. Our data indicated that FSTL1 is essential for the immunosuppressive action of MSCs on inflammatory macrophages during liver fibrotic therapy. FSTL1 silencing attenuated this capacity by inhibiting the downstream JAK/STAT1/IDO pathway. Conclusions: Our data suggest that FSTL1 facilitates the immunosuppression of MSCs on macrophages and that guarantee the anti-fibrotic effect of MSCs in liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: Despite emerging evidence on the therapeutic potential of mesenchymal stem cells (MSCs) for liver fibrosis, the underlying mechanisms remain unclear. At present, MSC-derived exosomes (MSC-EXOs) are widely accepted as crucial messengers for intercellular communication. This study aimed to explore the therapeutic effects of MSC-EXOs on liver fibrosis and identify the mechanisms underlying the action of MSC-EXOs. Methods: Carbon tetrachloride was used to induce a liver fibrosis model, which was intravenously administered with MSCs or MSC-EXOs to assess treatment efficacy. The resulting histopathology, fibrosis degree, inflammation and macrophage polarization were analyzed. RAW264.7 and BMDM cells were used to explore the regulatory effects of MSC-EXOs on macrophage polarization. Then, the critical miRNA mediating the therapeutic effects of MSC-EXOs was screened via RNA sequencing and validated experimentally. Furthermore, the target mRNA and downstream signaling pathways were elucidated by luciferase reporter assay, bioinformatics analysis and western blot. Results: MSCs alleviated liver fibrosis largely depended on their secreted exosomes, which were visualized to circulate into liver after transplantation. In addition, MSC-EXOs were found to modulate macrophage phenotype to regulate inflammatory microenvironment in liver and repair the injury. Mechanically, RNA-sequencing illustrates that miR-148a, enriched in the MSC-EXOs, targets Kruppel-like factor 6 (KLF6) to suppress pro-inflammatory macrophages and promote anti-inflammatory macrophages by inhibiting the STAT3 pathway. Administration of miR-148a-enriched MSC-EXOs or miR-148a agomir shows potent ameliorative effects on liver fibrosis. Conclusions: These findings suggest that MSC-EXOs protect against liver fibrosis via delivering miR-148a that regulates intrahepatic macrophage functions through KLF6/STAT3 signaling and provide a potential therapeutic target for liver fibrosis. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of different dosage regimens of saffron supplementation on improving sleep quality among healthy adults, patients with insomnia or type 2 diabetes and patients under Methadone maintenance treatment (MMT).Methods: PubMed, Embase, The Cochrane Library and other databases were searched from inception until October 2021. Randomized controlled trials (RCTs) investigating the efficacy saffron supplementation on sleep quality were included. Data were extracted independently by 2 investigators and assessed the study quality by the Cochrane risk-of-bias tool. The measurements include Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and Restorative Sleep Questionnaire (RSQ).Results: The pooling of the effect sizes showed that saffron group achieve a notable treatment effect on PSQI (MD: -2.14; 95% CI: -2.86 to -1.42; P < 0.01), ISI (MD: -2.63; 95% CI: -3.70 to -2.55; P < 0.01) and RSQ (MD: 7.05; 95% CI: 1.48 to 12.62; P = 0.01) compared with placebo group.Conclusion: Saffron supplementation as a treatment for improving sleep quality have promising clinical application as its great improvement on all efficacy outcomes and no serious adverse advents occurred as the dose was increased. The dose of 100 mg saffron supplementation per day was proved to achieve excellent and more stable curative effect on improving sleep quality in our subgroup analysis. However, further investigation is necessary to confirm the efficacy and long-term safety of different doses of saffron for insomnia. [ABSTRACT FROM AUTHOR]

Esketamine is a promising drug which can induce antidepressant effects in Major Depression Disorder (MDD). Several randomized controlled trials (RCTs) have been implemented to assess the efficacy and safety of esketamine for the treatment of MDD. Therefore, we carried out a meta-analysis to assess adverse effect profiles of esketamine for the treatment of MDD. We searched RCTs which were implemented from January 2010 to June 2020 by searching PubMed, Embase and Cochrane Library databases. Finally, four RCTs with 551 patients were included in our study. We pooled 551 patients from 4 RCTs. Compared with placebo, an increased risk of adverse effects was observed in our analysis. After using esketamine, the risk of nausea (RR = 2.34, 95% CI, 1.04 to 5.25, P = 0.04), dissociation (RR = 4.54, 95% CI, 2.36 to 8.73, P < 0.00001), dizziness (RR = 3.00, 95% CI, 1.80 to 5.00, P < 0.0001), vertigo (RR = 7.47, 95% CI, 2.55 to 21.86, P = 0.0002), hypoesthesia (RR = 5.68, 95% CI, 2.06 to 15.63, P = 0.0008), sedation (RR = 3.96, 95% CI, 1.29 to 12.15, P = 0.02) and paresthesia(RR = 3.05, 95% CI, 1.07 to 8.65, P = 0.04)were significantly increased compared with placebo. Our synthesized data analysis revealed drug specific risk profiles. The most frequent adverse effects under treatment with esketamine were nausea, dissociation, dizziness, vertigo, hypoesthesia,sedation and paresthesia. [ABSTRACT FROM AUTHOR]

Abstract: Epigenetic changes are of crucial importance in the etiopathogenesis of autoimmune liver diseases. Among these, there is limited agreement on the definitions and treatment of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) overlap syndromes, we evaluated a large series of consecutive patients with PBC (n = 565) and AIH (n = 196) to identify a group of patients with corticosteroid-responsive PBC-AIH overlap syndrome. Within this series, a total of 490 patients were biopsied based upon staging or diagnostic needs. Review of the biopsies in conjunction with the International AIH Group criteria identified 80 patients with suspected overlap syndrome and 52 patients agreed to participate in the study and were prospectively treated with corticosteroids. Of these, 40/52 (77%) achieved a complete biochemical response (i.e. normal ALT, AST, and IgG) within 12 months of treatment. A survey of pre-treatment characteristics of the 40 responders revealed more severe interface hepatitis. Serum IgG levels ≥1.3x the upper limit of normal had 60% sensitivity and 97% specificity rates for steroid-responsiveness while the use of a higher threshold (≥2.0x) reduced sensitivity to 10%. When the Paris criteria for PBC-AIH were applied to the steroid-responsive patients, 29/40 (73%) cases fulfilled at least two of the three Paris criteria. Applying the recently designed simplified IAIHG scoring system, 35/40 (88%) had a “definite” diagnosis of AIH. This study supports the hypothesis that a complete response to corticosteroids may denote a variant of a PBC-AIH overlap syndrome which could be identified prior to treatment by modified Paris criteria in concert with the simplified IAIHG scoring system. [Copyright &y& Elsevier]

Adaptive dynamic programming (ADP) is a promising research field for design of intelligent controllers, which can both learn on-the-fly and exhibit optimal behavior. Over the past decades, several generations of ADP design have been proposed in the literature, which have demonstrated many successful applications in various benchmarks and industrial applications. While many of the existing researches focus on multiple-inputs-single-output system with steepest descent search, in this paper we investigate a generalized multiple-input-multiple-output (GMIMO) ADP design for online learning and control, which is more applicable to a wide range of practical real-world applications. Furthermore, an improved weight-updating algorithm based on recursive Levenberg–Marquardt methods is presented and embodied in the GMIMO approach to improve its performance. Finally, we test the performance of this approach based on a practical complex system, namely, the learning and control of the tension and height of the looper system in a hot strip mill. Experimental results demonstrate that the proposed approach can achieve effective and robust performance. [ABSTRACT FROM AUTHOR]

Erythroid parameters have been indicated to be important prognostic factors for liver diseases. The present study aimed to evaluate the prognostic value of the erythrocyte count in Chinese patients with primary biliary cholangitis (PBC) and develop a prognostic model. The clinical data of 301 patients with PBC were retrospectively reviewed. Univariate and multivariate Cox regression analysis was performed to identify potential prognostic risk factors. Bivariate correlation analysis was used to determine the correlation coefficient of the erythrocyte count and biochemical indices. The prognostic values of different factors were compared by receiver operating characteristic (ROC) curve analysis. A novel prognostic model was constructed using multivariate logistic regression. Multivariate regression analysis suggested that the erythrocyte count was an independent risk factor/prognostic index (P=0.042). The erythrocyte count in peripheral blood decreased as the histological stage progressed (P<0.001). The erythrocyte count was correlated with albumin, liver stiffness and Fibrosis-4. Compared with that of platelets, the area under the ROC curve of the erythrocyte count was significantly greater. A similar area under the ROC curve was determined for the erythrocyte count, albumin and total bilirubin (P>0.05). A novel prognostic model was established as follows: P=1/{1 + e-[6.140–3.193 × Ln(erythrocyte count) −0.184 × albumin + 0.827 × Ln(total bilirubin)]}. The novel model had a comparable prognostic value to that of the GLOBE score and UK-PBC risk score, and had a better performance than the Mayo risk score at baseline (0.838 vs. 0.787). In conclusion, the erythrocyte count is an independent risk factor/prognostic index in Chinese patients with PBC. It was correlated with liver function and fibrosis in Chinese patients. The novel model incorporating the erythrocyte count and biochemical indices at baseline may serve as a prognostic tool in Chinese patients with PBC (Trial registration number, ChiCTR-ONRC-10002070; date of registration, 2010-05-10). [ABSTRACT FROM AUTHOR]

No consensus has been achieved on the superiority between neuroendoscopy (NE) and craniotomy (CT) for the treatment of supratentorial hypertensive intracerebral hemorrhage (HICH). The purpose of this study is to analyze the efficacy and safety of NE versus CT for supratentorial HICH. A systematic search of English databases (PubMed, Embase, the Cochrane Library, and Web of Science) was performed to identify related studies reported from September 1994 to June 2019. The Newcastle-Ottawa Scale and the Cochrane Reviewer's Handbook 5.0.0 were separately used to evaluate the quality of the included observational studies and randomized controlled trials. RevMan 5.3 software was adopted to conduct the meta-analysis. The outcome measures included the primary and secondary outcomes. Subgroup analysis was performed to explore the impact of year of publication, initial Glasgow Coma Scale (GCS) score, age, time to surgery, hematoma volume, and surgical methods on the outcome measures. Fifteen studies (3 randomized controlled trials and 12 observational studies), comprising 1859 patients with supratentorial HICH, were included in this meta-analysis. The pooled results showed that NE could increase the good functional outcome (GFO) (P < 0.0003) and hematoma evacuation rate (P = 0.0007) and reduce the mortality (P < 0.00001), blood loss (P = 0.004), operation time (P < 0.00001), hospital stays (P = 0.006), and intensive care unit stays (P < 0.0001) compared with CT. In addition, NE could also have a positive effect on preventing postoperative infection (P < 0.00001) and total complications (P < 0.00001). However, in postoperative rebleeding incidence (P = 0.12), no obvious difference was found between the 2 groups. Publication bias was low regarding GFO, mortality, and hematoma evacuation rate. Subgroup analysis suggested that year of publication, initial GCS score, age, hematoma volume, and surgical methods did not affect the hematoma evacuation rate significantly. The difference in mortality was not statistically significant in the subgroup of hematoma volume <50 mL (P = 0.44) and initial GCS score >8 (P = 0.09). In addition, the data suggested that time to surgery and surgical methods might be the important factors affecting GFO and mortality. NE might be a safer and more effective surgical method than CT in the treatment of patients with supratentorial HICH. However, because of the existence of some limitations, the safety and validity of NE were weakened. More high-quality trials should be included to verify our conclusion. [ABSTRACT FROM AUTHOR]

Aortic valve interstitial cells (AVICs) have the potential to undergo calcification, which has been regarded as a critical issue during the pathology of calcific aortic valve disease (CAVD). In the past decade, epigenetics, in particular, DNA methylation dysregulation, has been reported to play a vital role in the occurrence and development of CAVD. In the present study, the expression of Notch1, which can inhibit the osteogenesis differentiation of valve interstitial cells, was downregulated whereas the expression of methyltransferases was upregulated in CAVD tissues, suggesting the potential role of DNA methylation in Notch1 expression and CAVD progression. As revealed by DNA extraction and bisulfite sequencing polymerase chain reaction (PCR), the methylation level in Notch1 promoter was much higher in CAVD tissues and human AVICs on Day 14 of osteogenesis differentiation induction. The silence of Notch1 intercellular domain (NICD) promoted while the treatment of demethylation agent, 5‐Aza‐dC, inhibited the osteogenesis differentiation. Moreover, NICD overexpression significantly suppressed the transcriptional activity of β‐catenin on TCF4, and the expression of osteogenesis differentiation factors, indicating the involvement of Wnt/β‐catenin signaling in Notch1 modulating the osteogenesis differentiation in human AVICs (hAVICs). Taken together, Notch1 promoter methylation leads to a decreased Notch1 expression and subsequent decreased release of NICD in the nucleus of hAVICs, therefore promoting the activation of Wnt/β‐catenin signaling and the expression of osteogenesis differentiation factors, finally promoting the osteogenesis differentiation in hAVICs. DNA methylation might act as an important bridge to link epigenetic variation and CAVD progression. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related death among both men and women every year, mainly due to metastasis. Although natural compound deguelin has been reported to inhibited cell migration and invasion in various cancer cells, the details of this regulation progress remain to be fully elucidated. In this study, we investigated the underlying mechanism of deguelin-suppressed metastasis of non-small cell lung cancer (NSCLC) cells. Our results demonstrate that deguelin inhibits NSCLC cell migration, invasion, and metastasis both in vitro and in vivo . These inhibitory effects of deguelin were mediated by suppressing of Cathepsin Z (CtsZ) expression and interrupting the interaction of CtsZ with integrin β3. Moreover, deguelin inhibits the activation of CtsZ downstream FAK/Src/Paxillin signaling. Knockdown of CtsZ mimicked the effect of deguelin on NSCLC cells migration and invasion. Our study reveals that deguelin exerts its anti-metastatic effect both in vitro and in vivo is partly dependent on the suppression of CtsZ signaling. Deguelin would be a potential anti-metastasis agent against NSCLC. [ABSTRACT FROM AUTHOR]

To study I Flnc i in adult cardiomyocytes, we generated icKO mice (inducible cardiomyocyte-specific knockout) by crossing I Flnc i -floxed mice with MHC-MerCreMer mice and subjected them to tamoxifen treatment (TAM) at 2 months of age. Analysis of heart weight to body weight ratios revealed significantly increased heart mass in icKO mice at 2 weeks after TAM compared with control mice, whereas no differences were observed in body weight. Mass spectrometry analysis identified 380 proteins that were upregulated more than 2-fold and 27 proteins that were downregulated more than 2-fold in icKO hearts relative to control hearts. [Extracted from the article]

Reducing costs is a pragmatic method for promoting the widespread usage of indoor localization technology. Conventional indoor localization systems (ILSs) exploit relatively expensive wireless chips to measure received signal strength for positioning. Our work is based on a cheap and widely-used commercial off-the-shelf (COTS) wireless chip, i.e., the Nordic Semiconductor nRF24LE1, which has only several output power levels, and proposes a new power level based-ILS, called Plils. The localization procedure incorporates two phases: an offline training phase and an online localization phase. In the offline training phase, a self-organizing map (SOM) is utilized for dividing a target area into k subregions, wherein their grids in the same subregion have similar fingerprints. In the online localization phase, the support vector machine (SVM) and back propagation (BP) neural network methods are adopted to identify which subregion a tagged object is located in, and calculate its exact location, respectively. The reasonable value for k has been discussed as well. Our experiments show that Plils achieves 75 cm accuracy on average, and is robust to indoor obstacles. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in China and is an exceptionally drug-resistant tumor with a 5-year survival rate less than 15%. Cisplatin is the most commonly used conventional chemotherapeutic drug for the treatment of ESCC, but some patients have a poor response to cisplatin-based chemotherapy. New strategies that could enhance chemosensitivity to cisplatin are needed.Methods: We used reverse transcription-RCR (RT-PCR), immunoblot, immunohistochemical (IHC) staining, anchorage-dependent and -independent growth assays, co-immunoprecipitation (Co-IP) assay, RNA interference and in vivo tumor growth assay to study the expression of MCL-1 in ESCCs and the response of ESCC cells to cisplatin.Results: The present study showed that MCL-1 expression was significantly increased in ESCC tissues compared to normal adjacent tissues and was associated with depth of invasion and lymph node metastasis. Knockdown of MCL-1 produced significant chemosensitization to cisplatin in association with caspase-3 activation and PARP cleavage in KYSE150 and KYSE510 cells. The selective MCL-1 inhibitor UMI-77 caused dissociation of MCL-1 from the proapoptotic protein BAX and BAK, and enhanced KYSE150 and KYSE510 cells to cisplatin-induced apoptosis accompanied by caspase-3 activation and PARP cleavage.Conclusions: The current study suggests that MCL-1 contributes to the development of ESCC and is a promising therapeutic target for chemosensitization of ESCC cells to cisplatin. This might provide a scientific basis for developing effective approaches to treat the subset of ESCCs patients with MCL-1 overexpression. [ABSTRACT FROM AUTHOR]

Kindlin-2 regulates integrin activation[2] and integrin-independent pathways.[3] A potential role for Kindlin-2 in developing cardiomyocytes, and whether any requirement for Kindlin-2 reflects an integrin-dependent or integrin-independent role for Kindlin-2, remains to be addressed. Kindlin-2/ 1 integrin pathway in cardiomyocytes is essential for preserving the integrity of the developing heart and preventing ventricular rupture. SB 1 sb integrin activation was dramatically reduced in KN2-cKO hearts versus controls (Figure E), indicating that Kindlin-2 was required for SB 1 sb integrin activation in cardiomyocytes. [Extracted from the article]

Background: This study was conducted to assess expression of Galectin-3 (Gal-3) in patients with different types of left ventricle (LV) hypertrophy geometry, and the relationship between Gal-3 expression and LV remodelling in patients with aortic valve stenosis (AS).Methods: Galectin-3 expression was measured in the plasma and myocardia of AS patients who underwent an aortic valve replacement procedure.Results: The study enrolled 77 consecutive patients with severe AS. Fifty-five (71.43%) of the enrolled patients had concentric hypertrophy (CH group), and had the highest degree of fibrosis (27.10±5.25%; p<0.001) and expression of Gal-3 in both plasma (19.11±2.06 ng/mL) and myocardial tissue (3.01±0.79). There was a strong positive correlation between the levels of fibrosis and Gal-3 expression in both plasma (r=0.584, p<0.001) and myocardium (r=0.522, p<0.001). Relative wall thickness (RWT) was strongly correlated with Gal-3 expression in both myocardium (r=0.594, p<0.001) and plasma (r=0.323, p=0.005). Additionally, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were positively correlated with both fibrosis (r=0.313, p=0.036) and LV mass index (r=0.559, p<0.001).Conclusions: Concentric hypertrophy geometry was the most common type of myocardium remodelling, and AS patients with CH geometry showed the highest levels of Gal-3 expression. Galectin-3 levels were positively correlated with fibrosis and RWT, both of which are crucial indicators of geometric remodelling. Galectin-3 and NT-proBNP levels may be valuable prognostic predictors in AS patients with myocardial remodelling. [ABSTRACT FROM AUTHOR]

Icaritin (ICT) is a traditional Chinese medicinal herb proved to be neuroprotective and exerts promoting effects on cardiac differentiation. However, its role in cardioprotection against myocardial ischemia/reperfusion (MI/R) injury remains largely unknown. This study aimed to investigate the effects of ICT treatment on MI/R injury and the underlying mechanisms. Rats were subjected to 30 min of myocardial ischemic insult followed by 3 h of reperfusion. ICT (3, 10, and 30 mg/kg) was administered intraperitoneally 10 min before reperfusion. ICT treatment at the dose of 10 and 30 mg/kg improved cardiac function and limited infarct size following MI/R. Meanwhile, ICT reduced plasma creatine kinase (CK), lactate dehydrogenase (LDH) activities and cardiomyocyte apoptosis in I/R heart tissue. Moreover, ICT treatment not only inhibited the pro-inflammatory cytokine TNF-α production and increased the anti-inflammatory cytokine IL-10 level in myocardium but also reduced the increase in the generation of superoxide content and malondialdehyde (MDA) formation and simultaneously increased the anti-oxidant capability in I/R hearts. Furthermore, ICT treatment increased Akt phosphorylation and inhibited PTEN expression in I/R hearts. PI3K inhibitor wortmannin inhibited ICT-enhanced Akt phosphorylation, and blunted ICT-mediated anti-oxidative and anti-inflammatory effects and cardioprotection. Our study indicated for the first time that ICT reduces inflammation and oxidative stress and protects against MI/R injury in rats, which might be via a PI3K-Akt-dependent mechanism. [ABSTRACT FROM AUTHOR]

Abstract: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown etiology and abnormality of hepatobiliary transport might contribute to its pathogenesis. In this study, we aimed to isolate and identify new molecules associated with PBC. With hepatocyte canalicular membrane vesicles (CMVs) of PBC patients as immunogens, we screened the monoclonal antibody 1F9 (mAb1F9), whose antigen dominantly recognized the subapical domains in hepatocytes in normal livers. Immunohistochemistry revealed that the expression of mAb1F9 antigen (mAb1F9-Ag) significantly increased in PBC livers compared with control groups including normal livers, cirrhosis or cholestasis other than PBC. Interestingly, the augmented expression of mAb1F9-Ag was correlated with the severity of PBC, and ursodeoxycholic acid treatment may significantly improve the recovery of mAb1F9-Ag. In addition, redistribution of mAb1F9-Ag was found in 46% of PBC. mAb1F9-Ag was isolated and analyzed with mass spectrometry, which indicated lysosome-associated membrane protein 2 (LAMP-2) as the candidate. Further studies showed that mAb1F9 recognized LAMP-2 immunoprecipitates and vice verse, mAb1F9 reacted with recombinant LAMP-2. mAb1F9 and LAMP-2 antibody exhibited similar staining pattern and displayed similar subcellular localization. Together, the identity of mAb1F9-Ag is LAMP-2, suggesting that LAMP-2 may assist in the differentiation of PBC and predict a poor outcome in patients with PBC. Biological significance: This manuscript describes the expression of a specific antibody, named mAb1F9. The antigen recognized by mAb1F9 may assist in the differentiation of primary biliary cirrhosis (PBC) and predict a poor outcome in patients with PBC. Through antigen identification, we confirm the identity of mAb1F9-Ag as lysosome-associated membrane protein 2 (LAMP-2). The clinical relevance of the manuscript is well regarded since markers are rare and usually not successful for PBC diagnosis and treatment. [Copyright &y& Elsevier]

Open heart surgery supported by cardiopulmonary bypass is associated with heart and lung ischemia–reperfusion injury (IRI). Limb remote ischemic preconditioning (RIPC) reduces injury caused by ischemia–reperfusion in multiple distant organs. We conducted a prospective clinical trial (randomized and controlled) to test the feasibility and safety of limb RIPC, as well as its protective effects against myocardial and pulmonary IRI for infants undergoing repair of simple congenital heart defects. Infants undergoing repair of ventricular septal defects were enrolled in our study and randomly assigned to one of two treatment groups: limb RIPC or control. RIPC was induced twice (24 h and 1 h preoperatively) via three 5-min cycles of ischemia and reperfusion on the left upper arm using a blood pressure cuff. Lung compliance, respiratory index (RI), and cardiac inotropic score (IS) were calculated for each patient. Serum concentrations of the following factors were measured perioperatively: interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α; lactate dehydrogenase (LDH), creatine kinase (CK), and its isoenzyme (CK-MB), and troponin I (TnI); malondialdehyde (MDA) and superoxide dismutase (SOD). The expression of heat shock protein 70 (HSP 70) in cardiomyocytes was analyzed by Western blot. Surgical outcomes, including limb movement and sensory function, were recorded in detail. Sixty infants weighting less than 7 kg were studied, with 30 patients in the RIPC group and 30 in the control group. Within 6 months of discharge from the hospital, no limb disability, sensory disturbance, or other surgical complications were found in any patient. Compared with the control group, patients in the RIPC group had higher Cs and Cd, along with lower RI and IS at various postoperative phases. At the beginning of the operation, serum concentrations of IL-6, IL-8, IL-10, TNF-α, LDH, CK, and TnI were higher in the RIPC group than the control group. Postoperatively, release of cytokines and leakage of heart enzymes were attenuated in the RIPC group; serum concentrations of cytokines and heart enzymes were lower in the RIPC group at some, but not all, postoperative time points. Furthermore, the RIPC group had lower coronary sinus venous concentrations of MDA and higher concentrations of SOD. Similarly, the expression of HSP 70 was upregulated in cardiomyocytes from the RIPC group. Limb RIPC can be applied safely and easily in infants, can attenuate systemic inflammatory response syndrome, and can increase systemic tolerance to IRI, imparting a protective effect against myocardial and pulmonary IRI. The expression of HSP 70 has an important role in the mechanism of action for RIPC. [ABSTRACT FROM AUTHOR]

Abstract: A geometric active contour model without re-initialization for color images is proposed in this paper. It combines directional information about edge location based on local squared contrast as a part of driving force, together with the improved geodesic active contour containing Bayes error based statistical region information as well as an extra term that penalizes deviation of the level set function from a signed distance function. All these measures are integrated in a unified frame thus the costly re-initialization procedure can be completely eliminated. Experimental results on real color images have shown that our model can extract contours of objects in images precisely and its performance is much better than the Geodesic-Aided C-V (GACV) model. [Copyright &y& Elsevier]

Abstract: In this paper, a novel geometric active contour model for color image is presented. It combines squared local contrast based alignment term about directional information of edge location as part of driving force, together with the improved geodesic active contour model containing Bays error based two-region segmentation information. And all these measures are integrated as a unified framework. Finally, an unconditionally stable and simple numerical scheme, including the narrow band and fast marching methods, is introduced for efficiently implementing this novel model. Experimental results on color image segmentation show that it can extract the contour of color images precisely and its performance is shown much better than the geodesic-aided C–V (GACV) method when directional information about edge location is supplied. [Copyright &y& Elsevier]

Abstract: Although many clustering methods have been presented in the literature, most of them suffer from some drawbacks such as the requirement of user-specified parameters and being sensitive to outliers. For general divisive hierarchical clustering methods, an obstacle to practical use is the expensive computation. In this paper, we propose an automatic divisive hierarchical clustering method (DIVFRP). Its basic idea is to bipartition clusters repeatedly with a novel dissimilarity measure based on furthest reference points. A sliding average of sum-of-error is employed to estimate the cluster number preliminarily, and the optimum number of clusters is achieved after spurious clusters identified. The method does not require any user-specified parameter, even any cluster validity index. Furthermore it is robust to outliers, and the computational cost of its partition process is lower than that of general divisive clustering methods. Numerical experimental results on both synthetic and real data sets show the performances of DIVFRP. [Copyright &y& Elsevier]

Abstract: This paper provides some new evidences on stratigraphic sequence, zircon SHRIMP dating from ophiolite, granitoids, and fold-and-thrust tectonic styles in the South China Block (SCB). Stratigraphic studies suggest that the eastern and central parts of the SCB show a SW-dipping palaeoslope framework during the Late Palaeozoic–Early Mesozoic. These areas were not in a deep-sea environment, but in a shallow-sea or littoral one. Coeval volcanic rocks are missing. Deep-water deposits and submarine volcanism only took place in the western part of the SCB. The three ophiolitic mélanges of the eastern SCB formed in the Neoproterozoic, but not in the Permian or the Triassic. The sedimentary rocks associated with the Neoproterozoic oceanic relics contain abundant Proterozoic acritarchs, but no radiolarians. The Early Mesozoic granitoids (235–205Ma) belong to the post-collision peraluminous S-type granites; they are widely exposed in the central-western SCB, and rare in the eastern SCB. The fold-and-thrust belt developed in the eastern SCB shows a top-to-the-south displacement, whereas the Xuefengshan Belt of central SCB indicates a north- or northwest-directed shearing. The geodynamic settings of the different parts of the SCB during the Triassic are discussed. [Copyright &y& Elsevier]

Alteration in transforming growth factor-β (TGF-β) signaling pathway is one of the main causes of esophageal squamous cell carcinoma (ESCC). The human runt-related transcription factor 3 (RUNX3), an important component of TGF-β pathway which is located at 1p36, is commonly deleted in a variety of human cancers, including ESCC. Hypermethylation of RUNX3 promoter was frequently found in gastrointestinal cancers, including those of stomach, liver, colon and pancreas. However, RUNX3 promoter methylation status in ESCC has not been studied. The aim of this study was to determine whether promoter methylation of the RUNX3 gene correlates with ESCC tumor progression.Accordingly, we first determined RUNX3 mRNA expression and methylation status of its promoter region in 42 primary tumors with ESCC and Eca-109, an ESCC cell line. Loss of RUNX3 mRNA expression was detected by RT-PCR in 23 out of 42 (54.8%) ESCC specimens and Eca-109 cells. The Promoter hypermethylation was detected by Methylation Specific Polymerase Chain Reaction (MS-PCR) in 27 out of 42 (64.3%) ESCC specimen and Eca-109 cells.Importantly, we found positive correlations, not only between the promoter hypermethylation and tumor clinical pathologic stages (P = 0.003), but also between the loss of RUNX3 mRNA expression and the tumor progression (P = 0.016). Finally, we observed that the loss of RUNX3 mRNA expression is statistically correlated with the promoter hypermethylation in these tumors (P < 0.001). Our results suggest that epigenetic silencing of RUNX3 gene expression by promoter hypermethylation may play an important role in ESCC development. [ABSTRACT FROM AUTHOR]

Abstract: Here we investigated the roles of DARPP-32 in multidrug resistance (MDR) of gastric cancer cells and the possible underlying mechanisms. We constructed the eukaryotic expression vector of DARPP-32 and transfected it into human vincristine-resistant gastric adenocarcinoma cell line SGC7901/VCR. Up-regulation of DARPP-32 could significantly enhance the sensitivity of SGC7901/VCR cells towards vincristine, adriamycin, 5-fluorouracil and cisplatin, and could decrease the capacity of cells to efflux adriamycin. What''s more, the results of subrenal capsule assay confirmed that DARPP-32 might play a certain role in MDR of gastric cancer. DARPP-32 could significantly down-regulate the expression of P-gp and zinc ribbon domain-containing 1 (ZNRD1), but not alter the expression of multidrug resistance-associated protein (MRP) or the glutathione S-transferase (GST). DARPP-32 could also significantly decrease the anti-apoptotic activity of SGC7901/VCR cells. Further study of the biological functions of DARPP-32 might be helpful for understanding the mechanisms of MDR in gastric cancer. [Copyright &y& Elsevier]

The meadow ecosystem on the Qinghai-Tibetan Plateau is considered to be sensitive to climate change. An understanding of the alpine meadow ecosystem is therefore important for predicting the response of ecosystems to climate change. In this study, we use the coefficients of variation (Cv) and stability (E) obtained from the Haibei Alpine Meadow Ecosystem Research Station to characterize the ecosystem stability. The results suggest that the net primary production of the alpine meadow ecosystem was more stable (Cv = 13.18%) than annual precipitation (Cv = 16.55%) and annual mean air temperature (Cv = 28.82%). The net primary production was insensitive to either the precipitation (E = 0.0782) or air temperature (E= 0.1113). In summary, the alpine meadow ecosystem on the Qinghai- Tibetan Plateau is much stable. Comparison of alpine meadow ecosystem stability with other five natural grassland ecosystems in Israel and southern African indicates that the alpine meadow ecosystem on the Qinghai-Tibetan Plateau is the most stable ecosystem. The alpine meadow ecosystem with relatively simple structure has high stability, which indicates that community stability is not only correlated with biodiversity and community complicity but also with environmental stability. An average oscillation cycles of 3-4 years existed in annual precipitation, annual mean air temperature, net primary production and the population size of consumers at the Haibei natural ecosystem. The high stability of the alpine meadow ecosystem may be resulting also from the adaptation of the ecosystem to the alpine environment. [ABSTRACT FROM AUTHOR]

Discusses how a single zircon LAM-ICPMS U-Pb dating indicates that the Guidong granitic complex is a multistage batholith formed during Indosinian-Yanshanian time. Consideration of how the Luxi body (239 ± 5 Ma) and the Xiazhuang body (235.8 ± 7.6 Ma) intruded during Indosinian time, whereas the Aizi body (160.1 ± 6.1 Ma) and the Siqian body (151 ± 11 Ma) formed during Yanshanian time; Reference to the Inherited zircons in the Xiazhuang body which imply that at least part of the source rocks of the Guidong complex are from the Proterozoic basement of southeast China; Focus on the detailed single zircon LAM-ICPMS U-Pb dating results which provide important evidence for understanding the evolution of tectonic plates.

Trace element patterns of spinel- and garnet peridotite xenoliths from the Nushan and Mingxi basalts (SE China) reflect the interplay between partial melting and subsequent enrichment by metasomatism. Trace element patterns indicate the common addition of Th, Sr and LREE, but not of significant Ti and Zr, which suggests a metasomatising agent (or agents) with characteristics of H2O-rich and CO2-rich fluids.Laser Ablation Microprobe linked to an Inductively Coupled Plasma Mass Spectrometer (LAM-ICPMS) analyses of volatile-bearing minerals (including amphibole, phlogopite and apatite) and glasses show that they are important hosts for K, Rb, Sr, Ba, U and rare earth elements (REE) in the mantle, and play an important role in the fractionation of these elements in mantle processes. However, mass-balance calculations require that significant proportions of LREE, Th and Sr are situated in intergranular phases. 87Sr/86Sr ratios of whole-rock samples from each locality are higher, and 143Nd/144Nd lower, than those of the corresponding acid-leached clinopyroxenes (cpx), suggesting that highly radiogenic Sr and relatively unradiogenic Nd reside in these intergranular phases.The Sr/Nd isotopic compositions of clinopyroxenes separated from the peridotites are correlated with metasomatic style, as reflected in the trace element compositions of the clinopyroxenes. Clinopyroxenes in fertile peridotites from Nushan and Mingxi have high 143Nd/144Nd and low 87Sr/86Sr, reflecting long-term depletion of the mantle. Clinopyroxenes from metasomatised peridotites define trends toward lower 143Nd/144Nd and higher 87Sr/86Sr, consistent with a metasomatic fluid having a Sr/Nd isotopic composition near Bulk Earth, and 147Sm/144Nd≤0.09. Metasomatism by a similar type of fluid can explain the isotopic systematics of clinopyroxenes from most eastern China localities reported in the literature, but a few localities interpreted as on-craton would require fluids with still lower 143Nd/144Nd and higher 87Sr/86Sr. The minimum age of the major element depletion may be given by a Sm/Nd regression line of 733±340 Ma for cpx from unmetasomatised peridotites at Nushan. The age of the metasomatic event(s) cannot be constrained, but a few metasomatised samples with high 143Nd/144Nd indicate that a metasomatic event must have occurred shortly before eruption. [Copyright &y& Elsevier]

Studies the hafnium isotope composition of zircons in Yajiangqiao, China. Zircon morphology; Crustal origin of Yajiangqiao zircon population; Zonation pattern on zircon region.

Two localities on the Leizhou Peninsula, southern China (Yingfengling and Tianyang basaltic volcanoes) yield a wide variety of mantle-derived xenoliths including Cr-diopside series mantle wall rocks and two distinct types of Al-augite series pyroxenites. Metapyroxenites have re-equilibrated granoblastic microstructures whereas pyroxenites with igneous microstructures have not thermally equilibrated to the mantle conditions. An abundant suite of megacrysts and megacrystic aggregates (including garnet, plagioclase, clinopyroxene, ilmenite and apatite) is interpreted as the pegmatitic equivalents of the igneous pyroxenite suite. Layered spinel lherzolite/spinel websterite xenoliths were formed by metamorphic differentiation caused by mantle deformation, inferred to be related to lithospheric thinning. Some metapyroxenites have garnet websterite assemblages that allow calculation of their mantle equilibration temperatures and pressures and the construction of the first xenolith geotherm for the southernmost China lithosphere. Heat flow data measured at the surface in this region yield model conductive geotherms (using average crustal conductivity values) that are consistent with the xenolith geotherm for the mantle. The calculated mean surface heat flux is 110 mW/m2. This high heat flux and the high geotherm are consistent with young lithospheric thinning in southern China, and with recent tomography results showing shallow low-velocity zones in this region. The xenolith geotherm allows the construction of a lithospheric rock type section for the Leizhou region; it shows that the crust–mantle boundary lies at about 30 km, consistent with seismic data, and that the lithosphere–asthenosphere boundary lies at about 100 km. [Copyright &y& Elsevier]

Field relations and whole-rock geochemistry indicate that magma mixing has been important in the genesis of the late Mesozoic I-type igneous complexes at Pingtan and Tonglu in SE China. Morphological and trace-element studies of zircon populations in rocks from each of these complexes have defined several distinct growth stages [Mineral. Mag. (2001)]. In-situ LAM-MC-ICPMS microanalysis shows large variations in 176Hf/177Hf (up to 15 &epsiv;Hf units) between zircons of different growth stages within a single rock, and between zones within single zircon grains (up to 9 &epsiv;Hf units). These variations suggest that each of the observed magmas in both complexes developed through hybridisation of ≥2 magmas with different sources. Although this mixing has produced similar Sr and Nd isotopic compositions in the different rock types of each complex, the zircons have functioned as “tape recorders” and have preserved details of the assembly of the different magmas.In the Tonglu complex the most primitive magma is a mafic monzonite (preserved as enclaves), whose isotopic composition suggests derivation from the lower crust; rhyodacites, rhyolites and quartz diorites reflect the mixing of the monzonite with ≥2 more felsic magmas, derived from older crustal materials. In the Pingtan complex, zircons in a quartz diorite enclave suggest mixing between a crustal magma and a more primitive mantle-derived component. Zircons from granites and granodiorite enclaves indicate mixing between the quartz diorite and more felsic melts with lower 176Hf/177Hf. Major changes in 176Hf/177Hf correlate with discontinuous changes in the trace-element composition and morphology of the zircons, in particular the development of sector zoning that suggests rapid disequilibrium crystallisation. We suggest that the magma mixing recorded by the changes in 176Hf/177Hf occurred during transport in magma conduits. The in-situ analysis of Hf-isotopic stratigraphy in zircons is a new and powerful tool for the detailed study of magma generation processes. [Copyright &y& Elsevier]

Background Sedation therapy is vital for treating severe traumatic brain injury (TBI). Yet, types of sedation assessment tools and sedation levels that are suitable for sedation treatment have not been investigated. Objective To investigate the influence of different sedation levels guided by the Bispectral Index (BIS) on the therapeutic effects for severe TBI. Methods According to inclusion, exclusion, and rejection criteria, 35 patients were prospectively included and divided into Richmond Agitation Sedation Scale (RASS), BIS(I), and BIS(II) groups. The RASS group was controlled the level of sedation to within –2 or –3, and the BIS(I) and (II) groups within the range of 40–50 and 50–60, respectively. In addition to clinical data, RASS, BIS, and intracranial pressure (ICP) values were collected. RASS and ICP variability were introduced to investigate the different of sedative control effect with or without BIS monitor, and the control effect of ICP between different sedation levels. Statistical analysis was performed to estimate the effectiveness of different sedation levels guided by BIS in sedation treatment within 72 hours. Results There were no significant differences in demographics among the 3 groups. RASS variability of the BIS(I) and (II) groups was significantly lower than that of the RASS group ( P < 0.05), and in the BIS(I) group it was insignificantly lower than in the BIS(II) group. The ICP of the BIS(I) and (II) groups declined to <13.5 mm Hg significantly earlier than that of the RASS group ( P < 0.05), and the difference between BIS(I) and (II) was insignificant. ICP variability of RASS group was higher than those of the BIS(I) and (II) groups ( P < 0.05), and ICP variability of the BIS(I) group was significantly lower than that of the BIS(II) group ( P < 0.05). Differences in days in the neurosurgery intensive care unit and outcomes among the 3 groups were insignificant. Conclusions BIS is more reliable than RASS for maintaining a stable sedation status and ICP. Deeper sedation levels (BIS 40–50) cause ICP to decrease more quickly, with lower ICP variability. [ABSTRACT FROM AUTHOR]

Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology is a powerful tool to manipulate the genome with extraordinary simplicity and speed. To generate genetically modified animals, CRISPR/Cas9-mediated genome editing is typically accomplished by microinjection of a mixture of Cas9 DNA/mRNA and single-guide RNA (sgRNA) into zygotes. However, sgRNAs used for this approach require manipulation via molecular cloning as well as in vitro transcription. Beyond these complexities, most mutants obtained with this traditional approach are genetically mosaic, yielding several types of cells with different genetic mutations. Recently, a growing body of studies has utilized commercially available Cas9 protein together with sgRNA and a targeting construct to introduce desired mutations. Here, we report a cloning-free method to target the mouse genome by pronuclear injection of a commercial Cas9 protein:crRNA:tracrRNA:single-strand oligodeoxynucleotide (ssODN) complex into mouse zygotes. As illustration of this method, we report the successful generation of global gene-knockout, single-amino-acid-substituted, as well as floxed mice that can be used for conditional gene-targeting. These models were produced with high efficiency to generate non-mosaic mutant mice with a high germline transmission rate. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies with a 5-year survival rate less than 15%. Understanding of the molecular mechanisms involved in the pathogenesis of ESCC becomes critical to develop more effective treatments.Methods: Mcl-1 expression was measured by reverse transcription (RT)-PCR and Western blotting. Human Mcl-1 promoter activity was evaluated by reporter gene assay. The interactions between DNA and transcription factors were confirmed by electrophoretic mobility shift assay (EMSA) in vitro and by chromatin immunoprecipitation (ChIP) assay in cells.Results: Four human ESCC cell lines, TE-1, Eca109, KYSE150 and KYSE510, are revealed increased levels of Mcl-1 mRNA and protein compare with HaCaT, an immortal non-tumorigenic cell line. Results of reporter gene assays demonstrate that human Mcl-1 promoter activity is decreased by mutation of kappaB binding site, specific NF-kappaB inhibitor Bay11-7082 or dominant inhibitory molecule DNMIkappaBalpha in TE-1 and KYSE150 cell lines. Mcl-1 protein level is also attenuated by Bay11-7082 treatment or co-transfection of DNMIkappaBalpha in TE-1 and KYSE150 cells. EMSA results indicate that NF-kappaB subunits p50 and p65 bind to human Mcl-1-kappaB probe in vitro. ChIP assay further confirm p50 and p65 directly bind to human Mcl-1 promoter in intact cells, by which regulates Mcl-1 expression and contributes to the viability of TE-1 cells.Conclusions: Our data provided evidence that one of the mechanisms of Mcl-1 expression in human ESCC is regulated by the activation of NF-kappaB signaling. The newly identified mechanism might provide a scientific basis for developing effective approaches to treatment human ESCC. [ABSTRACT FROM AUTHOR]

OBJECTIVES A new surgical technique named triple-branched stent graft was developed and reported to have excellent clinical results for Stanford type A aortic dissection. However, we found some potential risks, in our experience, of this technique. We compared this technique with total arch replacement combined with stented elephant trunk implantation in patients with acute Stanford type A dissection. METHODS Thirty-eight patients with acute Stanford type A aortic dissection underwent surgical treatment from January to November 2010. These patients were divided into two groups: patients with total arch replacement combined with stented elephant trunk implantation (Group A, n = 22) and those with ascending aorta replacement combined with open placement of triple-branched stent graft (Group B, n = 16). RESULTS In-hospital mortality was not different in the two groups (9.1 and 6.25%, respectively). Cardiopulmonary bypass, aortic cross-clamp, circulation arrest, selective cerebral perfusion and low-body arrest times were shorter in Group B. Mechanical ventilation support, duration of intensive care unit (ICU) stay and hospitalization time were not different in the two groups. The incidence of postoperative stent graft-related complications was significantly higher in Group B. Actuarial survival rates and freedom from reoperation during the follow-up did not differ in the two groups. CONCLUSIONS The triple-branched stent graft technique truly has some advantages in simplifying the procedure and reducing the surgical time. However, this technique has some potential risks such as postoperative stent graft shifting or kinking, which may cause occlusion, aortic disruption and malperfusion syndrome. Long-term follow-up and further multicentre clinical trials are necessary to verify their use in this setting and the design of the grafts and surgical procedure should be further refined to reduce the incidence of stent graft complications. [ABSTRACT FROM AUTHOR]