ABSTRACT
High fructose intake during pregnancy increases insulin resistance (IR) and gestational diabetes mellitus (GDM) risk. IR during pregnancy primarily results from elevated hormone levels. We aim to determine the role of liver carbohydrate response element binding protein (ChREBP) in insulin sensitivity and lipid metabolism in pregnant mice and their offspring. Pregnant C57BL/6J wild-type mice and hepatocyte-specific ChREBP-deficient mice were fed with a high-fructose diet (HFrD) or normal chow diet (NC) pre-delivery. We found that the combination of HFrD with pregnancy excessively activates hepatic ChREBP, stimulating progesterone synthesis by increasing MTTP expression, which exacerbates IR. Increased progesterone levels upregulated hepatic ChREBP via the progesterone-PPARγ axis. Placental progesterone activated the progesterone-ChREBP loop in female offspring, contributing to IR and lipid accumulation. In normal dietary conditions, hepatic ChREBP modestly affected progesterone production and influenced IR during pregnancy. Our findings reveal the role of hepatic ChREBP in regulating insulin sensitivity and lipid homeostasis in both pregnant mice consuming an HFrD and female offspring, and suggest it as a potential target for managing gestational metabolic disorders, including GDM.
Subject(s)
Insulin Resistance , Pregnancy , Female , Mice , Animals , Insulin Resistance/genetics , Fructose/adverse effects , Fructose/metabolism , Progesterone/metabolism , Mice, Inbred C57BL , Placenta/metabolism , Liver/metabolism , Lipids , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolismABSTRACT
Chiral plasmonic structures have garnered increasing attention owing to their distinctive chiroptical response. Localized surface plasmon resonance can significantly enhance the circular dichroism and local electromagnetic field of chiral plasmonic structures, resulting in enhanced electromagnetic forces acting on surrounding nanoparticles. Moreover, the circular dichroism response of chiral structures provides an effective means for macroscopic adjustment of microscopic electromagnetic fields. However, chiral plasmon effects are naturally related to angular momentum, and particle control studies of chirality usually focus on angular momentum. This paper proposes a particle manipulation method utilizing chiral light-matter interactions. Through optimization of the optical response of the chiral structure, the direction of electromagnetic forces exerted on surrounding polystyrene particles reverses upon a change in the incident light's handedness. According to this characteristic, the movement direction control of polystyrene particles with a diameter of 100 nm was achieved. By altering the handedness of a single circularly polarized light, more than 94% high-precision particle manipulation was achieved, reducing the complexity of particle manipulation. This microfluidic method has significant implications for advancing microfluidic research and chiral applications.
ABSTRACT
Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3ß, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 µM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3ß pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF. GE exerts anti-oxidative stress properties by binding to MMP2, inhibiting ROS generation in HFpEF through the SIRT1/Nrf2 signaling pathway. In addition, GE can also affect the inhibition of the downstream MMP2 target GSK3ß, thereby suppressing the inflammatory and apoptotic responses in HFpEF. Taken together, GE alleviates oxidative stress/apoptosis/fibrosis and metabolic disorders as well as HFpEF through the MMP2/SIRT1/GSK3ß signaling pathway.
ABSTRACT
The NDPK gene family is an important group of genes in plants, playing a crucial role in regulating energy metabolism, growth, and differentiation, cell signal transduction, and response to abiotic stress. However, our understanding of the NDPK gene family in Brassica napus L. remains limited. This paper systematically analyzes the NDPK gene family in B. napus, particularly focusing on the evolutionary differences within the species. In this study, sixteen, nine, and eight NDPK genes were identified in B. napus and its diploid ancestors, respectively. These genes are not only homologous but also highly similar in their chromosomal locations. Phylogenetic analysis showed that the identified NDPK proteins were divided into four clades, each containing unique motif sequences, with most NDPKs experiencing a loss of introns/exons during evolution. Collinearity analysis revealed that the NDPK genes underwent whole-genome duplication (WGD) events, resulting in duplicate copies, and most of these duplicate genes were subjected to purifying selection. Cis-acting element analysis identified in the promoters of most NDPK genes elements related to a light response, methyl jasmonate response, and abscisic acid response, especially with an increased number of abscisic acid response elements in B. napus. RNA-Seq results indicated that NDPK genes in B. napus exhibited different expression patterns across various tissues. Further analysis through qRT-PCR revealed that BnNDPK genes responded significantly to stress conditions such as salt, drought, and methyl jasmonate. This study enhances our understanding of the NDPK gene family in B. napus, providing a preliminary theoretical basis for the functional study of NDPK genes and offering some references for further revealing the phenomenon of polyploidization in plants.
Subject(s)
Brassica napus , Gene Expression Regulation, Plant , Multigene Family , Phylogeny , Plant Proteins , Stress, Physiological , Brassica napus/genetics , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Genome, Plant , Evolution, Molecular , Gene Expression Profiling , Gene DuplicationABSTRACT
High-performance perovskite materials with excellent physical, electronic, and optical properties play a significant role in artificial neuromorphic devices. However, the development of perovskites in microelectronics is inevitably hindered by their intrinsic non-ideal properties, such as high defect density, environmental sensitivity, and toxicity. By leveraging materials engineering, integrating various materials with perovskites to leverage their mutual strengths presents great potential to enhance ion migration, energy level alignment, photoresponsivity, and surface passivation, thereby advancing optoelectronic and neuromorphic device development. This review initially provides an overview of perovskite materials across different dimensions, highlighting their physical properties and detailing their applications and metrics in two- and three-terminal devices. Subsequently, we comprehensively summarize the application of perovskites in combination with other materials, including organics, nanomaterials, oxides, ferroelectrics, and crystalline porous materials (CPMs), to develop advanced devices such as memristors, transistors, photodetectors, sensors, light-emitting diodes (LEDs), and artificial neuromorphic systems. Lastly, we outline the challenges and future research directions in synthesizing perovskite composites for neuromorphic devices. Through the review and analysis, we aim to broaden the utilization of perovskites and their composites in neuromorphic research, offering new insights and approaches for grasping the intricate physical working mechanisms and functionalities of perovskites.
ABSTRACT
As a replacement for bisphenol A (BPA), bisphenol AF (BPAF) showed stronger maternal transfer and higher fetal accumulation than BPA. Therefore, concerns should be raised about the health risks of maternal exposure to BPAF during gestation on the offspring. In this study, SD rats were exposed to BPAF (0, 50, and 100 mg/kg/day) during gestation to investigate the bioaccumulation and adverse effects in liver, spleen, and kidney tissues of the offspring at weaning period. Bioaccumulation of BPAF in these tissues with concentrations ranging from 1.56 ng/mg (in spleen of males) to 55.44 ng/mg (in liver of females) led to adverse effects at different biological levels, including increased relative weights of spleen and kidneys, histopathological damage in liver, spleen, and kidney, organ functional damage in liver, spleen, and kidney, upregulated expression of genes related to lipid metabolism (in liver), oxidative stress response (in kidney), immunity and inflammatory (in spleen). Furthermore, dysregulated metabolomics was identified in spleen, with 217 differential metabolites screened and 9 KEGG pathways significantly enriched. This study provides a comprehensive insight into the systemic toxicities of prenatal exposure to BPAF in SD rats. Given the broad applications and widespread occurrence of BPAF, its safety should be re-considered.
ABSTRACT
INTRODUCTION: Vascular calcification, a devastating vascular complication accompanying atherosclerotic cardiovascular disease and chronic kidney disease, increases the incidence of adverse cardiovascular events and compromises the efficacy of vascular interventions. However, effective therapeutic drugs and treatments to delay or prevent vascular calcification are lacking. OBJECTIVES: This study was designed to test the therapeutic effects and mechanism of Moscatilin (also known as dendrophenol) from Dendrobium huoshanense (an eminent traditional Chinese medicine) in suppressing vascular calcification in vitro, ex vivo and in vivo. METHODS: Male C57BL/6J mice (25-week-old) were subjected to nicotine and vitamin D3 (VD3) treatment to induce vascular calcification. In vitro, we established the cellular model of osteogenesis of human aortic smooth muscle cells (HASMCs) under phosphate conditions. RESULTS: By utilizing an in-house drug screening strategy, we identified Moscatilin as a new naturally-occurring chemical entity to reduce HASMC calcium accumulation. The protective effects of Moscatilin against vascular calcification were verified in cultured HASMCs. Unbiased transcriptional profiling analysis and cellular thermal shift assay suggested that Moscatilin suppresses vascular calcification via binding to interleukin 13 receptor subunit A2 (IL13RA2) and augmenting its expression. Furthermore, IL13RA2 was reduced during HASMC osteogenesis, thus promoting the secretion of inflammatory factors via STAT3. We further validated the participation of Moscatilin-inhibited vascular calcification by the classical WNT/ß-catenin pathway, among which WNT3 played a key role in this process. Moscatilin mitigated the crosstalk between WNT3/ß-catenin and IL13RA2/STAT3 to reduce osteogenic differentiation of HASMCs. CONCLUSION: This study supports the potential of Moscatilin as a new naturally-occurring candidate drug for treating vascular calcification via regulating the IL13RA2/STAT3 and WNT3/ß-catenin signalling pathways.