In utero chronic intermittent nicotine aerosol exposure increases ischemic heart injury in adult offspring via programming of Angiotensin II receptor-derived TGFß/ROS/Akt signaling pathway.

BACKGROUND: In utero cigarette smoking/nicotine exposure during pregnancy significantly affects fetal development and increases the risk of cardiovascular disease late in life. However, the underlying molecular mechanisms remain largely unknown. We tested the hypothesis that fetal nicotine aerosol exposure reprograms ischemia-sensitive gene expressions, resulting in increased heart susceptibility to ischemic injury and cardiac dysfunction in adulthood. METHODS: Pregnant rats were exposed to chronic intermittent nicotine aerosol (CINA) or saline aerosol control from gestational day 4 to day 21. Experiments were performed on 6-month-old adult offspring. RESULTS: CINA exposure increased ischemia-induced cardiac injury and cardiac dysfunction compared to the control group, which was associated with over- expression of angiotensin II receptor (ATR) protein in the left ventricle (LV) of adult offspring. Meanwhile, CINA exposure up-regulated cardiac TGF-ß/SMADs family proteins in the LV. In addition, CINA exposure enhanced cardiac reactive oxygen species (ROS) production and increased the DNA methylation level. The levels of phosphorylated-Akt were upregulated but LC3B-II/I protein abundances were downregulated in the hearts isolated from the CINA-treated group. CONCLUSION: Fetal nicotine aerosol exposure leads to cardiac dysfunction in response to ischemic stimulation in adulthood. Two molecular pathways are implicated. First, fetal CINA exposure elevates cardiac ATR levels, affecting the TGFß-SMADs pathway. Second, heightened Angiotensin II/ATR signaling triggers ROS production, leading to DNA hypermethylation, p-Akt activation, and autophagy deficiency. These molecular shifts in cardiomyocytes result in the development of a heart ischemia-sensitive phenotype and subsequent dysfunction in adult offspring.

3D power frequency intensive electric field sensor based on a lithium niobate electro-optic crystal.

In order to conveniently measure the power frequency intensive electric field in any direction in space, a lithium niobate (LN) crystal-based three dimensional (3D) intensive electric field sensor with an all-dielectric structure has been developed. A regular triangular prism structure with three 1D (one-dimensional) electric field sensors fixed on its three sides is designed and fabricated. By setting the orientation of the z-axes of the three 1D electric field sensors at 54.7° with respect to the three edges of the prism, the detection directions of the three 1D electric field sensors are perpendicular to each other. Compared to existing 3D electric field sensors that directly arrange three 1D electric field sensors along three mutually perpendicular directions, the overall device volume of the newly designed 3D sensor is significantly reduced. Experimental results reveal that the linear measurement ranges of the 3D electric field sensor along the three axes are 3.71 kV/m-388 kV/m, 2.78 kV/m-403 kV/m, and 4.50 kV/m-375 kV/m, respectively. When the electric field strength is 82.05 kV/m, the measurement error is less than 4.97% when the 3D electric field sensor is rotated 360° in the y o z and x o y planes.

Metabolomics investigation of the chemical variations in white teas with different producing areas and storage durations.

In this study, we employed nontargeted metabolomics and quantitative analysis to explore the variations in metabolites among white teas from different production areas and with varying storage durations. A total of 83 compounds exhibited differential levels between Zhenghe and Fuding white tea, 89 between Zhenghe and Jinggu, and 75 between Fuding and Jinggu white tea. Concerning the storage of white tea, the concentrations of flavanols, dimeric catechins, and amino acids decreased over time, while N-ethyl-2-pyrrolidone-substituted flavanols (EPSFs), caffeine, adenosine monophosphate (AMP), and adenosine increased. Galloylated flavanols showed a higher propensity to form EPSFs with theanine compared to nongalloylated flavanols during storage. Theanine and epigallocatechin gallate were more inclined to generate S-configuration EPSFs during storage in Fuding and Jinggu white tea samples, while R-configuration EPSFs were more readily formed in Zhenghe white tea samples. This study offers a comprehensive understanding of the changes in metabolites during the storage of white tea.

Switchable Kirigami Structures as Window Envelopes for Energy-Efficient Buildings.

Efficient regulation of thermal radiation is an effective way to conserve energy consumption of buildings. Because windows are the least energy-efficient part of buildings, their thermal radiation regulation is highly demanded, especially in the changing environment, but is still a challenge. Here, by employing a kirigami structure, we design a variable-angle thermal reflector as a transparent envelope of windows for their thermal radiation modulation. The envelope can be easily switched between heating and cooling modes by loading different pre-stresses, which endow the envelope windows with the ability of temperature regulation, and the interior temperature of a building model can be reduced by ~3.3 °C under cooling mode and increased by ~3.9 °C under heating mode in the outdoor test. The improved thermal management of windows by the adaptive envelope provides an extra heating, ventilation, and air-conditioning energy savings percentage of 13% to 29% per year for buildings located in different climate zones around the world, making the kirigami envelope windows a promising way for energy-saving utilization.

Fluid-solid coupling model and biological features of large vestibular aqueduct syndrome.

Objective: Computed tomography (CT) images of the temporal bone of large vestibular aqueduct syndrome (LVAS) patients were used to establish 3D numerical models based on the structure of the inner ear, which are, in turn, used to construct inner ear fluid-solid coupling models. The physiological features and pathophysiology of LVAS were analyzed from a biomechanical perspective using finite element analysis. Methods: CT images of the temporal bone were collected from five children attending the Second Hospital of Dalian Medical University in 2022. The CT images were used to build 3D models of the inner ear containing the vestibular aqueduct (VA) by Mimics and Geomagic software, and round window membrane models and fluid-solid coupling models were built by ANSYS software to perform fluid-solid coupling analysis. Results: By applying different pressure loads, the deformation of the round window membranes occurred, and their trend was basically the same as that of the load. The deformation and stress of the round window membranes increased with the increase in load. Under the same load, the deformation and stress of the round window membranes increased with the expansion of the midpoint width of the VA. Conclusion: CT images of the temporal bone used clinically could establish a complete 3D numerical model of the inner ear containing VA. Fluctuations in cerebrospinal fluid pressure could affect inner ear pressure, and VA had a limiting effect on the pressure from cerebrospinal fluid. The larger the VA, the smaller the limiting effect on the pressure.

One-step synthesis of nitrogen-rich organic polymers for efficient catalysis of CO2 cycloaddition.

Nitrogen-rich organic polymer poly(chloride triazole) (PCTs) was synthesized by a one-step method as metal-halogen-free heterogeneous catalyst for the solvent-free CO2 cycloaddition. PCTs had abundant nitrogen sites and hydrogen bond donors, exhibited great activity for the cycloaddition of CO2 and epichlorohydrin, and achieved 99.6% yield of chloropropene carbonate under the conditions of 110 ℃, 6 h, and 0.5 MPa CO2. The activation of epoxides and CO2 by hydrogen bond donor and nitrogen sites was further explained by density functional theory (DFT) calculations. In summary, this study showed that nitrogen-rich organic polymer is a versatile platform for CO2 cycloaddition, and this paper provides a reference for the design of CO2 cycloaddition catalysts.

Competing risk models versus traditional Cox models for prognostic factors' prediction and care recommendation in patients with advanced laryngeal squamous carcinoma: a population-based study.

PURPOSE: To explore the prognostic factors and the optimal treatment modalities for patients with stage IVA laryngeal squamous cell carcinoma (LSCC), so as to improve the survival rate of patients. METHODS: Patients with stage IVA LSCC between 2004 and 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. We used competing risk models to build nomograms for predicting cancer-specific survival (CSS). The effectiveness of the model was assessed using the calibration curves and the concordance index (C-index). The above results were compared with the nomogram established by Cox regression analysis. The patients were grouped into low-risk and high-risk groups by competing risk nomogram formula. And the Kaplan-Meier (K-M) method and log-rank test were used to make sure that these groups had a survival difference. RESULTS: Overall, 3612 patients were included. Older age, black race, a higher N stage, a higher pathological grade, and a larger tumor size were independent risk factors for CSS; married marital status, total/radical laryngectomy, and radiotherapy were protective factors. The C-index was 0.663, 0.633, and 0.628 in the train set and 0.674, 0.639, and 0.629 in the test set of the competing risk model, and 0.672, 0.640, and 0.634 in the traditional Cox nomogram for 1, 3, and 5 years. In overall survival and CSS, the prognosis of the high-risk group was poorer than that of the low-risk group. CONCLUSION: For patients with stage IVA LSCC, a competing risk nomogram was created to help screen risk population and guide clinical decision-making.

Efficient Electrochemical Water Oxidation Mediated by Pyridylpyrrole-Carboxylate Ruthenium Complexes.

Spurred by the rapid growth of Ru-based complexes as molecular water oxidation catalysts (WOCs), we propose novel ruthenium(II) complexes bearing pyridylpyrrole-carboxylate (H2ppc) ligands as members of the WOC family. The structure of these complexes has 4-picoline (pic)/dimethyl sulfoxide (DMSO) in [Ru(ppc)(pic)2(dmso)] and pic/pic in [Ru(ppc)(pic)3] as axial ligands. Another ppc2- ligand and one pic ligand are located at the equatorial positions. [Ru(ppc)(pic)2(dmso)] behaves as a WOC as determined by electrochemical measurement and has an ultrahigh electrocatalytic current density of 8.17 mA cm-2 at 1.55 V (vs NHE) with a low onset potential of 0.352 V (vs NHE), a turnover number of 241, a turnover frequency of 203.39 s-1, and kcat of 16.34 s-1 under neutral conditions. The H2O/pic exchange of the complexes accompanied by oxidation of a ruthenium center is the initial step in the catalytic cycle. The cyclic voltametric measurements of [Ru(ppc)(pic)2(dmso)] at various scan rates, Pourbaix diagrams (plots of E vs pH), and kinetic studies suggested a water nucleophilic attack mechanism. HPO42- in a phosphate buffer solution is invoked in water oxidation as the proton acceptor.

Metal-Ligand Cooperation in Cp*Ir-Pyridylpyrrole Complexes: Rational Design and Catalytic Activity in Formic Acid Dehydrogenation and CO2 Hydrogenation under Ambient Conditions.

Interconversion between CO2 + H2 and FA/formate is the most promising strategy for the fixation of carbon dioxide and reversible hydrogen storage; however, FA dehydrogenation and CO2 hydrogenation are usually studied separately using different catalysts for each reaction. This report describes of the catalysis of [Cp*Ir(N∧N)(X)]n+ (Cp* = 1,2,3,4,5-pentamethylcyclopentadienyl; X = Cl, n = 0; X = H2O, n = 1) bearing a proton-responsive N∧N pyridylpyrrole ligand for both reactions. Complex 2-H2O catalyzes FA dehydrogenation at 90 °C with a TOFmax of 45 900 h-1. Its catalysis is more active in aqueous solution than in neat solution under base-free conditions. These complexes also catalyze CO2 hydrogenation in the presence of base to formate under atmospheric pressure (CO2/H2 = 0.05 MPa/0.05 MPa) at 25 °C with a TOF value of 4.5 h-1 in aqueous solution and with a TOF value of 29 h-1 in a methanol/H2O mixture solvent. The possible mechanism is proposed by intermediate characterization and KIE experiments. The extraordinary activity of these complexes are mainly attributed to the metal-ligand cooperative effect of the the pyrrole group to accept a proton in the dehydrogenation of formic acid and assist cooperative heterolytic H-H bond cleavage in CO2 hydrogenation.

A machine learning-based pulmonary venous obstruction prediction model using clinical data and CT image.

PURPOSE: In this study, we try to consider the most common type of total anomalous pulmonary venous connection and established a machine learning-based prediction model for postoperative pulmonary venous obstruction by using clinical data and CT images jointly. METHOD: Patients diagnosed with supracardiac TPAVC from January 1, 2009, to December 31, 2018, in Guangdong Province People's Hospital were enrolled. Logistic regression were applied for clinical data features selection, while a convolutional neural network was used to extract CT images features. The prediction model was established by integrating the above two kinds of features for PVO prediction. And the proposed methods were evaluated using fourfold cross-validation. RESULT: Finally, 131 patients were enrolled in our study. Results show that compared with traditional approaches, the machine learning-based joint method using clinical data and CT image achieved the highest average AUC score of 0.943. In addition, the joint method also achieved a higher sensitivity of 0.828 and a higher positive prediction value of 0.864. CONCLUSION: Using clinical data and CT images jointly can improve the performance significantly compared with other methods that using only clinical data or CT images. The proposed machine learning-based joint method demonstrates the practicability of fully using multi-modality clinical data.

Forsythiaside a plays an anti-inflammatory role in LPS-induced mastitis in a mouse model by modulating the MAPK and NF-κB signaling pathways.

Forsythiaside A, a major bioactive component extracted from Forsythiae fructus, possesses multiple biological properties, especially anti-inflammatory properties. In the present study, the anti-inflammatory effect of forsythiaside A was investigated in lipopolysaccharide (LPS)-induced acute mastitis in mice. Our results showed that the expression levels of IL-1ß, IL-6, TNF-α, p38 MAPK, IκBα, and NF-κB p65 in the LPS group were all up-regulated, and obvious pathological changes were observed by sectioning. Compared with those in the LPS group, the expression levels of the above factors were significantly reduced, and the inflammation symptoms were also significantly reduced by section observation after forsythiaside A intervention. These results indicated that forsythiaside A effectively inhibited LPS-induced mammary inflammation in mice by attenuating the activation of the NF-κB and p38 MAPK signaling pathways.

LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells.

Long non-coding RNA (lncRNA) DANCR has been reported to participate in key processes such as stem cell differentiation and tumorigenesis. In a high throughput screening for lncRNAs involved in Doxorubicin-induced apoptosis, we found DANCR was suppressed by Doxorubicin and it acted as an important repressor of apoptosis in colorectal cancer. Further studies demonstrated that DANCR promoted the oncogenic lncRNA MALAT1 expression via enhancing the RNA stability of MALAT1 to suppress apoptosis. MALAT1 could efficiently mediate the suppressive function of DANCR on apoptosis. Mechanistic studies found the RNA-binding protein QK served as an interacting partner of both DANCR and MALAT1, and the protein level of QK was subjected to the regulation by DANCR. Furthermore, QK was able to modulate the RNA stability of MALAT1, and the interaction between QK and MALAT1 was controlled by DANCR. In addition, QK could mediate the function of DANCR in regulating the expression of MALAT1 and suppressing apoptosis. These results revealed DANCR played a critical role in Doxorubicin-induced apoptosis in colorectal cancer cells, which was achieved by the interaction between DANCR and QK to enhance the expression of MALAT1.

Isatis root polysaccharide promotes maturation and secretory function of monocyte-derived dendritic cells.

BACKGROUND: Pseudorabies virus (PRV) is an animal virus that is globally responsible for the high economic losses in the swine industry. Isatis root is a traditional Chinese medicinal herb that possesses immune-enhancing and antiviral properties. However, the molecular mechanisms underlying the effects of the active component of the isatis root polysaccharide (IRPS) extract on immature dendritic cells remain elusive. METHODS: In this study, we investigated the molecular changes in primary porcine peripheral blood monocyte-derived dendritic cells (MoDCs) during PRV infection, using enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription-polymerase chain reaction. Additionally, we studied the effect of IRPS on PRV-infected DCs. RESULTS: The results showed that IRPS stimulated the maturation of MoDCs, induced IL-12 secretion, and downregulated IL-6 expression. CONCLUSIONS: Collectively, these results suggest that IRPS is a promising candidate for promoting maturation of DCs and enhancing their secretory potential after PRV infection.

Zinc complexes supported by pyridine-N-oxide ligands: synthesis, structures and catalytic Michael addition reactions.

New dipyridylpyrrole N-oxide ligands HL1 and HL2 are designed and synthesized via oxidation of 2-(5-(pyridin-2-yl)-1H-pyrrol-2-yl)pyridine (Hdpp) by using 3-chloroperbenzoic acid (m-CPBA) in CH2Cl2. The treatment of ZnEt2 with two equiv. of HL1 and HL2 affords [Zn(L1)2] and [Zn(L2)2] in medium yield, respectively. These ligands and zinc complexes are fully characterized by NMR, IR, UV-vis and ESI-MS spectroscopy and X-ray diffraction analysis. The structure of HL1 and HL2 shows a planar geometry. The intramolecular hydrogen-bond interactions between the imino hydrogen and N-oxide oxygen atom are observed. In [Zn(L1)2] and [Zn(L2)2], two ligands chelate to the zinc metal with a cross perpendicular geometry. The zinc complexes were employed as a highly efficient catalyst for the thiol-Michael addition of thiols to α,ß-unsaturated ketones in EtOH at room temperature. The loading of the catalyst is lowered to 0.01 mol%. The catalytic mechanism was proposed based on NMR and ESI-MS experiments.

Antiviral activities of Radix isatidis polysaccharide against pseudorabies virus in swine testicle cells.

BACKGROUND: Radix isatidis has been used in China and other Asian countries for its antiviral and anti-inflammatory effects for thousands of years. However, the antiviral effect of Radix isatidis polysaccharide against pseudorabies virus (PRV) is still unknown. METHODS: The polysaccharide were isolated from extract of the roots of Radix isatidis. MTT assays were used to determine the preventive effect, inhibitory effect and antiviral effect of Radix isatidis polysaccharide on PRV in vitro. RESULTS: This study found that different concentrations of polysaccharides from this plant can inhibit PRV replication by 14.674-30.840%, prevent infection at rates of 6.668-14.923%, and kill this virus at rates of 32.214-67.422%. CONCLUSION: These results broaden the understanding of this traditional Chinese herb and provide a theoretical basis for further research. Moreover, Radix isatidis polysaccharide could be used for antiviral therapy.

Epigenetic Down-Regulation of Sirt 1 via DNA Methylation and Oxidative Stress Signaling Contributes to the Gestational Diabetes Mellitus-Induced Fetal Programming of Heart Ischemia-Sensitive Phenotype in Late Life.

Rationale: The incidence of gestational diabetes mellitus (GDM) is increasing worldwide. However, whether and how GDM exposure induces fetal programming of adult cardiac dysfunctional phenotype, especially the underlying epigenetic molecular mechanisms and theranostics remain unclear. To address this problem, we developed a late GDM rat model. Methods: Pregnant rats were made diabetic on day 12 of gestation by streptozotocin (STZ). Experiments were conducted in 6 weeks old offspring. Results: There were significant increases in ischemia-induced cardiac infarction and gender-dependent left ventricular (LV) dysfunction in male offspring in GDM group as compared to controls. Exposure to GDM enhanced ROS level and caused a global DNA methylation in offspring cardiomyocytes. GDM attenuated cardiac Sirt 1 protein and p-Akt/Akt levels, but enhanced autophagy-related proteins expression (Atg 5 and LC3 II/LC3 I) as compared to controls. Ex-vivo treatment of DNA methylation inhibitor, 5-Aza directly inhibited Dnmt3A and enhanced Sirt 1 protein expression in fetal hearts. Furthermore, treatment with antioxidant, N-acetyl-cysteine (NAC) in offspring reversed GDM-mediated DNA hypermethylation, Sirt1 repression and autophagy-related gene protein overexpression in the hearts, and rescued GDM-induced deterioration in heart ischemic injury and LV dysfunction. Conclusion: Our data indicated that exposure to GDM induced offspring cardiac oxidative stress and DNA hypermethylation, resulting in an epigenetic down-regulation of Sirt1 gene and aberrant development of heart ischemia-sensitive phenotype, which suggests that Sirt 1-mediated signaling is the potential therapeutic target for the heart ischemic disease in offspring.

Effects of Estrogen in Gender-dependent Fetal Programming of Adult Cardiovascular Dysfunction.

BACKGROUND: Epidemiological studies and experimental studies have demonstrated that intrauterine adverse environment increases the risk of Cardiovascular Disease (CVD) in adulthood. However, whether an individual develops a cardiovascular dysfunctional phenotype may depend on genetic background, age, and sex. METHODS: In this review, we summarize some of the recent experimental animal studies in the developmental programming of adult CVD with an emphasis on sex differences and the potential role of estrogen in mediating sexual dimorphism. RESULTS: Few epidemiological studies report the effect of sex on the developmental programming of CVD. However, numerous experimental animal studies have shown a sex difference in fetal programming of adult cardiovascular dysfunction. Most of the animal studies indicate that male offspring develop cardiovascular dysfunction and CVD in adulthood, whereas adult females appear to be protected. Estrogen is one of the key factors that contributes to the sex difference of adult CVD. Estrogen/its Receptor (ER) may interact with the RAS system by changes of DNA methylation patterns at the target gene promoter, serve as an antioxidant to counteract the prenatal insults-induced heightened ROS, and function as an eNOS activator to increase vasodilation, resulting in the protection of female offspring from the development of hypertension and other CVDs. CONCLUSION: These studies suggest that estrogen/ER may contribute to sex differences in cardiovascular response to an adverse intrauterine environment and play a significant role in modulating the cardiovascular response in adulthood.

Long-term exposure to high altitude hypoxia during pregnancy increases fetal heart susceptibility to ischemia/reperfusion injury and cardiac dysfunction.

BACKGROUND: High altitude hypoxia (HAH) exposure affects fetal development. However, the fetal cardiovascular responses to the HAH are not well understood. We have tested the hypothesis that long-term HAH exposure alters the hypoxia/ischemia-sensitive gene expressions, leading to an increase in fetal heart susceptibility to ischemia/reperfusion (I/R) injury and cardiac dysfunction. METHODS: Time-dated pregnant sheep were exposed to high-altitude (3820 m) or were maintained at sea level (~300 m) for 110 days. Fetal hearts were isolated from the near-term ewes and subjected to I/R in a Langendorff preparation. RESULTS: HAH decreased the fetal body and heart weights in the female but not male fetuses. HAH had no effect on the left ventricle (LV) function at baseline, but increased the LV infarct size and attenuated the post-ischemic recovery of LV function in both male and female fetuses, as compared with the normoxic groups. HAH increased the protein levels of hypoxia-inducible factor (HIF)-1α and DNA methyltransferases type 3b (DNMT3b), but attenuated protein kinase C epsilon (PKCε) levels in the fetal hearts. AHA induced a 4.3 fold increase of miR-210 in the males and a 2.9 fold increase in female hearts. In addition, HAH had no effect on mTOR protein and phosphorylation levels but increased the autophagy biomarker, LC3B-II protein levels and LC3B-II/LC3B-I ratio in the fetal hearts. CONCLUSION: The results suggest that gestational HAH exposure induces in utero programming of the hypoxia/ischemia-sensitive gene expression pattern in the developing heart and increases cardiac susceptibility to I/R injury.

MicroRNA-29a suppresses cardiac fibroblasts proliferation via targeting VEGF-A/MAPK signal pathway.

Cardiac fibroblasts proliferation is the most important pathophysiological character of cardiac fibrosis while the underlying mechanisms are still incompletely known. MicroRNAs (miRNAs) regulate gene expression by binding to specific sites. Studies have been indicated that miRNA-29a play a key role in cardiac fibrosis. VEGF-A carries out its functions through MAPK signaling pathway in cardiac fibrosis. Existing proofs predict that the VEGF-A is one of the potential targets of miRNA-29a. We therefore probe the role of miRNA-29a and its latent target VEGF-A during cardiac fibrosis. In our study, miRNA-29a was down-regulated while VEGF-A was up-regulated in cardiac fibrosis tissues. The rat cardiac fibroblasts that were transfected with miRNA-29a inhibitor exhibited low-expression of miRNA-29a, enhanced VEGF-A protein and mRNA expression. Nevertheless, the cardiac fibroblasts transfected with miRNA-29a mimics obtained the opposite expression result. Furthermore, over-expression of miRNA-29a suppresses cardiac fibroblasts proliferation. In conclusion, these results suggested that miRNA-29a suppresses cardiac fibrosis and fibroblasts proliferation via targeting VEGF-A/MAPK signal pathway implicating that miRNA-29a might play a role in the treatment of cardiac fibrosis.