Pulmonary toxicity induced by three forms of titanium dioxide nanoparticles via intra-tracheal instillation in rats

Titanium dioxide (TiO2) nanoparticles are in wide commercial use worldwide. To evaluate if acute pulmonary toxicity can be induced by nano-TiO2 particles, rats were intra-tracheally instilled with 0.5, 5, or 50 mg/kg of 5, 21, and 50 nm TiO2 primary particles. Toxic effects were determined with the coefficients of lung tissues to body weight, histopathology, biochemical parameters of blood, activity of lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and acid phosphatase (ACP) in tissues, and the phagocytotic ability of alveolar macrophages (AMs). All the indicators were observed in sacrificed rats one week post-exposure. There was a significant difference of coefficients of pulmonary tissues between the high-dose group and the low- or moderate-dose groups with an exposure of 5 nm TiO2. At the same time, 5 nm TiO2 primary particles increased the activity of LDH and ALP when exposure dose was >5 mg/kg. A significant difference in LDH and ALP activity was observed between the 50 mg/kg group and 0.5 or 5 mg/kg group with exposure of 5 nm TiO2. Lung tissues showed increased ALP activity only if treated with 5 and 50 mg/kg of 21 nm TiO2 particles. There was no significant difference in LDH and ALP activity in the 50 nm TiO2 group and control group. Histopathologic examination of lung tissues indicated that the pulmonary response to exposure to TiO2 particles in rats manifested as dosedependent inflammatory lesions, which mainly consisted of infiltration of inflammatory cells and interstitial thickening. Analysis of uptake of neutral red dye showed that 50 nm TiO2 particles significantly increased phagocytotic ability of AMs compared with controls (P < 0.05), whereas exposure with 5 nm TiO2 reduced the phagocytotic ability of AMs when the exposure dose was 50 mg/kg. These results suggest that particle size and exposure dose may have important roles in pulmonary toxicity. The toxic effect of TiO2 nanoparticles in lung tissue exhibited a dose–response relationship. After exposure with TiO2 particles of >5.0 mg/kg, 5 and 21 nm TiO2 particles induced standing pulmonary lesions; and 5 nm TiO2 particles may suppress the phagocytotic ability of AMs if exposure dose was ≥50 mg/kg. Pulmonary toxicity caused by 5 nm TiO2 particles was more severe than that caused by 21 and 50 nm TiO2 particles.     

GLP-1R agonists therapy for type 2 diabetes

Glucagon-like peptide-1 receptor （GLP-1R） agonists are widely used for treating type 2 diabetes mellitus （T2DM） be- cause of their glucose-lowering and weight-losing effects, and low risk of hypoglycemia. Hence, there is considerable interest in understanding the mechanism underlying the beneficial effects of GLP-I and developing stable and effective GLP-1R agonists. Here, we summarize the presently known mechanism of GLP-I actions, which are mainly through regulating cAMP-PKA signaling pathway; the latest developments in novel clinical GLP-1R agonists are also introduced, which are characterized with multiple properties, such as extended half-life, reduced side-effects, lower production costs and more convenient drug dosing mode. The potential risk of GLP-I-based therapeutics, an often-ignored fact, is also discussed.     

Carbon Emission Modeling and Analysis in Manufacturing Process for Numerical Control Machine Tools

Reducing carbon emissions（ CEs） is the urgent demand all over the world. In order to realize the low-carbon numerical control（ NC） machining, the evaluation model of a part＇s manufacturing carbon emission with NC machine tools was built by considering the influences of the cutting tool geometrical parameters.The manufacturing CEs were produced by electric power,cutting tools,and cutting fluid consumed in manufacturing process. The parameters of cutting tools affected not only the CEs,but also the machining quality. Then the actual constraint models of the machine performance,machining quality were given in order to optimize the cutting parameters and achieve the low-CEs. Finally,a case was given to analyze the influences of the cutting tool angles on the manufacturing CEs. The results show that the CEs decrease as the rake angle and edge angle increase under the constraints of the machine specifications and machining quality.     

Performance of Sequencing Biofilm Batch Reactor（SBBR） under Micro-aerobic Condition for Aniline-Contaminated Wastewater Treatment

The performance of sequencing biofilm batch reactor（ SBBR） under micro-aerobic condition for aniline-contaminated wastewater treatment was investigated in this study. Dissolved oxygen（ DO） and aniline concentrations were selected as the operating variables to analyze,model,and optimize the process. In order to analyze the process,5 dependent parameters,chemical oxygen demand（ COD）,aniline,ammonium,total nitrogen（ TN）,and total phosphorous（ TP） removal as the process responses were studied. From the results, increase in DO concentration could promote the removal of COD,aniline,ammonium,and TN,while increase in aniline concentration has a slightly negative impact on the removal of pollutants. The optimum DO concentration was found to be 0. 4-0. 5 mg /L. The removal efficiencies for COD,aniline,ammonium,and TN at the optimum point（ DO concentration0. 5 mg /L,aniline concentration 11 mg /L） were 95. 84%,100%,75. 72%,and 45. 39%,respectively. The oxidative deamination was the main degradation method for aniline under micro-aerobic condition. Simultaneously nitrification-denitrification（ SND）process performed under micro-aerobic condition and about 20%-40% nitrogen was removed by SND.     

Influence of Mica Particles on the Rheological Properties and Thermal Stability of Poly（ lactic acid）

The influence of mica particles on the rheological and thermal properties of poly（ lactic acid）（ PLA） / mica composites were investigated by capillary rheometer and thermogravimetric（ TG）analysis. The results show that the PLA / mica blends are nonNewtonian pseudoplastic and display shear-thinning. The value of non-Newtonian index of the blends melt decreased obviously with the addition of mica particles but somehow even increased when shear rate exceeded 4 500 s- 1. In this work,it could be indicated that appropriate amount of mica particles could somehow enhance the resistance of PLA melt under high shear rate to deviate from Newtonian fluid. TG analysis shows that the thermal stability of PLA decreases a little after the incorporation of the mica particles.As mica particles decompose in a completely different way in contrast to PLA,this abnormal decrease of thermal stability of PLA / mica composite may be attributed to moisture stored between mica layers released at high temperature.     

Global Mission Sensitivity Study for Phased MissionSystem with Analysis of Variance Method

A comprehensive mission sensitivity analysis index based on Sobol＇s index called global mission sensitivity（ GMS） was proposed in this paper which focused on analyzing the mission sensitivity of components of phased mission systems（ PMS）. The simulation strategy of GMS based on a Petri net and Monte Carlo method was presented which had broad applicability. Finally,the GMS and Birnbaum＇s sensitivity of components in a PMS example were compared. The GMS of component is demonstrated to be more adaptable to reflect the component mission sensitivity when the rated reliability parameters of components cannot be obtained, and components have state dependency or the system is subjected to common cause failure.     

Combinatorial Optimization Based Analog Circuit Fault Diagnosis with Back Propagation Neural Network

Electronic components＇ reliability has become the key of the complex system mission execution. Analog circuit is an important part of electronic components. Its fault diagnosis is far more challenging than that of digital circuit. Simulations and applications have shown that the methods based on BP neural network are effective in analog circuit fault diagnosis. Aiming at the tolerance of analog circuit,a combinatorial optimization diagnosis scheme was proposed with back propagation（ BP） neural network（ BPNN）.The main contributions of this scheme included two parts：（ 1） the random tolerance samples were added into the nominal training samples to establish new training samples,which were used to train the BP neural network based diagnosis model;（ 2） the initial weights of the BP neural network were optimized by genetic algorithm（ GA） to avoid local minima,and the BP neural network was tuned with Levenberg-Marquardt algorithm（ LMA） in the local solution space to look for the optimum solution or approximate optimal solutions. The experimental results show preliminarily that the scheme substantially improves the whole learning process approximation and generalization ability,and effectively promotes analog circuit fault diagnosis performance based on BPNN.     

Importance Analysis of a Multi-state System Based on Direct Partial Logic Derivatives and Multi-valued Decision Diagrams

Importance analysis quantifies the critical degree of individual component. Compared with the traditional binary state system,importance analysis of the multi-state system is more aligned with the practice. Because the multi-valued decision diagram（ MDD） can reflect the relationship between the components and the system state bilaterally, it was introduced into the reliability calculation of the multi-state system（ MSS）. The building method,simplified criteria,and path search and probability algorithm of MSS structure function MDD were given,and the reliability of the system was calculated. The computing methods of importance based on MDD and direct partial logic derivatives（ DPLD） were presented. The diesel engine fuel supply system was taken as an example to illustrate the proposed method. The results show that not only the probability of the system in each state can be easily obtained,but also the influence degree of each component and its state on the system reliability can be obtained,which is conducive to the condition monitoring and structure optimization of the system.     

Structure Changes of Silk Fibroin（SF） by Blending with Poly（ε-caprolactone）（PCL）：Characterization of SF and PCL Blended Electrospinning Films

The mechanical properties and water solubility of electrospinning SF films limit their use as biomaterials. In order to develop a tissue engineering biomaterial with both satisfying biological properties and sufficient biomechanical properties,blended films composed of silk fibroin（ SF） and poly（ ε-caprolactone）（ PCL） were fabricated by electrospinning in this study. Scanning electron microscope（ SEM）, X-ray diffraction（ XRD）,thermal analysis,Fourier transform-infrared（ FT-IR）,Raman spectra,mechanical testing,and water solubility were used to characterize the morphological, structural and mechanical properties of the blended electrospinning films. Results showed that the diameter of the blended fiber was distributed between 600 and1000 nm,and the fiber diameter increased as the PCL content increased. There is no obvious phase separation due to the similarity and intermiscibility,as well as the interactions（ mainly hydrogen bonds）, between the two polymers. Meanwhile, the secondary structures of SF changed from random coils and Silk I to Silk II because of the interactions between SF and PCL. For this reason,the tensile strength and elongation at break of the electrospinning films improved significantly,and the water solubility decreased. In conclusion,the blended electrospinning films fabricated in this study showed satisfying mechanical properties and water insolubilities,and they may be promising biomaterials for applications in tissue engineering for blood vessels,nerve conduits,tendons,ligaments and other tissues.     

Albumin resuscitation protects against traumatic/hemorrhagic shock-induced lung apoptosis in rats

Objective： To determine the effects of albumin administration on lung injury and apoptosis in traumatic/hemorrhagic shock （T/HS） rats. Methods： Studies were performed on an in vivo model of spontaneously breathing rats with induced T/HS; the rats were subjected to femur fracture, ischemia for 30 min, and reperfusion for 20 min with Ringer＇s lactate solution （RS） or 5% （w/v） albumin （ALB）, and the left lower lobes of the lungs were resected. Results： Albumin administered during reperfusion markedly attenuated injury of the lung and decreased the concentration of lactic acid and the number of in situ TdT-mediated dUTP nick-end labelling （TUNEL）-positive cells. Moreover, immunohistochemistry performed 24 h after reperfusion revealed increases in the level of nuclear factor κB （NF-κB）, and phosphorylated p38 mitogen-activated protein kinase （MAPK） in the albumin-untreated group was down-regulated by albumin treatment when compared with the sham rats. Conclusion： Resuscitation with albumin attenuates tissue injury and inhibits T/HS-induced apoptosis in the lung via the p38 MAPK signal transduction pathway that functions to stimulate the activation of NF-κB.     

Cellular mechanism of cardiac alternans： an unresolved chicken or egg problem

T-wave alternans, a specific form of cardiac alternans, has been associated with the increased suscep- tibility to cardiac arrhythmias and sudden cardiac death （SCD）. Plenty of evidence has related cardiac alternans at the tissue level to the instability of voltage kinetics or Ca^2＋ handling dynamics at the cellular level. However, to date, none of the existing experiments could identify the exact cellular mechanism of cardiac alternans due to the bi-directional coupling between voltage kinetics and Ca^2＋ handling dynamics. Either of these systems could be the origin of alternans and the other follows as a secondary change, therefore making the cellular mechanism of alternans a difficult chicken or egg problem. In this context, theoretical analysis combined with experimental techniques provides a possibility to explore this problem. In this review, we will summarize the experimental and theoretical advances in understanding the cellular mechanism of alternans. We focus on the roles of action potential duration （APD） restitution and Ca^2＋ handling dynamics in the genesis of alternans and show how the theoretical analysis combined with experimental techniques has provided us a new insight into the cellular mechanism of alternans. We also discuss the possible reasons of increased propensity for alternans in heart failure （HF） and the new possible therapeutic targets. Finally, according to the level of electrophysiological recording techniques and theoretical strategies, we list some critical experimental or theoretical challenges which may help to determine the origin of alternans and to find more effective therapeutic tar- gets in the future.     

Temperature Prediction Model Identification Using Cyclic Coordinate Descent Based Linear Support Vector Regression

Temperature prediction plays an important role in ring die granulator control, which can influence the quantity and quality of production. Temperature prediction modeling is a complicated problem with its MIMO, nonlinear, and large time-delay characteristics. Support vector machine （SVM） has been successfnlly based on small data. But its accuracy is not high, in contrast, if the number of data and dimension of feature increase, the training time of model will increase dramatically. In this paper, a linear SVM was applied combing with cyclic coordinate descent （ CCD） to solving big data regression. It was mathematically strictly proved and validated by simulation. Meanwhile, real data were conducted to prove the linear SVM model＇s effect. Compared with other methods for big data in simnlation, this algorithm has apparent advantage not only in fast modeling but also in high fitness.     

Relationship between precipitation and the infiltration depth over the middle and lower reaches of the Yellow River and Yangtze-Huaihe River Valley

The purpose of the paper is to extract and make the best use of rainfall information contained in the Chinese historical archives of Qing Dynasty, and reconstruct the precipitation series during 1736-1911. The study followed the Yu-Fen-Cun （rainfall infiltration depth） observation method in Qing Dynasty, to conduct soil infiltration experiment under the natural rainfall conditions during 2004-2006. The related parameters, such as precipitation, intensity, initial soil moisture content and infiltration depth have been measured at 10 stations （east of 105°E, 30°-40°N） with representative climatic conditions and soil physical texture in the middle and lower reaches of the Yellow River and Yangtze-Huaihe River Valley. The statistical results indicate that precipitation is the primary influencing factor to infiltration depth and is positively correlated with the infiltration depth. Additionally, the effects of every factor on infiltration depth are significantly different between the middle and lower reaches of the Yellow River and Yangtze-Huaihe River Valley. Finally, the relationship equations of precipitation and infiltration depth are established for each site, most of which can pass over 60% of the variance explanations and provide quantitative models to reconstruct the precipitation series using Yu-Fen-Cun records in Qing Dynasty.     

Review： Deregulation of microRNA expression in thyroid tumors

MicroRNAs （miRNAs or miRs） are endogenous non-coding RNAs that negatively regulate gene expres- sion by binding to the 3＇ non-coding regions of target mRNAs, resulting in their cleavage or blocking their translation. miRNAs may have an impact on cell differentiation, proliferation, and survival, and their deregulation can be inclined to diseases and cancers, including thyroid tumors. The purpose of this review is to summarize the existing findings of deregulated miRNAs in different types of thyroid tumors and to exhibit their potential target genes, especially to demonstrate those involved in tumor invasion and metastasis. In addition, new findings of circulating miRNA expres- sion profiles, single nucleotide polymorphism （SNP） in thyroid tumors, and the correlation of somatic mutations with deregulated miRNA expression in thyroid tumors were all included in this review.     

全球招聘新闻（英文）

正博士后[美国]University of Texas Health Science Center at Tyler A postdoctoral research associate position is available immediatelyat University of Texas Health Science Center at Tyler(UTHSCT),to study the mechanisms and repair of lung injuries.The potentialcandidates should have an MD and/or PhD degree and a strongbackground in molecular biology and animal studies of pulmonary     

pH-Compensation Effect of Lysine on the Acidic Degradation of Electrospun Poly（ lactide-co-glycolide） Fibers in PBS

Electrospun aligned ultrafine fibers of poly（ lactide-coglycolide）（ PLGA） can be used to construct biomimetic scaffolds for engineering those structurally anisotropic and dense tissues（ e. g.,tendon,ligament,etc.）. But the acidic degradation products of the PLGA could result in p H decrease in the vicinity of the scaffolds,which may give rise to biocompatibility concerns. To address the noted problem, this study was designed to evaluate the p Hcompensation capacity of using Lysine（ Lys） —a kind of basic amino acid on the acidic degradation products of PLGA. Ultrafine PLGA（ 50∶ 50） fibers with 0,10%,20%,and 30% by weight of Lys loadings were prepared by a stable jet electrospinning（ SJES）approach. The morphology,structure,and mechanical properties of the electrospun aligned fibrous mats of Lys-incorporated PLGA（ 50∶50） were characterized by scanning electron microscope（ SEM）,Fourier transform infrared spectroscopy（ FTIR）,and tensile testing,respectively. Thereafter,the fibrous PLGA（ 50 ∶50） scaffolds were subjected to degradation by being immersed in phosphate buffered saline（ PBS,p H 6. 86） solution at 37 ℃ for 5weeks. Our results show that the formed Lys / PLGA composite ultrafine fibers have a well-aligned and uniform morphology with a fineness of ca. 1 #m in diameter. Introduction of Lys led to increased mechanical performance; that is,when the Lys loading is less than 30%,tensile strength and Young＇s modulus of the aligned Lys / PLGA fibers reached up to the impressive values of 84. 5 MPa and 2. 4 GPa,respectively. Degradation results show that the p H of the PLGA group fell to 5. 6 in 5 weeks while the p H of the Lys /PLGA groups with 10%,20%, and 30% of Lys loadings was maintained at 6. 3, 6. 5 and 6. 7, respectively. This work demonstrated that incorporation of Lys into electrospun PLGA fibers could be an effective approach in mediating the p H decrease caused by the acidic degradation products of the PLGA.     

Developing the plate tectonics from oceanic subduction to continental collision

The studies of continental deep subduction and ultrahigh-pressure metamorphism have not only promoted the development of solid earth science in China, but also provided an excellent opportunity to advance the plate tectonics theory. In view of the nature of subducted crust, two types of subduction and collision have been respectively recognized in nature. On one hand, the crustal subduction occurs due to underflow of either oceanic crust （Pacific type） or continental crust （Alpine type）. On the other hand, the continental collision proceeds by arc-continent collision （Himalaya-Tibet type） or continent-continent collision （Dabie-Sulu type）. The key issues in the future study of continental dynamics are the chemical changes and differential exhumation in continental deep subduction zones, and the temporal-spatial transition from oceanic subduction to continental subduction.     

Improved AODV Routing Protocol Based on Link Stability and Channel Switching

Ad hoc on-demand distance vector （AODV） routing is one of the typical reactive routing protocols of vehicular ad hoc networks （V ANET ）. Considering link stability and channel switching can greatly improve the QoS of protocols, in this paper, we propose a novel routing protocol： optimized cross-layer AODV （CL _ AODV） designed for V ANET. It utilizes the frame transmission efficiency （FIE）, path bandwidth in media access control （MAC） layer and signal-to-noise ratio （SNIR） in physical （PHY） layer to improve the link stability. In other words, it can increase packet delivery ratio effectively. In addition, end-to-end delay will be decreased based on the channel switching. According to the simulation, it is shown that the packet delivery ratio of CL_AODV is almost up to 99% and the highest compared to AODV and muti-constrained QoS AODV （MQ _ AODV）. The delay of CL_ AODV is almost half of MQ_AODV＇s and 1/3 of AODV＇s. Meanwhile, CL_AODV has the highest routing overhead or energy consuming. Because of the feature of V ANET, the disadvantage can be ignored.     

Study on cellular internalization of poly（vinyldiaminotriazine）-based hydrogen bonding type non-viral transgene vector

Previously we successfully prepared poly（vinyldiaminotriazine）（PVDT）-based non-viral vectors which complexed piasmid DNA via hydrogen bonding with adenine-thymine base pairs, in this report, surface charges and complex sizes of this system were further examined. The results showed that PVDT-based polymer could cover surface charges of DNA resulting in slightly negative or neutral complexes. It was also found that the complex sizes were governed by two events： the aggregation induced by the instability of neutral particles, and more compact complexes produced by PVDT-based polymers. In the study of cellular uptake, chlorpromazine and filipin III were used to inhibit clathrin-and caveolae-mediated endocytosis, respectively. We found that PVDT-based systems were transported into cells via a non-clathrin, non-caveolae mediated endocytosis. This special process was studied by temperature inhibition and kinetics assays. It was revealed that such a pathway was characterized by （i） a more en- ergy dependent process and （ii） a much slow transfection-effective internalization.