Bile acid metabolism is altered in learning and memory impairment induced by chronic lead exposure.

Lead is a neurotoxic contaminant that exists widely in the environment. Although lead neurotoxicity has been found to be tightly linked to gut microbiota disturbance, the effect of host metabolic disorders caused by gut microbiota disturbance on lead neurotoxicity has not been investigated. In this work, the results of new object recognition tests and Morris water maze tests showed that chronic low-dose lead exposure caused learning and memory dysfunction in mice. The results of 16 S rRNA sequencing of cecal contents and fecal microbiota transplantation showed that the neurotoxicity of lead could be transmitted through gut microbiota. The results of untargeted metabolomics and bile acid targeted metabolism analysis showed that the serum bile acid metabolism profile of lead-exposed mice was significantly changed. In addition, supplementation with TUDCA or INT-777 significantly alleviated chronic lead exposure-induced learning and memory impairment, primarily through inhibition of the NLRP3 inflammasome in the hippocampus to relieve neuroinflammation. In conclusion, our findings suggested that dysregulation of host bile acid metabolism may be one of the mechanisms of lead-induced neurotoxicity, and supplementation of specific bile acids may be a possible therapeutic strategy for lead-induced neurotoxicity.

Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway.

Lead is an environmentally widespread neurotoxic pollutant. Although the neurotoxicity of lead has been found to be closely associated with metabolic disorders, the effects of short-chain fatty acids on the neurotoxicity of lead and its mechanisms have not yet been explored. In this study, the results of open field tests and Morris water maze tests demonstrated that chronic lead exposure caused learning and memory deficits and anxiety-like symptoms in mice. The serum butyric acid content of lead-treated mice decreased in a dose-dependent manner, and oral administration of butyrate significantly improved cognitive memory impairment and anxiety symptoms in lead-exposed mice. Moreover, butyrate alleviated neuroinflammation caused by lead exposure by inhibiting the STAT3 signaling in microglia. Butyrate also promoted the expression of acetyl-CoA synthetase ACSS2 in hippocampal neurons, thereby increasing the content of acetyl-CoA and restoring the expression of both histone H3K9ac and the downstream BDNF. We also found that the median butyric acid concentration in high-lead exposure humans was remarkably lower than that in the low-lead exposure humans (45.16 µg/L vs. 60.92 µg/L, P < 0.01), and that butyric acid significantly mediated the relationship of lead exposure with the Montreal cognitive assessment scores, with a contribution rate of 27.57 %. In conclusion, our results suggest that butyrate supplementation is a possible therapeutic strategy for lead-induced neurotoxicity.

Studying Plant ER-PM Contact Site Localized Proteins Using Microscopy.

As in most eukaryotic cells, the plant endoplasmic reticulum (ER) network is physically linked to the plasma membrane (PM), forming ER-PM contact sites (EPCS). The protein complex required for maintaining the EPCS is composed of ER integral membrane proteins (e.g., VAP27, synaptotagmins), PM-associated proteins (e.g., NET3C), and the cytoskeleton. Here, we describe methods for studying EPCS structures and identifying possible EPCS-associated proteins. These include using artificially constructed reporters, GFP tagged protein expression followed by image analysis, and immunogold labelling at the ultrastructural level. In combination, these methods can be used to identify the location of putative EPCS proteins, which can aid in predicting their potential subcellular function.

Iterative learning fault diagnosis and fault tolerant control for stochastic repetitive systems with Brownian motion.

In this paper, the issue of iterative learning fault diagnosis (ILFD) and fault tolerant control (FTC) is studied for stochastic repetitive systems with Brownian motion. Different from existing fault diagnosis (FD) methods, a state/fault simultaneous estimation observer based on iterative learning method is designed. The convergence condition of the ILFD algorithm is given. By employing the fault estimation information, the FTC algorithm is proposed to compensate for the fault effect on the system and to keep the stochastic input-to-state stability of the control system. Finally, the simulation results of an induction motor system and a single-link robotic flexible manipulator system are given to show that the proposed method is validated.

Fault Diagnosis and Minimum Rational Entropy Fault Tolerant Control of Stochastic Distribution Collaborative Systems.

In this paper, a fault-tolerant control scheme is presented for a class of stochastic distribution collaborative control systems, which are composed of three subsystems connected in series to complete the control target. The radial basis function neural network is used to approximate the output probability density function of the third subsystem, which is also the output of the entire system. When fault occurs in the first subsystem, an adaptive diagnostic observer is designed to estimate the value of fault. However, the first subsystem does not have the ability of self-recovery, minimum rational entropy controllers are designed in the latter subsystems to compensate the influence of the fault and minimize the entropy of the system output. A numerical simulation is given to verify the effectiveness of the proposed scheme.

A new supramolecular gel via host-guest complexation with cucurbit[8]uril and N-(4-diethylaminobenzyl)chitosan.

A novel supramolecular gel has been prepared via host-guest interaction between cucurbit[8]uril (Q[8]) and N-(4-diethylaminobenzyl)chitosan (EBCS). The structure of supramolecular gel has been characterized. The spectrum of (1)H NMR demonstrated the benzene ring of EBCS is reside inside the hydrophobic cavity of Q[8] and the host-guest interaction between Q[8] and EBCS was the main driving force for the formation of the supramolecular gel. The network structure of the xerogel of Q[8]/EBCS gel was observed by SEM. The Q[8]/EBCS gel system showed thermosensitive and pH-sensitive properties. The physical characterization by SEM, DSC, TG demonstrated the distinguished characters, which proved the formation of supramolecular gel instead of physical blending. The in vitro release study of the 5-fluorouracil-loaded supramolecular gel showed that sustained release profile in acidic condition, suggesting that Q[8]/EBCS gel could be a potential carrier for pH-sensitive drug controlled release system.

Preparation of a crosslinked bioimprinted lipase for enrichment of polyunsaturated fatty acids from fish processing waste.

Geotrichum sp. lipase modified with a combined method composed of crosslinking and bioimprinting was employed to selectively hydrolyze waste fish oil for enrichment of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in glycerides. Crosslinked polymerization by monomer (polyethylene glycol 400 dimethyl acrylate), crosslinker (trimethylolpropane trimethylacrylate), and photoinitiator (benzoin methyl ether) coupled to bioimprinting using palmitic acid as imprint molecule, resulted in much more effective enzyme preparation used in aqueous hydrolysis reaction. Since the crosslinked polymerization modification maintained bioimprinted property and gave good dispersion of enzyme in reaction mixture, the crosslinked bioimprinted enzyme exhibited higher hydrolysis temperature, enhanced specific activity, shorter hydrolysis time, and better operational stability compared to free lipase. Crude fish oil was treated at 45 degrees C with this crosslinked bioimprinted lipase for 8 h, and 46% hydrolysis degree resulted in the production of glycerides containing 41% of EPA and DHA (EPA+DHA), achieving 85.7% recovery of initial EPA and DHA. The results suggested that bioimprinted enzymes did not lose their induced property in aqueous environment when prepared according to the described crosslinking-bioimprinting method. It could also be seen that the crosslinked bioimprinted lipase was effective in producing glycerides that contained a higher concentration of polyunsaturated fatty acid with better yield.