Transboundary air pollution from coal-fired power generation.

To what extent do the short-term negative externalities of fossil fuel use traverse national borders? Transnational negative externalities are thought to motivate international environmental cooperation, but we often lack detailed data on their occurrence. Using a Hybrid Single Particle Lagrangian Integrated Trajectory Model (HYSPLIT), we offer global estimates of the extent of transboundary air pollution from coal-fired power generation. In an advance of the existing literature, we attribute the air pollution experienced in different locales to specific coal-fired power plants, allowing us to evaluate the extent to which pollution from the coal industry is experienced across different jurisdictions. Our results indicate that the issue is most severe in South Asia and East Asia. When weighting by the population of "receiving" locations, India is found to be the largest emitter of transboundary air pollution, followed by China. Residents of Bangladesh are found to experience the most transboundary air pollution by a wide margin.

Later bedtimes predict President Trump's performance.

Technology and social media use are increasingly associated with delays in nightly sleep. Here, we consider the timing of President Trump's official Twitter account posts as a proxy for sleep duration and how it relates to his public performance. The President wakes around 6am, a routine which has not changed since early 2017. In contrast, the frequency of Twitter activity 11pm-2am increased 317% from under one day per week in 2017 to three days a week in 2020. The President's increased late-night activity is not accounted for by increases in the frequency of his use of social media over time, his travel schedule, or seasonality. On the day following one where he posts late at night, his Twitter followers interact less with his posts, described as "official statements by the President of the United States". He receives 7400 fewer likes per tweet, 1300 fewer retweets per tweet, and 1400 fewer replies per tweet after a late night (drops of 6.5%-8%). Tweets aside, the President's speeches and interview transcripts have previously been coded for their dominant emotion through text analysis. On the day following a late night, the President's inferred emotion is less likely to be "happy" and nearly three times more likely to be "angry" in his interviews and speeches. Finally, the 2020 election odds of the President's chief opponent also increase after a late night, while the President's are unchanged. The pattern we document is consistent with a progressive shortening of the President's sleep over his first term and compromised performance from sleep deprivation.

Identification and immunological evaluation of novel TLR2 agonists through structure optimization of Pam3CSK4.

Toll-like receptor 2 (TLR2) is a bridge between innate immunity and adaptive immunity. TLR2 agonists have been exploited as potential vaccine adjuvants and antitumor agents. However, no TLR2 agonists have been approved by FDA up to now. To discover drug-like TLR2 selective agonists, a novel series of Pam3CSK4 derivatives were designed based on the crystal structure of hTLR2-hTLR1-Pam3CSK4 complex, synthesized and evaluated for their immune-stimulatory activities. Among them, 35c was identified as a murine-specific TLR2 agonist, while 35f was a human-specific TLR2 agonist. Besides, 35d (human and murine TLR2 agonist) showed TLR2 agonistic activity comparable to Pam3CSK4, which included: elevated IL-6 expression level (EC50 = 83.08 ±â€¯5.94 nM), up-regulated TNF-α and IL-6 mRNA expression and promoted maturation of DCs through activating the NF-κB signaling pathway. TLRs antibodies test showed that 35a and 35d were TLR2/1 agonists, while 35f was a TLR2/6 agonist.

Discovery of novel 6,7-disubstituted-4-phenoxyquinoline derivatives bearing 5-(aminomethylene)pyrimidine-2,4,6-trione moiety as c-Met kinase inhibitors.

A series of novel quinoline derivatives bearing 5-(aminomethylene)pyrimidine-2,4,6-trione moiety were designed, synthesized, and evaluated for their c-Met kinase inhibitory activities and antiproliferative activities against 5 cancer cell lines (HT-29, H460, MKN-45, A549, and U87MG) in vitro. Most compounds showed moderate to excellent potency, with the most promising analogue 45 (c-Met half-maximal inhibitory concentration [IC50]=1.15 nM) showing high selectivity versus 5 other tyrosine kinases, VEGFR-2, Flt-3, PDGFR-ß, c-Kit, and EGFR. Structure-activity relationship studies indicated that electron-donating groups on the phenyl ring at the 3-position of pyrimidine-2,4,6-trione were required to increase the electron density on the 5-(aminomethylene)pyrimidine-2,4,6-trione moiety.

Combination of High-Throughput Screening and Assembly to Discover Efficient Metal-Organic Frameworks on Kr/Xe Adsorption Separation.

Recycling Kr and Xe from used nuclear fuel (UNF) is conducive to regenerating economy and protecting the environment, and it is urgent to screen or design high-performance cutting-edge metal-organic framework (MOF) materials for Kr/Xe adsorption separation. After grand canonical Monte Carlo (GCMC) simulations of Kr/Xe adsorption separation on 11,000 frameworks in CoRE MOFs (2019), the important structure-adsorption property relationship (SAPR) was induced; that is, the porosity (φ) at 0.30-0.40, LCD/PLD at 1.00-1.49, density (ρ) range between 1.20 and 2.30 g/cm3, and PLD at 2.40-3.38 Å can be utilized to screen for high-performance G-MOFs and hMOFs. In addition, the key "genes" (metal nodes and linkers) of MOFs determining the Kr/Xe adsorption separation were data-mined by a machine learning technique, which were assembled into novel MOFs. After comprehensive consideration of thermal stability and the adsorbent performance score (APS), eight promising MOFs on Kr/Xe separation with the APS more than 1290.89 were screened out and assembled, which are better than most of the reported frameworks. Note that the adsorption isotherms of these MOFs on Kr and Xe belong to type I curve with the thermodynamic equilibrium mechanism on Kr/Xe based on the confinement effect. Furthermore, according to the electronic structure calculations of the independent gradient model based on Hirshfeld partition (IGMH) and energy decomposition analysis, it is found that the interactions between guests and frameworks are vdW forces with dominant induction energy (Eind). In addition, the electrostatic potential gradients of frameworks are generally linearly negative correlated with Kr uptakes. Therefore, both the geometrical and electronic structures dominate the adsorption separation performance on Kr/Xe. Interestingly, these eight MOFs are also suitable for the separation of CH4/H2 with considerable selectivities and CH4 uptakes of up to 2566.67 and 3.04 mmol/g, respectively. Herein, the accurately constructed SAPR and material genomics strategy should be helpful for the experimental discovery of novel MOFs on Kr/Xe separation experimentally.

Reduced trolling on Russian holidays and daily US Presidential election odds.

Russian trolls generally supported the Trump campaign and were particularly active on Twitter 2015-2017. We find that trolling fell 35% on Russian holidays and to a lesser extent, when temperatures were cold in St. Petersburg. Exogenous variation in trolling by day allows us to consider indirectly-affected political behaviors in the US-outcomes that are less traceable via tweet sharing but potentially more important to policymakers than the direct dissemination previously studied. As a case in point, we describe reduced form evidence that Russian holidays affected daily trading prices in 2016 election betting markets. This response is consistent with successful Russian interference in support of Trump.

A novel assay for measuring recombinant human lysophosphatidylcholine acyltransferase 3 activity.

Lysophosphatidylcholine acyltransferase 3 (LPCAT3) is an important enzyme in phospholipid remodeling, a process that influences the biophysical properties of cell membranes and thus cell function. Multiple lines of evidence suggest that LPCAT3 is involved in several diseases, including atherosclerosis, non-alcoholic steatohepatitis, and carcinoma. Thus, LPCAT3 may have potential as a therapeutic target for these diseases. In the present study, we devised an assay based on reversed-phase HPLC to measure LPCAT3 activity, which may facilitate the identification of LPCAT3 inhibitors and activators. We found that optimal pH and temperature of recombinant human LPCAT3 are 6.0 and 30 °C, respectively. The enzyme Km values for substrates NBD-labelled lysophosphatidylcholine and arachidonoyl CoA were 266.84 ± 3.65 and 11.03 ± 0.51 µmol·L-1 , respectively, and the Vmax was 39.76 ± 1.86 pmol·min-1 ·U-1 . Moreover, we used our new method to determine the IC50 of a known LPCAT inhibitor, TSI-10. In conclusion, this novel assay can be used to measure the effects of compounds on LPCAT3 activity.

miR-30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy.

Chemotherapy is an important treatment modality for gastric cancer, and multidrug resistance (MDR) represents a major obstacle for successful cancer chemotherapy. There is a lack of research on whether microRNA (miR)-30a regulation affects the chemosensitivity of resistant gastric cancer cells, and mechanisms underlying the effects of miR-30a on drug resistance and cell autophagy require further investigation. In the present study, the expression of miR-30a and its effects in cisplatin (CDDP)-resistant human gastric cancer cells were investigated. A CDDP-resistant variant of the SGC-7901 cell line (SGC-7901/CDDP) was established by exposing the cells to gradually increasing drug concentrations, and miR-30a expression was detected by reverse transcription-semi quantitative polymerase chain reaction (RT-sqPCR). To examine the effect of miR-30a expression in the SGC-7901/CDDP cells, miR30a mimics or negative control miRNA were transfected into the cells, and a Cell Counting Kit-8 assay was performed to analyze the chemosensitivity of the different cell groups. RT-sqPCR and western blot analysis were also used to measure MDR1 mRNA and P-glycoprotein expression, and the light chain (LC)3-II/LC3-I ratio. Furthermore, apoptosis induced by the chemotherapeutic CDDP in the different groups was assessed using flow cytometry. The results demonstrated that low expression of miR-30a was associated with chemoresistance in gastric cancer cells, and in the chemoresistant cell line SGC7901/CDDP, CDDP-induced apoptosis was weakened. Additionally, it was demonstrated that the LC3-II/LC3-I ratio was elevated in SGC7901/CDDP cells compared with chemosensitive SGC7901 cells (P<0.001), which could be attenuated by upregulating miR-30a expression (P<0.001 vs. SGC7901/CDDP control cells). These results suggested that autophagy may contribute to drug resistance in gastric cancer cells, and that the reduction of LC3-II in response to miR-30a overexpression may inhibit chemoresistance-associated autophagy in gastric cancer cells.

Brominated flame retardants (BFRs): A review on environmental contamination in China.

Brominated flame retardants (BFRs) which were detected extensively in environmental and biota samples worldwide, have raised significant concerns during past decades for their persistence, bioaccumulation and potential toxicity to ecological environment and human health. In this paper, we have compiled and reviewed existing literature on the contamination status of BFRs in abiotic and biotic environments in China, including polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane, tetrabromobisphenol A and new BFRs. Temporal trends were also summarized and evaluated. Based on this review, it has been concluded that (1) high concentrations of PBDEs were generally related to the e-waste disposal processing, while the spatial distribution pattern of other BFRs was not necessarily in accordance with this; (2) extremely high concentrations of BFRs in indoor dust emphasized the importance of indoor contamination to human body burdens, while more work need to be done to confirm its contribution; (3) PBDEs in electronics dismantling workers were higher compared to the general population, indicating the occupational exposure should be of particular concern; (4) more data are now becoming available for BFRs in aquatic and terrestrial organisms not previously studied, while studies that consider the occurrence of BFRs in organisms of different trophic levels are still of urgent need for evaluating the fate of BFRs in the food web; and (5) limited data showed a decreasing trend for PBDEs, while more data on time trends of BFR contamination in various matrices and locations are still needed before the impact of regulation of BFRs can be assessed.

Design, synthesis, and structure-activity relationships of novel 6,7-disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents.

Two series of quinoline derivatives bearing the pyridine/pyrimidine scaffold were synthesized, and evaluated for their c-Met kinase inhibitory activity and antiproliferative activity against 5 cancer cell lines (HT-29, H460, MKN-45, A549, and U87MG) were evaluated in vitro. Most compounds showed moderate to excellent potency, and compared to foretinib, the most promising analog 18b (c-Met half-maximal inhibitory concentration [IC50] = 1.39 nM) showed a 7.3-fold increase in activity against HT-29 cell line in vitro. Structure-activity relationship studies indicated that regulation of the electron density on the pyridine/pyrimidine ring to a proper degree was a key factor in improving the antitumor activity.