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Schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are common neuropsychiatric disorders that lead to neuroinflammation in the pathogenesis. It is possible to further explore the connection between inflammation in the brain and SCZ, BD, and MDD. Therefore, we systematically reviewed PubMed and Web of Science on brain inflammatory markers measured in SCZ, BD, and MDD postmortem brains. Out of 2166 studies yielded by the search, 46 studies met the inclusion criteria in SCZ, BD, and MDD postmortem brains. The results were variable across inflammatory markers. For example, 26 studies were included to measure the differential expression between SCZ and control subjects. Similarly, seven of the included studies measured the differential expression of inflammatory markers in patients with BD. The heterogeneity from the included studies is not clear at present, which may be caused by several factors, including the measured brain region, disease stage, brain source, medication, and other factors.

For centuries, Sophora alopecuroides L. has been used both as a food and an herbal medicine in northern China. A new cytisine-type alkaloid, N-methylene-(5,7,4[Formula: see text]-trihydroxy)-isoflavone (LY01), was found in the fruits of Sophora alopecuroides L. and shows neuroprotective effects against Parkinson’s disease (PD). PD is a frequently occurring, irreversible neurodegenerative disease that seriously threatens the health of the elderly population. There is no cure for PD. The available treatments help manage the symptoms, but their use is limited by multiple side effects. Therefore, more pharmacological treatments addressing this pathology are urgently required. This study aimed to evaluate the neuroprotective effects of LY01 against PD, as well as their underlying mechanisms, using both in vitro and in vivo experimental models. A 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP)-induced mouse model of PD was used to assess the effects of LY01 on the motor coordination deficit, progression of the pathology, and molecular characteristics. 1-Methyl-4-phenylpyridinium (MPP[Formula: see text])-activated SH-SY5Y cells and lipopolysaccharide (LPS)-activated BV-2 cells were used to evaluate LY01 effects on oxidative damage and neuroinflammation. In the rotarod test, LY01 alleviated the impaired motor coordination in PD mice. Furthermore, LY01 treatment prevented the loss of dopaminergic neurons in the substantia nigra and striatum of the PD mice, reduced neuroinflammation in the mice with MPTP-induced PD and the LPS-activated BV-2 cells, and diminished oxidative stress in the PD mice and the MPP[Formula: see text]-induced SH-SY5Y cells. In conclusion, these results suggest the potential of LY01 as a therapeutic agent for treating PD.

Biocompatible photo-driven producers of singlet oxygen can inhibit the growth of drug-resistant bacteria and tumors. In order to develop bacteria targeting generator of singlet oxygen for tumor and bacterial treatment, a metal porphyrin liposome (Phy–Mn–Ls) was prepared by the metal coordination reaction and self-assembly of porphyrin compounds with bacteria targeting polymer (HS–PEG–chol). The photo-driven production of 1O2, binding with bovine serum protein (BSA) and lipase, toxicity to MCF-7 breast cancer cells and inhibitory effect on the growth of Escherichia coli have been investigated. Fluorescence analysis results show that Phy–Mn–Ls can bind to lipase, and it shows less effect on the conformation of BSA and is low cytotoxicity without irradiation. In particular, the good biocompatibility made Phy–Mn–Ls exhibit good photosensitive antibacterial activity and anti-tumor properties. The results demonstrate that the coordination of HS–PEG–chol with metal-phorphrin coodination is an effective way to develop bacteria targeting nano-complexes (Phy–Mn–Ls) for lipase affinity and photodriven bacteria treatment.

A new type of near α high temperature titanium alloy of Ti-Al-Sn-Zr-Mo-Si-Er was studied. The samples with different primary α phase content were prepared by solid solution at 950 °C/1 h—1010 °C/1 h. The multi-step hot compression experiments were carried out by Gleeble-3500 in a sequence of upper region of α + β phase, then followed by lower region of α + β phase. The effects of primary α phase content and deformation temperature on the microstructure of the alloy were studied by means of true stress-strain curve and optical microscope. The results show that the content of primary α phase gradually decreases from 45.4% at 950°C to 0% at 1010°C. As the deformation temperature decreases from 940°C to 900°C, the content of α phase increases gradually from 65% to 94%, which is changed from dynamic recrystallization to deformed structure elongated along RD direction. It is found that the arrangement of α phase along RD direction is the longest at 920°C. With the increase of the deformation temperature in the multi-step high temperature region from 970°C to 990°C, the width of deformed α phase decreases from 3.64 μm at 970°C to 2.71 μm at 990°C. The optimized microstructure is composed of 20% primary α phase arranged along RD direction. This process has a certain potential in the process of hot deformation of the alloy. Key words: high temperature titanium alloy, primary α phase, multi-step hot deformation

The abuse of antibiotics has led to a rapid increase in the resistance of bacteria and the environmental pollution. Attenuating the bactarial membrane and metabolism by functional celluloses is an effective strategy to find bacteriostatic agents as replacers of traditional antibiotics. Herein, a novel fluorescent cellulose (CEL-THPP) was synthesized by the covalent coupling of cellulose with porphyrin derivatives (THPP). The coordination of Zn (II) ion with CEL-THPP induced the self-assembly of CEL-THPP producing CEL-THPP@Zn with near-infrared light absorption. CEL-THPP@Zn is a porous rod-like structure cellulose. CEL-THPP@Zn exhibits strong fluorescence emission at 662 nm in solid and the optical band gaps was 1.69 eV. Moreover, CEL-THPP@Zn have excellent inhibitory and adsorption effects on both Escherichia coli and Staphylococcus aureus. Therefore, this study provides a novel solution for cellulose surface modification, and the CEL-THPP@Zn can be applied to bacterial inhibition and filtration.

Parkinson’s disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.

Major depressive disorder (MDD) is a common mental disorder with high morbidity. Stress negatively affects for MDD development, whereby transport of stress-induced inflammatory mediators to the central nervous system (CNS) is associated with the etiology of mood disorders. Muscone is a pharmacologically active ingredient isolated from musk, with anti-inflammatory and neuroprotective effects. We hypothesized that muscone may ameliorate depression-like behavior by regulating inflammatory responses. To test this hypothesis, we used the chronic restraint stress (CRS) depression model, and CRS mice were treated with muscone (10 mg/kg, i.g., respectively) for 14 days. The effects of the drug on depressive-like behaviors were evaluated via the open field test (OFT), novelty-suppressed feeding test (NSFT), tail suspension test (TST), and forced swimming test (FST). Quantitative reverse transcription-PCR (qRT-PCR) was utilized to assess levels of proinflammatory cytokines (IL-6, TNF-α, COX2, and IL-1) and the anti-inflammatory cytokines (IL-4 and IL-10). We also determined levels of oxidative stress factors (malondialdehyde, superoxide dismutase, and glutathione peroxidase), as well as doublecortin (DCX) expression by immunofluorescence. The results showed that depression-like behavior and inflammatory levels were improved after muscone treatment. Muscone also significantly improved neurogenesis in the CRS mouse hippocampus and decreased oxidative stress in both the central and peripheral nervous systems. In conclusion, this work is the first to demonstrate that muscone has an antidepressant effect using a CRS model. Oxidative stress, neurogenesis, and inflammatory pathways are key factors affected by the drug and may represent new therapeutic targets to treat MDD, in this impact. These results may represent a new therapeutic target for MDD.

Drug dependence may affect the neurotransmitter system levels in the human body. This study recruited 113 healthy control subjects, 118 heroin-dependent patients and 118 methamphetamine-dependent patients and examined the serum 5-HT, dopamine, glutamate and norepinephrine levels in the 349 volunteers. ELISA assays demonstrated that the serum 5-HT levels were significantly reduced in the drug-dependent patients, whereas the serum dopamine and glutamate levels were both significantly increased in the drug-dependent patients when compared with control subjects. In contrast, the norepinephrine levels did not exhibit a significant difference between the drug-dependent and control subjects. We also used qRT-PCR to analyze the transcriptional expression levels of 5-HT1A, 5-HT1B, dopmaine-D1 and dopamine-D2 receptors in the blood of drug-dependent patients and controls, and the results show that only 5-HT1B receptor levels were dysfunctional in the heroin abusers. In addition, our results suggest that serum 5-HT, dopamine, and glutamate levels had the potential to differ between drug abusers and controls, and combining those three potential biomarkers provided an accurate means to differentiate between the drug-dependent and control subjects. Taken together, our study reveals a differential profile of neurotransmitters in the heroin-dependent patients and methamphetamine-dependent patients, and this revelation may contribute to understanding the pathophysiology of drug addiction.

A series of 1-(2-alkoxyethyl)-3-methylimidazolium + [anion] ionic liquids including 1-(2-methoxyethyl) -3-methylimidazolium chloride, 1-(2-methoxyethyl) -3-methylimidazolium dl-threonine, and 1-(2-...

Autoantibodies to beta amyloid (Aβ) have been suggested to be involved in the pathogenesis of Alzheimer's disease (AD). However, data from clinical studies were inconsistent on autoantibody to Aβ levels in patients with AD. Therefore, we systematically searched the literature and performed meta-analysis to summarize the data of autoantibodies to Aβ in AD patients. The systematic search from PubMed and Web of Science included thirty case-control studies with a total of 2901 individuals (1311 AD patients and 1590 healthy control subjects). Random-effect meta-analysis showed a significant increased endogenous IgG autoantibody to Aβ levels in blood when compared with controls (Hedges' g = 0.337, 95% CI = 0.020 to 0.654, P = 0.03). In contrast, blood IgM autoantibody to Aβ levels was significantly decreased in patients with AD relative to control subjects (Hedges' g = - 0.962, 95% CI = - 1.797 to - 0.126, P = 0.024). Furthermore, cerebrospinal fluid Aβ levels were not significantly different between AD patients and control subjects (Hedges' g = - 0.446, 95% CI = - 2.357 to 1.464, P = 0.647). Subgroup analysis revealed that detection method contributed to the heterogeneity for studies measuring blood IgG autoantibody to Aβ levels in AD patients. Meta-regression analyses suggested that sex is a confounder for the outcome of the meta-analysis. Taken together, the results of this meta-analysis clarified circulating autoantibodies to Aβ levels in AD patients and suggested that endogenous IgG and IgM-class antibodies to Aβ may play a role in the pathogenesis of AD.

Biocompatible photo-driven producers of singlet oxygen can inhibit the growth of drug-resistant bacteria and tumors. In order to bacteria targeting generator of singlet oxygen for tumor and bacterial treatment, a metal porphyrin liposome (Phy-Mn-Ls) was prepared by the metal coordination reaction and self-assembly of porphyrin compounds with bacteria targeting polymer (HS-PEG-chol). The photo-driven production of 1O2, binding with protein (BSA) and lipase, toxicity to MCF-7 breast cancer cells and inhibitory effect on the growth of Escherichia coli were investigated. Fluorescence analysis results show that Phy-Mn-Ls can bind to lipase, and it shows less effect on the conformation of BSA and is low cytotoxicity without irradiation. In particular, the good biocompatibility made Phy-Mn-Ls exhibit good photosensitive antibacterial activity and anti-tumor properties. The results demonstrate that the coordination of HS-PEG-chol with metal-phorphrin coodination is an effective way to develop bacteria targeting nano-complexes (Phy-Mn-Ls) for lipase affinity and photodriven bacteria treatment.

Genetic variants conferring risk for schizophrenia (SCZ) have been extensively studied, but the role of posttranscriptional mechanisms in SCZ is not well studied. Here we performed the first genome-wide microRNA (miRNA) expression profiling in serum-derived exosome from 49 first-episode, drug-free SCZ patients and 46 controls and identified miRNAs and co-regulated modules that were perturbed in SCZ. Putative targets of these SCZ-affected miRNAs were enriched strongly for genes that have been implicated in protein glycosylation and were also related to neurotransmitter receptor and dendrite (spine) development. We validated several differentially expressed blood exosomal miRNAs in 100 SCZ patients as compared with 100 controls by quantitative reverse transcription-polymerase chain reaction. The potential regulatory relationships between several SCZ-affected miRNAs and their putative target genes were also validated. These include hsa-miR-206, which is the most upregulated miRNA in the blood exosomes of SCZ patients and that previously reported to regulate brain-derived neurotrophic factor expression, which we showed reduced mRNA and protein levels in the blood of SCZ patients. In addition, we found 11 miRNAs in blood exosomes from the miRNA sequence data that can be used to classify samples from SCZ patients and control subjects with close to 90% accuracy in the training samples, and approximately 75% accuracy in the testing samples. Our findings support a role for exosomal miRNA dysregulation in SCZ pathophysiology and provide a rich data set and framework for future analyses of miRNAs in the disease, and our data also suggest that blood exosomal miRNAs are promising biomarkers for SCZ.

Two hydrophobic ionic liquids (ILs) 1-alkyl-2, 3-dimethylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([C2mmim][NTf2] and [C4mmim][NTf2]) were synthesized. The binary mixtures of the two ILs were prepared with dimethyl carbonate (DMC) or diethyl carbonate (DEC) over the entire mole fraction range, respectively. The density and viscosity of the binary mixtures were investigated at temperature ranging from 293.15 to 328.15 K. The excess molar volumes and viscosity deviations were calculated for the four binary mixtures. The effects of the extension of the alkyl chain of the cation on the above properties are discussed. The Redlich-Kister equation was used for the fitting of the excess molar volumes and viscosity deviations versus mole fraction. The thermal expansion coefficients of the systems were obtained according to the density.

Two hydrophobic ionic liquids (ILs) 1-alkyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([C2mim][NTf2] and [C4mim][NTf2]) were synthesized. The binary mixtures of the two ILs were prepared with dimethyl carbonate (DMC) or diethyl carbonate (DEC) over the entire mole fraction range, respectively. The density and viscosity of the binary mixtures were determined by an automated DMA 5000 M and a Lovis 2000 ME Anton Paar Rotational Stabinger Viscometer at temperatures ranging from 288.15 to 328.15 K. The uncertainties of the density and viscosity are ur(ρ) = 0.00120 and ur(η) = 0.01. The excess molar volumes and viscosity deviations were calculated for the four binary mixtures by the measurement values. The effects of the extension of the alkyl chain of the cation and anion on the above properties are discussed. The effects of the methyl introduction on the cation was also discussed with the literature. The excess molar volumes and viscosity deviations were fitted versus mole fraction according to ...

Foot electrical stimulation (FES) has been considered as a classic stressor that can disturb homeostasis. Acute anemia was observed in the model induced by FES. The aim of this study was to explore the role of inflammatory cytokines underlying the acute anemia and gastrointestinal (GI) mucosal injury in the FES. Twenty-four male Kunming mice (20 ± 2 g) were randomly divided into control group and experimental group. The mice were placed in a footshock chamber that can generate 0.5 mA electrical impulse periodically for 0.5 h. After the process, red blood cell count, hemoglobin concentration and hematocrit, the levels of corticotropin releasing hormone (CRH) in serum and hypothalamus, and adrenocorticotropic hormone (ACTH) in serum and pituitary were detected separately. In addition, we investigated the expressions of inflammatory cytokines (IL-1, IL-6, TNF-α, iNOS, and IL-10) in the hypothalamus and duodenum by Polymerase Chain Reaction (PCR). Results showed that this FES model induced anemia, increased CRH and ACTH activity in the serum after the FES. Moreover, the expressions of IL-1β, IL-6, TNF-α, and iNOS were significantly increased following the process, while IL-10 was not activated. These findings suggest that anemia, the inflammatory cytokines in the hypothalamus and duodenum of the mice in the model induced by FES is closely related to GI mucosal injury/bleeding. Taken together, these results underscore the importance of anemia, GI mucosal injury/bleeding and stress, future studies would be needed to translate these findings into the benefit of affected patients.

Ethnopharmacological relevance The traditional Chinese medicine Sanweidoukou decoction (DK-3) was a classical formula for the treatment of nervous system diseases, recorded in the Chinese medical classic Sibu Yidian. Aim of the study The present study is aim to investigate the neuroprotective effects of DK-3 on β-amyloid (Aβ) protein -induced AD-like pathologies and underlying molecular mechanisms both in vitro and in vivo studies. Materials and methods Hydrolysates of DK-3 were analyzed by LC-ESI-MS/MS. In vitro, MTT was utilized to examine effects of DK-3 on Aβ25-35-induced cytotoxicity in PC12 cells. In vivo, male Sprague-Dawley rats were administered with Aβ25-35 to induce AD-like pathologies and behavioral evaluations were conducted via Morris water maze (MWM) test. Histopathological changes were observed by Hematoxylin-eosin (HE) straining. Immunohistochemistry (IHC) was used to detect the tau hyperphosphorylation at Thr181 site. The expression levels of tau hyperphosphorylation, inflammation-related cytokines such as COX-2, iNOS, TNF-α, IL-1β, IL-6, the phosphorylated state of various mitogen-activated protein kinase (MAPK) signaling molecules (p38 MAPK, ERK, and JNK) and activation of nuclear factor κB (NF-κB) in vitro and in vivo were assessed via Western blot. Results In vitro, DK-3 dose-dependently increased cell viability of PC12 cells induced by Aβ25-35. In vivo, DK-3 improved learning and memory abilities of Aβ25-35-induced AD-like rats. Moreover, DK-3 reversed hyperphosphorylation of tau and reduced the production of inflammation-related cytokines through significantly inhibited MAPK and NF-κB signaling pathways both in vitro and in vivo studies. Conclusion The present study suggested that the traditional Chinese medicine DK-3 may play a role in preventing and treating AD by reducing the hyperphosphorylation of tau protein and the expressions of inflammation-related cytokines via modulating the MAPK/NF-κB signaling pathways.

Background: Estrogen replacement therapy (ERT) is a common treatment method for menopausal syndrome; however, its therapeutic value for the treatment of neurological diseases is still unclear. Epidemiological studies were performed, and the effect of postmenopausal ERT on treating neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), was summarized through a meta-analysis.Methods: Twenty-one articles were selected using a systematic searching of the contents listed on PubMed and Web of Science before June 1, 2019. Epidemiological studies were extracted, and relevant research data were obtained from the original articles based on the predefined inclusion criteria and data screening principles. The Comprehensive Meta-Analysis Version 2 software was used to pool effective size, test heterogeneity, conduct meta-regression and subgroup analysis, and to calculate publication bias.Results: Our results showed that ERT significantly decreased the risk of onset and/or development of AD [odds ratio (OR): 0.672; 95% CI: 0.581–0.779; P < 0.001] and PD (OR: 0.470; 95% CI: 0.368–0.600; P < 0.001) compared with the control group. A subgroup and meta-regression analysis showed that study design and measure of effect were the source of heterogeneity. Age, sample size, hormone therapy ascertainment, duration of the treatment, or route of administration did not play a significant role in affecting the outcome of the meta-analysis.Conclusion: We presented evidence here to support the use of estrogen therapy for the treatment of AD and PD.

Mallotus oblongifolius (MO), an edible medicinal plant from Hainan in China, shows a wide range of bioactivities. The daily consumption of MO or its extracts has been observed to ameliorate ischemic nerve injury. However the mechanisms remain unclear. In this study, the effects of MO both in vitro and in vivo were investigated. The results indicated that MO improved the motor ability, neurosensory ability, balance and grasping ability of mice with ischemic injuries, induced by bilateral common carotid artery ligation (BCCAL). In addition, MO improved the morphology of neurons, resisted the loss of neurons, and enhanced the content of the nestin protein in the cerebral cortex and subgranular zone (SGZ) area. Furthermore, in the oxygen-glucose deprivation and reperfusion (OGD/R) treated cell model, MO could effectively activate the Wnt/β-catenin signaling pathway and promote the proliferation of neural stem cells (NSCs) and increase the protein expression levels of β-catenin and CyclinD1. Our results suggest that Mallotus oblongifolius may be used as nutraceuticals or functional foods to alleviate ischemic nerve damage and promote recovery from ischemic stroke.

Aims Alzheimer's disease (AD) is an incurable neurodegenerative disorder characterized by global cognitive impairment that involves accumulation of amyloid-beta peptides (Aβ) in the brain. Herbal approaches can be used as alternative medicines to slow the progression of AD. This study aimed to determine the beneficial effects and potential underlying mechanisms of total flavonoid extract from Dracoephalum moldavica L. (TFDM) for attenuating Alzheimer-related deficits induced by Aβ. Main methods We used amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice and copper-injured APP Swedish mutation overexpressing SH-SY5Y cells to evaluate the beneficial effects of TFDM. Further, identifying the mechanisms of action was conducted on anti-amyloidogenic and neurotrophic transductions. Key findings Our results indicated that TFDM treatment ameliorated cognitive impairments and neurodegeneration and improved the antioxidant defense system in APP/PS1 mice. TFDM also reduced Aβ burden by relieving Aβ deposition, decreasing insoluble Aβ levels, and inhibiting β-amyloidogenic processing pathway involving downregulation of β-secretase and β-C-terminal fragment in the brain. In the in vitro model of AD, TFDM treatment protected injured cells, and combined with the beneficial effects of decreasing APP levels, lowered Aβ1–42 and regulated the redox imbalance. Moreover, TFDM preserved the extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway both in vitro and in vivo. Significance In conclusion, TFDM clearly demonstrated neuroprotective effects by restoring the anti-amyloidogenic and neurotrophic transductions in the context of AD-associated deficits. These findings indicate the potential use of herb-based substances as supplements or potential alternative supplements for attenuating the progression of AD.

To rapidly and accurately screen compounds present in traditional Chinese herbal medicines for α-glycosidase inhibitors, we synthesized a novel nano-affinity material to enable the targeted screening and enrichment of α-glycosidase inhibitors. This nano-affinity material was synthesized by self-assembly involving α-glycosidase and Cu2+. A systematic analysis revealed the flower-like structure of this nano-material, with a diameter of 7.564 μm. The highest enzyme activity was 214.03% compared to free enzymes. This novel material was used to screen and enrich α-glycosidase inhibitors from Chinese rhubarb. Ten compounds were detected. Of these, L-epicatechin and anthraquinone displayed inhibitory activity. This novel nano-hybrid affinity material allows the rapid screening and separation of active components in complex systems.

Ionic liquids (ILs) have attracted remarkable attention as a new class of novel reaction medium and soft functional materials in the framework of Green Chemistry, and the polarity of ionic liquids is one of the primary concerns in the scientific community. Here, we introduce a new and simple scale of polarity, δμ, for ILs. Initially, two kinds of representative ionic liquids, {1-alkyl-3-methyllimidazolium acetate} [Cnmim][AcO] (n = 2,4,5,6) and {1-alkyl-2,3-dimethyimidazolium-N, N-bis(trifluoromethyl sulfonyl)imide} [Cnmmim][NTf2] (n = 2,4) are prepared and confirmed by 1H NMR spectroscopy and 13C NMR spectroscopy, respectively. Furthermore, a spectroscopic method based on solvatochromic probes is used to obtain the polarity of room temperature ILs (RTILs). In this work we mainly introduce that the scale of solvent polarity, ET(30) values, is determined by means of Reichardt’s dye (30), and π* values are determined by N,N-diethyl-4-nitroaniline. Simultaneously, in terms of the values of enthalpy of vapori...

Amino acid ionic liquids [Cnmim][Ala] (n = 3, 4, 5) (1-alkyl-3-methylimidazolium alanine salt) were prepared by the neutralization method. The density and viscosity for aqueous solutions of the ionic liquids (ILs) with various molalities were measured at T = (288.15 to 328.15) K with an interval of 5 K. In terms of the Jones–Dole equation, the viscosity B-coefficients with large positive values and dB/dT < 0 were obtained, and these facts implied that the ionic liquids are water-structure-making. According to Feakins, the contribution of the solute per mole to the free energy of activation for viscous flow of the solution, Δμ2⧧0, or called as the standard molar activation free energy, was obtained at different temperatures. Under the constant molality of solution, ΔH2⧧0 (the activation enthalpy of the activation for viscous flow of aqueous [Cnmim][Ala] (n = 3, 4, 5)) is a temperature-independent constant. This implies that the activation process of the solute for viscous flow of aqueous [Cnmim][Ala] (n = ...

In order to efficiently screen and isolate β-tubulin inhibitors, β-tubulin was immobilized on core–shell PMMA/CS (poly(methyl methacrylate)/Chitosan) nanoparticles to produce a new type of immobilized affinity material named β-tubulin-immobilized nanoparticles (β-TIN). The selectivity and adsorption performance of β-TIN were characterized using various control drugs. The β-TIN, the paclitaxel molecularly imprinted ploymers (MIP), and the C18 adsorbing material were compared for selectivity and enrichment ratio. Microtubule-targeting antitumor compounds were screened and isolated from a typical Chinese medicine, Chloranthus multistachys, by β-TIN. Three active compounds (curcolnol, zedoarofuran, and codonolactone) in Chloranthus multistachys extract were captured successfully. Microscale thermophoresis demonstrated that these three compounds strongly bind to β-tubulin, and the dissociation constants (Kd) between the three active compounds and β-tubulin were 1820 ± 0.68 nM, 1640 ± 0.52 nM, and 284 ± 1.00 nM...

The major bioactive ingredient THSG of Polygonum multiflorum is well established for its anti-oxidation, anti-aging and anti-inflammation properties. Increasing evidence supports the capacity of THSG to ameliorate the biochemistry of neurotrophins and their downstream signaling axis in mouse models to attenuate neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this study, the neuroprotective effects of THSG were studied in vitro and in vivo. In cultured mesencephalic dopamine neurons and SH-SY5Y cell line, it was found that THSG protected the integrity of the cell body and neurite branching from MPP+-induced toxicity by restoring the expression of FGF2 and BDNF and their downstream signaling pathways to inhibit apoptosis and promote cell survival. The inhibition of Akt signaling by LY294002 or TrkB activity by K252a eliminated the neuroprotective effects of THSG. In the MPTP-induced mouse models of Parkinson's disease, THSG ameliorated the animal behaviors against MPTP-induced neurotoxicity, which was demonstrated by the pole test and the tail suspension test. Biochemical and immunohistochemical analysis verified the THSG-mediated restoration of the FGF2-Akt and BDNF-TrkB signaling axis in the substantia nigra and corpus striatum and the recovery of dopaminergic neurons. These results establish the neuroprotective effects of THSG in vitro and in vivo and unravel the underlying mechanism against toxin-induced neural atrophy, providing a new avenue for the use and pharmacological research of edible medicine for anti-neurodegenerative diseases.

Exosomal microRNAs (miRNAs) have been suggested to participate in the pathogenesis of neuropsychiatric diseases, but their role in major depressive disorder (MDD) is unknown. We performed a genome-wide miRNA expression profiling of blood-derived exosomes from MDD patients and control subjects and revealed the top differentially expressed exosomal miRNA, i.e. hsa-miR-139-5p (upregulation), had good performance to differentiate between MDD patients and controls. Tail vein injection of blood exosomes isolated from MDD patients into normal mice caused their depressive-like behaviors as determined by the forced swimming, tail suspension, and novelty suppressed feeding tests, and injection of blood exosomes isolated from healthy volunteers into unpredictable mild stress (CUMS)-treated mice alleviated their depressive-like behaviors. CUMS mice also showed significantly increased blood and brain levels of exosomal miR-139-5p. Furthermore, the depressive-like behaviors in CUMS-treated mice were rescued by intranasal injection of miR-139-5p antagomir, suggesting that increased exosomal miR-139-5p levels may mediate stress-induced depression-like behavior in mice. Both exosome treatment and miR-139-5p antagomir treatment increased hippocampal neurogenesis in the CUMS-treated mice, and treatment of exosome from MDD patients decreased hippocampal neurogenesis in the normal mice. The role of miR-139-5p in neurogenesis was validated by in vitro experiments, demonstrating that miR-139-5p is a negative regulator for neural stem cell proliferation and neuronal differentiation. Our findings together suggest that exosomes from patients with major depression caused depressive-like behaviors in mice with involvement of miR-139-5p-regulated neurogenesis. Therefore, exosomal miRNAs are promising targets for the diagnosis and treatment of MDD.

Background: Guillain Barre Syndrome (GBS) is an autoimmune disorder caused by the immune-mediated damage of the peripheral nervous system. Increasing evidence suggests that inflammatory cytokines are important mediators for the onset and progression of GBS. A number of clinical studies have demonstrated elevated levels of T helper-1 (Th1-), Th2-, and Th17-related cytokines in patients with GBS; however, the results were inconsistent across studies. Methods: We performed a systematic review and a meta-analysis of studies comparing the levels of inflammatory cytokines in the cerebrospinal fluid and peripheral blood between patients with GBS and healthy individuals, using Comprehensive Meta-Analysis Version 2 software. A database search identified 30 studies comprising 1,302 patients with GBS and 1,073 healthy controls. Results: The random-effects meta-analysis demonstrated that peripheral blood tumor necrosis factor-α (Hedges g, 1.544; 95% confidence interval (CI), 0.923–2.165; p < 0.001), interleukin-1β (IL-1β; Hedges g, 0.678; 95% CI, 0.183–1.172; p = 0.007), IL-6 (Hedges g, 0.630; 95% CI, 0.100–1.160; p = 0.02), IL-4 (Hedges g, 0.822; 95% CI, 0.220–1.423; p = 0.007), IL-17 (Hedges g, 1.452; 95% CI, 0.331–2.573; p = 0.011), interferon-γ (Hedges g, 1.104; 95% CI, 0.490–1.719; p < 0.001), and C-reactive protein (Hedges g, 0.909; 95% CI, 0.453–1.365; p < 0.001) levels were significantly increased in patients with GBS when compared with healthy controls. Contrastingly, the blood IL-10 and transforming growth factor-β levels were not significantly associated with GBS. Furthermore, the meta-analysis found that cerebrospinal fluid IL-17 levels were significantly associated with GBS (Hedges g, 1.882; 95% CI, 0.104–3.661; p = 0.038). Conclusion: Altogether, our results clarified the circulating inflammatory cytokine profile in patients with GBS, and revealed that Th1-, Th2-, and Th17-related cytokines were highly elevated in the GBS patients, suggesting the potential use of these cytokines as biomarkers for GBS.

Two of hydrophobic functionalized ionic liquids (FILs) were synthesized according to the traditional method. The FILs are 1-(cyanomethyl)-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([MCNMIM][NTf2]) and 1-(2-hydroxyethyl)-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([EOHMIM][NTf2]). Density, dynamic viscosity, and electrical conductivity of the two FILs were determined in the range of T = (283.15 to 353.15) K. The other important physico-chemical properties, like molecular volume, standard molar entropy, and lattice energy, of the two FILs were estimated by empirical equations on the bases of the experimental density. The Vogel–Fulcher–Tamman (VFT) and Arrhenius equations were used for fitting of the temperature dependence of the dynamic viscosity and electrical conductivity. The activation of electrical conductivity and dynamic viscosity were calculated by the final version VFT equation. The molar conductivities were determined from density and electrical conductivity by the empirical equation. According to Walden rule, the Walden equation was used for description of the density, dynamic viscosity, and electrical conductivity. The introduction of the functional group (cyano and hydroxy) on imidazolium ring can provided hydrogen bond formation. The FILs exhibited the higher density, dynamic viscosity and lower electrical conductivity than traditional non-functional ILs.

A novel non-isometric helically coiled heat exchanger, with first-dense-then-sparse type structure, was proposed to improve the performance of Joule-Thomson (J-T) cryocoolers. The physical model and analysis model of exergy destruction of this new non-isometric helically coiled heat exchanger were developed. The influence of three key geometrical parameters (the separation position i, the fin pitch of the dense part fp1, the fin pitch of the sparse part fp2) on the performance of heat exchanger were investigated, and the structure of recuperator was further optimized using response surface methodology (RSM). The results show that the total exergy destruction of the optimum recuperator decreased by 8% and the material consumption reduced by 4%. Furthermore, the refrigeration capacity increased by 9%, which proves the potential of this novel non-isometric helically coiled heat exchanger in heat transfer performance and material consumption. This study provides helpful guidance for geometrical optimization of the recuperator for J-T cryocoolers.

It has been suggested that cytokine-mediated inflammation plays a key role for the onset and/or development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). However, clinical studies have yielded inconsistent results for the aberrant cytokine levels in circulation of patients with AD, PD, and ALS. Previous studies have used meta-analysis to address the inconsistent data for blood cytokine levels in the patients with AD, PD, and ALS. Here, we performed a systemic review of cerebrospinal fluid inflammatory cytokine data in patients with AD, PD and ALS, and sought to quantitatively summarize the CSF inflammatory cytokine data with a meta-analytical technique. The systematic search from Pubmed and Web of Science identified 71 articles with 2629 patients and 2049 controls for the meta-analysis. Random-effects meta-analysis demonstrated that CSF TGF-β, MCP-1, and YKL-40 levels were significantly elevated in AD patients when compared with controls. In addition, patients with PD had heightened levels of TGF-β1, IL-6, and IL-1β in CSF. Furthermore, G-CSF, IL-2, IL-15, IL-17, MCP-1, MIP-1α, TNF-α, and VEGF levels were significantly increased in patients with ALS as compared with controls. Taken together, these results not only strengthen the clinical evidence that neurodegenerative diseases are accompanied by the increased inflammatory response, but also reveal the unique inflammatory response profile in the central nervous system of patients with AD, PD and ALS. Given the robust associations between some cytokines and neurodegenerative diseases found in this meta-analysis, CSF inflammatory cytokines may be used as biomarkers for these diseases in the future.

Oxidative stress has been suggested to play a key role in Parkinson's disease, but inconsistent results were found in clinical studies. This study sought to quantitatively summarize the blood and cerebrospinal fluid (CSF) oxidative stress marker data in PD patients. We performed a systematic search of PubMed and Web of Science, and studies were included if they provided data on peripheral blood and CSF oxidative stress marker concentrations in PD patients and healthy control (HC) subjects. Data were extracted by three independent investigators from 80 included studies encompassing 7,212 PD patients and 6,037 HC subjects. Of the 22 oxidative stress markers analyzed, random effects meta-analysis showed that blood concentrations of 8-OhdG, MDA, nitrite, and ferritin were increased in patients with PD compared with HC subjects. In contrast, we showed that blood levels of catalase, uric acid, glutathione, and total-cholesterol were significantly down-regulated in patients with PD when compared with controls. There were no significant differences between PD patients and HC subjects for blood, Mn, Cu, Zn, Fe, SOD, albumin, glutathione peroxidase, vitamin E, ceruloplasmin, triglycerides, lactoferrin, transferrin, LDL-cholesterol, and HDL-cholesterol. Due to the limited number of CSF studies with small sample size, this meta-analysis only showed non-significant association between CSF 8-OhdG and PD. The findings of our meta-analysis demonstrated higher blood concentrations of 8-OhdG, MDA, nitrite and ferritin, and lower blood concentrations of catalase, uric acid, glutathione and total-cholesterol in PD patients, strengthening the clinical evidence that PD is accompanied by increased oxidative stress.

Objective To obtain immobilized nanomaterials with good performance, the preparation condition of chitosan nanospheres by miniemulsion crosslinking method was optimized. Methods The chitosan nanospheres were synthesized by miniemulsion crosslinking method with Span80 and Tween80 as the emulsifier, glutaraldehyde as the crosslinker, n-hexane and paraffin liquid as oil phase,chitosan acetic acid solution as aqueous phase. The particle size was measured by Zetasizer nanoanalyzer. Results The results of the univariate tests show that the optimal preparation condition of chitosan nanospheres can be obtained when water/oil volume ratio is 3:2. The size distribution of chitosan nanospheres is 18.17nm to 190.1nm. Conclusion The chitosan nanospheres by miniemulsion crosslinking method are suitable materials as enzymes and proteins immobilized carrier.

To study the performance of chitosan nanoparticles systematically, we characterized MMA, chitosan and synthesized chitosan nanoparticles by Raman spectroscopy. Through analyzing the characteristic peaks of each substance, we found MMA grafted chitosan by opening its carbon-carbon double bond. So Raman spectroscopy is a very effective way in terms of the characterization of nanomaterials .

Molecular imprinting technology (MIT) is a developing technique with high recognition which is just like the recognition between enzymes and antibodies in the organism. Molecularly imprinted polymers (MIPs), synthetic materials obtained using the imprinting technology, have played a huge advantage and been used in many fields. Especially, MIPs have been applied to the extraction and separation of analytes as the selective adsorbent of solid-phase extraction (SPE), which is known as molecularly imprinted polymer solid-phase extraction (MISPE) in recent years. In the present review, the methodology of MIPs preparation and evaluation are explained. Moreover, recent great developments of SPE and MISPE are discussed, and the potential application of MISPE in extraction of traditional Chinese medicine (TCM) active ingredients are also presented briefly.