Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes

Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.

Development of self-generated proppant based on modified low-density and low-viscosity epoxy resin and its evaluation

Hydraulic fracturing is a critical technology for the economic development of unconventional oil and gas reservoirs.The main factor influencing fracture propping and reservoir stimulation effect is proppant performance.The increasing depth of fractured oil and gas reservoirs is causing growing difficulty in hydraulic fracturing.Moreover,the migration of conventional proppants within the fracture is always limited due to small fracture width and rigid proppant structure.Thus,proppants with good transportation capacity and fracture propping effects are needed.First,a novel self-generated proppant based on toughened low-viscosity and low-density epoxy resin was developed to satisfy this demand.Then,proppant performances were evaluated.Low-viscosity and low-density epoxy resin was generated when the thiol-ene click chemical reaction product of eugenol and 1-thioglycerol reacts with the epichlorohydrin.Then,the resin was toughened with graphite particles to increase its compressive strength from50.8 to 72.1 MPa based on micro-cracking mechanism and crazing-nail anchor mechanism.The adduct of diethylene triamine and butyl glycidyl ether and the Si O2 nanoparticles were treated as the curing agent and emulsifier respectively to form the emulsion.The emulsion is transformed into solid particles of various sizes within a reservoir to prop the fracture.Evaluation shows good migration capacity of this self-generated proppant due to the low density of epoxy resin.

Cognitive impairment after traumatic brain injury is associated with reduced long-term depression of excitatory postsynaptic potential in the rat hippocampal dentate gyrus

Traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal excitability is strongly correlated with cognitive dysfunction and remote symptomatic epilepsy. In this study, we examined the relationship between traumatic brain injury-induced neuronal loss and subsequent hippocampal regional excitability. We used hydraulic percussion to generate a rat model of traumatic brain injury. At 7 days after injury, the mean modified neurological severity score was 9.5, suggesting that the neurological function of the rats was remarkably impaired. Electrophysiology and immunocytochemical staining revealed increases in the slope of excitatory postsynaptic potentials and long-term depression（indicating weakened long-term inhibition）, and the numbers of cholecystokinin and parvalbumin immunoreactive cells were clearly reduced in the rat hippocampal dentate gyrus. These results indicate that interneuronal loss and changes in excitability occurred in the hippocampal dentate gyrus. Thus, traumatic brain injury-induced loss of interneurons appears to be associated with reduced long-term depression in the hippocampal dentate gyrus.

Microstructural evolution and sintering kinetics during spark plasma sintering of Fe and Al blended powder

The reaction diffusion between Fe and Al during spark plasma sintering(SPS)was studied.Microstructural evolution wasinvestigated by X-ray diffraction(XRD)and scanning electron microscopy(SEM)and the sintering kinetics was disclosed.The maininterphase of the SPS sample was Fe2Al5at773-873K.Ball-milling enabled a large number of lattice defects and grain boundariesthus the reaction kinetics was accelerated,although the direct current can also promote those defects.After milling,the phasetransformation kinetics was improved from0.207before mill to4.56×10-3.Besides,this work provided more details for thegeneration of Joule heating.The resistance offered to the electric path was considered to be the source of Joule heating,andparticularly the resistance offered by the different contact interfaces of die,punch,graphite foil and the sample played a leading rolefor the generation of Joule heating during spark plasma sintering.

NO_(x) removal by non-thermal plasma reduction:experimental and theoretical investigations

Green and efficient NO_(x)removal at low temperature is still desired.NO_(x)removal via non-thermal plasma(NTP)reduction is one of such technique.This work presents the experimental and theoretical study on the NO_(x)removal via NTP reduction(NTPRD)in dielectric barrier discharge reactor(DBD).The effect of O_(2)molar fraction on NO_(x)species in the outlet of DBD,and effects of NH_(3)/NO_(x)molar ratio and discharge power of DBD on NO_(x)removal efficiency are investigated.Results indicate that anaerobic condition and higher discharge power is beneficial to direct removal of NO_(x),and the NO_(x),removal efficiency can be up to 98.5%under the optimal operating conditions.It is also found that adding NH_(3)is favorable for the reduction of NO_(x),to N_(2)at lower discharge power.In addition,the NO_(x)removal mechanism and energy consumption analysis for the NTPRD process are also studied.It is found that the reduced active species(N^(+),N^(-),N^(+),N_(2)^(*),NH_(2)^(+),etc.)generated in the NTPRD process play important roles for the reduction of NO_(x),to N_(2).Our work paves a novel pathway for NO_(x)removal from anaerobic gas in industrial application.