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Background: Ubiquitin-specific protease 18 (USP18), is a member of the ubiquitin-specific protease family. Previous studies have shown that USP18 expression is upregulated in the patients with heart failure and USP18 is considered as a novel target for the treatment of heart failure. However, the role of USP18 in atherosclerosis remains unclear. In this study, we aimed to investigate the expression pattern of USP18 in atherosclerosis and its relationship between the extent of atherosclerotic and the cholesterol transporter protein ABCG1. Methods: GSE6054 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed by using the "limma" package in R (version 4.1.3). H-DOCK was applied to perform protein-protein docking for predicting the interaction between USP18 and ATP-binding cassette transporter protein G1 (ABCG1). Immunohistochemistry(IHC), immunofluorescence(IF), and Western blot were used to assess the protein expression of USP18 and ABCG1 in human coronary arteries. Dual immunofluorescencewas performed for co-localization analysis of USP18 and ABCG1 Results: Bioinformatics analysis identified 462 DEGs including 239 upregulated and 223 downregulated genes in familial hypercholesterolaemia (FH) patients, of which USP18 was upregulated in monocytes. Gene Ontology enrichment analysis indicated that the biological functions of USP18 were mainly enriched in endopeptidase activity and cytokine-mediated signaling. Protein-protein docking by H-DOCK showed that USP18 and ABCG1 interacted at a free energy of -20 kcal/mol (free energy < 0 was considered meaningful). USP18 expression is upregulated in patients with coronary artery disease and negatively correlates with the extent of atherosclerosis. At the same time, The expression of ABCG1 is downregulated in CHD and SCD patients and is more pronounced in SCD patients. In atherosclerotic tissues, USP18 and ABCG1 expression were positively correlated. In addition, double immunofluorescence assay showed co-localization of USP18 and ABCG1. Conclusions: USP18 is a differentially expressed gene of FH, and its expression in atherosclerosis is closely related to the extent of atherosclerosis.

Soil inorganic carbon (SIC) is an essential component of the soil carbon pool and plays a vital role in the global carbon cycle and climate change. However, few studies have examined the effects of different agronomic practices on the SIC content. This paper aims to study the effects of different agronomic practices on the SIC content in the 0- to 40-cm soil layer of dryland fields; the innovations are intended to explore the relative importance and synergistic effects of different agronomic practices on the SIC content of the plough layer of dryland fields. We screened out 136 peer-reviewed articles worldwide from 1990–2022, with a total of 2612 valid data pairs, using meta-analysis to assess the effects of different agronomic practices on the SIC content of the plough layer of dryland fields. Compared to conventional tillage (CT), both no-tillage (NT) and plastic film mulching (PM) were able to increase the SIC content in the 0- to 40-cm soil layer of dryland fields. NT increased the SIC content by 15.07 ± 3.48%, while PM gradually increased SIC accumulation as the soil layer deepened, with the greatest increase in SIC content in the 30- to 40-cm soil layer at 11.61 ± 5.89%. When organic manure application (M) and straw return mulching (SM) were applied, the SIC content in the 0- to 40-cm soil layer of dryland fields showed a non-significant reduction trend, with the largest changes in SIC content in the 0- to 10-cm soil layer, at 5.23 ± 2% and 4.69 ± 3.53% reductions, respectively. No-tillage straw return (NTS) significantly increased the SIC content in the 0- to 40-cm soil layer of dryland fields by 77.34 ± 5.6%, which was significantly higher than the independent effects of NT and SM, showing a more substantial synergistic effect. Different agronomic practices have different effects on the SIC content of dryland fields in the 0- to 40-cm soil layer, with NTS > NT > PM > SM > M. Among practices, NTS, NT and PM can increase the SIC content of the plough layer of dryland fields; in particular, NTS can increase the SIC content of 0- to 40-cm in dryland fields to the greatest extent through a synergistic effect. At the same time, SM and M showed an insignificant reduction effect.

In theory, nanoplastics (NPs) can adsorb biological macromolecules, such as proteins, in the surrounding environment to form protein corona (PC). In this study, we focus on amino polystyrene (PS) NPs and horseradish peroxidase (HRP) to explore the dynamic process of the formation of PS-HRP PC and their influence on PS and HRP. This work used atomic force microscopy, laser particle size and Zeta potential analyzer, and UV-vis spectrophotometer. According to the adsorption behavior of HRP to NPs, the surface morphology characteristics of NPs can be observed to change at 60 min. Meanwhile, the increase in size and hydrodynamic diameter, the decrease in Zeta potential, surface roughness and HRP activity, and the change in HRP structure attest to the PC formation. The thickness of the PC was approximately 30 nm and there are differences in the dynamic and static variations in the size of the PC. The PC formation process progresses gradually from 0 min to 240 min. Overall, the formation of PS-HRP PC is identified, and the changes in its properties are confirmed from the perspective of nanoplastics and peroxidase, which help study the effects of nanoplastics on the environment and creatures.

Background Improper use of strychnine can cause death. The aim of this study was to identify and evaluate toxic mechanisms of action associated with active compounds in strychnine using a network toxicology approach, and explore potential pathogenic targets. Methods In the present study, strychnine target and central nervous system-related gene set were established using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and four disease gene databases (Genecards, OMIM, PharmGkb, TTD). An “ingredient-target” interactive active network map was constructed using Cytoscape software (version 3.8.0). Functional enrichment analysis was performed based on the hub genes. A protein-protein interaction network was constructed using STRING database. The pharmacokinetics (ADMET) properties of strychnine were evaluated using SwissADME tool. Molecular docking was performed using Autodock Vina to explore the interactions between the active compounds and the target protein. Results Five strychnine toxicity-related components and a gene set of 40 genes were obtained. GO and KEGG analyses showed that Strychnine acts on the central nervous system through G protein-coupled receptor signaling pathway. Analysis of “ADMET” related parameters showed a high gastrointestinal tract absorption of (S)-stylopine and isobrucine and the compounds could cross the blood brain barrier. CHRM1 was selected as a key gene in strychnine toxicity. Molecular docking results showed that the co-crystalized ligands did not form hydrogen bond with CHRM1. (S)-stylopine had the highest binding affinity (binding energy = − 8.5 kcal/mol) compared with the other two compounds. Conclusion Network toxicology and molecular docking reveal the toxicity mechanisms of strychnine active compounds. The findings showed that CHRM1 is a potential neurotoxic target. (S)-stylopine showed stronger neurotoxic effect compared with the other ligands.

The cross-cultural adaptation of social-emotional learning (SEL) has cast doubts. Although there are significant differences between low- and high-context cultures, few analyses have been conducted on the effects of SEL intervention in high-context cultures. To explore the effectiveness of the SEL program in China, which is different from low-context cultural background, this study presents findings from a meta-analysis of 86 randomized SEL programs involving 8,736 students. Compared with the control group, SEL participants significantly improved social-emotional competence (SEC), including SEL skills, attitudes, positive social behavior, and emotional distress (reduction). However, there was no significant improvement in behavioral problems. Due to the lack of emotional education in China and the Hawthorne effect, compared with SEL programs in low-context countries, China's SEL programs have improved SEC more, up to three times that of low-context countries. The general area of the school, SEL framework, intervention object, and educational level of participants moderates SEL positive outcomes. Types of textbooks, SEL framework, participant features, and educational level of participants moderate SEL negative outcomes. These findings provide empirical evidence for the positive impact of SEL programs in China. To improve the SEC of Chinese students, policymakers should actively implement SEL programs in China.

The long-term survival of patients with advanced urothelial carcinoma (UCa) is limited because of innate resistance to treatment. We identified elevated expression of the histone methyltransferase EZH2 as a hallmark of aggressive UCa and hypothesized that EZH2 inhibition, via a small-molecule catalytic inhibitor, might have antitumor effects in UCa. Here, in a carcinogen-induced mouse bladder cancer model, a reduction in tumor progression and an increase in immune infiltration upon EZH2 inhibition were observed. Treatment of mice with EZH2i causes an increase in MHC class II expression in the urothelium and can activate infiltrating T cells. Unexpectedly, we found that the lack of an intact adaptive immune system completely abolishes the antitumor effects induced by EZH2 catalytic inhibition. These findings show that immune evasion is the only important determinant for the efficacy of EZH2 catalytic inhibition treatment in a UCa model.

Background Ubiquitin-specific protease 18 (USP18), also known as UBP43, is a member of the ubiquitin-specific protease family involved in suppressing viral activity and promoting tumor migration. Previous studies have shown that USP18 expression is upregulated in the patients with heart failure and USP18 is considered as a novel target for the treatment of heart failure. However, the role of USP18 in atherosclerosis remains unclear. In this study, we sought to explore the role of USP18 on ATP-binding cassette transporter protein G1 (ABCG1)-dependent cholesterol efflux. Methods GSE6054 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed by using the "limma" package in R (version 4.1.3). H-DOCK was applied to perform protein-protein docking for predicting the interaction between USP18 and ABCG1. Immunohistochemistry(IHC), immunofluorescence(IF), and Western blot were used to assess the protein expression of USP18 and ABCG1 in human coronary arteries. Dual immunofluorescence was performed for co-localization analysis of USP18 and ABCG1 Results Bioinformatics analysis identified 462 differentially expressed genes including 239 upregulated and 223 downregulated genes in familial hypercholesterolaemia (FH) patients, of which USP18 was upregulated in monocytes. Gene Ontology enrichment analysis indicated that the biological functions of USP18 were mainly enriched in endopeptidase activity and cytokine-mediated signaling. Protein-protein docking by H-DOCK showed that USP18 and ABCG1 interacted at a free energy of -20 kcal/mol (free energy < 0 was considered meaningful). IHC, IF and Western blot analyses revealed an increased expression level of USP18 in coronary arteries from patients with coronary atherosclerotic heart disease (CHD) , but Western blot analyses revealed a decreased expression level of USP18 in coronary arteries from patients with sudden cardiac death (SCD) compared with controls. At the same time, ABCG1 expression was decreased in coronary arteries from both CHD and SCD patients with a higher significance in SCD patients. In addition, double immunofluorescence assay showed no significant co-localization of USP18 and ABCG1. Conclusions USP18 may contribute to the development of atherogenesis through regulating ABCG1-dependent cholesterol efflux from macrophages.

Recently, microplastic pollution has become an environmental issue with widespread concern. As a bigger reservoir of microplastics than the ocean, microplastic pollution borne by soil has an impact on its structure and properties that cannot be ignored. Furthermore, with the help of plants, soil animals and microorganisms, this emerging pollutant will eventually threaten human health. Microplastics are difficult to recycle due to their small particle size, making it hard for traditional methods of plastic pollution management to work. In contrast, biodegradation methods are gaining attention because of its environmental sustainability and wide treatment range. This paper reviews the most popular microplastic biodegradation methods and their influencing factors, aiming to provide ideas and references for the biodegradation of microplastics.

Cancer treatment utilizing infusion therapies to enhance the patient’s own immune response against the tumor have shown significant functionality in a small subpopulation of patients. Additionally, advances have been made in the utilization of nanotechnology for the treatment of disease. We have previously reported the potent effects of 3-4 daily intravenous infusions of immune modifying poly(lactic-co-glycolic acid) (PLGA) nanoparticles (IMPs; named ONP-302) for the amelioration of acute inflammatory diseases by targeting myeloid cells. The present studies describe a novel use for ONP-302, employing an altered dosing scheme to reprogram myeloid cells resulting in significant enhancement of tumor immunity. ONP-302 infusion decreased tumor growth via the activation of the cGAS/STING pathway within myeloid cells, and subsequently increased NK cell activation via an IL-15-dependent mechanism. Additionally, ONP-302 treatment increased PD-1/PD-L1 expression in the tumor microenvironment, thereby allowing for functionality of anti-PD-1 for treatment in the B16.F10 melanoma tumor model which is normally unresponsive to monotherapy with anti-PD-1. These findings indicate that ONP-302 allows for tumor control via reprogramming myeloid cells via activation of the STING/IL-15/NK cell mechanism, as well as increasing anti-PD-1 response rates.

The thriving nano-enabled agriculture facilitates the interaction of nanomaterials with plants. Recently, these interactions and their biological effects are receiving increasing attention. Upon entering plants via leaves, roots, stems, and other organs, nanoparticles adsorb numerous biomolecules inside plants and form bio-corona. In addition, nanoparticles that enter plants through roots may have formed eco-corona with root exudates in the rhizosphere environment before contacting with plant exogenous proteins. The most significant biological effects of plant protein corona include changes in protein structure and function, as well as changes in nanoparticle toxicity and targeting ability. However, the mechanisms, particularly how protein corona affects plant protein function, plant development and growth, and rhizosphere environment properties, require further investigation. Our review summarizes the current understanding of the formation and biological effects of nanoparticle-plant protein corona and provides an outlook on future research.

Nanoplastics, as an emerging pollutant in the environment, have the potential to adsorb various macromolecules onto the surface to form protein corona that may change the physicochemical properties and environmental fate of themselves, which deepens the uncertainty of their environmental hazards. Hence, in present study, we investigated the interaction between polystyrene nanoplastics and urease that forms protein corona over time in different conditions with atomic force microscopy, zeta potential, hydrodynamic diameter, and infrared spectroscopy. According to our results, polystyrene nanoplastics adsorbed urease and formed hard corona, changing the secondary structure of urease, and that the physicochemical properties of protein corona changed and stabilized over time. We concluded that even in a single-protein system, a dynamic process where protein molecules simultaneously adsorb onto and desorb from the surface of nanoplastics runs through the entire interaction. And we found that the formation and evolution of protein corona were governed by various interlinked factors (e.g., pH and nanoplastic surface modification types) instead of dominated by individual factor. This study aims to improve the knowledge about the formation of nanoplastic-protein corona and thus provide a reference for better evaluation of their environmental risk.

Objective This study was designed to observe the expression of important hedgehog (Hh) signal factors in the bone tissue of rats with chronic fluorosis and cultured osteoblasts in order to investigate the role and significance of the Hh signal in fluoride-induced bone injury. Methods Healthy Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the fluorosis group (F Group), the fluoride + blocker group (F + Cycl group: rats were treated with fluoride + cyclopamine), and the fluoride + blocker control group (F + DMSO group). After 6 months of intervention, the urinary fluoride content of rats in each group was detected. The primary osteoblasts of rats were selected for cell experiment, and the experiment was carried out after the cells were passaged from the second to the fourth generation. Results The proliferation rate of primary rat osteoblasts presented time-affected and dose-affected relationships in a short time under treatment with a low dose of sodium fluoride (NaF), but the proliferation of osteoblasts was inhibited by long-term and high-dose NaF exposure. In the F group, the alkaline phosphatase (ALP) activity of osteoblasts increased gradually. The ALP activity was lower in the F + Cycl group than in the F group, and there was no significant difference between the F + DMSO group and F group. With the increase in fluoride exposure, the expression of Hh signal factors and osteogenic-related factor proteins increased gradually. The expressions of Indian hedgehog (Ihh), smoothened (Smo), Glioma-associated oncogene homolog (Gli) 2, and Runt-related transcription factor 2 (Runx2)in the F + Cycl group increased with the dose of fluoride but they were significantly inhibited compared with the F group. Compared with the control group, the content of urinary fluoride in the F group was significantly higher (P < 0.05), but there was no significant change in urinary fluoride content in the F + Cycl group and the F + DMSO group. Compared with the control group, the serum bone alkaline phosphatase (BALP) contents of rats in the other groups increased after 6 months’ intake of fluoride water (P < 0.05). After drug blocking, the serum BALP content in the F + Cycl group was lower than that in the F + DMSO group (P < 0.05). The BALP content in the F + DMSO group was similar to that in the F group: it did not decrease. The mRNA expressions of Ihh, Smo, Gli2, and Runx2 in bone tissue of the F group were significantly higher than those in the control group (P < 0.05). After cyclopamine blocking, the expressions decreased (P < 0.05), but the differences between the F + DMSO group and F group were not statistically significant. Conclusion Hh signal plays an important role in fluoride-induced bone injury. The effective inhibition of cyclopamine is expected to be a new target for the treatment of skeletal damage caused by fluorosis.

Significance: The study of the effects and pathways of catechol and pyrogallic acid on soil organic carbon mineralization has a positive effect on mastering soil carbon transformation. Methods and objectives: In this study, we took 0–20 cm soil from Pinus tabulaeformis forest as an object to investigate the effects of catechol and pyrogallic acid with different concentrations on soil organic carbon mineralization through a 60-day mineralization incubation test. The soil active carbon content and changes in soil microbial diversity and community composition were analyzed by using single exponential fitting, quantitative PCR, and high-throughput sequencing to explore the influencing mechanisms of catechol and pyrogallic acid on soil organic carbon excitation. Results: Catechol and pyrogallic acid had the effect of enhancing the soil organic carbon mineralization and soil active carbon content, and the higher the concentration, the stronger the enhancement effect. Catechol reduced the Ace index, Chao1 index, and Shannon index of bacteria and fungi, and further changed the relative abundance of two dominant groups (Proteobacteria and Acidobacteriota) in bacteria and Basidiomycota in fungi at high concentrations. There was no obvious regularity in the effects of pyrogallic acid on bacteria and fungi, but the Ace index and Chao1 index of bacteria underwent drastic and disordered changes. Conclusions: Catechol and pyrogallic acid can trigger positive excitation of the soil organic carbon through two pathways: increasing the soil active carbon content and modulating soil microorganisms, but the way they modulate soil microorganisms are different. Catechol regulates soil microorganisms by reducing the number, richness, and evenness of the bacteria and fungi species, as well as the community composition, while the way pyrogallic acid regulates only closely relates to the changes in the number, richness, and evenness of bacteria species.

Cancer cells accumulate somatic mutations as result of DNA damage, inaccurate repair and other mechanisms. Different genetic instability processes result in characteristic non-random patterns of DNA mutations, also known as mutational signatures. We developed mutSignatures, an integrated R-based computational framework aimed at deciphering DNA mutational signatures. Our software provides advanced functions for importing DNA variants, computing mutation types, and extracting mutational signatures via non-negative matrix factorization. Specifically, mutSignatures accepts multiple types of input data, is compatible with non-human genomes, and supports the analysis of non-standard mutation types, such as tetra-nucleotide mutation types. We applied mutSignatures to analyze somatic mutations found in smoking-related cancer datasets. We characterized mutational signatures that were consistent with those reported before in independent investigations. Our work demonstrates that selected mutational signatures correlated with specific clinical and molecular features across different cancer types, and revealed complementarity of specific mutational patterns that has not previously been identified. In conclusion, we propose mutSignatures as a powerful open-source tool for detecting the molecular determinants of cancer and gathering insights into cancer biology and treatment.

PurposeThis study aims to provide a literature review and bibliometric analysis of sustainable supply chain management using big data. We reviewed the literature on sustainable supply chain management under big data from 2012 to 2019 and extracted 777 articles.Design/methodology/approachWe conducted quantitative analysis and data network visualization of the chosen literature, including authors, journals, countries, research institutions and citations.FindingsWe discovered that the development of this interdisciplinary field has gained increasing popularity among researchers around the world, such as China and the US publishing the most articles and Western states having more cooperation, which indicates this research topic is growing in significance globally.Originality/valueScientific and technological revolutions such as big data have been incorporated in various industries. Modern supply chain management has also been combined with the advances in data science to achieve sustainability goals. No studies have reviewed the sustainable supply chain management based on big data. This study fills this gap.

To explore the relationship between total intelligence quotient (IQ), verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and fluoride exposure in children aged 8–12 years in coal-burning fluorosis area of Dafang County, Guizhou Province, China. The Wechsler Intelligence Scale for Children Revised in China (WISC-CR) was used to test the total IQ, VIQ, and PIQ in 99 children aged 8–12 years (55 in dental fluorosis group and 44 in control group). The differences in the intellectual levels between the two groups were compared, and the correlation between the intellectual level of children exposed to fluoride and the exposure dose of fluoride was analyzed. The VIQ, PIQ, and total IQ in the dental fluorosis group were 85.64 ± 16.53, 94.87 ± 12.73, and 88.51 ± 12.77, respectively, and these were lower than those in the control group (94.34 ± 16.04, 99.23 ± 12.44, and 96.64 ± 11.70, respectively). Significant difference was observed in VIQ and total IQ between the two groups (P = 0.002, P = 0.01), but not in the PIQ (P > 0.05). Each item of VIQ impairment (common sense, similar, arithmetic, vocabulary, and understanding) was significantly lower than those without VIQ impairment in the dental fluorosis group (P

Although the physical effects of air pollution on humans are well documented, there may be even greater impacts on the emotional state and health. Surveys have traditionally been used to explore the impact of air pollution on people’s subjective well-being (SWB). However, the survey techniques usually take long periods to properly match the air pollution characteristics from monitoring stations to each respondent’s SWB at both disaggregated spatial and temporal levels. Here, we used air pollution data to simulate fixed-scene images and psychophysical process to examine the impact from only air pollution on SWB. Findings suggest that under the atmospheric conditions in Beijing, negative emotions occur when PM2.5 (particulate matter with a diameter less than 2.5 µm) increases to approximately 150 AQI (air quality index). The British observers have a stronger negative response under severe air pollution compared with Chinese observers. People from different social groups appear to have different sensitivities to SWB when air quality index exceeds approximately 200 AQI., Air pollution can affect people’s emotional status and well-being. Here, the authors simulate fixed-scene images to show that under the atmospheric conditions in Beijing, negative emotions occur when air quality index of PM2.5 increases to approximately 150.

Nanoparticles interacting with proteins to form protein corona represent one of the most fundamental problems in the rapid development of nanotechnology. In the past decade, thousands of studies have pointed out this issue. Within multi-protein systems, the formation of protein corona is a homeostasis process in which proteins compete for the limited surface sites of nanoparticles. Besides, the formation of protein corona generally shows a tendency of evolving with time and involves many different driving forces controlled by properties of nanoparticles, proteins and environment. Therefore, recent research on the dynamic process and mechanisms of protein corona formation in both animals and plants are summarized in this review. The factors that affect the formation and the techniques that commonly used for protein corona analysis are proposed. Furthermore, in order to provide reference for the future research, the limitations and challenges in protein corona studies are assessed and the future perspectives are proposed.

INTRODUCTION AND OBJECTIVE:Men are three times more likely to develop bladder cancer (BC) than women. Mouse models have demonstrated that androgens are necessary for BC tumorigenesis. Herein, we as...

The chemical industry is a key energy-consuming sector in China. This paper aims to examine total-factor green growth performance, including energy efficiency and carbon shadow price of China's chemical sector from 1980 to 2013. On the basis of no-radial directional distance function, this paper takes into account both desirable and undesirable outputs. To investigate policy effects, we check the Granger causality test between shadow prices of emission and total-factor green energy efficiency. The results demonstrate that increased environmental regulation costs have substantial effect on total-factor green energy efficiency of the chemical industry in the last decade. The latter also causes significant improvement of the former.

As the world's second-largest economy, China plays a pivotal role in global CO2 emission abatement. In this study, we used an IPAT model to design 48 peak CO2 emission scenarios. We used a centralized DEA to evaluate the allocative efficiency of scenario-based CO2 emission paths by maximizing the aggregated potential GDP under fixed emission quantities. We found that maintaining relatively high GDP growth (around 6%), reducing energy intensity by about 75% of average annual decline rate of 2005–2015 (around 4%), and increasing non-fossil energy to 21% to meet the Innovation plan of energy technology revolution 2016–2030 requirements is the most efficient low-carbon behaviors towards 2030 peak CO2 emissions of 10.57 Gt. We also found that China can potentially reduce CO2 emission intensity (CEI) by up to 72.7% compared to the 2005 level in 2030, and therefore that official CEI reduction targets (60–65%) are well within reach. CEI will not readily converge in future years due to the large differences in energy-saving and emission abatement potential across different regions in China; the rank of convergence is CO2>CO2 per capita > CEI. Hebei, Shandong, Shanxi, Liaoning, Inner Mongolia, and Xinjiang are key areas in whether or not their respective regions complete the emission reduction task. To this effect, these provinces merit special attention.

China began a pilot carbon emissions trading scheme (ETS) in 2013. However, the real carbon mitigation effects of this policy are unclear. Moreover, the potential cost savings from internal or external trading among provinces are also uncertain. Based on panel data of 30 provincial industries from 2006 to 2015, this paper first employs a difference-in-differences model to explore the effects of the pilot ETS on industrial carbon emissions and carbon intensity. A Stochastic Frontier Analysis is then conducted to measure industrial energy efficiency and identify any carbon mitigation effects. We next use a parameterized directional output distance function to estimate the industrial carbon marginal abatement costs and analyze the potential cost savings/gains from internal trading among provinces within the same geographical regions and from external trading across regions. Results show that: (a) the pilot ETS has significant negative effects on industrial carbon emissions (10.1%) and carbon intensity (0.78%). (b) Energy efficiency plays an important role in the carbon mitigation effects. (c) the distribution of marginal abatement cost (MAC) shows significant geographical characteristics. (d) Provinces can realize greater potential cost saving/gains through regional external trading than internal trading.

e14552 Background: Recent advances in the field of cancer immunology have highlighted the importance of the immune system for eliminating tumors. Numerous studies have shown that tumor-infiltrating immune cells such as antigen-presenting cells (APCs), T cells, and natural killer (NK) cells play critical roles in tumor control. However, the inflammatory anti-tumor immune response is counteracted by the induction of immune regulatory mechanisms within the tumor microenvironment (TME). These findings have led to the development of immune-targeted therapies, which are aimed at activating anti-tumor immune signaling pathways and enhancing anti-tumor immune function. While immunotherapies, have revolutionized the treatment of several solid tumors and leukemias, at best response rates remain low at 25%-30%, and a portion of patients eventually develop resistance to therapy leading to disease progression and mortality. Methods: We have previously reported the potent effects of 3-4 daily intravenous infusions of immune modifying poly(lactic- co-glycolic acid) (PLGA) nanoparticles, ONP-302, free from drugs or other bioactive agents, for the amelioration of acute inflammatory diseases by targeting myeloid cells. The present studies describe a novel use for ONP-302 nanoparticles, employing an altered dosing scheme to reprogram myeloid cells resulting in significant enhancement of tumor immunity. The efficacy of ONP-302 nanoparticles at inducing an anti-tumor immune response was evaluated using syngeneic mouse tumor models. Results: ONP-302 infusion decreased tumor growth via the activation of the cGAS/STING pathway within myeloid cells, and subsequently increased NK cell activation via an IL-15-dependent mechanism. Additionally, ONP-302 treatment increased PD-1/PD-L1 expression in the tumor microenvironment, thereby allowing for functionality of anti-PD-1 for treatment in the B16.F10 melanoma tumor model which is normally unresponsive to monotherapy with anti-PD-1. Conclusions: These findings indicate that ONP-302 allows for tumor control via reprogramming myeloid cells via activation of the STING/IL-15/NK cell mechanism, as well as increasing anti-PD-1 response rates.

The present study investigated and evaluated the correlation between the expression of LACTB and LC3 and the clinical outcomes of patients with advanced gastric cancer treated with oxaliplatin plus S-1 neoadjuvant chemotherapy (NACT). A total of 51 patients with advanced gastric cancer underwent NACT treatment between June 2015 and June 2017. Pathomorphological changes in gastric cancer were analyzed by H&E staining. The expression level and subcellular localization of LACTB and LC3 in paraffin-embedded biopsies were detected by immunohistochemistry and immunofluorescence. The mRNA and protein expression of LACTB were investigated by reverse transcription quantitative polymerase chain reaction and Western blotting, respectively. Statistical analysis was performed to determine the association between the expression of LACTB and LC3 and clinical chemotherapy efficacy of NACT for gastric cancer. Among the 51 patients, 3 (5.88%), 27 (52.94%), 13 (25.49%) and 8 (15.69%) displayed complete remission, partial remission, stable disease and progressive disease, respectively. The rate of decreased LACTB expression was 68.6%, while the rate of increased LC3 expression was 60.8%. Furthermore, there was a significant negative correlation between the expression of LACTB and that of LC3 following NACT (P

This study was aimed at identifying molecular markers associated with the pathogenesis of sudden cardiac death (SCD). It provides a proteomic analysis of human left anterior descending coronary artery from subjects diagnosed with SCD through histological examination and cases of nondisease accidental deaths through autopsy. A total of 2784 proteins were obtained from label-free quantitative proteomic analysis. This included a total of 265 differential proteins which were involved in SCD-related processes, such as inflammation, muscle system process regulation, metal ion transport, and lysosomal pathway. Western blotting was carried out to measure the expressions of cathepsin C (CTSC), focal adhesion kinase (FAK), p-FAK, and proteins related to the p38/MAPK signaling pathway, whereas immunohistochemistry was performed to determine the localization and expression of CTSC, TNF-α, and CD206 in arterial tissues. It was found that CTSC were the most expressed proteins with a significant upward trend in SCD cases. Besides, CTSC regulated macrophage polarization to M1 through the FAK-induced p38/MAPK signaling pathway. This promoted the release of inflammatory factors and eventually increased the inflammatory response. In conclusion, this study implies that CTSC may be one of the key molecular targets for promoting macrophage M1 polarization in SCD, which may provide new therapeutic insights into the treatment of inflammatory diseases.

Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced-stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling. We identify five distinctive genetic and transcriptomic programs and validate these in an independent neoadjuvant CPI trial to identify the features of response or resistance to CPI. By modeling the regulatory network, we identify the histone demethylase KDM5B as a repressor of tumor immune signaling pathways in one resistant subtype (S1, Luminal-excluded) and demonstrate that inhibition of KDM5B enhances immunogenicity in FGFR3-mutated BCa cells. Our study identifies signatures associated with response to CPI that can be used to molecularly stratify patients and suggests therapeutic alternatives for subtypes with poor response to neoadjuvant immunotherapy.

Additional file of Significances of viable synergistic autophagy-associated cathepsin B and cathepsin D (CTSB/CTSD) as potential biomarkers for sudden cardiac death

Background The Cathepsins family, including cathepsin B and cathepsin D, potentially affects the entire processes involved in atherosclerosis. Although coronary heart disease (CHD) has been widely studied as the basis of Sudden Cardiac Death (SCD), the relationship between CHD and CTSB/D remains unclear. Methods We screened for differentially expressed proteins (DEPs) associated with autophagy by limma package in R. For the genes corresponding to the DEPs after screening, we used various databases to carry out functional enrichment of related DEGs to explore their possible influence on a specific aspect of the disease. Functional enrichment analysis of DEGs was performed by DAVID, Metascape and GSEA. STRING and Cytoscape were obtained the hub genes, the analysis of interaction networks through the GENMANIA and Networkanalyst. Western Blot was used to validate the protein expression level of target genes. TF and miRNA prediction were performed using Networkanalyst and visualized using Cytoscape. Results The expression levels of members of the cathepsin family were up regulated in CHD tissues compared with the control. GO and KEGG revealed that cathepsin was markedly enriched in endopeptidase activities, immune responses, lysosome pathways, et al. The correlation analysis showed that in patients with CHD, the CTSB/CTSD expression were negatively correlated with ATG4D and BNIP3, but positively with BCL2L1, CAPNS1, and TP53. In the TF-mRNA-miRNA network, has-miR-24-3p and has-miR-128-3p had higher degrees, CTSB/CTSD could be targeted by them. Conclusions Our findings elucidated the expression and regulatory role of cathepsins in coronary heart disease induced SCD and might further explore the potential mechanisms of autophagy in CHD.

Oxaliplatin (OXA), as a third-generation platinum anticancer drug, is a treatment drug for gastric cancer (GC). However, OXA resistance has become the main reason for OXA treatment failure. Serine beta-lactamase-like protein (LACTB), acts as a mitochondrial protein, can affect multiple cancer processes. Here, we aimed to investigate the function and mechanism of LACTB in OXA-resistant GC. After LACTB overexpression or autophagy activator (RAPA) treatment, cell proliferation, reactive oxygen species (ROS), apoptosis, mitochondrial dysfunction were evaluated through CCK-8 assay, Edu staining, flow cytometry and immunofluorescence assay. Moreover, DNA double-stranded damage and autophagy-related proteins were examined via western blot. We revealed that LACTB was downregulated in OXA-resistant MGC-803 cells, and overexpression of LACTB reduced the resistance of GC cells to OXA. Besides, our results uncovered that overexpression of LACTB induced apoptosis, reduced the mitochondrial membrane potential (MMP) and accelerated ROS accumulation in OXA-resistant MGC-803 (MGC-803/OXA) cells. Meanwhile, we verified that overexpression of LACTB decreased glucose uptake and ATP synthesis, induced mitochondria and DNA damages, and inhibited autophagy of MGC-803/OXA cells. Furthermore, our results certified that RAPA could weaken the function of LACTB on apoptosis and mitochondrial morphology and function in OXA-resistant MGC-803 cells with OXA treatment. Therefore, we demonstrated that LACTB could attenuate the resistance of MGC-803/OXA cells to OXA through autophagy-mediated mitochondrial morphological changes, mitochondrial dysfunction, and apoptosis, suggesting that LACTB, functions as a suppressor, is conducive to the therapy of OXA-resistant GC.

ObjectiveThis study aims to analyze the expressions of autophagy-related factors light chain 3 alpha (LC3A) and Beclin 1 and apoptosis-related factors B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (BAX) in primary osteoblasts treated with sodium fluoride (NaF).MethodsOsteoblasts were extracted from Sprague-Dawley rats and treated with 0, 2.5, 5, and 10 mg/L NaF solutions, followed by 10 mmol/L 3-methyladenine (3-MA) for 24 h. The apoptotic rate was determined by flow cytometry, and the expressions of the autophagy- and apoptosis-related factors were measured by western blotting and real-time quantitative polymerase chain reaction.ResultsThe mRNA expressions of LC3A, Beclin 1, and BAX in the NaF-treated osteoblast group were higher than those in the control group, while the protein expressions of these factors in the NaF-treated group were significantly higher than those in the control group. However, the Bcl-2 protein expression in the NaF-treated osteoblasts was significantly decreased compared to that in the control cells. After the 3-MA treatment, the protein expressions of LC3A, Beclin 1, and Bcl-2 were significantly decreased compared with those of the NaF-treated group, whereas the expression of BAX increased. Moreover, the apoptosis rate was increased after the addition of the 3-MA inhibitor.ConclusionNaF stimulation promoted autophagy and apoptosis of the osteoblasts, suggesting the involvement of fluoride damage in these processes.

Patients with locally advanced and metastatic urothelial carcinoma have a low survival rate (median 15.7 months, 13.1–17.8), with only a 23% response rate to monotherapy treatment with anti-PDL1 checkpoint immunotherapy. To identify new therapeutic targets, we profiled the immune regulatory signatures during murine cancer development using the BBN carcinogen and identified an increase in the expression of the T cell inhibitory protein B7-H4 (VTCN1, B7S1, B7X). B7-H4 expression temporally correlated with decreased lymphocyte infiltration. While the increase in B7-H4 expression within the bladder by CD11b+ monocytes is shared with human cancers, B7-H4 expression has not been previously identified in other murine cancer models. Higher expression of B7-H4 was associated with worse survival in muscle-invasive bladder cancer in humans, and increased B7-H4 expression was identified in luminal and luminal-papillary subtypes of bladder cancer. Evaluation of B7-H4 by single-cell RNA-Seq and immune mass cytometry of human bladder tumors found that B7-H4 is expressed in both the epithelium of urothelial carcinoma and CD68+ macrophages within the tumor. To investigate the function of B7-H4, treatment of human monocyte and T cell co-cultures with a B7-H4 blocking antibody resulted in enhanced IFN-γ secretion by CD4+ and CD8+ T cells. Additionally, anti-B7-H4 antibody treatment of BBN-carcinogen bladder cancers resulted in decreased tumor size, increased CD8+ T cell infiltration within the bladder, and a complimentary decrease in tumor-infiltrating T regulatory cells (Tregs). Furthermore, treatment with a combination of anti-PD-1 and anti-B7-H4 antibodies resulted in a significant reduction in tumor stage, a reduction in tumor size, and an increased level of tumor necrosis. These findings suggest that antibodies targeting B7-H4 may be a viable strategy for bladder cancers unresponsive to PD-1 checkpoint inhibitors.

Climate change and environmental management are issues of global concern. The advent of the era of Big Data has created a new research platform for the assessment of environmental governance and policies. However, little is known about Big Data application to climate change and environmental management research. This paper adopts bibliometric analysis in conjunction with network analysis to systematically evaluate the publications on carbon emissions and environmental management based on Big Data and Streaming Data using R package and VOSviewer software. The analysis involves 274 articles after rigorous screening and includes citation analysis, co-citation analysis, and co-word analysis. Main findings include (1) Carbon emissions and environmental management based on big data and streaming data is an emerging multidisciplinary research topic, which has been applied in the fields of computer science, supply chain design, transportation, carbon price assessment, environmental policy evaluation, and CO2 emissions reduction. (2) This field has attracted the attention of nations which are major contributors to the world economy. In particular, European and American scholars have made the main contributions to this topic, and Chinese researchers have also had great impact. (3) The research content of this topic is primarily divided into four categories, including empirical studies of specific industries, air pollution governance, technological innovation, and low-carbon transportation. Our findings suggest that future research should bring greater depth of practical and modeling analysis to environmental policy assessment based on Big Data.

This paper examines the dynamic behaviour of energy intensity across Chinese cities. It employs a dynamic distribution approach which takes economic size into consideration. The results support the existence of convergence in terms of energy intensity among Chinese cities during the sample period. However, bimodality is the dominant characteristic in the long-term distribution using the full sample. The results also show that the distribution dynamics of energy intensity differ greatly among city groups in terms of geographical location, environmental policy, and population size. Weighting by economic size does not change the convergence trend of energy intensity, but has a significant influence on the long-term distribution. Neglecting economic size may overstate the energy reduction performance in Chinese cities. Furthermore, the results also suggest that geographical location, income level, and city population size have a significant impact on the spatial distribution dynamics of energy intensity. However, the formation of convergence clubs is complicated and thus requires further investigation.

The N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) mouse model is an attractive model system of muscle-invasive bladder cancer (MIBC) as it recapitulates the histology of human tumors in a background with intact immune system. However, it was unknown whether this carcinogen-induced model also mimicked human MIBC at the molecular and mutational level. In our study, we analyzed gene expression and mutational landscape of the BBN model by next-generation sequencing followed by a bioinformatic comparison to human MIBC using data from The Cancer Genome Atlas and other repositories. BBN tumors showed overexpression of markers of basal cancer subtype, and had a high mutation burden with frequent Trp53 (80%), Kmt2d (70%), and Kmt2c (90%) mutations by exome sequencing, similar to human MIBC. Many variants corresponded to human cancer hotspot mutations, supporting their role as driver mutations. We extracted two novel mutational signatures from the BBN mouse genomes. The integrated analysis of mutation frequencies and signatures highlighted the contribution of aberrations to chromatin regulators and genetic instability in the BBN tumors. Together, our study revealed several similarities between human MIBC and the BBN mouse model, providing a strong rationale for its use in molecular and drug discovery studies.

A striking empirical feature of the currently overheated Chinese housing market is the coexistence of the steady growth in real prices and excess supply. In this study, we provide a new perspective to explain this feature, demonstrating that water resources availability plays a significant role in the formation of the housing market equilibrium. By using water resources, local governments can improve the waterfront amenities to entice consumers to participate in the housing market, which will increase the equilibrium price and may ultimately result in an increase in fiscal revenue and social welfare. We propose a theoretical model to describe the formation mechanism of the housing market equilibrium and use panel data on 31 provinces from 2004 to 2014 to test our theory. The results of our empirical study show that water resources availability positively affects the growth in housing prices, but that the marginal effect decreases. Our policy suggestion is that the central government of China should adopt customized policies to the housing markets of different provinces, considering their water resources availability and waterfront amenities.

APOBEC enzymes are responsible for a mutation signature (TCW>T/G) implicated in a wide variety of tumors. We explore the APOBEC mutational signature in bladder cancer and the relationship with specific mutations, molecular subtype, gene expression, and survival using sequencing data from The Cancer Genome Atlas (n = 395), Beijing Genomics Institute (n = 99), and Cancer Cell Line Encyclopedia. Tumors were split into “APOBEC-high” and “APOBEC-low” based on APOBEC enrichment. Patients with APOBEC-high tumors have better overall survival compared to those with APOBEC-low tumors (38.2 vs. 18.5 months, p = 0.005). APOBEC-high tumors are more likely to have mutations in DNA damage response genes (TP53, ATR, BRCA2) and chromatin regulatory genes (ARID1A, MLL, MLL3), while APOBEC-low tumors are more likely to have mutations in FGFR3 and KRAS. APOBEC3A and APOBEC3B expression correlates with mutation burden, regardless of bladder tumor molecular subtype. APOBEC mutagenesis is associated with increased expression of immune signatures, including interferon signaling, and expression of APOBEC3B is increased after stimulation of APOBEC-high bladder cancer cell lines with IFNγ. In summary, APOBEC-high tumors are more likely to have mutations in DNA damage response and chromatin regulatory genes, potentially providing more substrate for APOBEC enzymes, leading to a hypermutational phenotype and the subsequent enhanced immune response.

Despite rapid economic development, the transport industry has been claimed to account for a major part of climate change. This paper investigates total factor carbon-sensitive productivity growth in the regional transport sector in China and decomposes its dynamic changes over time taking account of the regional heterogeneity of different provinces. Thus, the contemporaneous metafrontier Malmquist-Luenberger approach that combined with non-radial directional distance functions is proposed and define a new indicator called the contemporaneous metafrontier Malmquist-Luenberger carbon emission performance index (CMML). This total factor indicator includes the metafrontier efficiency-change index (MEC), the metafrontier technology-change index (MTC), and the metafrontier technology-gap-change index (TGC). Results show an about 4% increase in overall total factor carbon emission productivity during the period of 2000–2012. Different growth patterns are also observed in the transport sector across different area of China. In the eastern region, the growth of carbon productivity is driven mainly by pure efficiency changes, whereas the central region is driven mainly by innovations in the low-carbon transport technology.

The command and control mechanism and the market trading mechanism have been adopted by Chinese government to reduce the industrial carbon emissions. Concerns have arisen over which policy is more effective and what are the potential gains from carbon emissions trading for industrial sectors. A Data Envelopment Analysis based linear programming technology is used to compare the industrial potential gains including both the economic potential gains and the environmental potential gains from the command and control and carbon emissions trading mechanisms. An empirical study containing the data set of 38 sub-industries in China from 2006–2014 is conducted. The empirical results show that the carbon emissions trading mechanism can produce more potential gains compared with the command and control mechanism, with an average of 69.6 and 92.0% economic potential gains and 49.1 and 21.0% environmental potential gains in terms of the overall level and industrial level, respectively. Additionally, the environmental potential gains of each sub-industry can provide theoretical support for the emission quotas allocation. Finally, several policy implications based on the empirical results are proposed.

The rapidly increasing consumption of energy and fossil fuel dominated energy structure have caused great pressure on energy security and carbon reduction policies in China, and the Chinese government has attempted to substitute fossil with non-fossil energy. To investigate the feasibility of replacing fossil energy with non-fossil energy in China, we apply an input distance function to estimate the substitutability of non-fossil energy for fossil energy and compare shadow prices. The result confirms the feasibility of substituting non-fossil energy for fossil energy. We then divide the non-fossil energy into nuclear energy and renewable energy and find that nuclear energy is more suitable than renewable energy to substitute for fossil energy. The shadow price ratio of non-fossil to fossil energy is 268.41 on average in the study period. The ratio experiences several fluctuations and shows a declining trend at the end of the study period, implying that improving energy structure in China is very promising.

This paper uses spatial econometric models to analyze the spatial distribution of Chinese airports from 2002 to 2012, taking into consideration the factors that explain the distribution of airports around the country. A cost function allowing for latitude and longitude is estimated based on spatial location, which leads us to advise the implementation of policies that take into account the spatial distribution of the airports. Results show that the development of airports in China needs to consider the spatial relationship among the many different regions of China. To improve the cost efficiency, airports should be located in more economically developed areas. Meanwhile, it also helps to reduce the cost when listing on the stock market.

The ferrous metal industry is the largest energy-consuming industrial sector in China. This paper examines the low-carbon production characteristics of this industry during the period 1980–2013. We employ the duality theory of the Weighted Russell Directional Distance Function to propose a general procedure for modeling production characteristics with carbon emissions being considered the undesirable output. Using the Weighted Russell Directional Distance Function model, we measure the carbon-adjusted technical efficiency and environmental regulatory costs for this industry. To investigate policy effects, we test the Porter hypothesis using the Granger causality between regulatory cost and technical efficiency. By using the dual model of Weighted Russell Directional Distance Function, we estimate the carbon shadow pricing and inter-factor substitution possibilities. Results show that the carbon-adjusted technical efficiency and environmental regulation costs of the Chinese ferrous metal industry have significantly increased in recent decades. However, the latter does not significantly cause the improvement of former. The indirect Morishima elasticities of substitution reflect that the increase of fixed assets will effectively improve the carbon emissions performance of the Chinese ferrous metal industry. Finally, some policy implications are suggested.

In this study we propose a global metafrontier Luenberger productivity indicator (GMLPI) to investigate the effect of the establishment of the Poyang Lake Eco-economic Zone (PLEEZ), one of China's typical ecological civilization zones, on regional environmental total-factor productivity growth. We combine the global environmental technology, metafrontier approach, and the non-radial Luenberger productivity indicator and incorporate the regional heterogeneities into the environmental productivity growth analysis. This GMLPI includes the efficiency change, technological change, and metafrontier technology gap change indices. An empirical study of the PLEEZ has been conducted using the county level data covering a period from 2009 to 2013. Empirical results show that the environmental productivity growth has increased by 8.71% on average, with growth primarily driven by technological change. These results suggest that the establishment of the PLEEZ is effective in encouraging eco-innovation; however the PLEEZ lacks an eco-leadership effect. Significant heterogeneities in environmental productivity growth and its patterns among three major functional zones in the PLEEZ remain.

Murine bladder tumor models are critical for the evaluation of new therapeutic options. Bladder tumors induced with the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen are advantageous over cell line-based models because they closely replicate the genomic profiles of human tumors, and, unlike cell models and xenografts, they provide a good opportunity for the study of immunotherapies. However, bladder tumor generation is heterogeneous; therefore, an accurate assessment of tumor burden is needed before randomization to experimental treatment. Described here is a BBN mouse model and protocol to evaluate bladder cancer tumor burden in vivo using a fast and reliable magnetic resonance (MR) sequence (true FISP). This method is simple and reliable because, unlike ultrasound, MR is operator-independent and allows for the straightforward post-acquisition image processing and review. Using axial images of the bladder, analysis of regions of interest along the bladder wall and tumor allow for the calculation of bladder wall and tumor area. This measurement correlates with ex vivo bladder weight (rs= 0.37, p = 0.009) and tumor stage (p = 0.0003). In conclusion, BBN generates heterogeneous tumors that are ideal for evaluation of immunotherapies, and MRI can quickly and reliably assess tumor burden prior to randomization to experimental treatment arms.

Education, as an investment in human capital, is regarded as an important determinant of sustainable economic growth [1,2]. The purpose of this study is to explore the cointegration and causality between the investment in education and sustainable economic growth in Guangdong province by using the panel data of 21 cities from 2000 to 2016. We construct a variable intercept panel data model with an individual fixed effect based on the Cobb-Douglas production function, estimating the contribution of the investment in education to economic growth by introducing lags. The findings show the existence of the feedback causality between education and sustainable economic growth. Also, the results reveal that the local financial investment in education plays a positive and statistically significant role in promoting sustainable economic growth. However, the contribution of the local financial investment in education to economic growth varies in different areas. The investment in education in the Pearl River Delta region have the most obvious pull effects on its regional economy, whereas the Western region takes the second place. Meanwhile, the local financial investment in education for its role in promoting economic growth obviously has a two-year hysteresis effect. These findings have important implications for Guangdong&rsquo, s solution to the imbalance between regional educational investment and sustainable economic growth.

Previous studies have not estimated the abatement costs of pollutants related to energy use for China. Hence, this paper attempts to fill this gap by using a slacks-based measure based on Data Envelopment Analysis framework for regional economies of China. We develop the dual model of slack-based measure to estimate the abatement costs of three pollutants, specifically carbon dioxide, sulfur dioxide, and Chemical Oxygen Demand. The results show that the marginal abatement cost of pollutants decreased from 2001 to 2005 but then, starting in 2006, it began to increase. Finally, some policy suggestions for an emissions trading scheme are also presented.

This empirical study investigates the driving factors in the adoption of corporate social responsibility (CSR) practices by Chinese firms. Following the stakeholder theory, the hypothesis of this study is that stakeholder pressures positively impact Chinese firms’ adoption of CSR practices. Studies on the relationship between stakeholder pressure and CSR practices have been inconclusive. In order to identify the missing links amid those inconclusive results, this study examines the mediating role of CSR-oriented organizational culture in the relationship between stakeholder pressure and the adoption of CSR practices. The empirical findings provide strong evidence that a CSR-oriented organizational culture has a fully mediating role on the relationship between stakeholder pressure and the adoption of CSR practices. These results suggest that Chinese companies should promote a well-established CSR-oriented culture within a CSR paradigm shift more effectively and thus gain a sustainable competitive advantage over their competitors.

Background As CDK-16 has been shown to be upregulated in several transformed cancer lines, we hypothesized that the cyclin-dependent kinase 16 (CDK-16) may be upregulated in serous epithelial ovarian cancer (EOC) cells. Therefore, we comparatively examined the mRNA and protein expression of CDK-16 in samples resected from serous EOC patients and normal controls. Material/Methods Tissue samples were collected from 70 serous EOC patients and 40 normal controls. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was conducted to assess mRNA expression. CDK-16 protein expression was assessed by semi-quantitative immunohistochemical staining. Differences in mRNA and protein expression between serous EOC cells and normal tissue cells were tested with the Kruskal-Wallis test and analysis of variance (ANOVA). Results Both CDK-16 mRNA and protein expression were significantly higher in serous EOC tumor cells as compared to normal control ovarian cells (p