Harmonizing existing climate change mitigation policy datasets with a hybrid machine learning approach.

With the rapid proliferation of climate policies in both number and scope, there is an increasing demand for a global-level dataset that provides multi-indicator information on policy elements and their implementation contexts. To address this need, we developed the Global Climate Change Mitigation Policy Dataset (GCCMPD) using a semisupervised hybrid machine learning approach, drawing upon policy information from global, regional, and sector-specific sources. Differing from existing climate policy datasets, the GCCMPD covers a large range of policies, amounting to 73,625 policies of 216 entities. Through the integration of expert knowledge-based dictionary mapping, probability statistics methods, and advanced natural language processing technology, the GCCMPD offers detailed classification of multiple indicators and consistent information on sectoral policy instruments. This includes insights into objectives, target sectors, instruments, legal compulsion, administrative entities, etc. By aligning with the sector classification of the Intergovernmental Panel on Climate Change (IPCC) emission datasets, the GCCMPD serves to help policy-makers, researchers, and social organizations gain a deeper understanding of the similarities and distinctions among climate activities across countries, sectors, and entities.

Modeled small airways lung deposition of two fixed-dose triple therapy combinations assessed with in silico functional respiratory imaging.

BACKGROUND: Small airways disease plays a key role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and is a major cause of obstruction; therefore, it is a critical pharmacotherapy target. This study evaluated lung deposition of two inhaled corticosteroid (ICS)/long-acting ß2-agonist/long-acting muscarinic antagonist single-inhaler triple therapies using in silico functional respiratory imaging (FRI). Deposition was assessed using real-world inhalation profiles simulating everyday use where optimal inhalation may be compromised. METHODS: Three-dimensional airway models were produced from 20 patients with moderate-to-very severe COPD. Total, central, and regional small airways deposition as a percentage of delivered dose of budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) 160/7.2/5 µg per actuation and fluticasone furoate/umeclidinium/vilanterol (FF/UM/VI) 100/62.5/25 µg were evaluated using in silico FRI based on in vitro aerodynamic particle size distributions of each device. Simulations were performed using multiple inhalation profiles of varying durations and flow rates representing patterns suited for a pressurized metered-dose inhaler or dry-powder inhaler (four for BGF, two for FF/UM/VI, with one common profile). For the common profile, deposition for BGF versus FF/UM/VI was compared post-hoc using paired t-tests. RESULTS: Across inhalation profiles, mean total lung deposition was consistently higher with BGF (47.0-54.1%) versus FF/UM/VI (20.8-22.7%) and for each treatment component, with greater deposition for BGF also seen in the central large airways. Mean regional small airways deposition was also greater across inhalation profiles with BGF (16.9-23.6%) versus FF/UM/VI (6.8-8.7%) and for each treatment component. For the common profile, total, central, and regional small airways deposition were significantly greater for BGF versus FF/UM/VI (nominal p < 0.001), overall and for treatment components; notably, regional small airways deposition of the ICS components was approximately five-fold greater with budesonide versus fluticasone furoate (16.1% vs. 3.3%). CONCLUSIONS: BGF was associated with greater total, central, and small airways deposition for all components versus FF/UM/VI. Importantly, using an identical inhalation profile, there was an approximately five-fold difference in small airways deposition for the ICS components, with only a small percentage of the ICS from FF/UM/VI reaching the small airways. Further research is needed to understand if the enhanced delivery of BGF translates to clinical benefits.

Boosting Oxygen Evolution Reaction of (Fe,Ni)OOH via Defect Engineering for Anion Exchange Membrane Water Electrolysis Under Industrial Conditions.

Developing non-precious catalysts with long-term catalytic durability and structural stability under industrial conditions is the key to practical alkaline anion exchange membrane (AEM) water electrolysis. Here, an energy-saving approach is proposed to synthesize defect-rich iron nickel oxyhydroxide for stability and efficiency toward the oxygen evolution reaction. Benefiting from in situ cation exchange, the nanosheet-nanoflake-structured catalyst is homogeneously embedded in, and tightly bonded to, its substrate, making it ultrastable at high current densities. Experimental and theoretical calculation results reveal that the introduction of Ni in FeOOH reduces the activation energy barrier for the catalytic reaction and that the purposely created oxygen defects not only ensure the exposure of active sites and maximize the effective catalyst surface but also modulate the local coordination environment and chemisorption properties of both Fe and Ni sites, thus lowering the energy barrier from *O to *OOH. Consequently, the optimized d-(Fe,Ni)OOH catalyst exhibits outstanding catalytic activity with long-term durability under both laboratory and industrial conditions. The large-area d-(Fe,Ni)OOH||NiMoN pair requires 1.795 V to reach a current density of 500 mA cm-2 at an absolute current of 12.5 A in an AEM electrolyzer for overall water electrolysis, showing great potential for industrial water electrolysis.

Hierarchical Interconnected NiMoN with Large Specific Surface Area and High Mechanical Strength for Efficient and Stable Alkaline Water/Seawater Hydrogen Evolution.

NiMo-based nanostructures are among the most active hydrogen evolution reaction (HER) catalysts under an alkaline environment due to their strong water dissociation ability. However, these nanostructures are vulnerable to the destructive effects of H2 production, especially at industry-standard current densities. Therefore, developing a strategy to improve their mechanical strength while maintaining or even further increasing the activity of these nanocatalysts is of great interest to both the research and industrial communities. Here, a hierarchical interconnected NiMoN (HW-NiMoN-2h) with a nanorod-nanowire morphology was synthesized based on a rational combination of hydrothermal and water bath processes. HW-NiMoN-2h is found to exhibit excellent HER activity due to the accomodation of abundant active sites on its hierarchical morphology, in which nanowires connect free-standing nanorods, concurrently strengthening its structural stability to withstand H2 production at 1 A cm-2. Seawater is an attractive feedstock for water electrolysis since H2 generation and water desalination can be addressed simultaneously in a single process. The HER performance of HW-NiMoN-2h in alkaline seawater suggests that the presence of Na+ ions interferes with the reation kinetics, thus lowering its activity slightly. However, benefiting from its hierarchical and interconnected characteristics, HW-NiMoN-2h is found to deliver outstanding HER activity of 1 A cm-2 at 130 mV overpotential and to exhibit excellent stability at 1 A cm-2 over 70 h in 1 M KOH seawater.

Diverse changes in shipping emissions around the Western Pacific ports under the coeffect of the epidemic and fuel oil policy.

The Western Pacific Ocean (the WPO), as one of the busiest shipping areas in the world, holds a complex water traffic network. In 2020, the International Maritime Organization (IMO) low-sulfur fuel regulations were implemented globally, while the COVID-19 outbreak influenced shipping activities together. This study aimed to assess the combined impact of epidemics and low-sulfur fuel policies on ship emissions, as well as their environmental effects on the WPO. The ship emission model based on the Automatic Identification System (AIS) data was applied to analyze the monthly emission variations during 2018-2020. It was found that the epidemic had obvious diverse influences on the coastal ports in the WPO. Overall, shipping emissions declined by 15 %-30 % in the first half of 2020 compared with those in 2019 due to the COVID-19 lockdown, whereas they rebounded in the second half as a result of trade recovery. The pollutants discharged per unit of cargo by ships rose after the large-range lockdown. China's multiphase domestic emission control areas (DECAs) and the IMO global low-sulfur fuel regulation have greatly reduced SO2 emissions from ships and caused them to "bypass and come back" to save fuel costs around emission control areas from 2018 to 2020. Based on satellite data and land-based measurements, it was found that the air quality over sea water and coastal cities has shown a positive response to changes in ship-emitted NOx and SO2. Our results reveal that changes in shipping emissions during typical periods, depending on their niches in the complex port traffic network, call for further efforts for cleaner fuel oils, optimized ECA and ship lane coordination in the future. Shipping related air pollutions during the later economic recovery also needs to be addressed after international scale standing-by events.

Multifunctional Nanoplatform for Mild Microwave-Enhanced Thermal, Antioxidative, and Chemotherapeutic Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is usually associated with excessive proliferation of M1-type proinflammatory macrophages, resulting in severe hypoxia and excess reactive oxygen species (ROS) in the joint cavity. Inhibiting M1-type proinflammatory macrophages and/or repolarizing them into M2 phenotype anti-inflammatory cells by alleviating hypoxia and scavenging ROS could be a promising strategy for RA treatment. In this work, a microwave-sensitive metal-organic framework of UiO-66-NH2 is constructed for coating a nanoenzyme of cerium oxide (CeO2) and loading with the drug celastrol (Cel) to give UiO-66-NH2/CeO2/Cel, which is ultimately wrapped with hyaluronic acid (HA) to form a nanocomposite UiO-66-NH2/CeO2/Cel@HA (UCCH). With the microwave-susceptible properties of UiO-66-NH2, the thermal effect of microwaves can eliminate the excessive proliferation of inflammatory cells. In addition, superoxide-like and catalase-like activities originating from CeO2 in UCCH are boosted to scavenge ROS and accelerate the decomposition of H2O2 to produce O2 under microwave irradiation. The nonthermal effect of microwaves could synergistically promote the repolarization of M1-type macrophages into the M2 phenotype. Accompanied by the release of the anti-RA chemotherapeutic drug Cel, UCCH can efficiently ameliorate RA in vitro and in vivo through microwave-enhanced multisynergistic effects. This strategy could inspire the design of other multisynergistic platforms enhanced by microwaves to exploit new treatment modalities in RA therapies.

The unbalanced trade-off between pollution exposure and energy consumption induced by averting behaviors.

Behavioral responses to environmental risks create gains and losses. We use high-frequency datasets to elucidate such behavior responses against air pollution and find a "double-peaked" time pattern in reducing outdoor exposure and in increasing electricity consumption. Despite that one standard deviation increase in the Air Quality Index induces 2% less outdoor population and 6% more household electricity consumption at peak, most responses fail to match with the intra-day pollution peaks, implying ineffective exposure avoidance. We find an unbalanced trade-off between health benefits and energy co-damages. The behavior-induced change in annual residential power consumption (+1.01% to +1.20%) is estimated to be 20 times more than that in the population-based exposure (-0.02% to -0.05%), and generates 0.13-0.15 million more metric tons of citywide carbon emissions. Our results imply that by targeting peak pollution periods, policies can shrink the trade-off imbalance and achieve mutual improvements in exposure reduction and energy conservation.

Occurrence, vertical distribution and transport of organic amine pesticides in the seawater from the East China Sea and the South China Sea.

Organic amine pesticides (OAPs) are widely used as insecticides, fungicides and herbicides in agricultural production. China is a large agricultural country, and the sprayed pesticides may impact the fragile marine environment through surface runoff. This study revealed the pollution characteristics of thirty-three OAPs in the East China Sea (ECS) and the South China Sea (SCS) and investigated their vertical variations in water columns. The ∑OAPs ranged from below method detection limits to 3.4 ng/ L, with an average value of 0.93 ng/ L. Diphenylamine and beflubutamid were the two most abundant compounds, contributing 64 % and 14 % of the ∑OAPs, respectively. The ∑OAPs in the ECS were significantly (M-W U test, p < 0.01) higher than that in the SCS, and OAPs exhibited different composition profiles. Diphenylamine was the most abundant compound in the ECS, while beflubutamid was dominant in the SCS, which may be related to industrial production (such as rubber synthesis) and agricultural activities. In the water columns, OAPs concentrations were higher in deep layers compared to that in surface seawater, which may be due to weak light and low temperature reducing the degradation of pesticides, indicating the deep ocean is a sink for OAPs. Under the dilution of seawater, the concentrations of OAPs decreased from the Pearl River Estuary to the open sea, and the South China Sea Warm Current also caused the decrease of OAPs from south to north. A preliminary risk assessment indicated that OAPs in the water pose no significant risk to aquatic organisms.

[Pollution Characteristics of Microplastics in Sediments of Xiamen Bay Beach].

Microplastics widely exist in various environmental media and have become a global environmental problem. To investigate the pollution characteristics, deposition patterns, and influencing factors of microplastics in the sediments of bay beach, five typical beaches were selected in Xiamen Bay. According to the tidal variation, 0-10 cm, 10-20 cm, and 20-30 cm sediment column samples were collected in layers at the high tide line, middle tide line, and low tide line at the same time, and the characteristics of the horizontal and vertical distribution of microplastics in the beach sediments were studied. The results showed that the abundance of microplastics in 45 sediment samples in Xiamen Bay beach ranged from 39 to 260 n·kg-1, with an average abundance of (114±26) n·kg-1. The shapes of microplastics were mainly fibers, fragments, granules, and foams, with fibers making up the largest proportion. The main components were polyethylene terephthalate (PET), cellophane, and polyethylene (PE). The colors of microplastics included transparent, yellow, blue, black, white, etc. The average abundance of microplastics showed a certain pattern depending on the beach location, intertidal zone, and sampling depth. Moreover, the abundance and distribution of microplastics on the beach were affected by various natural and human factors such as waves, tides, shoreline shape, the number of tourists, and the cleaning of marine floating debris. These results aid the understanding of the distribution characteristics and sources of microplastics in beach sediments, provide a basis for the transport of microplastics from land to sea, and provide data support for the collection of sea floating garbage and shoreline garbage.

Machine learning based regional epidemic transmission risks precaution in digital society.

The contact and interaction of human is considered to be one of the important factors affecting the epidemic transmission, and it is critical to model the heterogeneity of individual activities in epidemiological risk assessment. In digital society, massive data makes it possible to implement this idea on large scale. Here, we use the mobile phone signaling to track the users' trajectories and construct contact network to describe the topology of daily contact between individuals dynamically. We show the spatiotemporal contact features of about 7.5 million mobile phone users during the outbreak of COVID-19 in Shanghai, China. Furthermore, the individual feature matrix extracted from contact network enables us to carry out the extreme event learning and predict the regional transmission risk, which can be further decomposed into the risk due to the inflow of people from epidemic hot zones and the risk due to people close contacts within the observing area. This method is much more flexible and adaptive, and can be taken as one of the epidemic precautions before the large-scale outbreak with high efficiency and low cost.

Identification and Validation of Three-Gene Signature in Lung Squamous Cell Carcinoma by Integrated Transcriptome and Methylation Analysis.

Since DNA methylation (DNAm) is associated with the carcinogenesis of various cancers, this study aimed to explore potential DNAm prognostic signatures of lung squamous cell carcinoma (LUSC). First, transcriptomic and methylation profiles of LUSC were obtained from The Cancer Genome Atlas database (TCGA). DNAm-related genes were screened by integrating DNAm and transcriptome profiles via MethylMix package. Subsequently, a prognostic signature was conducted with the least absolute shrinkage and selector operation (LASSO) Cox analysis. This signature combined with the clinicopathological parameters was then utilized to construct a prognostic nomogram via the rms package. A signature based on three DNAm-related genes claudin 1 (CLDN1), ATP-binding cassette subfamily C member 5 (ABCC5), and cystatin A (CSTA) that were hypomethylated and upregulated in LUSC was constructed. Univariate and multivariate Cox regression analysis suggested that this signature, combined with age and TNM.N stage, was significantly correlated with survival rate. Time-dependent receiver operating characteristics and calibration curves suggested the nomogram constructed with age and TNM.N stage variables could accurately evaluate the 3- and 5-year outcome of LUSC. Finally, the average mRNA and protein expression levels of CLDN1, ABCC5, and CSTA in LUSC were verified to be significantly higher than those in paracancerous tissues. Moreover, silencing CLDN1, ABCC5, and CSTA expressions could significantly reduce the carcinogenesis of the A549 cell line. The DNAm-driven prognostic signature consists of CLDN1, ABCC5, and CSTA incorporated with age and TNM. N stage could facilitate the prediction outcome of LUSC.

A Nonlinear Magnetoelastic Energy Model and Its Application in Domain Wall Velocity Prediction.

In this letter, we propose a nonlinear Magnetoelastic Energy (ME) with a material parameter related to electron interactions. An attenuating term is contained in the formula of the proposed nonlinear ME, which can predict the variation in the anisotropic magneto-crystalline constants induced by external stress more accurately than the classical linear ME. The domain wall velocity under stress and magnetic field can be predicted accurately based on the nonlinear ME. The proposed nonlinear ME model is concise and easy to use. It is important in sensor analysis and production, magneto-acoustic coupling motivation, magnetoelastic excitation, etc.

Hyperamylasemia Caused by the Hantaan Virus: A Retrospective Study of 101 Patients with Hemorrhagic Fever with Renal Syndrome in West China.

Background: Hyperamylasemia (HA) is an inconspicuous manifestation of hemorrhagic fever with renal syndrome (HFRS) in Baoji city, West China. Hantaan virus (HTNV) is the only pathogen-caused HFRS in this region, but the knowledge about HA in the local HFRS patients has been limited. The aim of this study was to investigate the characteristics of HA and its predictive risk factors for doctors to engage in timely monitoring and dealing with the possible serious changes prewarned by HA in the early stages of the disease to improve the final outcome. Methods: All HFRS patients with and without HA (HA and nHA groups, respectively) were treated in Baoji People's Hospital. The clinical characteristics between the two groups were compared by Student's t-test or Chi-square test. The risk factors for prognosis were measured by the logistic regression analysis. The predictive effects of prognosis in clinical and laboratory parameters were analyzed by the receiver operating characteristic curves. Results: 46.53% of the patients demonstrated HA, among which 71.7% were severe and critical types of HFRS, greater than that in the nHA group (19.57%, P < 0.001). The hospitalization day and the general incidence of acute pancreatitis (AP) were longer or greater in the HA group than in the nHA group (P < 0.01). Age and the time from the onset of the first symptom to the patient being admitted to hospital (T OA) were the predictive risk factors for HA. The best cut-off values were the age of 54 years and T OA of 5.5 days. Conclusion: HTNV-induced HA is a common clinical presentation of HFRS patients in West China. It can increase the severity, the hospitalization days of patients, and the incidence of AP in HFRS. Age and T OA constituted independent risk factors for HA caused by HTNV.

China industrial environmental database 1998-2015.

There has been a rapid-growing trend in studying China's environmental problems in the past decade. However, the existing environmental statistics data are far from meeting researchers' requirements. The biggest problem is that the official environmental statistics data are only provided at either regional level or sectoral level. Considering the huge heterogeneities in different regions and sectors, researchers are unable to conduct comprehensive policy evaluations. In this study, we constructed the time-series industrial environmental database for China (CIED) at both regional and sectoral level. The database includes totally 31 regions and four types of pollutants: chemical oxygen demand (COD), sulphur dioxide (SO2), ammonia-nitrogen (NH3-N), and nitrogen oxide (NOX). This study also clarifies several important concepts for researchers to better understand China's official environmental statistics data.

Efficient Alkaline Water/Seawater Hydrogen Evolution by a Nanorod-Nanoparticle-Structured Ni-MoN Catalyst with Fast Water-Dissociation Kinetics.

Achieving efficient and durable nonprecious hydrogen evolution reaction (HER) catalysts for scaling up alkaline water/seawater electrolysis is desirable but remains a significant challenge. Here, a heterogeneous Ni-MoN catalyst consisting of Ni and MoN nanoparticles on amorphous MoN nanorods that can sustain large-current-density HER with outstanding performance is demonstrated. The hierarchical nanorod-nanoparticle structure, along with a large surface area and multidimensional boundaries/defects endows the catalyst with abundant active sites. The hydrophilic surface helps to achieve accelerated gas-release capabilities and is effective in preventing catalyst degradation during water electrolysis. Theoretical calculations further prove that the combination of Ni and MoN effectively modulates the electron redistribution at their interface and promotes the sluggish water-dissociation kinetics at the Mo sites. Consequently, this Ni-MoN catalyst requires low overpotentials of 61 and 136 mV to drive current densities of 100 and 1000 mA cm-2 , respectively, in 1 m KOH and remains stable during operation for 200 h at a constant current density of 100 or 500 mA cm-2 . This good HER catalyst also works well in alkaline seawater electrolyte and shows outstanding performance toward overall seawater electrolysis with ultralow cell voltages.

Main Applications and Recent Research Progresses of Additive Manufacturing in Dentistry.

In recent ten years, with the fast development of digital and engineering manufacturing technology, additive manufacturing has already been more and more widely used in the field of dentistry, from the first personalized surgical guides to the latest personalized restoration crowns and root implants. In particular, the bioprinting of teeth and tissue is of great potential to realize organ regeneration and finally improve the life quality. In this review paper, we firstly presented the workflow of additive manufacturing technology. Then, we summarized the main applications and recent research progresses of additive manufacturing in dentistry. Lastly, we sketched out some challenges and future directions of additive manufacturing technology in dentistry.

Comparison of tumor and two types of paratumoral tissues highlighted epigenetic regulation of transcription during field cancerization in non-small cell lung cancer.

BACKGROUND: Field cancerization is the process in which a population of normal or pre-malignant cells is affected by oncogenic alterations leading to progressive molecular changes that drive malignant transformation. Aberrant DNA methylation has been implicated in early cancer development in non-small cell lung cancer (NSCLC); however, studies on its role in field cancerization (FC) are limited. This study aims to identify FC-specific methylation patterns that could distinguish between pre-malignant lesions and tumor tissues in NSCLC. METHODS: We enrolled 52 patients with resectable NSCLC and collected resected tumor (TUM), tumor-adjacent (ADJ) and tumor-distant normal (DIS) tissue samples, among whom 36 qualified for subsequent analyses. Methylation levels were profiled by bisulfite sequencing using a custom lung-cancer methylation panel. RESULTS: ADJ and DIS samples demonstrated similar methylation profiles, which were distinct from distinct from that of TUM. Comparison of TUM and DIS profiles led to identification of 1740 tumor-specific differential methylated regions (DMRs), including 1675 hypermethylated and 65 hypomethylated (adjusted P < 0.05). Six of the top 10 tumor-specific hypermethylated regions were associated with cancer development. We then compared the TUM, ADJ, and DIS to further identify the progressively aggravating aberrant methylations during cancer initiation and early development. A total of 332 DMRs were identified, including a predominant proportion of 312 regions showing stepwise increase in methylation levels as the sample drew nearer to the tumor (i.e. DIS < ADJ < TUM) and 20 regions showing a stepwise decrease pattern. Gene set enrichment analysis (GSEA) for KEGG and GO terms consistently suggested enrichment of DMRs located in transcription factor genes, suggesting a central role of epigenetic regulation of transcription factors in FC and tumorigenesis. CONCLUSION: We revealed distinct methylation patterns between pre-malignant lesions and malignant tumors, suggesting the essential role of DNA methylation as an early step in pre-malignant field defects. Moreover, our study also identified differentially methylated genes, especially transcription factors, that could potentially be used as markers for lung cancer screening and for mechanistic studies of FC and early cancer development.

Vertical distribution and river-sea transport of microplastics with tidal fluctuation in a subtropical estuary, China.

The river-sea transport of microplastic with complex environmental conditions and diverse driving factors has received growing attention in the estuary. This research investigated the vertical distribution of microplastics in the water column and surface sediments and explored the effect of tidal variation on the transport of microplastics in Jiulong Estuary and Xiamen Bay, China. Results show that the microplastics in the estuary (630 ± 515 µm) was significantly larger than that in the bay (344 ± 420 µm, p < 0.01). Low-density microplastics are present in the whole water column, while high-density microplastics was apt to accumulate in the bottom water and surface sediment suggesting biofouling and material density of microplastics synergistic affect its vertical distribution. Every 1-2 h high-frequency samples collected in a whole tide found the increase of fine size (45-300 µm) and decrease of large size (>300 µm) in the flood tide, which implied fine microplastics were easily driven into the estuary from the bay at flood tide than large microplastics. The abundance of microplastics in the sediments decreased in the fast-rising and fast-falling period implies the tide influences the fragmentation and resuspension of microplastics in the estuary. Finally, the flux of microplastics entering Xiamen Bay was 53.5 t/month in the moderate flow month were estimated based on the abundance of different water layers instead of floating microplastics in the surface water.

Effects of High-Glucose Environment on Periodontal Ligament Cell Proliferation and Apoptosis via NF-κB Signaling Pathway.

The purpose of this study was to discuss the function of the high-glucose environment on the periodontal ligament cell (PDLC) proliferation and apoptosis and the action mechanism of the NF-κB signaling pathway in this process. For this purpose, the human PDLCs were cultured in vitro using 5.5 mM (control group)/24.0 mM glucose (HG group) of glucose and 10 µM of QNZ+24.0 mM of glucose (HG+QNZ), respectively, and the cell proliferation level was checked through CCK-8 assay. TUNEL assay was used to perform cell apoptosis. ELISA was utilized to explore the secretion levels of the proinflammatory factors interleukin (IL)-1ß and IL-6 proteins. The p65 and p50 proteins level were tested via the Western blotting (WB) assay. Results showed that in comparison with the control group, 24.0 mM of glucose could significantly decrease the proliferation ability of the PDLCs (p<0.01), cause cell apoptosis (p<0.05) and promote the secretion of IL-6 and IL-1ß (p<0.05). The expressions of p65 and p50 proteins were up-regulated obviously in the high-glucose environment (p<0.05). QNZ could exert a specific inhibitory effect on the NF-κB activity to significantly down-regulate the expressions of p65 and p50 proteins (p<0.05) and reverse the effects of the high-glucose environment on the cell apoptosis and proliferation (p<0.05). In conclusion, hyper-glucose may affect PDLC proliferation and apoptosis by suppressing the NF-κB signaling pathway activity.

Microarray Identifies a Key Carcinogenic Circular RNA 0008594 That Is Related to Non-Small-Cell Lung Cancer Development and Lymph Node Metastasis and Promotes NSCLC Progression by Regulating the miR-760-Mediated PI3K/AKT and MEK/ERK Pathways.

PURPOSE: This study aimed to explore the circular RNA (circRNA/circ) profile engaged in non-small cell lung cancer (NSCLC) development and metastasis and to investigate potentially key carcinogenic circRNAs related to NSCLC. METHODS: CircRNA profiles between 10 NSCLC tissues and 10 adjacent tissues and between five NSCLC tissues with lymph node metastasis (LNM) and five NSCLC tissues without LNM were detected by Arraystar Human circRNA Array followed by bioinformatics. Circ_0008594 knockdown, circ_0004293 overexpression, and circ_0003832 overexpression plasmids were transfected into H23 and H460 cells to sort potential oncogenic circRNA. Then circ_0008594 overexpression and knockdown plasmids were transfected, followed by that circ_0008594 knockdown plus miR-760 knockdown plasmids were transfected into these cells. Cell proliferation, apoptosis, invasion, stemness, and pathways were detected. In addition, xenograft mice models were constructed via injecting H23 cells with circ_0008594 overexpression or knockdown to validate the findings. RESULTS: A total of 455 dysregulated circRNAs in NSCLC tissues versus adjacent tissues and 353 dysregulated circRNAs in NSCLC tissues with LNM versus those without LNM were discovered. Via cross-analysis, 19 accordant circRNAs were uncovered, among which three candidate circRNAs (circ_0008594, circ_0004293, circ_0003832) were chosen for functional experiments, during which it was observed that circ_0008549 affected H23 and H460 cell proliferation and apoptosis more obviously than circ_0004293 and circ_0003832. Subsequent experiments showed that circ_0008594 promoted H23 and H460 cell proliferation and invasion but affected stemness less and negatively regulated miR-760 via direct binding. Furthermore, miR-760 attenuated the effect of circ_0008549 on regulating H23 and H460 cell functions and the PI3K/AKT and MEK/ERK pathways. In vivo experiments further confirmed that circ_0008549 increased tumor volume, epithelial-mesenchymal transition, and the PI3K/AKT and MEK/ERK pathways while reducing tumor apoptosis and miR-760 NSCLC xenograft models. CONCLUSION: Our study identifies several valuable circRNAs related to NSCLC development and LNM. Furthermore, as a key functional circRNA, circ_0008594 was observed to promote NSCLC progression by regulating the miR-760-mediated PI3K/AKT and MEK/ERK pathways.