Computational drug discovery for castration-resistant prostate cancers through in vitro drug response modeling.

Prostate cancer (PC) is the most frequently diagnosed malignancy and a leading cause of cancer deaths in US men. Many PC cases metastasize and develop resistance to systemic hormonal therapy, a stage known as castration-resistant prostate cancer (CRPC). Therefore, there is an urgent need to develop effective therapeutic strategies for CRPC. Traditional drug discovery pipelines require significant time and capital input, which highlights a need for novel methods to evaluate the repositioning potential of existing drugs. Here, we present a computational framework to predict drug sensitivities of clinical CRPC tumors to various existing compounds and identify treatment options with high potential for clinical impact. We applied this method to a CRPC patient cohort and nominated drugs to combat resistance to hormonal therapies including abiraterone and enzalutamide. The utility of this method was demonstrated by nomination of multiple drugs that are currently undergoing clinical trials for CRPC. Additionally, this method identified the tetracycline derivative COL-3, for which we validated higher efficacy in an isogenic cell line model of enzalutamide-resistant vs. enzalutamide-sensitive CRPC. In enzalutamide-resistant CRPC cells, COL-3 displayed higher activity for inhibiting cell growth and migration, and for inducing G1-phase cell cycle arrest and apoptosis. Collectively, these findings demonstrate the utility of a computational framework for independent validation of drugs being tested in CRPC clinical trials, and for nominating drugs with enhanced biological activity in models of enzalutamide-resistant CRPC. The efficiency of this method relative to traditional drug development approaches indicates a high potential for accelerating drug development for CRPC.

Bioaccumulation and Trophodynamics of Novel Brominated Flame Retardants (NBFRs) in Marine Food Webs from the Arctic and Antarctic Regions.

The pervasive contamination of novel brominated flame retardants (NBFRs) in remote polar ecosystems has attracted great attention in recent research. However, understanding regarding the trophic transfer behavior of NBFRs in the Arctic and Antarctic marine food webs is limited. In this study, we examined the occurrence and trophodynamics of NBFRs in polar benthic marine sediment and food webs collected from areas around the Chinese Arctic Yellow River Station (n = 57) and Antarctic Great Wall Station (n = 94). ∑7NBFR concentrations were in the range of 1.27-7.47 ng/g lipid weight (lw) and 0.09-1.56 ng/g lw in the Arctic and Antarctic marine biota, respectively, among which decabromodiphenyl ethane (DBDPE) was the predominant compound in all sample types. The biota-sediment bioaccumulation factors (g total organic carbon/g lipid) of NBFRs in the Arctic (0.85-3.40) were 4-fold higher than those in the Antarctica (0.13-0.61). Trophic magnification factors (TMFs) and their 95% confidence interval (95% CI) of individual NBFRs ranged from 0.43 (95% CI: 0.32, 0.60) to 1.32 (0.92, 1.89) and from 0.34 (0.24, 0.49) to 0.92 (0.56, 1.51) in the Arctic and Antarctic marine food webs, respectively. The TMFs of most congeners were significantly lower than 1, indicating a trophic dilution potential. This is one of the very few investigations on the trophic transfer of NBFRs in remote Arctic and Antarctic marine ecosystems, which provides a basis for exploring the ecological risks of NBFRs in polar regions.

Tracing Organophosphate Ester Pollutants in Hadal Trenches─Distribution, Possible Origins, and Transport Mechanisms.

Unraveling the mysterious pathways of pollutants to the deepest oceanic realms holds critical importance for assessing the integrity of remote marine ecosystems. This study tracks the transport of pollutants into the depths of the oceans, a key step in protecting the sanctity of these least explored ecosystems. By analyzing hadal trench samples from the Mariana, Mussau, and New Britain trenches, we found the widespread distribution of organophosphate ester (OPE) flame retardants but a complex transport pattern for the OPE in these regions. In the Mariana Trench seawater column, OPE concentrations range between 17.4 and 102 ng L-1, with peaks at depths of 500 and 4000 m, which may be linked to Equatorial Undercurrent and topographic Rossby waves, respectively. Sediments, particularly in Mariana (422 ng g-1 dw), showed high OPE affinity, likely due to organic matter serving as a transport medium, influenced by "solvent switching", "solvent depletion", and "filtering processes". Amphipods in the three trenches had consistent OPE levels (29.1-215 ng g-1 lipid weight), independent of the sediment pollution patterns. The OPEs in these amphipods appeared more linked to surface-dwelling organisms, suggesting the influence of "solvent depletion". This study highlights the need for an improved understanding of deep-sea pollutant sources and transport, urging the establishment of protective measures for these remote marine habitats.

Soil's Hidden Power: The Stable Soil Organic Carbon Pool Controls the Burden of Persistent Organic Pollutants in Background Soils.

Persistent organic pollutants (POPs) tend to accumulate in cold regions by cold condensation and global distillation. Soil organic matter is the main storage compartment for POPs in terrestrial ecosystems due to deposition and repeated air-surface exchange processes. Here, physicochemical properties and environmental factors were investigated for their role in influencing POPs accumulation in soils of the Tibetan Plateau and Antarctic and Arctic regions. The results showed that the soil burden of most POPs was closely coupled to stable mineral-associated organic carbon (MAOC). Combining the proportion of MAOC and physicochemical properties can explain much of the soil distribution characteristics of the POPs. The background levels of POPs were estimated in conjunction with the global soil database. It led to the proposition that the stable soil carbon pools are key controlling factors affecting the ultimate global distribution of POPs, so that the dynamic cycling of soil carbon acts to counteract the cold-trapping effects. In the future, soil carbon pool composition should be fully considered in a multimedia environmental model of POPs, and the risk of secondary release of POPs in soils under conditions such as climate change can be further assessed with soil organic carbon models.

Occurrence and Trophic Transfer of Polychlorinated Naphthalenes (PCNs) in the Arctic and Antarctic Benthic Marine Food Webs.

Information about the occurrence and trophic transfer of polychlorinated naphthalenes (PCNs) in polar ecosystems is vital but scarce. In this study, PCNs were analyzed in benthic marine sediment and several biological species, collected around the Chinese polar scientific research stations in Svalbard in the Arctic and South Shetland Island in Antarctica. Total PCNs in biota ranged from 28 to 249 pg/g of lipid weight (lw) and from 11 to 284 pg/g lw in the Arctic and Antarctic regions, respectively. The concentrations and toxic equivalent (TEQ) of PCNs in polar marine matrices remained relatively low, and the compositions were dominated by lower chlorinated homologues (mono- to trichlorinated naphthalenes). Trophic magnification factors (TMFs) were calculated for congeners, homologues, and total PCNs in the polar benthic marine food webs. Opposite PCN transfer patterns were observed in the Arctic and Antarctic regions, i.e., trophic dilution and trophic magnification, respectively. This is the first comprehensive study of PCN trophic transfer behaviors in remote Arctic and Antarctic marine regions, providing support for further investigations of the biological trophodynamics and ecological risks of PCNs.

Novel biomonitoring method for determining five classes of legacy and alternative flame retardants in human serum samples.

Flame retardants (FRs) are ubiquitous in environment and biota and may pose harm to human health. In recent years, concern regarding legacy and alternative FRs has been intensified due to their widespread production and increasing contamination in environmental and human matrices. In this study, we developed and validated a novel analytical method for simultaneous determination of legacy and alternative FRs, including polychlorinated naphthalenes (PCNs), short- and middle-chain chlorinated paraffins (SCCPs and MCCPs), novel brominated flame retardants (NBFRs), and organophosphate esters (OPEs) in human serum. Serum samples were prepared by liquid-liquid extraction using ethyl acetate, and purified with Oasis® HLB cartridge and Florisil-silica gel columns. Instrumental analyses were carried out using gas chromatography-triple quadrupole mass spectrometry, high-resolution gas chromatography coupled with high-resolution mass spectrometry, and gas chromatography coupled with quadrupole time-of-flight mass spectrometry, respectively. The proposed method was validated for linearity, sensitivity, precision, accuracy, and matrix effects. Method detection limits for NBFRs, OPEs, PCNs, SCCPs, and MCCPs were 4.6 × 10-4-8.6 × 10-2, 4.3 × 10-3-1.3, 1.1 × 10-5-1.0 × 10-4, 1.5, and 9.0 × 10-1 ng/mL, respectively. Matrix spike recoveries ranged from 73%-122%, 71%-124%, 75%-129%, 92%-126%, and 94%-126% for NBFRs, OPEs, PCNs, SCCPs, and MCCPs, respectively. The analytical method was applied for detection of real human serum. CPs were the dominant FRs in serum, indicating CPs were widely presented in human serum and should be pay more attention for their health risk.

PM2.5-bound polyhalogenated carbazoles (PHCZs) in urban Beijing, China: Occurrence and the source implication.

Polyhalogenated carbazoles (PHCZs) are recently raising much attention due to their toxicity and ubiquitous environmental distribution. However, little knowledge is known about their ambient occurrences and the potential source. In this study, we developed an analytical method based on GC-MS/MS to simultaneously determine 11 PHCZs in PM2.5 from urban Beijing, China. The optimized method provided low method limit of quantifications (MLOQs, 1.45-7.39 fg/m3) and satisfied recoveries (73.4%-109.5%). This method was applied to analyze the PHCZs in the outdoor PM2.5 (n = 46) and fly ash (n = 6) collected from 3 kinds of surrounding incinerator plants (steel plant, medical waste incinerator and domestic waste incinerator). The levels of ∑11PHCZs in PM2.5 ranged from 0.117 to 5.54 pg/m3 (median 1.18 pg/m3). 3-chloro-9H-carbazole (3-CCZ), 3-bromo-9H-carbazole (3-BCZ), and 3,6-dichloro-9H-carbazole (36-CCZ) were the dominant compounds, accounting for 93%. 3-CCZ and 3-BCZ were significantly higher in winter due to the high PM2.5 concentration, while 36-CCZ was higher in spring, which may be related to the resuspending of surface soil. Furthermore, the levels of ∑11PHCZs in fly ash ranged from 338 to 6101 pg/g. 3-CCZ, 3-BCZ and 36-CCZ accounted for 86.0%. The congener profiles of PHCZs between fly ash and PM2.5 were highly similar, indicating that combustion process could be an important source of ambient PHCZs. To the best of our knowledge, this is the first research providing the occurrences of PHCZs in outdoor PM2.5.

Associations between Novel and Legacy Per- and Polyfluoroalkyl Substances in Human Serum and Thyroid Cancer: A Case and Healthy Population in Shandong Province, East China.

Per- and polyfluoroalkyl substances (PFASs) are widely detected in the environment and may cause adverse human health effects after exposure. Studies on the effect of PFASs on some health end points, including cancer, are still limited and show inconsistent results. In this research, 319 participants were recruited from Shandong Province, East China, consisting of patients with thyroid cancer and healthy controls. Seven novel and legacy PFASs were frequently detected (detection rate > 75%) in the serum samples of the participants. The concentrations of perfluorooctanoic acid (PFOA) were the highest in the case and control groups. Males showed significantly higher concentrations of PFASs than females. Exposure to PFASs was inversely associated with the risk of thyroid cancer. In the control group, we identified significant positive associations between PFASs and free thyroxine (FT4) as well as between PFOA and thyroid stimulating hormone (TSH) in females. A significant negative association between perfluorononanoic acid (PFNA) and triiodothyronine (T3) was observed in males. Our results suggest that exposure to certain PFASs could interfere with thyroid function. To our knowledge, this is the first case-control study demonstrating associations between novel and legacy PFASs in human and thyroid cancer.

Parent and Halogenated Polycyclic Aromatic Hydrocarbons in the Serum of Coal-Fired Power Plant Workers: Levels, Sex Differences, Accumulation Trends, and Risks.

Workers in coal-fired power plants are at a high risk of exposure to polycyclic aromatic hydrocarbons (PAHs) and their halogenated derivatives (HPAHs), yet no studies have investigated such exposure of HPAHs. In this study, 12 PAHs and 8 chlorinated PAHs, but no brominated PAHs, were detected in >80% of serum samples from workers of a coal-fired power plant in eastern China. Serum HPAH concentrations were higher in plant workers (16-273 ng/g lipid) than in people without occupational exposure (12-51 ng/g lipid), and serum PAH and HPAH concentrations both in male and female workers were positively correlated with the occupational exposure duration, with an estimated doubling time of 11-17 years. Correlations were found between concentrations of ∑8HPAHs and ∑12PAHs but not between 7-chlorobenz[a]anthracene (7-ClBaA) and 1-chloropyrene (1-ClPyr) and their respective parent PAHs. In males, total concentrations of PAHs and HPAHs were positively correlated with pulmonary hypofunction and hypertension but not with abnormal electrocardiogram. The benzo[a]pyrene equivalents ratio of ∑8HPAHs/∑12PAHs was 0.3 ± 0.1. Among the HPAHs in the serum, 9-chlorophenanthrene, 7-ClBaA, and 1-ClPyr showed high health risks. This study is the first report on HPAH exposure in coal-fired power plant workers and provides new evidence on the health risks of PAHs and HPAHs in humans.

Exposure to Novel Brominated Flame Retardants and Organophosphate Esters and Associations with Thyroid Cancer Risk: A Case-Control Study in Eastern China.

Novel brominated flame retardant (NBFR) and organophosphate ester (OPE) exposure may engender adverse effects on human health. However, present epidemiological information regarding the effects of such exposure is limited and controversial. In this case-control study, 481 serum samples were collected from patients with thyroid cancer (n = 242) and healthy controls (n = 239) in Shandong Province, eastern China. The levels of NBFRs and OPEs, thyroid hormones, and serum lipid parameters were measured in all the participants. Pentabromotoluene, 2,3-dibromopropyl 2,4,6 tribromophenyl ether, decabromodiphenylethane (DBDPE), tris (2-chloroethyl) phosphate (TCEP), and triphenyl phosphate (TPP) were widely detected (detection frequency > 60%) in all the participants. A significantly high risk association was found between exposure of NBFRs and OPEs (namely 1,2,3,4,5-pentabromobenzene, DBDPE, tri-n-propyl phosphate, tri[(2R)-1-chloro-2-propyl] phosphate, tris (1,3-dichloro-2-propyl) phosphate, and tris (2-butoxyethyl) phosphate) and thyroid cancer in both males and females. In the females of the control group, TCEP levels exhibited a significantly positive association with thyroid-stimulating hormone and a negative association with triiodothyronine (T3), free triiodothyronine (FT3), and free thyroxine (FT4) levels. Weighted quantile sum regression evaluated the mixed effects of the compounds on thyroid hormones levels and thyroid cancer. As a result, TPP accounted for the majority of the T3, thyroxine, and FT3 amounts. Our results suggest that NBFR and OPE exposure contributes to alterations in thyroid function, thereby increasing thyroid cancer risk.

iRGD-liposomes enhance tumor delivery and therapeutic efficacy of antisense oligonucleotide drugs against primary prostate cancer and bone metastasis.

Nucleotide-based drugs, such as antisense oligonucleotides (ASOs), have unique advantages in treating human diseases as they provide virtually unlimited ability to target any gene. However, their clinical translation faces many challenges, one of which is poor delivery to the target tissue in vivo. This problem is particularly evident in solid tumors. Here, we functionalized liposomes with a tumor-homing and -penetrating peptide, iRGD, as a carrier of an ASO against androgen receptor (AR) for prostate cancer treatment. The iRGD-liposomes exhibited a high loading efficiency of AR-ASO, and an efficient knockdown of AR gene products was achieved in vitro, including AR splice variants. In vivo, iRGD-liposomes significantly increased AR-ASO accumulation in the tumor tissue and decreased AR expression relative to free ASOs in prostate tumors established as subcutaneous xenografts. Similar results were obtained with intra-tibial xenografts modeling metastasis to bones, the predominant site of metastasis for prostate cancer. In treatment studies, iRGD-liposomes markedly improved the AR-ASO efficacy in suppressing the growth of both subcutaneous xenografts and intra-tibial xenografts. The inhibitory effect on tumor growth was also significantly prolonged by the delivery of the AR-ASO in the iRGD-liposomes. Meanwhile, iRGD-liposomes did not increase ASO accumulation or toxicity in healthy organs. Overall, we provide here a delivery system that can significantly increase ASO accumulation and efficacy in solid tumors. These benefits are achieved without significant side effects, providing a way to increase the antitumor efficacy of ASOs.

CircSOS2 promotes cervical squamous cell carcinoma by regulation of proliferation, cell cycle, apoptosis, migration, invasion, and glycolysis by targeting miR-543/FNDC3B axis.

BACKGROUND: Cervical squamous cell carcinoma (SCC) is a common subtype of cervical cancer. Circular RNAs (circRNAs) have been demonstrated as vital regulators in gene regulation and malignant tumor progression. Therefore, the precise role of circular RNA salt overly-sensitive 2 (circSOS2) was investigated in SCC. METHODS: The relative expression levels of circSOS2, microRNA-543 (miR-543), and Fibronectin type III domain containing 3B (FNDC3B) were determined by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assays. The correlation between percent survival times of SCC patients and circSOS2 level was presented by Kaplan-Meier Plotter analysis. The cell proliferation was measured by MTT and colony-forming assays. Flow cytometry assay was used to assess apoptosis and cell cycle distribution. The migration and invasion were measured by transwell assay. The glycolysis was analyzed by extracellular acidification rate (ECAR) assay, Glucose Assay Kit, and Lactate Assay Kit. The interaction relationship between miR-543 and circSOS2 or FNDC3B was analyzed by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. A xenograft experiment was established to clarify the functional role of circSOS2 inhibition in viv. RESULTS: CircSOS2 was highly expressed in SCC tissues and cells; besides, its expression level was closely associated with poor prognosis. Loss-of-functional experiments revealed that suppression of circSOS2 repressed proliferation, cell cycle process, migration, invasion, and glycolysis while induced apoptosis in SCC cells, which was overturned by inhibition of miR-543. In addition, miR-543 was downregulated and negatively correlated with circSOS2 expression in SCC tissues. We also found that overexpression of miR-543 impeded proliferation, cell cycle process, migration, invasion, and glycolysis while induced apoptosis in SCC cells by targeting FNDC3B. The silencing of circSOS2 impeded tumorigenesis in vivo. CONCLUSION: CircSOS2 conferred an oncogenic function in SCC by regulation of proliferation, cell cycle, apoptosis, migration, invasion, and glycolysis of SCC cells, which was contributed to its interactions with miR-543 and FNDC3B.

Katabatic Wind and Sea-Ice Dynamics Drive Isotopic Variations of Total Gaseous Mercury on the Antarctic Coast.

Clarifying the sources and fates of atmospheric mercury (Hg) in the Antarctic is crucial to understand the global Hg circulation and its impacts on the fragile ecosystem of the Antarctic. Herein, the annual variations in the isotopic compositions of total gaseous Hg (TGM), with 5-22 days of sampling duration for each sample, were presented for the first time to provide isotopic evidence of the sources and environmental processes of gaseous Hg around the Chinese Great Wall Station (GWS) in the western Antarctic. Different from the Arctic tundra and lower latitude areas in the northern hemisphere, positive δ202Hg (0.58 ± 0.21‰, mean ± 1SD) and negative Δ199Hg (-0.30 ± 0.10‰, mean ± 1SD) in TGM at the GWS indicated little impact from the vegetation-air exchange in the Antarctic. Correlations among TGM Δ199Hg, air temperature, and ozone concentrations suggested that enhanced katabatic wind that transported inland air masses to the continental margin elevated TGM Δ199Hg in the austral winter, while the surrounding marine surface emissions controlled by sea-ice dynamics lowered TGM Δ199Hg in the austral summer. The oxidation of Hg(0) might elevate Δ199Hg in TGM during atmospheric Hg depletion events but have little impact on the seasonal variations of atmospheric Hg isotopes. The presented atmospheric Hg isotopes were essential to identify the transport and transformation of atmospheric Hg and further understand Hg cycling in the Antarctic.

Modeling of Flame Retardants in Typical Urban Indoor Environments in China during 2010-2030: Influence of Policy and Decoration and Implications for Human Exposure.

Novel flame retardants (FRs) are of increasing concern, given growing evidence of health effects and use to replace polybrominated diphenyl ethers (PBDEs). This study modeled combined effects of use policies and decoration on indoor FRs and human exposure for 18 widely used PBDEs, organophosphate esters (OPEs), and novel brominated flame retardants in typical urban indoor environments in China. The current estimated indoor emission rates and average concentrations in air and dust of the 18 FRs were 102-103 ng/h, 561 ng/m3, and 1.5 × 104 ng/g, respectively, with seven OPEs dominant (>69%). Different use patterns exist between China and the US and Europe. Scenarios modeled over 2010-2030 suggested that decoration would affect indoor concentrations of FRs more than use policies, and use policies were mainly responsible for shifts of FR composition. Additional use of hexabromobenzene and 2,3,4,5,6-pentabromotoluene and removal of BDE-209 would make the total human exposure to the modeled FR mixture increase after the restriction of penta- and octa-BDE but decrease after deca-BDE was banned. Better knowledge of the toxicity of substitutes is needed for a complete understanding of the health implications of such changes. Toddlers may be more affected by use changes than adults. Such studies are supportive to the management of FR use.

Long-Term Investigation of the Temporal Trends and Gas/Particle Partitioning of Short- and Medium-Chain Chlorinated Paraffins in Ambient Air of King George Island, Antarctica.

The presence of anthropogenically emitted chlorinated paraffins (CPs) has been reported in the pristine regions, providing evidence of their long-range transport. This study comprehensively analyzed the short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in both gas and particle phases at King George Island, West Antarctica (the Chinese Great Wall Station), from 2014 to 2018. The atmospheric levels of CPs ranged between 71.4 and 4230 pg/m3, with an increasing temporal trend during the sampling time. Three different models (J-P model, H-B model, and L-M-Y model) were built to estimate the progress of gas/particle partitioning of CPs at the measurement site. Furthermore, we compared the measured data of the gas/particle partitioning with the data estimated using three different models. We found that the steady-state model (L-M-Y model) was more suitable for investigating the gas/particle partitioning of CPs instead of equilibrium state models (J-P model and H-B model). The result indicated that steady-state approximation rather than the equilibrium state represents the most predominant contribution to the transport of CPs to the Antarctic region. The steady-state further made it conducive to sustaining the levels of CPs for a more extended period in the atmosphere of West Antarctica.

A case-control study on the association of mineral elements exposure and thyroid tumor and goiter.

Thyroid tumor and thyroid goiter are prevalent disease around the world. In this case-control study, we investigated the association between exposure to a total of twelve mineral elements and thyroid disease as well as thyroid functions. Participants with thyroid tumor or goiter (N = 197) were matched with a healthy population (N = 197) by age (± 2 years old) and same sex. Questionnaires were used to collect data about the demographic characteristics and information of subjects. Serum and urine samples were collected simultaneously for each of the subjects. Mineral elements, iodine level of urine and levels of the total seven thyroid function indexes in serum were detected respectively. Conditional logistic regression was applied to estimate the associations between mineral elements and the risk of thyroid tumor and goiter through single-element models and multiple-element models. Multiple linear regression was used to evaluate relationships between mineral elements and percentage changes of thyroid functions. Higher concentrations of mineral elements in the recruited population were found in this study than other comparable studies, and the levels of chromium (Cr), manganese (Mn), nickel (Ni), arsenic (As), cadmium (Cd), selenium (Se), antimony (Sb), thallium (Tl) and lead (Pb) in the case group were lower than the control group. According to the single-element models, Cr, Mn, Ni, Sb and Tl showed significant negative associations with the risk of thyroid tumor and goiter, and, Cd showed nonmonotonic dose response. Cd and mercury (Hg) showed a nonmonotonic percentage change with T4, while Tl was associated with the increased FT4 in the control group. Therefore, Cd, Hg and Tl may disturb the balance of thyroid function to some extent, and Cr, Mn, Ni, Cd, Sb, and Tl may become potential influencing factors for the risk of thyroid tumor and goiter.

Green process innovation, green product innovation and its economic performance improvement paths: A survey and structural model.

Green technology innovation is an important driving force for high-quality development in China. Recently, much attention has focused on the connotation, influencing factors and mode selection of green technology innovation, yet few studies have systematically tested the transmission paths between green technology innovation and economic performance. Green technology innovation can be divided into green process innovation and green product innovation, both of which can improve the environmental and economic performance of enterprises. Drawing on previous research, this study constructs a model of economic performance transmission for green technology innovation and upgrading, and conducts an empirical analysis based on data from 642 industrial enterprises in China. The results show that green process innovation and green product innovation can effectively improve the economic performance of enterprises. The environmental performance and market competitiveness of enterprises are important mediating variables in the paths of economic performance improvement. An enterprise's green process innovation can positively promote green product innovation, and there is also room for technological innovation upgrading. There are two main differences in the transmission paths for different types of green technology innovation: (1) Green process innovation can improve economic performance directly, whereas green product innovation can only do this indirectly; (2) In most cases, the path from green product innovation to economic performance is more important than that from green process innovation to economic performance. This study deepens understanding of the green technology innovation process and has implications for optimizing policy design for green development.

Bioaccumulation and Trophic Transfer of Polybrominated Diphenyl Ethers and Their Hydroxylated and Methoxylated Analogues in Polar Marine Food Webs.

Arctic and Antarctic marine ecosystems, which are important components of global biodiversity, have been severely threatened by environmental pollutants in recent decades. In this study, polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated analogues (OH-PBDEs and MeO-PBDEs) were analyzed in seawater, sediment, and marine organisms (algae, invertebrates, and fishes) collected surrounding the Arctic Yellow River Station (n = 83) and the Antarctic Great Wall Station (n = 72). PBDEs and the analogues were detectable in all polar marine matrices, except MeO-PBDEs in seawater. The concentrations of ∑PBDEs, ∑MeO-PBDEs, and ∑OH-PBDEs in the marine organisms were in the range of 0.33-16 ng/g lipid weight (lw), n.d.-2.6 ng/g lw, and 0.12-2.3 ng/g lw in the Arctic and 0.06-31 ng/g lw, n.d.-5.8 ng/g lw, and 0.17-35 ng/g lw in Antarctica, respectively. Biota-sediment bioaccumulation factor (BSAF, g TOC/g lipid) values of MeO-PBDEs (0.002-0.14) and OH-PBDEs (0.004-0.18) were lower than the BSAF values of PBDEs (0.85-12). Trophic magnification was found for ∑MeO-PBDEs, whereas trophic dilution was observed for ∑OH-PBDEs in both regions. This is one of very few investigations on trophic transfer of PBDE metabolites in the Antarctic and Arctic regions and will further strengthen concerns about the ecological risk of PBDE metabolites in remote areas.

Occurrence and human exposure assessment of organophosphate esters in atmospheric PM2.5 in the Beijing-Tianjin-Hebei region, China.

Organophosphate esters (OPEs) in atmospheric fine particles (PM2.5) were comprehensively investigated in the Beijing-Tianjin-Hebei (BTH) region from April 2016 to March 2017. The concentrations of Σ8OPEs in all the five sampling sites ranged from 90 to 8291 pg/m3 (mean 1148 ± 1239 pg/m3; median 756 pg/m3). The highest level (median 1067 pg/m3) was found at one of the urban sites in Beijing, followed by Tianjin (746 pg/m3) and Shijiazhuang (724 pg/m3). Tris(2-chloroethyl) phosphate (TCEP) and tri[(2R)-1-chloro-2-propyl] phosphate (TCPP) were the dominant compounds across the five sampling locations. Generally, the concentrations of chlorinated OPEs were relatively higher in summer than in winter (p < 0.05), but no significant seasonal difference was discovered for non-chlorinated individual OPEs. The concentrations of tri-n-butyl phosphate (TBP), TCEP, TCPP and triphenyl phosphate (TPP) were positively correlated with the meteorological parameters (i.e. temperature and relative humidity) (p < 0.05), indicating an evident influence of meteorological condition on OPE distribution. We observed a negative correlation (p < 0.05) between octanol-air partition coefficients (logKoa) and the ratio of PM2.5-bound OPE concentrations to total suspended particulates-bound OPE concentrations, suggesting that physicochemical properties affect the particle-size distribution of OPEs. Furthermore, the median value of cancer hazard quotients (HQs) of TCEP was higher than TBP and tris(2-ethylhexyl) phosphate (TEHP). The health risk assessment showed that HQ values for children were ~1.6 times higher than those for adults. Relatively higher health risk induced by PM2.5-bound OPEs via inhalation was found during severe hazy days than in clear days.

Exposure to organochlorine pesticides and the risk of type 2 diabetes in the population of East China.

Organochlorine pesticides (OCPs) have been reported to be associated with an elevated risk of type 2 diabetes, although no study has focused on such associations in Chinese populations. In this case-control study, we aimed to explore the associations between OCPs and type 2 diabetes and their potential mechanisms in a population from East China. Participants diagnosed with type 2 diabetes and nondiabetic participants from Shandong Province, East China, were enrolled in this case-control study. Six OCPs (ß-HCH, trans-chlordane, trans-nonachlor, p,p'-DDE, p,p'-DDT and mirex/kepone) were detected in more than 75% of serum samples. Logistic regression analysis and multiple linear regression analysis were used to assess the associations between OCP exposure and the outcomes. After adjusting for potential confounding factors such as age, sex and body mass index, all six OCPs showed positive associations with type 2 diabetes in a linear dose-response manner. Serum concentrations of ß-HCH and p,p'-DDE were associated with higher levels of fasting plasma glucose in participants without diabetes, although no OCPs showed significant associations with hemoglobin A1c. In addition, certain OCPs showed significantly positive associations with triglycerides, total cholesterol, and low-density lipoprotein cholesterol and negative relationships with high-density lipoprotein cholesterol in nondiabetics, indicating that OCP exposure may disrupt lipid metabolism. Findings in the current study indicated that OCPs may be a diabetogenic factor in the population of this study. To our knowledge, this is the first study to investigate the associations between OCP exposure and type 2 diabetes in a Chinese population.