Chemometrics and genome mining reveal an unprecedented family of sugar acid-containing fungal nonribosomal cyclodepsipeptides.

Xylomyrocins, a unique group of nonribosomal peptide secondary metabolites, were discovered in Paramyrothecium and Colletotrichum spp. fungi by employing a combination of high-resolution tandem mass spectrometry (HRMS/MS)-based chemometrics, comparative genome mining, gene disruption, stable isotope feeding, and chemical complementation techniques. These polyol cyclodepsipeptides all feature an unprecedented d-xylonic acid moiety as part of their macrocyclic scaffold. This biosynthon is derived from d-xylose supplied by xylooligosaccharide catabolic enzymes encoded in the xylomyrocin biosynthetic gene cluster, revealing a novel link between carbohydrate catabolism and nonribosomal peptide biosynthesis. Xylomyrocins from different fungal isolates differ in the number and nature of their amino acid building blocks that are nevertheless incorporated by orthologous nonribosomal peptide synthetase (NRPS) enzymes. Another source of structural diversity is the variable choice of the nucleophile for intramolecular macrocyclic ester formation during xylomyrocin chain termination. This nucleophile is selected from the multiple available alcohol functionalities of the polyol moiety, revealing a surprising polyspecificity for the NRPS terminal condensation domain. Some xylomyrocin congeners also feature N-methylated amino acid residues in positions where the corresponding NRPS modules lack N-methyltransferase (M) domains, providing a rare example of promiscuous methylation in the context of an NRPS with an otherwise canonical, collinear biosynthetic program.

Re-Engineering Fungal Nonribosomal Peptide Synthetases by Module Dissection and Duplicated Thiolation Domains.

Unnatural product (uNP) nonribosomal peptides promise to be a valuable source of pharmacophores for drug discovery. However, the extremely large size and complexity of the nonribosomal peptide synthetase (NRPS) enzymes pose formidable challenges to the production of such uNPs by combinatorial biosynthesis and synthetic biology. Here we report a new NRPS dissection strategy that facilitates the engineering and heterologous production of these NRPSs. This strategy divides NRPSs into "splitting units", each forming an enzyme subunit that contains catalytically independent modules. Functional collaboration between the subunits is then facilitated by artificially duplicating, at the N-terminus of the downstream subunit, the linker - thiolation domain - linker fragment that is resident at the C-terminus of the upstream subunit. Using the suggested split site that follows a conserved motif in the linker connecting the adenylation and the thiolation domains allows cognate or chimeric splitting unit pairs to achieve productivities that match, and in many cases surpass those of hybrid chimeric enzymes, and even those of intact NRPSs, upon production in a heterologous chassis. Our strategy provides facile options for the rational engineering of fungal NRPSs and for the combinatorial reprogramming of nonribosomal peptide production.

Nocardioides cremeus sp. nov., Nocardioides abyssi sp. nov. and Nocardioides oceani sp. nov., three actinobacteria isolated from Western Pacific Ocean sediment.

Three Gram-stain-positive, non-motile, short rod-shaped, catalase-positive and oxidase-negative actinomycete strains (SOB44T, SOB72T and SOB77T) were isolated from a deep-sea sediment sample collected from the Western Pacific Ocean. Cells of the three strains showed optimum growth at 30 °C and pH 7.0. Strains SOB44T, SOB72T and SOB77T could tolerate up to 10, 9 and 9 % (w/v) NaCl concentration and grow at pH 5.0-12.0, 5.0-11.0 and 5.0-11.0, respectively. Phylogenetic results based on 16S rRNA gene sequences showed that the three isolates belonged to the genus Nocardioides and were identified as representing three novel species based on 78.0-93.1 % average nucleotide identity and 21.3-50.0 % DNA-DNA hybridization values with closely related reference strains. Strains SOB44T, SOB72T and SOB77T showed highest 16S rRNA gene sequence similarity to Nocardioides salarius CL-Z59T (99.2 %), Nocardioides deserti SC8A-24T (99.2 %) and Nocardioides marmotae zg-579T (98.5 %), respectively. All three strains had MK-8(H4) as the respiratory quinone, iso-C16 : 0 as the major fatty acid, and phosphatidylglycerol, diphosphatidylglycerol and phosphatidylinositol as the major polar lipids. The diagnostic diamino acid in the cell-wall peptidoglycan of all three isolates was ll-diaminopimelic acid. The DNA G+C contents of strains SOB44T, SOB72T and SOB77T were 71.1, 72.9 and 72.9 mol%, respectively. Based on the phenotypic, phylogenetic and genotypic data, strains SOB44T, SOB72T and SOB77T clearly represent three novel taxa within the genus Nocardioides, for which the names Nocardioides cremeus sp. nov. (type strain SOB44T=JCM 35774T= MCCC M28400T), Nocardioides abyssi sp. nov. (type strain SOB72T=JCM 35775T=MCCC M28318T) and Nocardioides oceani sp. nov. (type strain SOB77T=JCM 35776T=MCCC M28544T) are proposed.

Impedance spectroscopy for identifying tau protein to monitor anesthesia-based issues.

Anesthesia-related drugs cause various side effects and health-related illnesses after surgery. In particular, neurogenerative disorder is a common problem of anesthesia-related drugs. A patient gets anesthesia as a requirement of the preoperative evaluation to diagnose the medical illness, which is caused by anesthetic drug treatment. Different blood-based biomarkers help in identifying the changes appearing in patients after anesthesia treatment. Among them, tau protein is a sensitive biomarker of neurodegenerative diseases, and the fluctuations in tau proteins are highly associated with various diseases. Furthermore, researchers have found unstable levels of tau protein after the anesthesia process. The current research has focused on quantifying tau protein via impedance spectroscopy to identify the problems caused by anesthesia-related drugs. An impedance spectroscopy electrode was modified into a multiwalled carbon nanotube, and an amine-ended aptamer was then attached. This electrode surface was used to quantify the tau protein level and reached the detection limit of 1 fM. The determination coefficient was found to be y = 369.93x + 1144.9, with R2 = 0.9846 in the linear range of 1 fM-1 nM. Furthermore, tau protein spiked human serum was clearly identified on the immobilized aptamer surface, indicating the specific detection.

Interactions between Two Kinds of Gold Nanoclusters and Calf Thymus Deoxyribonucleic Acid: Directions for Preparations to Applications.

Gold nanoclusters (AuNCs) have shown promising applications in biotherapy owing to their ultrasmall size and unique molecular-like properties. In order to better guide the preparations and applications of AuNCs, dihydrolipoic acid-protected AuNCs (DHLA-AuNCs) and glutathione-protected AuNCs (GSH-AuNCs) were selected as models and the interactions between them and calf thymus DNA (ctDNA) were studied in detail. The results showed that there was a small difference in the binding mechanisms and forces between both AuNCs and ctDNA. The quenching mechanisms of both AuNCs to (ctDNA-HO) were completely different. The binding constants indicated that the binding strength between DHLA-AuNCs and ctDNA was greater than those of GSH-AuNCs. The conformation investigations showed that GSH-AuNCs had a greater impact on the conformation of ctDNA, and both AuNCs were more inclined to interact with the A-T base pairs of ctDNA. These results indicate that the surface ligand had a significant effect on the interactions between AuNCs and DNA and might also further affect the applications of AuNCs, and these results could guide the preparations of AuNCs. For DHLA-AuNCs, their good biocompatibility made them a potential candidate for application in imaging, drug treatment, sensing, and so on. The resulting base accumulation of ctDNA and weak interactions made GSH-AuNCs have great potential for application in gene therapy, which was consistent with the current reports on the applications of these two AuNCs. This work has pointed out the directions for the preparations and applications of AuNCs.

Research on the fate of polymeric nanoparticles in the process of the intestinal absorption based on model nanoparticles with various characteristics: size, surface charge and pro-hydrophobics.

BACKGROUND: The use of drug nanocarriers to encapsulate drugs for oral administration may become an important strategy in addressing the challenging oral absorption of some drugs. In this study-with the premise of controlling single variables-we prepared model nanoparticles with different particle sizes, surface charges, and surface hydrophobicity/hydrophilicity. The two key stages of intestinal nanoparticles (NPs) absorption-the intestinal mucus layer penetration stage and the trans-intestinal epithelial cell stage-were decoupled and analyzed. The intestinal absorption of each group of model NPs was then investigated. RESULTS: Differences in the behavioral trends of NPs in each stage of intestinal absorption were found to result from differences in particle properties. Small size, low-magnitude negative charge, and moderate hydrophilicity helped NPs pass through the small intestinal mucus layer more easily. Once through the mucus layer, an appropriate size, positive surface charge, and hydrophobic properties helped NPs complete the process of transintestinal epithelial cell transport. CONCLUSIONS: To achieve high drug bioavailability, the basic properties of the delivery system must be suitable for overcoming the physiological barrier of the gastrointestinal tract.

The regulation of BbLaeA on the production of beauvericin and bassiatin in Beauveria bassiana.

Beauvericin and bassiatin are two valuable compounds with various bioactivities biosynthesized by the supposedly same nonribosomal peptide synthetase BbBEAS in entomopathogenic fungus Beauveria bassiana. To evaluate the regulatory effect of global regulator LaeA on their production, we constructed BbLaeA gene deletion and overexpression mutants, respectively. Deletion of BbLaeA resulted in a decrease of the beauvericin titer, while overexpression of BbLaeA increased its production by 1-2.26 times. No bassiatin could be detected in ΔBbLaeA and wild type strain of B. bassiana, but 4.26-5.10 µg/mL bassiatin was produced in OE::BbLaeA. Furthermore, additional metabolites with increased production in OE::BbLaeA were isolated and identified as primary metabolites. Among them, 4-hydroxyphenylacetic acid showed antibacterial bioactivity against Ralstonia solanacearum. These results indicated that BbLaeA positively regulates the production of beauvericin, bassiatin and various bioactive primary metabolites.

Intelligent Escape System for the Oral Delivery of Liraglutide: A Perfect Match for Gastrointestinal Barriers.

Epithelial cells are known to impede the oral delivery of polypeptides, and the accumulation of mucus and regular dynamic renewal also significantly impede drug absorption. In this work, we prepared a core-shell (COS) nanosystem using poly-N-(2-hydroxypropyl)methacrylamide (pHPMA)/chitosan (CTS). Liraglutide (NN2211) was isolated from the gastrointestinal environment and smoothly passes through the mucous layer. CSKSSDYQC (CSK) peptide and hemagglutinin-2 (HA2) were introduced into the COS nanosystem to establish a complete path from the oral cavity to the epithelial basal side. The fate of nanocapsules in vivo was studied by fluorescence detection. The results showed that the nanocapsules escaped smoothly from the mucus. Taking into account the characteristics of CSK targeting goblet cells, we conducted cell-level studies, and the results showed that after the modification of CSK and pHPMA, more nanocapsules entered the cells. In vitro and in vivo evaluation results showed that the system successfully established a complete path from mucus to epithelial cells by responding to the gastrointestinal environment multiple times.

Thermodynamics, Kinetics and Mechanisms of Noncompetitive Allosteric Inhibition of Chymotrypsin by Dihydrolipoic Acid-Coated Gold Nanoclusters.

Enzymes are an important class of biomacromolecules which catalyze many metabolic processes in living systems. Nanomaterials can be synthesized with tailored sizes as well as desired surface modifications, thus acting as promising enzyme regulators. Fluorescent gold nanoclusters (AuNCs) are a representative class of ultrasmall nanoparticles (USNPs) with sizes of ∼2 nm, smaller than most of proteins including enzymes. In this work, we chose α-chymotrypsin (ChT) and AuNCs as the model system. Activity assays and inhibition kinetics studies showed that dihydrolipoic acid (DHLA)-coated AuNCs (DHLA-AuNCs) had a high inhibitory potency (IC50 = 3.4 µM) and high inhibitory efficacy (>80%) on ChT activity through noncompetitive inhibition mechanism. In distinct contrast, glutathione (GSH)-coated AuNCs (GSH-AuNCs) had no significant inhibition effects. Fluorescence spectroscopy, agarose gel electrophoresis and circular dichroism (CD) spectroscopy were conducted to explore the underlying mechanisms. A two-step interaction model was proposed. First, both DHLA-AuNCs and GSH-AuNCs might be bound to the positively charged sites of ChT through electrostatic forces. Second, further hydrophobic interactions occurred between three tyrosine residues of ChT and the hydrophobic carbon chain of DHLA, leading to a significant structural change thus to deactivate ChT on the allosteric site. On the contrary, no such interactions occurred with GSH of zwitterionic characteristic, which explained no inhibitory effect of GSH-AuNCs on ChT. To the best of our knowledge, this is the first example of the allosteric inhibition of ChT by nano regulators. These findings provide a fundamental basis for the design and development of nano regulators.

A Multifrequency Brain Network-Based Deep Learning Framework for Motor Imagery Decoding.

Motor imagery (MI) is an important part of brain-computer interface (BCI) research, which could decode the subject's intention and help remodel the neural system of stroke patients. Therefore, accurate decoding of electroencephalography- (EEG-) based motion imagination has received a lot of attention, especially in the research of rehabilitation training. We propose a novel multifrequency brain network-based deep learning framework for motor imagery decoding. Firstly, a multifrequency brain network is constructed from the multichannel MI-related EEG signals, and each layer corresponds to a specific brain frequency band. The structure of the multifrequency brain network matches the activity profile of the brain properly, which combines the information of channel and multifrequency. The filter bank common spatial pattern (FBCSP) algorithm filters the MI-based EEG signals in the spatial domain to extract features. Further, a multilayer convolutional network model is designed to distinguish different MI tasks accurately, which allows extracting and exploiting the topology in the multifrequency brain network. We use the public BCI competition IV dataset 2a and the public BCI competition III dataset IIIa to evaluate our framework and get state-of-the-art results in the first dataset, i.e., the average accuracy is 83.83% and the value of kappa is 0.784 for the BCI competition IV dataset 2a, and the accuracy is 89.45% and the value of kappa is 0.859 for the BCI competition III dataset IIIa. All these results demonstrate that our framework can classify different MI tasks from multichannel EEG signals effectively and show great potential in the study of remodelling the neural system of stroke patients.

Synthesis of CSK-DEX-PLGA Nanoparticles for the Oral Delivery of Exenatide to Improve Its Mucus Penetration and Intestinal Absorption.

The oral absorption of exenatide, a drug for type 2 diabetes treatment, can be improved by using nanoparticles (NPs) for its delivery. To improve the mucus penetration and intestinal absorption of exenatide, we designed a block copolymer, CSKSSDYQC-dextran-poly(lactic-co-glycolic acid) (CSK-DEX-PLGA), and used it for the preparation of exenatide-loaded NPs. The functionalized exenatide-loaded NPs composed of CSK-DEX-PLGA were able to target intestinal epithelial cells and reduce the mucus-blocking effect of the intestine. Moreover, the CSK modification of DEX-PLGA was found to significantly promote the absorption efficiency of NPs in the small intestine based on in vitro ligation of the intestinal rings and an examination of different intestinal absorption sites. Compared to DEX-PLGA-NPs (DPs), the absorption of CSK-DEX-PLGA-NPs (CDPs) was increased in the villi, allowing the drug to act on gobletlike Caco-2 cells through clathrin-, caveolin-, and gap-mediated endocytosis. Furthermore, the enhanced transport ability of CDPs was observed in a study on Caco-2/HT-29-MTX cocultured cells. CDPs exhibited a prolonged hypoglycemic response with a relative bioavailability of 9.2% in diabetic rats after oral administration. In conclusion, CDPs can target small intestinal goblet cells and have a beneficial effect on the oral administration of macromolecular peptides as a nanometer-sized carrier.

Aquatic obstacle training improves freezing of gait in Parkinson's disease patients: a randomized controlled trial.

OBJECTIVE: Our aim was to evaluate the effect of aquatic obstacle training on balance parameters in comparison with a traditional aquatic therapy in patients with Parkinson's disease. DESIGN: A randomized single-blind controlled trial. SETTING: Outpatients in the rehabilitation department. SUBJECTS: A total of 46 patients with Parkinson's disease in Hoehn-Yahr stage 2-3. INTERVENTIONS: Participants were randomly assigned to (1) aquatic therapy or (2) obstacle aquatic therapy. All participants undertook aquatic therapy for 30 minutes, five times per week for six weeks. MAIN MEASURES: The Freezing of Gait Questionnaire, Functional Reach Test, Timed Up and Go test and Berg Balance Scale were assessed at baseline, posttreatment and at six-month follow-up. RESULTS: Both groups of patients had improved primary outcomes after the training program. A between-group comparison of the changes revealed that obstacle aquatic therapy was significantly higher for the Freezing of Gait Questionnaire (after treatment: 8.7 ± 3.3 vs 6.2 ± 2.1, P = 0.004; posttest: 7.7 ± 3.1 vs 5.3 ± 2.0, P = 0.003) and Timed Up and Go test (after treatment: 17.1 ± 2.9 vs 13.8 ± 1.9, P < 0.001; posttest: 16.3 ± 2.8 vs 12.9 ± 1.4, P < 0.001). CONCLUSION: Obstacle aquatic therapy in this protocol seems to be more effective than traditional protocols for gait and balance in patients with Parkinson's disease, and the effect lasts for six months.

Thermodynamics and Mechanisms of the Interactions between Ultrasmall Fluorescent Gold Nanoclusters and Human Serum Albumin, γ-Globulins, and Transferrin: A Spectroscopic Approach.

Noble metal nanoclusters (NCs) show great promise as nanoprobes for bioanalysis and cellular imaging in biological applications due to ultrasmall size, good photophysical properties, and excellent biocompatibility. In order to achieve a comprehensive understanding of possible biological implications, a series of spectroscopic measurements were conducted under different temperatures to investigate the interactions of Au NCs (∼1.7 nm) with three model plasmatic proteins (human serum albumin (HSA), γ-globulins, and transferrin). It was found that the fluorescence quenching of HSA and γ-globulins triggered by Au NCs was due to dynamic quenching mechanism, while the fluorescence quenching of transferrin by Au NCs was a result of the formation of a Au NC-transferrin complex. The apparent association constants of the Au NCs bound to HSA, γ-globulins, and transferrin demonstrated no obvious difference. Thermodynamic studies demonstrated that the interaction between Au NCs and HSA (or γ-globulins) was driven by hydrophobic forces, while the electrostatic interactions played predominant roles in the adsorption process for transferrin. Furthermore, it was proven that Au NCs had no obvious interference in the secondary structures of these three kinds of proteins. In turn, these three proteins had a minor effect on the fluorescence intensity of Au NCs, which made fluorescent Au NCs promising in biological applications owing to their chemical and photophysical stability. In addition, by comparing the interactions of small molecules, Au NCs, and large nanomaterials with serum albumin, it was found that the binding constants were gradually increased with the increase of particle size. This work has elucidated the interaction mechanisms between nanoclusters and proteins, and shed light on a new interaction mode different from the protein corona on the surface of nanoparticles, which will highly contribute to the better design and applications of fluorescent nanoclusters.

Triggering Receptor Expressed on Myeloid Cells 2 Overexpression Inhibits Proinflammatory Cytokines in Lipopolysaccharide-Stimulated Microglia.

Microglia play an important role in mediating inflammatory processes in the central nervous system (CNS). Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor and could decrease neuropathology in Alzheimer's disease (AD). However, the detailed mechanism remains unclear. This study was designed to elucidate the effect of TREM2 on microglia. We showed that lipopolysaccharide (LPS) stimulation significantly increases proinflammatory cytokines and suppressed TREM2 in microglia. In addition, TREM2 overexpression inhibited LPS-induced microglia activation and elevated M2 phenotype of microglia. Together, our results demonstrate that TREM2 overexpression reduced LPS-induced proinflammatory cytokine release in microglia and increased M2 phenotype of microglia. These findings provide novel insights that the regulation of microglia polarization may be an approach for ameliorating microglia inflammation in neurodegenerative diseases.

Hydrotherapy vs. conventional land-based exercise for improving walking and balance after stroke: a randomized controlled trial.

OBJECTIVE: To investigate the effects of hydrotherapy on walking ability and balance in patients with chronic stroke. DESIGN: Single-blind, randomized controlled pilot trial. SETTING: Outpatient rehabilitation clinic at a tertiary neurological hospital in China. SUBJECTS: A total of 28 participants with impairments in walking and controlling balance more than six months post-stroke. INTERVENTION: After baseline evaluations, participants were randomly assigned to a land-based therapy (control group, n = 14) or hydrotherapy (study group, n = 14). Participants underwent individual sessions for four weeks, five days a week, for 45 minutes per session. MAIN MEASURES: After four weeks of rehabilitation, all participants were evaluated by a blinded assessor. Functional assessments included the Functional Reach Test, Berg Balance Scale, 2-minute walk test, and Timed Up and Go Test. RESULTS: After four weeks of treatment, the Berg Balance Scale, functional reach test, 2-minute walk test, and the Timed Up and Go Test scores had improved significantly in each group (P < 0.05). The mean improvement of the functional reach test and 2-minute walk test were significantly higher in the aquatic group than in the control group (P < 0.01). The differences in the mean values of the improvements in the Berg Balance Scale and the Timed Up and Go Test were not statistically significant. CONCLUSION: The results of this study suggest that a relatively short programme (four weeks) of hydrotherapy exercise resulted in a large improvement in a small group (n = 14) of individuals with relatively high balance and walking function following a stroke.

Vestibular Rehabilitation of Patient with Hypertrophic Olivary Degeneration: A Case Report.

Background Hypertrophic olivary degeneration (HOD) is a rare disorder that typically develops in the weeks to months following a structural brainstem or cerebellar lesion in the Guillain-Mollaret triangle (GMT). Clinically, patients with HOD present with palatal myoclonus and nystagmus, which are difficult to treat and rarely resolve. Purpose The purpose of this case is to present the results of vestibular and balance assessments of a patient with bilateral HOD before and after vestibular rehabilitation. Methods This case report describes a 43-year-old trucker who presented with dizziness, blurred vision, and balance problems for more than 10 months, accompanied by new-onset tremors and ataxia for more than 6 months. The patient's characteristic clinical manifestations were palatal myoclonus and nystagmus. Magnetic resonance imaging (MRI) revealed bilateral HOD after an acute pontine hemorrhage. Comprehensive vestibular and balance assessments were performed. Results Vestibular and balance assessments demonstrated nystagmus, impaired vestibulo-ocular reflex (VOR), optokinetic reflex (OKR), and balance function. Following 4 months of vestibular rehabilitation, the patient's eye symptoms and balance function were improved. Conclusions The case presented here highlights the rare clinical manifestations of HOD after pontine hemorrhage. Vestibular rehabilitation training may be beneficial for the recovery of patients with HOD.

Structure-activity relationship between gold nanoclusters and human serum albumin: Effects of ligand isomerization.

The interactions between gold nanoclusters (AuNCs) and proteins have been extensively investigated. Nevertheless, the structure-activity relationship between gold nanoclusters and proteins in terms of ligand isomerization remained unclear. Here, interactions between Au25NCs modified with para-, inter- and ortho-mercaptobenzoic acid (p/m/o-MBA-Au25NCs) and human serum albumin (HSA) were analyzed. The results of the multispectral approach showed that all three gold nanoclusters bound to the site I in dynamic modes to increase the stability of HSA. There were significant differences in the binding intensity, thermodynamic parameters, main driving forces, and binding ratios between these three gold nanoclusters and HSA, which might be related to the existence forms of the three ligands on the surface of AuNCs. Due to the different polarities of AuNCs themselves, the impact of three AuNCs on the microenvironment of amino acid residues in HSA was also different. It could be seen that ligand isomerization significantly affected the interactions between gold nanoclusters and proteins. This work will provide theoretical guidance for ligand selection and biological applications of metal nanoclusters.

Electroacupuncture pretreatment inhibits ferroptosis and inflammation after middle cerebral artery occlusion in rats by activating Nrf2.

OBJECTIVE: Electroacupuncture (EA) pretreatment can effectively increase the tolerance of the brain to ischemic stroke. The mechanism of ischemic tolerance induced by EA is related to Nrf2, but its specific mechanism has not been elucidated. This paper was designed to explore the effect of EA pretreatment on brain injury and the related mechanisms. METHODS: Rats were pretreated with EA before middle cerebral artery occlusion (MCAO) modeling. The symptoms of neurological deficit and the volume of cerebral infarction were measured. The levels of inflammatory factors, oxidative stress-related factors, LPO, ROS, and Fe2+ were evaluated by the corresponding kits. Cell apoptosis was determined through TUNEL staining. The mRNA expression of inflammatory factors was examined by RT-qPCR, and the protein expression of ferroptosis-related factors, pyroptosis-related proteins, Keap1, Nrf2, HO-1, and NQO1 by western blotting. RESULTS: EA pretreatment improved the symptoms of neurological deficit and reduced the volume of cerebral infarction. EA pretreatment significantly inhibited oxidative stress, inflammatory response, ferroptosis, pyroptosis, and apoptosis in brain tissues of MCAO rats. Mechanistically, EA pretreatment could activate Nrf2 expression and reduce Keap1 expression. CONCLUSION: EA pretreatment reduced inflammation and oxidative stress and inhibited ferroptosis by activating Nrf2 expression, ultimately delaying the development of ischemic stroke.

Neural substrates for regulating self-grooming behavior in rodents. / 啮齿动物自我梳理行为调控的神经基质.

Grooming, as an evolutionarily conserved repetitive behavior, is common in various animals, including humans, and serves essential functions including, but not limited to, hygiene maintenance, thermoregulation, de-arousal, stress reduction, and social behaviors. In rodents, grooming involves a patterned and sequenced structure, known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style, beginning from the nose to the face, to the head, and finally ending with body licking. The context-dependent occurrence of grooming behavior indicates its adaptive significance. This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes. We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models, holding promise for translational psychiatry. Herein, we mainly focus on rodent self-grooming. Allogrooming (grooming being applied on one animal by its conspecifics via licking or carefully nibbling) and heterogrooming (a form of grooming behavior directing towards another animal, which occurs in other contexts, such as maternal, sexual, aggressive, or social behaviors) are not covered due to space constraints.

Mucus- and pH-mediated controlled release of core-shell chitosan nanoparticles in the gastrointestinal tract for diabetes treatment.

For the successful oral delivery of peptide drugs, considerable barriers created by the harsh environment of the gastrointestinal tract, mucus, and epithelial cells must be overcome. This study was to establish a core-shell structure with chitosan (CS) nanoparticles (NP) as the core and poly-N-(2-hydroxypropyl) methacrylamide (pHPMA) as the intelligent escape shell to overcome pH and mucus barriers and improve the delivery efficiency of peptide drugs. A core-shell system (COS) composed of pHPMA-AT-1002-cys-chitosan (LRA-PA-CNPs) was prepared and used for the treatment of type 2 diabetes mellitus with the large-molecule peptide drug liraglutide (LRA). The complete COS system was observed through electron microscopy; the particle size of the LRA-PA-CNPs was approximately 160 nm; the encapsulation efficiency was approximately 69% ± 5%; the zeta potential was close to neutral; the mucus and epithelial penetration of the COS system were increased; and animal experiments showed that the COS system enhanced the oral hypoglycaemic effect of LRA.HIGHLIGHTSIntelligent escape material of poly-N-(2-hydroxypropyl) methacrylamide as the shell.Core-shell nanoparticles penetrate the mucus layer and exposing the chitosan core.Overcome pH and mucus barriers to improve the delivery efficiency of peptide drugs.