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One of the fundamental reactions of the innate immune responses to pathogen infection is the release of pro-inflammatory cytokines, including IL-1β, processed by the NLRP3 inflammasome. The stimulator of interferon genes (STING) has the essential roles in innate immune response against pathogen infections. Here we reveal a distinct mechanism by which STING regulates the NLRP3 inflammasome activation, IL-1β secretion, and inflammatory responses in human cell lines, mice primary cells, and mice. Interestingly, upon HSV-1 infection and cytosolic DNA stimulation, STING binds to NLRP3 and promotes the inflammasome activation through two approaches. First, STING recruits NLRP3 and facilitates NLRP3 localization in the endoplasmic reticulum, thereby facilitating the inflammasome formation. Second, STING interacts with NLRP3 and attenuates K48- and K63-linked polyubiquitination of NLRP3, thereby promoting the inflammasome activation. Collectively, we demonstrate that the cGAS-STING-NLRP3 signaling is essential for host defense against HSV-1 infection.

Background: Altered functional connectivity (FC) is related to pathophysiology of patients with cervical dystonia (CD). However, inconsistent results may be obtained due to different selected regions of interest. We explored voxel-wise brain-wide FC changes in patients with CD at rest in an unbiased manner and analyzed their correlations with symptomatic severity using the Tsui scale.Method: A total of 19 patients with CD and 21 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. Global-brain FC (GFC) was applied to analyze the images. Support vector machine was used to distinguish the patients from the controls.Results: Patients with CD exhibited decreased GFC in the right precentral gyrus and right supplementary motor area (SMA) that belonged to the M1-SMA motor network. Significantly negative correlation was observed between GFC values in the right precentral gyrus and symptomatic severity in the patients (r = −0.476, p = 0.039, uncorrected). Decreased GFC values in these two brain regions could be utilized to differentiate the patients from the controls with good accuracies, sensitivities and specificities (83.33, 85.71, and 80.95% in the right precentral gyrus; and 87.59, 89.49, and 85.71% in the right SMA).Conclusions: Our investigation suggests that patients with CD show reduced GFC in brain regions of the M1-SMA motor network and provides further insights into the pathophysiology of CD. GFC values in the right precentral gyrus and right SMA may be used as potential biomarkers to recognize the patients from the controls.

Dengue virus (DENV) infection causes several diseases ranging from dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome characterized by endothelial dysfunction, vascular leakage, and shock. Here, we identify a potential mechanism by which DENV induces tissue injury and vascular leakage by promoting the activation of interleukin (IL)-1β. DENV facilitates IL-1β secretion in infected patients, mice, human peripheral blood mononuclear cells (PBMCs), mouse bone marrow-derived macrophages (BMDMs), and monocyte-differentiated macrophages (THP-1) via activating the NLRP3 inflammasome. The accumulated data suggest that IL-1β probably induces vascular leakage and tissue injury in interferon-alpha/beta receptor 1 deficient C57BL/6 mice (IFNAR–/– C57BL/6), whereas IL-1 receptor antagonist (IL-1RA) alleviates these effects of IL-1β. Finally, administration of recombinant IL-1β protein results in vascular leakage and tissue injury in C57BL/6 mice. Together, the accumulated results demonstrate that IL-1β contributes to DENV-associated pathology and suggest that IL-1RA acts as a potential agent for the treatment of DENV-associated diseases.

Background: The Frank-Starling curve is the basis of hemodynamics. Changes in cardiac output (CO) caused by central venous pressure (CVP) are the most important concerns in the treatment of critically ill patients.Objectives: To explore the use of CVP and its relevant mechanisms with respect to CO in the clinic.Methods: A total of 134 patients with circulatory shock were retrospectively included and analyzed. Hemodynamic data were recorded and analyzed at PICCO initiation and 24 h after PICCO. Data regarding 28-day mortality and renal function were also collected.Results: The patients were divided into a CVP↑+ CO↑ group (n = 23), a CVP↑+ CO↓ group (n = 29), a CVP↓+ CO↑ group (n = 44), and a CVP↓+ CO↓ group (n = 38) based on values at PICCO initiation and 24 h after PICCO. Post- hoc tests showed that the CVP↓+ CO↑ group had a higher 28-day survival than the other groups [log-rank (Mantel-Cox) = 8.758, 95%, CI, 20.112–23.499, P = 0.033]. In terms of hemodynamic characteristics, the CVP↓+ CO↑ group had a lower cardiac function index (CFI) (4.1 ± 1.4/min) and higher extravascular lung water index (EVLWI) (11.0 ± 4.7 ml/kg) at PICCO initiation. This group used more cardiotonic drugs (77.3%, P < 0.001) and had a negative fluid balance (−780.4 ± 1720.6 ml/24 h, P = 0.018) 24 h after PICCO than the other three groups. Cardiotonic drug use and dehydration treatment were associated with increased CFI (from 4.1 ± 1.4 /min to 4.5 ± 1.3/min, P = 0.07) and reduced ELVWI (from 11.0 ± 4.7 ml/kg to 9.0 ± 3.5 ml/kg, P = 0.029). Renal function tests showed that SCr and BUN levels in the CVP↓+ CO↑ group were significantly improved (SCr from 197.1 ± 128.9 mmol/L to 154.4 ± 90.8 mmol/L; BUN from 14.3 μmol/L ± 7.3 to 11.6 ± 7.0 μmol/L, P < 0.05).Conclusions: Lower CVP was associated with increased CO, which may improve the 28-day prognosis in patients with circulatory shock. Notably, higher CO derived from lower CVP may also contribute to renal function improvement.

The NLRP3 inflammasome plays an important role in antiviral host responses. Here, the authors reveal that the polymerase of Zika virus binds NLRP3 to facilitate inflammasome complex assembly and induce production of IL-1β in human macrophages, human PBMCs and mice, resulting in pathogenesis in mice.

Background: Measurement of general microcirculation remains difficult in septic shock patients. The peripheral perfusion index (PI) and sublingual microcirculation monitoring are thought to be possible methods. This study was performed to determine whether assessing microcirculation by PI and a new parameter, proportion of perfusion vessel change rate (△PPV) from sublingual microcirculation monitoring, can be associated with patients' outcome. Methods: A prospective observational study was carried out, including 74 patients with septic shock in a mixed intensive care unit. Systemic hemodynamic variables were obtained at T0 and 6 h after (T6). PI and sublingual microcirculation indicators were obtained using a bedside monitor and a sidestream dark-field device, respectively. The t-test, analysis of variance, Mann-Whitney U-test, Kruskal-Wallis test, receiver operating characteristic curve analysis with the Hanley-McNeil test, survival curves using the Kaplan-Meier method, and the log-rank (Mantel-Cox) test were used to statistical analysis. Results: Systemic hemodynamics and microcirculation data were obtained and analyzed. Patients were divided into two groups based on whether the first 6 h lactate clearance (LC) was ≥20%; PI and △PPV were lower at T6 in the LC

Abstract Background Opioids and benzodiazepines are frequently used in the intensive care unit (ICU). Regular use and prolonged exposure to opioids in ICU patients followed by abrupt tapering or cessation may lead to iatrogenic withdrawal syndrome (IWS). IWS is well described in pediatrics, but no prospective study has evaluated this syndrome in adult ICU patients. The objective of this study was to determine the incidence of IWS caused by opioids in a critically ill adult population. This multicenter prospective cohort study was conducted at two level-1 trauma ICUs between February 2015 and September 2015 and included 54 critically ill patients. Participants were eligible if they were 18 years and older, mechanically ventilated and had received more than 72 h of regular intermittent or continuous intravenous infusion of opioids. For each enrolled patient and per each opioid weaning episode, presence of IWS was assessed by a qualified ICU physician or senior resident according to the 5th edition of Diagnostic and Statistical Manual of Mental Disorders criteria for opioid withdrawal. Results The population consisted mostly of males (74.1%) with a median age of 50 years (25th–75th percentile 38.2–64.5). The median ICU admission APACHE II score was 22 (25th–75th percentile 12.0–28.2). The overall incidence of IWS was 16.7% (95% CI 6–27). The median cumulative opioid dose prior to weaning was higher in patients with IWS (245.7 vs. 169.4 mcg/kg, fentanyl equivalent). Patients with IWS were also exposed to opioids for a longer period of time as compared to patients without IWS (median 151 vs. 125 h). However, these results were not statistically significant. Conclusions IWS was occasionally observed in this very specific population of mechanically ventilated, critically ill ICU patients. Further studies are needed to confirm these preliminary results and identify risk factors.

Coated controlled-release fertilizers (CRFs) have been widely applied in agriculture due to their increased efficiency. However, the widespread and a lot of coated CRFs application may leave undesired coating residues in the soil due to their slow degradation. Limited information is available on the effects of substantial residual coatings on the soil bacterial community. By adding 0, 5, 10, 20, and 50 times quantities of residual coating from conventional application amount of resin and water-soluble coated CRFs, we studied the responses of soil properties and bacterial community composition to these two residual coatings in black soil. The results showed that the resin and water-soluble coatings did not essentially alter the properties of black soil or cause dramatic changes to bacterial diversity within the test concentration range. The residual resin and water-soluble coatings also did not distinctly alter the relative abundance of the top ten bacteria at phylum level. Heatmap results suggested that the treatments were basically clustered into two groups by concentration rather than types of coating material. Pearson correlation analysis showed that the Simpson's diversity index of the bacterial community was significantly correlated with microbial biomass carbon (MBC, r=0.394, P

ObjectiveTraditionally, the absence of insulin resistance risk factors (IRRFs) was considered a low risk for insulin resistance (IR). However, IR also existed in certain individuals without IRRFs; thus this study aims to explore predictors of IR targeted at the population without IRRFs.DesignCross-sectional survey.SettingNational Health and Nutrition Examination Survey.ParticipantsParticipants without regular IRRFs (IRRF-Free, n=2478) and a subgroup without optimal IRRFs (IRRF-Optimal, n=1414) were involved in this study.Primary and secondary outcome measureIRRFs and the optimal cut-off value of triglyceride (TG) to predict IR.ResultsOverall, the prevalence of IR was 6.9% and 5.7% in the IRRF-Free group and the IRRF-Optimal group, respectively. TG and waist circumference were independently associated with the prevalence of IR in both the groups (OR=1.010 to 10.20; p

Background Natural disasters can indirectly induce epidemics of infectious diseases through air and water pollution, accelerated pathogen reproduction, and population migration. This study aimed to explore the epidemiological characteristics of the main infectious diseases in Sichuan, a province with a high frequency of natural disasters. Methods Data were collected from the local Centers for Disease Control infectious disease reports from Lu, Shifang and Yuexi counties from 2011 to 2015 and from the baseline survey of the Disaster Mitigation Demonstration Area in Western China in 2016. Principal component regression was used to explore the main influencing factors of respiratory infectious diseases (RIDs). Results The incidence rates of RIDs and intestinal infectious diseases (IIDs) in 2015 were 78.99/100,000, 125.53/100,000, 190.32/100,000 and 51.70/100,000, 206.00/100,000, 69.16/100,000 in Lu, Shifang and Yuexi respectively. The incidence rates of pulmonary tuberculosis (TB) was the highest among RIDs in the three counties. The main IIDs in Lu and Shifang were hand-foot-mouth disease (HFMD) and other infectious diarrhea; however, the main IIDs in Yuexi was bacillary dysentery. The proportions of illiterate and ethnic minorities and per capita disposable income were the top three influencing factors of RIDs. Conclusions TB was the key point of RIDs prevention among the three counties. The key preventable IIDs in Lu and Shifang were HFMD and other infectious diarrhea, and bacillary dysentery was the major IIDs in Yuexi. The incidence rates of RIDs was associated with the population composition, the economy and personal hygiene habits.

The notion of dysconnectivity in schizophrenia has been put forward for many years and results in substantial attempts to explore altered functional connectivity (FC) within different networks with inconsistent results. Clinical, demographical, and methodological heterogeneity may contribute to the inconsistency. Forty-four patients with first-episode, drug-naive schizophrenia, 42 unaffected siblings of schizophrenia patients and 44 healthy controls took part in this study. Global-brain FC (GFC) was employed to analyze the imaging data. Compared with healthy controls, patients with schizophrenia and unaffected siblings shared enhanced GFC in the left superior frontal gyrus (SFG). In addition, patients had increased GFC mainly in the thalamo-cortical network, including the bilateral thalamus, bilateral posterior cingulate cortex (PCC)/precuneus, left superior medial prefrontal cortex (MPFC), right angular gyrus, and right SFG/middle frontal gyrus and decreased GFC in the left ITG/cerebellum Crus I. No other altered GFC values were observed in the siblings group relative to the control group. Further ROC analysis showed that increased GFC in the left SFG could separate the patients or the siblings from the controls with acceptable sensitivities. Our findings suggest that increased GFC in the left SFG may serve as a potential endophenotype for schizophrenia.

Dengue fever is a major worldwide public health problem that, as estimated by the WHO, causes epidemics in over 100 countries, resulting in hundreds of millions of dengue virus (DENV) infections every year. In China, dengue fever mainly occurs in coastal areas. Recurring dengue outbreaks were reported by Guangdong Province almost every year since the first epidemic in 1978. DENV infections persisted in Guangzhou in consecutive years since 2000, with the dengue epidemic reaching a historical peak in 2014. Because Guangzhou is one of the largest cities for opening up in China, understanding the epidemiological characteristics of dengue fever in the city can hopefully provide a significant basis for developing effective dengue prevention strategies. In this study, a total of 34 DENV strains, including 29 DENV-1 strains and 5 DENV-2 strains, were isolated from a blood samples drawn from patients who were diagnosed with dengue fever by hospitals in Guangzhou during 2018. To explore the epidemiological characteristics of dengue fever, the envelope (E) gene obtained from the isolates was amplified for phylogenetic analysis. The results from the phylogenetic analysis showed that DENV in Guangzhou was mainly imported from Southeast Asian countries. Additionally, propagation paths based on phylogeographical analysis suggested potential local dengue transmission in Guangzhou.

SARS-CoV-2 is highly pathogenic in humans and poses a great threat to public health worldwide. Clinical data shows a disturbed type I interferon (IFN) response during the virus infection. In this study, we discovered that the nucleocapsid (N) protein of SARS-CoV-2 plays an important role in the inhibition of interferon beta (IFN-β) production. N protein repressed IFN-β production induced by poly(I:C) or upon Sendai virus (SeV) infection. We noted that N protein also suppressed IFN-β production, induced by several signaling molecules downstream of the retinoic acid-inducible gene I (RIG-I) pathway, which is the crucial pattern recognition receptor (PRR) responsible for identifying RNA viruses. Moreover, our data demonstrated that N protein interacted with the RIG-I protein through the DExD/H domain, which has ATPase activity and plays an important role in the binding of immunostimulatory RNAs. These results suggested that SARS-CoV-2 N protein suppresses the IFN-β response through targeting the initial step, potentially the cellular PRR–RNA-recognition step in the innate immune pathway. Therefore, we propose that the SARS-CoV-2 N protein represses IFN-β production by interfering with RIG-I.

The nuclear receptor (NR) superfamily has been studied extensively in many solid tumors and some receptors have been targeted to develop therapies. However, their roles in leukemia are less clear and vary considerably among different types of leukemia. Some NRs participate in mediating the differentiation of myeloid cells, making them attractive therapeutic targets for myeloid leukemia. To date, the success of all-trans retinoic acid (ATRA) in treating acute promyelocytic leukemia (APL) remains a classical and unsurpassable example of cancer differentiation therapy. ATRA targets retinoic acid receptor (RAR) and forces differentiation and/or apoptosis of leukemic cells. In addition, ligands/agonists of vitamin D receptor (VDR) and peroxisome proliferator-activated receptor (PPAR) have also been shown to inhibit proliferation, induce differentiation, and promote apoptosis of leukemic cells. Encouragingly, combining different NR agonists or the addition of NR agonists to chemotherapies have shown some synergistic anti-leukemic effects. This review will summarize recent research findings and discuss the therapeutic potential of selected NRs in acute and chronic myeloid leukemia, focusing on RAR, VDR, PPAR, and retinoid X receptor (RXR). We believe that more mechanistic studies in this field will not only shed new lights on the roles of NRs in leukemia, but also further expand the clinical applications of existing therapeutic agents targeting NRs.

Natural products and their derivatives have long been used as pharmacological agents in the fight against cancer. Human natural killer (NK) cells are critical in our immune system in that they are capable of destroying tumor cells directly. However, there are few reports that elucidate the role of natural products in activating NK cells. In this study, we discovered that a synthetic disaccharide derivative of diphyllin, 4-O-{[2′′,3′′,4′′-tri-O-acetyl-α-D-arabinopyranosyl-(1′′→4′)]-2′,3′-di-O-acetyl-α-L-rhamnopyranosyl}diphyllin (TAARD), can alone stimulate interferon (IFN)-γ secretion in primary human NK cells and the NKL cell line. Additionally, it had an additive effect with IL-12 or IL-15 on IFN-γ production, but little adverse effects on NK cells. Mechanistically, TAARD induced the phosphorylation of NF-κB and STAT3, resulting in their binding on the IFNG promoter, which was dependent on TLR1 and TLR3 signaling, respectively. STAT3 and NF-κB knockdown with lentivirus shRNA as well as the NF-κB-specific inhibitor, N-tosyl-l-phenylalaninechloromethyl ketone, significantly suppressed TAARD-induced IFN-γ generation in primary NK cells. Blockade of TLR1 and TLR3 with neutralizing antibodies considerably decreased TAARD-induced activation of NF-κB and STAT3, respectively, as well as IFN-γ generation in NK cells. Collectively, our data suggest that TAARD can induce NK cell IFN-γ production through TLR1-NF-κB and TLR3-STAT3 signaling pathways, rendering its potential use as an agent for cancer prevention or treatment.

Septic cardiomyopathy is one of the most serious complications of sepsis or septic shock. Basic and clinical research has studied the mechanism of cardiac dysfunction for more than five decades. It has become clear that myocardial depression is not related to hypoperfusion. As the heart is highly dependent on abundant adenosine triphosphate (ATP) levels to maintain its contraction and diastolic function, impaired mitochondrial function is lethally detrimental to the heart. Research has shown that mitochondria play an important role in organ damage during sepsis. The mitochondria-related mechanisms in septic cardiomyopathy have been discussed in terms of restoring mitochondrial function. Mitochondrial uncoupling proteins located in the mitochondrial inner membrane can promote proton leakage across the mitochondrial inner membrane. Recent studies have demonstrated that proton leakage is the essential regulator of mitochondrial membrane potential and the generation of reactive oxygen species (ROS) and ATP. Other mechanisms involved in septic cardiomyopathy include mitochondrial ROS production and oxidative stress, mitochondria Ca 2+ handling, mitochondrial DNA in sepsis, mitochondrial fission and fusion, mitochondrial biogenesis, mitochondrial gene regulation and mitochondria autophagy. This review will provide an overview of recent insights into the factors contributing to septic cardiomyopathy.

Natural products comprise an important class of biologically active molecules. Many of these compounds derived from natural sources exhibit specific physiologic or biochemical effects. An example of a natural product is chitosan, which is enriched in the shells of certain seafood that are frequently consumed worldwide. Like other natural products, chitosan has the potential for applications in clinical medicine and perhaps in cancer therapy. Toward this end, the immunomodulatory or anti-cancer properties of chitosan have yet to be reported. In this study, we discovered that chitosan enhanced the anti-tumor activity of natural killer (NK) cells by activating dendritic cells (DCs). In the presence of DCs, chitosan augmented IFN-γ production by human NK cells. Mechanistically, chitosan activated DCs to express pro-inflammatory cytokines such as interleukin (IL)-12 and IL-15, which in turn activated the STAT4 and NF-κB signaling pathways, respectively, in NK cells. Moreover, chitosan promoted NK cell survival, and also enhanced NK cell cytotoxicity against leukemia cells. Finally, a related in vivo study demonstrated that chitosan activated NK cells against B16F10 tumor cells in an immunocompetent syngeneic murine melanoma model. This effect was accompanied by in vivo upregulation of IL-12 and IL-15 in DCs, as well as increased IFN-γ production and cytolytic degranulation in NK cells. Collectively, our results demonstrate that chitosan activates DCs leading to enhanced capacity for immune surveillance by NK cells. We believe that our study has future clinical applications for chitosan in the prevention or treatment of cancer and infectious diseases.

[This corrects the article DOI: 10.1371/journal.ppat.1006123.].

Natural killer (NK) cells are an essential component of innate immunity against cancer development. Many studies have been conducted to evaluate immune-modulating effects using dietary compounds. Our laboratory has been investigating the chemopreventive potential of black raspberries (BRBs) and previously demonstrated their beneficial modulation of genetic and epigenetic biomarkers in patients with colorectal cancer (CRC). The current study investigated their potential on modulating NK cells. To avoid the excessive inflammation caused by the dextran sulfate sodium (DSS) treatment that leads to colitis, we treated the mice with overnight DSS so that it would slightly irritate the colon but still promote colon carcinogenesis with 100% incidence in both the ApcMin/+ mice and azoxymethane (AOM)-treated mice. A significant decrease of tissue-infiltrating NK cells along the progression of microadenoma-to-adenoma and adenoma-to-adenocarcinoma was observed in the ApcMin/+/DSS and AOM/DSS mice, respectively. Depletion of NK cells significantly promoted the development of CRC, suggesting a critical role of NK cells in combating CRC progression. BRBs significantly suppressed the CRC progression and increased the number of tissue-infiltrating NK cells in both mouse models. Moreover, we further determined BRBs’ effects on NK cells in the human biopsy specimens collected from our previously completed clinical trial, in which CRC patients consumed BRBs for an average of 4 weeks during a presurgical window. We observed an increased number and an enhanced cytotoxicity of NK cells by BRB intervention. The current study provides evidence that BRBs have the potential to enhance the tumor immunesurveillance of NK cells that can be beneficial in the setting of CRC prevention and treatment.

Activation of NLRP3 inflammasome is important for effective host defense against invading pathogen. Together with apoptosis-associated speck-like protein containing CARD domain (ASC), NLRP3 induces the cleavage of caspase-1 to facilitate the maturation of interleukin-1beta (IL-1β), an important pro-inflammatory cytokine. IL-1β subsequently plays critical roles in inflammatory responses by activating immune cells and inducing many secondary pro-inflammatory cytokines. Although the role of NLRP3 inflammasome in immune response is well defined, the mechanism underlying its assembly modulated by pathogen infection remains largely unknown. Here, we identified a novel mechanism by which enterovirus 71 (EV71) facilitates the assembly of NLRP3 inflammasome. Our results show that EV71 induces production and secretion of IL-1β in macrophages and peripheral blood mononuclear cells (PBMCs) through activation of NLRP3 inflammasome. EV71 replication and protein synthesis are required for NLRP3-mediated activation of IL-1β. Interestingly, EV71 3D protein, a RNA-dependent RNA polymerase (RdRp) was found to stimulate the activation of NLRP3 inflammasome, the cleavage of pro-caspase-1, and the release of IL-1β through direct binding to NLRP3. More importantly, 3D interacts with NLRP3 to facilitate the assembly of inflammasome complex by forming a 3D-NLRP3-ASC ring-like structure, resulting in the activation of IL-1β. These findings demonstrate a new role of 3D as an important player in the activation of inflammatory response, and identify a novel mechanism underlying the modulation of inflammasome assembly and function induced by pathogen invasion.

A multi-objective optimization method for the structural design of horizontal-axis wind turbine (HAWT) blades is presented. The main goal is to minimize the weight and cost of the blade which uses glass fiber reinforced plastic (GFRP) coupled with carbon fiber reinforced plastic (CFRP) materials. The number and the location of layers in the spar cap, the width of the spar cap and the position of the shear webs are employed as the design variables, while the strain limit, blade/tower clearance limit and vibration limit are taken into account as the constraint conditions. The optimization of the design of a commercial 1.5 MW HAWT blade is carried out by combining FEM analysis and a multi-objective evolutionary algorithm under ultimate (extreme) flap-wise load and edge-wise load conditions. The best solutions are described and the comparison of the obtained results with the original design is performed to prove the efficiency and applicability of the method.

Understanding mechanistic details of the nickel-catalyzed coupling reactions of Csp3 alcohol derivatives is key to developing selective reactions of this widely prevalent functional group. In this manuscript, we utilize a combination of experimental data and DFT studies to define the key intermediates, stereochemical outcome, and competing pathways of a nickel-catalyzed cross-electrophile coupling reaction of 1,3-dimesylates. Stereospecific formation of a 1,3-diiodide intermediate is achieved in situ by the Grignard reagent. The overall stereoablative stereochemical outcome is due to a nickel-catalyzed halogen atom abstraction with a radical rebound that is slower than epimerization of the alkyl radical. Finally, lifetimes of this alkyl radical intermediate are compared to radical clocks to enhance the understanding of the lifetime of the secondary alkyl radical.

A process of detailed CFD and structural numerical simulations of the 1.5 MW horizontal axis wind turbine (HAWT) blade is present. The main goal is to help advance the use of computer-aided simulation methods in the field of design and development of HAWT-blades. After an in-depth study of the aerodynamic configuration and materials of the blade, 3-D mapping software is utilized to reconstruct the high fidelity geometry, and then the geometry is imported into CFD and structure finite element analysis (FEA) software for completely simulation calculation. This research process shows that the CFD results compare well with the professional wind turbine design and certification software, GH-Bladed. Also, the modal analysis with finite element method (FEM) predicts well compared with experiment tests on a stationary blade. For extreme wind loads case that by considering a 50-year extreme gust simulated in CFD are unidirectional coupled to the FE-model, the results indicate that the maximum deflection of the blade tip is less than the distance between the blade tip (the point of maximum deflection) and the tower, the material of the blade provides enough resistance to the peak stresses the occur at the conjunction of shear webs and center spar cap. Buckling analysis is also included in the study.