RÉSUMÉ
Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis. We first identified five genome-wide significant variants associated with both diseases. Four of the variants did not demonstrate clear colocalization between GWAS and healthy lung eQTL signals. Instead, two of the four variants colocalized only in cell-type and disease-specific eQTL datasets. These analyses pointed to higher ATP11A expression from the C allele of rs12585036, in monocytes and in lung tissue from primarily smokers, which increased risk of IPF and decreased risk of critically ill COVID-19. We also found lower DPP9 expression (and higher methylation at a specific CpG) from the G allele of rs12610495, acting in fibroblasts and in IPF lungs, and increased risk of IPF and critically ill COVID-19. We further found differential expression of the identified causal genes in diseased lungs when compared to non-diseased lungs, specifically in epithelial and immune cell types. These findings highlight the power of integrating GWAS, context-specific eQTLs, and transcriptomics of diseased tissue to harness human genetic variation to identify causal genes and where they function during multiple diseases.
RÉSUMÉ
This study was designed to compare the antioxidant, antitumor and anti-inflammatory effects of essential oils from the bark and flower of Magnolia officinalis Rehd. et Wils. Distillation extraction and steam distillation were used to extract EOs from the bark and flower. The results showed that the contents of EOs of SDE-F and SDE-B were much higher than that of SD-F and SD-B. EOs from the bark were rich in eudesmol (especially α-eudesmol) and exhibited a stronger antioxidant effect than the flower. The anti-tumor effects of SD-B and SD-F on HepG2 and MDA-MB-231 cells were better than that of SDE-B and SDE-F. The inhibitory rates of SD-B and SD-F on MDA-MB-231 cells were 59.21% and 48.27%, exceeding that of positive control 5-fluorouracil (47.04%) at 50 µg/mL. All four EOs exhibited excellent anti-inflammatory activities through the regulation of nitric oxide production and pro-inflammation cytokines in LPS-induced RAW 264.7 cells and they also remarkably suppressed the mRNA expressions of nitric oxide synthase, IL-6 and TNF-α at the concentration higher than that of positive control dexamethasone. These results indicated significant differences in the composition, and anti-inflammatory and anti-tumor activities of EOs extracted by different methods and provided a theoretical basis for their development and utilization.
RÉSUMÉ
The Rosa cymosa Tratt, an herbal plant from the Rosaceae family, has historically been valued in China for its medicinal and edible properties. In this study, a novel polysaccharide from R. cymosa fruit, termed PRCP (purified R. cymosa polysaccharide), was isolated using water extraction, decolorization, deproteinization, and ion-exchange chromatography. The structural characteristics of PRCP were investigated using monosaccharide composition analysis, methylation, GPC, FTIR, CD, and NMR spectroscopy. The immunomodulatory effect and potential mechanism of PRCP were evaluated in vitro using a macrophage cell model. Results indicated that PRCP (37.28 kDa) is a highly branched polysaccharide (72.61 %) primarily composed of arabinogalactan, rhamnogalacturonan, and galactoglucan domains with 13 types of glycosidic linkage fragments. Furthermore, PRCP appears to modulate immunomodulatory effects by influencing the phosphorylation of P38 and JNK proteins in the MAPK pathway. Collectively, these findings highlight the potential of PRCP as a promising natural functional food ingredient for immunostimulation.
Sujet(s)
Fruit , Système de signalisation des MAP kinases , Polyosides , Rosa , Rosa/composition chimique , Polyosides/pharmacologie , Polyosides/composition chimique , Polyosides/isolement et purification , Souris , Système de signalisation des MAP kinases/effets des médicaments et des substances chimiques , Fruit/composition chimique , Animaux , Cellules RAW 264.7 , Facteurs immunologiques/pharmacologie , Facteurs immunologiques/composition chimique , Facteurs immunologiques/isolement et purification , Macrophages/effets des médicaments et des substances chimiques , Macrophages/métabolisme , Oses/analyse , Phosphorylation/effets des médicaments et des substances chimiquesRÉSUMÉ
Objective: In this study, we aimed to determine whether proly4-hydroxylase-III (P4HA3) could be used as a biomarker for the diagnosis of colorectal cancer (CRC) as well as for determining prognosis. Methods: We used The Cancer Genome Atlas (TCGA) database to analyze P4HA3 expression in CRC and further investigated the association between P4HA3 and clinicopathological parameters, immune infiltration, and prognosis of patients with CRC. Enrichment analysis was conducted to investigate the potential biological role of P4HA3 in CRC. To verify the results of TCGA analysis, we performed immunohistochemical staining of 180 clinical CRC tissue samples to probe into the relationship of P4HA3 expression with lymphocyte infiltration and immune checkpoints expression. Results: The expression of P4HA3 was significantly higher in CRC tissues and associated with a higher degree of malignancy and poorer prognosis in CRC. The results of enrichment analysis indicated that P4HA3 may be associated with the epithelial-mesenchymal transition process and the immune response. Immunohistochemical staining results showed that high P4HA3 expression was associated with high infiltration levels of CD8+ and Foxp3+ TILs and high PD-1/PD- L1 expression. Lastly, patients with CRC co-expressing P4HA3 and PD-1 had a significantly worse prognosis. Conclusion: High expression of P4HA3 is associated with adverse clinical features and immune cell infiltration in CRC, and has the potential to serve as a biomarker for predicting CRC prognosis.
RÉSUMÉ
BACKGROUND: While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remains poorly understood. METHODS: Single-cell RNA sequencing data generated with SmartSeq2 (≈8000 genes/cell) in 16â 588 single cells isolated during atherosclerosis progression in Ldlr-/-Apob100/100 mice with human-like plasma lipoproteins and from humans with asymptomatic and symptomatic carotid plaques was clustered into multiple subtypes. For clinical and pathophysiological context, the advanced-stage and symptomatic subtype clusters were integrated with 135 tissue-specific (atherosclerotic aortic wall, mammary artery, liver, skeletal muscle, and visceral and subcutaneous, fat) gene-regulatory networks (GRNs) inferred from 600 coronary artery disease patients in the STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) study. RESULTS: Advanced stages of atherosclerosis progression and symptomatic carotid plaques were largely characterized by 3 smooth muscle cells (SMCs), and 3 macrophage subtype clusters with extracellular matrix organization/osteogenic (SMC), and M1-type proinflammatory/Trem2-high lipid-associated (macrophage) phenotypes. Integrative analysis of these 6 clusters with STARNET revealed significant enrichments of 3 arterial wall GRNs: GRN33 (macrophage), GRN39 (SMC), and GRN122 (macrophage) with major contributions to coronary artery disease heritability and strong associations with clinical scores of coronary atherosclerosis severity. The presence and pathophysiological relevance of GRN39 were verified in 5 independent RNAseq data sets obtained from the human coronary and aortic artery, and primary SMCs and by targeting its top-key drivers, FRZB and ALCAM in cultured human coronary artery SMCs. CONCLUSIONS: By identifying and integrating the most gene-rich single-cell subclusters of atherosclerosis to date with a coronary artery disease framework of GRNs, GRN39 was identified and independently validated as being critical for the transformation of contractile SMCs into an osteogenic phenotype promoting advanced, symptomatic atherosclerosis.
Sujet(s)
Athérosclérose , Réseaux de régulation génique , Analyse sur cellule unique , Humains , Animaux , Athérosclérose/génétique , Athérosclérose/métabolisme , Athérosclérose/anatomopathologie , Souris , Myocytes du muscle lisse/métabolisme , Myocytes du muscle lisse/anatomopathologie , Mâle , Plaque d'athérosclérose , Évolution de la maladie , Femelle , Macrophages/métabolisme , Macrophages/anatomopathologie , Souris knockout , Récepteurs aux lipoprotéines LDL/génétique , Récepteurs aux lipoprotéines LDL/métabolisme , Souris de lignée C57BL , Muscles lisses vasculaires/métabolisme , Muscles lisses vasculaires/anatomopathologieRÉSUMÉ
The treatment of acute myeloid leukemia (AML) remains unsatisfactory, owing to the absence of efficacious therapy regimens over decades. However, advances in molecular biology, including inhibiting the CXCR4/CXCL12 biological axis, have introduced novel therapeutic options for AML. Additionally, self-stimulated phototherapy can solve the poor light penetration from external sources, and it will overcome the limitation that traditional phototherapy cannot be applied to the treatment of AML. Herein, we designed and manufactured a self-stimulated photodynamic nanoreactor to enhance antileukemia efficacy and suppress leukemia recurrence and metastasis in AML mouse models. To fulfill our design, we utilized the CXCR4/CXCL12 biological axis and biomimetic cell membranes in conjunction with self-stimulated phototherapy. This nanoreactor possesses the capability to migrate into the bone marrow cavity, inhibit AML cells from infiltrating into the visceral organ, significantly enhance the antileukemia effect, and prolong the survival time of leukemic mice. Therefore, this nanoreactor has significant potential for achieving high success rates and low recurrence rates in leukemia treatment.
Sujet(s)
Leucémie aigüe myéloïde , Photothérapie dynamique , Récepteurs CXCR4 , Animaux , Récepteurs CXCR4/métabolisme , Récepteurs CXCR4/antagonistes et inhibiteurs , Souris , Humains , Leucémie aigüe myéloïde/traitement médicamenteux , Leucémie aigüe myéloïde/anatomopathologie , Leucémie aigüe myéloïde/métabolisme , Leucémie aigüe myéloïde/thérapie , Photosensibilisants/composition chimique , Photosensibilisants/pharmacologie , Photosensibilisants/usage thérapeutique , Lignée cellulaire tumorale , Chimiokine CXCL12/métabolisme , Antinéoplasiques/composition chimique , Antinéoplasiques/pharmacologieRÉSUMÉ
BACKGROUND: Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery. RESULT: This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype. CONCLUSION: This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.
Sujet(s)
Polyarthrite rhumatoïde , Cérium , Composés du manganèse , Nanoparticules , Oxydes , Humains , Manganèse/pharmacologie , Espèces réactives de l'oxygène/pharmacologie , Polyarthrite rhumatoïde/traitement médicamenteux , Macrophages , Inflammation , Cérium/pharmacologieRÉSUMÉ
Five trichothecenes including a new one, together with two previously undescribed benzene derivatives were isolated from the solid culture of Trichothecium sp. Their structures were established by 1D and 2D NMR data in conjunction with HR-ESI-MS analysis. Compounds 1-5 exhibited cytotoxicity against MCF-7 cell lines at various levels ranging from IC50 of 7.23 to 16.95 µM. Compound 6 decreased the concentration of blood lipids in zebra fish at the concentration of 20 µM.
RÉSUMÉ
Prenatal exposure to pyrethroids is linked to adverse health effects in early life and proper placental function is critical to fetal development. This study explores the impact of prenatal pyrethroid exposure, as well as factors impacting exposure and effect, on the placental transcriptome, to understand pyrethroid exposures' relationship to placental function. The study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) recruited pregnant farm-working women from two agricultural districts in the Chiang Mai province of Thailand between 2017 and 2019. This cohort was predominantly exposed to cypermethrin (type II), alongside pyrethroids such as cyfluthrin (type II) and permethrin (type I). In 253 participants, maternal urinary pyrethroid metabolites, 3-phenoxybenzoic acid (PBA), cis-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (CDCCA), and trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (TDCCA) were measured in early, middle, and late pregnancy and adjusted for urinary creatinine. The placental transcriptome was analyzed using RNA-Seq. Using generalized linear regression, we identified differentially expressed genes (DEGs) associated with the sum of each metabolite across pregnancy, as well as those associated with location of residence and season of birth. Pathway and upstream transcription factor analyses were performed to examine potential mechanisms associated with DEGs. Notably, TDCCA and CDCCA levels peaked in late pregnancy, with significant regional differences, particularly higher levels in the Fang region. Placental gene expression analysis showed no DEGs associated with individual metabolites at FDR<0.05. However, 251 DEGs by location, implicating immune response and oxidative phosphorylation pathways, were identified, while season of birth was associated with 2585 DEGs, over-represented in fibrosis signaling and metabolism pathways. Finally, transcription factor analysis identified 226 and 282 transcription factors associated with location and season, respectively, related to cell proliferation, differentiation, and the immune system. These alterations may have significant implications for fetal development and other pathologic processes, highlighting the importance of monitoring environmental exposures during pregnancy.
Sujet(s)
Exposition maternelle , Placenta , Pyréthrines , Saisons , Transcriptome , Adulte , Femelle , Humains , Grossesse , Jeune adulte , Agriculteurs , Fermes , Insecticides/métabolisme , Exposition maternelle/statistiques et données numériques , Placenta/métabolisme , Pyréthrines/métabolisme , Peuples d'Asie du Sud-Est , ThaïlandeRÉSUMÉ
Water-soluble inorganic ions (WSIIs, primarily NH4+, SO42-, and NO3-) are major components in ambient PM2.5, but their reproductive toxicity remains largely unknown. An animal study was conducted where parental mice were exposed to PM2.5 WSIIs or clean air during preconception and the gestational period. After delivery, all maternal and offspring mice lived in a clean air environment. We assessed reproductive organs, gestation outcome, birth weight, and growth trajectory of the offspring mice. In parallel, we collected birth weight and placenta transcriptome data from 150 mother-infant pairs from the Rhode Island Child Health Study. We found that PM2.5 WSIIs induced a broad range of adverse reproductive outcomes in mice. PM2.5 NH4+, SO42-, and NO3- exposure reduced ovary weight by 24.22% (p = 0.005), 14.45% (p = 0.048), and 16.64% (p = 0.022) relative to the clean air controls. PM2.5 SO42- exposure reduced the weight of testicle by 5.24% (p = 0.025); further, mice in the PM2.5 SO42- exposure group had 1.81 (p = 0.027) fewer offspring than the control group. PM2.5 NH4+, SO42-, and NO3- exposure all led to lower birth than controls. In mice, 557 placenta genes were perturbed by exposure. Integrative analysis of mouse and human data suggested hypoxia response in placenta as an etiological mechanism underlying PM2.5 WSII exposure's reproductive toxicity.
Sujet(s)
Polluants atmosphériques , Humains , Grossesse , Femelle , Enfant , Polluants atmosphériques/toxicité , Polluants atmosphériques/analyse , Eau , Matière particulaire/toxicité , Matière particulaire/analyse , Poids de naissance , Surveillance de l'environnement , Ions/analyse , ChineRÉSUMÉ
The active ingredients of Citrus aurantium have been shown to possess a variety of biological activities, especially anti-inflammatory effects. However, its antiatherosclerotic effects need to be further investigated. The aim of this study is to identify compounds with antiatherosclerotic effects from C. aurantium and to further investigate their mechanisms. Three compounds were separated, and then their antiatherosclerotic effect on foam cells induced by oxidized low-density lipoprotein (ox-LDL) was screened by oil red O staining, BODIPY staining, and Dil-ox-LDL uptake measurement. Cholesterol uptake, cholesterol efflux, RT-PCR, and Western blot analysis were used to comprehensively and comparatively explore the potential mechanisms. Nobiletin (NOB), caffeine (CAF), and naringin (NARG), which were separated from C. aurantium, mainly inhibit the formation of foam cells in different ways. NOB reduced cholesterol uptake and enhanced cholesterol efflux and mainly regulated the expressions of ABCA1, ABCG1, and SRA1. CAF promoted cholesterol efflux, mainly by stimulating the expressions of ABCA1 and ABCG1. NARG was more effective in reducing the expression of SRA1 and CD36, which indicated that NARG mainly prevented atherosclerosis by blocking cholesterol uptake. The above results show in detail the antiatherosclerotic activity and mechanism of these compounds, making contributions to their potential applications.
RÉSUMÉ
Alcohol consumption during pregnancy can result in a range of adverse postnatal outcomes among exposed children. However, identifying at-risk children is challenging given the difficulty to confirm prenatal alcohol exposure and the lack of early diagnostic tools. Placental surveys present an important opportunity to uncover early biomarkers to identify those at risk. Here, we report the first transcriptome-wide evaluation to comprehensively evaluate human placental pathways altered by fetal alcohol exposure. In a prospective longitudinal birth cohort in Cape Town, South Africa, we performed bulk tissue RNAseq in placenta samples from 32 women reporting heavy drinking during pregnancy and 30 abstainers/light drinkers. Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis were performed to assess associations between fetal alcohol exposure and placental gene expression patterns at a network-wide and single gene level, respectively. The results revealed altered expression in genes related to erythropoiesis and angiogenesis, which are implicated in established postnatal phenotypes related to alcohol exposure, including disruptions in iron homeostasis, growth, and neurodevelopment. The reported findings provide insights into the molecular pathways affected by prenatal alcohol exposure and highlight the potential of placental biomarkers for detecting and understanding the effects of alcohol on fetal development.
Sujet(s)
Placenta , Effets différés de l'exposition prénatale à des facteurs de risque , Enfant , Humains , Femelle , Grossesse , Placenta/métabolisme , Études prospectives , Effets différés de l'exposition prénatale à des facteurs de risque/induit chimiquement , République d'Afrique du Sud , Éthanol/pharmacologie , Consommation d'alcool/effets indésirables , Consommation d'alcool/génétique , Marqueurs biologiques/métabolismeRÉSUMÉ
BACKGROUND: Fetal alcohol spectrum disorders (FASD) are the most common preventable cause of birth defects and neurodevelopmental disorders worldwide. The placenta is the crucial interface between mother and fetus. Prenatal alcohol exposure (PAE) has been shown to alter placental structure and expression of genes in bulk placental tissue samples, but prior studies have not examined effects on placental cell-type composition or taken cell-type into consideration in transcriptome analyses. METHODS: We leveraged an existent placenta single-cell RNA-seq dataset to perform cell-type deconvolution of bulk placental RNA-seq data from 35 heavy drinking pregnant women and 33 controls in a prospective birth cohort in Cape Town, South Africa. We used bivariate analyses and multivariable adjusted linear regression models to assess the relation of PAE on inferred placental cell-type proportions. We also examined differential expression of inflammatory response genes and PAE, using multivariable adjusted linear models. RESULTS: Deconvolution analyses showed heterogeneous placenta cell-type composition in which stromal (27 %), endothelial (26 %) and cytotrophoblasts (18 %) were the predominant cell-types. PAE around conception was associated with a higher proportion of Hofbauer cells (B = 0.51, p = 0.035) in linear models adjusted for maternal age, infant sex, and gestational age. Among the 652 inflammatory genes examined, 35 were differential expressed in alcohol exposed placentas (FDR p < 0.05). CONCLUSIONS: Our findings suggest that heavy alcohol exposure during pregnancy can influence the proportion of fetal placental villi macrophages (Hofbauer cells) and increased expression of inflammatory genes. Future studies are needed to further characterize these effects and to assess the potential functional roles of placental inflammation in FASD.
Sujet(s)
Troubles du spectre de l'alcoolisation foetale , Effets différés de l'exposition prénatale à des facteurs de risque , Femelle , Grossesse , Humains , Placenta/métabolisme , Troubles du spectre de l'alcoolisation foetale/génétique , Troubles du spectre de l'alcoolisation foetale/métabolisme , Études prospectives , RNA-Seq , Effets différés de l'exposition prénatale à des facteurs de risque/génétique , Effets différés de l'exposition prénatale à des facteurs de risque/métabolisme , République d'Afrique du Sud , Éthanol/toxicité , Expression des gènesRÉSUMÉ
ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifolia Willd. has been widely used in the treatment of cancer, forgetfulness, depression and other diseases. AIM OF REVIEW: The purpose of this study was to investigate the sleep-enhancing effect and mechanism of P. tenuifolia saponins (PTS). MATERIALS AND METHODS: The total saponin (YZ-I) and purified saponin (YZ-II) fractions were extracted and ICR mice model of insomnia was established by p-chlorophenylalanine (PCPA) induction to observe anxiety and depression behaviors. Effects of YZ-I and YZ-II on the levels of neurotransmitters, hormones, and inflammation cytokines were detected by ELISA, RT-qPCR and western blotting. RESULTS: The results showed that YZ-I and YZ-II reduced the immobility time of mice and prolonged the sleep time of mice and significantly increased the concentrations of 5-HT, NE, PGD2, IL-1ß and TNF-α. YZ-I and YZ-II regulated GABAARα2, GABAARα3, GAD65/67, 5-HT1A and 5-HT2A, while regulated the levels of inflammatory cytokines such as DPR, PGD2, iNOS and TNF-α to exert sedative and hypnotic effects. CONCLUSION: PTS are mainly achieved sedative and hypnotic effects by altering serotonergic, GABAergic and immune systems, but the effects and mechanisms of action of YZ-I were different from YZ-II.
Sujet(s)
Polygala , Saponines , Troubles de l'endormissement et du maintien du sommeil , Animaux , Souris , Hypnotiques et sédatifs/pharmacologie , Troubles de l'endormissement et du maintien du sommeil/traitement médicamenteux , Saponines/pharmacologie , Facteur de nécrose tumorale alpha , Sérotonine , Souris de lignée ICR , Acide gamma-amino-butyriqueRÉSUMÉ
Prenatal alcohol exposure (PAE) is associated with alterations in maternal and infant iron homeostasis that are consistent with changes seen in the setting of inflammation. We hypothesized that PAE leads to alterations in the placental expression of genes related to iron metabolism and inflammation that play functional roles in the teratogenic effects of alcohol on iron homeostasis. A total of 126 heavy-drinking women (≥1 oz (30 mL) absolute alcohol/day (~1.67 standard drinks/day) or women reporting binge drinking (≥2 drinks/occasion)) and 80 control women (<0.5 oz AA per day, no binging) in Cape Town, South Africa were interviewed prenatally regarding demographics, and alcohol, smoking, and drug use around conception and during pregnancy. Prenatal/maternal and infant hemoglobin and ferritin were measured. Whole-transcriptome RNA sequencing analysis was performed on flash-frozen transplacental tissue samples. Gene sets related to iron metabolism (n = 398) and inflammation (n = 467) were constructed by searching the Molecular Signatures Database for related ontology terms. Principal component analysis (PCA) yielded 59 factors for each theme. In multivariable regression models, PAE was related to 2 iron metabolism PCA factors (PCs) and 5 inflammation PCs, among which 2 iron metabolism and 4 inflammation factors were related to at least 1 key maternal or infant iron outcome. In causal inference analyses based on marginal structural models and the product method, the alterations in the expression profile of genes with functions in immune cell regulation, cytokine activity, angiogenesis, hematopoiesis, and ubiquitous cell processes appeared to partially mediate the relation of prenatal drinking frequency (days/week) around conception to a lower maternal hemoglobin-to-log(ferritin) ratio (proportion mediation = 51.35%). These findings suggest that placental inflammation may be partly responsible for the differences in alcohol-related iron homeostasis patterns between pregnant and non-pregnant adults.
Sujet(s)
Placenta , Effets différés de l'exposition prénatale à des facteurs de risque , Nourrisson , Adulte , Femelle , Humains , Grossesse , Placenta/métabolisme , République d'Afrique du Sud , Consommation d'alcool/effets indésirables , Fer/métabolisme , Ferritines/métabolisme , Éthanol , Inflammation , Hémoglobines/métabolisme , Vitamines , Homéostasie , Expression des gènesRÉSUMÉ
Various additives have been introduced to assist in film preparation and defect passivation. Herein, fluoroiodobenzene (FIB) molecules with different numbers of F atoms were incorporated into perovskite films to optimize the film quality as well as passivate defects. Based on the calculation and experimental results, it was found that the FIB additives were inclined to exist at the bottom of the film because of the strong affinity between F atoms stemming from FIB molecules and O atoms stemming from TiO2, especially for molecules with more F atoms. By optimization of the FIB molecule, the perovskite film crystallinity was significantly improved, the carrier lifetimes were prolonged, and the charge extraction ability was also enhanced. The device with FIB with one F atom achieved a photoelectrical conversion efficiency as high as 22.89% with a Voc of 1.118 V, fill factor (FF) of 80.44%, and Jsc of 25.45 mA cm-2, which was much higher than that of the control device with an efficiency of 20.87%. Furthermore, FIB molecules with three and five F atoms also achieved higher efficiency than that of the control device. The devices with FIB molecules showed better stability than the devices without additives. The unencapsulated devices with FIB additives held 90% of their original efficiencies in an ambient environment with a temperature of 15-25 °C and a relative humidity of 20-30%, while the control device dropped to 76% after more than 1000 h.
RÉSUMÉ
A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
Sujet(s)
Étude d'association pangénomique , Placenta , Femelle , Humains , Grossesse , Poids de naissance/génétique , Développement foetal/génétique , Insuline , Placenta/métabolisme , MâleRÉSUMÉ
The role of Semen Ziziphus jujube saponins in sedative and hypnosis has attracted much attention. The study aimed to investigate its possible UV damage protection and anti-aging effects. Total saponins (SZR I) and purified saponins (SZR II) were analyzed and compared by infrared spectroscopy and high-performance liquid chromatography (HPLC). The protective effects of SZR I, SZR II, and their three monomers on HaCaT cells damaged by UV were studied, and their anti-aging activities were observed by Caenorhabditis elegans with paraquat-induced oxidative stress. The results showed that SZR I and SZR II differ in chemical composition but both have the same three monomers. The cell survival rate treated with SZR I and SZR II at a concentration of 400 µg/mL increased by 34.45 and 88.98%, respectively, indicating that they could promote the proliferation of UVB-damaged HaCaT cells. Jujuboside A, Jujuboside B, and spinosin from the saponins exhibited similar effects on UVB-damaged HaCaT cells. SZR I and SZR II had little effect on reproductive performance but could delay the senescence caused by heat and oxidative stress of the C. elegans model. These results provide useful data that Semen Z. jujube saponin is a potential natural product with UV damage protection and anti-aging characteristics.