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Immune-responsive gene 1 (IRG1) encodes aconitate decarboxylase (ACOD1) that catalyzes the production of itaconic acids (ITAs). The anti-inflammatory function of IRG1/ITA has been established in multiple pathogen models, but very little is known in cancer. Here, we show that IRG1 is expressed in tumor-associated macrophages (TAMs) in both human and mouse tumors. Mechanistically, tumor cells induce Irg1 expression in macrophages by activating NF-κB pathway, and ITA produced by ACOD1 inhibits TET DNA dioxygenases to dampen the expression of inflammatory genes and the infiltration of CD8 + T cells into tumor sites. Deletion of Irg1 in mice suppresses the growth of multiple tumor types and enhances the efficacy of anti–PD-(L)1 immunotherapy. Our study provides a proof of concept that ACOD1 is a potential target for immune-oncology drugs and IRG1 -deficient macrophages represent a potent cell therapy strategy for cancer treatment even in pancreatic tumors that are resistant to T cell–based immunotherapy.

As one of the most induced genes in activated macrophages, immune-responsive gene 1 (IRG1) encodes a mitochondrial metabolic enzyme catalysing the production of itaconic acid (ITA). Although ITA has an anti-inflammatory property, the underlying mechanisms are not fully understood. Here we show that ITA is a potent inhibitor of the TET-family DNA dioxygenases. ITA binds to the same site on TET2 as the co-substrate α-ketoglutarate, inhibiting TET2 catalytic activity. Lipopolysaccharide treatment, which induces Irg1 expression and ITA accumulation, inhibits Tet activity in macrophages. Transcriptome analysis reveals that TET2 is a major target of ITA in suppressing lipopolysaccharide-induced genes, including those regulated by the NF-κB and STAT signalling pathways. In vivo, ITA decreases the levels of 5-hydroxymethylcytosine, reduces lipopolysaccharide-induced acute pulmonary oedema as well as lung and liver injury, and protects mice against lethal endotoxaemia, depending on the catalytic activity of Tet2. Our study thus identifies ITA as an immune modulatory metabolite that selectively inhibits TET enzymes to dampen the inflammatory responses.

In order to effectively recognize and identify liquor quality by nuclear magnetic resonance (NMR) spectrum data, we propose a hybrid data processing and recognition algorithm. In this algorithm Kernel principal component analysis (KPCA) was used to remove the correlation and reduce dimension of the NMR spectrum, and then convolutional neural network (CNN) was used for classification and identification of the processed spectrum. The compared experiment result show that the proposed KPCA+CNN method can obtain higher accuracy than CNN and PCA+CNN methods based on the NMR spectrum. The KPCA+CNN algorithm has good application prospect and reference value.

Preterm infants with long-term parenteral nutrition (PN) therapy are at risk for cholestasis associated with total parenteral nutrition (PNAC). This study examined the safety and efficacy of ursodeoxycholic acid (UDCA) in preventing PNAC in preterm infants. Our research aimed to investigate the prophylactic effect of preventive oral UDCA on PNAC in preterm infants.We compared oral administration of UDCA prophylaxis with no prophylaxis in a randomized, open-label, proof-of-concept trial in preterm neonates with PN therapy. The low-birth-weight preterm infants ( 1800 g) who were registered to the neonatal intensive care unit (NICU) within 24 hours after birth were randomized. The main endpoint was the weekly values of direct bilirubin (DB) of neonates during the NICU stay.Eventually, a total of 102 preterm neonates from January 2021 to July 2021 were enrolled in this prospective study (42 in the UDCA group and 60 in the control group). Notably, the peak serum level of DB [13.0 (12-16) vs. 15.2 (12.5-19.6) μmol/L, P 0.05)] was significantly lower in the UDCA group than that in the control group without prevention. The peak serum level of total bilirubin (101.1 ± 34 vs. 116.5 ± 28.7 μmol/L, P 0.05) was also significantly lower in the UDCA group than in the control group. Furthermore, the proportion of patients who suffered from neonatal cholestasis (0.0% vs. 11.7%, P 0.05) in the UDCA group was significantly lower.UDCA prophylaxis is beneficial in preventing PNAC in NICU infants receiving prolonged PN.

Youcui Wang,1– 3 Xiaoqin Zhang,1– 3 Fenghua Chen,1– 3 Leilei Chen,1– 3 Jun Wang,1– 3 Junxia Xie1– 3 1Institute of Brain Science and Disease, Qingdao University, Qingdao, People’s Republic of China; 2Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao, People’s Republic of China; 3Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Junxia XieInstitute of Brain Science and Disease, Qingdao University, No. 308, Ningxia Road, Qingdao, 266071, People’s Republic of ChinaEmail jxiaxie@public.qd.sd.cnAbstract: Neuroinflammation plays an important role in the pathogenesis of Parkinson’s disease (PD). However, the molecular mechanisms involved in extracellular α‑synuclein-induced proinflammatory microglial responses through Toll-like receptor 2 (TLR2) are unclear. Leucine-rich repeat kinase 2 (LRRK2) is a serine/threonine kinase, and its mutations are closely related to autosomal dominant PD. Recently, Masliah et al characterized a novel-specific neuroinflammation cascade dependent on LRRK2-NFATc2 in microglia activated by neuron-released α-synuclein. LRRK2 selectively phosphorylated and induced nuclear translocation of NFATc2 to activate a neuroinflammation cascade. In this cascade, LRRK2 kinase was activated by neuron-released α-synuclein in microglia via TLR2. Further, NFATc2, as a kinase substrate for LRRK2, was directly phosphorylated, which accelerated nuclear translocation of NFATc2, where cytokine/chemokine gene expression including TNF-α and IL-6 is regulated by NFATc2 transcriptional activity, resulting in a neurotoxic inflammatory environment. Moreover, an abnormal increase of NFATc2 in nuclear was observed in the brains of patients and a mouse model of PD. Additionally, the administration of an LRRK2 inhibitor could ameliorate neuroinflammation, prevent neuronal loss, and improve motor function. Therefore, modulation of LRKK2-NFATc2 signaling cascade might be a potential therapeutic target for the treatment of PD.Keywords: Parkinson’s disease, neuroinflammation, LRKK2, NFATc2, α-synuclein

Acute ST-elevation myocardial infarction (STEMI) is associated with a high incidence of complications as well as a considerable hospitalization rate and economic burden. Preliminary evidence suggests that remote ischemic conditioning (RIC) is a promising non-invasive intervention that may effectively and safely reduce myocardial infarct size, subsequent cardiac events and complications, and mortality. However, RIC’s cardio-protective effect remains under debate, especially for single timepoint RIC programs. Adequately powered large-scale randomized controlled trials investigating clinical outcomes are thus needed to clarify the role of full disease cycle RIC programs. The intelligent “Internet Plus”-based full disease cycle remote ischemic conditioning (i-RIC) trial is a pragmatic, multicenter, randomized controlled, parallel group, clinical trial. The term, intelligent “Internet Plus”-based full disease cycle, refers to smart devices aided automatic and real-time monitoring of remote ischemic pre-, per- or post-conditioning intervention for patients with STEMI undergoing percutaneous coronary intervention (PCI). Based on this perspective, 4700 STEMI patients from five hospitals in China will be randomized to a control and an intervention group. The control group will receive PCI and usual care, including pharmacotherapy, before and after PCI. The intervention group will receive pre-, per-, and post-operative RIC combined with long-term i-RIC over a one-month period in addition. A smartphone application, an automated cuff inflation/deflation device and “Internet Plus”-based administration will be used in the long-term phase. The primary outcome is the combined cardiac death or hospitalization for heart failure rate. Secondary outcomes include clinical and functional outcomes: major adverse cardiac and cerebrovascular events rate, all-cause mortality, myocardial reinfarction rate, readmission rate for heart failure and ischemic stroke rate, unplanned revascularization rate, plasma concentration of myocardial infarction-related key biomarkers, infarct size, cardiac function, cardiopulmonary endurance, health-related quality of life, total hospital length of stay, total medical cost, and compliance with treatment regime. The i-RIC trial is designed to test the hypothesis that clinical and functional outcomes can be improved with the i-RIC program in STEMI patients undergoing PCI. The concept of RIC is expected to be enhanced with this intelligent “Internet Plus”-based program focusing on the full disease cycle. If the i-RIC program results in superior improvement in primary and secondary outcomes, it will offer an innovative treatment option for STEMI patients and form the basis of future recommendations. Chinese Clinical Trial Registry ( http://www.chictr.org.cn ): ChiCTR2000031550, 04 April 2020.

As a pathological biomarker of Parkinson’s disease, α-synuclein is thought to be a prion-like protein, but evidence for the transmission of α-synuclein from blood to the brain is unclear. The goals of this study were to determine whether blood-derived α-synuclein could enter the brains of mice and whether α-synuclein in the brain could be cleared by parabiosis. Heterochronic parabiosis was performed on SNCAA53T transgenic mice (A53T mice) and wildtype mice. The levels of human α-synuclein in the blood and substantia nigra of wildtype mice were significantly increased after 4-month parabiosis with A53T mice. Moreover, the expression of α-synuclein filament, but not of total α-synuclein, was significantly increased in the substantia nigra of wildtype mice that were paired with A53T mice. However, the levels of human α-synuclein displayed no significant change in the serum, blood, or substantia nigra of A53T mice. These results provide direct evidence that pathological α-synuclein can be transmitted from blood to the brain in the heterochronic parabiosis system, however, it appears to be difficult to clear it from the brain in a short period of time.

Glacial tills are widely distributed in Tibet, China, and are highly susceptible to landslides under intense rainfalls. Failures of the slope during rainfall are closely related to the shear behavior of glacial tills at different moisture conditions. This study investigates the shear behavior and critical state of saturated and unsaturated glacial tills through a series of drained direct shear tests. The tests were conducted on two types of compacted glacial tills with different water contents and total normal stresses. A strain softening mode of failure is observed for all water content conditions accompanied by noticeable dilation. Dilatancy is found to decrease with increasing water content. Unsaturated samples showed increased rates of dilation as water content is decreased for all applied normal stresses a behavior which cannot be predicted well by classical stress-dilatancy models. Furthermore, it was found that the Critical State Line (CSL), plotted on the (e-lnσn) plane, can be used to define the shear behavior of unsaturated glacial tills at different water contents. The CSL of saturated glacial tills run parallel to this line. The experimental results in this study are aimed to provide a basic understanding to the underlying failure mechanisms of glacial tills.

Reciprocating compressors are widely used in petroleum industry. Due to containing complex nonlinear signal, it is difficult to extract the fault features from its vibration signals. This paper proposes a new method named Convolutional Neural Network based on Multisource Raw vibration signals (MSRCNN). The proposed method uses multisource raw vibration signals collected by several sensors as input and uses the designed CNN to operate both the feature extraction and classification. The gas valve signals of reciprocating compressor in different states are used as the experimental data. In order to test the effectiveness of the proposed method, it is compared with the traditional BP (Back-Propagation) neural network fault diagnosis method based on power spectrum energy and wavelet packet energy. In order to further test the antinoise performance of the proposed method, some noisy signals with different signal-to-noise ratios were constructed by adding white noise into sampled signals for testing. The results show that the MSRCNN model has higher fault recognition rate than the traditional methods. This indicates that the MSRCNN method not only has good fault recognition effect, but also has certain antinoise performance.

Glacial tills are highly compressible soils composed of loosely cemented sandy silt particles. Their role, for instance, as initial filler materials in geo-technical projects along temperate glacier regions warrant a systematic evaluation of their compressive characteristics. As such, we carry out a series of one-dimensional compression tests on re-compacted glacial till samples obtained from Tianmo Gully, Tibet, with the aims of evaluating their compressive behavior under controlled initial stress conditions. The yield stress was determined from the void ratio versus consolidation pressure (e-log σv) planes. Its compression and swelling behaviors were observed during the primary and secondary compressions of the consolidation tests. From the compression curves, a correlation can be found between the consolidation stress and the void index. In addition, we find that the compression curves of glacial tills collapse into a single curve when normalized by the compression index. The experimental results in this study provide a basic understanding of the compression characteristics of the glacial tills in Tibet, China.

Parkinson&rsquo, s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Several brain&ndash, gut peptides are able to exert neuroprotective effects on the nigrostriatal dopaminergic system. Apelin-13 is a neuropeptide, conveying potential neuroprotective activities. However, whether, and how, apelin-13 could antagonize rotenone-induced neurotoxicity has not yet been elucidated. In the present study, rotenone-treated SH-SY5Y cells and rats were used to clarify whether apelin-13 has protective effects on dopaminergic neurons, both in vivo and in vitro. The results showed that apelin-13 could protect SH-SY5Y cells from rotenone-induced injury and apoptosis. Apelin-13 was able to activate autophagy, and restore rotenone induced autophagy impairment in SH-SY5Y cells, which could be blocked by the autophagy inhibitor 3-Methyladenine. Apelin-13 activated AMPK/mTOR/ULK-1 signaling, AMPK&alpha, inhibitor compound C, as well as apelin receptor blockage via siRNA, which could block apelin-13-induced signaling activation, autophagy activation, and protective effects, in rotenone-treated SH-SY5Y cells. These results indicated that apelin-13 exerted neuroprotective properties against rotenone by stimulating AMPK/mTOR/ULK-1 signaling-mediated autophagy via the apelin receptor. We also observed that intracerebroventricular injection of apelin-13 could alleviate nigrostriatal dopaminergic neuron degeneration in rotenone-treated rats. Our findings provide new insights into the mechanism by which apelin-13 might attenuate neurotoxicity in PD.

First-principles calculations were performed to investigate the effects of boron/nitrogen dopant on the geometry, electronic structure and magnetic properties of the penta-graphene system. It was found that the electronic band gap of penta-graphene could be tuned and varied between 1.88 and 2.12 eV depending on the type and location of the substitution. Moreover, the introduction of dopant could cause spin polarization and lead to the emergence of local magnetic moments. The main origin of the magnetic moment was analyzed and discussed by the examination of the spin-polarized charge density. Furthermore, the direction of charge transfer between the dopant and host atoms could be attributed to the competition between the charge polarization and the atomic electronegativity. Two charge-transfer mechanisms worked together to determine which atoms obtained electrons. These results provide the possibility of modifying penta-graphene by doping, making it suitable for future applications in the field of optoelectronic and magnetic devices.

Alzheimer disease (AD) is the most common neurodegenerative disease characterized by the deposition of amyloid plaque in the brain. The autophagy-associated PIK3C3-containing phosphatidylinositol 3-kinase (PtdIns3K) complex has been shown to interfere with APP metabolism and amyloid beta peptide (Aβ) homeostasis via poorly understood mechanisms. Here we report that NRBF2 (nuclear receptor binding factor 2), a key component and regulator of the PtdIns3K, is involved in APP-CTFs homeostasis in AD cell models. We found that NRBF2 interacts with APP in vivo and its expression levels are reduced in hippocampus of 5XFAD AD mice; we further demonstrated that NRBF2 overexpression promotes degradation of APP C-terminal fragments (APP-CTFs), and reduces Aβ1–40 and Aβ1-42 levels in human mutant APP-overexpressing cells. Conversely, APP-CTFs, Aβ1–40 and Aβ1-42 levels were increased in Nrbf2 knockdown or nrbf2 knockout cells. Furthermore, NRBF2 positively regulates autophagy in neuronal cells and NRBF2-mediated reduction of APP-CTFs levels is autophagy dependent. Importantly, nrbf2 knockout attenuates the recruitment of APP and APP-CTFs into phagophores and the sorting of APP and APP-CTFs into endosomal intralumenal vesicles, which is accompanied by the accumulation of the APP and APP-CTFs into RAB5-positive early endosomes. Collectively, our results reveal the potential connection between NRBF2 and the AD-associated protein APP by showing that NRBF2 plays an important role in regulating degradation of APP-CTFs through modulating autophagy.

An efficient and practical Cu(I)-catalyzed oxidative cyclization cascade reaction of diverse amines, alkyne esters and maleimides has been developed. The reactions can afford 4,6-dioxopyrrolo[3,4-b]pyrrole-2,3-dicarboxylates and related derivatives with satisfactory yields by altering the reaction conditions slightly. The substrate scope highlights the flexibility of the catalyst, and a reaction mechanism is also proposed.

Recent studies have demonstrated that dysregulation of macroautophagy/autophagy may play a central role in the pathogenesis of neurodegenerative disorders, and the induction of autophagy protects against the toxic insults of aggregate-prone proteins by enhancing their clearance. Thus, autophagy has become a promising therapeutic target against neurodegenerative diseases. In this study, quantitative phosphoproteomic profiling together with a computational analysis was performed to delineate the phosphorylation signaling networks regulated by 2 natural neuroprotective autophagy enhancers, corynoxine (Cory) and corynoxine B (Cory B). To identify key regulators, namely, protein kinases, we developed a novel network-based algorithm of in silico Kinome Activity Profiling (iKAP) to computationally infer potentially important protein kinases from phosphorylation networks. Using this algorithm, we observed that Cory or Cory B potentially regulated several kinases. We predicted and validated that Cory, but not Cory B, downregulated a well-documented autophagy kinase, RPS6KB1/p70S6K (ribosomal protein S6 kinase, polypeptide 1). We also discovered 2 kinases, MAP2K2/MEK2 (mitogen-activated protein kinase kinase 2) and PLK1 (polo-like kinase 1), to be potentially upregulated by Cory, whereas the siRNA-mediated knockdown of Map2k2 and Plk1 significantly inhibited Cory-induced autophagy. Furthermore, Cory promoted the clearance of Alzheimer disease-associated APP (amyloid β [A4] precursor protein) and Parkinson disease-associated SNCA/α-synuclein (synuclein, α) by enhancing autophagy, and these effects were dramatically diminished by the inhibition of the kinase activities of MAP2K2 and PLK1. As a whole, our study not only developed a powerful method for the identification of important regulators from the phosphoproteomic data but also identified the important role of MAP2K2 and PLK1 in neuronal autophagy.

Nonmotor symptoms (NMS) of Parkinson’s disease (PD) have devastating impacts on both patients and their caregivers. Jiawei-Liujunzi Tang (JLT) has been used to treat some NMS of PD based on the Chinese medicine theory since Qing dynasty. Here we report a double-blind, randomized, placebo-controlled, add-on clinical trial aiming at evaluating the efficacy and safety of the JLT in treating NMS in PD patients. We randomly assigned 111 patients with idiopathic PD to receive either JLT or placebo for 32 weeks. Outcome measures were baseline to week 32 changes in Movement Disorder Society-Sponsored Revision of Unified PD Rating Scale (MDS-UPDRS) Parts I–IV and in NMS assessment scale for PD (NMSS). We observed improvements in the NMSS total score (p=0.019), mood/cognition (p=0.005), and reduction in hallucinations (p=0.024). In addition, post hoc analysis showed a significant reduction in constipation (p<0.001). However, there was no evidence of improvement in MDS-UPDRS Part I total score (p=0.216) at week 32. Adverse events (AEs) were mild and comparable between the two groups. In conclusion, long-term administration of JLT is well tolerated and shows significant benefits in improving NMS including mood, cognition, and constipation.

Transplantation of mesenchymal stem cells (MSCs) is a promising therapeutic option for patients with acute myocardial infarction. We show here that the ectopic overexpression of endothelial nitric oxide synthases (eNOS), an endothelial form of NOS, could enhance the ability of MSCs in treating ischemic heart damage after the occlusion of the coronary artery. Adenoviral delivery of human eNOS gene into mouse bone marrow-derived MSCs (BM-MSCs) conferred resistance to oxygen glucose deprivation (OGD)-induced cell death in vitro, and elevated the bioavailability of nitric oxide when injected into the myocardium in vivo. In a rat model of acute myocardial infarction, the transplantation of eNOS-overexpressing BM-MSCs significantly reduced myocardial infarct size, corrected hemodynamic parameters and increased capillary density. We also found that the synergistic effects were consistently better than either treatment alone. These findings reveal a positive role of elevated eNOS expression in cardiac repair, and suggest the combination of eNOS and MSC transplant therapy as a potential approach for treating myocardial infarction.

Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc). Although both iron accumulation and a defective autophagy-lysosome pathway contribute to the pathological development of PD, the connection between these two causes is poorly documented. The autophagy-lysosome pathway not only responds to regulation by iron chelators and channels but also participates in cellular iron recycling through the degradation of ferritin and other iron-containing components. Previously, ferritin has been posited to be the bridge between iron accumulation and autophagy impairment in PD. In addition, iron directly interacts with α-synuclein in Lewy bodies, which are primarily digested through the autophagy-lysosome pathway. These findings indicate that some link exists between iron deposition and autophagy impairment in PD. In this review, the basic mechanisms of the autophagy-lysosome pathway and iron trafficking are introduced, and then their interaction under physiological conditions is explained. Finally, we finish by discussing the dysfunction of iron deposition and autophagy in PD, as well as their potential relationship, which will provide some insight for further study.

To investigate and quantify the potential dose-response association between alcohol consumption and risk of coronary artery disease (CAD).We searched the PubMed database from inception to March 2015 and reviewed the reference list of relevant articles to identify prospective studies assessing the association between alcohol consumption and risk of CAD. Study-specific relative risk (RR) estimates were combined using a random-effects model. Publication bias was estimated using Begg's funnel plot and Egger's regression asymmetry test. The meta-analysis included 18 prospective studies, with a total of 214 340 participants and 7756 CAD cases. The pooled adjusted RRs were 0.62 (95% confidence interval [CI] 0.56-0.68) for highest alcohol consumption amount versus lowest amount. Begg's and Egger's regression tests provided no evidence of substantial publication bias (P = 0.762 for Begg's test and 0.172 for Egger's test).In a dose response analysis, we observed a nonlinear association between alcohol consumption and risk of CAD (P for nonlinearity0.00). Compared with non-drinkers, the RRs (95% CI) of CAD across levels of alcohol consumption were 0.75 (0.70-0.80) for 12 g/d, 0.70 (0.66-0.75) for 24 g/d, 0.69 (0.64-0.75) for 36 g/d, 0.70 (0.64-0.77) for 60 g/d, 0.74 (0.67-0.83) for 90 g/d, and 0.83 (0.67-1.04) for 135 g/d.Alcohol consumption in moderation is associated with a reduced risk of CAD with 36 grams/d of alcohol conferring a lower risk than other levels.

The realization of nontrivial fermions in three-dimensional carbon allotropes greatly facilitates topological applications in carbon based-materials. In this work, we find a topological phase transition from T-carbon to bct-C16 based on first principles calculations. After carrying out a heating or a doping process on T-carbon, a new carbon phase termed bct-C16 is obtained. The potential energy and the crystal orbital Hamilton population confirm the phase transition process, respectively. Importantly, we also investigate the quantized Berry phase and drumhead surfaces states, confirming the topological nodal line semimetallic features of bct-C16. Due to the extremely weak spin–orbital coupling effect in carbon, the nodal ring in bct-C16 can be guaranteed to be nearly intact. This work not only provides two methods to obtain the carbon phase bct-C16, but also an avenue for bct-C16 to observe nontrivial fermions.

// Jun Wang 1, * , Li Ma 2, * , Tao Lin 2 , Shi-Jing Li 1 , Lei-Lei Chen 2 and De-Zhao Wang 2 1 Department of Cardiology, Beijing Mentougou District Hospital, Beijing 102300, China 2 Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China * These authors have contributed equally to this work Correspondence to: De-Zhao Wang, email: docwdz@163.com Keywords: eosinophil; acute ischemic stroke; national institute of health stroke scale Received: August 01, 2017 Accepted: September 24, 2017 Published: October 31, 2017 ABSTRACT Background: Previous studies have shown that tumor-associated tissue eosinophilia have a role in various types of solid tumors. However, the relationship between eosinophil and acute ischemic stroke (AIS) is unclear. We aimed to investigate the diagnostic significance of eosinophil in AIS patients. Methods: This study included 300 AIS patients without hypereosinophilic syndrome (HES). The hematologic indices were collected from each patient, including white blood count, eosinophil count, eosinophil percentage, neutrophil count, red blood count, and platelet. The severity of AIS was estimated by national institute of health stroke scale (NIHSS). Logistic regression analyses were performed to confirm the biomarkers for NIHSS and in-hospital non-death among the cases. Moreover, receiver-operating characteristics (ROC) analyses were used to investigate the clinical performances of eosinophils and NIHSS in prediction of non-death. Results: The admission NIHSS ( P

The influence of the solution treatment (at the temperature of 500-520°C for 4-12 h) on microstructures and mechanical properties of Mg-Gd-Y-Zr alloy was investigated by means of optical microscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) and Vickers hardness measurement. The as-cast alloy contains a microstructure consisting of α-Mg matrix, Mg5Gd phase and Mg24Y5phase. With increasing solution temperature and time, the quantity of the primary particles (Mg5Gd and Mg24Y5) in the alloy continually decreased, and the degree of recrystallization gradually increased, which result in the gradual decrease of the Vickers hardness of the solution-treated alloys.

Peptaibols, mainly produced by Trichoderma, play a pivotal role in controlling plant disease caused by fungi, virus, and Gram-positive bacteria. In the current study, we evaluated the control effect of Trichokonins, antimicrobial peptaibols from Trichoderma pseudokoningii SMF2, on soft rot disease of Chinese cabbage caused by a Gram-negative bacterium Pectobacterium carotovorum subsp. carotovorum and analyzed the mechanism involved. Trichokonins treatment (0.3 mg L(-1) ) enhanced the resistance of Chinese cabbage against Pcc infection. However, Trichokonins could hardly inhibit the growth of Pcc in vitro, even at high concentration (500 mg L(-1) ). Therefore, the direct effect of Trichokonins on Pcc may not the main reason why Trichokonins could control soft rot of Chinese cabbage. Trichokonin treatment led to an obvious increase in the production of reactive oxygen species hydrogen peroxide and superoxide radical, a significant enhance of the activities of pathogenesis-related enzymes catalase, polyphenoloxidase and peroxidase, and upregulation of the expression of salicylic acid - responsive pathogenesis-related protein gene acidic PR-1a in Chinese cabbage. These results indicate that Trichokonins induce resistance in Chinese cabbage against Pcc infection through the activation of salicylic acid signaling pathway, which imply the potential of Trichoderma and peptaibols in controlling plant disease caused by Gram-negative bacteria.

Saprotrophy on plant biomass is a recently developed nutrition strategy for Trichoderma. However, the physiology and evolution of this new nutrition strategy is still elusive. We report the deep sequencing and analysis of the genome of Trichoderma longibrachiatum, an efficient cellulase producer. The 31.7-Mb genome, smallest among the sequenced Trichoderma species, encodes fewer nutrition-related genes than saprotrophic T. reesei (Tr), including glycoside hydrolases and nonribosomal peptide synthetase-polyketide synthase. Homology and phylogenetic analyses suggest that a large number of nutrition-related genes, including GH18 chitinases, β-1,3/1,6-glucanases, cellulolytic enzymes, and hemicellulolytic enzymes, were lost in the common ancestor of T. longibrachiatum (Tl) and Tr. dN/dS (ω) calculation indicates that all the nutrition-related genes analyzed are under purifying selection. Cellulolytic enzymes, the key enzymes for saprotrophy on plant biomass, are under stronger purifying selection pressure in Tl and Tr than in mycoparasitic species, suggesting that development of the nutrition strategy of saprotrophy on plant biomass has increased the selection pressure. In addition, aspartic proteases, serine proteases, and metalloproteases are subject to stronger purifying selection pressure in Tl and Tr, suggesting that these enzymes may also play important roles in the nutrition. This study provides insights into the physiology and evolution of the nutrition strategy of Trichoderma.

The effect of Nd on the mechanical properties of magnesium alloy AZ91 has been studied. The results show that the addition of 1wt.%Nd can refine the grain size, cause the formation of high melting point Al2Nd phase and reduce the amount of β-Mg17Al12 phase. and enhance the mechanical properties of magnesium alloy AZ91 at room temperature and 150°C.

The microstructure and mechanical properties of Mg-9Gd-2Y-1Sm-0.5Zr alloy have been studied by micro-analysis and tensile tests. The results showed that the alloy mainly consists of α-Mg matrix, Mg5Gd and Mg24Y5. With the increase of temperature, the tensile strength of the alloy increases at first and then decreases, and the peak appears at 250°C.

To investigate the relationship between Helicobacter pylori (Hp) infection and the long-term outcome in acute coronary syndrome (ACS) patients with drug-eluting stent (DES) implantation and so as to explore the significance of Hp eradication therapy in preventing major adverse cardiac events (MACE) and upper gastrointestinal bleeding (UGIB). 539 ACS patients with DES implantation from January 1, 2010 to December 31, 2012 were analyzed. All the patients were divided into two groups according to the result of 13C urea breath test. 253 patients with Hp infection were put into group A (Hp+), and 286 cases without Hp infection were put into group B (Hp−). Demographic data was collected and all patients went through biochemical indicators and other routine blood examinations. We explored the correlations of Hp infection with MACE and UGIB after 3 to 5 years of follow-up using survival analysis. Survival analysis showed that Hp infection was a predictor of MACE and UGI. Sub-group analysis showed that patients with Hp eradication therapy had no relationship with MACE but had a lower rate of UGIB than those without Hp eradication therapy.

Aim There is evidence suggesting that inflammatory responses play a critical role in the development of coronary artery disease (CAD). Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine. It increases during inflammatory processes and is associated with cardiometabolic risk. However, the relation between GDF-15 and CAD remains largely unknown. Herein, we aimed to evaluate serum GDF-15 levels and predictive values in patients with CAD. Methods Serum levels of GDF-15 in 105 patients with CAD and 96 healthy controls were measured by the enzyme-linked immunosorbent assay. Gensini scores were used to assess severity of CAD. The correlations between the serum GDF-15 levels and Gensini scores were examined using Spearman's correlation. Receivers operating characteristic (ROC) curve analysis was performed to determine the predictive values of GDF-15 levels. Results We found that serum GDF-15 levels were significantly increased in CAD group compared with healthy controls group (P

Objective: This double-blind, randomized, placebo-controlled, add-on pilot study aimed at providing information for conducting a full-scale trial assessing “Di-tan decoction” (DTD), which is a traditional Chinese medicine (TCM) formula frequently used in TCM to treat symptoms that are now defined as Alzheimer’s disease (AD), in treating AD in the future. Methods: We randomly assigned 38 patients with AD to receive either DTD or placebo for 24 weeks. Primary outcome was changes in the total score of AD Assessment Scale-cognitive subscale (ADAS-cog) and secondary outcome was changes in the total score of Chinese version of the Disability Assessment for Dementia (C-DAD). Results: Although we observed some improvement in the total scores of ADAS-cog in the DTD group comparing to the placebo group, the changes were not statistically significant. The ADAS-cog sub-scores of the DTD group also showed non-significant trends of improvement in ideational praxis (p=0.100) and in comprehension (p=0.106) comparing to placebo group. Adverse events were mild and comparable between two groups. Conclusion: This is the first rigorous randomized control trial of DTD focusing on AD. At least five factors could explain the failure of the trends to be significant, namely length of trial, size of trial, stage of AD, palatability of the drug, and sensitivity of the scoring system. Given the limitation but with the safety and century’s use of DTD, a modified pilot study is needed to support the clinical effects of DTD. In conclusion, there is no evidence supporting the efficacy of DTD to act as a single treatment for AD.

Feature specifications are important composite parts in the new generation of geometrical product specifications and verification (GPS). According to the theories of specification model of shaft parts, this paper presents a method to generation of specification model of concentricity. Firstly, the mathematical model of concentricity is established in terms of nominal geometrical features of product for the parts the functional requirement are satisfied. Secondly, the simulation points of the model are generated by using the methods of axial stratification and circumferential multi-angles. The concentricity specification model could be generated after these operations of association and collection. Finally, an example is applied to illustrate the new method. The experiment results show the effectiveness of the proposed method.

Y and Gd are vital alloying elements to the AZ magnesium alloys. It is due to their functions mainly on solid solution strengthening and age strengthening. This paper reviews effect of Y, Gd on mechanical properties of AZ-series magnesium alloys. The future development direction is pointed.

Trichoderma spp. are well-known biocontrol agents because of their antimicrobial activity against bacterial and fungal phytopathogens. However, the biochemical mechanism of their antiviral activity remains largely unknown. In this study, we found that Trichokonins, antimicrobial peptaibols isolated from Trichoderma pseudokoningii SMF2, could induce defense responses and systemic resistance in tobacco (Nicotiana tabacum var. Samsun NN) against tobacco mosaic virus (TMV) infection. Local Trichokonin (100 nM) treatment led to 54% lesion inhibition, 57% reduction in average lesion diameter and 30% reduction in average lesion area in systemic tissue of tobacco compared with control, indicating that Trichokonins induced resistance in tobacco against TMV infection. Trichokonin treatment increased the production of reactive oxygen species and phenolic compounds in tobacco. Additionally, application of Trichokonins significantly increased activities of pathogenesis-related enzymes PAL and POD, and upregulated the expression of several plant defense genes. These results suggested that multiple defense pathways in tobacco were involved in Trichokonin-mediated TMV resistance. We report on the antivirus mechanism of peptaibols, which sheds light on the potential of peptaibols in plant viral disease control.

Endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) may play an important role in attenuating cardiac remodeling and apoptosis after myocardial infarction. However, the anti-inflammation effects of eNOS in infarcted myocardium and the role of MAPK signaling in eNOS/NO mediated cardiac remodeling have not yet been elucidated. Adenovirus carrying Human eNOS gene was delivered locally into heart 4 days prior to induction of myocardial infarction (MI) by left anterior descending coronary artery ligation. Monocyte/macrophage infiltration was detected by ED-1 immunohistochemistry. Western blot was employed to examine the activation of MAPK. eNOS gene transfer significantly reduced myocardial infarct size and improved cardiac contractility as well as left ventricle (LV) diastolic function at 7 days after MI. In addition, eNOS gene transfer decreased monocyte/macrophage infiltration in the infarct region of the heart. Phosphorylation of MAPK after MI were also dramatically reduced by eNOS gene transfer. All the protective effects of eNOS were blocked by N(ω)-nitro-L-arginine methyl ester (L-NAME) administration, indicating a NO-mediated event. These results demonstrate that the eNOS/NO system provides cardiac protection after MI injury through inhibition of inflammation and suppression of MAPK signaling.