Nickel Nanoparticles Protruding from Molybdenum Carbide Micropillars with Carbon Layer-Protected Biphasic 0D/1D Heterostructures for Efficient Water Splitting.

It remains a tremendous challenge to achieve high-efficiency bifunctional electrocatalysts for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) for hydrogen production by water splitting. Herein, a novel hybrid of 0D nickel nanoparticles dispersed on the one-dimensional (1D) molybdenum carbide micropillars embedded in the carbon layers (Ni/Mo2C@C) was successfully prepared on nickel foam by a facile pyrolysis strategy. During the synthesis process, the nickel nanoparticles and molybdenum carbide were simultaneously generated under H2 and C2H2 mixed atmospheres and conformally encapsulated in the carbon layers. Benefiting from the distinctive 0D/1D heterostructure and the synergistic effect of the biphasic Mo2C and Ni together with the protective effect of the carbon layer, the reduced activation energy barriers and fast catalytic reaction kinetics can be achieved, resulting in a small overpotential of 96 mV for the HER and 266 mV for the OER at the current density of 10 mA cm-2 together with excellent durability in 1.0 M KOH electrolyte. In addition, using the developed Ni/Mo2C@C as both the cathode and anode, the constructed electrolyzer exhibits a small voltage of 1.55 V for the overall water splitting. The novel designed Ni/Mo2C@C may give inspiration for the development of efficient bifunctional catalysts with low-cost transition metal elements for water splitting.

Asthma susceptibility in prenatal nicotine-exposed mice attributed to ß-catenin increase during CD4+ T cell development.

Cigarette smoke is a common global environmental pollutant. Asthma, the most frequent allergic airway disease, is related to maternal exposure to cigarette smoke. Our previous studies demonstrated that prenatal exposure to nicotine (PNE), the major active product of smoking, impairs fetal thymopoiesis and CD4+ T cell development after birth. This study aimed to investigate whether PNE contributes to asthma susceptibility through CD4+ T cell development alterations. First, A PNE model was established by administering 3 mg/kg/day nicotine to maternal mice, and then an ovalbumin-induced asthma model was established in the offspring. Further, ß-catenin and downstream pathways were inhibited in vitro to confirm the molecular mechanisms underlying the phenotype observed during the in vivo phase. The results showed that PNE induced Th2 and Th17 biases at developmental checkpoints and aggravated asthma symptoms in the offspring. In fetuses, PNE up-regulated α7 nAChR, activated PI3K-AKT, promoted ß-catenin level increase, and established potential Th2- and Th17-biased gene expression patterns during thymopoiesis, which persisted after birth. Similar results were also observed in 1 µM nicotine-treated thymocytes in vitro. Moreover, inhibiting PI3K-AKT by LY294002 abrogated nicotine-mediated ß-catenin level increase and thymopoiesis abnormalities, and an α7 nAChR antagonist (α-btx) also reversed nicotine-induced PI3K-AKT activation. Our findings provide strong evidence that PNE is a risk factor for T cell deviation and postnatal asthma, and revealed that nicotine-induced ß-catenin level increase induces thymopoiesis abnormalities.

Augmented autophagy suppresses thymocytes development via Bcl10/p-p65 pathway in prenatal nicotine exposed fetal mice.

Tobacco smoke is a common global environmental pollutant. Maternal tobacco smoke/nicotine exposure has long-term toxic effects on immune organs. We previously found that prenatal nicotine exposure (PNE)-induced programmed immune diseases caused by fetal thymic hypoplasia, but the mechanism still unknown. Autophagy has important functions in maintaining thymopoiesis, whether autophagy was involved in PNE-inhibited fetal thymocytes development is also obscure. Therefore, this study aimed to investigate how nicotine changed the development of fetal thymocytes from the perspective of autophagy in vivo and in vitro. PNE model was established by 3 mg/kg nicotine administration in Balb/c mice from gestational day 9 to 18. The results showed that PNE reduced the percentage and absolute number of CD69-CD4+SP cells, suggesting a block of fetal thymocytes mature. PNE promoted autophagosome formation, autophagy related proteins (Beclin1, LC3I/II) expression, and upregulated α7 nAChR as well as AMPK phosphorylation in fetal thymus. Moreover, PNE promoted Bcl10 degradation via autophagy-mediated proteolysis and inhibited p65 activation, blocking the transition of thymocytes between the DP to SP stage. Further, primary thymocytes were treated with nicotine in vitro and showed induced autophagy in a dose- and time-dependent manner. In addition, nicotine-inhibited CD69-CD4+SP cells and the Bcl10/p-p65 pathway have been reversed by an autophagy inhibitor. The α7 nAChR specific antagonist abrogated nicotine-induced AMPK phosphorylation and autophagy initiation. In conclusion, our findings showed that PNE repressed the Bcl10/p-p65 development pathway of CD4+SP cells by triggering autophagy, and illuminated the developmental origin mechanism of programmed immune diseases in PNE offspring.

Attenuated cholesterol metabolism pathway suppresses regulatory T cell development in prenatal nicotine exposed female mice.

The recession of regulatory T cells (Tregs) contributes to development of autoimmune disease. Our previous study suggested that prenatal nicotine exposure (PNE) inhibited Tregs frequency in offspring, but the mechanisms are still uncertain. This study aimed to explore the molecular mechanisms of PNE-induced Tregs inhibition from the perspective of cellular cholesterol homeostasis both in vivo and in vitro. PNE mice model were established by 3 mg/kg/d nicotine administration in Balb/c strain from gestational day (GD) 9 to GD 18. The results showed that PNE significantly decreased thymic Tregs frequency in neonatal offspring. The activation of mTOR and downregulation of p-STAT5/Foxp3 pathway of Tregs were observed in PNE offspring. Mechanism study found that PNE elevated ATP-binding cassette transporter G1 (ABCG1) expression and decreased intracellular cholesterol content of Tregs in offspring, indicating impaired intracellular cholesterol homeostasis. Similar results were observed in 1 µM nicotine-treated primary thymocytes in vitro. Further, cholesterol-replenishment can abrogate nicotine-induced mTOR activation and the following suppression of p-STAT5/Foxp3 pathway and Tregs frequency. In addition, Abcg1 siRNA transfection can partly reverse the nicotine-decreased intracellular cholesterol content and cell frequency of Tregs. In conclusion, this study showed that PNE could suppress Tregs development in female mice by up-regulating ABCG1-dependent cholesterol efflux, and suggested that PNE-induced thymic Tregs recession of offspring at early life was the developmental origin mechanism of immune dysfunction in later life.

Attenuated Tregs increase susceptibility to type 1 diabetes in prenatal nicotine exposed female offspring mice.

The recession of regulatory T cells (Tregs) is pivotal for type 1 diabetes (T1D) progressing. Our previous study observed the decreased Tregs in prenatal nicotine exposure (PNE) offspring, but whether this led to the onset of T1D remains uncertain. Thus, this study aimed to investigate the effects of PNE on T1D susceptibility and the role of PNE-suppressed Tregs in T1D of female offspring. The decreased body weights and elevated blood glucose levels from postnatal day (PND) 21 to PND 42 indicated that PNE caused persistent impaired glucose homeostasis in offspring. The elevated serum glutamic acid decarboxylase autoantibody, the "Gold Standard" for the detection of T1D, was observed on PND 42, suggesting the early stage of T1D in PNE offspring during adolescence. The reduced pancreatic islet areas and beta cells number in PNE offspring were observed at neonatal period and became more severe during adolescence. In addition, PNE caused immune dysfunction in offspring, manifested as suppressed thymic Tregs percentage from PND 4 to PND 42 and splenic Tregs/Th17 ratio on PND 42. In conclusion, PNE resulted in metabolic changes of offspring that were consistent with T1D characteristics, which could be the consequence of Tregs recession from early life to adolescence.

Prenatal nicotine exposure induces thymic hypoplasia in mice offspring from neonatal to adulthood.

Clinical study showed that smoking during pregnancy deceased the thymus size in newborns. However, the long-term effect remains unclear. This study was aimed to observe the effects of prenatal nicotine exposure (PNE) on the development of thymus and the T-lymphocyte subpopulation in mice offspring from the neonatal to adulthood. Both the thymus weight and cytometry data indicated that PNE caused persistent thymic hypoplasia in male offspring from neonatal to adult period and transient changes in female offspring from neonatal to prepuberal period. Flow cytometry analysis disclosed a permanent decreased proportion and number of mature CD4 single-positive (SP) T cells in thymus of both sex. In addition, the PNE male offspring showed a more serious thymus atrophy in the ovalbumin (OVA)-sensitized model. Moreover, increased autophagic vacuole and elevated mRNA expression of Beclin 1 were noted in PNE fetal thymus. In conclusion, PNE offspring showed thymus atrophy and CD 4 SP T cell reduction at different life stages. Mechanically, PNE induced excessive autophagy in fetal thymocytes might be involved in these changes. All the results provided evidence for elucidating the PNE-induced programmed immune diseases.

Prenatal caffeine ingestion increases susceptibility to pulmonary inflammation in adult female rat offspring.

This study aimed to investigate the association between prenatal caffeine ingestion (PCI) and risk of postnatal pulmonary inflammation. Pregnant Wistar rats were administered 60mg/kg/d caffeine intragastrically from gestational day (GD) 7 to GD 20. The results showed that PCI obviously increased intrauterine growth retardation rate to 39.2% and suppressed weight growth of the offspring. PCI also enhanced the expression of transforming growth factor ß, α-smooth muscle actin, interleukin (IL)-1ß, and IL-8 in lungs and caused pulmonary interstitial thickening in the offspring. Further, with lipopolysaccharide stimulation on postnatal day 77, PCI offspring showed more serious inflammatory infiltration, higher injury scores, and higher levels of IL-6 and tumor necrosis factor-α in lungs than those of the control. Our findings showed, for the first time, that PCI is a certainly threat to postnatal pulmonary inflammation. The potential mechanism is that PCI alter the expression of pulmonary interstitial thickening-associated genes in the offspring.

Intrauterine growth retardation-associated syncytin b hypermethylation in maternal rat blood revealed by DNA methylation array analysis.

BackgroundEmerging evidence suggests that DNA methylation in maternal blood is a promising target for intrauterine growth retardation (IUGR) screening, a common developmental toxicity. Here, we aimed to screen out IUGR-related DNA methylation status in maternal blood via high-throughput profiling.MethodsPregnant Wistar rats were subcutaneously administered nicotine (1 mg/kg) twice per day from gestational day (GD) 11 to GD20 to establish the IUGR model. MeDIP array assays and the following GO analysis were used to evaluate DNA methylation status in maternal blood. One placental development-associated gene was selected for further confirmation.ResultsGenes regulating the development of multiple organs and major body systems had changed DNA methylation frequencies in the maternal blood of IUGR rats. Placental development, which can affect the development of multiple fetal organs and induce IUGR, is a hypermethylated cluster consisting of four significantly changed genes, including syncytin b (Synb), Lrrc15, Met, and Tex19.1. With the most significant change, Synb hypermethylation in maternal blood was confirmed by bisulfite-sequencing PCR (BSP). Moreover, decreased Synb expression and histological changes were observed in IUGR placentae.ConclusionThe IUGR-associated DNA methylation profile in maternal blood, such as placenta-related Synb hypermethylation, provides evidence for further studies on possible IUGR biomarkers.

Increased Fetal Thymocytes Apoptosis Contributes to Prenatal Nicotine Exposure-induced Th1/Th2 Imbalance in Male Offspring Mice.

Nicotine, a definite risk factor during pregnancy, is an immunomodulator. This study was designed to investigate the effects of prenatal nicotine exposure (PNE) on the balance of Th1/Th2 in offspring, and further explore the developmental origin mechanisms from the perspective of fetal thymocytes apoptosis. Pregnant Balb/c mice were administered 1.5 mg/kg nicotine subcutaneously twice per day from gestational day (GD) 9 to GD18. Results showed that PNE could cause a Th2 shift in male offspring, manifested as increased ratio of IgG1/IgG2a, IL-4 production in serum, and IL-4/IFN-γ expression ratio in spleen. Increased apoptosis of total thymocytes and CD4SP and reduced cell proportion of CD4SP were found in PNE male offspring on postnatal day (PND) 14 and PND 49. In the fetuses, decreased body weight and organ index of fetal thymus, histological changes in fetal thymus, reduced CD4SP proportion and increased fetal thymocyte apoptosis were observed in nicotine group. The increased mRNA expression of genes involved in Fas-mediated apoptotic pathway and protein expression of Fas were also detected. In conclusion, PNE could cause a Th2 shift in male offspring mediated by reduced CD4+ T cells output, which may result from the increasing apoptosis of total thymocytes and CD4SP.

Prenatal and lactation nicotine exposure affects morphology and function of brown adipose tissue in male rat offspring.

The aim of this study was to investigate the effects of prenatal and lactation nicotine exposure on the morphology and function of brown adipose tissue (BAT) in male rat offspring. We conducted a morphological assay and gene expression study of interscapular BAT (iBAT) in male rat offspring. The male offspring from nicotine-exposed dams exhibited higher body weight and iBAT weight. Hematoxylin and eosin staining and transmission electron microscopy showed that iBAT from nicotine-exposed male offspring presented a "whitening" phenotype characterized by lipid droplet accumulation and impaired mitochondria with a randomly oriented and fractured cristae. The expression of the iBAT structure and function-related genes all decreased in nicotine-exposed male offspring. These data indicate that prenatal and lactation nicotine exposure affects morphology and function of iBAT in male rat offspring.