Evaluation of pharmaceutical consumption between urban and suburban catchments in China by wastewater-based epidemiology.

Wastewater-based epidemiology (WBE) is amply used for estimating human consumption of chemicals, yet information on regional variation of pharmaceuticals and their environmental fate are scarce. Thus, this study aims to estimate the consumption of three cardiovascular, four non-steroidal anti-inflammatory pharmaceuticals (NSAIDs), and four psychoactive pharmaceuticals between urban and suburban catchments in China by WBE, and to explore their removal efficiencies and ecological risks. Eleven analytes were detected in both influent and effluent samples. The estimated consumptions ranged from

Removal of organophosphorus flame retardant by biochar-coated nZVI activating persulfate: Synergistic mechanism of adsorption and catalytic degradation.

Triphenyl phosphate (TPhP) is a typical aromatic-based non-chlorinated organophosphorus flame retardant, which has been widely detected in a variety of environments and poses high environmental and human health risks. In this study, biochar coated nano-zero-valent iron (nZVI) was fabricated to activate persulfate (PS) to degrade TPhP from water. A range of biochars (BC400, BC500, BC600, BC700, and BC800) was prepared as potential support to coat nZVI by pyrolyzing corn stalk at 400, 500, 600, 700 and 800 °C. As outperformed other biochars in adsorption rate, adsorption capacity, and less reluctant to be influenced by environmental factors (pH, humic acid (HA), coexistence of anions), BC800 was to act as support to coat nZVI (labeled as BC800@nZVI). SEM, TEM, XRD and XPS characterization showed that nZVI was successfully supported on the BC800. Removal efficiency of 10 mg L-1 TPhP by BC800@nZVI/PS could reach to 96.9% with a high catalytic degradation kinetic rate of 0.0484 min-1 under optimal condition. The removal efficiency remained stable in a wide pH range (3-9) and moderate concentration of HA and coexistence of anions, demonstrated the promising of using BC800@nZVI/PS system to eliminate TPhP contamination. Results from the radical scavenging and electron paramagnetic resonance (EPR) experiments demonstrated radical pathway (i.e. SO4·- and HO·) and non-radical pathway via 1O2 both play important role in TPhP degradation. The TPhP degradation pathway was proposed based on the six degradation intermediates analyzed by LC-MS. This study illustrated the synergistic mechanism of adsorption and catalytic oxidation removal of TPhP by BC800@nZVI/PS system, and provided a cost-efficient approach for TPhP remediation.

Efficient removal of Tris(2-chloroethyl) phosphate by biochar derived from shrimp shell: Adsorption performance and mechanism study.

Tris(2-chloroethyl) phosphate (TCEP) has been detected all over the world as a typical refractory organic phosphate, especially in groundwater. This work applied a calcium-rich biochar derived from shrimp shell as a low-cost adsorbent for TCEP removal. Based on the kinetics and isotherm studies, the adsorption of TCEP on biochar was monolayer adsorbed on a uniform surface, with SS1000 (the biochar was prepared at the carbonization temperature of 1000 °C) achieving the maximum adsorption capacity of 264.11 mg·g-1. The prepared biochar demonstrated stable TCEP removal ability throughout a wide pH range, in the presence of co-existing anions, and in diverse water bodies. A rapid removal rate of TCEP was observed during the adsorption process. When the dosage of SS1000 was 0.2 g·L-1, 95% of TCEP could be removed within the first 30 min. The mechanism analysis indicated that the calcium species and basic functional groups on the SS1000 surface were highly involved in the TCEP adsorption process.

Discovery of novel benzofuran scaffold as 4-hydroxyphenylpyruvate dioxygenase inhibitors.

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) plays an important role in addressing the issue of plant protection research. This study sheds new light on the differences in molecular scaffold from commercialized HPPD inhibitors. RESULTS: The compounds A1-A18 and B1-B27 were synthesized for in vitro and greenhouse experiments. The greenhouse experiment data indicated that compounds B14 and B18 displayed excellent herbicidal activity, which was higher compared to that of mesotrione. In vitro testing indicated that the compounds were HPPD inhibitors. Moreover, molecular simulation results show that the compounds B14, B18, and mesotrione shared similar interplay with surrounding residues, which led to a perfect interaction with the active site of Arabidopsis thaliana HPPD. Based on crop selectivity results, compounds B14 and B18 were selected for maize studies (injury≤10%), indicating its potential for weed control in maize fields. CONCLUSION: These results showed that the pyrazole-benzofuran structure could be used as possible lead compounds for the development of HPPD inhibitors. © 2020 Society of Chemical Industry.

Discovery of novel arylthioacetic acid derivatives as 4-hydroxyphenylpyruvate dioxygenase inhibitors.

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) plays an important role in addressing the issue of plant protection research. In a continuing effort to discover novel HPPD inhibitors, we adopted a bioisosterism strategy to design a series of novel arylthioacetic acid scaffold based on the previously discovered aryloxyacetic acid scaffold. This study sheds new light on the discovery of novel HPPD inhibitors. RESULTS: The compounds A1-A30 and B1-B39 were prepared through an efficient synthetic route for in vitro and glasshouse experiments (herbicidal activities, herbicidal activity spectrum, and crop selectivity). Preliminary bioassay results reveal that these derivatives are promising Arabidopsis thaliana HPPD inhibitors, compounds A11 (Ki = 0.021 µmol L-1 ) and B20 (Ki = 0.022 µmol L-1 ), which exhibit similar activities to that of mesotrione (Ki = 0.020 µmol L-1 ). The glasshouse experiments data indicated that compounds B34 displayed excellent herbicidal activity, which was higher compared to that of mesotrione. Moreover, molecular simulation results show that the compounds B20, B34, and mesotrione shared similar interplay with surrounding residues, which led to a perfect interaction with the active site of Arabidopsis thaliana HPPD. Based on herbicidal results, compound B34 was selected for crop selectivity studies (corn injury ≤ 10%), indicating its potential for weed control in corn fields. CONCLUSION: These bioassay results showed that the compound B34 could be used as a possible lead compound for the development of HPPD inhibitors. © 2020 Society of Chemical Industry.

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors.

A series of aryloxyacetic acid derivatives were designed and synthesized as 4-hydoxyphenylpyruvate dioxygenase (HPPD) inhibitors. Preliminary bioassay results reveal that these derivatives are promising Arabidopsis thaliana HPPD (AtHPPD) inhibitors, in particular compounds I12 (K i = 0.011 µM) and I23 (K i = 0.012 µM), which exhibit similar activities to that of mesotrione, a commercial HPPD herbicide (K i = 0.013 µM). Furthermore, the newly synthesized compounds show significant greenhouse herbicidal activities against tested weeds at dosages of 150 g ai/ha. In particular, II4 exhibited high herbicidal activity for pre-emergence treatment that was slightly better than that of mesotrione. In addition, compound II4 was safe for weed control in maize fields at a rate of 150 g ai/ha, and was identified as the most potent candidate for a novel HPPD inhibitor herbicide. The compounds described herein may provide useful guidance for the design of new HPPD inhibiting herbicides and their modification.

Design, synthesis, and pharmacological evaluation of 4- or 6-phenyl-pyrimidine derivatives as novel and selective Janus kinase 3 inhibitors.

As non-receptor tyrosine kinases, Janus kinases (JAKs) have become an attractive target for the treatment of autoimmune diseases and cancers. JAKs play a pivotal role in innate immunity, inflammation, and hematopoiesis by mediating the signaling of numerous cytokines, growth factors, and interferons (IFNs). Selective inhibitors of a variety of JAK members are expected to inhibit pro-inflammatory cytokine-mediated inflammation and immune responses, while preventing targeting other subtypes of JAKs. In this work, poorly selective compounds based on 4- or 6-phenyl-pyrimidine derivatives have been improved to highly potent and selective compounds by designing a covalent binding tether, which attaches to the unique cysteine (Cys909) residue in JAK3. Compound 12 exhibited potent JAK3 inhibitory activity (IC50 = 1.7 nM) with an excellent selectivity profile when compared to the other JAK isoforms (>588-fold). In a cellular assay, compound 12 strongly inhibited JAK3-dependent signaling and T cell proliferation. Moreover, in vivo data revealed that compound 12 significantly suppressed oxazolone (OXZ)-induced delayed hypersensitivity responses in Balb/c mice. Compound 12 also displayed decent pharmacokinetic properties and was suitable for in vivo use. Taken together, these results indicated that compound 12 may be a promising tool compound as a selective JAK3 inhibitor for treating autoimmune diseases.