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A two-dimensional axisymmetric model, employing a dynamic mesh and user-defined functions, is used to numerically simulate the transient multiphase flow field produced by an underwater gun. Furthermore, a visualized shooting experiment platform with a high-speed camera is built to observe the evolution process of such a multiphase flow field. The simulated phase distribution diagram is agreed well with the shadow photo of the experiment, indicating that the numerical model is reasonable. Further examinations of the multiphase flow fields by using the submerged and sealed launch methods show that use of the sealed launch can significantly improve the interior ballistic performance of an underwater gun. In the cases by using these two types of underwater launch methods, the displacement of the projectile within the range of the muzzle flow field meets the exponential law over time. Moreover, a not fully developed bottle-shaped shock wave is formed when t = 0.4 ms, but this bottle-shaped shock wave expands more rapidly for the sealed launch. In addition, the amplitude of pressure oscillation for the sealed launch is larger than that of the submerged launch, but the pressure oscillation of the sealed launch lasts shorter.

Aims Functional group composition of a plant community is mainly driven by environmental factors and is one of the main determinants of grassland biodiversity and productivity. Therefore, it is important to understand the role of plant functional groups (PFGs) in mediating the impact of environmental conditions on ecosystem functions and biodiversity. Methods We measured plant biomass and species richness (SR) of grasslands in 65 sites on the Mongolian Plateau and classified 157 perennial herbaceous plants into two main PFGs (namely grasses and forbs). Using the random forest model and ordinary least squares regression, we identified that environmental factors (i.e. aridity index, soil total nitrogen [STN] and pH) were significantly related to the SR and aboveground biomass (AGB) of PFGs. We then used structural equation modeling to explore the relationship between the identified environmental factors and community SR and biomass, and the role of PFGs in driving this relationship. Important Findings We found that aridity index had unimodal relationships with both AGB and SR of the PFGs and the whole community. All SR and biomass metrics were significantly related to STN and pH. The relationship between aridity index and community biomass was mediated by an increase in the AGB of grasses. The influence of STN and pH on community SR was mainly due to their regulation in the SR of forbs. Our results indicate that community composition and the identity of the PFGs play a key role in linking environmental factors to ecosystem functioning.

Background: Ischemic stroke is a complex pathological process, involving inflammatory reaction, energy metabolism disorder, free radical injury, cell apoptosis and other aspects. Accumulating evide...

Background AOC1 is a copper-containing amine oxidase that is responsible for catalyzing the deamination of polyamines, which produces reactive oxygen species. Previous studies have demonstrated that polyamines are involved in the regulation of proliferation, migration, and apoptosis of cells. However, very little is known about the functions and regulatory mechanisms of AOC1 in tumors. Methods Based on GEPIA data, we found that AOC1 was significantly upregulated in human gastric cancer tissues. We knocked down AOC1 in human AGS and MKN45 cells using siRNA transfection, then utilized qRT-PCR assay and Western blot to verify the effectiveness of AOC1 knockdown in gastric cancer cells. Results Function analysis demonstrated that knockdown of AOC1 inhibited the proliferation, invasion, and migration of human gastric cancer cells. Flow cytometry detection suggested that AOC1 knockdown induced apoptosis in human gastric cancer cells. Mechanism investigation suggested that AOC1 knockdown increased the ratio of Bax/Bcl2 and induced activation of the caspase cascade. Furthermore, the AKT signaling pathway was inactivated when AOC1 was silenced, including downregulated phosphorylation level of AKT and expression of downstream effectors, Cyclin D1, and p70S6K. Finally, we found that knockdown of AOC1 inhibited the epithelial-mesenchymal transition (EMT) in human gastric cancer by increasing the expression of epithelial markers E-cadherin, as well as decreasing mesenchymal marker N-cadherin, SNAIL and Slug. Conclusion Our study suggests that AOC1 functions as an oncogene in human gastric cancer by activating the AKT signaling pathway and EMT process and maybe a target of 6-mercaptopurine, which provides new insight in the clinical use of AOC1 in gastric cancer therapy.

OBJECTIVE: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P

Plant functional traits reflect species ecological strategies and determine how plants respond to environmental changes, however, how dominant species in the Inner Mongolia grassland adapt to different grazing systems by changing their functional traits has not been systematically investigated. In this study, we established four 7-year grazing treatments in the Inner Mongolia grassland: cattle grazing, sheep grazing, mixed sheep and cattle grazing, and no grazing. Fourteen functional traits of three dominant species (Stipa grandis, Leymus chinensis, and Cleistogenes squarrosa) were measured under the different grazing treatments. We found convergences of plant functional traits that indicate herbivory avoidance or tolerance. Plants reduced their vegetative height (VH) and stem: leaf ratio (SLR) to avoid grazing; increased their ability to acquire resources by increasing their specific leaf area (SLA), leaf nitrogen concentration (LNC), and leaf phosphorus concentration (LPC); and reduced their leaf dry matter content (LDMC) to tolerate grazing. Moreover, plants may adapt to grazing by increasing the intraspecific variability of their functional traits. Sheep-only grazing adversely affected L. chinensis growth and survival, while cattle-only grazing hindered S. grandis growth and increased the intraspecific variability of its plant functional traits. Our study emphasizes that intraspecific variability is an important indicator of the responses of plant functional traits to grazing. Since single grazing is more detrimental to the functional traits of dominant plants, we suggest that mixed cattle and sheep grazing may be a more environmentally friendly and sustainable practice for the Inner Mongolia grassland than single grazing.

Although soil respiration (Rs), as the largest flux of CO2 from terrestrial ecosystems to the atmosphere, has been measured and simulated widely, its drivers on different temporal scales in high-altitude regions are not well known. These driving factors were analysed at a site upstream of the Heihe River Basin based on measurements carried out using a field chamber over 3 years during three stages of the 5 cm soil layer: freezing and thawing (FT), completely frozen (CF), and completely thawed (CT). The analysis covered hysteresis with reference to soil respiration, photosynthesis, diurnal changes in soil temperature during CT in the growing season, and the contribution of carbon emissions outside the growing season (winter) to the total annual Rs. Results show that 1) the drivers of Rs on the diurnal scale during FT, CF, and CT were totally different: soil temperature (T5) and moisture (W5) at 5 cm depth for FT; air temperature near soil surface (Ta) and soil water content at 20 cm depth (W20) for CF, and T5 and photosynthetically active radiation (PAR) for CT; 2) at the diurnal scale during CT, Rs took 1.48–6.16 h less to reach its peak value than what T5 did, while 0.84–2.81 h more than PAR did; 3) cumulative Rs in winter was 132.31 g cm−2, accounted for approximately 16% of the annual carbon efflux from the subalpine meadow. Results suggest that the contribution of winter to the annual total Rs was large and should be considered in assessing carbon budget in high-altitude regions.

Microfluidic chip injection photocuring is a new method for microfluidic chip fabrication. The accuracy of microfluidic chip photocuring has an important impact on the reliability of microfluidic chip. The reaction rate of photocuring system directly affects the final quality and efficiency of microfluidic chip. The rapid reaction rate of photocuring system will lead to poor feeding effect of the reaction system. The forming accuracy is affected, and the reaction rate is too slow, which will increase the forming time and affect the forming efficiency. In this paper, the conversion rate and reaction rate of different active monomers and oligomers used in the formulation system of microfluidic chips were measured on-line. The photocuring reaction kinetics of microfluidic chips was studied, and the influence of the formulation system on the photocuring reaction was explored, which laid a foundation for optimizing the formulation of microfluidic chips.

Sr(Ti1−xFex)O3−δ (STF) is an alternative to Ni-based cermet fuel electrodes for solid oxide electrochemical cells (SOCs) that can provide an improved tolerance to redox cycling, fuel impurities, and hydrocarbon fuels. Sr(Ti0.3Fe0.7)O3−δ electrodes were recently found to exhibit an excellent performance, but lower Fe contents have not been studied. In this work, the electrochemical performance of STF-based fuel electrodes with 0.4 ≤ x ≤ 0.7 are explored in both full cells and symmetric cells at different fuel conditions. The electrode performance in the fuel cell mode (3% H2O humidified hydrogen) became slightly worse as x decreased from 0.7 to 0.5; however, it was much worse at x = 0.4. In the steam electrolysis mode from 50% H2O to 50% H2, the change in the electrode performance showed a similar trend, and a more significant degradation in the performance was found at x = 0.4. The worse electrochemical performance in a high-steam-concentration atmosphere is due to the higher electrode polarization and increased ohmic resistance. These results indicate that STF electrodes with x = 0.5 have a reasonable electrochemical performance for SOC applications.

Colon adenocarcinoma (COAD) is a type of common malignant tumor originating in the digestive tract. Recently, targeted therapy has had significant effects on the treatment of COAD. However, more effective molecular targets need to be developed. SET and MYND domain-containing protein 3 (SMYD3) is a type of methyltransferase which methylates histone and non-histone proteins. The effects of SMYD3 on cancer progression and metastasis have been widely revealed. However, its possible role in COAD remains unclear. The current study demonstrated that SMYD3 expression was upregulated in human COAD tissues via analyzing the The Cancer Genome Atlas (TCGA) database and the immunohistochemical assays. Furthermore, the expression of SMYD3 was correlated with prognosis and tumor stage (P=0.038) in patients with COAD. Colony formation, MTT, FCM assays and animal assays indicated SMYD3 affected the proliferation, apoptosis and the cell cycle of COAD cells in vitro and promoted tumor growth in mice in vivo. In summary, the results demonstrated the effects of SMYD3 on COAD progression and we hypothesized that SMYD3 is a novel molecular target for COAD treatment.

The influences of polymer chain mobility (flexibility) and film softness on protein adsorption at the solid/liquid interface were studied with a series of polymethacrylate (PMA) polymers (PMMA, PEMA, PPMA, PnBMA) which have similar chemical structures but different glass transition temperatures (Tgs). It is found that these PMA films all adsorb protein molecules when the adsorption temperature is lower than their Tgs, and the adsorption amount varies in response to different mechanical properties of PMAs, i.e. stiffness, modulus, deformation and adhesion as measured by scanning probe microscopy. PnBMA, which has the longest side chain and lowest stiffness, adsorbed the lowest amount of protein molecules, although it is the most hydrophobic polymer among these four PMAs. There is a significant reduction of protein adsorption on a polymer film in the rubbery state, even when the adsorption temperature is only 1.5 °C higher than the Tg. Our experiments suggest that the chain mobility and film softness of polymers can influence protein adsorption at the solid–liquid interface, and even overwhelm the hydrophilic effect under certain conditions. Polymers with high chain mobility and softness provide superior protein antifouling properties as a result of the high entropy barrier from film surfaces.

The relationships between community-weighted mean (CWM) functional traits and ecosystem functions have been extensively studied. However, how CWM traits and ecosystem functions respond to grazing types and whether the relationships between CWM traits and ecosystem functions mediate the response of ecosystem functions to grazing types remains controversial. In the present study, we set up a seven-year grazing experiment with four grazing types: no grazing (NG), cattle grazing (CG), sheep grazing (SG), and mixed grazing by sheep and cattle (MG) on Inner Mongolia grassland. Nine functional traits of dominant species and five ecosystem functions under different grazing types were determined, and the relationships between CWM traits and ecosystem functions were analyzed. The results showed that the CWM height decreased after grazing, while the CWM nitrogen and phosphorus contents increased after CG. SG caused a greater decrease in aboveground biomass (AGB) and a greater increase in the net ecosystem CO2 exchange (NEE) of grassland ecosystems than did CG. This result may be partially because the CWM nutrient content and NEE were more negatively related after CG, and the increase in the CWM nitrogen and phosphorus contents suppressed NEE after CG. Therefore, to protect the sustainability of grassland ecosystem functions, SG should be reduced. Additionally, our work emphasizes that the relationships between plant functional traits and ecosystem functions may mediate the response of ecosystem functions to grazing types.

Electronic supplementary material is available online at https://doi.org/10.6084/m9.figshare.c.4969886. Biotic mechanisms associated with species diversity are expected to stabilize communities in theoretical and experimental studies but may be difficult to detect in natural communities exposed to large environmental variation. We investigated biotic stability mechanisms in a multi-site study across Inner Mongolian grassland characterized by large spatial variations in species richness and composition and temporal fluctuations in precipitation. We used a new additive-partitioning method to separate species synchrony and population dynamics within communities into different species-abundance groups. Community stability was independent of species richness but was regulated by species synchrony and population dynamics, especially of abundant species. Precipitation fluctuations synchronized population dynamics within communities, reducing their stability. Our results indicate generality of biotic stability mechanisms in natural ecosystems and suggest that for accurate predictions of community stability in changing environments uneven species composition should be considered by partitioning stabilizing mechanisms into different species-abundance groups.

The entangled orbital angular momentum (OAM) photons propagating across a weakly turbulent atmosphere are investigated. Here, the paper uses the single-phase screen model based on the Kolmogorov theory of turbulence, and focuses on the influence of the backward scattering on OAM evolution. The results indicate that backward scattering plays an important role in the analysis of OAM entanglement evolution in the turbulent atmosphere. It cannot be negligible especially for higher-order OAM mode. Moreover, when OAM mode is greater than 4, entangled photon pairs composed of higher OAM modes are not more robust in turbulence within the weak scintillation regime. These results will be useful in future investigations of OAM-based optical wave propagation through turbulent atmosphere.

Graphene quantum dots (GQDs) are widely used for biomedical applications. Previously, the low-level toxicity of GQDs in vivo and in vitro has been elucidated, but the underlying molecular mechanisms remained largely unknown. Here, we employed the Illumina high-throughput RNA-sequencing to explore the whole-transcriptome profiling of zebrafish larvae after exposure to GQDs. Comparative transcriptome analysis identified 2116 differentially expressed genes between GQDs exposed groups and control. Functional classification demonstrated that a large proportion of genes involved in acute inflammatory responses and detoxifying process were significantly up-regulated by GQDs. The inferred gene regulatory network suggested that activator protein 1 (AP-1) was the early-response transcription factor in the linkage of a cascade of downstream (pro-) inflammatory signals with the apoptosis signals. Moreover, hierarchical signaling threshold determined the high sensitivity of complement system in zebrafish when exposed to the sublethal dose of GQDs. Further, 35 candidate genes from various signaling pathways were further validated by qPCR after exposure to 25, 50, and 100 μg/mL of GQDs. Taken together, our study provided a valuable insight into the molecular mechanisms of potential bleeding risks and detoxifying processes in response to GQDs exposure, thereby establishing a mechanistic basis for the biosafety evaluation of GQDs.

The important role of biological soil crusts (biocrusts) in determining the soil carbon balance in dryland ecosystems under future climate change has been widely explored. However, when assessing the effects of biocrusts on soil respiration, few studies have considered biocrusts in bare soil patches and shrub soil patches. A field experiment was performed with five simulated rainfall addition events (0, 5, 15, 25, and 40 mm) in shrub and bare soil patches in June (early growing season, EGS), July (middle growing season, MGS) and September (late growing season, LGS) in 2016 and 2017. Our objective was to examine whether biocrusts at shrub and bare soil patches have the same effect on soil respiration under altered rainfall regimes. The results showed that the removal of biocrusts from bare patches reduced soil respiration by 15 % after rainfall amounts of 5–40 mm and increased the subsurface soil temperature and decreased the soil moisture after various rainfall treatments. However, in shrub patches, the removal of biocrusts led to a significant increase in soil respiration of 57 % and subsequent increases in subsurface soil temperature and moisutre. The discrepancy in the soil respiration response between the two types of patches might be attributable to the increase in soil infiltration after biocrust removal, with a greater stimulating increase in soil carbon emissions stimulated in the shrub patches than in the bare patches due to more the greater amounts of roots distributed under the former shrub patches. Our results indicate that the destruction of biocrusts in shrub patches may reduce the ability of biocrust ecosystems to become a net carbon sinks, with potentially negative consequences for ecosystem function and sustainability in water-limited regions.

The mechanisms of species coexistence within a community have always been the focus in ecological research. Community phylogenetic structure reflects the relationship of historical processes, regional environments, and interactions between species, and studying it is imperative to understand the formation and maintenance mechanisms of community composition and biodiversity. We studied the phylogenetic structure of the shrub communities in arid and semiarid areas of the Mongolian Plateau. First, the phylogenetic signals of four plant traits (height, canopy, leaf length, and leaf width) of shrubs and subshrubs were measured to determine the phylogenetic conservation of these traits. Then, the net relatedness index (NRI) of shrub communities was calculated to characterize their phylogenetic structure. Finally, the relationship between the NRI and current climate and paleoclimate (since the Last Glacial Maximum, LGM) factors was analyzed to understand the formation and maintenance mechanisms of these plant communities. We found that desert shrub communities showed a trend toward phylogenetic overdispersion; that is, limiting similarity was predominant in arid and semiarid areas of the Mongolian Plateau despite the phylogenetic structure and formation mechanisms differing across habitats. The typical desert and sandy shrub communities showed a significant phylogenetic overdispersion, while the steppified desert shrub communities showed a weak phylogenetic clustering. It was found that mean winter temperature (i.e., in the driest quarter) was the major factor limiting steppified desert shrub phylogeny distribution. Both cold and drought (despite having opposite consequences) differentiated the typical desert to steppified desert shrub communities. The increase in temperature since the LGM is conducive to the invasion of shrub plants into steppe grassland, and this process may be intensified by global warming., Limiting similarity rather than habitat filtering is the main mechanism of community composition in temperate arid and semiarid areas desert. Low temperature is the main factor limiting shrub phylogeny distribution.

Accurate monitoring of grassland vegetation dynamics is essential for ecosystem restoration and the implementation of integrated management policies. A lack of information on vegetation changes in the Wulagai River Basin restricts regional development. Therefore, in this study, we integrated remote sensing, meteorological, and field plant community survey data in order to characterize vegetation and ecosystem changes from 1997 to 2018. The residual trend (RESTREND) method was utilized to detect vegetation changes caused by human factors, as well as to evaluate the impact of the management of pastures. Our results reveal that the normalized difference vegetation index (NDVI) of each examined ecosystem type showed an increasing trend, in which anthropogenic impact was the primary driving force of vegetation change. Our field survey confirmed that the meadow steppe ecosystem increased in species diversity and aboveground biomass, however, the typical steppe and riparian wet meadow ecosystems experienced species diversity and biomass degradation, therefore suggesting that an increase in NDVI may not directly reflect ecosystem improvement. Selecting an optimal indicator or indicator system is necessary in order to formulate reasonable grassland management policies for increasing the sustainability of grassland ecosystems.

The myodural bridge was proposed initially in 1995. The myodural bridge is a connective tissue bridge that connects a pair of deep muscles at the suboccipital region to the dura mater. There have been numerous studies concerning the morphology and function of the myodural bridge. To determine whether a myodural bridge exists in reptiles, six Siamese crocodiles were investigated using gross anatomy dissection and P45 sheet plastination technologies. As a result, we demonstrated that the posterior occipital muscles of the Siamese crocodile are directly or indirectly connected to the proatlas, atlas, and intermembrane between them. Multiple trabeculae existing in the posterior epidural space extended from the ventral surface of the proatlas, atlas, and intermembrane between them to the dorsal surface of the spinal dura mater. This study showed that the posterior occipital muscle in the suboccipital region of the Siamese crocodile is connected to the spinal dura mater through the proatlas, atlas, and the trabeculae. In conclusion, a myodural bridge-like structure exists in reptiles. This connection may act as a pump to provide cerebrospinal fluid (CSF) circulation at the occipitocervical junction. We hypothesize that a physiologic role of the Siamese crocodile's myodural bridge may be analogous to the human myodural bridge. Anat Rec, 299:1402-1408, 2016. © 2016 Wiley Periodicals, Inc.

Landfill leachate has become an important source of environmental pollution in past decades, due to the increase of waste volume. Acute toxic and genotoxic hazards to organisms can be caused by landfill leachate. Thus, how to efficiently recover water from landfill leachate and effectively eliminate combined toxicity of landfill leachate are the most pressing issues in waste management. In this study, EDTA-Na2Zn as draw solution (DS) was used to remove the toxicity of membrane bioreactor-treated landfill leachate (MBR-treated landfill leachate) in forward osmosis (FO) process, and nanofiltration (NF) was designed for recovering the diluted DS. Zebrafish and human cells were used for toxicity assay after the novel wastewater treatment process using EDTA-Na2Zn as DS. Results showed that the water recovery rate of MBR-treated landfill leachate (M-LL) in FO membrane system could achieve 66.5% and 71.2% in the PRO and FO mode respectively, and the diluted DS could be efficiently recovered by NF. Toxicity tests performed by using zebrafish and human cells showed that M-LL treated by EDTA-Na2Zn had no toxicity effect on zebrafish larvae and human cells, but it had very slight effect on zebrafish embryos. In conclusion, all results indicated that EDTA-Na2Zn as DS can effectively eliminate toxicity of landfill leachate and this method is economical and eco-friendly for treatment of different types of landfill leachate.

Hollow poly(cyclotriphosphazene-co-phloroglucinol) (PCPP) microspheres, synthesized by a facile precipitation polymerization method and then a simple solvent-treatment procedure, were evaluated as a potential adsorbent for the removal of cationic dyes from aqueous solution. The adsorbent was characterized by SEM, TEM, FTIR, N 2 adsorption/desorption isotherms, zeta potential and particle size analysis. The adsorption process with respect to operating parameters was investigated to evaluate the adsorption characteristics of the hollow PCCP microspheres for methylene blue (MB). Systematic research including equilibrium, kinetics and thermodynamic studies were performed. The results showed the hollow PCCP microsphere was a potential adsorbent with an adsorption capacity of 50.7 mg/g at 298 K. The adsorption behavior followed the pseudo-second-order kinetic model and the adsorption equilibrium data obeyed the Langmuir isotherm well. Thermodynamic analyses confirmed that the adsorption was a physisorption process with endothermic, spontaneous and random characteristics. In addition, the possible adsorption mechanism was also proposed based on the experimental results. The study of selective adsorption further indicated the hollow PCCP microspheres could also remove other cationic dyes efficiently and be used a selective adsorbent.

Excitotoxicity and neuronal death following epilepsy involve α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). It forms a protein complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and co-internalizes upon activation of AMPA receptors after epilepsy. Disruption of the GluA2/GAPDH complex with an interfering peptide, TAT-GluA2NT1-3-2, protects cells against AMPAR-mediated excitotoxicity, which have been identified in in-vitro and in-vivo models of brain ischemia. We postulated that disruption of the GluA2/GAPDH interaction with the TAT-GluA2NT1-3-2 peptide would also protect against AMPAR-induced neuronal injury in an in-vivo model of status epilepticus (SE). In the present study, we divided pilocarpine-induced SE Wistar rats into three main groups: the TAT-GluA2NT1-3-2 peptide group, the TAT-GluA2NT-scram peptide group, and the normal saline group, and injected different doses of peptides stereotaxically into the hippocampus of SE rats to investigate whether the GluA2/GAPDH interaction could be disrupted by our TAT-GluA2NT1-3-2 peptide and determine its most appropriate dose. Then, the dose was administered stereotaxically at different time points after SE to determine the best administration time of neuronal protection. We found that the TAT-GluA2NT1-3-2 peptide can disrupt the GluA2/GAPDH interaction and protects against epilepsy-induced neuronal damage. The GluA2/GAPDH interaction may be a novel therapeutic target for epilepsy.

Recently, the augmented utilization of silver nanoparticles (AgNPs) resulted in increasingrates of its release to aquatic environment, which potentially caused adverse effects to aquatic organisms. Therefore, this study investigated - reproductive toxicity and associated potential adverse outcome pathway (AOP) in zebrafish after chronic exposure to AgNPs. To serve the purpose, three-month-old adult zebrafish were exposed to different concentrations (0, 10, 33 and 100 μg/L) of AgNPs for five weeks. Exposure to 33 and 100 μg/L of AgNPs significantly decreased the fecundity in female zebrafish, accompanied by increasing apoptotic cells in the ovarian and testicular tissue using TUNEL assay. Increasing tissue burdens of AgNPs and reactive oxygen species (ROS) production were also found in both ovary and testis after five-week exposure to AgNPs. To explore the mechanism of the apoptotic pathway, the transcription levels of various genes (bax, bcl-2, caspase-3, and caspase-9) associated with the mitochondrion-mediated apoptosis pathway were examined in zebrafish after exposure to AgNPs. The results showed that the expression patterns of all the investigated genes were altered to some extent. These findings demonstrated that AgNPs exposure caused oxidative stress, induced germ cells apoptosis via mitochondrial-dependent pathway, and ultimately impaired the reproduction in zebrafish.

Polydopamine (PDA) microspheres were synthesized by a facile oxidative polymerization method and used as a high-efficiency adsorbent for the removal of a cationic dye (methylene blue, MB) from aqueous solution. Characterizations of the as-synthesized PDA microspheres and PDA microspheres-MB (MB absorbed PDA microspheres) systems were performed using several techniques such as SEM, TEM, FTIR, N2 adsorption/desorption isotherms, particle size and zeta potential analysis. The effects of initial solution pH, temperature, initial concentration, and contact time were systematically investigated. Results showed the adsorption capacity at 25 °C could reach up to 90.7 mg/g. Besides, adsorption kinetics showed that the adsorption behavior followed the pseudo-second-order kinetic model. The equilibrium adsorption data fitted the Langmuir isotherm well. Thermodynamic analyses showed that the adsorption was endothermic and spontaneous, and it was also a physisorption process. In addition, the possible adsorption mechanism was also proposed based on the experimental results.

OBJECTIVE: To observe the effects of initial doses and treatment timing of levothyroxine (L-T4) on the clinical effcacy in children with congenital hypothyroidism (CH). METHODS: This study included 98 children who had an abnormal level of thyroid stimulating hormone (TSH) in neonatal screening in four regions of Yunnan Province and who fnally had a confrmed diagnosis of CH. They received treatment with L-T4 and were divided into standard dose group (10-15 μg/kg per day) and low dose group ( < 10 μg/kg per day) by the therapeutic dose of L-T4. Meanwhile, these patients were also classifed into two treatment groups based on the starting time of L-T4 treatment, namely under 2 months old group and more than 2 months old group. The thyroid function and physical and neural development were examined before and after treatment. RESULTS: Compared with the low dose group, the standard dose group had a signifcantly lower TSH level and a signifcantly higher free thyroxine (FT4) level at 2 weeks after treatment (P < 0.05). There were no signifcant differences in TSH and FT4 levels at other time points after treatment between the standard and low dose groups (P > 0.05). The physical and neural development were not signifcantly different between the two dose groups before and at all time points after treatment (P > 0.05). At all time points after treatment, the levels of TSH and FT4 and physical development were not signifcantly different between the different starting time groups (P > 0.05). However, the Gesell score was signifcantly higher in the under 2 months old group than in the more than 2 months old group at all time points after treatment (P < 0.05). CONCLUSIONS: The standard dose group has a better treatment outcome than the low dose group, whereas the symptoms of hyperthyroidism deserve close attention. The treatment timing is vital to the neurodevelopment of children with CH. Once diagnosed, the patients should receive treatments immediately.

Graphene quantum dots (GQDs) has been widely used in enormous fields, however, the inherent molecular mechanism of GQDs for potential risks in biological system is still elusive to date. In this study, the outstanding reduced graphene quantum dots (rGOQDs) with the QY as high as 24.62% were successfully synthesized by the improved Hummers method and DMF hydrothermal treatment approach. The rGOQDs were N-doped photoluminescent nanomaterials with functional groups on the surface. The fluorescent bio-imaging was performed by exposing zebrafish in different concentrations of the as-prepared rGOQDs, and the distribution of rGOQDs was successfully observed. Moreover, the developmental toxicity and genotoxicity were evaluated to further investigate the potential hazard of rGOQDs. The result indicated that rGOQDs were responsible for the dose-dependent abnormalities on the development of zebrafish. Since the real-time polymerase chain reaction (RT-PCR) results showed that the expression of cyp1a was the highest expression in the selected genes and significantly up-regulated 8.49 fold in zebrafish, the perturbation of rGOQDs on aryl hydrocarbon receptor (AhR) pathway was investigated by using the Tg(cyp1a:gfp) zebrafish for the first time. The results demonstrated that rGOQDs significantly increased the green fluorescent protein (GFP) expression promoted by cyp1a in a dose-dependent manner, which was also further confirmed by the western blotting. This study offered an opportunity to reveal the potential hazards of in vivo bio-probes, which provided a valuable reference for investigating the graphene-based materials on the disturbance of AhR pathway in biological organisms.

The aim of this study was to investigate the role of Th17 and T reg cells in biliary atresia (BA) and to assess the liver cytokine environment in BA patients.The percentages of Th17 and T reg cells in peripheral blood mononuclear cells (PBMCs) of BA patients and healthy controls (HC) were evaluated. The serum concentrations of IL-17a and IL-23 as well as Foxp3, IL-17a, ROR-γt, IL-6, IL-1β and TGF-β1 m-RNA and protein expressions in liver tissues and the number of Foxp3, IL-17a, ROR-γt, CD4 expressing cells which infiltrated the hepatic tissues were determined.The Th17/T reg cell ratio (P0.001) and blood concentrations of IL-17a and IL-23 (P0.05) were increased in the BA as compared to the HC group. Expressions of Foxp3, ROR-γt, IL-17a, IL-1β, IL-6 as well as TGF-β1 mRNA and proteins were significantly increased in BA as compared to HC livers (P0.01, P0.05). High levels of IL-17a/ROR-γt-positive and moderate levels of Foxp3-positive cells infiltrated damaged BA bile ducts and the ratio of FoxP3+ T to CD4+ T cells was significantly lower in BA than in HC samples (P0.01).Cytokine-induced imbalance between Th17 and T reg cells in BA livers may be involved in bile duct damage.

In order to fine working states of a continuous miner hydraulic system, diagnose quickly and effectively its faults, reduce failure rate, save maintenance time and improve the reliability and productivity of a continuous miner, the GA-PSO hybrid optimization method of fuzzy neural network is used in fault diagnosis of a continuous miner hydraulic system in the paper, a intelligent fault diagnosis expert system of a hydraulic system is designed by means of taking VC 6.0 as the programming platform, using SQL SERVER 2000 as database, embedding MATLAB7.1 in the internal. The system is simple in man-machine interface and good in man-machine conversation, capable of analyzing accurately and judging properly failures of a continuous miner hydraulic system.

Carbon quantum dots (CDs) were widely investigated because of their tunable fluorescence properties and low toxicity. However, so far there have been no reports on in vivo functional studies of hair and skin derived CDs. Here, hair derived CDs (HCDs) and skin derived CDs (SCDs) were produced by using human hair and pig skin as precursors. The quantum yields (QYs) of HCDs and SCDs were quite high, compared to citric acid derived CDs (CCDs). HCDs and SCDs possess optimal photostability, hypotoxicity and biocompatibility in zebrafish, indicating that HCDs and SCDs possess the capacity of being used as fluorescence probes for in vivo biological imaging. The long-time observation for fluorescence alternation of CDs in zebrafish and the quenching assay of CDs by ATP, NADH and Fe3+ ions demonstrated that the decaying process of CDs in vivo might be induced by the synergistic effect of the metabolism process. All results indicated that large batches and high QYs of CDs can be acquired by employing natural and nontoxic hair and skin as precursors. To our knowledge, this is the first time to report SCDs, in vivo comparative studies of HCDs, SCDs and CCDs as bioprobes, and explore their mechanism of photostability in zebrafish.

Landfill leachate (LL) is harmful to aquatic environment because it contains high concentrations of dissolved organic matter, inorganic components, heavy metals, and other xenobiotics. Thus, the remediation of LL is crucial for environmental conservation. Here, a potential application of the forward osmosis (FO) filtration process with ammonium bicarbonate (NH4HCO3) as a draw solution (DS) was investigated to remediate membrane bioreactor-treated LL (M-LL). After the leachate treatment, the toxicity and removal efficiencies of polycyclic aromatic hydrocarbons (PAHs) were evaluated using zebrafish and cultured human cells. The water recovery rate was improved using the current protocol up to 86.6% and 91.6% by both the pressure retarded osmosis (PRO) mode and the forward osmosis (FO) mode. Water flux increased with the increasing DS concentrations, but solution velocities decreased with the operation time. Toxicity tests revealed that the M-LL treated by NH4HCO3 had no toxic effect on zebrafish and human cells. Moreover, green fluorescent protein (GFP) expression in the transgenic zebrafish Tg(cyp1a:gfp) induced by PAHs was very weak compared to the effects induced by untreated M-LL. Since the diluted DS met local safety requirements of liquid fertilizer, it could be directly applied as the liquid fertilizer for fertigation. In conclusion, this novel FO system using NH4HCO3 as the DS provides a cheap and efficient protocol to effectively remove PAHs and other pollutants in LL, and the diluted DS can be directly applied to crops as a liquid fertilizer, indicating that this technique is effective and eco-friendly for the treatment of different types of LL.

Background & aims Hypoxia is a common characteristic of solid tumors. Recent studies confirmed that Toll-like receptor 4 (TLR4) plays a significant role in cancer invasion and progression. In this study, the correlation between the expression of TLR4 and the change of the protein level of Hypoxia-inducible factor-1 alpha (HIF-1α) was studied. Methods We examined 84 human pancreatic cancer tissues for expression of HIF-1α and TLR4 proteins. Panc-1 cells were exposed to normoxia (20% O 2 ) or hypoxia ( 2 ) or treated with CoCl 2 . TLR4 protein was analyzed by flow cytometry and immunostaining. Growth studies were conducted on cells with the HIF-1α inhibition isolated from stable transfected cell lines. Finally, TLR4 protein was detected by immunohistochemistry in vivo tumors. Results There was a positive correlation between TLR4 and HIF-1α protein in pancreatic cancer tissues. Hypoxic stress induced TLR4 mRNA and protein expression in Panc-1 cells. Cells transfected with HIF-1α siRNA showed attenuation of hypoxia stress-induced TLR4 expression. In vivo growth decreased in response to TLR4 and HIF-1α inhibiton. Transient HIF-1α siRNA treatment could effectively curb tumor growth in vivo . Conclusion These results suggest that TLR4 expression in pancreatic cancer cells is up-regulated via HIF-1α in response to hypoxic stress and underscore the crucial role of HIF-1α-induced TLR4 in tumor growth.

Hypoxia is a critical event in solid tumor development, invasion, and metastasis. Cellular adaptation to hypoxic microenvironment is essential for tumor progression and is largely mediated by hypoxia-inducible factor-1α (HIF-1α) through coordinated regulation of hypoxia-responsive genes. In this study, we found that membrane type-2 matrix metalloproteinase (MT2-MMP), one of the matrix metalloproteinase (MMP) family members, was a novel hypoxia-responsive gene and was upregulated by HIF-1α under hypoxia. When cancer cells were subjected to hypoxia (1% O(2) ) treatment, the mRNA and protein levels of MT2-MMP were significantly increased in a time-dependent manner in all three tested cancer cell lines including pancreatic cancer cells (PANC-1), nonsmall cell lung cancer cells (A-549), and cervix cancer cells (HeLa). Further analyses indicated that there were two hypoxia-responsive elements (HREs) in the MT2-MMP promoter, and HRE1 but not HRE2 was essential for MT2-MMP transcriptional activation under hypoxia. HIF-1α specifically and directly bound to MT2-MMP promoter was analyzed by HIF-1α binding/competition and chromatin immunoprecipitation (ChIP) assays. Furthermore, we found that upregulation of MT2-MMP under hypoxia could confer resistance to hypoxia-induced apoptosis and increase invasiveness of cancer cells. These findings provided a new insight into how cancer cells overcome hypoxic stress and trend to survive and invade, demonstrated a new regulatory mechanism of MT2-MMP expression in caner cells, and also revealed that MT2-MMP was a novel hypoxia-responsive gene and was upregulated by HIF-1α under hypoxia. © 2011 Wiley-Liss, Inc.

Acute viral myocarditis (AVMC) is characterized by virus-triggered myocardial inflammation, and Coxsackievirus B3 (CVB3) is the primary pathogen. We previously proved that Th17 cells, besides having proinflammatory effects, were involved in AVMC by enhancing humoral response. However, the relationship between Th17 cells and CVB3 replication remains unknown. In this experiment, we infected BALB/c mice with CVB3 for establishing AVMC models and then found that, with the increase of viral replication, the expressions of splenic Th17 cells, serum IL-17, and cardiac IL-17 mRNA were elevated significantly, accompanied by the progressive cardiac injuries of AVMC. Furthermore, on day 5, the peak time for viral replication, correlation was positive between cardiac IL-17 mRNA and CVB3 RNA (correlation index = 0.835; p < 0.01). Although the expressions of Th1 and CD8+ T cells, which could secrete the antiviral cytokine IFN-γ and damage the heart, were also elevated, along with Th17 cells, in AVMC, the neutralization of IL-17 further upregulated the percentages of splenic Th1 and CD8+ T cells and the levels of cardiac IFN-γ mRNA. The cardiac pathological changes were obviously improved after neutralization, with reduced viral replication followed by decreases in the cardiac inflammatory cytokines IL-17, TNF-α, and IL-1β. These data suggest that Th17 cells contribute to CVB3 replication in AVMC, and that IL-17 might be an important target for regulating the balance of antiviral immunities.

Both TLR4 and TLR2 participated in the mediation of the inflammatory injury in the process of partial cerebral ischemia/reperfusion. However, it still remains unclear whether a crosstalk exists between TLR2 and TLR4 in ischemic cerebral damage. In the present study, we investigated the effect of TLR4 signaling on TLR2 expression during mimic cerebral I/R in vitro. BV-2 cells were cultured and treated with ischemia/reperfusion, then transfected with the plasmid pEGFP-H1/TLR4-siRNA, the plasmid pEGFP-H1/control sequence-siRNA and the blank plasmid, respectively. Interestingly, the expression of TLR2 and TLR4 mRNA and protein, NF-kappaB p65 mRNA and supernatant TNF-alpha level were significantly higher in ischemia/reperfusion treated cells than those lack of ischemia/reperfusion treatment, and as compared with those in ischemia/reperfusion treated cells without transfection, no significant differences about the above mentioned gene and protein expression were found in the blank plasmid tranfected cells and the plasmid pEGFP-H1/control sequence-siRNA transfected cells respectively, while the expression levels in the plasmid pEGFP-H1/TLR4-siRNA transfected cells were significantly lower. Additionally, in order to determine the effects of pyrrolidinediethyldithiocarbamate (PDTC), an NF-kappaB inhibitor, on the TLR4-induced TLR2 expression in BV-2 cells treated with ischemia/reperfusion, it was found that TLR4 and TLR2 mRNA expressions in PDTC pretreated cells were significantly lower in comparison with normal saline pretreated cells and non-pretreated cells. The data suggested that TLR2 activation, signaled by TLR4 and regulated by NF-kappaB, might be directly involved play an important role in ischemia/reperfusion induced brain damage.

To explore the role of protein kinase A (PKA) in regulating tau phosphorylation and spatial memory, we injected forskolin, an activator of PKA, at different concentrations into the rat brains. We found that forskolin at concentrations up to 80 microM enhanced tau phosphorylation and was associated with prominent spatial memory impairment. Higher concentrations of forskolin, up to 200 microM, were associated with reduced phosphorylation levels of tau and no memory deficits. Forskolin elevated cAMP and activated PKA in a dose-dependent manner. When infused at 200 microM, forskolin also resulted in the activation and overexpression of protein phosphatase-2A (PP-2A) and attenuated the okadaic acid-induced PP-2A inhibition. These data suggest that the upregulation of PKA by forskolin to a certain level may activate PP-2A but that the latter can ameliorate the PKA-induced tau phosphorylation and memory impairment in the rats.

Objective To approach the expressions of MDR1 and BCRP in breast cancer stem cells and differentiated cells.

The cytokine repertoire of ADP/ATP carrier-specific humoral immune responses and the cytokine-dependent anti-ADP/ATP carrier antibody IgG subclasses were examined in a cohort of ADP/ATP carrier-immunized BALB/c mice treated with anti-CD4 monoclonal antibody. Eighteen male BALB/c mice (6-8 weeks old) were randomized into 3 groups: dilated cardiomyopathy (DCM) group, DCM-tolerance (Tol) group and control group. The mice in DCM group were immunized with the peptides derived from human ADP/ATP carrier protein for 6 months and mice in the control group were sham-immunized, while the mice in DCM-Tol group were immunized with ADP/ATP carrier protein and anti-CD4 McAb simultaneously. Serum autoantibody against ADP/ATP carrier and IgG subclasses were measured by ELISA, intracellular cytokines IFN-gamma and IL-4 of Th cells were monitored with flow cytometry, and splenic T cell cytokines IFN-gamma, IL-2, IL-4 and IL-6 were detected by using real-time fluorescent quantitative PCR. The results showed that the autoantibody against ADP/ATP carrier was found in all mice in DCM group, and the antibody level, serum IgG1 and IgG2a subclasses, cytokines in T cells and Th cells were all elevated in DCM group, as compared with those in control group (P0.01). On the other hand, in DCM-Tol group, the autoantibody level and contents of all the cytokines were significantly different from those in DCM group (P0.01), and were close to those in control group. And the levels of IgG1, IgG2a, IgG2b and IgG3 were influenced, to varying degrees, by anti-CD4 McAb as compared with those in DCM group. All these four types of IgG subclasses were substantially decreased in DCM-Tol group as compared with DCM group. It is concluded that the treatment with anti-CD4 McAb could prevent the activation of T cells, reverse the abnormal secretion of cytokines and the imbalance between Th1/Th2 cell subsets and abnormal production of autoantibody against ADP/ATP carrier, and eventually avoid myocardial injuries.

Objective To investigated whether erythropoietin (EPO) would promote the proliferation of human cancer cell line MCF-7, Panc-1 and HepG2 so as to determine whether EPO would result a worse prognosis to the patients with malignant diseases.

Background T cell immune abnormalities in patients with dilated cardiomyopathy (DCM) has been intensively studied over the past 10 years. Our previous study has suggested that immunization of mice with the peptides derived from human adenine nucleotide translocator (ANT) result in the production of autoantibodies against the ANT and histopathological changes similar to those in human DCM. The ANT peptides can induce autoimmune cardiomyopathy like DCM in Balb/c mice. In this study we aimed to focus on the molecular mechanism of T cells in the autoimmune cardiomyopathy mouse model by detecting the expression of the two T cell signaling molecules. Methods The ANT peptides were used to cause autoimmune cardiomyopathy in Balb/c mice. Anti-L3T4 or rat anti-mouse IgG was administered to the mice (n = 6 in each group) simultaneously immunized with ANT. ELISA analysis was used to detect autoantibodies against the ANT peptides and the percentages of interferon-gamma and interleukin-4 producing cells among splenic CD4(+) lymphocytes was determined by using flow cytometry analysis. The expression of CD45 in spleen T cells was determined by immunohistochemistry and the mRNAs of T cell signaling molecules were detected by real-time PCR. Results Treatment of ANT immunized Balb/c mice with anti-CD4 mAb caused a reduction in the gene expression of P56lck and Zap-70 and a lower level of CD45 expression by spleen T cells. Also, a reverse of the Th1/Th2 ratio that results in the reduced production of antibodies against ANT was found in the anti-CD4 monoclonal antibodies (mAb) group. Whereas irrelevant antibody (rat anti-mouse IgG) did not suppress T cell signaling molecules nor inhibit CD45 expression, and control-antibody mice did not show any significant differences compared with the DCM group. Conclusion The results show that anti-CD4 mAb is a powerful inhibitor of the early initiating events of T cell receptor (TCR) signal transduction in mouse autoimmune dilated cardiomyopathy.

The myodural bridge was proposed initially in 1995. The myodural bridge is a connective tissue bridge that connects a pair of deep muscles at the suboccipital region to the dura mater. There have been numerous studies concerning the morphology and function of the myodural bridge. To determine whether a myodural bridge exists in reptiles, six Siamese crocodiles were investigated using gross anatomy dissection and P45 sheet plastination technologies. As a result, we demonstrated that the posterior occipital muscles of the Siamese crocodile are directly or indirectly connected to the proatlas, atlas, and intermembrane between them. Multiple trabeculae existing in the posterior epidural space extended from the ventral surface of the proatlas, atlas, and intermembrane between them to the dorsal surface of the spinal dura mater. This study showed that the posterior occipital muscle in the suboccipital region of the Siamese crocodile is connected to the spinal dura mater through the proatlas, atlas, and the trabeculae. In conclusion, a myodural bridge-like structure exists in reptiles. This connection may act as a pump to provide cerebrospinal fluid (CSF) circulation at the occipitocervical junction. We hypothesize that a physiologic role of the Siamese crocodile's myodural bridge may be analogous to the human myodural bridge. Anat Rec, 299:1402-1408, 2016. © 2016 Wiley Periodicals, Inc.