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Besides apoptosis, necrosis can also occur in a highly regulated and genetically controlled manner, defined as regulated necrosis, which is characterized by a loss of cell membrane integrity and release of cytoplasmic content. Depending on the involvement of its signal pathway, regulated necrosis can be further classified as necroptosis, ferroptosis, pyroptosis and parthanatos. Numerous studies have demonstrated that regulated necrosis is involved in the pathogenesis of many diseases covering almost all organs including the brain, heart, liver, kidney, intestine, blood vessel, eye and skin, particularly myocardial infarction and stroke. Most recently, growing evidence suggests that multiple types of regulated necrosis contribute to the degeneration of retinal ganglion cells, retinal pigment epithelial cells or photoreceptor cells, which are the main pathologic features for glaucoma, age-related macular degeneration or retinitis pigmentosa, respectively. This review focuses on the involvement of necroptosis and ferroptosis in these blinding diseases.

Micro-impurity pollution is always one of the key factors affecting the quality and service life of precision devices. Micro-nano impurity particles are difficult to remove by traditional cleaning methods (ultrasonic cleaning, etc.) and low removal efficiency by laser cleaning methods (dry laser cleaning, etc.). The laser plasma shock wave has high pressure and high temperature characteristics, which can remove nano-scaled impurity particles, and has great potential applications. In this work, we mainly study the thermodynamic effect of the laser plasma in the process of removing micro- and nano-particles. In this work, the Al particles on the Si substrate are removed by laser plasma shock wave, and the transformation of the particle state is discussed through the changes of the experimental sample morphology after different pulse effects. The experimental results show as follows With the increase of the pulse number, the micro- and nano-particle residues gradually decrease. At the same time, on the surface of the sample after these particles are removed, it can be found that large particles break up into small particles, and some of the particles will change into smooth spheres when their temperatures reach the melting point. These phenomena are the result of the interaction of the thermodynamic effect of the plasma. In order to study the transformation process of particle state, based on the plasma shock wave propagation theory, the evolution law of pressure characteristic and temperature characteristic of shock wave are obtained. From the evolution law, it can be seen that with the increase of shock wave radius, the pressure and temperature gradually decrease. When the shock wave propagates to the surface of a sample, it can reach the compression threshold and correspondingly the surface temperature arrives at melting temperature of particles, which are consistent with the experimental results. By using the finite element simulation method, the pressure and temperature of laser plasma shock wave acting on particles are studied. The stress distribution and temperature distribution in particles varying with time are obtained. The analysis results are consistent with the experimental results, and therefore the thermodynamic mechanism of plasma on particles is obtained.

We examined the effects of binary mixture of two different pharmaceutical and personal care products (PPCPs) on aquatic organisms. The topmouth gudgeon Pseudorasbora parva, native to northeast China, was used to study the combined effects of fluoxetine (FLX) and triclosan (TCS) on its different organs. After acute (4 h) and chronic (42 d) treatments, the combined effects of FLX/TCS on phase I and phase II detoxification enzymes, nervous system, digestive system and antioxidant system were evaluated. The results showed that the AChE activity in the brain of P. parva was transiently inhibited, whereas the activity of EROD in the liver was continuously inhi-bited. The activity of α-Glu in the intestine was induced after acute exposure but was inhibited after chronic exposure. Meanwhile, the level of lipid peroxidation in the liver was elevated after chronic exposure. In conclusion, the mixture of fluoxetine and triclosan produced toxic effects on multiple organs of P. parva, which could be alleviated after prolonged exposure, indicating an acclimation. However, the mechanisms of this acclimation needed further study.为探讨药品和个人护理产品(PPCPs)复合污染对水生生态系统的影响,本试验以东北地区土著鱼类麦穗鱼为试验材料,研究了氟西汀(FLX)与三氯生(TCS)复合暴露对其不同器官的毒性效应.经急性(4 h)与慢性(42 d)复合暴露试验后分别检测麦穗鱼Ⅰ相和Ⅱ相解毒酶、神经系统、消化系统及抗氧化系统等受到的影响.结果表明: 在FLX/TCS复合暴露条件下,麦穗鱼脑部乙酰胆碱酯酶活性受到短暂抑制,肝中细胞色素P450活性持续受到抑制,肠中α-葡萄糖苷酶活性在急性暴露后受到诱导但是长期暴露后被抑制,同时长期复合暴露导致肝中脂质过氧化水平升高.氟西汀和三氯生对麦穗鱼的复合暴露可对麦穗鱼多个器官产生急性毒性应激效应,而随着暴露时间的延长,麦穗鱼可产生一定的适应性,但这种适应作用的机制有待进一步研究.

Methyl protodioscin (MPD) is reported to relieve angina pectoris and myocardial ischemia, and mitochondrial E3 ubiquitin ligase 1 (Mul1) plays a key role in maintaining mitochondrial functions. Bioinformatic analysis shows potential interactions between MPD and Mul1. This study aims to explore whether MPD could protect rat brain against ischemia/reperfusion (I/R) injury through regulation of Mul1/ superoxide dismutase 2 (SOD2) pathway. The SD rat brains were subjected to 2 h of ischemia following by 24 h of reperfusion, which showed I/R injury (increase in neurological deficit score and infarct volume), up-regulation of Mul1 and down regulation of SOD2, these phenomena were attenuated by MPD treatment (3 or 10 mg/kg, i.g.). Consistently, in cultured HT22 cells, hypoxia-reoxygenation (H/R) treatment induced cellular injury (apoptosis and LDH release) concomitant with up-regulation of Mul1 and down regulation of SOD2, these phenomena were blocked in the presence of MPD (5 μM). Knockdown of Mul1 could also decrease SOD2 protein levels in HT22 cells accompanied by alleviation of H/R injury (reduction of apoptosis and LDH release). In agreement with the change of SOD2, reactive oxygen species generation was increased in H/R-treated HT22 cells while decreased in the presence of MPD. Based on these observations, we conclude that upregulation of Mul1 in rat brain contributes to cerebral I/R injury via suppression of SOD2 and that MPD protects rat brain from I/R injury through a mechanism involving regulation of Mul1/SOD2 pathway.

Cost-effective Bt resistance monitoring programmes exist to manage insect resistance to Bt crops. F2 screening is widely used in detecting rare resistant alleles. One way to establish numerous isofemale lines for F2 bioassays is acquiring many field-trapped copulated females. However, it is difficult to obtain sufficient Chilo suppressalis isofemale lines because females have low mating rates and fecundity. We developed a new method to establish C. suppressalis isofemale lines with field-collected egg masses. No significant difference in detection ability was observed in the F2 screen between the old and new methods. Moreover, the new method is economical, convenient and efficient.

There is accumulating evidence that decreased histone acetylation is involved in normal aging and neurodegenerative diseases. Recently, we found that ANP32A, a key component of INHAT (inhibitor of acetyltransferases) that suppresses histone acetylation, increased in aged and cognitively impaired C57 mice and expressing wild-type human full length tau (htau) transgenic mice. Downregulating ANP32A restored cognitive function and synaptic plasticity through upregulation of the expressions of synaptic-related proteins via increasing histone acetylation. However, there is no direct evidence that ANP32A can induce neurodegeneration and memory deficits. In the present study, we overexpressed ANP32A in the hippocampal CA3 region of C57 mice and found that ANP32A overexpression induced cognitive abilities and synaptic plasticity deficits, with decreased synaptic-related protein expression and histone acetylation. Combined with our recent studies, our findings reveal that upregulated ANP32A induced-suppressing histone acetylation may underlie the cognitive decline in neurodegenerative disease, and suppression of ANP32A may represent a promising therapeutic approach for neurodegenerative diseases including Alzheimer's disease.

In this paper, we mainly consider the stochastic second-order cone complementarity problem (SSOCCP). Due to the existence of stochastic variable, the SSOCCP may have no solutions. In order to deal with this problem, we first regard the merit function of the stochastic second-order cone complementarity problem as the loss function and then present a low-risk deterministic model that is a conditional value-at-risk (CVaR) model. However, there may be two difficulties for solving the CVaR model directly: One is that the objective function is a non-smoothing function. The other is that the objective function contains expectation. (In general, the value of expectation is not easy to be calculated.) In view of these two problems, we present the approximation problems of the model by using a smoothing method and a sample average approximation technique. Furthermore, we give the convergence results of global optimal solutions and the convergence results of stationary points of the approximation problems, respectively.

Purpose: Trophinin-associated protein (TROAP) is a cytoplasmic protein that plays a significant role in the processes of embryo transplantation and microtubule regulation. However, the relevant survival analysis and cancer progression analysis have not yet been reported. Methods: Eighteen matched pairs of tumor and adjacent non-tumor samples were evaluated to detect the TROAP mRNA level. Immunohistochemistry (IHC) was used to evaluate the TROAP expression in 108 hepatocellular carcinoma patients who underwent surgical resection. Meanwhile, data from the TCGA database was statistically evaluated. Results: In the present study, we detected a significant increase in the TROAP mRNA level in tumor tissues when compared with adjacent non-tumor tissues. Moreover, the upregulation of TROAP was associated with increased serum AFP and GGT; the greater the tumor number was, the larger the tumor size, differentiation grade, and cancer embolus in clinical analysis. In HCC patients, elevated TROAP expression in the primary tumor was positively related to clinical severity, such as poor overall survival and disease-free survival. In addition, both univariate and multivariate survival analysis validated that TROAP expression was a promising independent risk factor for overall survival and disease-free survival in HCC patients. Furthermore, the results derived from the analysis of data from the TCGA database were consistent with previous results. Altogether, our results show that TROAP is a novel crucial regulator of HCC progression and is a potential therapeutic biomarker for HCC patients. Conclusions: Elevated TROAP expression predicted a poor prognosis, and TROAP may serve as a potential biomarker for application in oncotherapy.

In the quasi-gregarious parasitoid wasp Anastatus disparis, a mother may lay more than one egg in a host during a single host encounter. This is conventionally known as self-superparasitism and, since only one adult offspring can complete development on the host, it may represent a waste of eggs and time. However, this behavior may be better described as “multiple-egg clutches,” which differs fundamentally from self-superparasitism and has seldom been addressed. The potential benefits of laying multiple-egg clutches are currently unclear, and we therefore aimed to investigate them in A. disparis. First, our results showed that production of multiple-egg clutches by A. disparis is not due to a lack of discrimination between unparasitized and parasitized hosts, as females preferred to lay eggs in unparasitized hosts. It was also unrelated to the age of the female or her mating status, or to the presence of conspecific females. However, compared to the temperatures of 26 and 32 °C, we observed that the frequency of multiple-egg clutches increased at the temperature of 20 °C. In addition, low developmental temperatures significantly decreased the rate of successful wasp eclosion from hosts in which a single egg was deposited, and this rate was increased by laying multiple-egg clutches. These results suggest that female A. disparis adults produce multiple-egg clutches to increase the probability of obtaining offspring from the host, and may have the ability to regulate oviposition and reproduction strategy based on environmental temperature. Anastatus disparis exhibited an oviposition behavior of facultative production of multiple-egg clutches, which is not due to a lack of host discrimination, or due to the age of the female or her mating status nor the presence of conspecific females. However, our results suggest that A. disparis adults produce multiple-egg clutches when it increased the probability of obtaining offspring from the host, and may have the ability to regulate their oviposition strategy based on environmental temperature.

Myeloperoxidase (MPO)-derived product hypochlorous acid (HOCl) is able to induce cellular senescence and MPO is also expressed in endothelial cells besides the well-recognized immune cells. This study aims to clarify the association of endothelium-derived MPO with endothelial senescence in hyperlipidemia. The rats were fed with high-fat diet for 8 weeks to establish a hyperlipidemic model, which showed an increase in plasma lipids, endothelium-derived MPO expression, endothelial senescence and endothelial dysfunction concomitant with a reduction in glycogen synthase kinase 3 beta (GSK-3β) activity and phosphorylated β-catenin (p-β-catenin) level as well as an increase in β-catenin and p53 levels within the endothelium. Next, human umbilical vein endothelial cells (HUVECs) were incubated with oxidized low density lipoprotein (ox-LDL, 100 μg/ml) for 24 h to establish a senescent cell model in vitro. Consistent with the finding in vivo, ox-LDL-induced MPO expression and HUVECs senescence, accompanied by a decrease in GSK-3β activity and p-β-catenin level as well as an increase in HOCl content, β-catenin and p53 levels; these phenomena were attenuated by MPO inhibitor. Replacement of ox-LDL with HOCl could also induce HUVECs senescence and activate the β-catenin/p53 pathway. Based on these observations, we conclude that endothelium-derived MPO is upregulated in hyperlipidemic rats, which may contribute to the accelerated vascular endothelial senescence through a mechanism involving the β-catenin/p53 pathway.

This study compared the calibration models generated by combinations of different mathematical and preprocessing treatments as well as regression algorithms to optimize the analysis of gelatinization properties of rice flour by using near-infrared spectroscopy, in comparison with conventional techniques of differential scanning calorimetry (DSC) and rapid viscosity analysis (RVA). A total of 220 milled rice flours were used for model construction. A model generated by the modified partial least squares regression (MPLS) with mathematical treatment “2, 8, 8, 2” (second-order derivative computed based on eight data points, and eight and two data points in the second smoothing, respectively) and detrend preprocessing was identified as the best for simultaneously measuring onset temperature (To), peak temperature (Tp), and conclusion temperature (Tc) of DSC. MPLS/“2, 8, 8, 2”/weighted multiplicative scattering correction preprocessing was identified as the best for RVA properties. The results indicated that n...

Nuclear myosin regulates gene transcription and this novel function might be modulated through phosphorylation of the myosin regulatory light chain (p-MLC20). Nonmuscle MLC20 (nmMLC20) is also present in the nuclei of cardiomyocytes and a potential nmMLC20 binding sequence has been identified in the promoter of the xanthine oxidase (XO) gene. Thus, we investigated its function in the regulation of XO transcription after myocardial ischemia/reperfusion (IR). In a rat model of myocardial IR and a cardiomyocyte model of hypoxia/reoxygenation (HR) injury, the cardiac or cell injury, myosin light chain kinase (MLCK) content, XO expression and activity, XO-derived products, and level of nuclear p-nmMLC20 were detected. Coimmunoprecipitation (co-IP), chromatin immunoprecipitation, DNA pull-down, and luciferase reporter gene assays were used to decipher the molecular mechanisms through which nmMLC20 promotes XO expression. IR or HR treatment dramatically elevated nuclear p-nmMLC20 level, accompanied by increased XO expression, activity, and products (H2O2 and uric acid), as well as the IR or HR injury; these effects were ameliorated by inhibition of MLCK or knockdown of nmMLC20. Our findings from these experiments demonstrated that nuclear p-nmMLC20 binds to the consensus sequence GTCGCC in the XO gene promoter, interacts with RNA polymerase II and transcription factor IIB to form a transcription preinitiation complex, and hence activates XO gene transcription. These results suggest that nuclear p-nmMLC20 plays an important role in IR/HR injury by transcriptionally upregulating XO gene expression to increase oxidative stress in myocardium. Our findings demonstrate nuclear nmMLC20 as a potential new therapeutic target to combat cardiac IR injury.

Previous studies have demonstrated that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-mediated oxidative stress plays a key role in brain injury following cerebral ischemia/reperfusion (I/R) and myosin regulatory light chain kinase (MLCK) has been reported to be involved in NOX activation in lung endothelium. This study was performed to explore the correlation between MLCK and NOX following cerebral I/R and the underlying mechanisms. Sprague-Dawley (SD) rats were subjected to 2 h middle cerebral artery occlusion and 24 h reperfusion to establish a model of focal cerebral I/R injury. At the end of experiments, neurological function, infarct volume, cellular apoptosis, activities of MLCK and NOX, messenger RNA (mRNA) and protein expression of NOX (NOX1-NOX4), phosphorylation level of myosin regulatory light chain (MLC20) and hydrogen peroxide (H2O2) level were determined. The results showed that I/R treatment led to increase in neurological deficit score, infarct volume and cellular apoptosis, accompanied by the elevated activities of MLCK and NOX, expressions of NOX2 and NOX4, levels of phosphorylation MLC20 and H2O2, these effects were attenuated by MLCK specific inhibitor (ML-7). NOX inhibitors (diphenylene iodonium (DPI) or apocynin) were able to achieve similar results to that of ML-7 except no effect on MLCK activity and MLC20 phosphorylation. These results suggest that activation of MLCK contributes to cerebral I/R oxidative injury through upregulation of NOX2 and NOX4 expression, which is involved in phosphorylation of MLC20.

Zinc induces protein phosphatase 2A (PP2A) inactivation and tau hyperphosphorylation through PP2A (tyrosine 307) phosphorylation in cells and the brain, but whether Zn(2+) has a direct inhibitory effect on PP2A is not clear. Here we explored the effect of Zn(2+) on PP2A and their direct interaction in vitro. The results showed that Zn(2+) mimicked the inhibitory effect of okadaic acid on protein phosphatase and prevented tau dephosphorylation in N2a cell lysates. PP2A activity assays indicated that a low concentration (10 μmol/L) of Zn(2+) inhibited PP2A directly. Further Zn(2+)-IDA-agarose affinity binding assays showed that Zn(2+) bound to and inhibited PP2Ac(51-270) but not PP2Ac(1-50) or PP2Ac(271-309). Taken together, Zn(2+) inhibits PP2A directly through binding to PP2Ac(51-270) in vitro.

Semaphoring is a transmembrane receptor which participates in many cytokine-mediated signal pathways that are closely related to the angiogenesis, occurrence and development of carcinoma. The present study was designed to access the effect of mono-antibody (mAb) guided radioimmunotherapy (RIT) on skin carcinoma and investigate the potential mechanisms. Semaphoring mAb was acquired from mice (Balb/c), purified with rProtein A column; purity, concentration and activity were tested with SDS-PAGE and indirect ELISA; specificity and expression on the cutanuem carcinoma line and tissue were tested by Western blotting; morphology change was assessed by microscopy. MTT assay and colony inhibition tests were carried out to test the influence on the proliferation of tumor cells; Western blotting was also carried out for expression of apoptosis-associated (caspase-3, Bax, Bcl-2) and proliferation-related (PI3K, p-Akt, Akt, p-ERK1/2, ERK1/2) proteins and analyse the change in signal pathways (PI3K/Akt and MEK/ERK). The purity of purified semaphorin mAb was 96.5% and the titer is about 1×10 6 . Western blotting showed semaphoring mAb to have specifically binding stripes with semaphoring b1b2 protein, B16F10, and A431 cells at 39KDa, 100KDa and 130KDa, respectively. Positive expression was detected both in cutanuem carcinoma line and tissue and it mostly located in cell membranes. MMT assay revealed dose-relate and time-relate inhibitory effect of semaphorin mAb on A431 and B16F10. Colony inhibition tests also showed dose-relate inhibitory effects. Western blotting demonstrated the expression of apoptosis and proliferation-related protein and changes in signal pathway. In conclusion, we demonstrated that semaphorin is highly expressed on the tumor cell-surfaces and RIT with semaphorin mAb has effect in inhibiting proliferation and accelerating apoptosis of tumor cells.

Background and aims Vascular peroxidase 1 (VPO1) plays a key role in mediation of cardiovascular oxidative injury. This study aims to determine whether VPO1 can promote programmed necrosis of endothelial cells and the underlying mechanisms. Methods and results Human umbilical vein endothelial cells (HUVECs) were incubated with oxidized low-density lipoprotein (ox-LDL, 100 μg/mL) for 48 h to induce cell injury, which showed an elevation in cell necrosis (reflected by the increased propidium iodide (PI) positive-staining cells, LDH release and decreased cell viability), concomitant with an increase in programmed necrosis-relevant proteins including receptor-interacting protein kinase 1/3 (RIPK1/3), p-RIPK3 and mixed lineage kinase domain like (MLKL); these phenomena were attenuated by necrostatin-1(Nec-1) and RIPK3 siRNA. Meanwhile, VPO1 was up-regulated in ox-LDL-treated endothelial cells accompanied by a decrease in GSK-3β activity and p-β-catenin levels, and an elevation of β-catenin levels; these phenomena were reversed in the presence of VPO1 siRNA or hypochlorous acid (HOCl) inhibitor; replacement of ox-LDL with HOCl could also induce endothelial programmed necrosis and activate the β-catenin signaling; β-catenin inhibitor could also suppress ox-LDL-induced RIPK-dependent necrosis. In hyperlipidemic patients, the plasma level of VPO1 was obviously increased concomitant with an elevation in plasma levels of RIPK1, RIPK3 and MLKL, and they were positively correlated. Conclusions VPO1 plays an important role in promotion of endothelial programmed necrosis under hyperlipidemic conditions through activation of β-catenin signaling. It may serve as a novel therapeutic target for prevention of endothelial dysfunction in hyperlipidemia.

Background & Aims Early life adversity is considered a risk factor for the development of gastrointestinal diseases, including inflammatory bowel disease. We hypothesized that early life colonic inflammation causes susceptibility to aggravated overexpression of interleukin (IL)1β. Methods We developed a 2-hit rat model in which neonatal inflammation (NI) and adult inflammation (AI) were induced by trinitrobenzene sulfonic acid. Results Aggravated immune responses were observed in NI + AI rats, including a sustained up-regulation of IL1β and other cytokines. In parallel with exacerbated loss of inhibitor of kappa B alpha expression, NI + AI rats showed hyperacetylation of histone H4K12 and increased V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A binding on the IL1B promoter, accompanied by high levels of norepinephrine/epinephrine. Propranolol, a β-blocker, markedly ameliorated the inflammatory response and IL1β overexpression by mitigating against epigenetic modifications. Adrenalectomy abrogated NI-induced disease susceptibility whereas yohimbine sensitized the epithelium for exacerbated immune response. The macrophages of NI rats produced more IL1β than controls after exposure to lipopolysaccharide (LPS), suggesting hypersensitization; incubation with LPS plus Foradil (Sigma, St. Louis, MO), a β2-agonist, induced a greater IL1β expression than LPS alone. Epinephrine and Foradil also exacerbated LPS-induced IL1β activation in human THP-1–derived macrophages, by increasing acetylated H4K12, and these increases were abrogated by propranolol. Conclusions NI sensitizes the colon epithelium for exacerbated IL1β activation by increasing stress hormones that induce histone hyperacetylation, allowing greater access of nuclear factor-κB to the IL1B promoter and rendering the host susceptible to aggravated immune responses. Our findings suggest that β blockers have a therapeutic potential for inflammatory bowel disease susceptibility and establish a novel paradigm whereby NI induces epigenetic susceptibility to inflammatory bowel disease.

Rice vermicelli is a main food consumed in China and Southeast Asia. Quality of rice vermicelli varies with rice cultivars. Parameters including amylose content, amylopectin distribution, thermal and pasting characteristics, gel texture and starch granules of three rice cultivars “Zhongjiazao 17”, “Xiangzaoxian 24” and “Thai Jasmine Rice”, were studied for their impacts on vermicelli quality. Results showed significant differences for the measurements of the quality traits and indicated that a favorable quality of vermicelli was not determined by any single factor instead of a combination of multi-parameters. A vermicelli with a favorable quality could be produced from a rice variety with a high apparent amylose content (>25%), a protein content of 11%, an intermediate gelatinization temperature and gel consistency, and a gel hardness (~3 N for a Rapid Viscosity Analyzer pasting) and moderate retrogradation capacity (a setback viscosity of 30–100 RVU).

Apoptosis and receptor-interacting protein kinase 1/3(RIPK1/3)-mediated necroptosis contribute to the cerebral ischemia/reperfusion (I/R) injury. Emricasan is an inhibitor of caspases in clinical trials for liver diseases while ponatinib could be a potential inhibitor for RIPK1/3. This study aims to investigate the effect of emricasan and/or ponatinib on cerebral I/R injury and the underlying mechanisms. Firstly, we evaluated the status of apoptosis and necroposis in a rat model of cerebral I/R under different conditions, which showed noticeable apoptosis and necroptosis under condition of 2-h ischemia and 24-h reperfusion; next, the preventive or therapeutic effect of emricasan or ponatinib on cerebral I/R injury was tested. Administration of emricasan or ponatinib either before or after ischemia could decrease the neurological deficit score and infarct volume; finally, the combined therapeutic effect of emricasan with ponatinib on I/R injury was examined. Combined application of emricasan and ponatinib could further decrease the I/R injury compared to single application. Emricasan decreased the activities of capase-8/-3 in the I/R-treated brain but not the protein levels of necroptosis-relevant proteins: RIPK1, RIPK3, and mixed lineage kinase domain-like (MLKL), whereas ponatinib suppressed the expressions of these proteins but not the activities of capase-8/-3. Combination of emricasan with ponatinib could suppress both capase-8/-3 and necroptosis-relevant proteins. Based on these observations, we conclude that combination of emricasan with ponatinib could synergistically reduce I/R injury in rat brain through simultaneous prevention of apoptosis and necroptosis. Our findings might lay a basis on extension of the clinical indications for emricasan and ponatinib in treating ischemic stroke.

Aero-engine development is a highly complex system engineering, which involves multiple coupled disciplines and components. With increasing demands in terms of performance, costs and environmental friendliness, it’s necessary for the commercial aero-engine to have an integrated design system, which can take the coupling effects of different disciplines into account. This paper focus on a multi-level multidisciplinary optimization framework presented for an aero-engine which include multiple objective functions. To demonstrate the framework, we present an optimization for a turbine fan aeroengine considering three complex coupled subsystems, six coupled disciplines, fifty four design variables, and nine constraints. Within the optimization, an overall performance subsystem, a one-stage fan subsystem, and a six-stage low pressure turbine subsystem are analyzed in detail. The overall performance subsystem involves analysis of thermodynamic cycle, as well as assessment of weight, noise and oxynitride emissions. To achieve an acceptable compromise among these coupled disciplines and conflicting objectives, eight related overall performance subsystem parameters are chosen as design variables. In addition, temperature limits of materials and pressure ratio limits of engine components are considered and treated as constraints. The fan subsystem and the low pressure turbine subsystem both involve analysis of aerodynamic performance and structural mechanics. To achieve an optimal design with respect to the aerodynamic performance and structural mechanics, thirty three fan subsystem parameters and thirteen low pressure turbine subsystem parameters are selected as design variables respectively. In addition, some requirements for aerodynamics and structure strength are considered and selected as constraints. The basic principle and characteristics of the collaborative optimization (CO) strategy are introduced in this paper. Besides, the CO strategy is employed to solve the large-scale optimization problem. Moreover, a newly improved collaborative optimization (ICO) strategy is also proposed in this paper. Furthermore, the performance of the CO strategy and that of the ICO strategy are compared in detail. The radial based function (RBF) surrogate models have been incorporated in the optimization process to reconcile high-fidelity CFD and FEA structural simulations of the fan subsystem, which are time-consuming. For constructing the surrogate models, a sampling technique termed orthogonal array design is employed to generate 108 sample points. The non-dominated sorting genetic algorithm (NSGA-II) is used to find the Pareto front solutions for the different objectives in the overall performance subsystem. The gradient-based sequential quadratic programming algorithm (NLPQL) is employed to find optimal solutions rapidly in the fan subsystem, as well as the low pressure turbine subsystem. The results show that the CO strategy and ICO strategy both produce a potential improvements for multiple objectives, when compared with the initial scheme. Additionally, when comparing the ICO strategy with CO strategy, we find that the ICO strategy has better optimization results.

Ommochrome is the major source for eye coloration of all insect species so far examined. Phenoxazinone synthetase (PHS) has always been regarded as the terminal step enzyme for ommochrome formation, which is encoded by cardinal or karmoisin genes. Our previous study indicated that the karmoisin ortholog gene (Nl-karmoisin) product in the brown planthopper (BPH) was a monocarboxylate transporter, while not a PHS. Here, based on full-length complementary DNA, the cardinal ortholog gene in BPH (Nl-cardinal) product was predicted to be a haem peroxidase rather than a PHS. We suggest for the first time that neither karmoisin nor cardinal encodes the PHS, but whether PHS participates in BPH eye pigmentation needs further research. Nymphal RNA interference (RNAi) experiments showed that knockdown Nl-cardinal transcript led the BPH ocelli and compound eye to color change from brown to red, while knockdown Nl-karmoisin only made the ocelli present the red phenotype. Notably, not only the Nl-cardinal transcript, dscd injection (Nl-cardinal targeting double-stranded DNA (dsRNA)) also significantly reduced the Nl-karmoisin transcript by 33.7%, while dska (Nl-karmoisin targeting dsRNA) injection did not significantly change the Nl-cardinal transcript. Considering the above RNAi and quantitative real-time polymerase chain reaction results, we propose that Nl-cardinal plays a more important role in ommochrome synthesis than Nl-karmoisin, and it may be an upstream gene of Nl-karmoisin. The present study suggested that both karmoisin and cardinal ortholog genes play a role in ommochrome synthesis in a hemimetabolous insect.

NADPH oxidase (NOX) is a major source of reactive oxygen species (ROS) in the body and it plays a key role in mediation of oxidative injury in the cardiovascular system. The purposes of this study are to evaluate the status of NOX in endothelial progenitor cells (EPCs) of hyperlipidemic rats and to determine whether NOX-derived ROS promotes the dysfunction of EPCs. The rats were fed on a high-fat diet for 8 weeks to establish a hyperlipidemic rat model, which showed the increased plasma lipids and the impaired functions of circulating EPCs (including the reduced abilities in migration and adhesion) accompanied by an increase in NOX activity and ROS production. Next, EPCs were isolated from normal rats and they were treated with oxidized low-density lipoprotein (ox-LDL) (100 μg/mL) for 24 h to induce a dysfunctional model in vitro. In agreement with our findings in vivo, ox-LDL treatment increased the dysfunctions of EPCs concomitant with an increase in NOX activity and ROS production; these phenomena were reversed by the NOX inhibitor. Based on these observations, we conclude that NOX-derived ROS involved in the dysfunctions of circulating EPCs in hyperlipidemic rats and inhibition of NOX might provide a novel strategy to improve EPC functions in hyperlipidemia.

Recent studies have uncovered that accumulation of glutamate after ischaemic stroke is closely associated with the down-regulation of glutamate transporter-1 (GLT-1) expression, suggesting that GLT-1 expression critically controls glutamate accumulation and the abnormal glutamate transport-elicited neuronal cell excitotoxicity in patients with ischaemic stroke. However, it remains unknown how GLT-1 expression is regulated under ischaemic stroke conditions. In the present study, we screened the expression of nine brain-specific or brain-enriched miRNAs in a focal cerebral ischaemia/reperfusion (I/R) injury rat model, which showed glutamate accumulation and down-regulated GLT-1 expression as expected, and revealed that the miR-107 level was elevated in both brain tissue and plasma in the model. Next, we examined the functional relationship of miR-107 with GLT-1 expression in a nerve cell hypoxia/reoxygenation (H/R) injury model. H/R treatment increased apoptosis of the nerve cells concomitant with glutamate accumulation, miR-107 elevation and suppressed GLT-1 expression, mimicking our in vivo findings in the cerebral I/R injury rat model in vitro. Co-treating the cells with an miR-107 inhibitor blocked all of the effects, demonstrating that miR-107 functions to inhibit GLT-1 expression and elevate glutamate accumulation. To extend these animal and cell-based studies to clinical patients, we measured the plasma levels of miR-107 and glutamate, and observed that both miR-107 and glutamate were elevated in patients with ischaemic stroke. On the basis of these observations, we conclude that elevated miR-107 expression after ischaemic stroke accounts, at least partially, for glutamate accumulation through suppression of GLT-1 expression. Our findings also highlight that the plasma level of miR-107 may serve as a novel biomarker for monitoring excitotoxicity in patients with ischaemic stroke.

Vitexin compound B-1 (VB-1) is a novel member of the vitexins family isolated from the seeds of the Chinese herb Vitex negundo. This study aims to investigate whether VB-1 is able to protect nerve cells against oxidative injury and whether the antioxidative effects of VB-1 occur through a mechanism involving the inhibition of NADPH oxidase (NOX) in a manner of hypoxia-inducible factor 1α (HIF-1α)-dependent. To establish a neuronal in vitro model of oxidative stress, the differentiated PC12 cells were subjected to 5 h of hypoxia followed by 20 h of reoxygenation (H/R). Three dosages of VB-1 (10(-8), 10(-7), and 10(-6) M) were chosen to evaluate the effect of VB-1 on H/R-induced injury and the underlying mechanisms. At the end of the experiments, culture mediums and cells were collected for analysis of cellular apoptosis, lactate dehydrogenase (LDH) and caspase 3/7-like activities, reactive oxygen species (ROS) levels, 4-hydroxynonenal (4-HNE) and malondialdehye (MDA) contents, and HIF-1α and NOX expression, respectively. Our results showed that cell injury (indicated by apoptosis ratio, caspase 3/7-like activity, and LDH release), oxidative stress (indicated by ROS production, 4-HNE, and MDA contents), NOX activity, and NOX expression (NOX2 and NOX4 isoforms) were dramatically increased in PC12 cells following H/R, which were attenuated in the presence of VB-1 at dosage of 10(-7) or 10(-6) M. There was no significant change in HIF-1α expression in all experimental groups. These results provide evidence that VB-1 is able to protect the PC12 cells against H/R-induced injury through a mechanism involving the suppression of NOX expression and subsequent reduction of ROS production. The effect of VB-1 on H/R-induced NOX expression is independent on HIF-1α inhibition.

The China Spallation Neutron Source (CSNS), intended to operate in 2018, is designed with 1.6 GeV proton energy and 25 Hz repetition rates, with an initial proton beam power of 100 kW that can be upgradable to 500 kW. Twenty neutron beam lines are provided by the CSNS target station for neutron scattering and neutron science research. The three neutron scattering instruments to be operated on day-one are the general purpose powder diffractometer, the multi-purpose reflectometer and the small angle neutron scattering instrument. These instruments present dissimilar shielding issues and their shielding calculation methods are presented in this paper. The thermal, fast and high-energy neutron source terms with angular distribution are individually calculated using target-moderator-reflector geometry and surface tally at a 1 m distance to the moderator. The thermal neutron losses in the guide system are calculated using a ray-tracing simulation. Possible worse case scenarios are also considered in the shielding analyses. Variance reduction methods, such as source biasing, are employed to speed up the convergence of calculations. As an example, multi-purpose reflectometer shielding analysis is introduced in this paper. All calculations are normalized to 500 kW proton beam power and a 2.5 µSv/h dose limitation are applied in accessible locations.

The damage problem of fused silica has always been one of the bottlenecks limiting the energy output of the high-power laser system. For optical components, the ionization breakdown by laser is the main factor causing damage, especially for laser plasma shock wave, which can cause large-scale fracture damage in fused silica. In this paper, the fused silica damage experiment was induced by nanosecond laser, and the damage morphology of fused silica in the thickness range of 0.8-5.0 mm was obtained under the action of 1-20 pulse. The damage size of fused silica decreases as the thickness of the material increases until the thickness of the material is greater than or equal to 1.4 mm. On the basis of theoretical analysis of plasma shock wave, the coupling and transmission of shock wave in fused silica were studied by finite element method, and the magnitude and direction distribution of stress were obtained. By analyzing the fracture characteristics and Raman spectra of the three damaged regions of fused silica, the structural differences of different damage regions are analyzed, and the relationship between the macroscopic damage of fused silica and the microstructure is explained. The research results can give a reference for understanding the characteristics and mechanism of damage characteristics induced by laser plasma shock wave.

Previous studies have demonstrated that NADPH oxidase (NOX)/vascular peroxidase (VPO1) pathway - mediated oxidative stress plays an important role in the pathogenesis of multiple cardiovascular diseases. This study aims to evaluate the correlation between NOX/VPO1 pathway and endothelial progenitor cells (EPCs) dysfunctions in hypoxia-induced pulmonary hypertension (PH). The rats were exposed to 10% hypoxia for 3 weeks to establish a PH model, which showed increases in right ventricle systolic pressure, right ventricular and pulmonary vascular remodeling, acceleration in apoptosis and impairment in functions of the peripheral blood derived - EPCs (the reduced abilities in adhesion, migration and tube formation), accompanied by up-regulation of NOX (NOX2 and NOX4) and VPO1. Next, normal EPCs were cultured under hypoxia to induce apoptosis in vitro. Consistent with the in vivo findings, hypoxia enhanced the apoptosis and dysfunctions of EPCs concomitant with an increase in NOX and VPO1 expression, hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) production; these phenomena were attenuated by NOX2 or NOX4 siRNA. Knockdown of VPO1 showed similar results to that of NOX siRNA except no effect on NOX expression and H2O2 production. Based on these observations, we conclude that NOX/VPO1 pathway-derived reactive oxygen species promote the oxidative injury and dysfunctions of EPCs in PH, which may contribute to endothelial dysfunctions in PH.

Using image analysis technology, the morphological measurements of paddy, brown (BR), and milled (MR) grains of 408 rice (Oryza sativa L.) lines representing a wide range of grain morphology were obtained, and the measurements' relationships with grain weight, milling quality, and chalkiness were investigated. The principal component analysis identified two morphological traits with a total variance of 95.7% in MR. Weight of MR was modeled as a function of the principal components using linear regression (R2 = 0.95). For milling quality measurements, dominance analyses indicated that single grain weight of the paddy and BR grains were two primary parameters in determination of BR and MR recovery, whereas surface area, perimeter, and diameter were primary parameters that controlled head milled rice (HR) recovery. All measured morphological properties (surface area, perimeter, diameter, length, width, length-to-width ratio, roundness, and thickness) and grain weight significantly correlated with pe...

Many studies demonstrate that accumulation of reactive aldehydes plays an important role in cellular oxidative injury and aldehyde dehydrogenase 2 (ALDH2)-mediated detoxification of reactive aldehydes is thought as an endogenous protective mechanism against cell injury. This study was performed to explore whether Alda-1, a newly identified ALDH2 activator, was able to protect brain against ischemia/reperfusion injury through clearance of reactive aldehydes. In a rat model of focal cerebral ischemia/reperfusion injury, neurological function, infarct volume, cellular apoptosis, mortality, ALDH2 activity and protein expression, contents of 4-hydroxy-2-nonenal (4-HNE), and malondialdehyde (MDA) were determined. The results showed that ischemia/reperfusion treatment led to increase in neurological deficit score, infarct volume, cellular apoptosis, and mortality accompanied by the elevated levels of reactive aldehydes (4-HNE and MDA). There was no significant change in ALDH2 activity and protein expression. Alda-1 treatment at both dosages (15 mg/kg × 2 or 50 mg/kg × 2, i.g.) was able to increase the activity of ALDH2 and decrease the accumulation of reactive aldehydes concomitantly with the improvement of brain injury (decrease in infarct volume, cellular apoptosis, and mortality) and neurological function (decrease in neurological deficit score). However, Alda-1 treatment did not affect ALDH2 protein expression. Our results suggest that the protective effect of Alda-1 on cerebral ischemia/reperfusion injury is related to ALDH2 activation and clearance of reactive aldehydes.

A new white striped leaf mutant wsl1 was discovered from Nipponbare mutated by ethyl methanesulfonate. The mutant showed white striped leaves at the seedling stage and the leaves gradually turned green after the tillering stage. The chlorophyll content of wsl1 was significantly lower than that of wild-type during the fourth leaf stage, tillering stage and booting stage. The numbers of chloroplast, grana and grana lamella were reduced and the thylakoids were degenerated in wsl1 compared with wild type. Genetic analysis showed that the wsl1 was controlled by a single recessive gene. Molecular mapping of the wsl1 was performed using an F2 population derived from wsl1/Nanjing 11. The wsl1 was finally mapped on the telomere region of chromosome 9 and positioned between simple sequence repeat markers RM23742 and RM23759 which are separated by approximately 486.5 kb. The results may facilitate map-based cloning of wsl1 and understanding of the molecular mechanism of the regulation of leaf-color by WSL1 in rice.

A recombinant inbred line (RIL) population bred from a cross between a javanica type (cv. D50) and an indica type (cv. HB277) rice was used to map seven quantitative trait loci (QTLs) for thousand grain weight (TGW). The loci were distributed on chromosomes 2, 3, 5, 6, 8 and 10. The chromosome 3 QTL qTGW3.2 was stably expressed over two years, and contributed 9-10% of the phenotypic variance. A residual heterozygous line (RHL) was selected from the RIL population and its selfed progeny was used to fine map qTGW3.2. In this "F2" population, the QTL explained about 23% of the variance, rising to nearly 33% in the subsequent "F2:3" generation. The physical location of qTGW3.2 was confined to a ~556 kb region flanked by the microsatellite loci RM16162 and RM16194. The region also contains other factors influencing certain yield-related traits, although it is also possible that qTGW3.2 affects these in a pleiotropic fashion.

MicroRNAs (miRNAs) have been shown to be closely associated with cellular apoptosis, but their involvement in response to ethanol-induced gastric mucosal epithelial cell apoptosis remains largely unknown. The purpose of this study was to investigate the expression profile of apoptosis-associated miRNAs in ethanol-induced acute gastric mucosal injury and the mechanisms underlying injury. Gastric mucosal injury was induced in rats by oral administration of ethanol, and gastric tissues were collected for analysis of gastric ulcer index, apoptosis ratio, caspase-3 activity, and miRNAs expression. Cell cultures of human gastric mucosal epithelial cells (GES-1) were incubated with ethanol to induce apoptosis. Mimics or inhibitors of miRNAs or c-Jun N-terminal kinase (JNK) inhibitor were added to the cell culture medium. GES-1 cells were collected for analysis of apoptosis ratio, caspase-3 activity, miRNAs expression, and protein phosphorylation levels of JNK, p38 mitogen-activated protein kinase (p38MAPK), or extracellular signal-regulated kinase (ERK). In the animal experiments, gastric ulcer index, cellular apoptosis, and caspase-3 activity were significantly increased, accompanied by up-regulation of miR-145 and down-regulation of the microRNAs miR-17, miR-19a, miR-21, miR-181a, and miR-200c. In the human cell culture experiments, the anti-apoptotic effects of miR-19a and miR-21 or pro-apoptotic effect of miR-145 were confirmed by their corresponding mimics or inhibitor; the ethanol-induced GES-1 apoptosis as well as the changes in miRNAs expression were significantly attenuated in the presence of JNK inhibitor. These results demonstrated that miR-145, miR-19a, and miR-21 were the apoptosis-associated miRNAs in gastric mucosal epithelial cells. The regulation of expression of these 3 miRNAs in ethanol-induced GES-1 apoptosis involved the JNK pathway.

To execute stall active control technology effectively and make clear of stall inception induced by modal disturbance, this paper carries out the correlative research on modal disturbance and rotating stall on the two-stage low-speed axial compressor. The results indicate that the stall inception of the compressor is modal style and the modal oscillation propagates at 38% rotor speed while the stall cell propagation speed is 42% rotor speed. The phase angles of modal oscillation and rotating stall along the axial direction are different, but their trajectories are both similar to the blade passage shape. The stall mechanisms of modal-type and spike-type inceptions are different. It doesnt appear that leading-edge tip clearance flow spillage blow the blade tip while the modal-type stall formation.

The two-dimensional network model proposed by Rosson and Seringhaus in 1995 was a key achievement in the study of trade fair functions. The model incorporates both exhibitor–visitor interactions and the multi-level functions of trade fairs and has attracted considerable scholarly attention. It is based on the case of Western market-oriented trade fairs in which material objects are displayed. However, the model is unable to explain certain aspects of China's travel marts, which are strongly controlled by the government and where the only exhibits are intangible services. Another of the model's shortcomings is that it is limited to two-dimensional exhibitor–visitor interactions. This study tests, complements and amends the Rosson Seringhaus network model for the special case of China. The authors investigate the differences between travel marts and traditional trade fairs, and amend several parts of the model, taking the China International Travel Mart (CITM) and China National Travel Mart (CNTM) as case studies. In light of their analysis, they propose an important amendment to the Rosson Seringhaus model, revising the relationship network, the network boundaries and the multiple participant identities. In addition, they find that the relationship network in a travel mart is much wider and more complex than that in a traditional trade fair, leading to greater complexity and diversification in the functions of a travel mart. Finally, they find that, in a three-dimensional exhibitor–visitor–organizer network, the overlap between identities and network expansion results in a highly complex interaction among stakeholders. Consequently, it is difficult for organizers and exhibitors to handle a travel mart successfully and improve the effectiveness of their trade fair participation.

Two-line hybrid rice as a novel hybrid breeding method has huge potential for yield increasing and utilization of intersubspecific heterosis, and it is of major significance for the food security of rice-consuming populations. Zhu1S is a thermosensitive genic male-sterile line of rice with low critical temperature and excellent combining ability, which has been widely exploited as a female parent in Chinese two-line hybrid rice breeding. Here, genetic mapping in F2 populations was used to show that its male sterility is inherited as a single recessive gene and that responsible gene (termed tms9) lies on the short arm of chromosome 2. A high-resolution linkage analysis which was based on the Zhu1S/R173 F2 population found that the thermosensitive genic male-sterile gene tms9 of Zhu1S was fine mapped between insertion–deletion (Indel) markers Indel 37 and Indel 57, and the genetic distance from the tms9 to the two markers was 0.12 and 0.31 cM, respectively. The physical distance between the two markers was about 107.2 kb. Sequence annotation databases showed that the two Indel markers (Indel 37 and Indel 57) were located on two BAC clones (B1307A11 and P0027A02). There are sixteen open reading frames (ORF) present in this region. The results of this study are of great significance for further cloning tms9 and molecular marker–assisted selection.

Fragrance is an important component of end-use quality in rice. A set of 516 fragrant rice accessions were genotyped and over 80% of them carried the badh2.7 allele. A subset of 144 mostly fragrant accessions, including nine of Oryza rufipogon, was then subjected to a detailed diversity and haplotype analysis. The level of linkage disequilibrium in the Badh2 region was higher among the fragrant accessions. Re-sequencing in the Badh2 region showed that badh2.7, badh2.2 and badh2.4–5 all arose in the japonica genepool, and spread later into the indica genepool as a result of deliberate crossing. However, loss-of-function alleles of Badh2 are also found in the indica genepools, and then transferred into japonica. Evidence for three new possible FNPs was obtained from the Badh2 sequence of 62 fragrant accessions. Based on these data, we have elaborated a model for the evolution of Badh2 and its participation in the rice domestication process.

In order to analyze the relation between wood surface roughness of plantation- Magnoliaceae glanca Blume and sanding parameters, an orthogonal test and a single factor test were performed. The results show that the mesh of the sandpaper has remarkable influence on wood surface roughness of plantation-Magnoliaceae glanca Blumes, but the feeding speed and sanding thickness don’t; when the mesh of the sandpaper is 150, the feeding speed is 6m/min and sanding thickness is 0.6 mm during the first sanding and the mesh of the sandpaper is 320, the feeding speed is 9m/min and sanding thickness is 0.2mm during the second sanding, the smallest roughness (Ra) was obtained as 2.45μm. In the theory optimization scheme, changing feeding speed into 9 m/min with considering production efficiency and changing the mesh of the sandpaper into 240 with reducing consumption of the sandpaper, then engineering optimization scheme was obtained, and the wood surface roughness (Ra) is 2.70μm.

Background Chronic Kidney Disease (CKD), a global public health problem, affects numerous people worldwide, and the prevalence is rising. Results from animal experiments and clinical investigations have demonstrated that drug metabolic enzymes and transporters-mediated non-renal clearance are dramatically impaired in CKD, co-respondent with alterations in the elimination of metabolized drugs. Accumulated uremic toxins may downregulate or directly inhibit the activity and/or the expression of drug metabolic enzymes and transporters, which may result in unintended alterations of drug exposure and response in cases when drugs dose are not adjusted for the renal dysfunction. Method The aim of this review is to highlight the impact of CKD on non-renal drug clearance involving metabolism enzyme system and transport pathways, and to provide insight into the impact of non-renal drug clearance on drug metabolism and distribution in CKD patients. Results Metabolic enzyme system and transport pathways are dysregulated in both rats and humans with renal failure. Conclusion The alterations of drug metabolic enzymes and transporters in the kidney, liver, and intestine play an important role in their pharmacokinetic changes, and thus, the metabolism and transportation of many medications used to treat CKD patients may be affected.

This study aims to identify both endothelia-specific/enriched and senescence-associated miRNAs as well as their functions. The rats were fed on high-fat diet to establish a hyperlipidemic model, which showed an increase in plasma lipids and acceleration in endothelial senescence and endothelial dysfunction, accompanied by alterations in 7 endothelia-specific/enriched and senescence-associated miRNAs. Among the 7 selected miRNAs, miR-21-5p and miR-203a-3p were significantly up-regulated in a human umbilical vein endothelial cells (HUVECs) senescent model induced by ox-LDL, consistent with their changes in the hyperlipidemic rats. After performing the bioinformatic analysis, dynamin-related protein 1 (Drp1) was predicted to be a potential target for both miR-21-5p and miR-203a-3p. In ox-LDL-induced senescent HUVECs, Drp1 was significantly down-regulated, concomitant with mitochondrial dysfunctions and the activation of AMPK-p53/p16 pathway, while these phenomena were attenuated by miR-21-5p or miR-203a-3p inhibitor. Luciferase reporter gene assay confirmed a direct interaction between miR-21-5p and Drp1 but not between miR-203a-3p and Drp1. Based on these observations, we conclude that miR-21-5p/203a-3p promote ox-LDL-induced endothelial senescence through down-regulation of Drp1 in a direct or indirect way. Our findings highlight the plasma levels of miR-21-5p/203a-3p may serve as novel biomarkers to evaluate the degree of endothelial senescence in hyperlipidemia.

Camptothecin (CPT) has anticancer, antiviral, and antifungal properties. However, there is a dearth of information about antibacterial activity of CPT. Therefore, in this study, we investigated the inhibitory effect of CPT on Acidovorax avenae subsp. avenae strain RS-2, the pathogen of rice bacterial brown stripe, by measuring cell growth, DNA damage, cell membrane integrity, the expression of secretion systems, and topoisomerase-related genes, as well as the secretion of effector protein Hcp. Results indicated that CPT solutions at 0.05, 0.25, and 0.50 mg/mL inhibited the growth of strain RS-2 in vitro, while the inhibitory efficiency increased with an increase in CPT concentration, pH, and incubation time. Furthermore, CPT treatment affected bacterial growth and replication by causing membrane damage, which was evidenced by transmission electron microscopic observation and live/dead cell staining. In addition, quantitative real-time PCR analysis indicated that CPT treatment caused differential expression of eight secretion system-related genes and one topoisomerase-related gene, while the up-regulated expression of hcp could be justified by the increased secretion of Hcp based on the ELISA test. Overall, this study indicated that CPT has the potential to control the bacterial brown stripe pathogen of rice.

Background/aims NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (NOX)-mediated oxidative stress plays a key role in promotion of oxidative injury in the cardiovascular system. The aim of this study is to evaluate the status of NOX in endothelial progenitor cells (EPCs) of hyperlipidemic patients and to assess the correlation between NOX activity and the functions EPCs. Methods A total of 30 hyperlipidemic patients were enrolled for this study and 30 age-matched volunteers with normal level of plasma lipids served as controls. After the circulating EPCs were isolated, the EPC functions (migration, adhesion and tube formation) were evaluated and the status of NOX (expression and activity) was examined. Results Compared to the controls, hyperlipidemic patients showed an increase in plasma lipids and a reduction in EPC functions including the attenuated abilities in adhesion, migration and tube formation, concomitant with an increase in NOX expression (NOX2 and NOX4), NOX activity, and reactive oxygen species production. The data analysis showed negative correlations between NOX activity and EPC functions. Conclusions There is a positive correlation between the NOX-mediated oxidative stress and the dysfunctions of circulating EPCs in hyperlipidemic patients, and suppression of NOX might offer a novel strategy to improve EPCs functions in hyperlipidemia.

Grain shape is an important component of end-use quality in rice. The genomic location of the grain shape QTL GS7 was narrowed to lie within a 4.8-kb segment on chromosome 7. The homologous region in cv. Nipponbare contains no annotated genes, while two open reading frames were predicted, one of which (ORF2) represented a likely candidate for GS7 gene on the basis of correlation between sequence variation and phenotype. Semi-quantitative and quantitative RT-PCR analysis of ORF2 transcription showed that the gene was active in both the leaf and panicle when the cv. D50 allele was present, but not in the presence of the cv. HB277 allele. A microsatellite-based phylogeny and a re-sequencing analysis of ORF2 among a set of 52 diverse rice accessions suggested that the cv. D50 GS7 allele may have originated from the tropical japonica genepool. The effect on grain length of the alternative alleles at GS7and GS3 showed that combination type 3/A was associated with longer grains than type 1/A. An Indel marker developed within the ORF2 sequence was informative for predicting grain length.

With 6 figures and 1 table Abstract 2-acetyl-1-pyrroline (2AP) is the principal compound responsible for grain fragrance in rice. In fragrant rice cultivars, BADH2 (betaine-aldehyde dehydrogenase 2) is inactivated. Here, we describe the effect of amiRNA (artificial microRNA) transgenesis targeted at BADH2 in rice. BADH2 (but not BADH1) expression was down-regulated in transgenic lines where the amiRNA was driven by the maize ubiquitin promoter, and in these lines, grain 2AP content was also significantly elevated; meanwhile, 2AP could not be detected in the grain of wild-type lines. The leaf proline content in the transgenics was increased through the simultaneous down-regulation of PRODH and up-regulation of P5CS. In transgenic lines where the same amiRNA was driven by the endosperm-specific promoter GluC, no effect on BADH2 expression was detectable, and the content of grain 2AP did not differ from that present in wild-type grains.

Two acidic polysaccharides (GP-B1 and GP-C1) were obtained from Gynostemma pentaphyllum. The molecular weights (Mw) of the two fractions were 79 kDa for GP-B1 and 126 kDa for GP-C1. GP-B1 was composed of Gal, Ara, Man, Rha, Xyl, Glc, GalA and GlcA in a molar ration of 3.5:3.2:0.6:0.9:0.3:0.5:0.6:0.4. GP-C1 consisted of Gal, Ara, Man, Rha, Glc, and GlcA in the proportions of 2.1:1.0:0.3:0.5:0.4:0.9. Among them, GP-B1 treatment had a significant inhibitory effect on the growth of melanoma B16 in vivo and in vitro. Meanwhile GP-B1 could increase the relative spleen weight and stimulate the splenocyte proliferation alone or combined with ConA. Moreover, GP-B1 treatment induced an evident increase in the level of serum TNF-α, IFN-γ, and IL-12 and a reduction for IL-10 production. These results indicate that the antitumor effects of GP-B1 are associated with immunostimulation.

Pesticides are widely used in agriculture, and epidemiological studies suggest that pesticide exposure is a risk factor for Alzheimer's disease (AD), but the mechanisms are elusive. Here, we studied the effects of pesticide exposure on the cognitive ability and the underlying mechanisms in rats. Deltamethrin and carbofuran were administered respectively into the rats once a day for 28 days by gavage. We found that pesticide exposure induced spatial learning and memory deficits with a simultaneous decrease of N-methyl-D-aspartate receptor 1, synaptophysin, and synapsin I, all of which are memory-related synaptic proteins. Pesticide exposure also induced tau hyperphosphorylation at multiple AD-related phosphorylation sites with activation of glycogen synthase kinase-3β and inhibition of protein phosphatase-2A. Additionally, neuron loss in the hippocampus and cortex was observed upon administration of the pesticides. These results indicate that the pesticides exposure could induce AD-like pathology and cognitive abnormality in rats.

In order to analyze the relation between wood surface roughness of plantation-Mytilaria laosensis and sanding parameters, two orthogonal experiment were performed. The results show that the mesh of the sandpaper has remarkable influence on wood surface roughness of plantation-Mytilaria laosensis,but the feeding speed and sanding thickness don’t; when the mesh of the sandpaper is 150, the feeding speed is 7 m/min and sanding thickness is 0.6 mm during the first sanding and the mesh of the sandpaper is 240, the feeding speed is 8m/min and sanding thickness is 0.15mm during the second sanding, the smallest roughness (Ra) was obtained as 2.79μm. Considering production efficiency, changing feeding speed into 9 m/min in the theory optimization scheme, engineering optimization scheme was obtained, and the wood surface roughness (Ra) is 2.80μm.

Recent studies demonstrate that alpha lipoic acid can prevent nitroglycerin tolerance by restoring aldehyde dehydrogenase 2 (ALDH2) activity and ALDH2-mediated detoxification of aldehydes is thought as an endogenous mechanism against ischemia-reperfusion injury. This study was performed to explore whether the cardioprotective effect of alpha lipoic acid was related to activation of ALDH2 and the underlying mechanisms. In a Langendorff model of ischemia-reperfusion in rats, cardiac function, activities of creatine kinase (CK) and ALDH2, contents of 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) were measured. In a cell model of hypoxia-reoxygenation, the apoptosis, ALDH activity, reactive oxygen species level, 4-HNE and MDA contents were examined. In the isolated hearts, ischemia-reperfusion treatment led to cardiac dysfunction accompanied by an increase in 4-HNE and MDA contents. Pretreatment with lipoic acid significantly up-regulated myocardial ALDH2 activity concomitantly with an improvement of cardiac dysfunction and a decrease in 4-HNE and MDA contents, these effects were blocked by the inhibitor of ALDH2. Similarly, in the cultured cardiomyocytes, hypoxia-reoxygenation treatment induced apoptosis accompanied by an increase in the production of reactive oxygen species, 4-HNE and MDA. Administration of lipoic acid significantly up-regulated cellular ALDH2 activity concomitantly with a reduction in apoptosis, production of reactive oxygen species, 4-HNE and MDA, these effects were reversed in the presence of ALDH2 or PKCε inhibitors. Our results suggest that the cardioprotective effects of lipoic acid on ischemia-reperfusion injury are through a mechanism involving ALDH2 activation. The regulatory effect of lipoic acid on ALDH2 activity is dependent on PKCε signaling pathway.