Comparative physiological, metabolomic, and transcriptomic analyses reveal developmental stage-dependent effects of cluster bagging on phenolic metabolism in Cabernet Sauvignon grape berries.

BACKGROUND: Light conditions significantly influence grape berry ripening and the accumulation of phenolic compounds, but the underlying molecular basis remains partially understood. Here, we applied integrated transcriptomics and pathway-level metabolomics analyses to investigate the effect of cluster bagging during various developmental stages on phenolic metabolism in Cabernet Sauvignon grapes. RESULTS: Bagging treatments had limited effects on berry quality attributes at harvest and did not consistently affect phenolic acid biosynthesis between seasons. Significantly elevated flavan-3-ol and flavonol contents were detected in re-exposed berries after bagging during early-developmental stages, while bagging after véraison markedly inhibited skin anthocyanin accumulation. Several anthocyanin derivatives and flavonol glycosides were identified as marker phenolic metabolites for distinguishing bagged and non-bagged grapes. Coordinated transcriptional changes in the light signaling components CRY2 and HY5/HYHs, transcription regulator MYBA1, and enzymes LAR, ANR, UFGT and FLS4, coincided well with light-responsive biosynthesis of the corresponding flavonoids. The activation of multiple hormone signaling pathways after both light exclusion and re-exposure treatments was inconsistent with the changes in phenolic accumulation, indicating a limited role of plant hormones in mediating light/darkness-regulated phenolic biosynthesis processes. Furthermore, gene-gene and gene-metabolite network analyses discovered that the light-responsive expression of genes encoding bHLH, MYB, WRKY, NAC, and MADS-box transcription factors, and proteins involved in genetic information processing and epigenetic regulation such as nucleosome assembly and histone acetylation, showed a high positive correlation with grape berry phenolic accumulation in response to different light regimes. CONCLUSIONS: Altogether, our findings provide novel insights into the understanding of berry phenolic biosynthesis under light/darkness and practical guidance for improving grape features.

Effects of climatic conditions and soil properties on Cabernet Sauvignon berry growth and anthocyanin profiles.

Climatic conditions and soil type have significant influence on grape ripening and wine quality. The reported study was conducted in two "Cabernet Sauvignon (Vitis vinifera L.V)" vineyards located in Xinjiang, a semiarid wine-producing region of China during two vintages (2011 and 2012). The results indicate that soil and climate affected berry growth and anthocyanin profiles. These two localities were within a distance of 5 km from each other and had soils of different physical and chemical composition. For each vineyard, the differences of anthocyanin concentrations, and parameters concerning berry growth and composition between the two years could be explained by different climatic conditions. Soil effect was studied by investigation of differences in berry composition and anthocyanin profiles between the two vineyards in the same year, which could be explained mainly by the different soil properties, vine water and nitrogen status. Specifically, the soils with less water and organic matter produced looser clusters, heavier berry skins and higher TSS, which contributed to the excellent performance of grapes. Compared with 2011, the increases in anthocyanin concentrations for each vineyard in 2012 could be attributed to smaller number of extreme temperature (>35 °C) days and rainfall, lower vine water status and N level. The explanation for higher anthocyanin concentrations in grape skins from the soils with less water and organic matter could be the vine status differences, lighter berry weight and heavier skin weight at harvest. In particular, grapes from the soils with less water and organic matter had higher levels of 3'5'-substituded, O-methylated and acylated anthocyanins, which represented a positive characteristic conferring more stable pigmentation to the corresponding wine in the future. The present work clarifies the effects of climate and soil on berry growth and anthocyanin profiles, thus providing guidance for production of high-quality wine grapes in different regions.

Analysis of Alterations in Intestinal Flora in Chinese Elderly with Cardiovascular Disease and Its Association with Trimethylamine.

To investigate the changes in the intestinal flora in the Chinese elderly with cardiovascular disease (CVD) and its correlation with the metabolism of trimethylamine (TMA), the intestinal flora composition of elderly individuals with CVD and healthy elderly individuals was analyzed using 16S rRNA sequencing, the TMA levels in the feces of elderly were detected using headspace-gas chromatography (HS-GC), and four kinds of characterized TMA-producing intestinal bacteria in the elderly were quantified using real-time fluorescence quantitative polymerase chain reaction (qPCR). The results showed that Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, and Verrucomicrobia are the dominant microorganisms of the intestinal flora in the Chinese elderly. And there were significant differences in the intestinal bacteria composition between healthy elderly individuals and those with CVD, accompanied by a notable difference in the TMA content. The richness and diversity of the intestinal flora in the elderly with CVD were higher than those in the healthy elderly. Correlation analysis indicated that certain significantly different intestinal flora were associated with the TMA levels. Our findings showed a significant difference in TMA-producing intestinal flora between healthy elderly individuals and those with CVD. The TMA levels were found to be positively and significantly correlated with Klebsiella pneumoniae, suggesting that this bacterium is closely linked to the production of TMA in the elderly gut. This may have implications for the development and progression of CVD in the elderly population.

An In Vitro Colonic Fermentation Study of the Effects of Human Milk Oligosaccharides on Gut Microbiota and Short-Chain Fatty Acid Production in Infants Aged 0-6 Months.

The impact of five human milk oligosaccharides (HMOs)-2'-fucosyllactose (2FL), 3'-sialyllactose (3SL), 6'-sialyllactose (6SL), lacto-N-tetraose (LNT), and lacto-N-neotetraose (LNnT)-on the gut microbiota and short-chain fatty acid (SCFA) metabolites in infants aged 0-6 months was assessed through in vitro fermentation. Analyses of the influence of different HMOs on the composition and distribution of infant gut microbiota and on SCFA levels were conducted using 16S rRNA sequencing, quantitative real-time PCR (qPCR), and gas chromatography (GC), respectively. The findings indicated the crucial role of the initial microbiota composition in shaping fermentation outcomes. Fermentation maintained the dominant genera species in the intestine but influenced their abundance and distribution. Most of the 10 Bifidobacteria strains effectively utilized HMOs or their degradation products, particularly demonstrating proficiency in utilizing 2FL and sialylated HMOs compared to non-fucosylated neutral HMOs. Moreover, our study using B. infantis-dominant strains and B. breve-dominant strains as inocula revealed varying acetic acid levels produced by Bifidobacteria upon HMO degradation. Specifically, the B. infantis-dominant strain yielded notably higher acetic acid levels than the B. breve-dominant strain (p = 0.000), with minimal propionic and butyric acid production observed at fermentation's conclusion. These findings suggest the potential utilization of HMOs in developing microbiota-targeted foods for infants.

Curing Behavior of UV-Initiated Surface-Modified Nano-TiO2/Epoxy Resin Prepolymers and the Properties of Cured Composites.

Nano-titanium dioxides (nano-TiO2) surface modified with isopropyl tri(dioctylpyrophosphate) titanate (NDZ-201), a titanate coupling agent, and 3-glycidoxypropyltrimethoxysilane (KH-560), a silane coupling agent, were separately mixed with bisphenol A epoxy resin (DEGBA) prepolymer and then cured using a UV-normal temperature synergistic curing process. Then, the isothermal curing process of the system was investigated by differential scanning calorimetry (DSC). The relationship between the organization structures, mechanical properties, and heat resistance properties of the cured composites and material formulation was studied, and the DSC results showed that the addition of nano-TiO2 reduced the curing reaction rate constant k1 and increased the k2 of the prepolymer, while the activation energy of the curing reaction after UV irradiation Ea1 decreased, and the activation energy in the middle and later periods Ea2 increased. The characterization results of the composite material showed that nano-TiO2 as a scattering agent reduced the photoinitiation efficiency of UV light, and due to its obvious agglomeration tendency in the epoxy resin, the mechanical properties of the composite material were poor. The dispersibility of the coupling-agent-modified nano-TiO2 in the epoxy resin was greatly enhanced, and the mechanical and heat resistance properties of the composite material improved remarkably. The comparison results of the two coupling agents showed that NDZ-201 had better performance in increasing the impact strength by 6.8% (minimum value, the same below) and the maximum thermal decomposition rate temperature by 4.88 °C of the composite, while KH-560 improved the tensile strength by 7.3% and the glass transition temperature (Tg) by 3.34 °C of the composite.

LiDAR-aid Inertial Poser: Large-scale Human Motion Capture by Sparse Inertial and LiDAR Sensors.

We propose a multi-sensor fusion method for capturing challenging 3D human motions with accurate consecutive local poses and global trajectories in large-scale scenarios, only using single LiDAR and 4 IMUs, which are set up conveniently and worn lightly. Specifically, to fully utilize the global geometry information captured by LiDAR and local dynamic motions captured by IMUs, we design a two-stage pose estimator in a coarse-to-fine manner, where point clouds provide the coarse body shape and IMU measurements optimize the local actions. Furthermore, considering the translation deviation caused by the view-dependent partial point cloud, we propose a pose-guided translation corrector. It predicts the offset between captured points and the real root locations, which makes the consecutive movements and trajectories more precise and natural. Moreover, we collect a LiDAR-IMU multi-modal mocap dataset, LIPD, with diverse human actions in long-range scenarios. Extensive quantitative and qualitative experiments on LIPD and other open datasets all demonstrate the capability of our approach for compelling motion capture in large-scale scenarios, which outperforms other methods by an obvious margin. We will release our code and captured dataset to stimulate future research.

Inhibiting leukocyte-endothelial cell interactions by Chinese medicine Tongxinluo capsule alleviates no-reflow after arterial recanalization in ischemic stroke.

AIMS: Despite successful vascular recanalization in stroke, one-fourth of patients have an unfavorable outcome due to no-reflow. The pathogenesis of no-reflow is fully unclear, and therapeutic strategies are lacking. Upon traditional Chinese medicine, Tongxinluo capsule (TXL) is a potential therapeutic agent for no-reflow. Thus, this study is aimed to investigate the pathogenesis of no-reflow in stroke, and whether TXL could alleviate no-reflow as well as its potential mechanisms of action. METHODS: Mice were orally administered with TXL (3.0 g/kg/d) after transient middle cerebral artery occlusion. We examined the following parameters: neurological function, no-reflow, leukocyte-endothelial cell interactions, HE staining, leukocyte subtypes, adhesion molecules, and chemokines. RESULTS: Our results showed stroke caused neurological deficits, neuron death, and no-reflow. Adherent and aggregated leukocytes obstructed microvessels as well as leukocyte infiltration in ischemic brain. Leukocyte subtypes changed after stroke mainly including neutrophils, lymphocytes, regulatory T cells, suppressor T cells, helper T type 1 (Th1) cells, Th2 cells, B cells, macrophages, natural killer cells, and dendritic cells. Stroke resulted in upregulated expression of adhesion molecules (P-selectin, E-selectin, and ICAM-1) and chemokines (CC-chemokine ligand (CCL)-2, CCL-3, CCL-4, CCL-5, and chemokine C-X-C ligand 1 (CXCL-1)). Notably, TXL improved neurological deficits, protected neurons, alleviated no-reflow and leukocyte-endothelial cell interactions, regulated multiple leukocyte subtypes, and inhibited the expression of various inflammatory mediators. CONCLUSION: Leukocyte-endothelial cell interactions mediated by multiple inflammatory factors are an important cause of no-reflow in stroke. Accordingly, TXL could alleviate no-reflow via suppressing the interactions through modulating various leukocyte subtypes and inhibiting the expression of multiple inflammatory mediators.

Analysis of fatty acid composition and sensitivity to dietary n-3 PUFA intervention of mouse n-3 PUFA-enriched tissues/organs.

PURPOSE: n-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA; C22:6 n3) and eicosapentaenoic acid (EPA; C20:5 n3), are of concern for their health-promoting effects such as anti-inflammatory, but the tissue selectivity for n-3 PUFA (i.e., which tissues and organs are rich in n-3 PUFA) is still not well known. In addition, it is unclear which tissues and organs are more sensitive to n-3 PUFA intervention. These unresolved issues have greatly hindered the exploring of the health benefits of n-3 PUFA. METHODS: Twenty-four 7-week-old male C57BL/6 J mice were assigned to the control, fish oil, DHA, and EPA groups. The last three groups were given a 4-week oral intervention of fatty acids in ethyl ester (400 mg/kg bw). The fatty acid profiles in 27 compartments were determined by gas chromatography. RESULTS: The proportion of long-chain n-3 PUFA (the total relative percentage of EPA, DPA n3, and DHA) was analyzed. Eight tissues and organs, including the brain (cerebral cortex, hippocampus, hypothalamus) and peripheral organs (tongue, quadriceps, gastrocnemius, kidney, and heart) were determined as being n-3 PUFA-enriched tissues and organs, owing to their high n-3 PUFA levels. The highest n-3 PUFA content was observed in the tongue for the first time. Notably, the content of linoleic acid (LA; C18:2 n6c) in peripheral organs was observed to be relatively high compared with that in the brain. Interestingly, the proportions of EPA in the kidney, heart, quadriceps, gastrocnemius, and tongue increased more markedly after the EPA intervention than after the DHA or fish oil intervention. As expected, the levels of proinflammatory arachidonic acid (AA; C20:4 n6) in the kidney, quadriceps, and tongue were markedly decreased after the three dietary interventions. CONCLUSION: Peripheral tissues and organs, including the tongue, quadriceps, gastrocnemius, kidney, and heart, besides the brain, showed obvious tissue selectivity for n-3 PUFA. In the whole body of mice, the tongue exhibits the strongest preference for n-3 PUFA, with the highest proportion of n-3 PUFA. Moreover, these peripheral tissues and organs, especially the kidney, are more sensitive to dietary EPA administration in comparison with the brain.

Association between maternal erythrocyte PUFAs during pregnancy and neurodevelopment in children at 2 years of age: a birth cohort study.

Background: Previous studies on prenatal polyunsaturated fatty acids (PUFAs) and children's neurodevelopment have shown inconsistent results, and evidence from the Asian population is scarce. Objective: To investigate the association between maternal erythrocyte PUFAs and neurodevelopment in children in the Chinese population. Methods: We included 242 mother-child pairs from the Yuexiu birth cohort. The composition of maternal erythrocyte fatty acids during pregnancy was measured by gas chromatography. Each PUFA was divided into 3 tertiles. Neurodevelopment in children was evaluated with the Ages and Stages Questionnaire at 2 years of age, including 5 domains of development: communication, gross motor, fine motor, problem solving, and personal-social skills. Results: Maternal eicosapentaenoic acid (EPA) [OR (95% CI): 0.34 (0.15, 0.74) for tertile 2, and 0.31 (0.13, 0.70) for tertile 3] was associated with a reduced risk of potential developmental delay in gross motor skills. Conversely, arachidonic acid (AA) [OR (95% CI): 2.54 (1.17, 5.70) for tertile 3] was associated with an increased risk of potential developmental delay in personal-social skills. The ratio of AA/EPA [OR (95% CI): 2.64 (1.18, 6.15) for tertile 3] was associated with an increased risk of potential developmental delay in gross motor skills. No significant association was found between other PUFAs and neurodevelopment. Conclusion: This birth cohort has first shown a beneficial association between maternal EPA and gross motor skills of children. Meanwhile, maternal AA and the ratio of AA/EPA have negative associations with neurodevelopment in children.

Banxia Xiexin Decoction Alleviated Cerebral Glucose Metabolism Disorder by Regulating Intestinal Microbiota in APP/PS1 Mice.

OBJECTIVE: To identify whether Banxia Xiexin Decoction (BXD) alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 mice. METHODS: Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table (n=15 per group), including a model group (MG), a liraglutide group (LG) and a BXD group (BG). Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group (CG). Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg•d) for 3 months, while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection (25 nmol/kg) for 3 months. Firstly, liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of BXD. Then, the cognitive deficits, Aß pathological change and synaptic plasticity markers, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), were measured in APP/PS1 mice. Brain glucose uptake was detected by micropositron emission tomography. Intestinal microbial constituents were detected by 16S rRNA sequencing. The levels of intestinal glucagon-like peptide 1 (GLP-1) and cerebral GLP-1 receptor (GLP-1R), as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3ß (PI3K/Akt/GSK3ß) insulin signaling pathway were determined by immunohistochemical (IHC) staining and Western blot analysis, respectively. RESULTS: BXD ameliorated cognitive deficits and Aß pathological features (P<0.01). The expressions of SYP and PSD95 in the BG were higher than those in the MG (P<0.01). Brain glucose uptake in the BG was higher than that in the MG (P<0.01). The intestinal microbial composition in the BG was partially reversed. The levels of intestinal GLP-1 in the BG were higher than those in the MG (P<0.01). Compared with the MG, the expression levels of hippocampal GLP-1R, Akt, PI3K and p-PI3K in the BG were significantly increased (P<0.01), while the levels of GSK3ß were reduced (P<0.01). CONCLUSION: BXD exhibited protective effects against Alzheimer's disease by regulating the gut microbiota/GLP-1/GLP-1R, enhancing PI3K/Akt/GSK3ß insulin signaling pathway, and improving brain glucose metabolism.

Efficacy and Safety of Intravitreal Injection of Triamcinolone Acetonide and Conbercept for Intraocular Lens after Cataract Surgery.

Objective: To investigate the effect of intravitreal injection of triamcinolone acetonide and conbercept on the efficacy and safety of diabetic macular edema (DME) after cataract intraocular lens (IOL) surgery. Methods: A total of 350 patients with cataract complicated with diabetic macular edema in our hospital from January 2017 to July 2021 were randomly divided into conbercept group and triamcinolone acetonide group. Patients in the conbercept group were given intravitreal injection of conbercept during IOL surgery, and patients in the triamcinolone acetonide group were given injection of triamcinolone acetonide during surgery. Results: Three months after treatment, the best-corrected visual acuity of the two groups was significantly higher than before, the corrected visual acuity of the conbercept group was more significant than the triamcinolone acetonide group, and the intraocular pressure of the triamcinolone acetonide group was higher than the conbercept group. The foveal thickness and macular volume were significantly reduced in both groups, and was reduced more in the conbercept group than in the triamcinolone acetonide group. The contents of VEGF, SDF-1, and IL-6 in both groups were significantly decreased, and the decrease was more significant in the conbercept group than in the triamcinolone acetonide group. The patients with elevated intraocular pressure, headache and vomiting, orbital swelling pain, eye swelling pain, and eye pain in the triamcinolone acetonide group were significantly higher than those in the conbercept group (P < 0.05). Conclusions: Conbercept and triamcinolone acetonide has a good therapeutic effect on DME in pseudophakic eyes after cataract IOL surgery, which can reduce the degree of macular edema and improve the visual function. However, the therapeutic effect of injection therapy with conbercept is safe, the prognosis is better, and the complication rate is low.

Association of Maternal Erythrocyte PUFA during Pregnancy with Offspring Allergy in the Chinese Population.

Findings on prenatal polyunsaturated fatty acids (PUFA) and offspring allergies have been inconsistent, and the majority of studies have focused on Western populations. This study aimed to investigate the associations between maternal erythrocyte PUFA and offspring allergies in the first 2 years in the Chinese population. We included 573 mother-infant pairs from a birth cohort. Based on the outpatient medical records, we identified the diagnosis and time of offspring allergic disease onset. We measured erythrocyte fatty acids by gas chromatography. Associations were examined using Cox regression. We found that higher maternal total PUFA levels (HR = 0.80; 95% CI: 0.68, 0.94), especially of arachidonic acid (AA) (HR = 0.79; 95% CI: 0.65, 0.97) and n-3 PUFA (HR = 0.77; 95% CI: 0.62, 0.97), were associated with reduced risk of offspring allergies. Similar results were found for eczema. Compared with children without a maternal allergy history, the associations of total PUFA (p = 0.028) and n-6 PUFA (p = 0.013) with offspring allergies were stronger in those with a maternal allergy history. Maternal erythrocyte total PUFA, especially AA, and n-3 PUFA were inversely associated with offspring allergies within 2 years of age. There was a significant interaction between maternal allergy history and maternal PUFA in offspring allergies.

Uncovering the Pharmacological Mechanisms of Gexia-Zhuyu Formula (GXZY) in Treating Liver Cirrhosis by an Integrative Pharmacology Strategy.

Liver cirrhosis (LC) is a fibrotic lesion of liver tissue caused by the repeated progression of chronic hepatitis. The traditional Chinese medicine Gexia-Zhuyu formula (GXZY) has a therapeutic effect on LC. However, its pharmacological mechanisms on LC remain elucidated. Here, we used the network pharmacology approach to explore the action mechanisms of GXZY on LC. The compounds of GXZY were from the traditional Chinese medicine systems pharmacology (TCMSP) database, and their potential targets were from SwissTargetPrediction and STITCH databases. The disease targets of LC came from GeneCards, DisGeNET, NCBI gene, and OMIM databases. Then we constructed the protein-protein interaction (PPI) network to obtain the key target genes. And the gene ontology (GO), pathway enrichment, and expression analysis of the key genes were also performed. Subsequently, the potential action mechanisms of GXZY on LC predicted by the network pharmacology analyses were experimentally validated in LC rats and LX2 cells. A total of 150 components in GXZY were obtained, among which 111 were chosen as key compounds. The PPI network included 525 targets, and the key targets were obtained by network topological parameters analysis, whereas the predicted key genes of GXZY on LC were AR, JUN, MYC, CASP3, MMP9, GAPDH, and RELA. Furthermore, these key genes were related to pathways in cancer, hepatitis B, TNF signaling pathway, and MAPK signaling pathway. The in vitro and in vivo experiments validated that GXZY inhibited the process of LC mainly via the regulation of cells proliferation and migration through reducing the expression of MMP9. In conclusion, through the combination of network pharmacology and experimental verification, this study offered more insight molecular mechanisms of GXZY on LC.

Association between maternal erythrocyte polyunsaturated fatty acid levels during pregnancy and offspring weight status: A birth cohort study.

Background: The findings of the association between maternal polyunsaturated fatty acid (PUFA) levels during pregnancy and offspring weight status are controversial. Furthermore, few studies have focused on Asian populations or used erythrocyte membranes as biological markers. We aimed to examine the associations between maternal erythrocyte PUFA and offspring weight status within the first 2 years among the Chinese population. Materials and methods: A total of 607 mother-child pairs were recruited from a birth cohort. Maternal erythrocyte n-3 and n-6 PUFA during pregnancy were measured by gas chromatography, and the ratio of PUFA was calculated. Weight- and body mass index (BMI)-for-age z (WAZ and BAZ) scores were calculated for offspring at 1, 3, 6, 8, 12, 18, and 24 months of age. The risk of overweight and obesity was defined by the WHO criterion. The Generalized Estimating Equation (GEE) model was carried out for repeated anthropometric data within 2 years of age. Results: Maternal erythrocyte docosapentaenoic acid (DPA, n-3) was inversely associated with offspring BAZ score [tertile 2 vs. tertile 1, ß: -0.18 (-0.29, -0.00)]. Higher maternal erythrocyte arachidonic acid (AA) was inversely associated with lower offspring WAZ and BAZ [tertile 3 vs. tertile 1, ß: -0.18 (-0.35, -0.02), -0.22 (-0.38, -0.06), respectively]. Furthermore, higher maternal erythrocyte AA [tertile 3 vs. tertile 1, odds ratio [OR]: 0.52 (0.36, 0.75), p trend < 0.001] and total n-6 PUFA [tertile 3 vs. tertile 1, OR: 0.56 (0.39, 0.81), p trend = 0.002] were associated with decreased risk of overweight and obesity in offspring. Maternal erythrocyte n-6/n-3 PUFA and AA/eicosapentaenoic acid (EPA) ratios were not associated with offspring weight status. Conclusion: Maternal erythrocyte PUFA might influence offspring weight status within 2 years of age in the Chinese population. Further Asian studies are still needed.

Shenzhiling oral liquid protects the myelin sheath against Alzheimer's disease through the PI3K/Akt-mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenzhiling oral liquid (SZL), a traditional Chinese medicine (TCM) compound, is firstly approved by the Chinese Food and Drug Administration (CFDA) for the treatment of mild to moderate Alzheimer's disease (AD). SZL is composed of ten Chinese herbs, and the precise therapy mechanism of its action to AD is far from fully understood. AIM OF THE STUDY: The purpose of this study was to observe whether SZL is an effective therapy for amyloid-beta (Aß)-induced myelin sheath and oligodendrocytes impairments. Notably, the primary aim was to elucidate whether and through what underlying mechanism SZL protects the myelin sheath through the PI3K/Akt-mTOR signaling pathway in Aß42-induced OLN-93 oligodendrocytes in vitro. MATERIALS AND METHODS: APP/PS1 mice were treated with SZL or donepezil continuously for three months, and Aß42-induced oligodendrocyte OLN-93 cells mimicking AD pathogenesis of myelin sheath impairments were incubated with SZL-containing serum or with donepezil. LC-MS/MS was used to analysis the active components of SZL and SZL-containing serum. The Y maze test was administered after 3 months of treatment, and the hippocampal tissues of the APP/PS1 mice were then harvested for observation of myelin sheath and oligodendrocyte morphology. Cell viability and toxicity were assessed using CCK-8 and lactate dehydrogenase (LDH) release assays, and flow cytometry was used to measure cell apoptosis. The expression of the myelin proteins MBP, PLP, and MAG and that of Aß42 and Aß40 in the hippocampi of APP/PS1 mice were examined after SZL treatment. Simultaneously, the expression of p-PI3K, PI3K, p-Akt, Akt, p-mTOR, and mTOR were also examined. The expression of proteins, including CNPase, Olig2, NKX2.2, MBP, PLP, MAG, MOG, p-PI3K, PI3K, p-Akt, Akt, p-mTOR, and mTOR, was determined by immunofluorescence and Western blot, and the corresponding gene expression was evaluated by qPCR in Aß42-induced OLN-93 oligodendrocytes. RESULTS: LC-MS/MS detected a total of 126 active compounds in SZL-containing serum, including terpenoids, flavones, phenols, phenylpropanoids and phenolic acids. SZL treatment significantly improved memory and cognition in APP/PS1 mice and decreased the G-ratio of myelin sheath, alleviated myelin sheath and oligodendrocyte impairments by decreasing Aß42 and Aß40 accumulation and increasing the expression of myelin proteins MBP, PLP, MAG, and PI3K/Akt-mTOR signaling pathway associated protein in the hippocampi of APP/PS1 mice. SZL-containing serum also significantly reversed the OLN-93 cell injury induced by Aß42 by increasing cell viability and enhanced the expression of MBP, PLP, MAG, and MOG. Meanwhile, SZL-containing serum facilitated the maturation and differentiation of oligodendrocytes in Aß42-induced OLN-93 cells by heightening the expression of CNPase, Olig2 and NKX2.2. SZL-containing serum treatment also fostered the expression of p-PI3K, PI3K, p-Akt, Akt, p-mTOR, and mTOR, indicating an activating PI3K/Akt-mTOR signaling pathway in OLN-93 cells. Furthermore, the effects of SZL on myelin proteins, p-Akt, and p-mTOR were clearly inhibited by LY294002 and/or rapamycin, antagonists of PI3K and m-TOR, respectively. CONCLUSIONS: Our findings indicate that SZL exhibits a neuroprotective effect on the myelin sheath by promoting the expression of myelin proteins during AD, and its mechanism of action is closely related to the activation of the PI3K/Akt-mTOR signaling pathway.

Shen-Zhi-Ling oral liquid ameliorates cerebral glucose metabolism disorder in early AD via insulin signal transduction pathway in vivo and in vitro.

BACKGROUND: Shen-Zhi-Ling oral liquid (SZL) is an herbal formula known for its efficacy of nourishing "heart and spleen", and is used for the treatment and prevention of middle- and early-stage dementia. This study investigated the effects of SZL on amelioration of AD, and examined whether the underlying mechanisms from the perspective of neuroprotection are related to brain glucose metabolism. METHODS: Firstly, LC-MS/MS was used to analysis the SZL mainly enters the blood component. Then, the effects of SZL on cognitive and behavioral ability of APP/PS1 double transgenic mice and amyloid protein characteristic pathological changes were investigated by behavioral study and morphological observation. The effects of SZL on the ultrastructure of mitochondria, astrocytes, and micrangium related to cerebral glucose metabolism were observed using transmission electron microscopy. Then, micro-PET was also used to observe the effects of SZL on glucose uptake. Furthermore, the effects of SZL on insulin signaling pathway InR/PI3K/Akt and glucose transporters (GLUT1 and GLUT3) were observed by immunohistochemistry, Western-blot and RT-qPCR. Finally, the effects of SZL on brain glucose metabolism and key enzyme were observed. In vitro, the use of PI3K and/or GSK3ß inhibitor to observe the effects of SZL drug-containing serum on GLUT1 and GLUT3. RESULTS: In vivo, SZL could significantly ameliorate cognitive deficits, retarded the pathological damage, including neuronal degeneration, Aß peptide aggregation, and ultrastructural damage of hippocampal neurons, improve the glucose uptake, transporters and glucolysis. Beyond that, SZL regulates the insulin signal transduction pathway the insulin signal transduction pathway InR/PI3K/Akt. Furthermore, 15% SZL drug-containing serum increased Aß42-induced insulin signal transduction-pathway related indicators and GLUT1 and GLUT3 expression in SH-SY5Y cells. The improvement of GLUT1 and GLUT3 in the downstream PI3K/Akt/GSK3ß signaling pathway was reversed by the use of PI3K and/or GSK3ß inhibitor. CONCLUSIONS: In summary, our results demonstrated that improving glucose uptake, transport, and glycolysis in the brain may underlie the neuroprotective effects of SZL, and its potential molecular mechanism may be related to regulate the insulin signal transduction pathway.

Investigation on Compression Mechanical Properties of Rigid Polyurethane Foam Treated under Random Vibration Condition: An Experimental and Numerical Simulation Study.

The mechanical failure properties of rigid polyurethane foam treated under random vibration were studied experimentally and by numerical simulation. The random vibration treatments were carried out in the frequency range of 5-500 Hz, 500-1000 Hz, and 1000-1500 Hz, respectively. The influence of the vibration frequency, mass block and acceleration on the mechanical performance of rigid polyurethane foam was further investigated by compression testing. The experimental results showed that the compression performance and energy absorption of foams decreased the least between 500-1000 Hz. In addition, in the 5-500 Hz range, the reduction rate of compression performance and energy absorption increased with the increase of the vibration mass block and acceleration. The resulting simulation indicated that the deformation degree of the sample was the most serious under the condition of 5-500 Hz. With the increase of deformation, the damage of the sample during the vibration process increased, which led to the decrease of compression property and energy absorption of rigid polyurethane foam. This further explained the variation mechanism of the compression test performance.

Changes in global aroma profiles of Cabernet Sauvignon in response to cluster thinning.

Cluster thinning (CT) is a common practice to prevent overcropping in viticulture. CT affects vine balance between vegetative and productive growth and further modifies grape composition. This study investigated the effects of cluster thinning treatments applied at pea-size stage (CT-AF) and the onset of veraison (CT-V), respectively, on volatile compounds of Cabernet Sauvignon in two seasons (2013-2014). The experimental vineyard was located in the north-west of China with semi-arid and monsoon climate. CT exhibited limited effects on the evolutions of volatile compounds. CT-AF exhibited an inhibition on 6-methyl-5-heptene-2-one accumulation. There were no differences in terpene concentrations between CT-treated and control grapes regardless of CT time. Regarding C6/C9 compounds and their derivatives, CT-AF decreased nonanal concentration whilst CT-V increased (Z)-3-hexen-1-ol concentration. Additionally, there were increases in nonanal, (E)-2-hexen-1-ol, (Z)-2-hexen-1-ol and (Z)-3-hexen-1-ol concentrations in grapes with delayed CT. Among benzene derivatives, earlier CT resulted in lower phenol concentrations.

Effects of cluster thinning on vine photosynthesis, berry ripeness and flavonoid composition of Cabernet Sauvignon.

Cluster thinning is a common practice for regulating vine yield and grape quality. The effects of cluster thinning on vine photosynthesis, berry ripeness and flavonoid composition of V. vinifera L. Cabernet Sauvignon were evaluated during two seasons. Half of the clusters were removed at pea-size and veraison relative to two controls, respectively. Both cluster thinning treatments significantly increased pruning weight and decreased yield. No effects of cluster thinning on berry growth, ripeness and flavonol composition were observed. Early cluster thinning decreased the photosynthetic rate at pea-size, but the effect diminished at post-veraison. Early cluster thinning significantly promoted the biosynthesis of anthocyanins but decreased the proportion of 3'5'-hydroxylated and acylated anthocyanins at veraison. Late cluster thinning decreased the proportions of 3'5'-hydroxylated and acylated anthocyanins. Additionally, Cluster thinning showed inconsistent effects on flavan-3-ol composition over the two seasons.

Synergistic inhibition of pseudorabies virus replication by porcine alpha/beta interferon and gamma interferon in vitro.

Interferon (IFN) is crucial for initiating the innate immune response and for the generation of the adaptive response. IFN, in most species, comprises IFN-alpha (IFN-alpha), IFN-beta (IFN-beta) and IFN-gamma (IFN-gamma). In this study, we compared the capacity of porcine IFN-alpha, -beta and -gamma, or a combination of them, to protect IBRS-2 cells (porcine kidney cells) from infection with pseudorabies virus (PRV). The results demonstrated that porcine IFN-beta (PoIFN-beta) was the most efficient of the three IFNs in conferring resistance PRV infection; 100 U/mL PoIFN-beta inhibited PRV plaque formation 5.3-fold. Compared with PoIFN-beta, porcine IFN-gamma (PoIFN-gamma) was less capable of inhibiting PRV plaque formation (3.3-fold inhibition). Porcine IFN-alpha (PoIFN-alpha) had the least capability of the three PoIFNs, and inhibited PRV plaque formation only 1.26-fold. The inhibitory capacity increased to only 2.3-fold with a treatment of 12,800 U/mL PoIFN-alpha. A combination of PoIFN-gamma and PoIFN-alpha or PoIFN-beta inhibited PRV plaque formation 12.8-fold or 100-fold, respectively. Treatment of IBRS-2 cells with PoIFN-alpha/beta and PoIFN-gamma inhibited PRV replication 29- or 146-fold. Additionally, real-time PCR analyses of the PRV immediate early (IE) gene revealed that IE mRNA expression was profoundly decreased in cells stimulated with PoIFN-alpha/beta and PoIFN-gamma (23.8-133.0-fold) compared with vehicle-treated cells. All the findings indicate that PoIFN-gamma acts synergistically with other PoIFNs (PoIFN-alpha and -beta) to potently inhibit PRV replication in vitro.