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ObjectiveParent-child relationship is critical for children’s well-being. In China, the large number of left-behind children (LBC, one or both parents leaving for work for at least 6 months) raises public concern. Although LBC often report poor mental health status and higher alienation towards parents, the dynamic trend of subjective well-being in this population, as well as the prediction of alienation towards parents on LBC’s subjective well-being, remain unrevealed. This study aimed to examine the dynamic trend of subjective well-being in Chinese LBC and further explore the predictional influence of alienation towards parents, with resilience as a potential mediator.MethodsWe recruited 916 rural LBC in China and investigated them at five waves (baseline, and 1, 3, 6, and 12 months later) using Inventory of Alienation towards Parents (IAP), Resilience Scale for Chinese Adolescents (RSCA) and Subjective Happiness Scale (SHS). We used hierarchical linear modeling (HLM) for analysis.ResultsAt baseline, no significant differences were found in the scores of alienation towards parents, resilience, and subjective well-being on gender, grade, or type of LBC. A significant correlation existed between the scores of alienation towards parents, resilience, and subjective well-being. HLM showed a linear increase in the subjective well-being of rural LBC. Alienation toward both mother and father negatively predicted the developmental trajectory of children’s subjective well-being over 12 months. Moreover, resilience partially mediated this prediction.ConclusionThis study is among the first to reveal that alienation towards parents predicts the developmental trajectory of later LBC’s subjective well-being, with resilience as a mediator. These findings warrant the necessity of paying attention to alienation toward parents to ensure the mental health of LBC, giving valuable guidance to parents, schools and governments.

Abstract Background More than half of patients with tuberous sclerosis complex (TSC) suffer from drug-resistant epilepsy (DRE), and resection surgery is the most effective way to control intractable epilepsy. Precise preoperative localization of epileptogenic tubers among all cortical tubers determines the surgical outcomes and patient prognosis. Models for preoperatively predicting epileptogenic tubers using 18F-FDG PET images are still lacking, however. We developed noninvasive predictive models for clinicians to predict the epileptogenic tubers and the outcome (seizure freedom or no seizure freedom) of cortical tubers based on 18F-FDG PET images. Methods Forty-three consecutive TSC patients with DRE were enrolled, and 235 cortical tubers were selected as the training set. Quantitative indices of cortical tubers on 18F-FDG PET were extracted, and logistic regression analysis was performed to select those with the most important predictive capacity. Machine learning models, including logistic regression (LR), linear discriminant analysis (LDA), and artificial neural network (ANN) models, were established based on the selected predictive indices to identify epileptogenic tubers from multiple cortical tubers. A discriminating nomogram was constructed and found to be clinically practical according to decision curve analysis (DCA) and clinical impact curve (CIC). Furthermore, testing sets were created based on new PET images of 32 tubers from 7 patients, and follow-up outcome data from the cortical tubers were collected 1, 3, and 5 years after the operation to verify the reliability of the predictive model. The predictive performance was determined by using receiver operating characteristic (ROC) analysis. Results PET quantitative indices including SUVmean, SUVmax, volume, total lesion glycolysis (TLG), third quartile, upper adjacent and standard added metabolism activity (SAM) were associated with the epileptogenic tubers. The SUVmean, SUVmax, volume and TLG values were different between epileptogenic and non-epileptogenic tubers and were associated with the clinical characteristics of epileptogenic tubers. The LR model achieved the better performance in predicting epileptogenic tubers (AUC = 0.7706; 95% CI 0.70–0.83) than the LDA (AUC = 0.7506; 95% CI 0.68–0.82) and ANN models (AUC = 0.7425; 95% CI 0.67–0.82) and also demonstrated good calibration (Hosmer‒Lemeshow goodness-of-fit p value = 0.7). In addition, DCA and CIC confirmed the clinical utility of the nomogram constructed to predict epileptogenic tubers based on quantitative indices. Intriguingly, the LR model exhibited good performance in predicting epileptogenic tubers in the testing set (AUC = 0.8502; 95% CI 0.71–0.99) and the long-term outcomes of cortical tubers (1-year outcomes: AUC = 0.7805, 95% CI 0.71–0.85; 3-year outcomes: AUC = 0.8066, 95% CI 0.74–0.87; 5-year outcomes: AUC = 0.8172, 95% CI 0.75–0.87). Conclusions The 18F-FDG PET image-based LR model can be used to noninvasively identify epileptogenic tubers and predict the long-term outcomes of cortical tubers in TSC patients.

To compare the effects of different drying methods on the solid spice of sweet potato, the fresh sweet potato was taken as the research object, and infrared drying, freeze drying, microwave vacuum drying and vacuum drying were carried out after baking. The volatile/semi volatile components of the solid spice of sweet potato were analyzed and detected by gas chromatography mass spectrometry (GC-MS), principal component analysis was used to explore the impact of different drying methods on volatile/semi volatile components, and scanning electron microscopy was used to explore the impact of different drying methods by its surface structure. The results showed that the content of volatile/semi-volatile substances in dried sweet potato solid flavor from high to low was vacuum drying, microwave vacuum drying, infrared drying and freeze drying, and the highest content was 128.87 μg/g, the main flavor substances include octyl p-methoxycinnamate, palmitoleic acid, geranyl linalool, 5-hydroxymethylfurfural, (9Z)-octadec-9,17-dialdehyde. Compared with the other three drying methods, the surface structure of vacuum dried solid spice had more water evaporation channels and holes, and the structural density was moderate, which had a positive impact on the adsorption capacity and volatile flavor of solid spice. In conclusion, vacuum drying was applicable to the drying and preparation of sweet potato solid spice, which laid a theoretical foundation for the development and application of sweet potato solid spice.

ABSTRACT: An acidic extracellular polysaccharide (EPS) was gained from Stropharia rugosoannulata fermentation broth by the alcohol precipitate method. Sulfated derivative of EPS (S-EPS) was gained by chlorosulfonic acid-pyridine method and the conditions were as follows: pyridine as the reaction solvent, temperature 80 °C, and reaction time 90 min. The chemical structure and chain conformation of EPS and S-EPS were characterized by FT-IR, NMR and size exclusion chromatography (SEC) coupled with multi-angle laser light scattering (MALLS) detection. FT-IR spectra indicated the sulfated group was linked to the polymer. The EPS mainly consists of mannose, glucose and glucuronic acid, and the glycosidic bond type is mainly (1→4)-linked and (1→6)-linked. C6 and C2 were substituted by sulfate groups. The EPS was degraded into smaller molecular weight (Mw) polysaccharides with the larger molecular size (Rg) after sulfation and S-EPS has better hydrophilicity. Moreover, the sulfated derivative S-EPS was found to have a better scavenging ability on hydroxyl radicals than EPS. It proved that the chemical modification of S. rugosoannulata polysaccharides by sulfation effectively enhanced their antioxidant activity.

Parkinson’s disease (PD) is characterized not only by motor symptoms but also by non-motor dysfunctions, such as olfactory impairment; the cause is not fully understood. Our study suggests that neuronal loss and inflammation in brain regions along the olfactory pathway, such as the olfactory bulb (OB) and the piriform cortex (PC), may contribute to olfactory dysfunction in PD mice, which might be related to the downregulation of the trace amine-associated receptor 1 (TAAR1) in these areas. In the striatum, although only a decrease in mRNA level, but not in protein level, of TAAR1 was detected, bioinformatic analyses substantiated its correlation with PD. Moreover, we discovered that neuronal death and inflammation in the OB and the PC in PD mice might be regulated by TAAR through the Bcl-2/caspase3 pathway. This manifested as a decrease of anti-apoptotic protein Bcl-2 and an increase of the pro-apoptotic protein cleaved caspase3, or through regulating astrocytes activity, manifested as the increase of TAAR1 in astrocytes, which might lead to the decreased clearance of glutamate and consequent neurotoxicity. In summary, we have identified a possible mechanism to elucidate the olfactory dysfunction in PD, positing neuronal damage and inflammation due to apoptosis and astrocyte activity along the olfactory pathway in conjunction with the downregulation of TAAR1.

Tumor diagnosis, especially at the early stages, holds immense significance. Focal adhesion kinase (FAK) is often highly expressed across various types of tumors, making it a promising target for both therapy and diagnosis. In this study, seven novel inhibitors were designed and synthesized. The inhibitory activity of these compounds against FAK was notably potent, with an IC50 range of 1.27–1968 nM. In particular, compounds 7a and 7c, with IC50 values of 5.59 nM and 1.27 nM, respectively, were radiolabeled with F-18 and then evaluated with S-180 tumor-bearing mice. Subsequently, they exhibited moderate-to-high tumor uptake values, with [18F]7a showing 1.39 ± 0.30%ID/g at 60 min post injection and [18F]7c demonstrating 6.58 ± 0.46%ID/g at 30 min post injection. In addition, the results from docking studies revealed the binding specifics of the studied compounds. Overall, these findings hold the potential to offer valuable guidance for enhancing the development of radiotracers and enzyme inhibitors.

Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson’s disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to PD is unknown. To answer this question, the mice received MPTP intraperitoneally to construct a subacute model of PD and were then supplemented with Akk orally for 21 consecutive days. Motor function, dopaminergic neurons, neuroinflammation, and neurogenesis were examined. In addition, intestinal inflammation, and serum and fecal short-chain fatty acids (SCFAs) analyses, were assessed. We found that Akk treatment effectively inhibited the reduction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and partially improved the motor function in PD mice. Additionally, Akk markedly alleviated neuroinflammation in the striatum and hippocampus and promoted hippocampal neurogenesis. It also decreased the level of colon inflammation. Furthermore, these aforementioned changes are mainly accompanied by alterations in serum and fecal isovaleric acid levels, and lower intestinal permeability. Our research strongly suggests that Akk is a potential neuroprotective agent for PD therapy.

γ-Glutamyl peptides can enhance basic taste sensations such as saltiness, sweetness, and umaminess, while the molecular mechanism and the difference in taste enhancement remain elusive. Thus, two complex conformations: taste type 1 receptor 1 (T1R1)-MSG and taste type 1 receptor 2 (T1R2)-sucrose were constructed to form binding receptors. These peptides showed affinity for the two receptors, but a higher affinity scores and more binding amino acid residues for the T1R1-MSG receptor, implying that they may exhibit a higher umami-enhancing effect. Thereinto, γ-glutamyl alanine (γ-EA) displayed the highest affinity for the two receptors through mobilizing multiple amino acid residues to form hydrophobic and hydrogen bonds, indicating it had the highest enhancement for umaminess and sweetness among these peptides. Sensory evaluation demonstrated the enhancement of γ-EA on umaminess was superior to that of sweetness. Generally, γ-glutamyl peptides could enhance basic taste sensation via activating taste receptor, and exhibited a highest umami-enhancing effect.

In this work, an egg yolk protein hydrolysate (EYPH) with a high iron-chelating ability (87.32%) was prepared. The fractionation using 60% (v/v) ethanol concentration (E3 fraction) led to the efficiently accumulating the iron-chelating peptides in EYPH. The characterization results showed that iron mainly chelated with carboxyl, amino and phosphate groups of peptides. From E3 fraction, six iron-chelating peptides with MW ranging from 1372.36 to 2937.04 Da were identified and a hypothesized molecular model of DDSSSpSpSpSpSpSVLSK-Fe was simulated. In vitro stability determination showed that E3-Fe chelate owned a good heat, alkalinity and digestion tolerance, but a relatively bad acid tolerance. Finally, iron transport analysis showed that iron in the E3-Fe would be absorbed in caco-2 cell membrane more effectively than that of iron salts, indicating that it was possible to apply the E3-Fe complex as iron supplements.

ObjectiveRecent evidence has demonstrated that unilateral carotid artery stenosis (CAS) can contribute to the development of cognitive impairment. However, the features of cognitive dysfunction induced by unilateral CAS remain unclear.MethodsSixty asymptomatic patients with unilateral CAS were divided into mild, moderate and severe stenosis groups. These patients and 20 healthy controls provided clinical data and serum, which was used to assess the levels of certain vascular risk factors. Then, they participated in a battery of neuropsychological tests. Additionally, all participants underwent a 3.0 T magnetic resonance imaging (MRI) scan of the brain. Chi-square tests and one-way ANOVA were used to determine significant differences in the risk factors and cognitive test scores between groups. Multiple logistic regression analysis and the receiver operating characteristic (ROC) curve analysis were performed to identify the independent risk factors for cognitive impairment in patients with CAS. Finally, fluid attenuated inversion recovery (FLAIR) T1-weighted MRI images were processed by voxel-based morphometry (VBM) analysis using the Statistical Parametric Mapping (SPM) 8 software.ResultsCompared with healthy controls, the scores of the Mini-Mental State Examination, Digital Span Test backward, and Rapid Verbal Retrieve were significantly reduced in patients with left CAS. The scores in all cognitive scales were significantly lower in patients with right CAS than in controls. Logistic regression analysis demonstrated that the degree of carotid stenosis was an independent risk factor for cognitive impairment in asymptomatic patients with unilateral CAS. Furthermore, VBM analysis showed that, compared with those in healthy controls, gray matter and white matter volumes in specific brain areas were markedly decreased in patients with severe unilateral CAS. However, in patients with moderate right CAS, there was a significant decline in the volume of gray matter in the left parahippocampal gyrus and supplementary motor area. Additionally, the volume of white matter in the left insula was obviously lower in patients with moderate right CAS than in healthy controls.ConclusionUnilateral asymptomatic CAS, especially on the right side, contributed to cognitive impairment, including memory, language, attention, executive function and visuospatial function. In addition, based on VBM analysis, both gray matter atrophy and white matter lesions were found in patients with unilateral asymptomatic CAS.

Accumulative studies suggest that inflammatory bowel disease (IBD) may cause multiple central nervous system (CNS) pathologies. Studies have found that indoleamine-2,3-dioxygenase (IDO, rate-limiting enzyme of the kynurenine (Kyn) pathway) deficient mice were protected from endotoxin induced cognitive impairment, and Kyn administration induced cognitive memory deficits in both control and IDO-deficient mice. However, there is no investigation of the brain Kyn pathway in IBD, thus we investigated whether dextran sulfate sodium (DSS)-induced colitis could cause dysregulation of Kyn pathway in brain, and also in serum. C57BL/6J mice were given drinking water with 2% DSS for 10 consecutive days to induce colitis. In serum, we found significant increase in Kyn and kynurenic acid (Kyna) level, which was regulated by IDO-1 and KAT2 (rate-limiting enzymes of Trp-Kyn-Kyna pathway). Similarly, by analyzing GEO datasets, higher IDO-1 levels in peripheral blood monocytes and colon of UC patients was found. Furthermore, the Kyn pathway was significantly upregulated in the cerebral cortex under the action of IDO-1 after DSS treatment, which ultimately induced the neurotoxic phenotype of astrocytes. To investigate whether gut microbiota is involved in IBD-induced Kyn pathway dysregulation, we performed intestinal flora 16S rRNA sequencing and found that DSS-induced colitis significantly altered the composition and diversity of the gut microbiota. Metabolic function analysis also showed that Tryptophan metabolism, NOD-like receptor signaling pathway and MAPK signaling pathway were significantly up-regulated in the 2% DSS group. A significant association between intestinal flora and Trp metabolism (both in serum and brain) was found by correlation analysis. Overall, this study revealed that DSS-induced colitis causes dysregulation of the Kyn pathway in serum and brain by affecting rate-limiting enzymes and intestinal flora.

This study aimed to obtain three Trp-containing peptides from β-lactoglobulin and study their effects on anxiety-like behaviors in zebrafish. Three Trp-containing peptides were prepared from β-lactoglobulin by selective enzymatic hydrolysis and identified by UPLC-Q-TOF MS/MS. The anxiety-like behaviors of zebrafish were reduced after two weeks of administrated of β-lactoglobulin Trp peptides (LAWP), VAGTWY, VAGTW and G TW(concentration of 56 μg/mL or 500 μg/mL). As an index of serotonergic activity, we assessed the enhancing abilities of 5-HT synthesis. The treatment remarkably enhanced the 5-HT synthesis by upregulation of Trp concentration and Trp hydroxylase activation. In addition, this study further validated the anti-anxiety effects of whey protein hydrolysate with a high Trp index in animal and the experimental results were consistent with those reported in previous studies. Our results showed that β-lactoglobulin Trp peptides ingestion has a significant anti-anxiety effect as evidenced by the increasing Trp concentration, TPH activation and 5-HT level compared to the control group, with the VAGTW being the more effective.

In view of a series of adverse side effects of drugs for anxiety/depression on the market at present, it is imminent to extract and develop novel anti-anxiety and depression drugs from plants and proteins (like casein hydrolysate) as adjuncts or substitutes for existing anti-anxiety and depression drugs. Consequently, this study investigated the improvement of the anxiety/depression function by the compound of casein hydrolysate and γ-aminobutyric acid (GABA) (casein hydrolysate: GABA = 4:1; CCHAA) on mice induced by chronic restraint stress-corticosterone injection. Animal experiments revealed that oral gavage administration of CCHAA significantly reversed the anxiety/depression-like behaviors. Compared to the model control group, body weights were increased after treatment with CCHAA groups [1.5, 0.75 mg/(g⋅d)]. As a diagnostic index of anxiety and depression, we assessed GABA and 5-HT levels in response to CCHAA ingestion. The GABA and 5-HT levels were increasingly enhanced by the CCHAA diet. In addition, histopathological changes in the hippocampus CA3 region of the anxious/depressed mice were also alleviated after the treatment with the CCHAA. Thus, the casein hydrolysate and GABA formula diets may induce beneficial effects on the mice with anxiety/depression.

Objective: Few studies have reported the direct effect of C–X–C motif chemokine ligand 10 (CXCL10) and Neuregulin 1 (Nrg1) on neurons after spinal cord injury (SCI). This study reports the role of CXCL10 in the regulation of neuronal damage after SCI and the potential therapeutic effect of Nrg1. Methods: The expression level of CXCL10 and Nrg1 in SCI mice was analyzed in the Gene Expression Omnibus DataSets, followed by immunohistochemical confirmation using a mouse SCI model. HT22 cells and NSC34 cells were treated with CXCL10 and Nrg1, individually or in combination, and then assayed for cell viability. The percentage of wound closure was determined through the cell scratch injury model using HT22 and NSC34 cells. Potential molecular mechanisms were also tested in response to either the individual administration of CXCL10 and Nrg1 or a mixture of both molecules. Results: CXCL10 expression was significantly increased in both young and old mice subjected to SCI, while Nrg1 expression was significantly decreased. CXCL10 induced a decrease in cell viability, which was partially reversed by Nrg1. CXCL10 failed to inhibit scratch healing in HT22 and NSC34 cells, while Nrg1 promoted scratch healing. At the molecular level, CXCL10-activated cleaved caspase 9 and cleaved caspase 3 were both inhibited by Nrg1 through pERK1/2 signaling in HT22 and NSC34 cells. Conclusions: CXCL10 is upregulated in SCI. Despite the negative effect on cell viability, CXCL10 failed to inhibit the scratch healing of HT22 and NSC34 cells. Nrg1 may protect neurons by partially antagonizing the effect of CXCL10.

As a group of naturally occurring peptides in various foods, γ-glutamyl peptides possess a unique Kokumi taste and health benefits. However, few studies have focused on the functionality of γ-glutamyl peptides. In this study, the γ-[glutamyl] (n=1, 2, 3)-tryptophan peptides were synthesized from a solution of glutamine (Gln) and tryptophan (Trp) employing L-glutaminase from Bacillus amyloliquefaciens. Four different γ-glutamyl peptides were identified from the reaction mixture by UPLC-Q-TOF-MS/MS. Under optimal conditions of pH 10, 37 °C, 3 h, 0.1 mol/L Gln: 0.1 mol/L Trp = 1:3, and glutaminase at 0.1% (m/v), the yields of γ-l-glutamyl-l-tryptophan (γ-EW), γ-l-glutamyl-γ-l-glutamyl-l-tryptophan (γ-EEW) and γ-l-glutamyl-γ-l-glutamyl-γ-l-glutamyl-l-tryptophan (γ-EEEW) were 51.02%, 26.12% and 1.91% respectively. The antioxidant properties of the reaction mixture and the two peptides (γ-EW, γ-EEW) identified from the reaction media were further compared. Results showed that γ-EW exhibited the highest DPPH•, ABTS•+ and O2•−-scavenging activity (EC50 = 0.2999 mg/mL, 67.6597 μg/mL and 5.99 mg/mL, respectively) and reducing power (EC50 = 4.61 mg/mL), while γ-EEW demonstrated the highest iron-chelating activity (76.22%). Thus, the synthesized mixture may be used as a potential source of antioxidant peptides for food and nutraceutical applications.

Observational studies have shown abnormal changes in trimethylamine N-oxide (TMAO) levels in the peripheral circulatory system of Parkinson’s disease (PD) patients. TMAO is a gut microbiota metabolite that can cross the blood–brain barrier and is strongly related to neuroinflammation. Neuroinflammation is one of the pathological drivers of PD. Herein, we investigated the effect of TMAO on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. TMAO pretreatment was given by adding 1.5% (w/v) TMAO to the drinking water of the mice for 21 days; then, the mice were administered MPTP (20 mg/kg, i.p.) four times a day to construct an acute PD model. Their serum TMAO concentrations, motor function, dopaminergic network integrity, and neuroinflammation were then assayed. The results showed that TMAO partly aggravated the motor dysfunction of the PD mice. Although TMAO had no effect on the dopaminergic neurons, TH protein content, and striatal DA level in the PD mice, it significantly reduced the striatal 5-HT levels and aggravated the metabolism of DA and 5-HT. Meanwhile, TMAO significantly activated glial cells in the striatum and the hippocampi of the PD mice and promoted the release of inflammatory cytokines in the hippocampus. In summary, higher-circulating TMAO had adverse effects on the motor capacity, striatum neurotransmitters, and striatal and hippocampal neuroinflammation in PD mice.

This study investigated the anti-anxiety/anti-depression potential of a formula containing red pomegranate fruit extract (RPFE; 40%, m/m), Lactobacillus rhamnosus (JB-1) (34%, m/m), magnesium gluconate (25%, m/m) and vanillin (1%, m/m). The RPFE formula (dose: 2.0, 1.5 or 1.0 mg/g day) reversed behavioral dysfunctions and body weight gain induced by chronic restraint stress combined with corticosterone injection in C57BL/6 male mice. The RPFE formula exhibited the abilities to normalize the levels of serum inflammatory cytokines (NF-κB, TNF-α, IL-6, IL-1β and IFN-γ) and malondialdehyde (MDA), and activities of superoxide dismutase (SOD), catalase (CAT) and nitric oxide synthase (NOS), as well as relieve the injury of hippocampal neurons. The serotonin (5-HT) levels in hippocampus were increasingly enhanced, which might be mediated by reducing the activity of indoleamine-2,3-dioxygenase (IDO) and increasing the activity of tryptophan hydroxylase (TPH). Thus, the neuroprotective and ameliorating effects on anxiety/depression-like behaviors resulting from the RPFE formula ingestion were possibly related to serotonergic activation, which might be mediated via anti-inflammatory and anti-oxidant actions.

BackgroundTransient receptor potential melastatin 8 (TRPM8) modulates tumor biology and sensitivity to treatment. The present study aimed to determine the part it plays in tumor immunity and physiology using pan-cancer analysis.MethodData from the GTEx, CCLE, TISIDB, GSCA, cBioportal, and TCGA databases were collected using Estimate, Scanneo, and GSEA, and the associations between TRPM8 and prognosis, molecular subtypes, mutational burden, microsatellite instability, immune gene functions, and drug sensitivity were analyzed in 33 tumor types.ResultTRPM8 levels were found to be elevated in most tumors, particularly in solid tumors, with variations according to clinical stage. Mutation frequency was greatest in endometrial carcinoma. High levels of TRPM8 were linked to unfavorable prognosis, immune cell infiltration, and the tumor microenvironment, as well as correlating with abnormalities in the transcription levels of genes associated with immunity and DNA repair. TRPM8 was also linked to unfavorable patient outcomes and cancer-associated signaling.ConclusionsTRPM8 is strongly associated with tumor physiology and immunity. The Pan-Cancer analysis suggests the potential of TRPM8 as a treatment target or biomarker for determining the prognosis of a specific type of cancer.

Neuroinflammation is one of the hallmarks of Parkinson’s disease, including the massive activation of microglia and astrocytes and the release of inflammatory factors. Receptor-interacting protein kinase 1 (RIPK1) is reported to mediate cell death and inflammatory signaling, and is markedly elevated in the brain in PD mouse models. Here, we aim to explore the role of RIPK1 in regulating the neuroinflammation of PD. C57BL/6J mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 20 mg/kg four times/day), followed by necrostatin-1 treatment (Nec-1, RIPK1 inhibitor; 1.65 mg/kg once daily for seven days. Notably, the first Nec-1 was given 12 h before MPTP modeling). Behavioral tests indicated that inhibition of RIPK1 greatly relieved motor dysfunction and anxiety-like behaviors of PD mice. It also increased striatal TH expression, rescue the loss of dopaminergic neurons, and reduce activation of astrocytes in the striatum of PD mice. Furthermore, inhibition of RIPK1 expression reduced A1 astrocytes’ relative gene expression (CFB, H2-T23) and inflammatory cytokine or chemokine production (CCL2, TNF-α, IL-1β) in the striatum of PD mice. Collectively, inhibition of RIPK1 expression can provide neuroprotection to PD mice, probably through inhibition of the astrocyte A1 phenotype, and thus RIPK1 might be an important target in PD treatment.

Auricularia auricula (AA) and Auricularia polytricha (AP) are popular edible fungi. This study successfully produced hypoglycemic polysaccharides from un-smashed or smashing and sieving (through a 10-mesh sieve) AA and AP (termed as AAP/AAP-10 and APP/APP-10) via scalable processes (water extraction, ethanolic precipitation and deproteinization). This is the first report to compare the effectiveness of AAP and APP in combating streptozotocin-induced oxidative stress and diabetes-related changes in mice (body weight, fasting blood glucose, serum insulin, proinflammatory mediator and cytokines, oxidative stress-related products, antioxidant enzymes). APP and AAP with different molecular weights and monosaccharide molar ratios could be therapeutic options for diabetes with a low dose (100 mg/kg/day) likely working better. At the same dose, APP generally performed more effective than AAP, and AAP-10/APP-10 seemed slightly more beneficial than AAP/APP. One mechanism underlying these antidiabetic functions might involve the NF-κB and associated signalling pathways. AP is cheaper than AA, thereby representing a favorable source of functional polysaccharides.

Fermented foods represent an important segment of current food markets, especially traditional or ethnic food markets. The demand for efficient utilization of agrowastes, together with advancements in fermentation technologies (microbial- and enzyme-based processing), are stimulating rapid growth and innovation in the fermented food sector. In addition, the health-promoting benefits of fermented foods are attracting increasingly attention. The microorganisms contained in many common fermented foods can serve as “microfactories” to generate nutrients and bioactives with specific nutritional and health functionalities. Herein, recent research relating to the manufacture of fermented foods are critically reviewed, placing emphasis on the potential health benefits of fermentation-enabled wellness foods. The importance of the correct selection of microorganisms and raw materials and the need for precise control of fermentation processes are explored. Major knowledge gaps and obstacles to fermented food production and market penetration are discussed. The importance of integrating multidisciplinary knowledge, communicating with consumers, establishing regulatory frameworks specifically for fermentation-enabled wellness foods and functional fermented foods, are highlighted. Keywords: Fermented foods, Microbial factories, Bioactive, Probiotics, Nutrients, Processing technologies

This study compared enhanced serotonin (5-HT) synthesis roles of γ-[Glu]n-Trp (EW) and whey protein hydrolysate (WPH, Val-Ala-Gly-Thr-Trp-Tyr, Val-Ala-Gly-Thr-Trp, Ser-Ala-Trp-Tyr, Trp-Tyr-Ser, Gly-Thr-Trp) using anxious depression C57BL/6 mice. As an index of serotonergic activity, we assessed 5-HT levels in response to Trp oligopeptide ingestion. The neuroprotective and hypothalamic-pituitaryadrenal (HPA) axis hormones were examined in order to characterize the suggested improvements of anxious depression observed in mice after ingestion Trp oligopeptide. The 5-HT levels were increasingly enhanced by the EW and WPH diet, with the EW being more effective. But WPH had higher capacity on anti-oxidative than EW. EW and WPH could normalize the levels of HPA axis hormones, and promote brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling. In conclusion, Trp oligopeptide ingestion neuroprotective and HPA regulation effects possibly related to serotonergic activation and anti-oxidation. Consumed Trp oligopeptide diets may induce beneficial effects on anxious depression.

This study follows recent attempts to discover and improve the effectiveness of dietary peptides as stimulators of cholecystokinin (CCK) secretion. This study is the first report about the effect of γ-[Glu](n=1,2,3,4)-Trp, produced via γ-glutamylation by glutaminase, on CCK release and Ca2+-sensing receptor (CaS) activation. All these Trp-containing γ-glutamyl peptides exhibited abilities to trigger CCK secretion at 2.5–10 mM, with the highest amount of CCK (187.19 ± 0.68 pg/mL) occurring at 10 mM of γ-Glu-Trp and 5 mM of [Ca2+]e. A CaSR-mediated Ca2+/CaM/CaMK pathway in γ-[Glu](n=0,1,2,3,4)-Trp-induced CCK secretion was proposed based on the following results: the exposure to γ-Glu-Trp increased the protein expression level (Western bolt analysis); The intracellular calcium ([Ca2+]i) mobilization in response to γ-[Glu](n=0,1,2,3,4)-Trp was strongly enhanced; The inhibitors of signaling pathway proteins (NPS-2143, BAPTA-AM and KN62) abolished partially γ-[Glu](n=1,2,3,4)-Trp-induced CCK secretion. Glutaminase-catalyzed γ-glutamylation might be a useful approach for producing superior CCK secretion peptide stimulators.

Interferon regulatory factor 7 plays a crucial role in the innate immune response. However, whether interferon regulatory factor 7-mediated signaling contributes to Parkinson’s disease remains unknown. Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine–induced mouse model of Parkinson’s disease and co-localizes with microglial cells. Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype. In addition, siRNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase, tumor necrosis factor α, CD16, CD32, and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1. Taken together, our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase–stimulator of interferon genes–interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson’s disease

BACKGROUND: Theoretically human embryonic stem cells (hESCs) have the capacity to self-renew and differentiate into all human cell types. Therefore, the greatest promise of hESCs-based therapy is to replace the damaged tissues of patients suffering from traumatic or degenerative diseases by the exact same type of cells derived from hESCs. Allo-graft immune rejection is one of the obstacles for hESCs-based clinical applications. Human leukocyte antigen (HLA) II leads to CD4+ T cells-mediated allograft rejection. Hence, we focus on optimizing hESCs for clinic application through gene modification RESULTS: Transcription activator-like effector nucleases (TALENs) were used to target MHC class II transactivator (CIITA) in hESCs efficiently. CIITA-/-hESCs did not show any difference in the differentiation potential and self-renewal capacity. Dendritic cells (DCs) derived from CIITA-/-hESCs expressed CD83 and CD86 but without the constitutive HLA II. Fibroblasts derived from CIITA-/-hESCs were powerless in IFN-γ inducible expression of HLA II CONCLUSION: We generated HLA II defected hESCs via deleting CIITA, a master regulator of constitutive and IFN-γ inducible expression of HLA II genes. CIITA-/-hESCs can differentiate into tissue cells with non-HLA II expression. It's promising that CIITA-/-hESCs-derived cells could be used in cell therapy (e.g., T cells and DCs) and escape the attack of receptors' CD4+ T cells, which are the main effector cells of cellular immunity in allograft

White matter hyperintensities (WMHs) and brain atrophy often coexist in the elderly. Additionally, WMH is often observed as occipital periventricular hyperintensities (OPVHs) with low-grade periventricular white matter lesions and is usually confined within an anatomical structure. However, the effects of OPVHs on gray matter atrophy remain largely unknown. In this study, we investigated gray matter atrophy in OPVHs patients and explored the relationship between such atrophy and clinical risk factors. T1-weighted and T2-weighted MRI were acquired, and voxel-based morphometry (VBM) analysis was applied. The clinical (demographic and cardiovascular) risk factors of the OPVHs patients and healthy controls were then compared. Lastly, scatter plots and correlation analysis were applied to explore the relationship between the MRI results and clinical risk factors in the OPVHs patients. OPVHs patients had significantly reduced gray matter in the right supramarginal gyrus, right angular gyrus, right middle temporal gyrus, right anterior cingulum and left insula compared to healthy controls. Additionally, OPVHs patients had gray matter atrophy in the left precentral gyrus and left insula cortex, and such atrophy is associated with a reduction in low-density lipoprotein cholesterol and apolipoprotein-B.

Protein-polysaccharide conjugates were generally prepared by dry-heating. However, it was time-consuming and the sample gained was inhomogeneous. A faster way of preparing protein-polysaccharide conjugates is needed. Accordingly, soy protein isolates (SPI)-Acacia gum (GA) conjugates prepared by the wet-heating method were studied in the present work. Physicochemical properties of SPI-GA conjugates were also determined. The results showed that the wet-heating method could improve the rate of the graft reaction of protein and polysaccharide. The solubility of SPI-GA conjugates was significantly (P < 0.05) higher than that of unreacted SPI-GA mixtures and SPI at the same pH values. The emulsion activity index (EAI) of the grafted SPI increased remarkably. Moreover, a significant (P < 0.05) improvement on the emulsifying stability index (ESI) was observed and emulsions with a smaller droplet size were obtained. No visible flocculation during extended storage (30 days) was observed. The time course of the development of the graft reaction of SPI with GA was also shown by SDS-PAGE.

Myofibrillar protein was extracted from grass carp, a freshwater fish, and hydrolysed using five commercial proteases (papain, pancreatin 6.0, bromelain, Neutrase 1.5MG, and Alcalase 2.4 L). The antioxidant activities of the hydrolysates were determined. Pancreatin 6.0 proved to be the most efficient protease for hydrolysing myofibrillar protein with a very high protein recovery (90.20%), its hydrolysates exhibiting the highest hydroxyl radical (*OH) scavenging activity (IC50 = 349.89 ± 11.50 μg/ml) out of all five hydrolysates. Molecular weight distribution analysis revealed that pancreatin 6.0 hydrolysate rendered a higher proportion of the 6-10 kDa fraction and a lower proportion of the 3-6 kDa fraction as compared with other hydrolysates. The maximum *OH scavenging activity for pancreatin 6.0 hydrolysate (IC50 = 229.90 µg/ml) was obtained at the enzyme to substrate ratio of 0.52%, the incubation time of 7.03 h, and the incubation temperature of 50.56°C, as optimised by response surface methodology. In vitro antioxidant experiments proved that pancreatin 6.0 hydrolysates had obvious inhibitory effects on lipid peroxidation and low-density lipoproteins oxidation under optimised conditions.

A novel spectrophotometric method for determination of tryptophan content in protein hydrolysates has been developed. The reagent used is diphenylamine sulphonate which is oxidised to diphenylbenzidine sulphonic acid after reacting with sodium nitrite in the sulphuric acid medium. The unstable oxidation product reacts quickly with sodium nitrite to produce a diazotized intermediate. When the diazotized intermediate is coupled with tryptophan, a pink colour product is developed, which is stable for at least 1 h at the ambient temperature. This coloured product has the absorption maximum at 522 nm and the molar absorptivity is 8900 L/(mol·cm). Beer’s law is obeyed in the range of 0.30–12 mg/mL. The method is applied for the analysis of tryptophan content in grass carp protein hydrolysates. Moreover, it is compared with the reversed-phase high-performance liquid chromatography analysis. There is no significant (p

To investigate the effect of neurogenic neuroprotection conferred by cerebellar fastigial nucleus stimulation (FNS) and the role of PPARγ-mediated inflammation in a rat model of cerebral ischemia reperfusion.After a continuous 1 hour fastigial nucleus electric stimulation, the male Sprague Dawley (SD) rats were given middle cerebral artery occlusion (MCAO) for 1, 3, 6, 9, 12 and 15 hours undergoing reperfusion with intravenous recombinant tissue plasminogen activator (rt-PA), while the control group received without FNS. After 72 h of reperfusion, the neurological deficits, infarct volume and brain edema were evaluated. The brain tissue in ischemic penumbra was determined the myeloperoxidase (MPO) activity by a spectrophotometer and expression of PPARγ was measured by Rt-PCR and Western blotting.Our findings showed that FNS group had significantly reduced infarct volume and brain edema, and improved neurological deficits compared with the control group, especially in 6 h and 9 h reperfusion subgroups (p

Controlled enzymatic modification proteins are currently being used as good sources of bioactive protein ingredients, and hydrolysates derived from bighead carp muscles may serve as antioxidants through the control of the processing-related parameters. The antioxidant ability was evaluated with regard to the scavenging effect on free radical DPPH·, OH· and O2 ·–. Due to the robustness, fault tolerance, high computational speed and self--learning ability, artificial neural network (ANN) can be employed to build a predictive model for hydrolysis and optimize the hydrolysis variables: pH, temperature, hydrolysis time, muscle/water ratio and enzyme/substrate ratio (E/S) for the production of antioxidant peptides. Optimum conditions to achieve the maximum antioxidant ability were obtained. The hydrolysates, which scavenged most effectively the DPPH·, OH· and O2 ·–, were hydrolyzed for 4.8 h with an activity of alcalase of 4.8 AU/kg, for 6 h with 3.84 AU/kg and for 4.3 h with 4.8 AU/kg, at pH=7.5 and 60 °C. Their respective muscle/water ratio was 1:1.9, 1:1.4 and 1:1. The present study confirmed that ANN could be used to simulate the hydrolysis process and predict hydrolysis conditions under which the hydrolysates could show the most effective scavenging ability on DPPH·, OH· and O2 ·–.