Artificial Neural Synapses Based on Microfluidic Memristors Prepared by Capillary Tubes and Ionic Liquid.

Neuromorphic simulation, i.e., the use of electronic devices to simulate the neural networks of the human brain, has attracted a lot of interest in the fields of data processing and memory. This work provides a new method for preparing a 1,3-dimethylimidazolium nitrate ([MMIm][NO3]:H2O) microfluidic memristor that is ultralow cost and technically uncomplicated. Such a fluidic device uses capillaries as memory tubes, which are structurally similar to interconnected neurons by simple solution treatment. When voltage is applied, the transmission of anions and cations in the tube corresponds to the release of neurotransmitters from the presynaptic membrane to the postsynaptic membrane. The change of synaptic weights (plasticity) also can be simulated by the gradual change of conductance of the fluid memristor. The learning process of microfluidic memristors is very obvious, and the habituation and recovery behaviors they exhibit are extremely similar to biological activities, representing its good use for simulating neural synapses.

Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson's Disease.

Parkinson's disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether the neuroprotective function of NaB on PD was mediated by the modulation of gut microbial dysbiosis and revealed its possible mechanisms. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to construct the PD model. NaB gavage was given 2 h after the daily MPTP injections for 21 days. NaB improved the motor functioning of PD mice, increased striatal neurotransmitter levels, and reduced the death of dopaminergic neurons. The 16S rRNA sequencing analysis revealed that NaB restored the gut microbial dysbiosis. NaB also attenuated the intestinal barrier's disruption and reduced serum, colon, and striatal pro-inflammatory cytokines, along with inhibiting the overactivation of glial cells, suggesting an inhibitory effect on inflammation from NaB throughout the gut-brain axis of the PD mice. Mechanistic studies revealed that NaB treatment suppressed the TLR4/MyD88/NF-kB pathway in the colon and striatum. In summary, NaB had a neuroprotective impact on the PD mice, likely linked to its regulation of gut microbiota to inhibit gut-brain axis inflammation.

Characteration of a novel arylesterase from probiotics Lacticaseibacillus rhamnosus GG with the preference for medium- and long-chain p-Nitrophenyl esters.

We prospected a novel arylesterase LggEst from the probiotics Lacticaseibacillus rhamnosus GG by genome mining strategy, and characterized the enzymatic properties in detail. Biochemical characterization revealed that arylesterase LggEst presented high activity at a wide range of temperatures from 25 to 65 °C with maximum activity at 50 °C. LggEst maintained high activity in the pH range from 5.5 to 7.5 with optimum pH of 6.5. LggEst might efficiently hydrolyze a series of aryl substrates p-nitrophenyl esters with different acyl chain lengths. LggEst displayed the Vmax from 2.8 to 77.3 µmol min-1 mg-1 protein and the k cat from 1.8 to 48.8 s-1 with the highest catalytic activity on pNPC6. The K M of LggEst on different substrates varied significantly from 4.9 µM to 5.6 mM with the highest affinity on pNPC10. LggEst exhibited the preference for medium- and long-chain p-nitrophenyl esters. LggEst showed remarkable thermostability at 45 °C. LggEst could be tolerant of several organic solvents at the concentration of 10% and DMSO and methanol at the concentration of 20%. Catalytic activity of LggEst was improved by 12% in the presence of 20% ethylene glycol. LggEst was resistant to high concentrations of sodium citrate and sodium chloride. Notably, enzymatic activity of LggEst was significantly enhanced in the presence of 0.1% sodium deoxycholate at high temperatures. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03053-7.

Bloodletting Puncture at Hand Twelve Jing-Well Points Relieves Brain Edema after Severe Traumatic Brain Injury in Rats via Inhibiting MAPK Signaling Pathway.

OBJECTIVE: To investigate whether blood-brain barrier (BBB) served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points (HTWP) in traumatic brain injury (TBI) and the potential molecular signaling pathways. METHODS: Adult male Sprague-Dawley rats were assigned to the sham-operated (sham), TBI, and bloodletting puncture (bloodletting) groups (n=24 per group) using a randomized number table. The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days. The neurological function and cerebral edema were evaluated by modified neurological severity score (mNSS), cerebral water content, magnetic resonance imaging and hematoxylin and eosin staining. Cerebral blood flow was measured by laser speckles. The protein levels of aquaporin 4 (AQP4), matrix metalloproteinases 9 (MMP9) and mitogen-activated protein kinase pathway (MAPK) signaling were detected by immunofluorescence staining and Western blot. RESULTS: Compared with TBI group, bloodletting puncture improved neurological function at 24 and 48 h, alleviated cerebral edema at 48 h, and reduced the permeability of BBB induced by TBI (all P<0.05). The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture (P<0.05 or P<0.01). In addition, the extracellular signal-regulated kinase (ERK) and p38 signaling pathways were inhibited by bloodletting puncture (P<0.05). CONCLUSIONS: Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways. Therefore, bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.

Determination of residues of 446 pesticides in fruits and vegetables by three-cartridge solid-phase extraction-gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry.

A method was developed for determination of residues of 446 pesticides in fruits and vegetables through the use of cleanup by a 3-cartridge solid-phase extraction-gas chromatography/ mass spectrometry (GC/MS) and liquid chromatography/tandem mass spectrometry (LC/MS/MS). Fruit and vegetable samples (20 g) were extracted with 40 mL acetonitrile, salted out, and centrifuged. Half of the supernatant was passed into an Envi-18 cartridge, eluted with acetonitrile, and cleaned up with Envi-Carb and aminopropyl Sep-Pak cartridges in series after concentration of the eluates. Pesticides were eluted with acetonitrile-toluene (3 + 1, v/v), and eluates were concentrated to 0.5 mL and then added into internal standards after solvent exchange with 2 mL hexane and used for determination of 383 pesticides by GC/MS. The other half of the supernatant was concentrated to 1 mL and cleaned up with Envi-Carb and aminopropyl Sep-Pak cartridges in series. Pesticides were eluted with acetonitrile-toluene (3 + 1, v/v), and the eluates were concentrated to 0.5 mL, dried with nitrogen gas, diluted to 1.0 mL with acetonitrile-water (3 + 2, v/v), and used for determination of 63 pesticides by LC/MS/MS. The limit of detection for the method was 0.2-600 ng/g depending on the individual pesticide. In the method, fortification recovery tests at high, medium, and low levels were conducted on 6 varieties of fruits and vegetables, i.e., apples, oranges, grapes, cabbage, tomatoes, and celery, with average recoveries falling within the range of 55.0-133.8% for 446 pesticides, among which average recoveries between 60.0-120.0% accounted for 99% of the results. The relative standard deviation was between 2.1-39.1%, of which a relative standard deviation of 2.1-25.0% made up 96% of the results. Experiments proved that the method was applicable for determination of residues of 446 pesticides in fruit and vegetables.

Validation study on 660 pesticide residues in animal tissues by gel permeation chromatography cleanup/gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry.

A new method using gel permeation chromatography (GPC) cleanup followed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) has been established for quantitative determination of 437 pesticide residues in animal tissues such as beef, mutton, pork, chicken, and rabbit. Based on an appraisal of the characteristics of both GC-MS and LC-MS-MS, validation experiments were conducted for 660 pesticides. In the method, 10 g animal samples were mixed with 20 g sodium sulfate and extracted with 35 mL of cyclohexane+ethyl acetate (1+1) twice by blender homogenization, centrifugation, and filtration. Evaporation was conducted and an equivalent of 5 g sample was injected into a 400 mm x 25 mm S-X3 GPC column, with cyclohexane+ethyl acetate (1+1) as the mobile phase at a flow rate of 5 mL/min. The 22-40 min fraction was collected for subsequent analysis. For the 368 pesticides determined by GC-MS, the portions collected from GPC were concentrated to 0.5 mL and exchanged with 5 mL hexane twice. For the 69 pesticides by LC-MS-MS, the portions collected from GPC were dissolved with acetonitrile+water (60+40) after taking the extract to dryness with nitrogen gas. In the linear range of each pesticide, the correlation coefficient was r > or = 0.98, exceptions being dinobuton, linuron, and fenamiphos sulfoxide. At the low, medium and high three fortification levels of 0.2-4800 microg/kg, recoveries fell within 40-120%, among which 417 pesticides recoveries between 60% and 120%, accounting for 95%, 20 analytes between 40% and 60%, accounting for 5%. The relative standard deviation was below 28% for all 437 pesticides. The limits of detection for the method were 0.2-600 microg/kg, depending on each pesticide.

Simultaneous determination of 405 pesticide residues in grain by accelerated solvent extraction then gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry.

A new method has been established for simultaneous determination of 405 pesticide residues in grain, using accelerated solvent extraction (ASE), solid-phase extraction (SPE), and GC-MS and LC-MS-MS. The method was based on appraisal of the GC-MS and LC-MS-MS characteristics of 660 pesticides, their efficiency of extraction from grain, and their purification. Samples of grain (10 g) were mixed with Celite 545 (10 g) and the mixture was placed in a 34-mL cell of an accelerated solvent extractor and extracted with acetonitrile in the static state for 3 min with two cycles at 1,500 psig and at 80 degrees C. For the 362 pesticides determined by GC-MS, half of the extracts were cleaned with an Envi-18 cartridge and then further cleaned with Envi-Carb and Sep-Pak NH2 cartridges in series. The pesticides were eluted with acetonitrile-toluene, 3:1, and the eluates were concentrated and used for analysis after being exchanged with hexane twice. For the 43 pesticides determined by LC-MS-MS the other half of the extracts were cleaned with Sep-Pak Alumina N cartridge and further cleaned with Envi-Carb and Sep-Pak NH2 cartridges. Pesticides were eluted with acetonitrile-toluene, 3:1. After evaporation to dryness the eluates were diluted with acetonitrile-water, 3:2, and used for analysis. In the linear range of each pesticide the linear correlation coefficient r was equal to or greater than 0.956 and 94% of linear correlation coefficients were greater than 0.990. At low, medium, and high fortification levels, at the limit of detection (LOD), twice the LOD and ten times LOD, respectively, recoveries ranged from 42 to 132%; for 382 pesticides, or 94.32%, recovery was from 60 to 120%. The relative standard deviation (RSD) was always below 38% and was below 30% for 391 pesticides, or 96.54%. The LOD was 0.0005-0.3000 mg kg(-1). The proposed method is suitable for determination of 405 pesticide residues in grain such as maize, wheat, oat, rice, and barley, etc.