Inhibition of TTX-S Na+ currents by a novel blocker QLS-278 for antinociception.

Genetic loss-of-function mutations of Nav1.7 channel, abundantly expressed in peripheral nociceptive neurons, cause congenital insensitivity to pain (CIP) in humans, indicating that selective inhibition of the channel may lead to potential therapy of pain disorders. In this study, we investigated a novel compound, 5-chloro-N-(cyclopropylsulfonyl)-2-fluoro-4-(2-(8-(furan-2-ylmethyl)-8-azaspiro [4.5] decan-2-yl) ethoxy) benzamide (QLS-278) that inhibits Nav1.7 channel and exhibits anti-nociceptive activity. Compound QLS-278 exhibits inactivation- and concentration-dependent inhibition of macroscopic currents of Nav1.7 channels stably expressed in HEK293 cells with an IC50 of 1.2 {plus minus} 0.2 µM. QLS-278 causes a hyperpolarization shift of the channel inactivation and delays recovery from inactivation, without an obvious effect on voltage-dependent activation. In mouse DRG neurons, QLS-278 suppresses native TTX-sensitive Nav currents and also reduces neuronal firing. Moreover, QLS-278 dose-dependently relieves neuropathic pain induced by spared nerve injury and inflammatory pain induced by formalin without significant alteration of spontaneous locomotor activity in mice. Altogether, our identification of the novel compound QLS-278 may hold developmental potential for the treatment of chronic pain. Significance Statement QLS-278, a novel voltage-gated sodium Nav1.7 channel blocker, inhibits native TTX-S Na+ current and reduces action potential firings in DRG sensory neurons. QLS-278 also exhibits antinociceptive activity in mouse models of pain, thus demonstrating potential for the development of a treatment for chronic pain.

[Temporal and Spatial Variation in Odor Pollution and Membrane Barrier Effect in Municipal Solid Waste Landfill].

In order to explore the source characteristics as well as the temporal and spatial variations in odor pollution in municipal waste landfills, gas samples were collected from a landfill in an eastern coastal area of China throughout winter and summer. The total concentration of malodorous substances reached 60000 µg·m-3. There were more types of odor pollutants detected in summer than in winter, the average concentration was 30-300 times higher than that in winter, and the concentration of sulfur compounds increased by 4.7-136.7 times in summer. Oxygenated compounds had the highest concentration, and the total concentration of sulfur compounds accounted for less than 10% of malodorous substances. However, sulfur compounds contributed more than 90% to the theoretical odor concentration. Sulfur compounds such as methyl mercaptan and propane mercaptan were the key odorants in the landfill. After the landfill unit was covered, the concentration of odorous substances and the theoretical odor concentration on the surface of the landfill showed an increasing trend with time, indicating that the covering had a certain odor barrier effect; however, the landfill unit still had a large odor release potential. The similarity analysis showed that the odorous gas accumulated in the unit with temporary cover and without an exhaust system could be released to the environment through the overlapping gap of the membrane and the location of membrane rupture, resulting in more serious odor pollution around the landfill at night than that during the day.

Upcycling waste polyvinyl chloride: One-pot synthesis of valuable carbon materials and pipeline-quality syngas via pyrolysis in a closed reactor.

Polyvinyl chloride (PVC) is one of the most commonly used plastics. The treatment and recycling of PVC waste is still challenging, due to its non-biodegradability, low thermal stability, high Cl content and low product value. In this study, a one-pot method was developed to upcycle PVC into valuable carbon materials, pipeline-quality pyrolysis gas and chlorides. The well-designed process included dechlorination by Cl-fixative (ZnO or KOH), carbonization of dechlorinated polyenes, and modification of carbon materials in sequence. ZnO and KOH converted 84.48% and 94.15% of total Cl into corresponding chlorides, respectively. CH4 and H2 accounted for 81.87-99.34 vol% of pyrolysis gas with higher heat values of 30.11-32.84 MJ m-3, which can be used as substitute natural gas. As high as 83.13% of the C element was converted into carbon materials. The morphology, structure and property of carbon materials can be modified by different Cl-fixatives. Millimeter-scale carbon spheres with mono-dispersity and porous carbon with a high specific surface area of 1922 m2 g-1 were obtained when ZnO and KOH were added, respectively. Moreover, the reaction mechanisms of PVC with Cl-fixatives were also deciphered through thermogravimetric analysis and thermodynamic simulation.

Novel selective κ agonists SLL-039 and SLL-1206 produce potent antinociception with fewer sedation and aversion.

SLL-039 (N-cyclopropylmethyl-7α-4'-(N'-benzoyl) amino-phenyl-6,14-endoethano-tetrahydronorthebaine) and SLL-1206 (N-cyclopropylmethyl-7α-3'-(p-methoxybenzyl) amino-phenyl-6,14-endoethano-tetrahydronorthebaine) are two 4,5-epoxymorphinan-based high selective κ receptor agonists that we recently discovered. In the present study we characterized their pharmacological properties in comparison with arylacetamide-based typical κ agonist U50,488H. We showed that both SLL-039 and SLL-1206 produced potent and long-lasting antinociceptive actions in three different rodent models of pain via activation of κ opioid receptor. In hot-plate assay, the antinociceptive potency of SLL-039 and SLL-1206 increased about 11-and 17.3-fold compared to U50,488H and morphine, respectively, with ED50 values of 0.4 mg/kg. Following repeated administration, SLL-1206, SLL-039, and U50,488H all developed analgesic tolerance tested in hot-plate assay. U50,488H and SLL-039 produced antipruritic effects in a dose-dependent manner, whereas SLL-1206 displayed some antipruritic effects only at very low doses. In addition, SLL-1206 was capable of decreasing morphine-induced physical dependence. More importantly, SLL-039 and SLL-1206 at effective analgesic doses did not cause sedation and conditioned place aversion (CPA), whereas U50,488H did. In comparison with SLL-039, SLL-1206 caused similar antinociceptive responses, but fewer sedation and CPA. In conclusion, our results suggest that SLL-039 and SLL-1206 have potential to be developed as novel analgesic agents, and 4,5-expoxymorphinan scaffold is an attractive structure for the development of selective κ agonists with fewer side effects.

Repercussions of clinical waste co-incineration in municipal solid waste incinerator during COVID-19 pandemic.

During coronavirus disease 2019 pandemic, the exponential increase in clinical waste (CW) generation has caused immense burden to CW treatment facilities. Co-incineration of CW in municipal solid waste incinerator (MSWI) is an emergency treatment method. A material flow model was developed to estimate the change in feedstock characteristics and resulting acid gas emission under different CW co-incineration ratios. The ash contents and lower heating values of the feedstocks, as well as HCl concentrations in flue gas showed an upward trend. Subsequently, 72 incineration residue samples were collected from a MSWI performing co-incineration (CW ratio <10 wt%) in Wuhan city, China, followed by 20 incineration residues samples from waste that were not co-incineration. The results showed that the contents of major elements and non-volatile heavy metals in the air pollution control residues increased during co-incineration but were within the reported ranges, whereas those in the bottom ashes revealed no significant changes. The impact of CW co-incineration at a ratio <10 wt% on the distribution of elements in the incineration residues was not significant. However, increase in alkali metals and HCl in flue gas may cause potential boiler corrosion. These results provide valuable insights into pollution control in MSWI during pandemic.

[Experimental Influence of Food Waste Fermentation Broth on the Soil Quality in a Loess Hilly Area].

Loess is widely distributed in northwestern China. Due to the arid climate and rainstorm erosion, lack of nutrients and microorganisms, as well as severe salinization limits the ecosystem carrying capacity of loess soil, which has become one of the major causes of regional land desertification. The fermentation broth derived from food waste usually contains substantial organic acids and nutrients such as nitrogen and phosphorus, and it has the advantages of being easily produced industrially and applied as fertilizer. Hence, this broth has the potential to become a soil amendment for loess soils. This work studied the Lanzhou loess, which is a typical soil of the Loess Plateau of China, fertilized with fermentation broth for the evaluation of physicochemical properties and microbial analyses. After the application of the broth amendment, the total nitrogen, available phosphorus and potassium, and organic matter content increased by 363%, 577%, 308%, and 204%, respectively. After planting grass, including Halogeton arachnoideus Moq. and Medicago sativa L., the comprehensive soil fertility level was further improved and the total salt content of the soil was decreased by 2.3 g·kg-1 and 1.2 g·kg-1, respectively. Meanwhile, the fermentation broth promoted the growth of microorganisms, including bacteria and archaea, which increased by 22 times, and fungi by 8.3 times. Therefore, food waste fermentation broth is conducive to further forming plant-microorganisms symbiosis, improving the ecological environment quality of loess soils.

Inhibition of Nav1.7 channel by a novel blocker QLS-81 for alleviation of neuropathic pain.

Voltage-gated sodium channel Nav1.7 robustly expressed in peripheral nociceptive neurons has been considered as a therapeutic target for chronic pain, but there is no selective Nav1.7 inhibitor available for therapy of chronic pain. Ralfinamide has shown anti-nociceptive activity in animal models of inflammatory and neuropathic pain and is currently under phase III clinical trial for neuropathic pain. Based on ralfinamide, a novel small molecule (S)-2-((3-(4-((2-fluorobenzyl) oxy) phenyl) propyl) amino) propanamide (QLS-81) was synthesized. Here, we report the electrophysiological and pharmacodynamic characterization of QLS-81 as a Nav1.7 channel inhibitor with promising anti-nociceptive activity. In whole-cell recordings of HEK293 cells stably expressing Nav1.7, QLS-81 (IC50 at 3.5 ± 1.5 µM) was ten-fold more potent than its parent compound ralfinamide (37.1 ± 2.9 µM) in inhibiting Nav1.7 current. QLS-81 inhibition on Nav1.7 current was use-dependent. Application of QLS-81 (10 µM) caused a hyperpolarizing shift of the fast and slow inactivation of Nav1.7 channel about 7.9 mV and 26.6 mV, respectively, and also slowed down the channel fast and slow inactivation recovery. In dissociated mouse DRG neurons, QLS-81 (10 µM) inhibited native Nav current and suppressed depolarizing current pulse-elicited neuronal firing. Administration of QLS-81 (2, 5, 10 mg· kg-1· d-1, i.p.) in mice for 10 days dose-dependently alleviated spinal nerve injury-induced neuropathic pain and formalin-induced inflammatory pain. In addition, QLS-81 (10 µM) did not significantly affect ECG in guinea pig heart ex vivo; and administration of QLS-81 (10, 20 mg/kg, i.p.) in mice had no significant effect on spontaneous locomotor activity. Taken together, our results demonstrate that QLS-81, as a novel Nav1.7 inhibitor, is efficacious on chronic pain in mice, and it may hold developmental potential for pain therapy.

[Pollutant Removal Efficiency of Different Units Along a Mature Landfill Leachate Treatment Process in a Membrane Biological Reactor-Nanofiltration Combined Facility].

Properties of landfill leachate are complex. Therefore, leachate should be treated by combined processes with both biological and advanced methods. Due to the shortage of engineering-scale assessment data about the pollutant treatment contribution of individual process units, existing optimization methods still lack theoretical support. Here, a membrane biological reactor (MBR)+nanofiltration (NF) system with a capacity of 800 m3·d-1 was examined. Conventional physiochemical parameters and fluorescent parameters were examined to analyze the contribution of each process unit to treating mature landfill leachate. Furthermore, the transformation of dissolved organic matter (DOM) was evaluated using excitation emission matrix fluorescence spectroscopy-parallel factor (EEMs-PARAFAC). Results showed that the biological treatment removed soluble nitrogen (dissolved nitrogen, DN) by 74.7%, 54.6% occurred in the first-stage denitrification unit. The external ultrafiltration unit reduced dissolved chemical oxygen demand (COD) and dissolved organic carbon (DOC) by 92.2% and 93.3%, respectively. The nanofiltration unit effectively removed heavy metals and salts. Based on the tracking of DOM using fluorescent parameters, the first-stage denitrification unit was found to remove 75.4% of protein-like substances. The ultrafiltration unit mainly retained DOM with high hydrophilicity, while humus with high aromaticity was mainly retained by nanofiltration. The higher the degree of humification, the better the interception effect that was obtained. This indicates that biological treatment using the MBR process can be simplified, and ultrafiltration should prove reliable at preventing clogging during the treatment of mature landfill leachate.

Upcycling of PET waste into methane-rich gas and hierarchical porous carbon for high-performance supercapacitor by autogenic pressure pyrolysis and activation.

The explosive growth of polyethylene terephthalate (PET) wastes has brought serious pollution to the environment. Here, PET waste was upcycled into methane-rich pyrolysis gas and carbon material for energy storage through autogenic pressure pyrolysis and post-activation. The pyrolysis gas contained 34.58 ± 0.23 vol% CH4. After CO2 removal, the high caloric value of the pyrolysis gas could reach 29.2 MJ m-3, which could be used as a substitute natural gas. Pyrolytic carbon was further activated by KOH and ZnCl2. KOH-activated carbon (AC-K) obtained a hierarchical porous structure, a high specific surface area of 2683 m2 g-1 and abundant surface functional groups. Working as supercapacitor electrodes, AC-K exhibited an outstanding specific capacitance of 325 F g-1 at a current density of 0.5 A g-1. After 5000 charge-discharge cycles, AC-K still retained 91.86% of the initial specific capacitance. This study provides a sustainable way to control plastic-derived pollution and alleviate the energy crisis.

Inhibition of chlorobenzenes formation by calcium oxide during solid waste incineration.

Solid waste incineration is a major emission source of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs). The injection of N- and S-containing compounds is an effective way to suppress the formation of PCDD/Fs, but this approach is still shortcoming because additional pollutants such as NH3 and SOx are emitted. To avoid the secondary pollutions, a de novo synthesis inhibition mechanism in the presence of CaO was postulated to transform CuCl2 to CuO and deplete Cl2 and HCl. Chlorobenzenes (CBzs), which are indicators and precursors of PCDD/Fs, were adopted to prove the inhibitory effect of CaO at 400 °C, using both simulated synthetic ash and extracted air pollution control residues. As the molar ratio of CaO to CuCl2 exceeded 3, the residual carbon increased, and the inhibition efficiency of CBzs exceeded 93 %. This performance is superior to the corresponding performance of NH4H2PO4, which has been proved to be a potential inhibitor. Furthermore, with CaO, chlorides remained in the solid phase and had inactive catalytic performance; and they were the major products rather than HCl, Cl2 and Cu2OCl2. The addition of CaO during waste incineration therefore can facilitate the abatement of PCDD/Fs contamination and reduce the emissions of acid gas simultaneously.