Large Virtual Transboundary Hazardous Waste Flows: The Case of China.

The Basel Convention and prior studies mainly focused on the physical transboundary movements of hazardous waste (transporting waste from one region to another for cheaper disposal). Here, we take China, the world's largest waste producer, as an example and reveal the virtual hazardous waste flows in trade (outsourcing waste by importing waste-intensive products) by developing a multiregional input-output model. Our model characterizes the impact of international trade between China and 140 economies and China's interprovincial trade on hazardous waste generated by 161,599 Chinese enterprises. We find that, in 2015, virtual hazardous waste flows in China's trade reached 26.6 million tons (67% of the national total), of which 31% were generated during the production of goods that were ultimately consumed abroad. Trade-related production is much dirtier than locally consumed production, generating 26% more hazardous waste per unit of GDP. Under the impact of virtual flows, 40% of the waste-intensive production and relevant disposal duty is unequally concentrated in three Chinese provinces (including two least-developed ones, Qinghai and Xinjiang). Our findings imply the importance of expanding the scope of transboundary waste regulations and provide a quantitative basis for introducing consumer responsibilities. This may help relieve waste management burdens in less-developed "waste havens".

Targeting SNORA38B attenuates tumorigenesis and sensitizes immune checkpoint blockade in non-small cell lung cancer by remodeling the tumor microenvironment via regulation of GAB2/AKT/mTOR signaling pathway.

BACKGROUND: Non-coding RNAs (ncRNAs), including small nucleolar RNAs (snoRNAs), are widely involved in the physiological and pathological processes of human beings. While up to date, although considerable progress has been achieved in ncRNA-related pathogenesis of non-small cell lung cancer (NSCLC), the underlying mechanisms and biological significance of snoRNAs in NSCLC still need to be further clarified. METHODS: Quantitative real-time polymerase chain reaction or RNAscope was performed to verify the expression of Small Nucleolar RNA, H/ACA Box 38B (SNORA38B) in NSCLC cell lines or clinical samples. BALB/c nude mice xenograft model or C57BL/6J mice syngeneic tumor model were estimated to detect the effects of SNORA38B in tumor growth or tumor immune microenvironment in vivo. Cytometry by time of flight, enzyme-linked immunosorbent assay and flow cytometry assay were conducted to clarify the effects and mechanisms of SNORA38B-mediated tumor immunosuppressive microenvironment. The binding activity between SNORA38B and E2F transcription factor 1(E2F1) was detected by RNA immunoprecipitation and RNA pull-down assays. Then, bioinformatics analysis and chromatin immunoprecipitation were utilized to demonstrate the regulation of GRB2-associated-binding protein 2 (GAB2) by E2F1. Moreover, the combinatorial treatment of SNORA38B locked nucleic acid (LNA) and immune checkpoint blockade (ICB) was used to treat murine Lewis lung carcinoma-derived tumor burden C57BL/6J mice to clarify the effectiveness of targeting SNORA38B in NSCLC immunotherapy. RESULTS: SNORA38B was found highly expressed in NSCLC tissues and cell lines, and associated with worse prognosis. Further results showed that SNORA38B functioned as an oncogene via facilitating cell proliferation, migration, invasion, and inhibiting cell apoptosis in vitro and promoting tumorigenesis of NSCLC cells in vivo. SNORA38B could also recruit the CD4+FOXP3+ regulatory T cells by triggering tumor cells to secrete interleukin 10, which in turn reduced the infiltration of CD3+CD8+ T cells in NSCLC tumor microenvironment (TME), favoring tumor progression and poorer immune efficacy. Mechanistically, SNORA38B mainly distributed in the nucleus, and promoted NSCLC progression by regulating GAB2 transcription to activate protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway through directly binding with E2F1. Moreover, we found that SNORA38B LNAs were able to ameliorate CD3+CD8+ T cell infiltration in TME, which sensitized NSCLC to the treatment of ICB. CONCLUSIONS: In conclusion, our data demonstrated that SNORA38B functioned as an oncogene in NSCLC both in vitro and in vivo at least in part by regulating the GAB2/AKT/mTOR pathway via directly binding to E2F1. SNORA38B could also sensitize NSCLC to immunotherapy, which may be a critical therapeutic target for NSCLC.

Nanocomposites consisting of nanoporous platinum-silicon and graphene for electrochemical determination of bisphenol A.

Three-dimensional nanoporous PtSi (NP-PtSi) alloy was prepared by dealloying ternary PtSiAl alloy ribbons. By combining the nanoporous morphology of PtSi and graphene (GR), a new composite material was developed, which was used to modify the surface of a glassy carbon electrode (GCE). The resulting modified electrodes showed an excellent electrocatalytic activity towards the electro oxidation of bisphenol A. Based on differential pulse voltammetry measurements, NP-PtSi/GR/GCE showed linear response over the concentration range 0.30 to 85 µM bisphenol A, while the detection limit was found to be 0.11 µM (S/N = 3). NP-PtSi/GR/GCE showed also satisfactory stability and selectivity over various compounds present in real samples, and they were successfully applied to the determination of bisphenol A in inoculated milk samples. Graphical abstract Nanoporous PtSi (NP-PtSi) was fabricated by dealloying PtSiAl alloy ribbons. Based on the NP-PtSi alloy and graphene (GR) composites that modified glassy carbon electrode (GCE), a sensitive and stable electrochemical sensor was developed for the determination of bisphenol A by differential pulse voltammetric (DPV) method.

Sex differences in morphine-induced trafficking of mu-opioid and corticotropin-releasing factor receptors in locus coeruleus neurons.

The locus coeruleus (LC)-norepinephrine (NE) system is a key nucleus in which endogenous opioid and stress systems intersect to regulate the stress response. LC neurons of male rats become sensitized to stress following chronic morphine administration. Whether sex dictates this pattern of opioid-induced plasticity has not been demonstrated. Delineating the neurobiological adaptations produced by chronic opioids will enhance our understanding of stress vulnerability in opioid-dependent individuals, and may reveal how stress negatively impacts addiction recovery. In the present study, the effect of chronic morphine on the subcellular distribution of mu-opioid (MOR) and CRF receptors (CRFR) was investigated in the LC of male and female rats using immunoelectron microscopy. Results showed that placebo-treated females exhibited higher MOR and CRFR cytoplasmic distribution ratio when compared to placebo-treated males. Chronic morphine exposure induced a shift in the distribution of MOR immunogold-silver particles from the plasma membrane to the cytoplasm selectively in male LC neurons. Interestingly, chronic morphine exposure induced CRFR recruitment to the plasma membrane of both male and female LC neurons. These findings provide a potential mechanism by which chronic opioid administration increases stress vulnerability in males and females via an increase in surface availability of CRFR in LC neurons. However, our results also support the notion that cellular adaptations to chronic opioids differ across the sexes as redistribution of MOR following morphine exposure was only observed in male LC neurons.