SIRT3 alleviates mitochondrial dysfunction induced by recurrent low glucose and improves the supportive function of astrocytes to neurons.

Hypoglycemia is an independent risk factor of cognitive impairment in patients with diabetes. Our previous study indicated that dysfunction of astrocytic mitochondria induced by recurrent low glucose (RLG) may account for hypoglycemia-associated neuronal injury and cognitive decline. Sirtuin 3 (SIRT3) is a key deacetylase for mitochondrial proteins and has recently been demonstrated to be an important regulator of mitochondrial function. However, whether mitochondrial dysfunction due to hypoglycemia is associated with astrocytic SIRT3 remains unclear, and few studies have focused on the impact of astrocytic SIRT3 on neuronal survival. In the present work, primary mouse cortical astrocytes cultured in normal glucose (5.5 mM) and high glucose (16.5 mM) were treated with five rounds of RLG (0.1 mM). The results showed that RLG suppressed SIRT3 expression in a glucose-dependent manner. High-glucose culture considerably increased the vulnerability of SIRT3 to RLG, leading to disrupted mitochondrial morphology in astrocytes. Overexpression of SIRT3 markedly improved astrocytic mitochondrial function and reduced RLG-induced oxidative stress. Moreover, SIRT3 suppressed a shift towards a neuroinflammatory A1-like reactive phenotype of astrocytes in response to RLG with reduced IL-1ß, IL-6, and TNFα levels. Furthermore, it elevated brain-derived neurotrophic factor (BDNF) levels and promoted neurite growth by activating BDNF/TrkB signaling in the co-cultured neurons. The present study reveals the probable crosstalk between neurons and astrocytes after hypoglycemic exposure and provides a potential target in treating hypoglycemia-associated neuronal injury.

Increased fatty acid metabolism attenuates cardiac resistance to ß-adrenoceptor activation via mitochondrial reactive oxygen species: A potential mechanism of hypoglycemia-induced myocardial injury in diabetes.

The mechanism of severe hypoglycemia (SH)-induced cardiovascular disease in diabetes remains unknown. Our previous study found that SH inhibits cardiac function and lipid metabolism in diabetic mice. Conversely, in nondiabetic mice, SH does not induce cardiac dysfunction but promotes cardiac lipid metabolism. This study aims to clarify the effect of increased fatty acid metabolism on the resistance of cardiomyocytes to ß-adrenoceptor activation during hypoglycemia in diabetes. Results revealed that cardiomyocytes with enhanced lipid metabolism were more vulnerable to damage due to ß-adrenoceptor activation, which presented as decreased cell viability, disorder of mitochondrial structure, dissipation of mitochondrial membrane potential, dysfunction of mitochondrial oxidative phosphorylation, nonapoptotic damage, and accumulation of ROS and calcium from mitochondria to cytoplasm, all of which were partially reversed by mitochondrial antioxidant Mito-TEMPO. The SH-induced cardiac dysfunction, and reduction of myocardial energy metabolism in diabetic mice were rescued by Mito-TEMPO. Our findings indicate that high fatty acid metabolism crippled cardiac resistance to ß-adrenoceptor hyperactivation, with mitochondrial ROS playing a pivotal role in this process. Reducing mitochondrial ROS in diabetes could disrupt this synergistic effect and prevent poor cardiac outcomes caused by SH.

Glucagon-like peptide-1 analogs mitigate neuroinflammation in Alzheimer's disease by suppressing NLRP2 activation in astrocytes.

Neuroinflammation is closely linked to the pathogenesis of Alzheimer's disease (AD). Glucagon-like peptide-1 (GLP-1) analogs exhibit anti-inflammatory and neuroprotective effects; hence, we investigated whether they reduce cognitive impairment and protect astrocytes from oxidative stress. We found that 5 × FAD transgenic mice treated with the synthetic GLP-1 receptor agonist exenatide had improved cognitive function per the Morris water maze test. Immunohistochemistry, western blotting, and ELISAs used to detect inflammatory factors revealed reduced neuroinflammation in extracted piriform cortexes of exenatide-treated mice as well as lower amyloid ß1-42-induced oxidative stress and inflammation in astrocytes treated with exendin-4 (the natural analog of exenatide). Adenovirus-mediated overexpression of nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 2 (NLRP2) revealed that exenatide/exendin-4 function may be attributed to NLRP2 inflammasome inhibition. Collectively, our results indicate that GLP-1 analogs improve cognitive dysfunction in vivo and protect astrocytes in vitro, potentially via the downregulation of the NLRP2 inflammasome.

Lactoferrin ameliorates pathological cardiac hypertrophy related to mitochondrial quality control in aged mice.

Pathological myocardial hypertrophy, which lacks effective prevention and treatment strategies, makes the elderly susceptible to various cardiovascular diseases. Based on the beneficial attributes of lactoferrin in aging-related diseases, we aimed to investigate whether lactoferrin could exert protection against aging-related cardiac hypertrophy and further explore the underlying mechanisms. Here, we assessed the effects of lactoferrin on myocardial pathology, apoptotic proteins, mitochondrial morphology, kinetics, autophagy, and aging-related markers, including lipofuscin deposition, overloaded iron, and oxidative stress, which are known to destabilize the mitochondrial-lysosomal axis in aged mice. Upon the administration of lactoferrin, aged hearts showed amelioration of pathological cardiac hypertrophy, which was associated with decreased apoptosis, improved morphology, rearrangement of mitochondrial dynamics, increased lysosome-dependent autophagy, and inhibition of factors detrimental to the mitochondrial-lysosomal axis. In conclusion, lactoferrin ameliorated pathological cardiac hypertrophy, potentially by improving the mitochondrial quality related to mitochondrial dynamics and the mitochondrial-lysosomal axis, thus reducing mitochondria-dependent apoptosis, which is the pivotal factor for cardiac hypertrophy in aged mice.

Combustion Characteristics, Kinetics, and Thermodynamics of Pine Wood Through Thermogravimetric Analysis.

The thermal conversion of woody biomass is increasingly critical for the development of the energy processing technologies and fire safety engineering. The combustion characteristics, kinetics, and thermodynamics of pine wood were characterized through a thermogravimetric analyzer in the air atmosphere. There were two apparent peaks in the derivative TG curves for pine wood. The combustion process of pine wood was divided into two stages. Therein, the first stage occurring in the conversion degree range of 0-0.6 may be considered a one-step reaction. It was easier for pine wood to decompose under air than under nitrogen. Moreover, the first stage of pine wood combustion may be characterized by the diffusion model g(α) = [1 - (1 - α)1/3]2. The kinetic modeling showed a good agreement between the predicted and experimental conversion degree curves. In addition, the high comprehensive combustion index of pine wood at 10 K min-1 (6.73 × 10-7 %2 min-2 K-3) showed its great potential for bioenergy generation. Besides, both the value of ΔH and ΔS exhibited similar patterns with the activation energy value versus conversion degree, while the ΔG value almost remained at a positive constant with conversion degree. The average ΔH, ΔG, and ΔS value was nearly equal under different heating rates.

Kinetic and volatile products study of micron-sized PMMA waste pyrolysis using thermogravimetry and Fourier transform infrared analysis.

Much attention has been devoted to disposing traditional-sized poly(methyl methacrylate) (PMMA) waste by pyrolysis for methyl methacrylate (MMA). The pyrolysis of micron-sized PMMA waste, which may be different from that of traditional-sized PMMA waste, received little concern. The present study investigated the kinetics and volatile products of micron-sized PMMA waste pyrolysis in inert atmosphere using thermogravimetry and Fourier transform infrared analysis. A global optimization algorithm namely Shuffled Complex Evolution (SCE) was employed to simultaneously optimize the kinetic parameters. Results indicated that one shoulder and one peak occurred in the MLR variations with temperature. The values of the MLR at the shoulder and peak, the average MLR all increased with the heating rate. The optimized kinetic parameters by SCE can be utilized to well reproduce the experimental thermogravimetric data. The values of activation energy and natural logarithm of pre-exponential factor were in the range of 235.95-248.61 kJ/mol and 16.96-28.76 min-1, respectively. The value of activation energy of micron-sized PMMA waste pyrolysis under the present study was greater than that of the traditional-sized PMMA pyrolysis in the previous studies. MMA and CO2 were the major volatile products generated from the micron-sized PMMA waste pyrolysis. The volatile products yield at peak was much larger than that at shoulder. The MMA and CO2 yield were in the range of 87.98-93.54% and 6.46-12.02%, respectively. High MMA yield may be obtained from the pyrolysis of micron-sized PMMA waste in inert atmosphere by appropriately increasing the heating rate adopted in the reactors in the practical applications.

Kinetics, Thermodynamics, and Volatile Products of Camphorwood Pyrolysis in Inert Atmosphere.

The kinetics, thermodynamics, and volatile products of camphorwood pyrolysis were investigated via thermogravimetry coupled with Fourier transform infrared (FTIR) spectroscopy at multiple heating rates. The kinetic triplets and thermodynamic parameters were estimated via model free combined with the model-fitting approach. The results showed that the pyrolysis of camphorwood in the conversion rate range from 0 to 0.85 might be considered as one-step process. The mean value of the activation energy and pre-exponential factor was 192.63 kJ/mol and 2.38 × 1013 s-1, respectively. The pyrolysis process (0 ≤ α ≤ 0.85) can be described by the three-dimensional diffusion model g(α) = [(1-α)-1/3 - 1]2. Furthermore, the predicted curves of the conversion rate α showed good agreement with the experimental curves. The values of ΔH, ΔG, and ΔS varied little with α and remained positive. In addition, the major gas products released from the camphorwood waste pyrolysis were H2O, methane, CO2, CO, C=O, O-H, C-O-C, and NH3, whose concentration in the order from highest to lowest was C=O > CO2 > O-H > H2O > methane > NH3 > C-O-C > CO. The main conclusions in the present study can provide guidance for the design and optimization of industrial reactor and selection of target biofuels or chemical raw materials.

Comparative Pyrolysis Characteristics and Kinetics of Typical Hardwood in Inert and Oxygenous Atmosphere.

Combustion (pyrolysis with oxygen) and pyrolysis without oxygen are two potential methods to convert wood into biofuels or biochemicals. To evaluate which is preponderant to convert wood into biofuels or biochemicals and provide guidance for optimization of product yield, the pyrolysis characteristics and kinetics of typical hardwood (black walnut) are comparatively investigated in nitrogen and air employing thermogravimetric analysis (TGA) and differential scanning calorimeter (DSC). Two model-free methods including Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) method are applied to obtain the kinetic parameters, and a model-fitting method called Coats-Redfern (CR) method is employed to estimate the reaction mechanism. The black walnut pyrolysis in nitrogen may be divided into two stages with the threshold of conversion rate α = 0.4, but that in air may be separated into three stages with the thresholds of α = 0.25 and 0.7. The reaction mechanism for pyrolysis in nitrogen may be assumed random nucleation and its subsequent growth, but that in air may be assumed random nucleation and its subsequent growth followed by chemical reaction. The average activation energy and natural logarithm of pre-exponential factor for the whole pyrolysis process in nitrogen and air are 211.59 and 187.73 kJ/mol and 32.33 and 28.36 min-1, respectively.

Pyrolysis Characteristics and Reaction Mechanisms of Pine Needles.

Pyrolysis has been considered as a promising method to utilize biomass by thermal cracking for energy or feedstock. In order to provide guidance for thermochemical process management of pine needle utilization by pyrolysis, the pyrolysis kinetics and reaction mechanism of one typical pine needle are investigated employing thermogravimetric analysis in nitrogen in the present study. Multi kinetics methods including model-free method and model-fitting method are adopted. Results indicate that one peak and three shoulders occur in the reaction rate curves. The maximum reaction rates decrease with the increasing of heating rates, and the average reaction rate of the whole process is 0.0021 K-1. The pyrolysis process of pine needles in nitrogen may be divided into four stages in the conversion rate range of 0~0.1, 0.1~0.5, 0.5~0.75, and 0.75~1, which may be mainly resulted by the reaction of the extractives, hemicellulose, cellulose, and lignin, respectively. The reaction mechanisms of stages I, II, and III may be regarded as random nucleation and nuclei growth, but the reaction mechanism of stage IV may be chemical reaction. The average value of activation energy and logarithm of the pre-exponential factor for the whole pyrolysis process is 215.99 kJ mol-1 and 38.75 min-1, respectively.

Complete Genome Sequence of Clostridium kluyveri JZZ Applied in Chinese Strong-Flavor Liquor Production.

Chinese strong-flavor liquor (CSFL), accounting for more than 70% of both Chinese liquor production and sales, was produced by complex fermentation with pit mud. Clostridium kluyveri, an important species coexisted with other microorganisms in fermentation pit mud (FPM), could produce caproic acid, which was subsequently converted to the key CSFL flavor substance ethyl caproate. In this study, we present the first complete genome sequence of C. kluyveri isolated from FPM. Clostridium kluyveri JZZ contains one circular chromosome and one circular plasmid with length of 4,454,353 and 58,581 bp, respectively. 4158 protein-coding genes were predicted and 2792 genes could be assigned with COG categories. It possesses the pathway predicted for biosynthesis of caproic acid with ethanol. Compared to other two C. kluyveri genomes, JZZ consists of longer chromosome with multiple gene rearrangements, and contains more genes involved in defense mechanisms, as well as DNA replication, recombination, and repair. Meanwhile, JZZ contains fewer genes involved in secondary metabolites biosynthesis, transport, and catabolism, including genes encoding Polyketide Synthases/Non-ribosomal Peptide Synthetases. Additionally, JZZ possesses 960 unique genes with relatively aggregating in defense mechanisms and transcription. Our study will be available for further research about C. kluyveri isolated from FPM, and will also facilitate the genetic engineering to increase biofuel production and improve fragrance flavor of CSFL.

Estimation of beech pyrolysis kinetic parameters by Shuffled Complex Evolution.

The pyrolysis kinetics of a typical biomass energy feedstock, beech, was investigated based on thermogravimetric analysis over a wide heating rate range from 5K/min to 80K/min. A three-component (corresponding to hemicellulose, cellulose and lignin) parallel decomposition reaction scheme was applied to describe the experimental data. The resulting kinetic reaction model was coupled to an evolutionary optimization algorithm (Shuffled Complex Evolution, SCE) to obtain model parameters. To the authors' knowledge, this is the first study in which SCE has been used in the context of thermogravimetry. The kinetic parameters were simultaneously optimized against data for 10, 20 and 60K/min heating rates, providing excellent fits to experimental data. Furthermore, it was shown that the optimized parameters were applicable to heating rates (5 and 80K/min) beyond those used to generate them. Finally, the predicted results based on optimized parameters were contrasted with those based on the literature.

Molecular characterization of echovirus 30-associated outbreak of aseptic meningitis in Guangdong in 2012.

BACKGROUND: Evaluation of the primary etiologic agents that cause aseptic meningitis outbreaks may provide valuable information regarding the prevention and management of aseptic meningitis. An outbreak of aseptic meningitis occurred from May to June, 2012, in Guangdong Province, China. In order to determine the etiologic agent, CSF specimens from 121 children hospitalized for aseptic meningitis at Luoding People's Hospital of Guangdong Province were tested for virus isolation and identification. RESULTS: Enterovirus RNA was positive in 62.0% of 121 CSF sspecimens by real-time polymerase chain reaction (RT-PCR). Amplification and sequencing of the VP1 region of enterovirus isolates revealed Echovirus 30 (E30) was the most common isolated serotype (80% of 40 enterovirus strains).For the molecular characterization of the E30 isolates, the VP1 gene sequence of 20 Luoding E30 isolates was compared pairwise using the MegAlign with reference strains from GenBank. The pairwise comparison of the nucleotide sequences of the VP1 genes demonstrated that the sequences of the strains differed from those of lineage groups C, D, E, F, and G. Reconstruction of the phylogenetic tree based on the VP1 nucleotide sequences resulted in a monophyletic tree, with seven clustered lineage groups. Most of the isolates were segregated from other lineage groups. Four E30 isolates causing this outbreak aggregated into the Lineage A cluster which was derived from E30 strains that circulated in other regions of China from 2003-2010. CONCLUSIONS: This study demonstrated the Luoding strains were a distinct lineage of E30, and a probable cause of this outbreak. The study also demonstrated that different E30 variants existed in the local meningitis outbreak.

Pharmacokinetics of natural borneol after oral administration in mice brain and its effect on excitation ratio.

Previous studies have indicated that borneol has double side effects on the central nervous system (CNS), but the mechanism is unknown. The aim of this study was to clarify the relationship between excitation ratio [contents of excitatory amino acids (AAs) versus that of inhibitory] and the content of natural borneol after a single oral dose. Mice were administered a 1.2 g/kg dose of natural borneol (containing 98% D: -borneol) by oral ingestion. Brain samples were collected before administration and at 0.083, 0.167, 0.25, 0.333, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4 and 5 h after administration. The brain concentration of natural borneol and contents of AA neurotransmitters in mice brain were determined by GC-MS and HPLC-FLU, respectively. After per oral application, natural borneol was absorbed rapidly into the brain and could be determined 5 min after dosing. The maximal brain concentration (86.52 µg/g) was reached after 1 h post-dosing. Natural borneol could affect the contents of AA neurotransmitters in mice brain: L: -aspartic acid increased significantly from 0.083 to 1 h after administration, L: -glutamic acid increased significantly at 0.333 h and decreased from 1.5 to 5 h, gamma-amino-N-butyric acid increased significantly from 0.167 to 5 h, whereas glycine was not affected. The excitation ratio is the contents of excitatory AAs versus that of inhibitory AAs, which reflects the excitatory or inhibitory state of the body. The excitation ratio elevated transitorily and then declined 0.5 h post-dosing; there were significant differences between 1.5-5 h post-dose compared with pre-dose. The present study indicated that natural borneol could affect the contents of AA neurotransmitters, and the change in excitatory ratio led to borneol's double side effects on the CNS.

[Accuracy of prenatal diagnosis of congenital heart defects by fetal echocardiography: a 7-year experience in a Chinese tertiary obstetric center].

OBJECTIVE: To evaluate the prenatal diagnostic accuracy of fetal echocardiography for congenital heart defects. METHODS: Fetal echocardiographic databases from 2001 to 2007 were searched for patients with a prenatal diagnosis of congenital heart defect, medical records were obtained and the prenatal echocardiographic findings were correlated with postnatal echocardiography results or autopsy findings, if the pregnancy was terminated or the fetus died in utero. RESULTS: Prenatal diagnosis of congenital heart defects was made in 113 pregnancies at a mean gestational age of 26.8 weeks. Pathology or postnatal echocardiography was available in 79 cases (70%) and the accuracy of prenatal diagnosis was 86% (68/79). Prenatal diagnosis was accurate in 24 of 31 patients (77%) with conotruncal malformations, 26 of 27 patients (96%) with septal defects, 9 of 10 patients (90%) with valve abnormalities, and 5 of 6 patients (83%) with univentricular hearts. There were 4 false-positives and the positive predictive value was 95% (75/79). CONCLUSION: Fetal echocardiography is a reliable tool for prenatal diagnosis of congenital heart defects despite limitations for correctly diagnosing some specific fetal heart defects.

[Fetal echocardiography in diagnosing congenital heart disease prenatally: a multicenter clinical study].

OBJECTIVE: To evaluate the detection and accuracy of fetal echocardiography for congenital heart defects among high-risk populations. METHODS: A prospective observational study of prenatal diagnosis of congenital heart disease was conducted in two tertiary obstetrics and gynecology hospitals between January 2003 and December 2004. Consecutive fetuses at risk of congenital heart disease underwent detailed fetal echocardiography during the study period. B-mode and colour/pulsed Doppler flow imaging were used in all cases. Follow-up was sought for all pregnancies. Indications for referral, maternal and gestational age at diagnosis, as well as prenatal and postnatal diagnosis were recorded prospectively. By comparing prenatal and postnatal diagnoses, sensitivity, specificity, and predictive values were estimated. RESULTS: A series of 2063 high-risk fetuses underwent detailed fetal echocardiography during the study period. The mean gestational age at examination was 26.5 weeks, ranging from 16 to 42 weeks. The most common indications for fetal echocardiography were advanced maternal age (31.7%), fetal arrhythmias (13.5%) and maternal infections (10.4%). Forty-three cases of fetal congenital heart disease were detected. The mean gestational age at prenatal diagnosis was 27.3 weeks ranging from 16 to 40 weeks. There were 3 false-negatives and 1 false-positive. The sensitivity, specificity, positive and negative predictive values were 92.1%, 99.9%, 97.2%, and 99.8%, respectively. Diagnostic accuracy was 86.1%. A cardiac defect suspected on routine prenatal sonography accounted for the highest proportion of abnormal cases (67.4%). As for pregnancy outcome, there were 24 (52.1%) terminations; 2.2% died in utero, 13% postnatally, and 28.3% survived. CONCLUSIONS: (1) Fetal congenital heart disease can be identified reliably by prenatal echocardiography. (2) Possible congenital heart disease or suspected heart defect noted on a screening obstetric sonogram is an important indication for fetal echocardiography. (3) A sequential segmental approach is critical for correct evaluation of the cardiac malformation. (4) The outcome of the patients with congenital heart disease is poor and a multidisciplinary approach is needed to the parental counseling and perinatal management planning.