Chronic restraint stress induces depression-like behaviors and alterations in the afferent projections of medial prefrontal cortex from multiple brain regions in mice.

INTRODUCTION: The medial prefrontal cortex (mPFC) forms output pathways through projection neurons, inversely receiving adjacent and long-range inputs from other brain regions. However, how afferent neurons of mPFC are affected by chronic stress needs to be clarified. In this study, the effects of chronic restraint stress (CRS) on the distribution density of mPFC dendrites/dendritic spines and the projections from the cortex and subcortical brain regions to the mPFC were investigated. METHODS: In the present study, C57BL/6 J transgenic (Thy1-YFP-H) mice were subjected to CRS to establish an animal model of depression. The infralimbic (IL) of mPFC was selected as the injection site of retrograde AAV using stereotactic technique. The effects of CRS on dendrites/dendritic spines and afferent neurons of the mPFC IL were investigaed by quantitatively assessing the distribution density of green fluorescent (YFP) positive dendrites/dendritic spines and red fluorescent (retrograde AAV recombinant protein) positive neurons, respectively. RESULTS: The results revealed that retrograde tracing virus labeled neurons were widely distributed in ipsilateral and contralateral cingulate cortex (Cg1), second cingulate cortex (Cg2), prelimbic cortex (PrL), infralimbic cortex, medial orbital cortex (MO), and dorsal peduncular cortex (DP). The effects of CRS on the distribution density of mPFC red fluorescence positive neurons exhibited regional differences, ranging from rostral to caudal or from top to bottom. Simultaneously, CRS resulted a decrease in the distribution density of basal, proximal and distal dendrites, as well as an increase in the loss of dendritic spines of the distal dendrites in the IL of mPFC. Furthermore, varying degrees of red retrograde tracing virus fluorescence signals were observed in other cortices, amygdala, hippocampus, septum/basal forebrain, hypothalamus, thalamus, mesencephalon, and brainstem in both ipsilateral and contralateral brain. CRS significantly reduced the distribution density of red fluorescence positive neurons in other cortices, hippocampus, septum/basal forebrain, hypothalamus, and thalamus. Conversely, CRS significantly increased the distribution density of red fluorescence positive neurons in amygdala. CONCLUSION: Our results suggest a possible mechanism that CRS leads to disturbances in synaptic plasticity by affecting multiple inputs to the mPFC, which is characterized by a decrease in the distribution density of dendrites/dendritic spines in the IL of mPFC and a reduction in input neurons of multiple cortices to the IL of mPFC as well as an increase in input neurons of amygdala to the IL of mPFC, ultimately causing depression-like behaviors.

Effects of the Roasting-Assisted Aqueous Ethanol Extraction of Peanut Oil on the Structure and Functional Properties of Dreg Proteins.

The effects of the roasting-assisted aqueous ethanol extraction of peanut oil on the structure and functional properties of dreg proteins were investigated to interpret the high free oil yield and provide a basis for the full utilization of peanut protein resources. The roasting-assisted aqueous ethanol extraction of peanut oil obtained a free oil yield of 97.74% and a protein retention rate of 75.80% in the dreg. The water-holding capacity of dreg proteins increased significantly, and the oil-holding capacity and surface hydrophobicity decreased significantly, reducing the binding ability with oil and thus facilitating the release of oil. Although the relative crystallinity and denaturation enthalpy of the dreg proteins decreased slightly, the denaturation temperatures remained unchanged. Infrared and Raman spectra identified decreases in the C-H stretching vibration, Fermi resonance and α-helix, and increases in random coil, ß-sheet and ß-turn, showing a slight decrease in the overall ordering of proteins. After the roasting treatment, 62.57-135.33% of the protein functional properties were still preserved. Therefore, the roasting-assisted aqueous ethanol extraction of peanut oil is beneficial for fully utilizing the oil and protein resources in peanuts.

Mechanisms on salt tolerant of Paenibacillus polymyxa SC2 and its growth-promoting effects on maize seedlings under saline conditions.

Soil salinity negatively affects microbial communities, soil fertility, and agricultural productivity and has become a major agricultural problem worldwide. Plant growth-promoting rhizobacteria (PGPR) with salt tolerance can benefit plant growth under saline conditions and diminish the negative effects of salt stress on plants. In this study, we aimed to understand the salt-tolerance mechanism of Paenibacillus polymyxa at the genetic and metabolic levels and elucidate the mechanism of strain SC2 in promoting maize growth under saline conditions. Under salt stress, we found that strain SC2 promoted maize seedling growth, which was accompanied by a significant upregulation of genes encoding for the biosynthesis of peptidoglycan, polysaccharide, and fatty acid, the metabolism of purine and pyrimidine, and the transport of osmoprotectants such as trehalose, glycine betaine, and K+ in strain SC2. To further enhance the salt resistance of strain SC2, three mutants (SC2-11, SC2-13, and SC2-14) with higher capacities for salt resistance and exopolysaccharide synthesis were obtained via atmospheric and room-temperature plasma mutagenesis. In saline-alkaline soil, the mutants showed better promoting effect on maize seedlings than wild-type SC2. The fresh weight of maize seedlings was increased by 68.10% after treatment with SC2-11 compared with that of the control group. The transcriptome analysis of maize roots demonstrated that SC2 and SC2-11 could induce the upregulation of genes related to the plant hormone signal transduction, starch and sucrose metabolism, reactive oxygen species scavenging, and auxin and ethylene signaling under saline-alkaline stress. In addition, various transcription factors, such as zinc finger proteins, ethylene-responsive-element-binding protein, WRKY, myeloblastosis proteins, basic helix-loop-helix proteins, and NAC proteins, were up-regulated in response to abiotic stress. Moreover, the microbial community composition of maize rhizosphere soil after inoculating with strain SC2 was varied from the one after inoculating with mutant SC2-11. Our results provide new insights into the various genes involved in the salt resistance of strain SC2 and a theoretical basis for utilizing P. polymyxa in saline-alkaline environments.

Effect of sanxan on the composition and structure properties of gluten in salt-free frozen-cooked noodles during freeze-thaw cycles.

In this study, the mechanisms by which sanxan protected the quality of salt-free frozen-cooked noodles (SFFCNs) were investigated, with a focus on the composition and structural properties of gluten. The results showed that sanxan facilitated the formation of glutenin macropolymer and maintained the stabilization of glutenin subunits in freeze-thaw cycles (FTs). In terms of protein structure, sanxan weakened the disruption of secondary structure caused by FTs and increased the proportion of gauche-gauche-gauche (g-g-g) conformations in the disulfide (S-S) bonds bridge conformation. Simultaneously, sanxan reduced the exposure degree of tryptophan (Trp) and tyrosine (Tyr) residues on the protein surface. Moreover, the intermolecular interaction forces indicated that sanxan inhibited S-S bonds breakage and enhanced the intermolecular crosslinking of gluten through ion interactions, which was crucial for improving the stability of gluten. This study provides a more comprehensive theoretical basis for the role of sanxan in improving the quality of SFFCNs.

Eating Quality and In Vitro Digestibility of Brown Rice Improved by Ascorbic Acid Treatments.

The effects of ascorbic acid treatment alone and in combination with degreasing or hydrothermal treatment on eating quality and in vitro digestibility of brown rice were explored for improving poor mouthfeel and low digestibility, and the improvement mechanism was investigated. The results indicated that the texture of cooked brown rice was significantly improved by degreasing combined with ascorbic acid hydrothermal treatment; the hardness and chewiness decreased to the level of polished rice; the stickiness increased three times of the cooked untreated brown rice; and the sensory score and in vitro digestibility were significantly enhanced from 68.20 and 61.37% to 83.70 and 79.53%, respectively. In addition, the relative crystallinity and water contact angle of treated brown rice were respectively reduced from 32.74% and 113.39° to 22.55% and 64.93°, and normal temperature water uptake significantly increased. Scanning electron microscope showed that the separation of starch granules occurred inside cooked brown rice grain obviously. The improvement of eating quality and in vitro digestibility of brown rice is conducive to enhancing the consumers acceptance and human health.

"Thiol-ene" crosslinked polybenzimidazoles anion exchange membrane with enhanced performance and durability.

To address the "trade-off" between conductivity and stability of anion exchange membranes (AEMs), we developed a series of crosslinked AEMs by using polybenzimidazole with norbornene (cPBI-Nb) as backbone and the crosslinked structure was fabricated by adopting click chemical between thiol and vinyl-group. Meanwhile, the hydrophilic properties of the dithiol cross-linker were regulated to explore the effect for micro-phase separation morphology and hydroxide ion conductivity. As result, the AEMs with hydrophilic crosslinked structure (PcPBI-Nb-C2) not only had apparent micro-phase separation morphology and high OH- conductivity of 105.54 mS/cm at 80 °C, but also exhibited improved mechanical properties, dimensional stability (swelling ratio < 15%) and chemical stability (90.22 % mass maintaining in Fenton's reagent at 80 °C for 24 h, 78.30 % conductivity keeping in 2 M NaOH at 80 °C for 2016 h). In addition, the anion exchange membranes water electrolysis (AEMWEs) using PcPBI-Nb-C2 as AEMs achieved the current density of 368 mA/cm2 at 2.1 V and the durability over 500 min operated at 150 mA/cm2 under 60 °C. Therefore, this work paves the way for constructing AEMs by introduction of norbornene into polybenzimidazole and formation of hydrophilic crosslinked structure based on "thiol-ene".

Revealing the reasons for the pasting property changes of rice during aging from the perspective of starch granule disaggregation.

BACKGROUND: The pasting properties of rice change markedly after aging, although the mechanism for this still remains unknown. Aged and fresh rice grains were ground and the flours were fractionated by particle size, and then the pasting properties, particle size distribution and microscopic morphology of the heated flour fractions were evaluated. RESULTS: Compared to the corresponding fresh flour fractions with the same particle size, a lower peak viscosity for those aged flour fractions from 80 µm to 450 µm and a higher peak viscosity for those aged flour fractions from 20 µm to 60 µm were observed. The amounts of smaller particles disaggregated from the aged flour fractions were significantly less and the separated entities were always larger than the corresponding fresh rice fractions. CONCLUSION: Disaggregation difficulty of starch granules was the reason for the changes in the pasting properties of rice after aging. This finding is helpful for understanding rice aging mechanisms and regulating eating quality of rice flour as an ingredient. © 2022 Society of Chemical Industry.

Overexpression of tousled-like kinase 2 predicts poor prognosis in HBV-related hepatocellular carcinoma patients after radical resection.

Background: Tousled-like kinase 2 (TLK2) is integral to DNA repair, replication, and cell cycle regulation, crucial for maintaining genome stability and integrity. However, the expression and prognostic value of TLK2 in hepatitis B viral (HBV) -related hepatocellular carcinoma (HCC) remains unclear. Methods: We examined TLK2 expression and prognostic implications in pan-cancer by using diverse databases. Subsequently, TLK2 expression in HBV-related HCC tissues and adjacent tissues was assessed using quantitative real-time PCR and immunohistochemistry. The prognostic value of TLK2 was assessed through ROC curves, time-dependent ROC curves, Cox regression, Kaplan-Meier curve, and decision curve analysis. Additionally, analyses of immune infiltration, protein-protein interactions, key molecules of tumor-related signaling pathways, molecular subtypes, and TLK2-associated differentially expressed genes (DEGs) were conducted, along with GO/KEGG and GSEA enrichment analyses. Results: TLK2 expression was significantly higher in HCC tissues compared to adjacent tissues and correlated with gender, AFP levels, albumin-bilirubin (ALBI) grade, microvascular invasion (MVI), maximum tumor diameter, tumor number, and TNM stage. TLK2 overexpression emerged as an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) in HBV-related HCC patients. An integrated OS nomogram model, incorporating TLK2, age, ALBI grade, MVI, and tumor number, displayed enhanced prognostic capability (C-index: 0.765, 95% CI: 0.732-0.798) in predicting OS and has a higher net benefit than the TNM stage. Moreover, TLK2 expression correlated closely with immune cell infiltration and key molecules of signaling pathways. Functional enrichment analyses highlighted significant associations with DNA duplex unwinding, double-strand break repair, DNA replication, cell cycle, E2F targets, G2M checkpoint, and MYC targets V1. Conclusion: TLK2 is notably overexpressed in HBV-related HCC and emerges as a promising prognostic biomarker, necessitating further validation.

Pretreatment Non-Invasive Biomarkers as Predictors to Estimate Portal Vein Tumor Thrombosis (PVTT) Risk and Long-Term Survival in HBV-Related Hepatocellular Carcinoma Patients Without PVTT.

Background: PVTT is a hallmark of advanced hepatocellular carcinoma (HCC). We aim to explore the influence of non-invasive biomarkers on the occurrence of PVTT and develop and validate models for predicting prognosis in HBV-related HCC patients without PVTT. Methods: A total of 1026 HBV-related HCC patients without PVTT were enrolled, with 515 in the training cohort, 216 in the internal validation cohort, and 295 in the external validation cohort. We conducted Cox regression analyses to discern the independent risk factors associated with PVTT events, PFS, and OS, then constructed and validated predictive models. The predictive and discriminatory capabilities of models were assessed using the calibration, time-dependent ROC, and DCA curves. Results: In our study, 136 patients (13.3%) experienced PVTT events during the follow-up period. The Cox regression analysis unveiled that male gender, AAPR ≤0.49, APRI >0.48, extrahepatic metastasis, and multiple tumors were independent risk factors for PVTT. In the training cohort, non-invasive biomarkers (AAR and APRI), AFP, ascites, and tumor-related characteristics (extrahepatic metastasis, tumor diameter, tumor number, and PVTT event) were independent risk factors for both OS and PFS, whereas age and ALBI grade independently correlated with OS. The C-indexes of OS and PFS nomogram models were 0.795 and 0.733 in the training cohort, 0.765 and 0.716 in the internal validation cohort, and 0.780 and 0.722 in the external validation cohort, respectively. Our models demonstrated strong predictive and discriminative abilities in all cohorts and yielded a greater net benefit compared to three traditional staging systems. Conclusion: Non-invasive biomarkers are expected to be reliable predictors for assessing PVTT risk and predicting prognosis among HBV-related HCC patients without PVTT.

Estradiol attenuates chronic restraint stress-induced dendrite and dendritic spine loss and cofilin1 activation in ovariectomized mice.

Ovarian hormone deprivation is associated with mood disorders, such as depression, and estradiol therapy is significantly more effective than placebos in treating major depression associated with menopause onset. However, the effect of estradiol on neuronal plasticity and its mechanisms remain to be further elucidated. In this study, behavioral assessments were used to examine the antidepressant effect of estradiol in ovariectomized (OVX) B6.Cg-TgN (Thy-YFP-H)-2Jrs transgenic mice on chronic restraint stress (CRS)-induced dendrite and dendritic spine loss; Yellow fluorescent protein (YFP) is characteristically expressed in excitatory neurons in transgenic mice, and its three-dimensional images were used to evaluate the effect of estradiol on the density of different types of dendritic spines. Quantification and distribution of cofilin1 and p-cofilin1 were determined by qPCR, Western blots, and immunohistochemistry, respectively. The results revealed that treatment with estradiol or clomipramine significantly improved depression-like behaviors. Estradiol treatment also significantly upregulated the dendritic density in all areas examined and increased the density of filopodia-type, thin-type and mushroom-type spines in the hippocampal CA1 and elevated the thin-type and mushroom-type spine density in the PFC. Consistent with these changes, estradiol treatment significantly increased the density of p-cofilin1 immunopositive dendritic spines. Thus, these data reveal a possible estradiol antidepressant mechanism, in that estradiol promoted the phosphorylation of cofilin1 and reduced the loss of dendrites and dendritic spines, which of these dendritic spines include not only immature spines such as filopodia-type, but also mature spines such as mushroom-type, and attenuated the depression-like behavior.

Pneumococcal vaccine effect on hospitalisation rates of pneumonia in children: A meta-analysis.

INTRODUCTION: Since the appearance of the pneumococcal conjugate vaccine, the frequency of community-acquired pneumonia hospitalisations was decreased significantly especially in children below the age of 2 years, but its effects are still conflicting. This meta-analysis study was performed to assess the relationship between the effects of different types of pneumococcal conjugate vaccines compared with each other on the frequency of community-acquired pneumonia hospitalisations in children aged below 2 years. METHODS: Through a systematic literature search up to December 2020, 20 studies were found recording relationships between the effects of different types of pneumococcal conjugate vaccines compared with each other on the frequency of community-acquired pneumonia hospitalisations in children aged below 2 years. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated between different types of pneumococcal conjugate vaccines compared with each other on the frequency of community-acquired pneumonia hospitalisations in children below the age of 2 years using the dichotomous methods with a random or fixed-effect model. RESULTS: The pneumococcal conjugate vaccine 10 was significantly related to a lower hospitalisation rate for pneumonia (OR, 0.64; 95% CI, 0.51-0.81, P < .001) compared with no vaccine and (OR, 0.78; 95% CI, 0.68-0.90, P < .001) compared with pneumococcal conjugate vaccine 7. The pneumococcal conjugate vaccine 13 was significantly related to a lower hospitalisation rate for pneumonia (OR, 0.63; 95% CI, 0.56-0.71, P < .001) compared with no vaccine and (OR, 0.56; 95% CI, 0.36-0.89, P = .01) compared with pneumococcal conjugate vaccine 7. The pneumococcal conjugate vaccine 13 was significantly related to a lower hospitalisation rate for pneumonia (OR, 0.67; 95% CI, 0.48-0.93, P = .02) compared with pneumococcal conjugate vaccine 10. CONCLUSIONS: The pneumococcal conjugate vaccines 10 or 13 may have independent relationships in reducing the frequency of community-acquired pneumonia hospitalisations in children aged below 2 years compared with no vaccine or pneumococcal conjugate vaccines 7. Also, the pneumococcal conjugate vaccine 13 may have the same independent relationship compared with pneumococcal conjugate vaccines 10. Further studies are needed to solidify the findings to other vaccines to have evidence-based information that could help in establishing future immunisation strategies.

The Antidepressant Effects of Resveratrol are Accompanied by the Attenuation of Dendrite/Dendritic Spine Loss and the Upregulation of BDNF/p-cofilin1 Levels in Chronic Restraint Mice.

Depression afflicts more than 300 million people worldwide, but there is currently no universally effective drug in clinical practice. In this study, chronic restraint stress (CRS)-induced mice depression model was used to study the antidepressant effects of resveratrol and its mechanism. Our results showed that resveratrol significantly attenuated depression-like behavior in mice. Consistent with behavioral changes, resveratrol significantly attenuated CRS-induced reduction in the density of dendrites and dendritic spines in both hippocampus and medial prefrontal cortex (mPFC). Meanwhile, in hippocampus and mPFC, resveratrol consistently alleviated CRS-induced cofilin1 activation by increasing its ser3 phosphorylation. In addition, cofilin1 immunofluorescence distribution in neuronal inner peri-membrane in controls, and cofilin1 diffusely distribution in the cytoplasm in CRS group were common in hippocampus. However, the distribution of cofilin1 in mPFC was reversed. Pearson's correlation analysis revealed that there was a significant positive correlation found between the sucrose consumption in sucrose preference test and the dendrite density in multiple sub-regions of hippocampus and mPFC, and a significant negative correlation between the immobility time in tail suspension test and the dendrite/dendritic spine density in several different areas of hippocampus and mPFC. P-cofilin1 was significantly positively correlated with the overall dendritic spine density in mPFC as well as with the overall dendrite density or BDNF in the hippocampus. Our results suggest that the BDNF/cofilin1 pathway, in which cofilin1 may be activated in a brain-specific manner, was involved in resveratrol's attenuating the dendrite and dendritic spine loss and behavioral abnormality.

RhoA/Rock2/Limk1/cofilin1 pathway is involved in attenuation of neuronal dendritic spine loss by paeonol in the frontal cortex of D-galactose and aluminum­induced Alzheimer's disease­like rat model.

Alzheimer's disease (AD) has become the most prevalent neurodegenerative disorder. Given the pathogenesis of AD is unclear, there is currently no drug approved to halt or delay the progression of AD. Therefore, it is pressing to explore new targets and drugs for AD. In China, polyphenolic Chinese herbal medicine has been used for thousands of years in clinical application, and no toxic effects have been reported. In the present study, using D­galactose and aluminum­induced rat model, the effects of paeonol on AD were validated via the Morris water maze test, open field test, and elevated plus maze test. Neuronal morphology in frontal cortex was assessed using ImageJ's Sholl plugin and RESCONSTRUCT software. RhoA/Rock2/Limk1/cofilin1 signaling pathway­related molecules were determined by Western blotting. Cofilin1 and p­cofilin1 were analyzed by immunofluorescence. Results showed that pre­treatment with paeonol attenuated D­galactose and aluminum­induced behavioral dysfunction and AD­like pathological alterations in the frontal cortex. Accompanied by these changes were the alterations in the dendrite and dendritic spine densities, especially the mushroom­type and filopodia­type spines in the apical dendrites, as well as actin filaments. In addition, the activity and intracellular distribution of cofilin1 and the molecules RhoA/Rock2/Limk1 that regulate the signaling pathway for cofilin1 phosphorylation have also changed. Our data suggests that paeonol may be through reducing Aß levels to alleviate the loss of fibrillar actin and dendrites and dendritic spines via the Rho/Rock2/Limk1/cofilin1 signaling pathway in the frontal cortex, and ultimately improving AD­like behavior.

Chronic asthma-induced behavioral and hippocampal neuronal morphological changes are concurrent with BDNF, cofilin1 and Cdc42/RhoA alterations in immature mice.

INTRODUCTION: Recent studies have found that persistent hypoxia caused by chronic asthma, especially during childhood, affects the development and function of the brain, but the mechanism is unclear. In the present study, BDNF and its signal pathway was investigated in mediating chronic asthma induced-neuronal changes that lead to behavior alterations. METHODS: The chronic asthma model was induced by sensitization with ovalbumin for more than 9 weeks in immature mice. Morris water maze test (MWMT), open field test (OFT) and elevated plus maze test (EPMT) were used to conduct behavioral evaluation. Neuronal morphology in hippocampal CA1, CA3 and DG was assessed using ImageJ's Sholl plugin and RESCONSTRUCT software. BDNF signaling pathway related molecules was determined by Western blotting. RESULTS: Chronic asthma does affect the behavioral performances of immature mice evaluated in MWMT, OFT, and EPMT. The analysis by three-dimensional reconstruction software found that following the behavioral alteration of asthmatic mice, dendritic changes also occurred in hippocampal neurons, including shortened dendrite length, significantly reduced number of dendritic branches, decreased density of dendritic spines, and reduced percentage of functional dendritic spine types. At the same time, by immunofluorescence and western blotting, we also found that alterations in dendritic morphology were consistent with activation of cofilin1 and changes in BDNF-Cdc42/RhoA levels. Some of the changes mentioned above can be alleviated by intranasal administration of budesonide. CONCLUSION: Our data suggest that response similar to nicotine withdrawal or/and hypoxia induced by childhood chronic asthma enhances the BDNF-Cdc42/RhoA signaling pathway and activates cofilin1, leading to the remodeling of actin, causing the loss of dendritic spines and atrophy of dendrites, eventually resulting in behavioral alterations.

Novel antidepressant effects of Paeonol alleviate neuronal injury with concomitant alterations in BDNF, Rac1 and RhoA levels in chronic unpredictable mild stress rats.

RATIONALE: Increasing evidence has suggested that major depressive disorder (MDD) is highly associated with brain-derived neurotrophic factor (BDNF) levels, dendrites atrophy, and loss of dendritic spines, especially in emotion-associated brain regions including the hippocampus. Paeonol is a kind of polyphenols natural product with a variety of therapeutic effects. Recent studies have reported its antidepressant effects. However, it is unclear what signaling pathways contribute to improve MDD. OBJECTIVE: The present study investigated the effect of Paeonol on hippocampal neuronal morphology and its possible signaling pathways in chronic unpredictable mild stress (CUMS) rat model. METHODS: Using CUMS rat model, the antidepressant-like effect of Paeonol was validated via depression-related behavioral tests. Neuronal morphology in hippocampal CA1 and DG was assessed using ImageJ's Sholl plugin and RESCONSTRUCT software. BDNF signaling pathway-related molecules was determined by Western blotting. RESULTS: Paeonol attenuated CUMS-induced depression-like behaviors, which were accompanied by hippocampal neuronal morphological alterations. After Paeonol treatment for 4 weeks, the dendritic length and complexity and the density of dendritic spines markedly increased in the hippocampal CA1 and the dentate gyrus (DG). However, CUMS or Paeonol treatment does not selectively affect dendritic spine types. Simultaneously, administration of Paeonol deterred CUMS-induced cofilin1 activation that is essential for remolding of dendritic spines. The induction of CUMS downregulated BDNF levels and upregulated Rac1/RhoA levels; however, the tendency of these was inhibited by treatment with Paeonol. CONCLUSION: Our data suggest that BDNF-Rac1/RhoA pathway may be involved in attenuation of CUMS-induced behavioral and neuronal damage by Paeonol that may represent a novel therapeutic agent for depression.

Novel derivative of Paeonol, Paeononlsilatie sodium, alleviates behavioral damage and hippocampal dendritic injury in Alzheimer's disease concurrent with cofilin1/phosphorylated-cofilin1 and RAC1/CDC42 alterations in rats.

Alzheimer's disease (AD) is a typical hippocampal amnesia and the most common senile dementia. Many studies suggest that cognitive impairments are more closely correlated with synaptic loss than the burden of amyloid deposits in AD progression. To date, there is no effective treatment for this disease. Paeonol has been widely employed in traditional Chinese medicine. This compound improves learning behavior in an animal model; however, the mechanism remains unclear. In this study, Paeononlsilatie sodium (Pa), a derivative of Paeonol, attenuated D-galactose (D-gal) and AlCl3-induced behavioral damages in rats based on evaluations of the open field test (OFT), elevated plus maze test (EPMT), and Morris water maze test (MWMT). Pa increased the dendritic complexity and the density of dendritic spines. Correlation analysis indicated that morphological changes in neuronal dendrites are closely correlated with behavioral changes. Pa treatment reduced the production of Aß, affected the phosphorylation and redistribution of cofilin1 and inhibited rod-like formation in hippocampal neurons. The induction of D-gal and AlCl3 promoted the expression of RAC1/CDC42 expression; however, the tendency of gene expression was inhibited by pretreatment with Pa. Taken together, our results suggest that Pa may represent a novel therapeutic agent for the improvement of cognitive and emotional behaviors and dendritic morphology in an AD animal model.

Two-Dimensional Zirconium-Based Metal-Organic Framework Nanosheet Composites Embedded with Au Nanoclusters: A Highly Sensitive Electrochemical Aptasensor toward Detecting Cocaine.

Two-dimensional (2D) zirconium-based metal-organic framework nanosheets embedded with Au nanoclusters (denoted as 2D AuNCs@521-MOF) were prepared via a one-pot method under mild conditions. The optimized 2D AuNCs@521-MOF nanosheets not only possessed high specific surface area, physicochemical stability, and good electrochemical activity but also exhibited strong bioaffinity toward biomolecule-bearing phosphate groups. Consequently, a large amount of cocaine aptamer strands can be immobilized onto the substrate modified by 2D AuNCs@521-MOF nanosheet, further leading to the formation of a constructed biosensitive platform, which can be used to successfully detect cocaine through the specific binding interactions between cocaine and aptamer strands. The results demonstrated that the 2D AuNCs@521-MOF-based aptasensor had high sensitivity for detecting cocaine within the broad concentration range of 0.001-1.0 ng·mL-1 and the low limit of detection of 1.29 pM (0.44 pg·mL-1) and 2.22 pM (0.75 pg·mL-1) as determined by electrochemical impedance spectroscopy and differential pulse voltammetry, respectively. As expected, with the advantages of high selectivity, repeatability, stability, and simple operation, this new strategy is believed to exhibit great potential for simple and convenient detection of cocaine.

Mechanism of Formation and Stabilization of Nanoparticles Produced by Heating Electrostatic Complexes of WPI-Dextran Conjugate and Chondroitin Sulfate.

Protein conformational changes were demonstrated in biopolymer nanoparticles, and molecular forces were studied to elucidate the formation and stabilization mechanism of biopolymer nanoparticles. The biopolymer nanoparticles were prepared by heating electrostatic complexes of whey protein isolate (WPI)-dextran conjugate (WD) and chondroitin sulfate (ChS) above the denaturation temperature and near the isoelectric point of WPI. The internal characteristics of biopolymer nanoparticles were analyzed by several spectroscopic techniques. Results showed that grafted dextran significantly (p < 0.05) prevented the formation of large aggregates of WD dispersion during heat treatment. However, heat treatment slightly induced the hydrophobicity changes of the microenvironment around fluorophores of WD. ChS electrostatic interaction with WD changed the fluorescence intensity of WD regardless of heat treatment. Far-UV circular dichroism (CD) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopies confirmed that glycosylation and ionic polysaccharide did not significantly cause protein conformational changes in WD and ChS (WDC) during heat treatment. In addition, hydrophobic bonds were the major molecular force for the formation and stabilization of biopolymer nanoparticles. However, hydrogen bonds slightly influenced their formation and stabilization. Ionic bonds only promoted the formation of biopolymer nanoparticles, while disulfide bonds partly contributed to their stability. This work will be beneficial to understand protein conformational changes and molecular forces in biopolymer nanoparticles, and to prepare the stable biopolymer nanoparticles from heating electrostatic complexes of native or glycosylated protein and polysaccharide.

Stable nanoparticles prepared by heating electrostatic complexes of whey protein isolate-dextran conjugate and chondroitin sulfate.

A simple and green method was developed for preparing the stable biopolymer nanoparticles with pH and salt resistance. The method involved the macromolecular crowding Maillard process and heat-induced gelation process. The conjugates of whey protein isolate (WPI) and dextran were produced by Maillard reaction. The nanoparticles were fabricated by heating electrostatic complexes of WPI-dextran conjugate and chondroitin sulfate (ChS) above the denaturation temperature and near the isoelectric point of WPI. Then, the nanoparticles were characterized by spectrophotometry, dynamic laser scattering, zeta potential, transmission electron microscopy, atomic force microscopy, and scanning electron microscopy. Results showed that the nanoparticles were stable in the pH range from 1.0 to 8.0 and in the presence of high salt concentration of 200 mM NaCl. WPI-dextran conjugate, WPI, and ChS were assembled into the nanoparticles with dextran conjugated to WPI/ChS shell and WPI/ChS core. The repulsive steric interactions, from both dextran covalently conjugated to WPI and ChS electrostatically interacted with WPI, were the major formation mechanism of the stable nanoparticles. As a nutrient model, lutein could be effectively encapsulated into the nanoparticles. Additionally, the nanoparticles exhibited a spherical shape and homogeneous size distribution regardless of lutein loading. The results suggested that the stable nanoparticles from proteins and strong polyelectrolyte polysaccharides would be used as a promising target delivery system for hydrophobic nutrients and drugs at physiological pH and salt conditions.