GIGANTEA accelerates wheat heading time through gene interactions converging on FLOWERING LOCUS T1.

Precise regulation of flowering time is critical for cereal crops to synchronize reproductive development with optimum environmental conditions, thereby maximizing grain yield. The plant-specific gene GIGANTEA (GI) plays an important role in the control of flowering time, with additional functions on the circadian clock and plant stress responses. In this study, we show that GI loss-of-function mutants in a photoperiod-sensitive tetraploid wheat background exhibit significant delays in heading time under both long-day (LD) and short-day photoperiods, with stronger effects under LD. However, this interaction between GI and photoperiod is no longer observed in isogenic lines carrying either a photoperiod-insensitive allele in the PHOTOPERIOD1 (PPD1) gene or a loss-of-function allele in EARLY FLOWERING 3 (ELF3), a known repressor of PPD1. These results suggest that the normal circadian regulation of PPD1 is required for the differential effect of GI on heading time in different photoperiods. Using crosses between mutant or transgenic plants of GI and those of critical genes in the flowering regulation pathway, we show that GI accelerates wheat heading time by promoting FLOWERING LOCUS T1 (FT1) expression via interactions with ELF3, VERNALIZATION 2 (VRN2), CONSTANS (CO), and the age-dependent microRNA172-APETALA2 (AP2) pathway, at both transcriptional and protein levels. Our study reveals conserved GI mechanisms between wheat and Arabidopsis but also identifies specific interactions of GI with the distinctive photoperiod and vernalization pathways of the temperate grasses. These results provide valuable knowledge for modulating wheat heading time and engineering new varieties better adapted to a changing environment.

Regulation of immune response genes in the skin of allergic and clinically tolerant individuals exposed to p-phenylenediamine.

BACKGROUND: p-Phenylenediamine (PPD) is a potent contact allergen found in many hair colour products. However, not all individuals develop allergic contact dermatitis (ACD) although they are regularly exposed to PPD. It is unclear whether these asymptomatic individuals are true non-responders to PPD or whether they mount a response to PPD without showing any symptoms. METHODS: Skin biopsies were collected from 11 asymptomatic hairdressers regularly exposed to PPD and from 10 individuals with known ACD on day 4 after patch testing with 1% PPD in petrolatum and petrolatum exclusively as control. RNA sequencing and confocal microscopy were performed. RESULTS: T cell activation, inflammation and apoptosis pathways were up-regulated by PPD in both asymptomatic and allergic individuals. Compared to asymptomatic individuals with a negative patch test, individuals with a strong reaction to PPD strongly up-regulated both pro- and anti-inflammatory cytokines genes. Interestingly, PPD treatment induced significant up-regulation of several genes for chemokines, classical type 2 dendritic cell markers and regulatory T cell markers in both asymptomatic and allergic individuals. In addition, apoptosis signalling pathway was activated in both non-responders and allergic individuals. CONCLUSION: This study demonstrates that there are no true non-responders to PPD but that the immune response elicited by PPD differs between individuals and can lead to either tolerance, subclinical inflammation or allergy.

Clinical Accuracy of Serum Neurofilament Light to Differentiate Frontotemporal Dementia from Primary Psychiatric Disorders is Age-Dependent.

BACKGROUND: Symptoms of behavioral variant frontotemporal dementia (bvFTD) overlap with primary psychiatric disorders (PPD) making diagnosis challenging. Serum neurofilament light (sNfL) is a candidate biomarker to distinguish bvFTD from PPD, but large-scale studies in PPD are lacking. OBJECTIVE: Determine factors that influence sNfL from a large database of PPD patients, and test its diagnostic accuracy. DESIGN, SETTINGS, SUBJECTS, MEASUREMENTS: Clinical data of people aged 40-81 were obtained from healthy subjects (n = 69), and patients with PPD (n = 848) or bvFTD (n = 82). sNfL was measured using Simoa technology on an HD-X instrument. Data were analyzed using general linear models, and Receiver Operating Characteristic (ROC) curve analyses to determine global and age-specific sNfL cutoffs to distinguish bvFTD from PPD, using the Youden Index. RESULTS: sNfL increased with age, while sex, BMI and diabetes status were modestly associated with sNfL. sNfL was slightly higher in PPD than healthy subjects (14.1 versus 11.7 pg/mL), when controlling for covariates. sNfL was markedly lower in PPD than bvFTD (14.1 versus 44.1 pg/mL). sNfL could differentiate PPD from bvFTD with an AUC = 0.868, but the effect was driven by the younger subjects between age 40-60 years at a cutoff of 16.0 pg/mL. No valid cutoff was detected over age 60, however, values of sNfL above 38.5 pg/mL, or below 13.9 pg/mL, provided 90% diagnostic certainty of bvFTD or PPD, respectively. CONCLUSION: PPD have mildly elevated sNfL compared to healthy subjects but much lower than bvFTD. Results support the use of sNfL as a biomarker to differentiate PPD from bvFTD at age 60 or below, but accuracy decreases in older ages.

Gossypium arboreum PPD2 facilitates root architecture development to increase plant resilience to salt stress.

The jasmonic acid (JA) signaling pathway plays an important role in plant responses to abiotic stresses. The PEAPOD (PPD) and jasmonate ZIM-domain (JAZ) protein in the JA signaling pathway belong to the same family, but their functions in regulating plant defense against salt stress remain to be elucidated. Here, Gossypium arboreum PPD2 was overexpressed in Arabidopsis thaliana and systematically silenced in cotton for exploring its function in regulating plant defense to salt stress. The GaPPD2-overexpressed Arabidopsis thaliana plants significantly increased the tolerance to salt stress compared to the wild type in both medium and soil, while the GaPPD2-silenced cotton plants showed higher sensitivity to salt stress than the control in pots. The antioxidant activities experiment showed that GaPPD2 may mitigate the accumulation of reactive oxygen species by promoting superoxide dismutase accumulation, consequently improving plant resilience to salt stress. Through the exogenous application of MeJA (methy jasmonate) and the protein degradation inhibitor MG132, it was found that GaPPD2 functions in plant defense against salt stress and is involved in the JA signaling pathway. The RNA-seq analysis of GaPPD2-overexpressed A. thaliana plants and receptor materials showed that the differentially expressed genes were mainly enriched in antioxidant activity, peroxidase activity, and plant hormone signaling pathways. qRT-PCR results demonstrated that GaPPD2 might positively regulate plant defense by inhibiting GH3.2/3.10/3.12 expression and activating JAZ7/8 expression. The findings highlight the potential of GaPPD2 as a JA signaling component gene for improving the cotton plant resistance to salt stress and provide insights into the mechanisms underlying plant responses to environmental stresses.

Environmentally Relevant Concentrations of S-6PPD-Quinone Caused More Serious Hepatotoxicity Than R-Enantiomer and Racemate in Oncorhynchus mykiss.

6PPD-quinone (6PPD-Q) is frequently detected in various environmental media, and the environmentally relevant concentrations can be fatal to Oncorhynchus mykiss. Notably, 6PPD-Q has two enantiomers (S-6PPD-Q and R-6PPD-Q). In this study, O. mykiss was separately exposed to each enantiomer and racemate of 6PPD-Q for 96 h at environmentally relevant concentrations, and livers were collected. Effects on the biochemical, pathological, and ultrastructural changes were assessed, and metabolomics was conducted to elucidate the potential hepatotoxicity mechanism. Compared with the control treatment, the levels of catalase (CAT, all treatments except for 0.1 µg/L rac-6PPD-Q), and glutathione-S-transferase (GST, all treatments) significantly declined. Hepatocyte space became smaller, nuclear morphology changed, and nucleolysis occurred. Mitochondrial malformation and vesicle-like structure dilation of the endoplasmic reticulum (ER) were observed in the hepatocytes, which was most serious after S-6PPD-Q exposure. Some amino acid metabolism, folate biosynthesis, taurine and hypotaurine metabolism and purine metabolism were disturbed, consistent with mitochondrial dysfunction and ER stress. The differential metabolites were in the order of S-6PPD-Q (216) > rac-6PPD-Q (88) > R-6PPD-Q (56). Thus, 6PPD-Q-induced hepatic mitochondrial dysfunction and ER stress, causing metabolic disturbance and oxidative stress might be the toxic mechanism of 6PPD-Q in O. mykiss liver, and S-6PPD-Q effects were the most serious.

In Vitro and In Vivo Biotransformation Profiling of 6PPD-Quinone toward Their Detection in Human Urine.

The antioxidant N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its oxidized quinone product 6PPD-quinone (6PPD-Q) in rubber have attracted attention due to the ecological risk that they pose. Both 6PPD and 6PPD-Q have been detected in various environments that humans cohabit. However, to date, a clear understanding of the biotransformation of 6PPD-Q and a potential biomarker for exposure in humans are lacking. To address this issue, this study presents a comprehensive analysis of the extensive biotransformation of 6PPD-Q across species, encompassing both in vitro and in vivo models. We have tentatively identified 17 biotransformation metabolites in vitro, 15 in mice in vivo, and confirmed the presence of two metabolites in human urine samples. Interestingly, different biotransformation patterns were observed across species. Through semiquantitative analysis based on peak areas, we found that almost all 6PPD-Q underwent biotransformation within 24 h of exposure in mice, primarily via hydroxylation and subsequent glucuronidation. This suggests a rapid metabolic processing of 6PPD-Q in mammals, underscoring the importance of identifying effective biomarkers for exposure. Notably, monohydroxy 6PPD-Q and 6PPD-Q-O-glucuronide were consistently the most predominant metabolites across our studies, highlighting monohydroxy 6PPD-Q as a potential key biomarker for epidemiological research. These findings represent the first comprehensive data set on 6PPD-Q biotransformation in mammalian systems, offering insights into the metabolic pathways involved and possible exposure biomarkers.

Small-Intensity Rainfall Triggers Greater Contamination of Rubber-Derived Chemicals in Road Stormwater Runoff from Various Functional Areas in Megalopolis Cities.

Rubber-derived chemicals (RDCs) originating from tire and road wear particles are transported into road stormwater runoff, potentially threatening organisms in receiving watersheds. However, there is a lack of knowledge on time variation of novel RDCs in runoff, limiting initial rainwater treatment and subsequent rainwater resource utilization. In this study, we investigated the levels and time-concentration profiles of 35 target RDCs in road stormwater runoff from eight functional areas in the Greater Bay Area, South China. The results showed that the total concentrations of RDCs were the highest on the expressway compared with other seven functional areas. N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), 6PPD-quinone, benzothiazole, and 1,3-diphenylguanidine were the top four highlighted RDCs (ND-228840 ng/L). Seasonal and spatial differences revealed higher RDC concentrations in the dry season as well as in less-developed regions. A lag effect of reaching RDC peak concentrations in road stormwater runoff was revealed, with a lag time of 10-90 min on expressways. Small-intensity rainfall triggers greater contamination of rubber-derived chemicals in road stormwater runoff. Environmental risk assessment indicated that 35% of the RDCs posed a high risk, especially PPD-quinones (risk quotient up to 2663). Our findings contribute to a better understanding of managing road stormwater runoff for RDC pollution.

Fragmentation Pattern-Based Screening Strategy Combining Diagnostic Ion and Neutral Loss Uncovered Novel para-Phenylenediamine Quinone Contaminants in the Environment.

Identifying transformed emerging contaminants in complex environmental compartments is a challenging but meaningful task. Substituted para-phenylenediamine quinones (PPD-quinones) are emerging contaminants originating from rubber antioxidants and have been proven to be toxic to the aquatic species, especially salmonids. The emergence of multiple PPD-quinones in various environmental matrices and evidence of their specific hazards underscore the need to understand their environmental occurrences. Here, we introduce a fragmentation pattern-based nontargeted screening strategy combining full MS/All ion fragmentation/neutral loss-ddMS2 scans to identify potential unknown PPD-quinones in different environmental matrices. Using diagnostic fragments of m/z 170.0600, 139.0502, and characteristic neutral losses of 199.0633, 138.0429 Da, six known and three novel PPD-quinones were recognized in air particulates, surface soil, and tire tissue. Their specific structures were confirmed, and their environmental concentration and composition profiles were clarified with self-synthesized standards. N-(1-methylheptyl)-N'-phenyl-1,4-benzenediamine quinone (8PPD-Q) and N,N'-di(1,3-dimethylbutyl)-p-phenylenediamine quinone (66PD-Q) were identified and quantified for the first time, with their median concentrations found to be 0.02-0.21 µg·g-1 in tire tissue, 0.40-2.76 pg·m-3 in air particles, and 0.23-1.02 ng·g-1 in surface soil. This work provides new evidence for the presence of unknown PPD-quinones in the environment, showcasing a potential strategy for screening emerging transformed contaminants in the environment.

Bioretention Design Modifications Increase the Simulated Capture of Hydrophobic and Hydrophilic Trace Organic Compounds.

Stormwater rapidly moves trace organic contaminants (TrOCs) from the built environment to the aquatic environment. Bioretention cells reduce loadings of some TrOCs, but they struggle with hydrophilic compounds. Herein, we assessed the potential to enhance TrOC removal via changes in bioretention system design by simulating the fate of seven high-priority stormwater TrOCs (e.g., PFOA, 6PPD-quinone, PAHs) with log KOC values between -1.5 and 6.74 in a bioretention cell. We evaluated eight design and management interventions for three illustrative use cases representing a highway, a residential area, and an airport. We suggest two metrics of performance: mass advected to the sewer network, which poses an acute risk to aquatic ecosystems, and total mass advected from the system, which poses a longer-term risk for persistent compounds. The optimized designs for each use case reduced effluent loadings of all but the most polar compound (PFOA) to <5% of influent mass. Our results suggest that having the largest possible system area allowed bioretention systems to provide benefits during larger events, which improved performance for all compounds. To improve performance for the most hydrophilic TrOCs, an amendment like biochar was necessary; field-scale research is needed to confirm this result. Our results showed that changing the design of bioretention systems can allow them to effectively capture TrOCs with a wide range of physicochemical properties, protecting human health and aquatic species from chemical impacts.

Automated Image-Based Fluorescence Screening of Mitochondrial Membrane Potential in Daphnia magna: An Advanced Ecotoxicological Testing Tool.

This study demonstrated the strengths of in vivo molecular staining coupled with automated imaging analysis in Daphnia magna. A multiwell plate protocol was developed to assess mitochondrial membrane potential using the JC-1 dye. The suitability of five common anesthetics was initially tested, and 5% ethanol performed best in terms of anesthetic effects and healthy recovery. The staining conditions were optimized to 30 min staining with 2 µM JC-1 for best J-aggregate formation. The protocol was validated with the model compound carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and used to measure the effect of four environmental contaminants, 2,4-dinitrophenol, triclosan, n-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), and ibuprofen, on mitochondrial health. Test organisms were imaged using an automated confocal microscope, and fluorescence intensities were automatically quantified. The effect concentrations for CCCP were lower by a factor of 30 compared with the traditional OECD 202 acute toxicity test. Mitochondrial effects were also detected at lower concentrations for all tested environmental contaminants compared to the OCED 202 test. For 2,4-dinitrophenol, mitochondria effects were detectable after 2 h exposure to environmentally relevant concentrations and predicted organism death was observed after 24 h. The high sensitivity and time efficiency of this novel automated imaging method make it a valuable tool for advancing ecotoxicological testing.

Synthesis and antibacterial activities of heterocyclic ring-fused 20(S)-protopanaxadiol derivatives.

Multidrug-resistant (MDR) bacterial infections are becoming a life-threatening issue in public health; therefore, it is urgent to develop novel antibacterial agents for treating infections caused by MDR bacteria. The 20(S)-protopanaxadiol (PPD) derivative 9 was identified as a novel antibacterial hit compound in screening of our small synthetic natural product-like (NPL) library. A series of novel PPD derivatives with heterocyclic rings fused at the C-2 and C-3 positions of the A-ring were synthesized and their antibacterial activities against Staphylococcus aureus (S. aureus) Newman strain and MDR S. aureus strains (USA300, NRS-1, NRS-70, NRS-100, NRS-108, NRS-271, XJ017, and XJ036) were evaluated. Among these compounds, quinoxaline derivative 56 (SH617) exhibited the highest activity with MICs of 0.5-4 µg/mL against the S. aureus Newman strain and the eight MDR S. aureus strains. Its antibacterial activity was comparable to that of the positive control, vancomycin. In the zebrafish, 56 revealed no obvious toxicity even at a high administered dose. In vivo, following a lethal infection induced by USA300 strains in zebrafish, 56 exhibited significantly increased survival rates in a dose-dependent manner.

Environmental fate of tire-rubber related pollutants 6PPD and 6PPD-Q: A review.

To enhance tire durability, the antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is used in rubber, but it converts into the toxic 6PPD quinone (6PPD-Q) when exposed to oxidants like ozone (O3), causing ecological concerns. This review synthesizes the existing data to assess the transformation, bioavailability, and potential hazards of two tire-derived pollutants 6PPD and 6PPD-Q. The comparative analysis of different thermal methods utilized in repurposing waste materials like tires and plastics into valuable products are analyzed. These methods shed light on the aspects of pyrolysis and catalytic conversion processes, providing valuable perspectives into optimizing the waste valorization and mitigating environmental impacts. Furthermore, we have examined the bioavailability and potential hazards of chemicals used in tire manufacturing, based on the literature included in this review. The bioavailability of these chemicals, particularly the transformation of 6PPD to 6PPD-Q, poses significant ecological risks. 6PPD-Q is highly bioavailable in aquatic environments, indicating its potential for widespread ecological harm. The persistence and mobility of 6PPD-Q in the environment, along with its toxicological effects, highlight the critical need for ongoing monitoring and the development of effective mitigation strategies to reduce its impact on both human health and ecosystem. Future research should focus on understanding the chronic effects of low-level exposure to these compounds on both terrestrial and aquatic ecosystems, as well as the potential for bioaccumulation in the food chain. Additionally, this review outlines the knowledge gaps, recommending further research into the toxicity of tire-derived pollutants in organisms and the health implications for humans and ecosystems.

Association between 6PPD-quinone exposure and BMI, influenza, and diarrhea in children.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-quinone) has received extensive attention due to its ubiquitous distribution and potential toxicity. However, the distribution characteristics of 6PPD-quinone in dust from e-waste recycling areas and the consequential health risks to children are unclear. A total of 183 dust samples were collected from roads (n = 40), homes (n = 91), and kindergartens (n = 52) in Guiyu (the e-waste-exposed group) and Haojiang (the reference group) from 2019 to 2021. The results show that the concentrations of 6PPD-quinone in kindergarten and house dust from the exposed group were significantly higher than those from the reference group (P < 0.001). These findings show that e-waste may be another potential source of 6PPD-quinone, in addition to rubber tires. The exposure risk of 6PPD-quinone in children was assessed using their daily intake. The daily intake of 925 kindergarten children was calculated using the concentration of 6PPD-quinone in kindergarten dust. The daily intake of 6PPD-quinone via ingestion was approximately five orders of magnitude higher than via inhalation. Children in the exposed group had a higher exposure risk to 6PPD-quinone than the reference group. A higher daily intake of 6PPD-quinone from kindergarten dust was associated with a lower BMI and a higher frequency of influenza and diarrhea in children. This study reports the distribution of 6PPD-quinone in an e-waste recycling town and explores the associated health risks to children.

Are 6 more accurate than 4? The influence of different modes of delivery on postpartum depression and PTSD.

BACKGROUND: Empirical evidence shows that 4.6-6.3% of all women develop a post-traumatic stress disorder (PTSD) and approximately 10-15% postpartum depression (PPD) following childbirth. This study explores the relationship between delivery mode and the occurrence of PTSD and PPD, specifically examining four distinct caesarean section (CS) modes: primary on maternal request (Grade 4), medically indicated primary (Grade 3), secondary CS from relative indication (Grade 2) and emergency secondary CS (Grade 1), compared to vaginal and assisted vaginal delivery (AVD). The research aims to understand how these six subcategories of delivery modes impact PPD and PTSD levels. Common predictors, including the need for psychological treatment before childbirth, fear of childbirth, planning of pregnancy, induction of labor, birth debriefing, and lack of social support after childbirth, will be analyzed to determine their association with postpartum mental health outcomes. METHODS: The study was planned and carried out by a research team of the psychology department at the Medical School Hamburg, Germany. Within an online-study (cross-sectional design) N = 1223 German speaking women with a baby who did not die before, during or after birth were surveyed once between four weeks and twelve months postpartum via an anonymous online questionnaire on demographic and gynecological data, delivery mode, PTSD (PCL-5) and PPD (EPDS). RESULTS: For both psychiatric disorders, ANOVA revealed significant differences between delivery mode and PPD and PTSD. With weak effects for PPD and medium to strong effects for PTSD. Post-hoc tests showed increased levels of PPD for two CS types (Grade 1, Grade 3) compared to vaginal delivery. For PTSD, secondary CS from relative indication (Grade 2), emergency secondary CS (Grade 1) and assisted vaginal delivery (AVD) were associated with elevated levels of PTSD. Regression analysis revealed delivery mode as a significant predictor of EPDS- (medium effect size) and PCL-5-Score (medium to high effect size). LIMITATION: Delivery was considered as the potential traumatic event, and any previous traumas were not documented. Additionally, the categorization of delivery modes relied on subjective reports rather than medical confirmation. CONCLUSION: The study highlights the influence of delivery mode on the mental health of postpartum mothers: different modes influence postpartum disorders in various ways. However, the definition of delivery mode was only stated subjectively and not medically confirmed. Further research should investigate which aspects of the different delivery modes affect maternal mental health and explore how the perception of childbirth may be influenced by specific delivery experiences.

Protective role of ghrelin against 6PPD-quinone-induced neurotoxicity in zebrafish larvae (Danio rerio) via the GHSR pathway.

The toxicity mechanisms of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q), an antioxidant derivative of 6PPD via ozone reaction commonly used in rubber and tire industries, were investigated in zebrafish larvae with concentrations ranging from 0 to 50 µg/L. Despite normal hatchability, 6PPD-Q exposure led to reduced body length and swimming distance in 120 hours post-fertilization (hpf) larvae. At the highest concentration (50 µg/L), 6PPD-Q significantly impaired dopaminergic neuron development and neurotransmitter levels, including dopamine, 5-hydroxytryptamine, and glutamate. Transcriptome profiling unveiled perturbations in growth and developmental gene expression, such as upregulation of runx2a, runx2b, and ghrl (ghrelin and obestatin prepropeptide), and downregulation of stat1b, auto1, and cidea. Notably, anamorelin, a growth hormone secretagogue receptor (GHSR) agonist, recovered the behavioral deficits induced by 6PPD-Q, implying a neuroprotective role of ghrelin possibly mediated via the ghrelin/GHSR pathway. Collectively, our findings indicate that ghrelin upregulation may counteract 6PPD-Q toxicity in zebrafish larvae, shedding light on potential therapeutic avenues for mitigating the adverse effects of this antioxidant byproduct.

Acute toxicity testing of 6PPD-quinone on the estuarine-dependent sport fish, Sciaenops ocellatus.

Recently, large-scale fish kills in the Pacific Northwest were linked to tire wear particles (TWPs) left on roadways, with the lethality attributed to 6PPD-quinone. which has a median lethal concentration of <1 µg/L for selected salmonids. However, there remains a paucity of 6PPD-quinone toxicity values developed for estuarine fish species, which is particularly significant because estuaries receiving inflows from highly urbanized watersheds are especially vulnerable to TWP contamination. Therefore, the present study aimed to determine the toxicity of 6PPD-quinone to an economically and ecologically important estuarine-dependent fish-red drum (Sciaenops ocellatus). Here, we examined the relative sensitivities of three early life stages within red drum: embryonic, larval, and post-settlement for 24-72 hours, depending on the life stage. Exposure concentrations ranged from 10 µg/L to 500 µg/L. We also assessed the sub-lethal impacts of 6PPD-quinone exposure on development during embryonic and larval stages, including body and organ sizes. Our results indicate that red drum are not acutely sensitive to 6PPD-quinone at each early life stage tested. We also found that yolk-sac larvae did not exhibit sub-lethal morphological impacts in a dose-dependent manner, regardless of exposure during embryonic and larval stages. These data are the first to assess the impacts of 6PPD-quinone on estuarine-dependent non-model fishes.

The relationship of dietary flavonoids and periodontitis in US population: a cross-sectional NHANES analysis.

OBJECTIVES: We investigated the association between dietary flavonoids intake and periodontitis. MATERIALS AND METHODS: This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2009-2010 on 3025 participants aged between 30 and 80 years who had full-mouth periodontal examination and dietary flavonoids intake data. This study used periodontal pocket depth (PPD) and clinical attachment loss (CAL) as periodontitis markers. Data were analyzed using multivariate linear regression. RESULTS: After adjusting confounders, the middle tertile of total dietary flavonoids was associated with decreased mean PPD (0.06 mm, P = 0.016) and mean CAL (0.13 mm, P = 0.001) and the top tertile of total dietary flavonoids was significantly associated with decreases in mean PPD (0.05 mm, P = 0.029) and mean CAL (0.11 mm, P = 0.010). Both the middle and top tertiles of total flavonoids intake were significantly related with decreased mean CAL in females, those flossing 0 days/week, overweight and non-diabetic population but not in males, smokers, those flossing 1-6 days/week and diabetic population. Higher anthocyanidins, flavones and flavonols intake was significantly associated with decreased mean PPD and mean CAL while higher flavanones intake was only significantly associated with decreased mean CAL. Higher anthocyanidins intake was particularly related with greatest decreases in mean CAL (top tertile: 0.22 mm, middle tertile: 0.17 mm, both P < 0.010). However, no significant associations were found between isoflavones and flavan_3_ols intake and mean CAL. CONCLUSIONS: Higher dietary flavonoids intake may be beneficial for periodontal health. CLINICAL RELEVANCE: Additional anthocyanidins, flavanones, flavones and flavonols intake was associated with improved periodontal health.

Ginsenoside Rb1, Compound K and 20(S)-Protopanaxadiol Attenuate High-Fat Diet-Induced Hyperlipidemia in Rats via Modulation of Gut Microbiota and Bile Acid Metabolism.

Hyperlipidemia, characterized by elevated serum lipid concentrations resulting from lipid metabolism dysfunction, represents a prevalent global health concern. Ginsenoside Rb1, compound K (CK), and 20(S)-protopanaxadiol (PPD), bioactive constituents derived from Panax ginseng, have shown promise in mitigating lipid metabolism disorders. However, the comparative efficacy and underlying mechanisms of these compounds in hyperlipidemia prevention remain inadequately explored. This study investigates the impact of ginsenoside Rb1, CK, and PPD supplementation on hyperlipidemia in rats induced by a high-fat diet. Our findings demonstrate that ginsenoside Rb1 significantly decreased body weight and body weight gain, ameliorated hepatic steatosis, and improved dyslipidemia in HFD-fed rats, outperforming CK and PPD. Moreover, ginsenoside Rb1, CK, and PPD distinctly modified gut microbiota composition and function. Ginsenoside Rb1 increased the relative abundance of Blautia and Eubacterium, while PPD elevated Akkermansia levels. Both CK and PPD increased Prevotella and Bacteroides, whereas Clostridium-sensu-stricto and Lactobacillus were reduced following treatment with all three compounds. Notably, only ginsenoside Rb1 enhanced lipid metabolism by modulating the PPARγ/ACC/FAS signaling pathway and promoting fatty acid ß-oxidation. Additionally, all three ginsenosides markedly improved bile acid enterohepatic circulation via the FXR/CYP7A1 pathway, reducing hepatic and serum total bile acids and modulating bile acid pool composition by decreasing primary/unconjugated bile acids (CA, CDCA, and ß-MCA) and increasing conjugated bile acids (TCDCA, GCDCA, GDCA, and TUDCA), correlated with gut microbiota changes. In conclusion, our results suggest that ginsenoside Rb1, CK, and PPD supplementation offer promising prebiotic interventions for managing HFD-induced hyperlipidemia in rats, with ginsenoside Rb1 demonstrating superior efficacy.

Restoring Wnt signaling in a hormone-simulated postpartum depression model remediated imbalanced neurotransmission and depressive-like behaviors.

BACKGROUND: Postpartum depression (PPD) is a prevalent mental disorder that negatively impacts mothers and infants. The mechanisms of vulnerability to affective illness in the postpartum period remain largely unknown. Drastic fluctuations in reproductive hormones during the perinatal period generally account for triggering PPD. However, the molecular mechanism underlying the PPD-like behaviors induced by the fluctuations in hormones has rarely been reported. METHODS: We utilized hormones-simulated pseudopregnancy (HSP) and hormones-simulated postpartum period (HSPP) rat models to determine how drastic fluctuations in hormone levels affect adult neurotransmission and contribute to depressive-like behaviors. The electrophysiological response of CA1 pyramidal neurons was evaluated by whole-cell patch clamping to identify the hormone-induced modulations of neurotransmission. The statistical significance of differences was assessed with One-way ANOVA and t-test (p < 0.05 was considered significant). RESULTS: Reproductive hormones withdrawal induced depressive-like behaviors and disturbed the balance of excitatory and inhibitory transmission in the pyramidal neurons in the hippocampus. Molecular analyses revealed that the blunted Wnt signaling might be responsible for the deficits of synaptic transmission and behaviors. Activation of Wnt signaling increased excitatory and inhibitory synaptic transmission in the hippocampus. Reactivation of Wnt signaling alleviated the anhedonic behaviors and abnormal synaptic transmission. CONCLUSIONS: Restoring Wnt signaling in the hormones-simulated postpartum period rat models remediated depression-related anhedonia symptoms and rebalanced the excitation/inhibition ratio by collectively enhancing the plasticity of GABAergic and glutamatergic synapses. The investigations carried out in this research might provide an alternative and prospective treatment strategy for PPD.

Photoperiod sensitivity of Ppd-H1 and ppd-H1 isogenic lines of a spring barley cultivar: exploring extreme photoperiods.

Barley is a long-day plant with a major gene (PPD-H1) that determines its photoperiod sensitivity. Under long days (i.e. 16 h), flowering occurs earlier in sensitive (Ppd-H1) than in insensitive (ppd-H1) genotypes, while under short days (i.e. 12 h) both flower late and more or less simultaneously. We hypothesized that (i) the sensitive line should flower later than the insensitive line under very short days (<12 h), and (ii) both the sensitive and insensitive lines should have similar phenology under very long days (>18 h). When comparing a pair of spring isogenic lines for sensitive and insensitive PPD-H1 alleles (introgressing the PPD-H1 allele into the barley cultivar 'WI4441'), we found responses fully in line with expectations for the commonly explored range from 12 to 16-18 h. When the responses were extended to very short days, sensitivity increased noticeably, and time to flowering of the sensitive line was longer than that of the insensitive one. Under very long days, the sensitive line did not respond further (it seemed to have reached its minimum time to flowering under a 16 h period), while the insensitive line continued shortening its time to flowering until c. 21 h. Consequently, both lines flowered similarly under very long days, which opens opportunities to easily test for differences in earliness per se, as in wheat.