Different responses of marine microalgae Phaeodactylum tricornutum upon exposures to WAF and CEWAF of crude oil: A case study coupled with stable isotopic signatures.

Increasing use of chemical dispersants for oil spills highlights the need to understand their adverse effects on marine microalgae and nutrient assimilation because the toxic components of crude oil can be more bioavailable. We employed the crude oil water-accommodated fraction (WAF) and chemically enhanced WAF (CEWAF) to compare different responses in marine microalgae (Phaeodactylum tricornutum) coupled with stable isotopic signatures. The concentration and proportion of high-molecular-weight polycyclic aromatic hydrocarbons (HMW PAHs), which are key toxic components in crude oil, increased after dispersant addition. CEWAF exposure caused higher percent growth inhibition and a lower chlorophyll-a level of microalgae than those after WAF exposure. Compared with WAF exposure, CEWAF led to an enhancement in the self-defense mechanism of P. tricornutum, accompanied by an increased content of extracellular polymeric substances. 13C-depletion and carbon assimilation were altered in P. tricornutum, suggesting more HMW PAHs could be utilized as carbon sources by microalgae under CEWAF. CEWAF had no significant effects on the isotopic fractionation or assimilation of nitrogen in P. tricornutum. Our study unveiled the impact on the growth, physiological response, and nutrient assimilation of microalgae upon WAF and CEWAF exposures. Our data provide new insights into the ecological effects of dispersant applications for coastal oil spills.

Correction: An E-selectin targeting and MMP-2-responsive dextran-curcumin polymeric prodrug for targeted therapy of acute kidney injury.

Correction for 'An E-selectin targeting and MMP-2-responsive dextran-curcumin polymeric prodrug for targeted therapy of acute kidney injury' by Jing-Bo Hu et al., Biomater. Sci., 2018, 6, 3397-3409, https://doi.org/10.1039/C8BM00813B.

Soft ferroelectret ultrasound receiver for targeted peripheral neuromodulation.

Bioelectronic medicine is a rapidly growing field where targeted electrical signals can act as an adjunct or alternative to drugs to treat neurological disorders and diseases via stimulating the peripheral nervous system on demand. However, current existing strategies are limited by external battery requirements, and the injury and inflammation caused by the mechanical mismatch between rigid electrodes and soft nerves. Here we report a wireless, leadless, and battery-free ferroelectret implant, termed NeuroRing, that wraps around the target peripheral nerve and demonstrates high mechanical conformability to dynamic motion nerve tissue. As-fabricated NeuroRing can act as an ultrasound receiver that converts ultrasound vibrations into electrostimulation pulses, thus stimulating the targeted peripheral nerve on demand. This capability is demonstrated by the precise modulation of the sacral splanchnic nerve to treat colitis, providing a framework for future bioelectronic medicines that offer an alternative to non-specific pharmacological approaches.

Molecular mechanism of the anti-inflammatory effects of plant essential oils: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Plant essential oils (PEOs) extracted from aromatic compounds of the plant contain complex mixtures of volatile and lipophilic bioactive compounds. In ancient Egypt, Arabia, Greece, and China, PEOs were traditional used in aromatherapy for various health disorders, including pain and inflammation. AIM OF THE STUDY: In this review, we provide an overview of the anti-inflammatory effects of PEOs and the underlying mechanisms associated with anti-inflammatory effects using in vitro and in vivo models. Further, clinical trials associated with PEOs were explored. MATERIALS AND METHODS: The literature search was performed using various web-based tools and databases like Google Scholar, Web of Science, PubMed, CNKI and SCOPUS. The keywords used for conducting the literature review were general terms like "essential oils" followed by (AND) the subject of interest like "in vitro and/or in vivo anti-inflammatory models," "inflammatory response," "inflammatory indicators," "pro-inflammatory cytokines," "signaling pathway," "anti-inflammatory mechanism," "toxicology and side effects" and "clinical trials." The articles selected were published between 2017 and 2022. The articles prior to 2017 were only considered if they were associated with molecular mechanisms or signaling pathways involved in the inflammatory responses. RESULTS: In vitro and in vivo inflammation models have been used to study the anti-inflammatory effects of 48 PEOs. Studies have reported that PEOs targets and inhibit multiple dysregulated signaling pathways associated with inflammation, including Toll-like receptors, nuclear transcription factor-κ B, mitogen-activated protein kinases, Nod-like receptor family pyrin domain containing 3, and auxiliary pathways like the nuclear factor erythroid 2-related factor 2/antioxidant response element and Janus kinase/signal transducers and activators of transcription) signaling pathways. CONCLUSION: PEOs extracted from different plant materials had varied qualitative and quantitative compositions of biologically active compounds. Different anti-inflammatory potentials and different molecular signal transduction have been attributed to PEOs-derived bioactive compounds with different chemical structures. The data on therapeutic efficacy and the long-term side effects of PEOs as an anti-inflammatory drug are still unknown due to the lack of clinical trials on PEOs. There is still insufficient evidence to draw conclusions on anti-inflammatory properties of PEOs without promising outcomes from clinical trials.

Preparation Process Optimization and Performance Characterization of Feed Plant Essential Oil Microcapsules.

The exploration of safe antibiotic substitutes is one of the research hotspots in animal husbandry. Adding suitable plant essential oils into feed could improve the growth performance and immune capacity of animals. In order to make plant essential oil play a better role in feed application, sodium alginate and chitosan were used as the wall materials, and blended plant essential oils (BEO) as the core material to prepare BEO microcapsules by the sharp-hole condensation method. On the basis of single-factor experiments, the optimal preparation conditions for BEO microcapsules were obtained by response surface experiments. The physicochemical properties were characterized and analyzed by Fourier-transform infrared spectroscopy (FTIR) and field scanning electron microscope (FSEM). Meanwhile, the release mechanism was studied by simulating a gastrointestinal sustained-release experiment. The results showed that under the optimal preparation conditions, the encapsulation efficiency of BEO microcapsules could reach 80.33 ± 2.35%. FTIR and SEM analysis displayed that the microcapsules obtained had uniform color and size and a complete and compact structure. In vitro study indicated that the release amount of BEO microcapsules in the simulated intestinal fluid is higher than that in the simulated intestinal fluid, which was consistent with animal digestive and absorptive characteristics.

Biofeedback electrostimulation for bionic and long-lasting neural modulation.

Invasive electrical stimulation (iES) is prone to cause neural stimulus-inertia owing to its excessive accumulation of exogenous charges, thereby resulting in many side effects and even failure of nerve regeneration and functional recovery. Here, a wearable neural iES system is well designed and built for bionic and long-lasting neural modulation. It can automatically yield biomimetic pulsed electrical signals under the driven of respiratory motion. These electrical signals are full of unique physiological synchronization can give biofeedback to respiratory behaviors, self-adjusting with different physiological states of the living body, and thus realizing a dynamic and biological self-matched modulation of voltage-gated calcium channels on the cell membrane. Abundant cellular and animal experimental evidence confirm an effective elimination of neural stimulus-inertia by these bioelectrical signals. An unprecedented nerve regeneration and motor functional reconstruction are achieved in long-segmental peripheral nerve defects, which is equal to the gold standard of nerve repair -- autograft. The wearable neural iES system provides an advanced platform to overcome the common neural stimulus-inertia and gives a broad avenue for personalized iES therapy of nerve injury and neurodegenerative diseases.

A Luminol-Based Self-Illuminating Nanocage as a Reactive Oxygen Species Amplifier to Enhance Deep Tumor Penetration and Synergistic Therapy.

The dense extracellular matrix (ECM) in tumor tissues resists drug diffusion into tumors and leads to a poor prognosis. To address this problem, glucose oxidase (GOx)-modified ferritin loaded with luminol-curcumin was fabricated. Once delivered to the tumor, this luminol-based self-illuminating nanocage could actively convert glucose to reactive oxygen species (ROS) to achieve starvation therapy. Then, excessive ROS were transmitted to luminol, thereby emitting 425 nm blue-violet light. Momentarily, light was further absorbed by curcumin and ROS production was amplified. Abundant ROS helps break down the ECM network to penetrate deep into tumors. In addition, ROS produced after cell internalization can induce apoptosis of tumor cells by decreasing the mitochondrial membrane potential and can promote ferroptosis by consuming reduced glutathione. Effective penetration and multiple pathways inducing tumor cell death contributed to the efficient antitumor effect (tumor inhibition rate of GOx-modified ferritin loaded with luminol-curcumin: 71.73%). This study developed a glucose-driven self-illuminating nanocage for active tumor penetration via ROS-mediated destruction of the ECM and provided the synergetic mechanism of apoptosis and ferroptosis.

Power Generation from Moisture Fluctuations Using Polyvinyl Alcohol-Wrapped Dopamine/Polyvinylidene Difluoride Nanofibers.

Despite the boom in the water-triggered electric power generation technologies, few attempts have been made with a broader horizonyielding the electricity from sweat, which is of great value for low-power-consumption wearable electronics. Here, an electromechanical coupling and humidity-actuated two-in-one humidity actuator-driven piezoelectric generator (HAPG) are reported, that can yield continuous electric power from fluctuations in the ambient humidity. It is composed of polyvinyl alcohol (PVA)-wrapped highly aligned dopamine (DA)/polyvinylidene fluoride (PVDF) shell/core nanofibers (PVA@DA/PVDF NFs). As-received PVA@DA/PVDF NFs can exchange water with the ambient humidity to perform expansion and contraction and convert them into electric power. An all-fiber-based portable HAPG is fabricated and tested on human palm skin. The devices show high sensitivity and accuracy for converting the mental sweating-derived continuous moisture fluctuations into electric power. This electric power can be stored in capacitors, which is expected to power micro- and nano-electronic devices or be used in electrotherapy such as electrical stimulation to promote wound healing. Beyond this, the obtained voltage profiles exhibit unique features that can reflect the typical sweat damping oscillation curve features.

Inhibition of Peripheral ERK Signaling Ameliorates Persistent Muscle Pain Around Trigger Points in Rats.

The purpose of this study was to investigate whether the ERK signaling pathway was involved in ameliorating chronic myofascial hyperalgesia from contused gastrocnemius muscle in rats. We established an animal model associated with myofascial pain syndrome and described the mechanism of muscle pain in an animal model. Changes in the mechanical pain threshold were observed 0.5, 1, 2, 3, 4, 5, 8, 12, 18, and 24 h after ERK inhibitor injection around myofascial trigger points (MTrPs) of the gastrocnemius muscle in rats. Morphological changes in gastrocnemius muscle cells were observed by hematoxylin and eosin (H&E) staining. ERK signaling pathway activation was detected through immunohistochemistry and Western blotting. The main morphological characteristics of injured muscle fibers around MTrPs include gathered circular or elliptical shapes of different sizes in the cross-section and continuous inflated and tapering fibers in the longitudinal section. After intramuscular injection of U0126 (ERK inhibitor), the mechanical pain threshold significantly increased. The reduction in mechanical hyperalgesia was accompanied by reduced ERK protein phosphorylation, myosin light chain kinase (MLCK) protein, p-MLC protein expression, and the cross-sectional area of skeletal muscle cells around MTrPs. An ERK inhibitor contributed to the attenuation of mechanical hyperalgesia in the rat myofascial pain model, and the increase in pain threshold may be related to MLCK downregulation and other related contraction-associated proteins by ERK.

[Study on GLI values of Polygonatum odoratum base on multi-temporal of unmanned aerial vehicle remote sensing].

Unmanned aerial vehicle(UAV) remote sensing and vegetation index have great potential in the field of Chinese herbal medicine planting. In this study, the visible light image of Polygonatum odoratum planting area in Changyi district of Jilin province were acquired by UAV, and the real-time monitoring of P. odoratum planting area was realized. The green leaf index(GLI) was established, and GLI values of P. odoratum were collected used the spatial sampling points. To compare the GLI values in different periods, it was found that the GLI values of P. odoratum have three stages changing rule of rising-gentle-falling related to the germination, vigorous growth and withered of P. odoratum growth. Meanwhile, the GLI values were compared with four biomass data of P. odoratum, including plant height, leaf area, chlorophyll a and chlorophyll b content in leaves, and it was found that the GLI value was related to the growth potential of P. odoratum. The GLI value with a rapid increase in rising stage or at a high level in the gentle stage means the P. odoratum was in a better growth potential. GLI value has a same change trend with plant height, and has certain correlation with plant height and leaf area. However, there is no obvious relationship between chlorophyll a and chlorophyll b contents in leaves and GLI value. The study clarified the change rule of GLI value of P. odoratum, explained the reason for the change of GLI value, and expanded the application range of GLI. The research shows that UAV and vegetation index can be applied to monitoring the Chinese herbal medicines planting, and provides a new idea for exploring more effective information extraction methods of Chinese herbal medicines.

Study on GLI values of Polygonatum odoratum base on multi-temporal of unmanned aerial vehicle remote sensing / 中国中药杂志

Unmanned aerial vehicle(UAV) remote sensing and vegetation index have great potential in the field of Chinese herbal medicine planting. In this study, the visible light image of Polygonatum odoratum planting area in Changyi district of Jilin province were acquired by UAV, and the real-time monitoring of P. odoratum planting area was realized. The green leaf index(GLI) was established, and GLI values of P. odoratum were collected used the spatial sampling points. To compare the GLI values in different periods, it was found that the GLI values of P. odoratum have three stages changing rule of rising-gentle-falling related to the germination, vigorous growth and withered of P. odoratum growth. Meanwhile, the GLI values were compared with four biomass data of P. odoratum, including plant height, leaf area, chlorophyll a and chlorophyll b content in leaves, and it was found that the GLI value was related to the growth potential of P. odoratum. The GLI value with a rapid increase in rising stage or at a high level in the gentle stage means the P. odoratum was in a better growth potential. GLI value has a same change trend with plant height, and has certain correlation with plant height and leaf area. However, there is no obvious relationship between chlorophyll a and chlorophyll b contents in leaves and GLI value. The study clarified the change rule of GLI value of P. odoratum, explained the reason for the change of GLI value, and expanded the application range of GLI. The research shows that UAV and vegetation index can be applied to monitoring the Chinese herbal medicines planting, and provides a new idea for exploring more effective information extraction methods of Chinese herbal medicines.

An E-selectin targeting and MMP-2-responsive dextran-curcumin polymeric prodrug for targeted therapy of acute kidney injury.

Based on the overproduction of matrix metalloproteinase-2 (MMP-2) in renal tissue during acute kidney injury (AKI) occurrence, we developed a MMP-2 enzyme-triggered polymeric prodrug with sialic acid (SA) as the targeting group to the inflamed vascular endothelial cells for enhanced therapeutic outcomes. An MMP-2-responsive peptide, PVGLIG, was used to endow the polymeric prodrug with the ability to rapidly release the anti-inflammatory drug, curcumin (CUR), after the targeted site is reached and to improve the drug concentration in the target tissue. The sialic acid-dextran-PVGLIG-curcumin (SA-DEX-PVGLIG-CUR) polymeric prodrug was successfully synthesized via multi-step chemical reactions and characterized by 1H NMR. The water solubility of CUR was significantly increased in the polymeric prodrug and was approximately 23-fold higher than that of free CUR. The in vitro drug release results showed that the release rate of SA-DEX-PVGLIG-CUR was significantly enhanced compared to that of SA-DEX-CUR in a dissolving medium containing the MMP-2 enzyme, suggesting that SA-DEX-PVGLIG-CUR had rapid drug release characteristics in an inflammatory environment. A cellular uptake test confirmed that SA-DEX-PVGLIG-CUR was effectively internalized by inflamed vascular endothelial cells in comparison with that by normal cells, and the mechanism was associated with the specific interaction between SA and E-selectin receptors specifically expressed on inflamed vascular endothelial cells. Bio-distribution results further demonstrated the rapid and increased renal accumulation of SA-DEX-PVGLIG-CUR in AKI mice. Benefiting from the rapid drug release in renal tissue, SA-DEX-PVGLIG-CUR effectively ameliorated the pathological progression of AKI compared with free CUR and SA-DEX-CUR, as reflected by the improved renal functions, histopathological changes, pro-inflammatory cytokine production, oxidative stress and expression of apoptosis related proteins. Altogether, this study provided a new therapeutic strategy for the treatment of AKI.

Live or let die: Neuroprotective and anti-cancer effects of nutraceutical antioxidants.

Diet sources are closely involved in the pathogenesis of diverse neuropsychiatric disorders and cancers, in addition to inherited factors. Currently, natural products or nutraceuticals (commonly called medical foods) are increasingly employed for adjunctive therapy of these patients. However, the potential molecular mechanisms of the nutrient efficacy remain elusive. In this review, we summarized the neuroprotective and anti-cancer mechanisms of nutraceuticals. It was concluded that the nutraceuticals exerted neuroprotection and suppressed tumor growth possibly through the differential modulations of redox homeostasis. In addition, the balance between reactive oxygen species (ROS) production and ROS elimination was manipulated by multiple molecular mechanisms, including cell signaling pathways, inflammation, transcriptional regulation and epigenetic modulation, which were involved in the therapeutic potential of nutraceutical antioxidants against neurological diseases and cancers. We specifically proposed that ROS scavenging was integral in the neuroprotective potential of nutraceuticals, while alternation of ROS level (either increase or decrease) or disruption of redox homeostasis (ROS addiction) constituted the anti-cancer property of these compounds. We also hypothesized that ROS-associated ferroptosis, a novel type of lipid ROS-dependent regulatory cell death, was likely to be a critical mechanism for the nutraceutical antioxidants. Targeting ferroptosis is advantageous to develop new nutraceuticals with more effective and lower adverse reactions for curing patients with neuropsychiatric diseases or carcinomas.

The effects of CYP1A inhibition on alkyl-phenanthrene metabolism and embryotoxicity in marine medaka (Oryzias melastigma).

Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are the predominant form of PAHs in crude oils, of which, 3-5 ring alkyl-PAH may cause dioxin-like toxicity to early life stages of fish. Retene (7-isopropyl-1-methylphenanthrene), a typical alkyl-phenanthrene compound, can be more toxic than phenanthrene, and the mechanism of retene toxicity is likely related to its rapid biotransformation by cytochrome P450 (CYP) enzymes to metabolites with a wide array of structures and potential toxicities. Here, we investigated how α-naphthoflavone (ANF), a cytochrome P450 1A (CYP1A) inhibitor, affected the embryotoxicity of retene and the role that CYP1A inhibition may play in the interactions. Marine medaka (Oryzias melastigma) embryos were exposed, separately or together, to 200 µg/L retene with 0, 5, 10, 100, and 200 µg/L ANF for 14 days. The results showed that ANF significantly inhibited the induction of CYP1A activity by retene; however, ANF interacted with retene to induce significant developmental toxicity and genotoxicity at 10, 100, and 200 µg/L (p < 0.01). Tissue concentrations of retene and its metabolites and lipid hydroperoxide (LPO) activity also increased, whereas the inhibition of the glutathione S-transferase (GST) activity and the alteration in metabolic profiles of retene were observed. The interactions of retene with ANF indicate that CYP1A inhibition was possibly act through different mechanisms to produce similar developmental effects and genotoxicity. Retene metabolites and altered metabolic profile were likely responsible for retene embryotoxicity to marine medaka. Therefore, elevated toxicity of alkyl-phenanthrene under CYP1A inhibitor suggested that the ecotoxicity of PAHs in coastal water may have underestimated the threat of PAHs to fish or ecosystem.

[Pilot-scale cultivation of Spirulina plantensis with digested piggery wastewater ].

The swine waste pretreated with coagulation sedimentation was used for the outdoor pilot-scale cultivation of Spirulina platensis isolated from digested piggery wastewater (DPW) in a raceway pond. The growth of S. platensis and removal of nitrogen/ phosphorus were studied, moreover, the conversion efficiency of total nitrogen (TN) or total phosphorus (TP) from DPW to S. platensis was calculated. On this basis, the existing problems and countermeasures during outdoor pilot-scale culture were analyzed and summarized combined with the laboratory research. We conducted 6 batches culture experiments, only 3 of which could reach the S. platensis harvest requirements (D560 >0. 8). Meanwhile, the 3 successful batches achieved removal of COD, ammonia nitrogen, TN, TP with corresponding 28. 6% -48. 5% , 0.4% -48. 5% , 41. 8% -48. 6% , 14. 3% -94. 5% , and the conversion efficiency of TN or TP from DPW to S. platensis reached 12. 1% -98. 5% , 21.2% -83.7% , respectively. High concentration of ammonia nitrogen and insect attack of remaining egg hatching in the pretreated swine waste were the main factors to cause the slow-growing of the 3 batches of S. platensis. Therefore, it is highly necessary for the removal of ammonia nitrogen with biological treatment technology and insect eggs with membrane to achieve a stable high productivity.

Comparative effects of biological and chemical dispersants on the bioavailability and toxicity of crude oil to early life stages of marine medaka (Oryzias melastigma).

The authors assessed the bioavailability and chronic toxicity of water-accommodated fractions of crude oil (WAFs) and 2 dispersants plus dispersed crude oil (chemical dispersant + crude oil [CE-WAF] and biological dispersant + crude oil [BE-WAF]) on the early life stages of marine medaka, Oryzias melastigma. The results showed that the addition of the 2 dispersants caused a 3- and 4-fold increase in concentrations of summed priority polycyclic aromatic hydrocarbons (PAHs) and high-molecular-weight PAHs with 3 or more benzene rings. The chemical and biological dispersants increased the bioavailability (as measured by ethoxyresorufin-O-dethylase activity) of crude oil 6-fold and 3-fold, respectively. Based on nominal concentrations, chronic toxicity (as measured by deformity) in WAFs exhibited a 10-fold increase in CE-WAF and a 3-fold increase in BE-WAF, respectively. When total petroleum hydrocarbon was measured, the differences between WAF and CE-WAF treatments disappeared, and CE-WAF was approximately 10 times more toxic than BE-WAF. Compared with the chemical dispersant, the biological dispersant possibly modified the toxicity of oil hydrocarbons because of the increase in the proportion of 2- and 3-ringed PAHs in water. The chemical and biological dispersants enhanced short-term bioaccumulation and toxicity, through different mechanisms. These properties should be considered in addition to their efficacy in degrading oil when oil spill management strategies are selected.

The effect of sodium selenite on lead induced cognitive dysfunction.

The effect of lead (Pb) on spatial memory and hippocampal long-term potentiation (LTP) as a key risk factor has been widely recognized and the oxidative damage has been proposed as a possible mechanism of lead neurotoxicity. Selenium (Se) is a nutritionally essential trace element with known antioxidant potential. In this study we investigated the effect and the underlying mechanisms of Se supplementary on Pb induced cognition and synaptic plasticity impairment. Lactating Sprague-Dawley rats (SD rats) were randomly divided to four groups: 0ppm lead acetate (Pb); 0ppm Pb and 0.2ppm sodium selenite (Se); 100ppm Pb; 100ppm Pb and 0.2ppm Se. Lactating rats were treated with or without Pb and/or Se throughout lactation until weaning. The levels of hippocampal LTP, the spatial memory, the apoptosis of hippocampal neurons, the levels of lactate dehydrogenase (LDH) release, and the serum level of superoxide dismutase (SOD) and malondialdehyde (MDA) were assayed. It had been observed that in Pb group the spatial memory, the induce level of LTP, the serum SOD level decreased, the LDH release level, the neurons apoptosis level, the serum MDA level increased, while in the Se supplements groups, the spatial memory, the induce level of LTP increased significantly. Compared with the Pb group, Se supplements shown down regulated the level of LDH, the neurons apoptosis and the serum MDA, and up regulated the level of serum SOD. We could draw the conclusion that Se supplements could alleviate toxic effect of lead on hippocampal LTP and spatial memory. The treated with selenium around 0.2ppm may protect against spatial memory dysfunction induced by lead exposure.

[Identification of the prior regions for agricultural and rural pollution control in Changshu].

The characteristics such as wide area, dispersion and randomness of agricultural and rural pollution make it difficult to seize the key to pollution control in rural areas. On the scale of township, using inventory analysis, accounting for emissions and emission intensity of the chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP) in Changshu, Jiangsu Province, which exists in a total of 4 classes and 6 kinds of agricultural and rural sources such as farmland cultivation (chemical fertilizer application and crop straw abandoned), animal breeding, aquaculture, rural life (domestic sewage and human waste, solid waste), using cluster analysis, identify the prior regions and the prior pollution sources for agricultural and rural pollution control by the sensitivity evaluation, and make agricultural and rural pollution control and management measures more focused. It shows that: in 2007, COD, TN and TP emissions of agricultural and rural pollution sources were 5496.07, 4161.03, and 647.54 t x a(-1), and the emission intensity of COD, TN and TP was 48.84, 36.98, and 5.75 kg x hm(-2). The main pollution source of COD was rural life and aquaculture, and the contribution rate was more than 75%; the main pollution source of TN and TP was agricultural cultivation and aquaculture, and the contribution rate was more than 80%. The sensitivity evaluation identified that the town of Guli and Shajiabang were the prior regions for agricultural and rural pollution control in Changshu; farmland cultivation and aquaculture were the prior pollution sources in the two areas.

Action of a Novel PDE4 inhibitor ZL-n-91 on lipopolysaccharide-induced acute lung injury.

In the present study, we investigated the effect of classic PDE4 inhibitor rolipram and novel PDE4 inhibitor ZL-n-91 on LPS-induced acute lung injury (ALI) in mice and its mechanism. ALI was induced in ICR mice by instilling intratracheally with LPS, and mice were divided into seven groups: control (Saline), LPS group, ZL-n-91 (3 microg, 10 microg, and 30 microg kg(-1), ip), Rolipram (1.0 mg kg(-1), ip) and dexamethasone (0.5 mg kg(-1), ip). After the 6h of instilling intratracheally with LPS in mice, total leukocyte number, neutrophil number and protein content in BALF increased rapidly, a large number of neutrophil infiltration around the pulmonary vessel and airway, the lung wet weight/dry weight (w/d)ratio raised significantly. MPO activity, TNF-alpha level and cAMP-PDE, PDE4 activity in lung homogenate raised significantly. P(a)O(2), P(a)CO(2) and PH value in peripheral arterial blood also changed obviously, P(a)O(2) and PH value dropped slightly and P(a)CO(2) increased significantly in LPS group. ZL-n-91 (3 microg, 10 microg, 30 microg kg(-1)) dose-dependently reduced the total leukocyte number, neutrophil number and total protein content in BALF, MPO activity, TNF-alpha level and cAMP-PDE, PDE4 activity in lung homogenate, but the effect of ZL-n-91 in pathological changes and lung wet w/d ratio is slight; Rol and Dex significantly reduced lung wet w/d ratio and improved pathological changes, neutrophil around the pulmonary vessel and airway significantly reduced, symptoms of lung edema relieved; The PH value, P(a)O(2) and P(a)CO(2) in ZL-n-91 high dosage group and Rol group had changes, but there was no significant difference compared with LPS group or saline group; After the administration, the righting reflex recovery time significantly shorten in every group of ZL-n-91. the righting reflex recovery time of Rol group was similar with ZL-n-91 30 microg kg(-1) group, while Dex group was similar with saline group. The present study confirms that the inhibitory effect of ZL-n-91(30 microg kg(-1)) on the inflammatory reactivity, including inhibition of inflammatory cell and protein exudation, MPO and PDE4 activity, improvement of the blood gas, those effects were equivalent with rolipram 1 mg kg(-1), and suggested that ZL-n-91 was stronger than rolipram in PDE4 inhibition. So we speculated that ZL-n-91 may have stronger therapeutic potential for treatment of inflammatory disease than rolipram, meantime have stronger nervous system effect than rolipram.

Anti-allodynic effect of intracerebroventricularly administered antioxidant and free radical scavenger in a mouse model of orofacial pain.

AIMS: To evaluate possible effects of the intracerebroventricular (icv) injection of either O-Tricyclo [5.2.1.0(2,6)] dec-9-yl dithiocarbonate potassium salt (D609), a potent antioxidant and inhibitor of phosphatidylcholine specific phospholipase C (PtdCho-PLC) and acid sphingomyelinase (ASMase), or the spin trap/free radical scavenger N-tert-Butyl-alpha-phenylnitrone (PBN), on mechanical allodynia induced by facial carrageenan injection in mice. METHODS: Balb/c mice received icy injection of D609/PBN plus facial carrageenan injection, and the number of face wash strokes to von Frey hair mechanical stimulation of the maxillary skin was quantified. PtdCho-PLC and ASMase activities were also assayed in the brainstem, thalamus, and somatosensory cortex. RESULTS: Mice that received the icy injection of 10 nmol D609 plus facial carrageenan injection showed significantly fewer face wash strokes evoked by von Frey hair stimulation (indicating reduced mechanical allodynia) at 1 and 3 days post-injection, compared to mice that received icy injection of isotonic saline plus facial carrageenan injection. Mice that received icy injection of 1.13 micromol PBN plus facial carrageenan injection likewise showed significantly fewer face wash strokes after facial carrageenan injection, compared to isotonic saline-injected plus carrageenan-injected controls. D609 injection also resulted in significantly reduced ASMase activity in the brainstem, thalamus, and somatosensory cortex 3 days after injection, compared to controls. CONCLUSION: The icv injections of D609 and PBN were effective in reducing mechanical allodynia after facial carrageenan injection-induced pain. Together, the results point to a possible role of central nervous system sphingolipids and/or free radicals in orofacial pain.