Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive cardiopulmonary disease with a high mortality rate. Although growing evidence has revealed the importance of dysregulated energetic metabolism in the pathogenesis of PH, the underlying cellular and molecular mechanisms are not fully understood. In this study, we focused on ME1 (malic enzyme 1), a key enzyme linking glycolysis to the tricarboxylic acid cycle. We aimed to determine the role and mechanistic action of ME1 in PH. METHODS: Global and endothelial-specific ME1 knockout mice were used to investigate the role of ME1 in hypoxia- and SU5416/hypoxia (SuHx)-induced PH. Small hairpin RNA and ME1 enzymatic inhibitor (ME1*) were used to study the mechanism of ME1 in pulmonary artery endothelial cells. Downstream key metabolic pathways and mediators of ME1 were identified by metabolomics analysis in vivo and ME1-mediated energetic alterations were examined by Seahorse metabolic analysis in vitro. The pharmacological effect of ME1* on PH treatment was evaluated in PH animal models induced by SuHx. RESULTS: We found that ME1 protein level and enzymatic activity were highly elevated in lung tissues of patients and mice with PH, primarily in vascular endothelial cells. Global knockout of ME1 protected mice from developing hypoxia- or SuHx-induced PH. Endothelial-specific ME1 deletion similarly attenuated pulmonary vascular remodeling and PH development in mice, suggesting a critical role of endothelial ME1 in PH. Mechanistic studies revealed that ME1 inhibition promoted downstream adenosine production and activated A2AR-mediated adenosine signaling, which leads to an increase in nitric oxide generation and a decrease in proinflammatory molecule expression in endothelial cells. ME1 inhibition activated adenosine production in an ATP-dependent manner through regulating malate-aspartate NADH (nicotinamide adenine dinucleotide plus hydrogen) shuttle and thereby balancing oxidative phosphorylation and glycolysis. Pharmacological inactivation of ME1 attenuated the progression of PH in both preventive and therapeutic settings by promoting adenosine production in vivo. CONCLUSIONS: Our findings indicate that ME1 upregulation in endothelial cells plays a causative role in PH development by negatively regulating adenosine production and subsequently dysregulating endothelial functions. Our findings also suggest that ME1 may represent as a novel pharmacological target for upregulating protective adenosine signaling in PH therapy.

Enhancing anticancer treatment: Development of cRGD-Conjugated F-OH-Evo prodrugs for targeted delivery.

Small molecule drugs sourced from natural products are pivotal for novel therapeutic discoveries. However, their clinical deployment is often impeded by non-specific activity and severe adverse effects. This study focused on 3-fluoro-10-hydroxy-Evodiamine (F-OH-Evo), a potent derivative of Evodiamine, whose development is curtailed due to suboptimal tumor selectivity and heightened cytotoxicity. By harnessing the remarkable stability, specificity, and αvß3 integrin affinity of c(RGDFK), a novel prodrug by conjugating F-OH-Evo with cRGD was synthesized. This innovative prodrug substantially enhanced the tumor-specific targeting of F-OH-Evo and improved the anti-tumor activities. Among them, compound 3c demonstrated the best selective inhibitory activity toward U87 cancer cells in vitro. It selectively enterd U87 cells by binding to αvß3 integrin, releasing the parent molecule under the dual response of ROS and GSH to exert inhibitory activity on topo I. The results highlight the potential of cRGD-conjugated prodrugs in targeted cancer therapy. This approach signifies a significant advancement in developing safer and more effective chemotherapy drugs, emphasizing the role of prodrug strategies in overcoming the limitations of traditional cancer treatments.

The effectiveness of digital psychosocial interventions on psychological distress, depression, anxiety, and health-related quality of life in patients with gynaecological cancer: a systematic review and meta-analysis.

PURPOSE: Patients with gynaecological cancer often experience psychological issues due to multiple stressors. Psychological disturbances have debilitating effects on patients with gynaecological cancer. In recent decades, digital psychosocial interventions have rapidly advanced and been incorporated into mental health interventions. Digital psychosocial interventions could provide patients with several benefits over traditional in-person interventions, including convenience, anonymity, flexible scheduling, and geographic mobility. The aim of this systematic review was to synthesize the effectiveness of digital psychosocial intervention in reducing psychological distress, depression, and anxiety and improving health-related quality of life in patients with gynaecological cancer. METHODS: Three-step extensive search was performed on 22 December 2022 from nine bibliographic databases, trial registries and grey literature. Experimental studies involving patients with gynaecological cancer utilizing digital psychosocial interventions for the improvement of mental health outcomes were included. Meta-analysis was conducted using RevMan 5.4 software. Heterogeneity was analysed by Cochran's Q test and I2. Subgroup analyses were attempted to evaluate relative effect sizes of subgroup features. RESULTS: Meta-analysis of nine studies revealed small effect size in reduction of depression post-intervention (d = 0.24, 95% CI - 0.46 to - 0.02) and medium effect size in reduction of psychological distress post-intervention (d = 0.51, 95% CI - 0.81 to - 0.21) and follow-up (d = 0.65, 95% CI - 1.25 to - 0.05) compared to the control group. The effects of digital psychosocial interventions on anxiety and health-related quality of life were not statistically significant. CONCLUSIONS: Digital psychosocial interventions probably reduced psychological distress and slightly reduced depression amongst patients with gynaecological cancer compared to the control group, which can be integrated into clinical practice. Additional trials with rigorous methodology and bigger sample sizes are needed to validate findings. TRIAL REGISTRATION: PROSPERO (CRD42023389502).

Abnormal microstructure of corpus callosum in children with primary nocturnal enuresis: a DTI study.

Primary nocturnal enuresis (PNE) is a common childhood disorder with abnormal sleep or arousal. The corpus callosum (CC) continues to develop into adulthood and plays an important role in sleep arousal. This study aimed to evaluate the microstructure of the CC in children with PNE. Diffusion tensor imaging (DTI) indices were extracted throughout the CC and its seven subregions were compared between the children with PNE and healthy children (HC). The correlation between abnormal DTI indices of the CC and cognitive condition was also tested. Compared to HC, decreased fiber number (NF) (F = 8.492, PFDR = 0.032) and fractional anisotropy (FA) value (F = 8.442, PFDR = 0.040) were found in the posterior midbody of the CC, increased RD was found in the posterior midbody (F = 6.888, PFDR = 0.040) and isthmus (F = 7.967, PFDR = 0.040) in children with PNE. The reduction of FA value was more obvious in boys than girls with PNE. In children with PNE, there was a significant positive correlation between the NF of the posterior midbody and full IQ (r = 0.322, P = 0.025) and between the FA value and the general knowledge memory (r = 0.293, P = 0.043). This study provides imaging evidence for abnormalities in the microstructure of the CC in children with PNE, especially in male PNE, which might affect the children's cognitive performance.

Eosinophils protect against pulmonary hypertension through 14-HDHA and 17-HDHA.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening disease featuring pulmonary vessel remodelling and perivascular inflammation. The effect, if any, of eosinophils (EOS) on the development of PH remains unclear. METHODS: EOS infiltration and chemotaxis were investigated in peripheral blood and lung tissues from pulmonary arterial hypertension (PAH) patients without allergic history and from sugen/hypoxia-induced PH mice. The role of EOS deficiency in PH development was investigated using GATA1-deletion (ΔdblGATA) mice and anti-interleukin 5 antibody-treated mice and rats. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was conducted to identify the critical oxylipin molecule(s) produced by EOS. Culture supernatants and lysates of EOS were collected to explore the mechanisms in co-culture cell experiments. RESULTS: There was a lower percentage of EOS in peripheral blood but higher infiltration in lung tissues from PAH patients and PH mice. PAH/PH lungs showed increased EOS-related chemokine expression, mainly C-C motif chemokine ligand 11 derived from adventitial fibroblasts. EOS deficiency aggravated PH in rodents, accompanied by increased neutrophil and monocyte/macrophage infiltration. EOS highly expressed arachidonate 15-lipoxygenase (ALOX15). 14-hydroxy docosahexaenoic acid (14-HDHA) and 17-HDHA were critical downstream oxylipins produced by EOS, which showed anti-inflammatory effects on recruitment of neutrophils and monocytes/macrophages through N-formyl peptide receptor 2. They also repressed pulmonary artery smooth muscle cell (PASMC) proliferation by activating peroxisome proliferator-activated receptor γ and blunting Stat3 phosphorylation. CONCLUSIONS: In PH development without external stimuli, peripheral blood exhibits a low EOS level. EOS play a protective role by suppressing perivascular inflammation and maintaining PASMC homeostasis via 14/17-HDHA.

Dauricine alleviates cognitive impairment in Alzheimer's disease mice induced by D-galactose and AlCl3 via the Ca2+/CaM pathway.

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly. Dysregulation of intracellular Ca2+ homeostasis plays a critical role in the pathological development of AD. Dauricine (DAU) is a bisbenzylisoquinoline alkaloid isolated from Menispermum dauricum DC., which can prevent the influx of extracellular Ca2+ and inhibit the release of Ca2+ from the endoplasmic reticulum. DAU has a potential for anti-AD. However, it is unclear whether DAU can exert its anti-AD effect in vivo by regulating the Ca2+ related signaling pathways. Here, we investigated the effect and mechanism of DAU on D-galactose and AlCl3 combined-induced AD mice based on the Ca2+/CaM pathway. The results showed that DAU (1 mg/kg and 10 mg/kg for 30 days) treatment attenuated learning and memory deficits and improved the nesting ability of AD mice. The HE staining assay showed that DAU could inhibit the histopathological alterations and attenuate neuronal damage in the hippocampus and cortex of AD mice. Studies on the mechanism indicated that DAU decreased the phosphorylation of CaMKII and Tau and reduced the formation of NFTs in the hippocampus and cortex. DAU treatment also reduced the abnormally high expression of APP, BACE1, and Aß1-42, which inhibited the deposition of Aß plaques. Moreover, DAU could decrease Ca2+ levels and inhibit elevated CaM protein expression in the hippocampus and cortex of AD mice. The molecular docking results showed that DAU may have a high affinity with CaM or BACE1. DAU has a beneficial impact on pathological changes in AD mice induced by D-galactose and AlCl3 and may act by negative regulation of the Ca2+/CaM pathway and its downstream molecules such as CaMKII and BACE1.

Hsa_circ_0080608 Attenuates Lung Cancer Progression by Functioning as a Competitive Endogenous RNA to Regulate the miR-661/ADRA1A Pathway.

Circular RNAs (circRNAs) participate in the progression of human cancers and have been broadly elucidated. Here, we aimed to elucidate the roles and functional mechanisms of hsa_circ_0080608 (circ_0080608) in lung cancer. Quantitative real-time PCR (qPCR) was performed to assess the mRNA expression levels of circ_0080608, miR-661, and adrenoceptor alpha 1A (ADRA1A). Western blotting was performed to measure ADRA1A protein levels. CCK-8, colony formation, and Transwell assays were performed to determine the effect of circ_0080608 on cell proliferation and migration. Animal models were used to assess how circ_0080608 influences tumor progression in vivo. The binding relationships of miR-661's with circ_0080608 and ADRA1A was confirmed using dual-luciferase reporter and RIP assays. Circ_0080608 exhibited relatively low expression in lung cancer samples and cells. Lung cancer cells overexpressing circ_0080608 exhibited reduced migratory and proliferative abilities. Additionally, circ_0080608 binds to miR-661 and operates as a competing endogenous RNA (ceRNA) and shares a miR-661 binding site with the 3' UTR of ADRA1A. Furthermore, circ_0080608 inversely regulates miR-661 expression, consequently restraining the aggressive behavior of lung cancer cells. Lung cancer cells overexpressing ADRA1A also exhibit repressed migratory and proliferative abilities. However, reintroduction of miR-661 led to a decline in ADRA1A expression, thereby attenuating the functional effects of ADRA1A. Circ_0080608 impedes lung cancer progression by regulating the miR-661/ADRA1A pathway. Our findings provide new insights into the progression of lung cancer.

A lightweight hierarchical convolution network for brain tumor segmentation.

BACKGROUND: Brain tumor segmentation plays a significant role in clinical treatment and surgical planning. Recently, several deep convolutional networks have been proposed for brain tumor segmentation and have achieved impressive performance. However, most state-of-the-art models use 3D convolution networks, which require high computational costs. This makes it difficult to apply these models to medical equipment in the future. Additionally, due to the large diversity of the brain tumor and uncertain boundaries between sub-regions, some models cannot well-segment multiple tumors in the brain at the same time. RESULTS: In this paper, we proposed a lightweight hierarchical convolution network, called LHC-Net. Our network uses a multi-scale strategy which the common 3D convolution is replaced by the hierarchical convolution with residual-like connections. It improves the ability of multi-scale feature extraction and greatly reduces parameters and computation resources. On the BraTS2020 dataset, LHC-Net achieves the Dice scores of 76.38%, 90.01% and 83.32% for ET, WT and TC, respectively, which is better than that of 3D U-Net with 73.50%, 89.42% and 81.92%. Especially on the multi-tumor set, our model shows significant performance improvement. In addition, LHC-Net has 1.65M parameters and 35.58G FLOPs, which is two times fewer parameters and three times less computation compared with 3D U-Net. CONCLUSION: Our proposed method achieves automatic segmentation of tumor sub-regions from four-modal brain MRI images. LHC-Net achieves competitive segmentation performance with fewer parameters and less computation than the state-of-the-art models. It means that our model can be applied under limited medical computing resources. By using the multi-scale strategy on channels, LHC-Net can well-segment multiple tumors in the patient's brain. It has great potential for application to other multi-scale segmentation tasks.

Epidemiological study of HPV infection in 40,693 women in Putian: a population study based on screening for high-risk HPV infection.

BACKGROUND: The infection rate of human papillomavirus (HPV) is high in the coastal regions of China. However, the infection rate among high-risk genotypes of women in Putian City is unknown. Therefore, this study aimed to analyse the epidemiology of high-risk HPV infection among women in Putian and provide a reference for the diagnosis, treatment and vaccination of cervical cancer in this region. METHODS: The data used were obtained from the Chinese government's public health program ("Cervical and Breast Cancer Screening Project"). A total of 40,693 female cervical cell exfoliation samples screened for high-risk HPV at the Affiliated Hospital of Putian University from July 2020 to December 2021 were enrolled. DNA was extracted using a fully automatic extractor. Then, 14 high-risk genotypes of HPV were detected by polymerase chain reaction. The characteristics of HPV infection, distribution of high-risk genotypes, infection types and thinprep cytologic test (TCT) classification at different age groups were analysed. RESULTS: Among the 40,693 samples, 3899 were infected with HPV, with an infection rate of 9.6%. Accordingly, HPV infection rates gradually increased with age, and statistically significant differences were observed among age groups (χ2 = 74.03, P < 0.01). The infection rates of high-risk HPV52, HPV58 and HPV16 were in the top three and increased with age. Single infection was dominant (84.7%), followed by double infections (12.7%). The cervical cytology of 3899 HPV-positive people can be classified into negative for intraepithelial lesion and malignancy (NILM, 88.0%), atypical squamous cells of undetermined significance (ASC-US, 6.6%), atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H, 1.4%), low-grade squamous intraepithelial lesion (LSIL, 3.2%) and high-grade squamous intraepithelial lesion (HSIL, 0.8%). HPV16 infection rate increased with increasing severity of cervical cytology (χ2trend = 43.64, P < 0.01), whereas the infection rates of HPV52 (χ2trend = 13.89, P < 0.01) and HPV58 (χ2trend = 13.50, P < 0.01) showed opposite trends. CONCLUSION: The infection rate of female HPV high-risk screening in this region was 9.6% and mainly involved single infections. In addition, HPV16, HPV52 and HPV58 were closely related to the severity of cervical cytology. Effective screening, vaccination and education are needed. The 9-valent vaccine will be effective in reducing cervical pre-invasive disease. It would also be reasonable to state that the rising trend in HPV infection and high grade cytology with age emphasises the need to target older women with screening. Vaccination of younger women (aged ≤ 25) will lay the foundation for better cancer outcomes in the future.

Fluorescent silicon nanoparticle-based quantitative hemin assay.

Hemin with functions such as oxygen carrying, oxygen storing, promoting redox, and performing electron transfer is important for the health of organisms. In this paper, green synthetic silicon nanoparticles (Si-NPs) were synthesized and used for free hemin detection in serum (a low limit of detection (LOD), 29.5 nM). The quenching mechanism was investigated by UV-vis absorption spectra, time-resolved luminescence decay curve, and circular dichroism (CD) spectra. It was confirmed that multiple redox centers of hemin led to intensified effective collision and increased the electron transfer rate, therefore enhancing the dynamic quenching, and it was undeniable that the inner filter effect (IFE) also played a role in the quenching.

In Vitro Study of the Effect of Inhibition of Quorum Sensing by Brominated Furanone on Peritoneal Dialysis-Associated Peritonitis Associated with Escherichia Coli Infection.

In recent years, the occurrence of peritoneal dialysis (PD)-associated peritonitis (PDAP) with Escherichia coli infection has gradually increased. The presence of quorum sensing (QS) among bacteria facilitates the expansion of antibiotic resistance. Brominated furanone (BMF), a halogenated furanone compound isolated from macroalgae, is a new type of quorum-sensing inhibitor that can inhibit bacterial quorum sensing and reduce bacterial resistance. In this study, we established an in vitro peritoneal dialysis-associated peritonitis biofilm model. After intervention with BMF, the biofilm was destroyed, as shown by scanning electron microscopy, and the number of viable bacteria was reduced. Crystal violet semiquantitative determination showed that biofilm absorption significantly decreased, and RT-PCR showed that luxS expression was downregulated after drug intervention. Therefore, we propose that BMF can effectively inhibit E. coli QS by disrupting the bacterial biofilm and downregulating QS gene expression to reduce the bacterial resistance, providing a direction for the development of novel antibacterial drugs.

Distribution of trace metals in a soil-tea leaves-tea infusion system: characteristics, translocation and health risk assessment.

The effects of metal pollution on tea are of great concern to consumers. We apply Geographic information systems technology to study the distribution of heavy metal elements in tea plantation ecosystems in Jiangsu Province, explore the relationships among metals in the soil, tea leaves and tea infusions, and assess the human safety risks of metals. The concentrations of nine metals in a soil-tea leaves-tea infusion system were studied at 100 randomly selected tea plantations in Jiangsu Province, China. Concentrations of selected metals, zinc (Zn), nickel (Ni), manganese (Mn), chromium (Cr) and copper (Cu), were quantified using an inductively coupled plasma-optical emission spectrometer (ICP-OES), and cadmium (Cd), arsenic (As), plumbum (Pb) and mercury (Hg) were quantified using inductively coupled plasma-mass spectrometry (ICP-MS). Arc-Map 10.3 was used for the spatial analysis of metals in soil, tea leaves and tea infusions. We found that the contents of Mn, Ni and Zn are high level in soil, tea leaves and tea infusions. The Mn level showed a spatial distribution pattern with greater concentrations at the junction of Nanjing and Yangzhou, southwest of Changzhou and west of Suzhou. The hazard index (HI) values in north-central Nanjing, southern Suzhou, southwestern Changzhou and northern Lianyungang were relatively greater. The Zn, Ni, Mn, Cr and Cu levels in the soil-tea infusion system were 17.3, 45.5, 54.5, 1.5 and 14.3%, respectively. The order of the leaching rates of the elements was Ni > Cr > Zn > Mn > Cu. The relative contribution ratios of HI were in the order of Mn > Ni > Cu > Zn > Cr > Pb > Cd > As > Hg. In tea infusions, the Mn level has the greatest potential health risks to consumers. Moreover, using Csoil it was inferred that the safety thresholds of Zn, Ni, Mn, Cr and Cu in soil were 27,700, 50, 1230, 493,000 and 16,800 mg L-1, respectively. The content of heavy metals in soil and tea varies greatly in different regions of Jiangsu Province, 92% of the soil has heavy metal content that meets the requirements of pollution-free tea gardens, 91% of tea samples met the requirements of green food tea. The thresholds for Ni (50 mg L-1) and Mn (1230 mg L-1) can be used as maximum limits in tea plantation soils. The consumption of tea infusions did not pose metal-related risks to human health.

Design of lung nodules segmentation and recognition algorithm based on deep learning.

BACKGROUND: Accurate segmentation and recognition algorithm of lung nodules has great important value of reference for early diagnosis of lung cancer. An algorithm is proposed for 3D CT sequence images in this paper based on 3D Res U-Net segmentation network and 3D ResNet50 classification network. The common convolutional layers in encoding and decoding paths of U-Net are replaced by residual units while the loss function is changed to Dice loss after using cross entropy loss to accelerate network convergence. Since the lung nodules are small and rich in 3D information, the ResNet50 is improved by replacing the 2D convolutional layers with 3D convolutional layers and reducing the sizes of some convolution kernels, 3D ResNet50 network is obtained for the diagnosis of benign and malignant lung nodules. RESULTS: 3D Res U-Net was trained and tested on 1044 CT subcases in the LIDC-IDRI database. The segmentation result shows that the Dice coefficient of 3D Res U-Net is above 0.8 for the segmentation of lung nodules larger than 10 mm in diameter. 3D ResNet50 was trained and tested on 2960 lung nodules in the LIDC-IDRI database. The classification result shows that the diagnostic accuracy of 3D ResNet50 is 87.3% and AUC is 0.907. CONCLUSION: The 3D Res U-Net module improves segmentation performance significantly with the comparison of 3D U-Net model based on residual learning mechanism. 3D Res U-Net can identify small nodules more effectively and improve its segmentation accuracy for large nodules. Compared with the original network, the classification performance of 3D ResNet50 is significantly improved, especially for small benign nodules.

Triazine-based covalent organic polymer: A promising coating for solid-phase microextraction.

Advancement of novel coating materials for solid-phase microextraction is highly needed for sample pretreatment. Herein, a triazine-based covalent organic polymer was constructed from the monomers of cyanuric chloride and trans-stilbene via the Friedel-Crafts reaction and thereafter used as a solid-phase microextraction fiber coating for the extraction of polycyclic aromatic hydrocarbons and their nitrated and oxygenated derivatives. The newly-developed solid-phase microextraction method coupled with gas chromatography/flame ionization detection gives enhancement factors of 548-1236 and limits of detection of 0.40-2.81 ng/L for the determination of polycyclic aromatic hydrocarbons and their derivatives. The one fiber precision for five replicate determinations of the analytes and the fiber-to-fiber precision with three parallel prepared fibers, expressed as relative standard deviations, was in the range of 4.6-9.4% and 6.2-10.9%, respectively. The relative recoveries of the analytes for environmental water samples were in the range of 88.6-106.4% with the relative standard deviations ranging from 4.0 to 11.7% (n = 5).

Genome-wide analysis of the SBP-box gene family transcription factors and their responses to abiotic stresses in tea (Camellia sinensis).

SQUAMOSA promoter-binding protein (SBP)-box gene family is one kind of plant-specific transcription factor that plays important roles in the process of resisting abiotic stress. The SBP-box gene family has been studied in many species, but their functions are not yet clear in Camellia sinensis var. sinensis (CSS) (tea) plants. In our study, 25 SBP-box genes in the CSS were identified in the reference genome and classified into six groups based on a phylogenetic tree. The expression pattern of CsSBP genes under temperature stresses showed that CsSBPs were involved in the process of resisting temperature stresses. CsSBP8 had a positive effect on the anthocyanin accumulation during high temperature exposures, but CsSBP12 has a high correlation with anthocyanin accumulation during both high and low temperature. This study provides a foundation for the further study of CsSBP genes involved in the anthocyanin biosynthesis pathway during the temperature stress in tea.

Rational integration of porous organic polymer and multiwall carbon nanotube for the microextraction of polycyclic aromatic hydrocarbons.

By integration of benzene-constructed porous organic polymer (KBF) and multiwalled carbon nanotube (MWCNT), a MWCNT-KBF hybrid material was constructed through in situ knitting benzene with formaldehyde dimethyl acetal in the presence of MWCNTs to form a network. MWCNT-KBF was then adopted as a novel solid-phase microextraction (SPME) fiber coating. Coupled to gas chromatography-flame ionization detection, the MWCNT-KBF-assisted SPME method showed large enhancement factors (483-2066), low limits of detection (0.04-0.12 µg L-1), good linearity (0.13-50 µg L-1), and acceptable reproducibility (4.2-10.2%) for the determination of polycyclic aromatic hydrocarbons (PAHs). The method recoveries of seven PAHs were in the range 80.1-116.3%, with relative standard deviations (RSDs) ranging from 3.5 to 11.9%. The SPME method was successfully applied to the determination of PAHs in river, pond, rain, and waste water, providing a good alternative for monitoring trace level of PAHs in environmental water. Graphical abstract Schematic representation of the rational integration of porous organic polymer (KBF) and multiwalled carbon nanotube (MWCNT) to form a MWCNT-KBF hybrid material through in situ knitting benzene with formaldehyde dimethyl acetal at the presence of MWCNT.

microRNA-539 functions as a tumor suppressor in papillary thyroid carcinoma via the transforming growth factor ß1/Smads signaling pathway by targeting secretory leukocyte protease inhibitor.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy, with growing incidence every year. microRNAs (miRs) are known to regulate the physiological and pathological processes of cancers, such as proliferation, migration, invasion, survival, and epithelial-mesenchymal transition (EMT). Herein, this study aimed to investigate the effect of miR-539 on cell proliferation, apoptosis, and EMT by targeting secretory leukocyte protease inhibitor (SLPI) via the transforming growth factor ß1 (TGF-ß1)/Smads signaling pathway in PTC. First, PTC-related differentially expressed genes and regulatory miR were screened using bioinformatics analysis, dual luciferase reporter gene assay, and ribonucleoprotein immunoprecipitation, which identified the SLPI gene and the regulatory miR-539 for this study. We identified SLPI as a highly expressed gene in PTC tissues, and SLPI was targeted and negatively regulated by miR-539. Then, we introduced a series of miR-539 mimics, miR-539 inhibitors, and small interfering RNA against SLPI plasmids into CGTHW-3 cells to examine the effects of miR-539 and SLPI on the expression of TGF-ß1/Smads signaling pathway-, EMT-, and apoptosis-related factors, as well as cell proliferation, migration, invasion, and apoptosis. The obtained results indicated that CGTHW-3 cells treated with silenced SLPI or overexpressed miR-539 suppressed the cell proliferation, migration, invasion abilities, and resistance to apoptosis of PTC cells, corresponding to increased expression of Bcl-2-associated X protein, TGF-ß1, Sekelsky mothers against dpp 4, and epithelial cadherin, and decreased B cell lymphoma 2, Vimentin, and N-cadherin. Altogether, we concluded that overexpressed miR-539 could inhibit the PTC cell proliferation and promote apoptosis and EMT by targeting SPLI via activation of the TGF-ß1/Smads signaling pathway.

RORA Overexpression Alleviates Nasal Mucosal Injury and Enhances Red Blood Cell Immune Adhesion Function in a Mouse Model of Allergic Rhinitis via Inactivation of the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND: In this study, we examined whether RORA (retinoic acid receptor-related orphan receptor alpha) was capable of alleviating the progression of allergic rhinitis (AR). METHODS: In order to elucidate the possible effects of RORA and the regulatory mechanism between RORA and the Wnt/ß-catenin signaling pathway, mouse AR models were established and treated with RORA vector, siRNA against RORA, or the Wnt/ß-catenin pathway inhibitor WIF-1. Subsequently, the serum levels of inflammatory cytokines (IgE, INF-γ, IL-1ß, IL-4, and IL-17), red blood cell (RBC) immune adhesion function, the levels of RORA, ß-catenin, and GSK3ß, as well as the extent of ß-catenin and GSK-3ß phosphorylation were evaluated and measured. RESULTS: The OVA-induced AR mouse model exhibited obvious nasal mucosal injury and inflammatory cell infiltration. RORA overexpression or the inactivation of the Wnt/ß-catenin signaling pathway was uncovered as a way to ameliorate nasal mucosal injury and eosinophil infiltration of the OVA-induced AR mouse model. On the other hand, it reduced the number of eosinophils and mast cells, which also resulted in downregulated expression of IgE, INF-γ, IL-1ß, IL-4, IL-17, ß-catenin, and GSK-3ß. Moreover, this led to a decreased extent of ß-catenin and GSK-3ß phosphorylation, while the rates of C3b receptor rosette and Ic rosette were elevated. CONCLUSION: Taken together, the key findings provided evidence suggesting that the elevated RORA could potentially alleviate nasal mucosal injury and simultaneously enhance RBC immune adhesion function through the inhibition of the Wnt/ß-catenin signaling pathway activation in an OVA-induced AR mouse model. This emphasizes a novel therapeutic target for the treatment of AR.

Growth differentiation factor 9 promotes follicle-stimulating hormone-induced progesterone production in chicken follicular granulosa cells.

The function of oocyte-derived growth differentiation factor 9 (GDF9) in ovarian follicles has thus far been poorly defined in avian species compared with the defined function in mammals. Our aim here is to investigate the effects of GDF9 on steroidogenesis and on chicken ovarian granulosa cell (GC) mitosis. Primary GCs from both prehierarchical (6-8 mm in diameter, phGCs) and preovulatory follicles (F1-F5, poGCs) were cultured in the presence or absence of the GDF9 protein. The progesterone (P4) levels in the culture medium were then measured by radioimmunoassay (RIA), and the expression levels of steroidogenesis genes were detected by quantitative PCR. We found that GDF9 alone showed no significant effect on the P4 levels by regulating the expression of steroidogenesis genes, such as STAR, CYP11A1 and HSD3B. Further experiments indicated that GDF9 promoted follicle-stimulating hormone (FSH)-induced P4 production and STAR expression. GDF9 also rescued the FSH-induced decrease of FSH receptor (FSHR) expression but had no effect on the forskolin-induced P4, STAR and forskolin-inhibited FSHR expression levels, suggesting that GDF9 might achieve its regulatory role of P4 by enhancing FSHR and STAR expression. In addition, GDF9 also promoted GC cell cycle progression, regulated the gene transcription of related genes, potentiated DNA replication and inhibited apoptosis. Interestingly, these effects differed between the phGCs and the poGCs. To our knowledge, this is the first report that illustrates the function of GDF9 on chicken GCs and the effects on ovarian steroidogenesis. Our findings highlight the regulation of central oocytes on the surrounding granulosa cells and emphasize the interaction between paracrine signals and endocrine hormones on ovarian progesterone production; these findings contribute to the understanding of the development of avian ovarian follicles.

Embodied carbon dioxide flow in international trade: A comparative analysis based on China and Japan.

Carbon dioxide embodied flow in international trade has become an important factor in defining global carbon emission responsibility and climate policy. We conducted an empirical analysis for China and Japan for the years 2000-2014, using a multi-region input-output model and considering the rest of the world as a comparison group. We compared the two countries' direct and complete carbon dioxide emissions intensity and bilateral economic activities such as imports and exports, production and consumption to analyze the difference between China and Japan. The results showed that the intensities of carbon emissions in all sectors of China were higher than that in Japan and that China's annual production-based emissions were greater than consumption-based emissions, the opposite of these relationships in Japan. China was a typical net carbon export country, and carbon embodied in its imports and exports continued to increase throughout the study period. In contrast, Japan's volume and growth rate of embodied carbon emissions were far less than China's and Japan was a typical net carbon import country. Finally, the conclusions of this study support recommendations for the formulation of international carbon emission responsibility allocation, domestic abatement policy as well as China's trade policy.