Cynaroside improved depressive-like behavior in CUMS mice by suppressing microglial inflammation and ferroptosis.

Depression is a common mental health disorder, and in recent years, the incidence of various forms of depression has been on the rise. Most medications for depression are highly dependency-inducing and can lead to relapse upon discontinuation. Therefore, novel treatment modalities and therapeutic targets are urgently required. Traditional Chinese medicine (TCM) offers advantages in the treatment of depression owing to its multi-target, multi-dimensional approach that addresses the root cause of depression by regulating organ functions and balancing Yin and Yang, with minimal side effects. Cynaroside (CNS), an extract from the traditional Chinese herb honeysuckle, is a flavonoid compound with antioxidant properties. In this study, network pharmacology identified 44 potential targets of CNS associated with depression and several highly correlated inflammatory signaling pathways. CNS alleviated LPS-induced M1 polarization and the release of inflammatory factors in BV-2 cells. Transcriptomic analysis and validation revealed that CNS reduced inflammatory polarization, lipid peroxidation, and ferroptosis via the IRF1/SLC7A11/GPX4 signaling pathway. In vivo experiments showed that CNS treatment had effects similar to those of fluoxetine (FLX). It effectively ameliorated anxiety-, despair-, and anhedonia-like states in chronic unpredictable mild stress (CUMS)-induced mice and reduced microglial activation in the hippocampus. Thus, we conclude that CNS exerts its therapeutic effect on depression by inhibiting microglial cells from polarizing into the M1 phenotype and reducing inflammation and ferroptosis levels. This study provides further evidence that CNS is a potential antidepressant, offering new avenues for the treatment of depression.

Identification of Dietary Supplements Associated with Blood Metabolites in the Hispanic Community Health Study/Study of Latinos Cohort Study.

BACKGROUND: Metabolomics approaches have been widely used to define the consumption of foods but have less often been used to study exposure to dietary supplements. OBJECTIVES: This study aimed to identify dietary supplements associated with metabolite levels and to examine whether these metabolites predicted incident diabetes risk. METHODS: We studied 3972 participants from a prospective cohort study of 18-74-y-old Hispanic/Latino adults. At a baseline examination, we ascertained use of dietary supplements using recall methods and concurrently, a serum metabolomic panel. After adjustment for potential confounders, we identified dietary supplements associated with metabolites. We then examined the association of these metabolites with incident diabetes at the 6-y study examination. RESULTS: We observed a total of 110 dietary supplement-metabolite associations that met the criteria for statistical significance adjusted for age, sex, field center, Hispanic/Latino background, body mass index, diet, smoking, physical activity, and number of medications (adjusted P < 0.05). This included 13 metabolites uniquely associated with only one dietary supplement ingredient. Vitamin C had the most associated metabolites (n = 15), including positive associations with oxalate, tartronate, threonate, and isocitrate, which were each in turn protective for the risk of incident diabetes. Vitamin C was also associated with higher N-acetylvaline level, which was an unfavorable diabetes risk factor. Other findings related to branched chain amino acid related compounds including α-hydroxyisovalerate and 2-hydroxy-3-methylvalerate, which were inversely associated with thiamine or riboflavin intake and also predicted higher diabetes risk. Vitamin B12 had an inverse association with γ-glutamylvaline, levels of which were positively associated with the risk of diabetes. CONCLUSIONS: Our data point to potential metabolite changes associated with vitamin C and B vitamins, which may have favorable metabolic effects. Knowledge of blood metabolites that can be modified by dietary supplement intake may aid understanding the health effects of dietary supplements and identify potential biological mediators.

Trends in Magnesium Intake among Hispanic Adults, the National Health and Nutrition Examination Survey (NHANES) 1999-2014.

This study aimed at examining trends in magnesium intake among U.S. Hispanic adults stratified by gender, Hispanic origins, age, and poverty income ratio (PIR) level. Data on 9304 Hispanic adults aged ≥20 years from eight National Health and Nutrition Examination Survey (NHANES) cycles (1999-2014) were included in this study. For each cycle, survey-weighted mean dietary and total magnesium intakes were estimated. The prevalence of dietary and total magnesium intake below the Recommended Dietary Allowance (RDA) was further estimated stratified by gender and age groups. Linear regression was used to test trend. Over the survey cycles, both dietary and total magnesium intakes were significantly increased among Hispanic adults. In the study period, magnesium intake tended to be lower in females, adults in other Hispanic-origin group, those aged ≥65 years old, and those with a PIR <1.0. The prevalence of magnesium intake inadequacy decreased among Hispanic adults; however, more than 70% of Hispanic males and females continued to have magnesium intake below the RDA in 2013-2014. From 1999/2000 to 2013/2014, despite several improvements in magnesium intake having been identified, additional findings showed insufficient intake in Hispanic males and females, suggesting the need to improve magnesium intake through diet and dietary supplementation for U.S. Hispanics.

A remote sensing emissions monitoring programme reduces emissions of gasoline and LPG vehicles.

Vehicle emissions are a major source of air pollution in Hong Kong affecting human health. A 'strengthened emissions control of gasoline and liquefied petroleum gas (LPG) vehicles' programme has been operating in Hong Kong since September 2014 utilising remote sensing (RS) technology. RS has provided measurement data to successfully identify high emitting gasoline and LPG vehicles which then need to be repaired or removed from the on-road vehicle fleet. This paper aims to evaluate the effectiveness of this globally unique RS monitoring programme. A large RS dataset of 2,144,422 records was obtained covering the period from 6th January 2012 to 30th December 2016, of which 1,206,762 records were valid and suitable for further investigation. The results show that there have been significant reductions of emissions factors (EF) for 40.5% HC, 45.3% CO and 29.6% NO for gasoline vehicles. Additionally, EF reductions of 48.4% HC, 41.1% CO and 58.7% NO were achieved for LPG vehicles. For the combined vehicle fleet, the reductions for HC, CO and NO were 55.9%, 50.5% and 60.9% respectively during this survey period. The findings demonstrate that the strengthened emissions control programme utilising RS has been very effective in identifying high emitting vehicles for repair so as to reduce the emissions from gasoline and LPG vehicles under real driving.

Transcription factor YY1 is essential for iNKT cell development.

Invariant natural killer T (iNKT) cells develop from CD4+CD8+ double-positive (DP) thymocytes and express an invariant Vα14-Jα18 T-cell receptor (TCR) α-chain. Generation of these cells requires the prolonged survival of DP thymocytes to allow for Vα14-Jα18 gene rearrangements and strong TCR signaling to induce the expression of the iNKT lineage-specific transcription factor PLZF. Here, we report that the transcription factor Yin Yang 1 (YY1) is essential for iNKT cell formation. Thymocytes lacking YY1 displayed a block in iNKT cell development at the earliest progenitor stage. YY1-deficient thymocytes underwent normal Vα14-Jα18 gene rearrangements, but exhibited impaired cell survival. Deletion of the apoptotic protein BIM failed to rescue the defect in iNKT cell generation. Chromatin immunoprecipitation and deep-sequencing experiments demonstrated that YY1 directly binds and activates the promoter of the Plzf gene. Thus, YY1 plays essential roles in iNKT cell development by coordinately regulating cell survival and PLZF expression.

Response characteristics of soil fractal features to different land uses in typical purple soil watershed.

As a fundamental characteristic of soil physical properties, the soil Particle Size Distribution (PSD) is important in the research on soil moisture migration, solution transformation, and soil erosion. In this research, the PSD characteristics with distinct methods in different land uses are analyzed. The results show that the upper bound of the volume domain of the clay domain ranges from 5.743 µm to 5.749 µm for all land-use types. For the silt domain of purple soil, the value ranges among 286.852~286.966 µm. For all purple soil land-use types, the order of the volume domain fractal dimensions is D clayD silt(U)>D sand (U)>D sand and D silt>D silt(U)>D sand>D sand(U), respectively. As it is compared with all Dvi, the D silt has the most significant correlativity to the soil texture and organic matter in different land uses of the typical purple soil watersheds. Therefore, Dsilt will be a potential indictor for evaluating the proportion of fine particles in the PSD, as well as a key measurement in soil quality and productivity studies.

SYUNZ-16, a newly synthesized alkannin derivative, induces tumor cells apoptosis and suppresses tumor growth through inhibition of PKB/AKT kinase activity and blockade of AKT/FOXO signal pathway.

Alkannin is the major bioactive compound of Arnebia euchroma roots, which is used in many therapeutic remedies in Chinese traditional medicine. SYUNZ-16 is a new derivative of alkannin. In this study, anticancer effects of SYUNZ-16 on human lung adenocarcinoma cell line GLC-82 and human hepatocarcinoma cell line Hep3B were tested in vitro. The results showed SYUNZ-16 could obviously inhibit the proliferation of these cancer cell lines via induction of apoptosis, with the evidence of increasing AnnexinV-positive cells and cleaved caspase-3 and PARP fragments. More importantly, we found that SYUNZ-16 could inhibit AKT activity in cell-free system. Treatment of cancer cells with SYUNZ-16 decreased the phosphorylation of AKT. Additionally, SYUNZ-16 partially attenuated the phosphorylation levels of FKHR and FKHRL1 in a dose-dependent and time-dependent fashion, and led to an increase in the nuclear accumulation of exogenous FKHR, and upregulated the mRNA expression of Bim and TRADD in cancer cells. Further study showed that constitutively activated AKT1 transfection could reduce apoptosis induction mediated by SYUNZ-16. The in vivo experiments showed that SYUNZ-16 had inhibitory effects on S-180 sarcoma implanted to mice. And in GLC-82 xenograft models, SYUNZ-16 at 20 mg/kg/qod remarkably inhibited the tumor growth with the T/C value of 45.3%. Taken together, SYUNZ-16 might be a potent inhibitor of AKT signaling pathway in tumor cells. These data provide evidence for the development of SYUNZ-16 as a potential antitumor drug candidate for further research and development.