The role of PI3K/Akt signalling pathway in spinal cord injury.

Spinal cord injury (SCI) is a severely disabling central nervous system injury with complex pathological mechanisms that leads to sensory and motor dysfunction. The current treatment for SCI is aimed at symptomatic symptom relief rather than the pathological causes. Several studies have reported that signaling pathways play a key role in SCI pathological processes and neuronal recovery mechanisms. The PI3K/Akt signaling pathway is an important pathway closely related to the pathological process of SCI, and activation of this pathway can delay the inflammatory response, prevent glial scar formation, and promote neurological function recovery. Activation of this pathway can promote the recovery of neurological function after SCI by reducing cell apoptosis. Based on the role of the PI3K/Akt pathway in SCI, it may be a potential therapeutic target. This review highlights the role of activating or inhibiting the PI3K/Akt signaling pathway in SCI-induced inflammatory response, apoptosis, autophagy, and glial scar formation. We also summarize the latest evidence on treating SCI by targeting the PI3K/Akt pathway, discuss the shortcomings and deficiencies of PI3K/Akt research in the field of SCI, and identify potential challenges in developing these clinical therapeutic SCI strategies, and provide appropriate solutions.

Acute toxicity and inactivation tests of CO2 on invertebrates in drinking water treatment systems.

In addition to the esthetic problem caused by invertebrates, researchers are recently starting to be more aware of their potential importance in terms of public health. However, the inactivation methods of invertebrates which could proliferate in drinking water treatment systems are not well developed. The objective of this study is to assess the acute toxicity and inactivation effects of CO2 on familiar invertebrates in water treatment processes. The results of this study revealed that CO2 has a definite toxicity to familiar invertebrates. The values of 24-h LC50 (median lethal concentration) were calculated for each test with six groups of invertebrates. The toxicity of CO2 was higher with increasing concentrations in solution but was lower with the increase in size of the invertebrates. Above the concentration of 1,000 mg/L for the CO2 solution, the 100% inactivation time of all the invertebrates was less than 5 s, and in 15 min, the inactivation ratio showed a gradient descent with a decline in concentration. As seen for Mesocyclops thermocyclopoides, by dosing with a sodium bicarbonate solution first and adding a dilute hydrochloric acid solution 5 min later, it is possible to obtain a satisfactory inactivation effect in the GAC (granular activated carbon) filters.

The synergy of porous substrates and functional genera for efficient nutrients removal at low temperature in a pilot-scale two-stage tidal flow constructed wetland.

A pilot-scale two-stage tidal flow constructed wetland (TFCW) with working volume of 0.46 m3/d packing with shale ceramsite (SC) and activated alumina (AA) was constructed (named as SC-AA-TFCW) for nutrients removal at low temperature (<15 °C). SC-AA-TFCW achieved stable removals of 78.1% nitrogen and 98.3% phosphorous. SC-TFCW contributed to 55.2% of organics and 85.6% of particulate phosphorous removal. Among 17 denitrifiers, the absolute abundance of aerobic denitrification bacteria (ADNB) was highest, followed by facultative anaerobic denitrification bacteria (FADNB) and autotrophic denitrification bacteria (AUDNB). Nitrogen assimilating into organic nitrogen, dissimilatory and assimilatory nitrate reduction and complete denitrification may be main nitrogen metabolic pathways. Some ADNB (e. g. Zoogloea, Pseudomonas and Acidovorax) showed positive interactions with various key functional genes related to nutrients removal. Dissolved oxygen and reducing elements were main environmental factors in changing ADNB compositions. This study highlights the importance of ADNB and their synergy to porous substrates in SC-AA-TFCW.

Intensified nitrogen removal by heterotrophic nitrification aerobic denitrification bacteria in two pilot-scale tidal flow constructed wetlands: Influence of influent C/N ratios and tidal strategies.

This study investigated the influence of C/N ratios and tidal strategies on nitrogen removal and bacterial communities in two pilot-scale tidal flow constructed wetlands (TFCWs) with simultaneous nitrification-denitrification process. Heterotrophic nitrification aerobic denitrification (HNAD) was the main nitrogen transformation pathway in both TFCWs. High C/N ratios and effluent circulation at low temperature promoted HNAD in TFCWs with high nitrogen removal efficiencies (72.6%-95.5% for NH4+-N and 70.9%~91.8% for TN). Effluent circulation had more influence on bacterial community structure and diversity than C/N ratios. Among 16 detected genera related to nitrogen removal, HNAD bacteria (HNADB) were abundant. Especially, some dominant HNADB (e.g. Aeromonas, Hydrogenophage and Gemmobacter) were core genera, showing positive interactions with other genera related to nitrogen removal. Tidal strategies had more contribution to the shifts in these genera than C/N ratios. This study highlights the importance of HNADB in pilot-scale TFCWs and their responses to C/N ratios and tidal strategies.

Reduction of amyloid beta by Aß3-10-KLH vaccine also decreases tau pathology in 3×Tg-AD mice.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive amyloid-ß (Aß) accumulation, neurofibrillary tangles (NFTs) formation and synaptic alterations. Active immunotherapy is regarded as one of the most promising strategies for AD prevention and treatment. In this research, we used APPswe/PS1M146 V/TauP301 L triple transgenic (3×Tg-AD) mice, in which the pathological changes are the most similar to those in AD patients. The Aß 3-10 -keyhole limpet haemocyanin (KLH) vaccine was administered to mice at 1 month, and no AD-associated changes were detected at that time. The vaccine effectively mitigated AD-like pathology and cognitive dysfunction in the 3×Tg-AD mice. Both soluble and insoluble Aß and tau protein in the brain tissues of the 3×Tg-AD mice were significantly decreased after the administration of Aß 3-10 -KLH. In addition, the level of phosphorylated tau also decreased following removal of the Aß pathological changes.

Prophylactic active immunization with a novel epitope vaccine improves cognitive ability by decreasing amyloid plaques and neuroinflammation in APP/PS1 transgenic mice.

Both amyloid-ß peptide (Aß) deposition and neuroinflammation are considered to be early events that play pivotal roles in Alzheimer's disease (AD) pathogenesis and its associated cognitive impairment. Prophylactic anti-Aß active immunotherapy is a promising therapeutic strategy for AD, if the Aß-specific autoimmune responses to self T cell epitopes of Aß can be avoided. This can be achieved by the use of antigen, which contains the B cell epitope of Aß and excludes the Aß-specific T cell epitope. In this study, we developed a novel peptide epitope vaccine, Aß3-10-KLH, by coupling the B cell epitope Aß3-10 to keyhole limpet hemocyanin (KLH) as the carrier protein, and subcutaneously injected it into 2.5-month-old APP/PS1 transgenic mice. Aß3-10-KLH immunization induced high levels of anti-Aß antibodies and significantly improved cognitive ability in APP/PS1 transgenic mice. Immunohistochemistry and immunofluorescence revealed that Aß3-10-KLH immunization significantly reduced cerebral amyloid plaque formation and alleviated gliosis. The results indicate that Aß3-10-KLH immunization successfully rescued cognitive impairment in APP/PS1 transgenic mice via decreasing cerebral Aß deposition and neuroinflammation. Aß3-10-KLH may potentially be safe and effective for prevention and treatment of AD.

An Aß3-10-KLH vaccine reduced Alzheimer's disease-like pathology and had a sustained effect in Tg-APPswe/PSEN1dE9 mice.

Alzheimer's disease is a neurodegenerative disease that affects many patients worldwide. The amyloid cascade hypothesis has been adopted by most researchers as the mechanism underlying Alzheimer's disease. Aß plaques have been considered the core factor in the neurotoxic effect in Alzheimer's disease, though some controversy remains. Further effort is necessary to elucidate the mechanism and to develop effective treatments. Previous studies have indicated that eliminating Aß plaques could improve synaptic plasticity and cognitive function. Researchers have developed various forms of vaccines to prevent Aß deposition or eliminate Aß plaques and have made some progress. We developed a new vaccine, Aß3-10-KLH, to increase the level of the anti-Aß immune response, and we show that this vaccine resulted in a sustained prevention of Aß deposition at 4 months after cessation of the vaccine treatment. At the same time point, the expression of synaptophysin and NMDAR2B in APP/PS1 transgenic mice was increased by immunization.

Active immunization with the peptide epitope vaccine Aß3-10-KLH induces a Th2-polarized anti-Aß antibody response and decreases amyloid plaques in APP/PS1 transgenic mice.

Active amyloid-ß (Aß) immunotherapy is effective in preventing Aß deposition, facilitating plaque clearance, and improving cognitive functions in mouse models of Alzheimer's disease (AD). Developing a safe and effective AD vaccine requires a delicate balance between inducing adequate humoral immune responses and avoiding T cell-mediated autoimmune responses. In this study, we designed 2 peptide epitope vaccines, Aß3-10-KLH and 5Aß3-10, prepared respectively by coupling Aß3-10 to the immunogenic carrier protein keyhole limpet hemocyanin (KLH) or by joining 5 Aß3-10 epitopes linearly in tandem. Young APP/PS1 mice were immunized subcutaneously with Aß3-10-KLH or 5Aß3-10 mixed with Freund's adjuvant, and the immunopotencies of these Aß3-10 peptide vaccines were tested. Aß3-10-KLH elicited a robust Th2-polarized anti-Aß antibody response and inhibited Aß deposition in APP/PS1 mice. However, 5Aß3-10 did not induce an effective humoral immune response. These results indicated that Aß3-10-KLH may be a safe and efficient vaccine for AD and that conjugating the antigen to a carrier protein may be more effective than linking multiple peptide antigens in tandem in applications for antibody production and vaccine preparation.

[Adsorption of crystal violet on activated sludge].

Crystal violet (CV) adsorption from aqueous solution on activated sludge (AS) and powdered activated carbon (PAC) was comparatively studied through batch jar tests. It was found that the adsorption isotherm of CV on AS satisfied both Langmuir and Freundlich models, while the adsorption of CV on PAC satisfied Freundlich model more than Langmuir model. The maximum adsorption capacity of CV on AS was 571.26 mg x g(-1), much higher than that on PAC, which was only 131.09 mg x g(-1). The adsorption of CV on AS was analyzed using pseudo first-order and pseudo second-order adsorption kinetic models, and the pseudo second-order kinetic model could better describe the adsorption. The impacts of stir speed and the ratio of AS/CV on CV adsorption were also investigated. Stir speed showed no effect on equilibrium CV concentration. At the AS/CV ratio of 10 : 1, the equilibrium CV concentration increased with increasing initial CV concentration, while the initial CV concentration showed no influence on equilibrium CV concentration at the AS/CV ratio of 20 : 1 or 50 : 1.