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Pesticides play a crucial role in securing global food production to meet increasing demands. However, because of their pervasive use, they are now ubiquitous environmental pollutants that have adverse effects on both ecosystems and human health. In this study, the environmental occurrence and fate of 16 current-use pesticides (CUPs) were investigated in 93 forest soil samples obtained from 11 distinct mountains in China. The concentrations of the target pesticides ranged from 0.36 to 55 ng/g dry weight. Cypermethrin, dicofol, chlorpyrifos, chlorothalonil, and trifluralin were the most frequently detected CUPs. The CUP concentrations were generally higher in the O-horizon than in the A-horizon. Chlorpyrifos, chlorothalonil, and dicofol were detected in most deep layers in soil profiles from three mountains selected to represent distinct climate zones. No clear altitudinal trend in organic carbon-normalized concentrations of CUPs was observed in the O- or A-horizons within individual mountains. A negative correlation was noted between the CUP concentrations and the altitudes across all sampling sites. This indicated that proximity to emission sources was a key factor affecting the spatial distribution of CUPs in mountain forest soil on a national scale. The ecological risk assessment showed that dicofol and cypermethrin pose potential risks to earthworms. This study emphasizes the importance of source control when setting management strategies for CUPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the material basis, targets and molecular mechanism of Scutellariae Radix against periodontitis to provide theoretical basis for clinical applications., Materials and Methods: The active compounds and targets of Scutellariae Radix were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, and the periodontitis-related targets were collected by integrating Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), Genecards and Gene Expression Omnibus (GEO) database together. The potential targets of Scutellariae Radix against periodontitis were obtained from the intersection of two target sets. Metascape database was used for Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Discovery Studio software was used for molecular docking between key targets and compounds to evaluate their binding affinity. Western blot was used to check the expression of PTGS2 and MMP9 to verify the regulatory effects of baicalein, the main active compound of Scutellariae Radix , on human periodontal ligament stem cells (hPDLSCs) cultured under inflammatory environment which induced by lipopolysaccharide (LPS)., Results: 15 active compounds of Scutellariae Radix and 53 common targets for periodontitis treatment were identified. Among these targets, the 10 core targets were AKT1, IL-6, TNF, VEGFA, TP53, PTGS2, CASP3, JUN, MMP9 and HIF1A. GO and KEGG analysis mainly focused on response to LPS and pathways in cancer. Molecular docking showed that the main active compounds had good binding affinity with key targets. Cell experiments confirmed that baicalein can interfere the expression of pro-inflammatory factors PTGS2 and MMP9 proteins and exert anti-inflammatory effects., Conclusion: Current study preliminarily analyzed the mechanism of Scutellariae Radix against periodontitis, which provide a new idea for the utilization of Scutellariae Radix and the development of novel medicine for the clinical treatment of periodontitis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Organophosphate esters (OPEs) are a class of emerging and ubiquitous contaminants that are attracting increasing attention, and their large-scale use as flame retardants and plasticizers has led to their pervasive presence in the environment, although their broader impacts remain unknown. In this study, 11 OPEs were measured in the atmosphere of Southeast Asia and Southwest China during 2016. The ∑ 11 OPEs were higher in this region (78.0-1670 pg/m 3 , mean 458 pg/m 3 ) than in many remote areas, lower than in developed regions, and comparable to levels in many developing country cities. Generally, the ∑ 11 OPEs were higher in urban (105-1670 pg/m 3 , mean 538 pg/m 3 ) than in suburban (78.0-1350 pg/m 3 , mean 388 pg/m 3 ). Seasonal variations of OPEs in the air were more pronounced in Cambodia and Laos, especially for Triphenyl Phosphate (TPHP). Seasonal variations of ∑ 11 OPEs in most regions correspond to changes in temperature and rainfall. Biomass burning may be also a factor in facilitating OPE emissions from biomass materials or soil into the atmosphere of Southeast Asia. The random forest analysis showed that among these, rainfall had the greatest effect on the seasonal variation of atmospheric OPE concentrations, followed by biomass burning and temperature. The inter-regional variation of ∑ 11 OPEs in Southeast Asia was related to population and economic development in each region. Airflow trajectories indicated that the OPEs in this region were mainly from local sources. The health risk assessment revealed that the inhalation exposure risks of OPEs to the residents in the study areas were very low during the sampling period, but may be increasing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Excitation-emission matrix (EEM) fluorescence spectroscopy is a widely-used method for characterizing the chemical components of brown carbon (BrC). However, the molecular basics and formation mechanisms of chromophores, which are decomposed by parallel factor (PARAFAC) analysis, are not yet fully understood. In this study, we characterized the water-soluble organic carbon (WSOC) in aerosols collected from Karachi, Pakistan, using EEM spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). We identified three PARAFAC components, including two humic-like components (C1 and C2) and one phenolic-like species (C3). We determined the molecular families associated with each component by performing Spearman correlation analysis between FT-ICR MS peaks and PARAFAC component intensities. We found that the C1 and C2 components were associated with nitrogen-enriched compounds, where C2 with the longest emission wavelength exhibited a higher level of aromaticity, N content, and oxygenation than C1. The C3 associated formulas have fewer nitrogen-containing species, a lower unsaturation degree, and a lower oxidation state. An oxidation pathway was identified as an important process in the formation of C1 and C2 components at the molecular level, particularly for the assigned CHON compounds associated with the gas-phase oxidation process, despite their diverse precursor types. Numerous C2 formulas were found in the "potential BrC" region and overlapped with the BrC-associated formulas. It can be inferred that the compounds that fluoresce C2 contributed considerably to the light absorption of BrC. These findings are essential for future studies utilizing the EEM-PARAFAC method to explore the sources, processes, and compositions of atmospheric BrC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The production and use of intentionally-produced polychlorinated biphenyls (PCBs) in China have a short history compared with countries of North America and Europe, where technical PCB mixtures were manufactured in large amounts for decades before being banned. Unintentionally-produced PCB emissions increased dramatically in China, leading to unique profiles of PCB burdens. This study first time evaluated 208 individual PCB congeners at 94 sites from surface sediments of the East China Marginal Seas (ECMSs) and explored their sources. Non-technical PCBs transported from atmospheric transport and river discharge played a dominant role in most areas of the ECMSs, while historical residuals of technical PCBs occupied the fine-grained sediments in muddy areas of the central Yellow Sea (YS), regarding to the low sedimentation rate in the central YS. Furthermore, emissions from Taizhou located on the coast of the East China Sea (ECS), which is an important electronic waste dismantling site in East China, contributed additional technical PCBs to the inner shelf of the ECS. Our results indicate that non-technical PCBs have become the dominant PCB species in the ECMSs, and emphasize the synergistic effects of large riverine input, long-range atmospheric transport, and muddy shelf deposition on PCB source and sink of in marginal seas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Hexachlorocyclohexanes (HCHs) are a group of highly persistent pesticides. The concentrations of HCHs and the enantiomeric fractions of α-HCH in the O- and A-horizons from 30 mountains across China were analyzed in this study. The concentrations of total HCHs ranged from 0.061 to 46.9 ng/g (mean 2.12 ng/g) and 0.046 to 16.1 ng/g (mean 0.792 ng/g) in the O- and A-horizons, respectively. The HCH residues were mainly derived from the historical applications of technical HCH and lindane. Higher concentrations of HCHs were typically found in northern China, and no significant correlations were found between historical technical HCH usage and HCH isomer concentrations in either the O- or A-horizons (p > 0.05). Conversely, the concentrations of HCH isomers were significantly correlated with the environmental parameters (temperature and precipitation), thus indicating a typical secondary distribution pattern. Some HCH isomers tended to be transported northward under the long-term effect of monsoon. Chiral α-HCH was non-racemic in soils and showed preferential degradation of (-) α-HCH in both the O- and A-horizons. The transformation from γ-HCH to α-HCH might alter the enantiomeric signatures of α-HCH in soils. Moreover, the deviation from racemic of α-HCH was positively correlated with the C/N ratio in the A-horizon (p < 0.01), thus suggesting that the C/N ratio could alter the microbial activity and significantly affect the enantioselective degradation extent of α-HCH in soils., Competing Interests: Declaration of competing interest The authors state that they have no known competitive financial interests or personal relationships, which may affect the work reported in this article. All authors were directly involved in the execution and/or analysis of this study. The contents of this manuscript have not been previously copyrighted or published. We declare that we have no commercial or affiliated interests that represent a conflict of interest in connection with the submitted work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Plant height is a key agronomic trait that affects yield and is controlled by both phytohormone gibberellin (GA) and ultraviolet-B (UV-B) irradiation. However, whether and how plant height is modulated by UV-B-mediated changes in GA metabolism are not well understood. It has not been reported that the E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) is involved in the regulation of plant growth in response to environmental factors. We perform a forward genetic screen in soybean and find that a mutation in Glycine max Increased Leaf Petiole Angle1 (GmILPA1), encoding a subunit of the APC/C, lead to dwarfism under UV-B irradiation. UV-B promotes the accumulation of GmILPA1, which ubiquitinate the GA catabolic enzyme GA2 OXIDASE-like (GmGA2ox-like), resulting in its degradation in a UV-B-dependent manner. Another E3 ligase, GmUBL1, also ubiquitinate GmGA2ox-like and enhance the GmILPA1-mediated degradation of GmGA2ox-like, which suggest that GmILPA1-GmGA2ox-like module counteract the UV-B-mediated reduction of bioactive GAs. We also determine that GmILPA1 is a target of selection during soybean domestication and breeding. The deletion (Indel-665) in the promoter might facilitate the adaptation of soybean to high UV-B irradiation. This study indicates that an evolutionary GmILPA1 variant has the capability to develop ideal plant architecture with soybean cultivars., (© 2023. Springer Nature Limited.)

Aerosol black carbon (BC) is a short-lived climate pollutant. The poorly constrained provenance of tropical marine aerosol BC hinders the mechanistic understanding of extreme climate events and oceanic carbon cycling. Here, we collected PM 2.5 samples during research cruise NORC2016-10 through South China Sea (SCS) and Northeast Indian Ocean (NEIO) and measured the dual-carbon isotope compositions (δ 13 C- Δ 14 C) of BC using hydrogen pyrolysis technique. Aerosol BC exhibits six different δ 13 C- Δ 14 C isotopic spaces (i.e., isotope provinces). Liquid fossil fuel combustion, from shipping emissions and adjacent land, is the predominant source of BC over isotope provinces "SCS close to Chinese Mainland" (53.5%), "Malacca Strait" (53.4%), and "Open NEIO" (40.7%). C 3 biomass burning is the major contributor to BC over isotope provinces "NEIO close to Southeast Asia" (55.8%), "Open NEIO" (41.3%), and "Open SCS" (40.0%). Coal combustion and C 4 biomass burning show higher contributions to BC over "Sunda Strait" and "Open SCS" than the others. Overall, NEIO near the Bay of Bengal, Malacca Strait, and north SCS are three hot spots of fossil fuel-derived BC; the first two areas are also hot spots of biomass-derived BC. The comparable δ 13 C- Δ 14 C between BC in aerosol and dissolved BC in surface seawater may suggest atmospheric BC deposition as a potential source of oceanic dissolved BC.

This study was designed to assess the distribution of organochlorines (OCs) in fish species, their spatio-temporal variations, bioaccumulation potential, and associated human health risks via dietary intake. The levels of twenty-three organochlorine pesticides (OCPs) and thirty-five polychlorinated biphenyls (PCBs) were analyzed in six fish species collected from the riverine ecosystem of Punjab Province, Pakistan. The results indicated that the mean levels of Σ 23 OCPs were 74.1 ng/g ww and 184 ng/g ww, and for Σ 35 PCBs the levels were 38.8 ng/g ww and 74.8 ng/g ww in herbivorous and carnivorous fish species, respectively. The most abundant contaminants in all fish species were DDTs (65%) and HCHs (14%) among OCPs and heavier PCB congeners (62%) among PCBs. As for dioxin-like PCBs, the WHO toxic equivalency values (ng TEQ/g ww) were in the range of 0.21 (Cyprinus Carpio) to 2.38 (Rita Rita), exceeding the maximum allowable limit of 0.004 ng TEQ/g, ww by the European Commission. Spatio-temporal analysis indicated relatively higher OC levels in winter season with elevated concentrations in fish samples from industrial zone. The bioconcentration factor (L/kg) values ranged from 723 to 2773 for PCBs and 315 to 923 for OCPs in all fish species, with higher levels were reported in carnivorous species. The human health risk assessment at both 50th and 95th percentiles revealed the absence of any significant non-carcinogenic risk as calculated HR was less than 1. However, the critical carcinogenic risk was found to be associated for most of the contaminants, signifying the dietary exposure to OCPs and PCBs might pose the public health concern., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in paired ambient and surface air fugacity samples were measured in the Tibetan Plateau (TP) from 2019 to 2022. The air concentrations of previously intentionally produced chemicals like dichlorodiphenyltrichloroethane (DDT) and hexachlorocyclohexane (HCH) declined. Their soil-air exchange direction ranged from equilibrium to volatilization, suggesting that the TP is acting as a secondary source of most OCPs and PCBs with the pollution alleviation. However, considerably high atmospheric levels of PCB-11, an indicator of unintentionally produced PCBs (UP-PCBs), were recorded in the southern TP. Strong episodic long-range atmospheric transport (LRAT) and deposition of PCB-11 events took place mostly in summer. Those events associated with winds from potential sources and less rainfall interception along the air mass transport routes accounted for a significant fraction of overall atmospheric deposition in the TP. Meanwhile, cryoturbation and plowing are suspected to be important factors contributing to the reemission of PCB-11 from surface soil. The high abundance of PCB-11 and strong deposition/evaporation events highlights potential environmental and health risks of UP-POPs in the TP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The aim of the present study was to determine the occurrence, spatio-temporal variations, source apportioning, and ecological risk assessment of selected PCBs and OCPs in surface water and sediments collected riverine environment of Punjab province, Pakistan. The concentration of ΣOCPs (water: 64-455 ng/L; sediments: 117-616 ng/g) and ΣPCBs (water: 2-132 ng/L; sediments: 3.27-200 ng/g) was found comparatively higher than the levels reported from other parts of the world. The higher concentrations of DDTs and HCHs were detected in both studied matrices, whereas among PCBs, CB-28, 49 and CB-37, 82 were dominant in water and sediments, respectively. The isomeric ratios including α-HCH/γ-HCH, (DDE + DDD) / DDTs, and α /β-endosulfan reflected the recent use of lindane, technical DDT, and endosulfan in the study area. The WHO-TEQ values of DL-PCBs ranged from 3.6 × 10 -6 to 0.115 ng/L and 8.7 × 10 -6 to 0.157 ng/g in surface water and sediments in both seasons, respectively. The spatial variation analysis revealed that the sites in the industrial and agricultural zones were highly contaminated. The OCPs and PCBs fluxes to downstream areas were estimated to be 12.4 tons/year and 1.9 tons/year, respectively. The significant ecological risks were estimated to be posed by OCPs and PCBs, as their levels in 67% and 62% of surface water and sediment samples were exceeding the threshold limits, highlighting effects to ecological integrities., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Biomass burning (BB) is an important source of atmospheric persistent organic pollutants (POPs) across the world. However, there are few field-based regional studies regarding the POPs released from BB. Due to the current limitations of emission factors and satellites, the contribution of BB to airborne POPs is still not well understood. In this study, with the simultaneous monitoring of BB biomarkers and POPs based on polyurethane foam-based passive air sampling technique, we mapped the contribution of BB to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in the Indo-China Peninsula. Spearman correlations between levoglucosan and 16 PCBs ( r s = 0.264-0.767, p < 0.05) and 2 OCPs ( r s = 0.250-0.328, p < 0.05) confirmed that BB may facilitate POP emissions. Source apportionment indicated that BB contributed 9.3% to the total PCB and OCP mass. The high contribution of positive matrix factorization-resolved BB to PCBs and OCPs was almost consistent with their concentration distributions in the open BB season but not completely consistent with those in the pre-monsoon and/or monsoon seasons. Their contribution distributions may reflect the use history and geographic distribution in secondary sources of POPs. The field-based contribution dataset of BB to POPs is significant in improving regional BB emission inventories and model prediction.

Wearing of vehicle parts could release many chemical additives into the environment, such as benzotriazoles (BTRs), benzothiazoles (BTHs), and p-phenylenediamines (PPDs), which are potentially toxic to wildlife and humans. This study investigated the occurrence, source, and risks of BTRs, BTHs, and PPDs in a source catchment providing water to Guangzhou, a megacity in South China, covering groundwater, surface water, and stormwater. The results showed that BTRs and BTHs were predominant in surface water and groundwater. Unexpectedly, the BTR and BTH concentrations were lower in surface water than groundwater in a third of the paired samples. For the first time, 6PPD-quinone, a toxic ozonation product of N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (6PPD), was extensively detected in source waters. Stormwater decreased the BTR concentrations but increased the 6PPD-quinone concentrations in surface water owing to their affiliation to suspended particles. From natural to urban segments of Liuxi river, a downstream increasing trend in BTR and BTH concentrations was observed, confirming that they are indicative of urban anthropogenic activities. Strong correlations between industrial activities and BTR or BTH concentrations in surface water indicated that industrial activities were their main sources. Six compounds were prioritized as potentially persistent, mobile, and toxic (PMT) chemicals, combing our monitoring results and REACH criterion. This study improves our understanding of the environmental fates and risks of water-soluble tire-wear chemicals, which provides important information for chemical management, and indicates attention should be paid to the risk posed by 6PPD-quinone in the source water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Field-based sampling can provide more accurate evaluation than MODIS in regional biomass burning (BB) emissions given the limitations of MODIS on unresolved fires. Polyurethane foam-based passive air samplers (PUF-PASs) are a promising tool for collecting atmospheric monosaccharides. Here, we deployed PUF-PASs to monitor monosaccharides and other BB-related biomarkers and presented a dataset of 31 atmospheric BB-related biomarkers in the Indo-China Peninsula (ICP) and Southwest China. The peak concentrations of monosaccharides in the ICP occurred before monsoon season. The highest concentrations were in the eastern Mekong plain, while the lowest were along the eastern coast. BB-related biomarkers displayed elevated concentrations after April, particularly in the monsoon season; however, fewer active fires were recorded by MODIS. This revealed the importance of MODIS unresolved fires (e.g., indoor biofuel combustion, small-scale BB incidents, and charcoal fires) to the regional atmosphere. The PAS derived levoglucosan concentrations indicated that, with the inclusion of MODIS unresolved fires, the estimated top-down emissions of PM (4194-4974 Gg/yr), OC (1234-1719 Gg/yr) and EC (52-384 Gg/yr) would be higher than previous bottom-up estimations in the ICP. Future studies on these MODIS unresolved fires and regional monitoring data of BB are vital for improving the modeling of regional BB emissions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

The global incidence rate of non-alcoholic fatty liver disease (NAFLD) is approximately 25%. With the global increase in obesity and its associated metabolic syndromes, NAFLD has become an important cause of chronic liver disease in many countries. Despite recent advances in pathogenesis, diagnosis, and therapeutics, there are still challenges in its treatment. In this review, we briefly describe diagnostic methods, therapeutic targets, and drugs related to NAFLD. In particular, we focus on evaluating carbohydrate and lipid metabolism, lipotoxicity, cell death, inflammation, and fibrosis as potential therapeutic targets for NAFLD. We also summarized the clinical research progress in terms of drug development and combination therapy, thereby providing references for NAFLD drug development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fu, Zhou, Shen, Li, Zhang, Cui, Zhang, Li, Chen, Zhao, Li and Ye.)

Incomplete understanding of the sources of secondary organic aerosol (SOA) leads to large uncertainty in both air quality management and in climate change assessment. Chemical reactions occurring in the atmospheric aqueous phase represent an important source of SOA mass, yet, the effects of anthropogenic emissions on the aqueous SOA (aqSOA) are not well constrained. Here we use compound-specific dual-carbon isotopic fingerprints (δ 13 C and Δ 14 C) of dominant aqSOA molecules, such as oxalic acid, to track the precursor sources and formation mechanisms of aqSOA. Substantial stable carbon isotope fractionation of aqSOA molecules provides robust evidence for extensive aqueous-phase processing. Contrary to the paradigm that these aqSOA compounds are largely biogenic, radiocarbon-based source apportionments show that fossil precursors produced over one-half of the aqSOA molecules. Large fractions of fossil-derived aqSOA contribute substantially to the total water-soluble organic aerosol load and hence impact projections of both air quality and anthropogenic radiative forcing. Our findings reveal the importance of fossil emissions for aqSOA with effects on climate and air quality., (© 2022. The Author(s).)

Total suspended particles (TSP) and gaseous samples were collected by using a high-volume sampler from March 2012 to March 2013 and January 2018 to January 2019 at a background site (Jinsha, JSH) in central China to study the chemical characteristics, seasonal variations, and potential sources of polycyclic aromatic hydrocarbons (PAHs). The average concentrations of ∑ 15 PAHs were 24.55 ± 9.19 ng m -3 in 2012/2013 and 20.98 ± 9.77 ng m -3 in 2018/2019. Low-ring PAHs were more concentrated in gas phase while high-ring PAHs were prone into particle phase. The concentrations of PAHs in the two sampling years were high in winter but low in summer and autumn. The relationships between the gas concentrations of PAHs and temperature indicated that most PAHs were influenced by long-range atmospheric transport (LRAT) in 2012/2013 and in 2018/2019, excluding anthracene (Ant) and pyrene (Pyr) were partially affected by air-surface re-volatilization in 2012/2013. The source of atmospheric PAHs at JSH was similar in 2012/2013 and 2018/2019,which was mainly due to the LRAT of PAHs emitted from biomass/fossil fuel combustion in the northern area of JSH. From 2012/2013 to 2018/2019, there was no significant difference between the concentrations of PAHs in spring and winter, whereas the concentrations of PAHs decreased from 2012/2013 to 2018/2019 in summer. In all, the control of PAHs at the source region was partially effective from 2012/2013 to 2018/2019., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Obtaining homogeneous blends of two covalently cross-linked polymers by mechanical mixing is not possible due to their permanent network topologies. Here, we demonstrate an effective route to prepare polymer blends from the common cross-linked epoxidized natural rubber (ENR) and epoxy resin vitrimer (EV) by mechanical mixing. Interfacial exchange reactions between these two networks occur by a dynamic transesterification. The as-prepared ENR-EV blends show excellent mechanical strength, extensibility, and thermal stability. Moreover, they also show typical vitrimeric properties, including self-healing, welding, and reprocessability. This work demonstrates a large-scale preparation of vitrimeric materials with high performance and versatility from commercially available polymers and affords a promising strategy to recycle both waste rubbers and resins.

Oxidative stress is a key mechanism by which ambient particulate matter induces adverse health effects. Most studies have focused on the oxidative potential (OP) of water-soluble constituents, while there has been limited work on the OP of solvent-extractable organic matter (EOM OP). In this study, the EOM OP of ambient total suspended particulate (TSP) from Bangkok, Thailand, was determined using the dithiothreitol (DTT) assay. Positive matrix factorization (PMF), combined with chemical analysis of molecular markers, was employed to apportion the contributions of various emission sources to EOM OP. The volume-normalized OP initially increased with organic carbon (OC) concentration and plateaued gradually, while the mass-normalized OP fitted well with OC concentration using a power function. Fossil fuel combustion (62%) and plastic waste burning (23%) were the major contributors to EOM OP, while biomass burning demonstrated only a limited contribution. EOM OP correlated well with each group of polycyclic aromatic hydrocarbons (PAHs), suggesting that secondary formation of quinones associated with fossil fuel combustion and plastic waste burning could be an important pathway of TSP toxicity. This study underscores the importance of considering different emission sources when evaluating potential health impacts and the implementation of air pollution regulations.

TGR5 is emerging as an important and promising target for the treatment of non-alcoholic steatohepatitis, type 2 diabetes mellitus (T2DM), and obesity. A series of novel 3-phenoxypyrazine-2-carboxamide derivatives were designed, synthesized and evaluated in vitro and in vivo . The most potent compounds 18g and 18k exhibited excellent hTGR5 agonist activity, which was superior to those of the reference drug INT-777. In addition, compound 18k could significantly reduce blood glucose levels in C57 BL/6 mice and stimulate GLP-1 secretion in NCI-H716 cells and C57 BL/6 mice., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

To discover antifungal compounds with broad-spectrum and stable metabolism, a series of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives was designed and synthesized. Compounds A30-A34 exhibited excellent broad-spectrum antifungal activity against Candida albicans with MIC values in the range of 0.03-0.5 μg/mL, and against Cryptococcus neoformans and Aspergillus fumigatus with MIC values in the range of 0.25-2 μg/mL. In addition, compounds A31 and A33 showed high metabolic stability in human liver microsomes in vitro, with the half-life of 80.5 min and 69.4 min, respectively. Moreover, compounds A31 and A33 showed weak or almost no inhibitory effect on the CYP3A4 and CYP2D6. The pharmacokinetic evaluation in SD rats showed that compound A31 had suitable pharmacokinetic properties and was worthy of further study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Organophosphate esters (OPEs) are still produced and used in large quantities in the world-wide, and the environmental burden and behavior have generated widespread concern, especially in some large-scale waterbodies. This study conducted a comprehensive assessment on the temporal and spatial variabilities and budget of OPEs to trace the source for the Bohai Sea (BS), based on a 5-year seasonal monitoring campaign (June 2014 to May 2019) of 12 atmospheric sites around the BS and our previous studies. The average concentration of Σ 10 OPEs in atmosphere during the sampling period was 7.65 ± 6.42 ng m -3 , and chlorinated OPEs were the major compounds. The Seasonal-Trend decomposition procedure based on Loess (STL) analyzed that during the 5-year sampling period, the atmospheric concentrations of Σ 10 OPEs had a slightly increasing trend with a rate of + 0.092 ng m -3 yr -1 , and the seasonal concentrations had a distinct seasonal distribution. The highest concentration of Σ 10 OPEs was observed at the sampling site of Dalian, followed by Tianjin, Yantai, and Beihuangcheng. The estimation of the fugacity ratios and air-water gas exchange fluxes established that the concentration levels of two major components of chlorinated OPEs (tris-(2-chloroethyl) phosphate (TCEP) and tris-(1-chloro-2-propyl) phosphate (TCPP)) in the atmosphere were dominated by their volatilization from BS's seawater (1.24 ± 0.46 t yr -1 for TCEP and 5.15 ± 2.15 t yr -1 for TCPP), with 73% deriving from the coastal seawater. The budget assessment suggested that the volatile fluxes of TCEP and TCPP accounted for 8% and 29% of their storages (15.6 ± 5.32 t for TCEP and 17.6 ± 6.70 t for TCPP) in the BS seawater, which were mainly contributed by continental river input (20% for TCEP and 42% for TCPP). The efforts indicated that river inputs of TCEP and TCPP needed to be paid more attention for the improvement of environmental quality of the BS., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A simple and efficient strategy to modify epoxy dynamic polymer networks (DPNs) is presented. The introduction of the flexible epoxidized form of naturally occurring soybean oil (ESO) into epoxy DPNs markedly improves their mechanical properties, stress relaxation rate and malleability. Specifically, at 7.5 wt% ESO loading, the elongation at break of the as-produced epoxy-ESO DPNs was increased from 10% to 108%, the stress relaxation time decreased from 6100 s to 2570 s at 120 °C, and the reprocessing temperature was reduced by 26 °C, which is advantageous for expanding the scope of applications of these materials, especially for reducing the energy consumption during reprocessing. At this composition, the epoxy-ESO DPNs also showed excellent self-healing, welding and chemical degradation properties. This work provides a novel pathway to fabricate epoxy-based DPNs with high performance in an energy-conserving manner.

Recovery of platinum group metals (PGMs) from secondary resources has attracted worldwide attention from environmental and economic points of view. Pyrometallurgical routes exhibit the superiority in terms of efficiency and contamination control compared to hydrometallurgical process. However, traditional pyrometallurgical processes face the challenges of excessive flux and energy consumption. In this paper, an iron capture process was proposed to recover low-grade PGMs from leaching residue of spent auto-exhaust catalysts. Slag design was explored aimed at reducing the addition amount of flux. The optimized smelting conditions were as follows: 1400 °C for 30 min, adding 40.0 wt% CaO, 22.7 wt% Na 2 CO 3 , 5.0 wt% Na 2 B 4 O 7 , 5.0 wt% CaF 2 , 15.0 wt% Fe, and 5.0 wt% C. The concentrations of Pt, Pd and Rh remaining in the smelting slag were 0.83 g/t, 4.99 g/t, and 1.47 g/t, respectively. Furthermore, the 50 kg-scale experiment implied positive economic feasibility because of saving flux dosage and smelting time. The capture mechanism was revealed by investigating the formation of the metals phase and slag phase. Matrix formed slag phase and separate with metals phase owing to differences in chemical bonding, density, viscosity, and surface tension. PGMs were proved solubilized in α-Fe as substitutional solid solutions. The formation energies for FePt, FePd, and FeRh alloys were -4.149 eV, -4.040 eV, and -4.360 eV, respectively. Finally, the obtained CaO-SiO 2 -Al 2 O 3 -Na 2 O glass slag was used for producing glass ceramics. To sum up, the iron capture process realized low energy and material consumption, high recovery efficiency of PGMs, and resource utilization of the glass slag., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Airborne particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) are significant contributors leading to many human health issues. Thus, this study was designed to perform chemical analysis and biological impact of airborne particulate matter 10 (PM 10 ) in the World heritage City of Kandy City in Sri Lanka. 12 priority PAHs and 34 metals, including 10 highly toxic HMs were quantified. The biological effects of organic extracts were assayed using an in vitro primary porcine airway epithelial cell culture model. Cytotoxicity, DNA damage, and gene expressions of selected inflammatory and cancer-related genes were also assessed. Results showed that the total PAHs ranged from 3.062 to 36.887 ng/m 3 . The metals were dominated by Na > Ca > Mg > Al > K > Fe > Ti, while a few toxic HMs were much higher in the air than the existing ambient air quality standards. In the bioassays, a significant cytotoxicity (p < 0.05) was observed at 300 μg/mL treatment, and significant (p < 0.05) DNA damages were noted in all treatment groups. All genes assessed were found to be significantly up-regulated (p < 0.05) after 24 h of exposure and after 48 h, only TGF-β1 and p53 did not significantly up-regulate (p < 0.05). These findings confirm that the Kandy city air contains potential carcinogenic and mutagenic compounds and thus, exposure to Kandy air may increase the health risks and respiratory tract-related anomalies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

To investigate photochemical ozone (O 3 ) pollution in urban areas in China, O 3 and its precursors and meteorological parameters were simultaneously measured in five megacities in China in summer 2018. Moderate wind speeds, strong solar radiation and high temperature were observed in all cities, indicating favorable meteorological conditions for local O 3 formation. However, the unusually frequent precipitation caused by typhoons reaching the eastern coastline resulted in the least severe air pollution in Shanghai. The highest O 3 level was found in Beijing, followed by Lanzhou and Wuhan, while relatively lower O 3 value was recorded in Chengdu and Shanghai. Photochemical box model simulations revealed that net O 3 production rate in Lanzhou was the largest, followed by Beijing, Wuhan and Chengdu, while it was the lowest in Shanghai. Besides, the O 3 formation was mainly controlled by volatile organic compounds (VOCs) in most cities, but co-limited by VOCs and nitrogen oxides in Lanzhou. Moreover, the dominant VOC groups contributing to O 3 formation were oxygenated VOCs (OVOCs) in Beijing and Wuhan, alkenes in Lanzhou, and aromatics and OVOCs in Shanghai and Chengdu. Source apportionment analysis identified six sources of O 3 precursors in these cities, including liquefied petroleum gas usage, diesel exhaust, gasoline exhaust, industrial emissions, solvent usage, and biogenic emissions. Gasoline exhaust dominated the O 3 formation in Beijing, and LPG usage and industrial emissions made comparable contributions in Lanzhou, while LPG usage and solvent usage played a leading role in Wuhan and Chengdu, respectively. The findings are helpful to mitigate O 3 pollution in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

l-amino alcohol derivatives exhibited high antifungal activity, but the metabolic stability of human liver microsomes in vitro was poor, and the half-life of optimal compound 5 was less than 5 min. To improve the metabolic properties of the compounds, the scaffold hopping strategy was adopted and a series of antifungal compounds with a dihydrooxazole scaffold was designed and synthesized. Compounds A33-A38 substituted with 4-phenyl group on dihydrooxazole ring exhibited excellent antifungal activities against C. albicans, C. tropicalis and C. krusei, with MIC values in the range of 0.03-0.25 μg/mL. In addition, the metabolic stability of compounds A33 and A34 in human liver microsomes in vitro was improved significantly, with the half-life greater than 145 min and the half-life of 59.1 min, respectively. Moreover, pharmacokinetic studies in SD rats showed that A33 exhibited favourable pharmacokinetic properties, with a bioavailability of 77.69%, and half-life (intravenous administration) of 9.35 h, indicating that A33 is worthy of further study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Secondary aluminum dross (SAD) from aluminum industry is classified as a hazardous solid waste due to containing aluminum nitride (AlN). In this work, AlN was first used to reduce heavy metals by pyrometallurgy. The reduction rates for iron, chromium and nickel were up to 90%, 80% and 100%, respectively. However, the reduction from AlN and oxygen oxidization of AlN occurred simultaneously. AlN which formed solid solution with alumina could reduce heavy metals, while the rest was oxidized by oxygen. In addition, the reduction rates for iron and chromium could be increased with increasing CaF 2 from 6.7 to 9.0 wt%. CaF 2 could decreased viscosity of molten slag, which favored the ion migration, and then increased the reduction rates. After the reduction, glass ceramics were manufactured from the molten slags. The bending strength, microhardness and alkali resistance of the glass ceramics were up to 77 MPa, 1011 HV and 98.7%, respectively. According to XRD and SEM results, glass ceramics with CaAl 2 SiO 6 crystal phase, crosslinked network structure grains and smaller pores exhibited better bending resistance. In addition, glass ceramics with CaAl 2 SiO 6 crystal phase possessed the highest microhardness and alkali resistance. After this process, hazardous pickling sludge and SAD were totally recycled., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ischemia/reperfusion (I/R) injury refers to the functional and structural changes in the process of blood flow recovery after ischemia. In addition to ischemia, the blood flow recovery can also lead to very harmful damage, such as the obvious cell swelling and the irreversible cell necrosis. I/R injury is related with many diseases, including myocardial I/R injury. Myocardial I/R injury refers to the aggravation of ischemic myocardial tissue injury due to sudden disorder of blood circulation. Although there are many studies on myocardial I/R injury, the exact mechanism is not fully understood. Hydrogen sulfide (H 2 S), like carbon monoxide and nitric oxide, is an important gas signal molecule. It plays an important role in many physiological and pathological processes. Recent studies indicate that H 2 S can improve myocardial I/R injury, however, its mechanism is not fully understood, especially the involved signal pathways. In this review, we summarize the related researches about the role of the signaling pathways involved in the protective effects of exogenous H 2 S on myocardial I/R injury, so as to provide theoretical reference for the future in-depth researches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lv, Li, Zhao, Liu and Wang.)

An increasing number of alternative flame retardants (FRs) are being introduced, following the international bans on the use of polybrominated diphenyl ether (PBDE) commercial mixtures. FRs' production capacity has shifted from developed countries to developing countries, with China being the world's largest producer and consumer of FRs. These chemicals are also imported with e-waste to China. Therefore, it is important to understand the current status of regulated brominated FRs, their phase-out in China, and their replacement by alternatives. In this study, a broad suite of legacy and alternative FRs, including eight PBDEs, six novel brominated FRs (NBFRs), two dechlorane plus variants (DP S ), and 12 organophosphate FRs (OPFRs) were evaluated in the air of 10 large Chinese cities in 2018. OPFRs are the most prevalent FRs in China, exhibiting a wide range of 1-612 ng/m 3 , which is several orders of magnitude higher than PBDEs (1-1827 pg/m 3 ) and NBFRs (1-1428 pg/m 3 ). BDE 209 and DBDPE are the most abundant compounds in brominated FRs (>80%). The North China Plain (NCP, excluding Beijing), Guangzhou, and Lanzhou appear to be three hotspots, although with different FR patterns. From 2013/2014 to 2018, levels of PBDEs, NBFRs, and DPs have significantly decreased, while that of OPFRs has increased by 1 order of magnitude. Gas-particle partitioning analysis showed that FRs could have not reached equilibrium, and the steady-state model is better suited for FRs with a higher log K OA (>13). To facilitate a more accurate FR assessment in fine particles, we suggest that, in addition to the conventional volumetric concentration (pg/m 3 ), the mass-normalized concentration (pg/g PM 2.5 ) could also be used.

Although organochlorine pesticides (OCPs) have been banned for more than three decades, their concentrations have only decreased gradually. This may be largely attributable to their environmental persistence, illegal application, and exemption usage. This study assessed the historic and current regional context for dichlorodiphenyltrichloroethane (DDT), chlordane, and hexachlorobenzene (HCB), which were added to the Stockholm Convention in 2001. An air sampling campaign was carried out in 2018 in nine cities of the Pearl River Delta (PRD), where the historical OCP application was the most intensive in China. Different seasonalities were observed: DDT exhibited higher concentrations in summer than in winter; chlordane showed less seasonal variation, whereas HCB was higher in winter. The unique coupling of summer monsoon with DDT-infused paint usage, winter monsoon with HCB-combustion emission, and local chlordane emission jointly presents a dynamic picture of these OCPs in the PRD air. We used the BETR Global model to back-calculate annual local emissions, which accounted for insignificant contributions to the nationally documented production (<1‰). Local emissions were the main sources of p,p' -DDT and chlordane, while ocean sources were limited (<4%). This study shows that geographic-anthropogenic factors, including source, history, and air circulation pattern, combine to affect the regional fate of OCP compounds.

Understanding the intra-city variation of PM 2.5 is important for air quality management and exposure assessment. In this study, to investigate the spatiotemporal variation of PM 2.5 in Guangzhou, we developed land use regression (LUR) models using data from 49 routine air quality monitoring stations. The R 2 , adjust R 2 and 10-fold cross validation R 2 for the annual PM 2.5 LUR model were 0.78, 0.72 and 0.66, respectively, indicating the robustness of the model. In all the LUR models, traffic variables (e.g., length of main road and the distance to nearest ancillary) were the most common variables in the LUR models, suggesting vehicle emission was the most important contributor to PM 2.5 and controlling vehicle emissions would be an effective way to reduce PM 2.5 . The predicted PM 2.5 exhibited significant variations with different land uses, with the highest value for impervious surfaces, followed by green land, cropland, forest and water areas. Guangzhou as the third largest city that PM 2.5 concentration has achieved CAAQS Grade II guideline in China, it represents a useful case study city to examine the health and economic benefits of further reduction of PM 2.5 to the lower concentration ranges. So, the health and economic benefits of reducing PM 2.5 in Guangzhou was further estimated using the BenMAP model, based on the annual PM 2.5 concentration predicted by the LUR model. The results showed that the avoided all cause mortalities were 992 cases (95% CI: 221-2140) and the corresponding economic benefits were 1478 million CNY (95% CI: 257-2524) (willingness to pay approach) if the annual PM 2.5 concentration can be reduced to the annual CAAQS Grade I guideline value of 15 μg/m 3 . Our results are expected to provide valuable information for further air pollution control strategies in China., Competing Interests: Declaration of competing interest We declare that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2021. Published by Elsevier B.V.)

There is a need for a simple water sampling technique to enable routine monitoring of community drug consumption through wastewater-based epidemiology (WBE). This study investigates the potential use of diffusive gradients in thin films to sample organic compounds (o-DGT) for WBE. Three types of resin gels (HLB, XAD 18, and XDA-1) within o-DGT samplers each were deployed in triplicate at the inlets of two sewage treatment plants of Southern Asian cities. The target compounds included 15 illicit drugs and 18 antibiotics. A comprehensive evaluation was undertaken regarding each resin's ability to accumulate the target compounds and accuracy by comparing active samples. The organic compounds accumulated on each resin gel were characterised at the molecular level using Fourier transform ion-cyclotron-resonance mass spectrometry (FT-ICR MS). The results showed that the HLB resin performed better than the XAD 18 and XDA-1 resins. Based on calculations using the HLB-DGT data, methamphetamine and heroin were the two most popular illicit drugs consumed among the studied populations, and were followed by ketamine and codeine, which agreed well with the authoritative reports and reference data. The total drug consumption in Hanoi was one order of magnitude higher than that in Guangzhou, thus implying a probably more serious drug situation in the former. Overall, the findings of this study demonstrate that o-DGT passive samplers are a promising tool for WBE studies, particularly at WWTPs or in urban streams where an automatic sampler for taking composite water samples is absent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Eva-1 homolog A (EVA1A) is regarded as TMEM166 (transmembrane protein 166) or FAM176A (family with sequence similarity 176) and a lysosome and endoplasmic reticulum-associated protein involved in regulating autophagy and apoptosis. EVA1A regulates embryonic neurogenesis, cardiac remodeling, islet alpha-cell functions, acute liver failure, and hepatitis B virus replication. However, the related mechanisms are not fully clear. Autophagy is a process in which cells transfer pathogens, abnormal proteins and organelles to lysosomes for degradation. It plays an important role in various physiological and pathological processes, including cancer, aging, neurodegeneration, infection, heart disease, development, cell differentiation and nutritional starvation. Recently, there are many studies on the important role of EVA1A in many physiological and pathological processes by regulating autophagy. However, the related molecular mechanisms need further study. Therefore, we summarize the above-mentioned researches about the role of EVA1A in physiological and pathological processes through regulating autophagy in order to provide theoretical basis for future researches.

Autophagy is a stable self-sustaining process in eukaryotic cells. In this process, pathogens, abnormal proteins, and organelles are encapsulated by a bilayer membrane to form autophagosomes, which are then transferred to lysosomes for degradation. Autophagy is involved in many physiological and pathological processes. Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, containing NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and pro-caspase-1, can activate caspase-1 to induce pyroptosis and lead to the maturation and secretion of interleukin-1 β (IL-1 β) and IL-18. NLRP3 inflammasome is related to many diseases. In recent years, autophagy has been reported to play a vital role by regulating the NLRP3 inflammasome in inflammatory nervous system diseases. However, the related mechanisms are not completely clarified. In this review, we sum up recent research about the role of the effects of autophagy on NLRP3 inflammasome in Alzheimer's disease, chronic cerebral hypoperfusion, Parkinson's disease, depression, cerebral ischemia/reperfusion injury, early brain injury after subarachnoid hemorrhage, and experimental autoimmune encephalomyelitis and analyzed the related mechanism to provide theoretical reference for the future research of inflammatory neurological diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Li, Wang and Wang.)

Endoplasmic reticulum (ER) is a kind of organelle with multiple functions including protein synthesis, modification and folding, calcium storage, and lipid synthesis. Under stress conditions, ER homeostasis is disrupted, which is defined as ER stress (ERS). The accumulation of unfolded proteins in the ER triggers a stable signaling network named unfolded protein response (UPR). Hydrogen sulfide is an important signal molecule regulating various physiological and pathological processes. Recent studies have shown that H 2 S plays an important role in many diseases by affecting ERS, but its mechanism, especially the signaling pathways, is not fully understood. Therefore, in this review, we summarize the recent studies about the signaling pathways involved in the effects of H 2 S on ERS in diseases to provide theoretical reference for the related in-depth researches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Li, Lu, Li, Sun and Wang.)

Takeda G-protein-coupled receptor 5 (TGR5) is emerging as an important and promising target for the development of anti-diabetic drugs. To understand the structural characteristics of TGR5 agonists, the common feature pharmacophore models were generated and molecular docking was performed. The ligand-based virtual screening combined with pharmacophore mapping and molecular docking was performed to identify novel nonsteroidal TGR5 agonists. Finally, 20 compounds were screened for in vitro TGR5 agonistic activity assay, and results showed most compounds exhibiting TGR5 agonistic activity at 40 μM. Among these compounds, V12 and V14 displayed obvious TGR5 agonist activity, with the EC 50 values of 19.5 μM and 7.7 μM, respectively. Compounds V12 and V14 could be considered potential TGR5 agonist candidates and also may be used as initial hits for developing novel TGR5 agonists., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Diabetic cardiomyopathy is an important complication of diabetes mellitus and the main cause of diabetes death. Diabetic cardiomyopathy is related with many factors, such as hyperglycemia, lipid accumulation, oxidative stress, myocarditis, and apoptosis. Hydrogen sulfide (H 2 S) is a newly discovered signal molecule, which plays an important role in many physiological and pathological processes. Recent studies have shown that H 2 S is involved in improving diabetic cardiomyopathy, but its mechanism has not been fully elucidated. This review summarizes the research on the roles and mechanisms of H 2 S in diabetic cardiomyopathy in recent years to provide the basis for in-depth research in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Li, Li, Wei and Wang.)

TGR5 is emerging as an important and promising target for the treatment of diabetes, obesity and other metabolic syndromes. A series of novel 1-benzyl-1H-imidazole-5-carboxamide derivatives was designed, synthesized and evaluated in vitro and in vivo. The most potent compounds 19d and 19e exhibited excellent agonistic activities against hTGR5, which was superior to those of the reference drugs INT-777 and LCA. In addition, compounds 19d and 19e exhibited good selectivity against FXR and presented significant glucose-lowering effects in vivo. Compound 19d could stimulate GLP-1 secretion by activating of TGR5., (Copyright © 2020. Published by Elsevier Ltd.)

Although some persistent organic pollutants (POPs) were prohibited or limited in use several decades ago, they are still frequently detected in the human body. The purpose of this study was to understand the levels and profiles of POPs in breast milk in China and assess their potential health risks among breastfed infants under six months of age. A literature review focused on China was performed for studies published from 2001 to 2020. The POP levels in breast milk along with other important variables were extracted, and then the average individual POP levels in breast milk were estimated. This review summarises the distribution of traditional and new POPs, including polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), legacy brominated flame retardants (BFRs), perfluorinated compounds (PFCs), and chlorinated paraffins (CPs) and reported notably high levels of short-chain chlorinated paraffins and 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p'-DDE) in breast milk. Although the levels of traditional POPs generally declined over time, especially p,p'-DDE and beta-hexachlorocyclohexane (β-HCH), women living in coastal areas, urban areas, and southern China still have a high body burden of certain POPs. In the present study, the estimated daily intake (EDI) of POPs through breastfeeding was used to evaluate the health risk for infants by comparing with acceptable levels. The findings suggested that infants born in coastal areas most likely suffered potential health risk from exposure to DDT, and the health risk of hexachlorobenzene (HCB) in infants in most nationwide regions remains a concern. More importantly, the EDI of PCBs for infants exceeds the safe limit on a national scale. Continuous surveillance of PCBs in breast milk is critical to evaluate the potential health effects on humans., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Farnesoid X receptor (FXR) agonists would be considered as an important therapeutic strategy for several chronic liver and metabolic diseases. Here we have employed an integrated virtual screening by combining ligand-based pharmacophore mapping and molecular docking to identify novel nonsteroidal FXR agonists. Eighteen compounds were selected for in vitro FXR agonistic activity assay, and results showed five compounds exhibiting promising FXR agonistic activity. Among these compounds, compounds F4 and F17 were the most remarkable in vitro activity by using homogeneous time resolved fluorescence (HTRF) assay and the full-length FXR reporter gene assay in HepG2 cells. Real-time PCR assay was performed to measure the expression of FXR target genes. Compounds F4 and F17 increased small heterodimer partner (SHP), in turn, suppress mRNA levels of cholesterol 7-alpha-hydroxylase (CYP7A1). The obtained compounds F4 and F17 from this study may be potential leads for developing novel FXR agonists in the treatment of metabolic diseases., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Cyano-containing compounds constitute important pharmaceuticals, agrochemicals and organic materials. Traditional cyanation methods often rely on the use of toxic metal cyanides which have serious disposal, storage and transportation issues. Therefore, there is an increasing need to develop general and efficient catalytic methods for cyanide-free production of nitriles. Here we report the reductive cyanation of organic chlorides using CO 2 /NH 3 as the electrophilic CN source. The use of tridentate phosphine ligand Triphos allows for the nickel-catalyzed cyanation of a broad array of aryl and aliphatic chlorides to produce the desired nitrile products in good yields, and with excellent functional group tolerance. Cheap and bench-stable urea was also shown as suitable CN source, suggesting promising application potential. Mechanistic studies imply that Triphos-Ni(I) species are responsible for the reductive C-C coupling approach involving isocyanate intermediates. This method expands the application potential of reductive cyanation in the synthesis of functionalized nitrile compounds under cyanide-free conditions, which is valuable for safe synthesis of (isotope-labeled) drugs.

Multiple types of persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), and hexachlorobenzene (HCB), can be unintentionally released from combustion or thermal industrial processes, which are speculated to be the main sources of these contaminants, as they were banned on production and use since several decades ago. In this study, concentrations and sources of 40 PCBs, 39 PCNs, and HCB were analyzed in air samples collected during the period 2012-2015 at a background site in east China. ΣPCBs, ΣPCNs, and HCB were in the range of 9-341 pg/m 3 , 6-143 pg/m 3 , and 14-522 pg/m 3 , respectively. Seasonal characteristics with high levels in winter and low levels in summer were observed for PCNs and HCB. PCBs also exhibited slightly higher levels in winter. Source apportionment was conducted, using polycyclic aromatic hydrocarbons (PAHs) as combustion sources indicator, combined with principal component analysis (PCA) and positive matrix factorization (PMF) model. The results indicated that the legacy of past produced and used commercial PCBs was the dominant contributor (∼56%) to the selected PCBs in the atmosphere in east China. PCNs were mainly emitted from combustion sources (∼64%), whereas HCB almost entirely originated from combustion process (>90%)., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Volatile organic compounds (VOCs) are ubiquitous in the atmosphere and the majority of them have been proved to be detrimental to human health. The hazardous VOCs were studied very insufficiently in China, despite the enormous emissions of VOCs. In this study, the concentrations and sources of 17 hazardous VOCs reported in literature were reviewed, based on which the health effects were assessed. In-depth survey indicated that benzene and toluene had the highest concentrations in eastern China (confined to the study regions reviewed, same for the other geographic generalization), which however showed significant declines. The southern China featured high levels of trichloroethylene. Dichloromethane and chloroform were observed to be concentrated in northern China. The distributions of 1,2-dichloropropane and tetrachloroethylene were homogeneous across the country. Basically consistent with the spatial patterns of ozone, the summertime formaldehyde exhibited higher levels in eastern and northern China, and increased continuously. While transportation served as the largest source of benzene and toluene, industrial emissions and secondary formation were the predominant contributors of halogenated hydrocarbons and aldehydes (formaldehyde and acetaldehyde), respectively. The chronic non-cancer effects of inhalation exposure to the hazardous VOCs were insignificant, however the probabilities of developing cancers by inhaling the hazardous VOCs in ambient air of China were quite high. Formaldehyde was identified as the primary carcinogenic VOC in the atmosphere of most regions. The striking results, especially the high inhalation cancer risks, alerted us that the emission controls of hazardous VOCs were urgent in China, which must be grounded upon full understanding of their occurrence, presence and health effects., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Polychlorinated biphenyls (PCBs) were not widely manufactured or used in China before they became the subject of international bans on production. Recent work has shown that they have reached China associated with imported wastes and that there are considerable unintentional sources of PCBs that have only recently been identified. As such, it was hypothesized that the source inventory and profile of PCBs may be different or unique in China, compared to countries where they were widely used and which have been widely studied. For the first time in this study, we undertook a complete analysis of 209 PCB congeners and assessed the contribution of unintentionally produced PCBs (UP-PCBs) in the atmosphere of China, using polyurethane foam passive air samplers (PUF-PAS) deployed across a wide range of Chinese locations. ∑ 209 PCBs ranged from 9 to 6856 pg/m 3 (median: 95 pg/m 3 ) during three deployments in 2016-2017. PCB 11 was one of the most detected congeners, contributing 33 ± 19% to ∑ 209 PCBs. The main sources to airborne PCBs in China were estimated and ranked as pigment/painting (34%), metallurgical industry/combustion (31%), e-waste (23%), and petrochemical/plastic industry (6%). For typical Aroclor-PCBs, e-waste sources were dominated (>50%). Results from our study indicate that UP-PCBs have become the controlling source in the atmosphere of China, and an effective control strategy is urgently needed to mitigate emissions from multiple industrial sources.

A series of β-azole-phenylacetone derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible fungal infections and drug-resistant fungal infections. The antifungal activity of the synthesized compounds was assessed against five susceptible strains and five fluconazole-resistant strains. Antifungal activity tests showed that most of the compounds exhibited excellent antifungal activities against five pathogenic strains with MIC values in the range of 0.03-1 μg/mL. Compounds with R 1  = 3-F substituted and 15o and 15ae exhibited moderate antifungal activities against fluconazole-resistant strains 17# and CaR with MIC values in the range of 1-8 μg/mL. Compounds with R 1  = H or 2-F (such as 15a, 15o, 15p) displayed moderate to good antifungal activity against fluconazole-resistant strains 632, 901 and 904 with MIC values in the range of 0.125-4 μg/mL. Notably, 15o and 15ae exhibited antifungal activity against five susceptible strains and five fluconazole-resistant strains. Preliminary mechanistic studies showed that the potent antifungal activity of compound 15ae stemmed from inhibition of C. albicans CYP51. Compounds 15o, 15z and 15ae were nearly nontoxic to mammalian A549 cells., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

To further explore the structure activity relationships (SARs) of our previously discovered antifungal lead compound (1), a series of biphenyl imidazole analogues were designed, synthesized and evaluated for their in vitro antifungal activity. Many of the synthesized compounds showed excellent activity against Candida albicans and Candida tropicalis. Among these compounds, 2-F substituted analogue 12m displayed the most remarkable in vitro activity against C. albicans, C. neoformans, A. fumigatus and fluconazole-resistant C. alb. strains, which is superior or comparable to the activity of the reference drugs fluconazole and itraconazole. Notably, the compound 12m exhibited low inhibition profiles for various human cytochrome P450 isoforms and showed low toxicity to mammalian A549 cells and U87 cells. The SARs and binding mode established in this study will be useful for further lead optimization., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To discover broad spectrum antifungal agents, two strategies were applied, and a novel class of l-amino alcohol derivatives were designed and synthesized. 3-F substituted compounds 14i, 14n, 14s and 14v exhibited excellent antifungal activities with broad antifungal spectra against C. albicans and C. tropicalis, with MIC values in the range of 0.03-0.06 μg/mL, and against A. fumigatus and C. neoformans, with MIC values in the range of 1-2 μg/mL. Notably, Compounds 14i, 14n, 14s and 14v also displayed moderate activities against fluconazole-resistance strains 17# and CaR that were isolated from AIDS patients. Moreover, only compounds in the S-configuration showed antifungal activity. Preliminary mechanistic studies showed that the potent antifungal activity of compound 14v stemmed from inhibition of C. albicans CYP51. Compounds 14n and 14v were almost nontoxic to mammalian A549 cells, and their stability in human plasma was excellent., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)