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In this work, the sulfur vacancies were successfully introduced into the ZnIn2S4 (ZIS) lattice through two facile approaches, plasma etching and annealing, for enhancing the photocatalytic performance. The optimized plasma-etched ZIS exhibited an enhanced H2 generation rate of 706 μmol g−1 h−1, which was 5 and 1.2 times higher than that of pure ZIS and annealed ZIS, respectively. Theoretical calculation demonstrated that surface S vacancy could arouse the catalytic activity of the adjacent S atoms in inert (001) basal plane, serving as the active site for hydrogen evolution reaction (HER). Although annealing could produce much more S vacancies than the plasma etching, a majority of bulk S vacancies usually acted as charge recombination center to lower the photocatalytic activity. Hence, even plasma-etched ZIS presented poor light absorption capacity, plasma etching showed a better effect on the HER improvement of ZIS than annealing. This work presents a simple and promising pathway for optimization of 3D ZIS photocatalysts to improve photocatalytic hydrogen evolution.

In this study, an Si nanowire (SiNW) array was prepared on a single-crystal Si wafer by a facile Ag-assisted wet-chemical etching route, followed by deposition of ultrathin Pt nanoparticles for enhancing the photoelectrochemical (PEC) performance. It was demonstrated that the PEC performance of SiNWs was enhanced significantly after Pt modification. A higher photocurrent density of − 12 mA cm−2 was achieved in Pt/SiNWs at − 0.845V versus a reversible hydrogen electrode, which was six times greater than that of bare SiNWs. The mechanism for the enhanced PEC performance was analyzed by combining the electrochemical impedance spectra and Mott–Schottky plots. As a result, the mechanism was attributed to the improved charge transfer ability at the solid electrode/electrolyte interfaces.

Pristine and Bi-doped lanthanum titanium oxide (La2Ti2O7) nanosheets have been synthesized as photocatalysts for overall solar water splitting. The surface hole trap is a critical factor that limits the photocatalytic activity of pristine La2Ti2O7. Deposition of cobalt phosphate (Co-Pi) and platinum (Pt) nanoparticles on La2Ti2O7 cannot remove the surface traps although they are essential for enabling the oxygen and hydrogen evolution reactions. It is interesting that doping bismuth (Bi) into La2Ti2O7 nanosheets has eliminated the surface traps due to surface enrichment of Bi. The Co-Pi/Bi-La2Ti2O7/Pt nanosheets exhibit increasing photocatalytic activity toward overall water splitting with increasing the Bi-dopant level up to 5 at.%. Further increasing the Bi-dopant level leads to the formation of localized states above the valence band, leading to the lifetime reduction of photogenerated charge-carriers, and jeopardizing the photocatalytic activity. This work proposes an effective strategy to address the surface trapping and surface catalysis issues in the nanostructured metal oxide photocatalysts.

In this paper, a series of experiments were performed to study the energy output characteristics of CL-20-based aluminized explosives in an explosion vessel. The influences of different aluminum mass contents on the shock wave pressure and the explosion power were systematically investigated. The results showed that the peak overpressure and the positive impulse of the initial shock wave decreased with the aluminum content increased from 10 to 30%. On the contrary, the quasi-static pressure increased. The deformation and damage degree of sealing steel plates of the explosion vessel decreased as the aluminum content increased. The analysis indicated that the maximum residual deflection of the steel plates mainly represented the energy of the initial shock wave. The explosion power of the CL-20-based aluminized explosives decreased with the increase in aluminum content, and this trend was more remarkable at a large charge mass. The contrast test with LiF showed that the energy released from the combustion of aluminum can improve the positive impulse of the initial shock wave and play a role in the deformation of steel plates.

In this paper, a heterojunction of hierarchically one-dimensional (1D) cadmium sulfide (CdS) nanowires decorated on the two-dimensional (2D) La2Ti2O7 (LTO) has been fabricated by a simple two-step hydrothermal process. The structure, morphology and surface chemical composition of CdS/LTO were studied by a variety of characterizations, in which the X-ray photoelectron spectroscopy (XPS) results showed a strong interaction between CdS and LTO through S–O bonds. The type II band alignment of CdS/LTO for favorable electron transfer from CdS to LTO and hole transfer from LTO to CdS was clarified by ultraviolet–visible (UV–Vis) diffuse reflectance spectroscopy and Mott–Schottky (M–S) plot measurements. In the absence of any co-catalyst, H2 production from water splitting and Rhodamine B (RhB) decomposition in aqueous solution were carried out to evaluate the photocatalytic activities, showing that the photocatalytic performance of CdS/LTO was superior to that of pure LTO and CdS under visible light and simulated sunlight. The optimal CdS content in the CdS/LTO system was determined to be 7.5 wt%. The present results show an effective pathway to design a 1D/2D heterojunction photocatalyst in the face of overwhelming problems of energy crisis and environmental pollution.

Single-site cocatalysts engineered on supports offer a cost-efficient pathway to utilize precious metals, yet improving the performance further with minimal catalyst loading is still highly desirable. Here we have conducted a photochemical reaction to stabilize ultralow Pt co-catalysts (0.26 wt%) onto the basal plane of hexagonal ZnIn2S4 nanosheets (PtSS-ZIS) to form a Pt-S3 protrusion tetrahedron coordination structure. Compared with the traditional defect-trapped Pt single-site counterparts, the protruding Pt single-sites on h-ZIS photocatalyst enhance the H2 evolution yield rate by a factor of 2.2, which could reach 17.5 mmol g−1 h−1 under visible light irradiation. Importantly, through simple drop-casting, a thin PtSS-ZIS film is prepared, and large amount of observable H2 bubbles are generated, providing great potential for practical solar-light-driven H2 production. The protruding single Pt atoms in PtSS-ZIS could inhibit the recombination of electron-hole pairs and cause a tip effect to optimize the adsorption/desorption behavior of H through effective proton mass transfer, which synergistically promote reaction thermodynamics and kinetics.

Adaptation has become the major approach to reduce the adverse effects of storm surge and sea-level rise. However, maladaptation can happen when adaptation actions unintentionally increase community vulnerability. To evaluate the adequacy and efficacy of adaptation policies under uncertain sea-level rise, this study presents an agent-based model by integrating the random nature of storm surges, private adaptation decisions, and real estate market valuation. We evaluated the evolving flood damage of different adaptation strategies under two bounding cases of real estate market change. Our model results quantitatively illustrate the accelerating damages of storm surges under climate-induced sea-level rise. A reform in flood insurance to risk-based rates with a means-tested voucher program and a government-subsidized “twice and out” buyout program could both substantially improve coastal resilience. However, community adaptation with a public seawall may deliver false risk perception to high-risk property owners and result in maladaptation when sea-level rise rate is high. The modeling approach developed in this study can be used as a policy analysis tool to measure the impacts of sea-level rise and the effectiveness of adaptation strategies in coastal communities.

New and enhanced functions were potentially imparted to the plant organelles after interaction with nanoparticles. In this study, we found that ∼ 44% and ∼ 29% of the accumulated graphene in the rice leaves passively transported to the chloroplasts and thylakoid, respectively, significantly enhanced the fluorescence intensity of chloroplasts, and promoted about 2.4 times higher adenosine triphosphate production than that of controls. The enhancement of graphene on the photophosphorylation was ascribed to two reasons: One is that graphene facilitates the electron transfer process of photosystem II in thylakoid, and the other is that graphene protects the photosystem II against photo-bleaching by acting as a scavenger of reactive oxygen species. Overall, our work here confirmed that graphene translocating in the thylakoid promoted the photosynthetic activity of chloroplast in vivo and in vitro, providing new opportunities for designing biomimetic materials to enhance the solar energy conversion systems, especially for repairing or increasing the photosynthesis activity of the plants grown under stress environment.

The embedding of small peptide ligands within large inactive pre-pro-precursor proteins encoded by orphan open reading frames (ORFs) makes them difficult to identify and study. To address this problem, we generated oligonucleotide ( 1200 amino acid EGF precursor protein or the orphan ECRG4 ORF, that encodes a 148 amino acid Esophageal Cancer Related Gene 4 (ECRG4), a putative cytokine precursor protein of up to eight ligands. After phage display and 3–4 rounds of biopanning for phage internalization into prostate cancer epithelial cells, sequencing identified the 53-amino acid EGF ligand encoded by the 5′ region of the EGF ORF and three distinct domains within the primary sequence of ECRG4: its membrane targeting hydrophobic signal peptide, an unanticipated amino terminus domain at ECRG437–63 and a C-terminus ECRG4133–148 domain. Using HEK-blue cells transfected with the innate immunity receptor complex, we show that both ECRG437–63 and ECRG4133–148 enter cells by interaction with the TLR4 immune complex but neither stimulate NFkB. Taken together, the results help establish that phage display can be used to identify cryptic domains within ORFs of the human secretome and identify a novel TLR4-targeted internalization domain in the amino terminus of ECRG4 that may contribute to its effects on cell migration, immune cell activation and tumor suppression.

Esophageal cancer related gene-4 (Ecrg4) has been shown to be a tumor suppressor in many organs. Exosomes are naturally secreted nanosized particles that carry signal molecules including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) among others. Upon internalization, exosomes unload their cargos that in turn modulate the biology of the recipient cells. Mounting evidence has shown that exosomal miRNAs are functional. However, reports that exosomes carry functional mRNAs remain scarce. We found that serum exosomes contain ECRG4 open reading frame. To simulate serum exosomal ECRG4, stable cell line expressing ECRG4 was created, from which exosomes were isolated and characterized, and the internalization and the resulting biological effects of exosomal ECRG4 were evaluated. Results showed that serum exosomes contain higher levels of ECRG4 mRNA in healthy individuals than their cancer counterparts. Exosomal ECRG4 can be internalized and unload the encapsulated ECRG4 into recipient cells, which subsequently suppressed cell proliferation in vitro, and inhibited tumor growth in a xenograft mouse model. Mechanistically, ECRG4-containing exosomes, when internalized, suppressed the expression of genes commonly implicated in inflammation, cell proliferation, and angiogenesis. Given that exosome is an ideal vehicle for therapeutics delivery and that ECRG4 is a tumor suppressor gene, the exosomal ECRG4 can be exploited as a formulation for cancer gene therapy.

It is easy for teenagers to view pornographic pictures on social networks. Many researchers have studied the detection of real pornographic pictures, but there are few studies on those that are artificial. In this work, we studied how to detect artificial pornographic pictures, especially when they are on social networks. The whole detection process can be divided into two stages: feature selection and picture detection. In the feature selection stage, seven types of features that favour picture detection were selected. In the picture detection stage, three steps were included. 1) In order to alleviate the imbalance in the number of artificial pornographic pictures and normal ones, the training dataset of artificial pornographic pictures was expanded. Therefore, the features which were extracted from the training dataset can also be expanded too. 2) In order to reduce the time of feature extraction, a fast method which extracted features based on the proportionally scaled picture rather than the original one was proposed. 3) Three tree models were compared and a gradient boost decision tree (GBDT) was selected for the final picture detection. Three sets of experimental results show that the proposed method can achieve better recognition precision and drastically reduce the time cost of the method.

The immune system plays a critical role in the establishment, development, and progression of head and neck squamous cell carcinoma (HNSCC). As treatment with single-immune checkpoint agent results in a lower response rate in patients, it is important to investigate new strategies to maintain favorable anti-tumor immune response. Herein, the combination immunotherapeutic value of CTLA4 blockade and SFKs inhibition was assessed in transgenic HNSCC mouse model. Our present work showed that tumor growth was not entirely controlled when HNSCC model mice were administered anti-CTLA4 chemotherapeutic treatment. Moreover, it was observed that Src family kinases (SFKs) were hyper-activated and lack of anti-tumor immune responses following anti-CTLA4 chemotherapeutic treatment. We hypothesized that activation of SFKs is a mechanism of anti-CTLA4 immunotherapy resistance. We, therefore, carried out combined drug therapy using anti-CTLA4 mAbs and an SFKs' inhibitor, dasatinib. As expected, dasatinib and anti-CTLA4 synergistically inhibited tumor growth in Tgfbr1/Pten 2cKO mice. Furthermore, dasatinib and anti-CTLA4 combined to reduce the number of myeloid-derived suppressor cells and Tregs, increasing the CD8+ T cell-to-Tregs ratio. We also found that combining dasatinib with anti-CTLA4 therapy significantly attenuated the expression of p-STAT3Y705 and Ki67 in tumoral environment. These results suggest that combination therapy with SFKs inhibitors may be a useful therapeutic approach to increase the efficacy of anti-CTLA4 immunotherapy in HNSCC.

To explore the difference in contrast-enhanced computed tomography (CT) features of intrahepatic cholangiocarcinomas (ICCs) with different isocitrate dehydrogenase (IDH) mutation status. Clinicopathological and contrast-enhanced CT features of 78 patients with 78 ICCs were retrospectively analysed and compared based on IDH mutation status. There were 11 ICCs with IDH mutation (11/78, 14.1%) and 67 ICCs without IDH mutation (67/78, 85.9%). IDH-mutated ICCs showed intratumoral artery more often than IDH-wild ICCs (p = 0.023). Most ICCs with IDH mutation showed rim and internal enhancement (10/11, 90.9%), while ICCs without IDH mutation often appeared diffuse (26/67, 38.8%) or with no enhancement (4/67, 6.0%) in the arterial phase (p = 0.009). IDH-mutated ICCs showed significantly higher CT values, enhancement degrees and enhancement ratios in arterial and portal venous phases than IDH-wild ICCs (all p

Two players, A and B, bargain to divide a perfectly divisible pie. In a bargaining model with constant discount factors, $$\delta _A$$ and $$\delta _B$$ , we extend Rubinstein (Econometrica 50:97–110, 1982)’s alternating offers procedure to more general deterministic procedures, so that any player in any period can be the proposer. We show that each bargaining game with a deterministic procedure has a unique subgame perfect equilibrium (SPE) payoff outcome, which is efficient. Conversely, each efficient division of the pie can be supported as an SPE outcome by some procedure if $$\delta _A+\delta _B\ge 1$$ , while almost no division can ever be supported in SPE if $$\delta _A+\delta _B < 1$$ .

Microorganism or chelate-assisted phytoextraction is an effective remediation tool for heavy metal polluted soil, but investigations into its impact on soil microbial activity are rarely reported. Consequently, cadmium (Cd)- and lead (Pb)-resistant fungi and citric acid (CA) were introduced to enhance phytoextraction by Solanum nigrum L. under varied Cd and Pb pollution levels in a greenhouse pot experiment. We then determined accumulation of Cd and Pb in S. nigrum and the soil enzyme activities of dehydrogenase, phosphatase, urease, catalase, sucrase, and amylase. Detrended canonical correspondence analysis (DCCA) was applied to assess the interactions between remediation strategies and soil enzyme activities. Results indicated that the addition of fungi, CA, or their combination enhanced the root biomass of S. nigrum, especially at the high-pollution level. The combined treatment of CA and fungi enhanced accumulation of Cd about 22-47 % and of Pb about 13-105 % in S. nigrum compared with the phytoextraction alone. However, S. nigrum was not shown to be a hyperaccumulator for Pb. Most enzyme activities were enhanced after remediation. The DCCA ordination graph showed increasing enzyme activity improvement by remediation in the order of phosphatase, amylase, catalase, dehydrogenase, and urease. Responses of soil enzyme activities were similar for both the addition of fungi and that of CA. In summary, results suggest that fungi and CA-assisted phytoextraction is a promising approach to restoring heavy metal polluted soil.

Background Cancer immunotherapy offers a promising approach in cancer treatment. The adenosine A2A receptor (A2AR) could protect cancerous tissues from immune clearance via inhibiting T cells response. To date, the role of A2AR in head and neck squamous cell carcinoma (HNSCC) has not been investigated. Here, we sought to explore the expression and immunotherapeutic value of A2AR blockade in HNSCC. Methods The expression of A2AR was evaluated by immunostaining in 43 normal mucosae, 48 dysplasia and 165 primary HNSCC tissues. The immunotherapeutic value of A2AR blockade was assessed in vivo in genetically defined immunocompetent HNSCC mouse model. Results Immunostaining of HNSCC tissue samples revealed that increased expression of A2AR on tumor infiltrating immune cells correlated with advanced pathological grade, larger tumor size and positive lymph node status. Elevated A2AR expression was also detected in recurrent HNSCC and HNSCC tissues with induction chemotherapy. The expression of A2AR was found to be significantly correlated with HIF-1α, CD73, CD8 and Foxp3. Furthermore, the increased population of CD4+Foxp3+ regulatory T cells (Tregs), which partially expressed A2AR, was observed in an immunocompetent mouse model that spontaneously develops HNSCC. Pharmacological blockade of A2AR by SCH58261 delayed the tumor growth in the HNSCC mouse model. Meanwhile, A2AR blockade significantly reduced the population of CD4+ Foxp3+ Tregs and enhanced the anti-tumor response of CD8+ T cells. Conclusions These results offer a preclinical proof for the administration of A2AR inhibitor on prophylactic experimental therapy of HNSCC and suggest that A2AR blockade can be a potential novel strategy for HNSCC immunotherapy. Electronic supplementary material The online version of this article (doi:10.1186/s12943-017-0665-0) contains supplementary material, which is available to authorized users.

Concentrations of aqueous-phase nonylphenol (NP), a well-known endocrine-disrupting chemical, are shown to be reduced effectively via reaction with lignin peroxidase (LiP) or horseradish peroxidase (HRP) and hydrogen peroxide. We systematically assessed their reaction efficiencies at varying conditions, and the results have confirmed that the catalytic performance of LiP toward NP was more efficient than that of HRP under experimental conditions. Mass spectrum analysis demonstrated that polymerization through radical-radical coupling mechanism was the pathway leading to NP transformation. Our molecular modeling with the assistance of ab initio suggested the coupling of NP likely proceeded via covalent bonding between two NP radicals at their unsubstituted carbons in phenolic rings. Data from acute immobilization tests with Daphnia confirm that NP toxicity is effectively eliminated by LiP/HRP-catalyzed NP removal. The findings in this study provide useful information for understanding LiP/HRP-mediated NP reactions, and comparison of enzymatic performance can present their advantages for up-scale applications in water/wastewater treatment.

The convergence to steady state solutions of the Euler equations for weighted compact nonlinear schemes (WCNS) [Deng X. and Zhang H. (2000), J. Comput. Phys. 165, 22–44 and Zhang S., Jiang S. and Shu C.-W. (2008), J. Comput. Phys. 227, 7294–7321] is studied through numerical tests. Like most other shock capturing schemes, WCNS also suffers from the problem that the residue can not settle down to machine zero for the computation of the steady state solution which contains shock waves but hangs at the truncation error level. In this paper, the techniques studied in [Zhang S. and Shu. C.-W. (2007), J. Sci. Comput. 31, 273–305 and Zhang S., Jiang S and Shu. C.-W. (2011), J. Sci. Comput. 47, 216–238], to improve the convergence to steady state solutions for WENO schemes, are generalized to the WCNS. Detailed numerical studies in one and two dimensional cases are performed. Numerical tests demonstrate the effectiveness of these techniques when applied to WCNS. The residue of various order WCNS can settle down to machine zero for typical cases while the small post-shock oscillations can be removed.

Seasonal topographical changes in the intertidal zone are of high interest in many parts of the world. Due to existing challenges in mapping this dynamics, little is known about the seasonal pattern of tidal flats. This research aims to fill the knowledge gap by using optical images from the Chinese HJ-1 satellites constellation. A case study was conducted at the Jiangsu middle coast, a typical tidal flat region in China. Firstly, 455 optical images from the HJ-1 Satellites were collected to construct seasonal tidal flat Digital Elevation Models (DEMs). Next, synchronous Light Detection and Ranging (LiDAR) DEM and ground survey data were collected to validate the accuracy of the seasonal tidal flat DEMs. Finally, seasonal pattern of the tidal flats was demonstrated based on a time series of DEM volume comparison. The results show: (1) the HJ-1 images are qualified data source to produce satisfactory tidal flat DEMs with high spatio-temporal resolution and acceptable vertical accuracy. (2) In general, there are apparent erosion-and-deposition cycles in the Jiangsu middle coast, with deposition during the Winter and erosion during the Summer. Furthermore, the derived seasonal patterns differ notably among the five major sandbanks.

The structurally related hydroxylated polybrominated diphenyl ether (PBDE) like hydroxylated 4,4'-dibromodiphenyl ether widely occur in precipitation, surface water, and biotic media. The origins of hydroxylated PBDEs (OH-PBDEs) are of particular interest due to their greater toxic potencies than the corresponding PBDEs. We studied the transformation behavior and products of 4,4'-dibromodiphenyl ether (BDE 15) mediated by lignin peroxidase (LiP), an extracellular enzyme that is produced by certain white rot fungus and is widely present in the natural environment. We found that BDE 15 can be effectively transformed through the reaction mediated by LiP, and two different mono-OH-dibromodiphenyl ethers were identified by using gas chromatography-mass spectrometry (GC-MS) and GC-MS/MS. In particular, we compared the reaction behavior for systems variously containing natural organic matter (NOM) and/or veratryl alcohol (VA), a metabolite that certain fungus produces along with LiP in nature. It was found that the VA's enhancement effect on LiP performance was impaired by the presence of NOM. The findings in this study provide useful information for better understanding the origins of OH-PBDEs found in the environment.

It is unclear whether certain plant species and plant diversity could reduce the impacts of multiple heavy metal pollution on soil microbial structure and soil enzyme activities. Random amplified polymorphic DNA (RAPD) was used to analyze the genetic diversity and microbial similarity in planted and unplanted soil under combined cadmium (Cd) and lead (Pb) pollution. A metal hyperaccumulator, Brassica juncea, and a common plant, Festuca arundinacea Schreb, were used in this research. The results showed that microorganism quantity in planted soil significantly increased, compared with that in unplanted soil with Cd and Pb pollution. The order of microbial community sensitivity in response to Cd and Pb stress was as follows: actinomycetes>bacteria>fungi. Respiration, phosphatase, urease and dehydrogenase activity were significantly inhibited due to Cd and Pb stress. Compared with unplanted soil, planted soils have frequently been reported to have higher rates of microbial activity due to the presence of additional surfaces for microbial colonization and organic compounds released by the plant roots. Two coexisting plants could increase microbe population and the activity of phosphatases, dehydrogenases and, in particular, ureases. Soil enzyme activity was higher in B. juncea phytoremediated soil than in F. arundinacea planted soil in this study. Heavy metal pollution decreased the richness of the soil microbial community, but plant diversity increased DNA sequence diversity and maintained DNA sequence diversity at high levels. The genetic polymorphism under heavy metal stress was higher in B. juncea phytoremediated soil than in F. arundinacea planted soil.

How to integrate environmental geographic information and biodiversity data combined with management measures to effectively assess soil health is still an unresolved problem. This paper suggests an approach for systematically estimating soil quality and guiding ecological management. First, canonical correspondence analysis is used to predict the distributions of plant species or microorganism communities, principle pollutants and environmental variables from which spatial and environmental data are extracted by the geographic information system (GIS). Secondly, geostatistical methodologies are then used to estimate and quantify the spatial distribution characteristic of the species and pollutants and to create maps of spatial uncertainty and hazard assessment through ArcGis technology. Finally, redundancy analysis provides a suggestion about better management strategy and environmental factor for improving soil health and biodiversity. The combination of these methods with “3S” techniques as an assessment approach effectively meets the challenges for estimation and management in different soil environments.

Lignin peroxidases (LiPs) are a group of extracellular enzymes excreted by certain fungi, e.g., Phanerochaete chrysosporium. These fungi also produce veratryl alcohol (VA) as a secondary metabolite to regulate the performance of LiP. 17ss-Estradiol (E2) is a natural female hormone that is strongly endocrine disruptive when released to the natural environment. The widespread occurrence of E2 and related hormonal chemicals in soil and water environments has been identified, representing an emerging contamination of concern. We report in this study that E2 can be effectively transformed and removed through reactions mediated by LiP and such reactions are significantly enhanced in the presence of VA. We systematically investigated LiP activity and enzymatic reaction kinetics in systems having VA absent or present. The results suggest that VA enhanced the transformation and removal of E2 by the combination of two effects: (i) mitigating LiP inactivation and (ii) modifying the enzyme catalytic kinetics. These findings provide insights into an important pathway that may govern the environmental transformation of E2 and other emerging endocrine-disrupting contaminants of similar nature in the environment, and provide a basis for potential development and optimization of enzyme-based processes for remediation and removal of these contaminants.

The microtubule-stabilizing drug epothilone B (epoB) has shown potential value in the treatment of spinal cord injury (SCI) through diverse mechanisms. However, it remains elusive why a limited overall effect was observed. We aim to investigate the limiting factors underlying functional recovery promoted by epoB. The same SCI model treated by epoB was established as discussed previously. We used a cerebrospinal fluid (CSF) sample to assess the changes in cytokines in milieu of the SCI lesion site after epoB treatment. We then analyzed the source of cytokines, the state of microglia/macrophages/monocytes (M/Ms), and the recruitment of neutrophil in the lesion site by using the results of antibody array. Following these findings, we further evaluated the motor functional recovery caused by the reshaped microenvironment. Systemic administration of epoB significantly increased levels of several cytokines in the CSF of the rat SCI model; macrophage colony-stimulating factor (M-CSF) secreted by intact central nervous system (CNS) cells was one of the cytokines with increased levels. Along with epoB and other cytokines, M-CSF reshapes the SCI milieu by activating the microglias, killing bone marrow-derived macrophages, polarizing the M/M to M1 phenotype, and activating downstream cytokines to exacerbate the SCI injury, but it also increases the expression of neurotrophic factors. Anti-inflammatory therapy using a neutralizing antibody mix shows encouraging results. Using in vivo experiments, our findings indicate that epoB inhibits the SCI functional recovery in many ways by reshaping the milieu, which counteracts the therapeutic efficacy that led to the limited overall effectiveness.

A laboratory study was conducted to evaluate the response of soil enzyme activities (namely dehydrogenase, phosphatase and urease) to different levels of trace element pollution in soil representative area. The improved ecological dose model and random-amplified polymorphic DNA (RAPD) were used to assess soil health. The 50% ecological dose (ED50) values modified by toxicant coefficient were calculated from the best-fit model, and determination values from the regression analysis for the three enzyme activities were studied after the incubation periods. The results showed that the elevated heavy metal concentration negatively affects the total population size of bacteria and actinomycetes and enzymatic activity; dehydrogenase (ED50 = 777) was the most sensitive soil enzyme, whereas urease activity (ED50 = 2,857) showed the lowest inhibition; combined pollution or elevated toxicant level would increase disappearing RAPD bands, and the number of denoting polymorphic bands was greater in combined polluted soils. All three mathematical modified models satisfactorily described the inhibition of soil enzyme activities caused by Cd and Pb, by giving the best fit.

Adult hippocampal neurogenesis has been demonstrated in several species and is regulated by both environmental and pharmacological stimuli. Repeated exposure to stress is known to induce the reduction of neurogenesis in the dentate gyrus (DG) of hippocampus. The present study aimed at determining whether the clinically effective antidepressant clomipramine may influence hippocampal proliferation and neurogenesis in adult rats subjected to the chronic unpredictable stress (CUS) procedure, a model of depression with predictive validity. Repeated administration of clomipramine (5 mg kg(-1), intraperitoneal) for 3 weeks, starting 2 weeks after the beginning of the stress procedure, significantly reversed the reduction of behavior measured by open-field test and forced swimming test. Moreover, rats subjected to stress exhibited a 49.9% reduction of cell proliferation at the end of a 5-week stress period, an effect which was suppressed by clomipramine treatment. These results demonstrated that exposure to CUS, which results in a state of behavioral depression, decreases hippocampal cell proliferation and that these effects can be counteracted by chronic clomipramine treatment.

Background The neuroinflammatory responses in the spinal cord following bone cancer development have been shown to play an important role in cancer-induced bone pain (CIBP). Lipoxins (LXs), endogenous lipoxygenase-derived eicosanoids, represent a unique class of lipid mediators that possess a wide spectrum of anti-inflammatory and pro-resolving actions. In this study, we investigated the effects of intrathecal injection with lipoxin and related analogues on CIBP in rats. Methods The CIBP model was induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. Mechanical thresholds were determined by measuring the paw withdrawal threshold to probing with a series of calibrated von Frey filaments. Lipoxins and analogues were administered by intrathecal (i.t.) or intravenous (i.v.) injection. The protein level of LXA4 receptor (ALX) was tested by western blot. The localization of lipoxin receptor in spinal cord was assessed by fluorescent immunohistochemistry. Real-time PCR was carried out for detecting the expression of pro-inflammatory cytokines. Results Our results demonstrated that: 1) i.t. injection with the same dose (0.3 nmol) of lipoxin A4 (LXA4), lipoxin B4 (LXB4) or aspirin-triggered-15-epi-lipoxin A4 (ATL) could alleviate the mechanical allodynia in CIBP on day 7 after surgery. ATL showed a longer effect than the others and the effect lasted for 6 hours. ATL administered through i.v. injection could also attenuate the allodynia in cancer rats. 2) The results from western blot indicate that there is no difference in the expression of ALX among the naive, sham or cancer groups. 3) Immunohistochemistry showed that the lipoxin receptor (ALX)-like immunoreactive substance was distributed in the spinal cord, mainly co-localized with astrocytes, rarely co-localized with neurons, and never co-localized with microglia. 4) Real-time PCR analysis revealed that, compared with vehicle, i.t. injection with ATL could significantly attenuate the expression of the mRNA of proinflammatory cytokines (IL-1β and TNF-α) in the spinal cord in CIBP. Conclusions Taken together, the results of our study suggest that LXs and analogues exert strong analgesic effects on CIBP. These analgesic effects in CIBP are associated with suppressing the expression of spinal proinflammatory cytokines.

Background Non-pharmaceutical strategies are vital in curtailing impacts of influenza and have been intensively studied in public health. However, few strategies have explicitly utilized the weekend effect, which has been widely reported to be capable of reducing influenza infections. This study aims to explore six weekend-extension strategies against seasonal and pandemic flu outbreaks. Methods The weekend-extension strategies were designed to extend regular two-day weekend by one, two and three days, respectively, and in combination with either a continuous or discontinuous pattern. Their effectiveness was evaluated using an established agent-based spatially explicit simulation model in the urbanized area of Buffalo, NY, US. Results If the extensions last more than two days, the weekend-extension strategies can remarkably reduce the overall disease attack rate of seasonal flu. Particularly, a three-day continuous extension is sufficient to suppress the epidemic and confine the spread of disease. For the pandemic flu, the weekend-extension strategies only produce a few mitigation effects until the extensions exceed three days. Sensitivity analysis indicated that a compliance level above 75% is necessary for the weekend-extension strategies to take effects. Conclusion This research is the first attempt to incorporate the weekend effect into influenza mitigation strategies. The results suggest that appropriate extensions of the regular two-day weekend can be a potential measure to fight against influenza outbreaks, while minimizing interruptions on normal rhythms of socio-economy. The concept of weekend extension would be particularly useful if there were a lack of vaccine stockpiles, e.g., in countries with limited health resources, or in the case of unknown emerging infectious diseases.