Boundary exchange completes the marine Pb cycle jigsaw.

Material fluxes at the land-ocean interface impact seawater composition and global cycling of elements. However, most attention has been focused on the fluvial dissolved fluxes. For elements like lead (Pb), whose fluvial particulate flux into the ocean is two orders of magnitude higher than the dissolved counterpart, the role of particulates in elemental cycling is potentially important but currently less appreciated. Using both chemical analyses on samples collected from around equatorial Southeast Asia and model simulations, we show that particulate-dissolved exchange is an important mechanism controlling the concentration and isotopic composition of dissolved Pb in the ocean. Our model indicates that Pb contributed from particulate-dissolved exchange at ocean boundaries is larger than, or at least comparable to, other major Pb sources to the seawater before the Anthropocene, when the anthropogenic Pb was absent. Our work highlights the importance of boundary exchange in understanding marine element cycling and weathering-climate feedback.

Small extracellular vesicles' enrichment from biological fluids using an acoustic trap.

Small extracellular vesicles (sEVs), a form of extracellular vesicles, are lipid bilayered structures released by all cells. Large-scale studies on sEVs from clinical samples are necessary, but a major obstacle is the lack of rapid, reproducible, efficient, and low-cost methods to enrich sEVs. Acoustic microfluidics have the advantage of being label-free and biocompatible, which have been reported to successfully enrich sEVs. In this paper, we present a highly efficient acoustic microfluidic trap that can offer low and large volume compatible ways of enriching sEVs from biological fluids by flexible structure design. It uses the idea of pre-loading larger seed particles in the acoustic trap to enable sub-micron particle capturing. The microfluidic chip is actuated using a piezoelectric plate transducer attached to a silicon-glass bonding plate with circular cavities. Each cavity works as a resonant unit, excited at the frequency of both the half wave resonance in the main plane and inverted quarter wave resonance in the depth direction, which has the ability to strongly trap seed particles at the center, thereby improving the subsequent nanoparticle capture efficiency. Mean trapping efficiencies of 35.62% and 64.27% were obtained using 60 nm and 100 nm nanobeads, respectively. By the use of this technology, we have successfully enriched sEVs from cell culture conditioned media and blood plasma at a flow rate of 10 µL min-1. The isolated sEV subpopulations are characterized by NTA and TEM, and their protein cargo is determined by WB. This acoustic trapping chip provides a rapid and robust method to enrich sEVs from biofluids with high reproducibility and sufficient quantities. Therefore, it can serve as a new tool for biological and clinical research such as cancer diagnosis and drug delivery.

Development of a physiologically based pharmacokinetic model for levetiracetam in patients with renal impairment to guide dose adjustment based on steady-state peak/trough concentrations.

Levetiracetam may cause acute renal failure and myoclonic encephalopathy at high plasma levels, particularly in patients with renal impairment. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict levetiracetam pharmacokinetics in Chinese adults with epilepsy and renal impairment and define appropriate levetiracetam dosing regimen.PBPK models for healthy subjects and epilepsy patients with renal impairment were developed, validated, and adapted. Furthermore, we predicted the steady-state trough and peak concentrations of levetiracetam in patients with renal impairment using the final PBPK model, thereby recommending appropriate levetiracetam dosing regimens for different renal function stages. The predicted maximum plasma concentration (Cmax), time to maximum concentration (Tmax), area under the plasma concentration-time curve (AUC) were in agreement (0.8 ≤ fold error ≤ 1.2) with the observed, and the fold error of the trough concentrations in end-stage renal disease (ESRD) was 0.77 - 1.22. The prediction simulations indicated that the recommended doses of 1000, 750, 500, and 500 mg twice daily for epilepsy patients with mild, moderate, severe renal impairment, and ESRD, respectively, were sufficient to achieve the target plasma concentration of levetiracetam.

Identification of multiple odorant receptors essential for pyrethrum repellency in Drosophila melanogaster.

Pyrethrum extract from dry flowers of Tanacetum cinerariifolium (formally Chrysanthemum cinerariifolium) has been used globally as a popular insect repellent against arthropod pests for thousands of years. However, the mechanistic basis of pyrethrum repellency remains unknown. In this study, we found that pyrethrum spatially repels and activates olfactory responses in Drosophila melanogaster, a genetically tractable model insect, and the closely-related D. suzukii which is a serious invasive fruit crop pest. The discovery of spatial pyrethrum repellency and olfactory response to pyrethrum in D. melanogaster facilitated our identification of four odorant receptors, Or7a, Or42b, Or59b and Or98a that are responsive to pyrethrum. Further analysis showed that the first three Ors are activated by pyrethrins, the major insecticidal components in pyrethrum, whereas Or98a is activated by (E)-ß-farnesene (EBF), a sesquiterpene and a minor component in pyrethrum. Importantly, knockout of Or7a, Or59b or Or98a individually abolished fly avoidance to pyrethrum, while knockout of Or42b had no effect, demonstrating that simultaneous activation of Or7a, Or59b and Or98a is required for pyrethrum repellency in D. melanogaster. Our study provides insights into the molecular basis of repellency of one of the most ancient and globally used insect repellents. Identification of pyrethrum-responsive Ors opens the door to develop new synthetic insect repellent mixtures that are highly effective and broad-spectrum.

Antenna-Biased Odorant Receptor PstrOR17 Mediates Attraction of Phyllotreta striolata to (S)-Cis-Verbenol and (-)-Verbenone.

Phyllotreta striolata, the striped flea beetle, is one of the most destructive pests in Brassicaceae plants worldwide. Given the drawbacks associated with long-term use of chemical insecticides, green strategies based on chemical ecology are an effective alternative for beetle control. However, the lack of information on beetle ecology has hindered the development of effective biocontrol strategies. In this report, we identified two odorants, (S)-cis-verbenol and (-)-verbenone, which displayed significant attraction for P. striolata (p < 0.05), indicating their great potential for P. striolata management. Using the Drosophila "empty neuron" system, an antenna-biased odorant receptor, PstrOR17, was identified as responsible for the detection of (-)-verbenone and (S)-cis-verbenol. Furthermore, the interactions between PstrOR17 and (-)-verbenone or (S)-cis-verbenol were predicted via modeling and molecular docking. Finally, we used RNAi to confirm that PstrOR17 is essential for the detection of (-)-verbenone and (S)-cis-verbenol to elicit an attraction effect. Our results not only lay a foundation for the development of new and effective nonchemical insecticide strategies based on (S)-cis-verbenol and (-)-verbenone, but also provide new insight into the molecular basis of odorant recognition in P. striolata.

Pyrite coupled with biochar alleviating the toxicity of silver nanoparticles on pollutants removal in constructed wetlands.

Silver nanoparticles (AgNPs) has been widely detected in the substrates of constructed wetlands (CWs), posing threaten to pollutants removal efficiency of CWs. However, the way to alleviate the toxicity of AgNPs on CWs is unclear. In this study, the gravel (GR), biochar (BC), pyrite (PY) and pyrite coupled with biochar matrix (PYBC) were selected as substrates to restore the pollutants removal efficiency of CWs under the exposure to the environment (0.2 mg/L) and accumulation (10 mg/L) concentration of AgNPs. Results showed that the BC and PY showed limited mitigation effects, while the PYBC alleviated the toxicity significantly. Especially in the exposure to the accumulation concentration of AgNPs, the removal of NH4+-N, TN, COD and TP in the PYBC were 10.2%, 8.3%, 9.4% and 10.7% higher than that in the GR, respectively. Mechanism analysis verified that AgNPs were transformed into Ag-Fe-S core shell aggregates (size >200 nm) decreasing bioavailability and the damage to cytomembrane. The PYBC restored the nitrogen removal efficiency by increasing the abundance of Nitrospira and Geothrix, which these bacteria were defined as nitrifiers and Feammox bacteria. This study provides a promising strategy to mitigate AgNPs' toxicity on the pollutant removal efficiency in CWs.

Leucine to tryptophane substitution in the pore helix IIP1 confer sodium channel resistance to pyrethroids and DDT.

Aedes aegypti is responsible for transmitting a variety of arboviral infectious diseases such as dengue and chikungunya. Insecticides, particularly pyrethroids, are used widely for mosquito control. However, intensive used of pyrethroids has led to the selection of kdr mutations on sodium channels. L982W, locating in the PyR1 (Pyrethroid receptor site 1), was first reported in Ae. aegypti populations collected from Vietnam. Recently, the high frequency of L982W was detected in pyrethroid-resistant populations of Vietnam and Cambodia, and also concomitant mutations L982W + F1534C was detected in both countries. However, the role of L982W in pyrethroid resistance remains unclear. In this study, we examined the effects of L982W on gating properties and pyrethroid sensitivity in Xenopus oocytes. We found that mutations L982W and L982W + F1534C shifted the voltage dependence of activation in the depolarizing direction, however, neither mutations altered the voltage dependence of inactivation. L982W significantly reduced channel sensitivity to Type I pyrethroids, permethrin and bifenthrin, and Type II pyrethroids, deltamethrin and cypermethrin. No enhancement was observed when synergized with F1534C. In addition, L982W and L982W + F1534C mutations reduced the channel sensitivity to DDT. Our results illustrate the molecular basis of resistance mediates by L982W mutation, which will be helpful to understand the interacions of pyrethroids or DDT with sodium channels and develop molecular markers for monitoring pest resistance to pyrethroids and DDT.

Antifungal Effect of Bacillus velezensis ZN-S10 against Plant Pathogen Colletotrichum changpingense and Its Inhibition Mechanism.

In order to optimize crop production and mitigate the adverse impacts associated with the utilization of chemical agents, it is necessary to explore new biocontrol agents. Bacillus velezensis has been widely studied as a biocontrol agent because of its efficient and ecofriendly plant disease control mechanisms. This study shows that the strain ZN-S10 effectively reduces the area of leaf spots caused by the pathogen Colletotrichum changpingense ZAFU0163-1, which affects conidia production and germination, inhibits mycelium growth, and induces mycelium deformation. In antifungal experiments with crude extracts, we observed a delay in the cell cycle of conidia, which may be responsible for the inhibition of conidial germination. Among the bioactive metabolites detected through integrated LC-MS- and GC-MS-based untargeted metabolomics, 7-O-Succinyl macrolactin A, telocinobufagin, and surfactin A may be the main antifungal metabolites of strain ZN-S10. The presence of 7-O-Succinyl macrolactin A could explain the cell damage in germ tubes. This is the first report of telocinobufagin detected in B. velezensis. These results are significant for understanding the inhibitory mechanisms employed by B. velezensis and should serve as a reference in the production of biocontrol agents.

Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression.

Heart failure after myocardial infarction (MI) is the leading cause of death worldwide. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese herbal medicine that has been used in the clinic for centuries. In this study, we aimed to investigate the roles of CRP in cardiac remodelling and heart failure after MI, as well as the molecular mechanisms involved. Male C57BL/6 mice aged 8 weeks were subjected to coronary artery ligation to mimic the clinical situation in vivo. Echocardiography was used to assess the systolic function of the mouse heart. Masson trichrome staining and Wheat germ agglutinin (WGA) staining were utilised to determine the fibrotic area and cross-sectional area of the mouse heart, respectively. Cardiomyocytes and fibroblasts were isolated from neonatal rats aged 0-3 days in vitro using enzyme digestion. TUNEL staining and EdU staining were performed to evaluate apoptosis and proliferation, respectively. Gene expression changes were analysed by qRT-PCR, and protein expression changes were assessed by Western blotting. Our findings revealed that CRP attenuated cardiac hypertrophy, fibrosis and apoptosis and alleviated heart failure after MI in vivo. Furthermore, CRP mitigated cardiomyocyte apoptosis and fibroblast proliferation and differentiation into myofibroblasts. In addition, the PPARγ inhibitor T0070907 completely abolished the abovementioned beneficial effects of CRP, and the PPARγ activator rosiglitazone failed to further ameliorate cardiac apoptosis and fibrosis in vitro. CRP alleviates cardiac hypertrophy, fibrosis, and apoptosis and can ameliorate heart failure after MI via activation of PPARγ.

Nr2f2 Overexpression Aggravates Ferroptosis and Mitochondrial Dysfunction by Regulating the PGC-1α Signaling in Diabetes-Induced Heart Failure Mice.

Diabetes is well recognized to increase the risk of heart failure, which is associated with higher mortality and morbidity. It is important for the development of novel therapeutic methods targeting heart failure in diabetic patients. Ferroptosis, an iron-dependent regulated cell death, has been implicated in the progression of diabetes-induced heart failure (DIHF). This study was designed to investigate the contribution of Nr2f2 to the activation of ferroptosis and mitochondrial dysfunction in DIHF. We established a diabetic model by a high-fat feeding diet combined with an intraperitoneal injection of streptozotocin. After 16 weeks, Nr2f2 expression was increased in heart tissue of DIHF mice. In vivo, DIHF mice overexpressing Nr2f2 (AAV9-cTNT-Nr2f2) exhibited severe heart failure and enhanced cardiac ferroptosis compared with DIHF control mice (AAV9-cTNT-ctrl), accompanied by mitochondrial dysfunction and aggravated oxidative stress reaction. In vitro, Nr2f2 knockdown ameliorated ferroptosis and mitochondrial dysfunction by negatively regulating PGC-1α, a crucial metabolic regulator. PGC-1α knockdown counteracted the protective effect of Nr2f2 knockdown. These data suggest that Nr2f2 promotes heart failure and ferroptosis in DIHF by modulating the PGC-1α signaling. Our study provides a new idea for the treatment of diabetes-induced heart failure.

Abundance interaction in Candida albicans and Candida glabrata mixed biofilms under diverse conditions.

Candida albicans and Candida glabrata are frequently coisolated from the oral cavity in immunosuppressive or immunocompromised individuals. Their relationship is usually defined as competition as C. glabrata can inhibit growth of C. albicans in cohabitation. In this study, eight C. albicans isolates as well as two C. glabrata strains were used to investigate the effects of culture medium (Roswell Park Memorial Institute [RPMI]-1640, YPD, YND), incubation time (24 h, 48 h, 72 h, 96 h), initial inoculum (C. glabrata: C. albicans = 2:1, 1:1, 1:2), and medium state (static and dynamic states) on viable cell enumeration and relative abundance in both Candida SB and MB. The results showed that in most cases, C. glabrata and C. albicans SB and MB flourished in RPMI-1640 at 24 h under dynamic state compared with other conditions. Except YPD medium, there were high proportions of preponderance of C. albicans over C. glabrata in MB compared with SB. High initial inoculum promoted corresponding Candida number in both SB and MB and its abundance in MB relative to SB. This study revealed an impact of several environmental conditions on the formation of C. albicans and C. glabrata SB and MB and their abundance in MB in comparison with SB, deepening our understanding of both Candida interaction and their resistance mechanism in MB. LAY SUMMARY: This study described the effects of diverse experimental conditions on the numbers of Candida albicans and Candida glabrata single biofilms and mixed biofilms and their abundance.

Simultaneous imaging of cancer biomarkers in live cells based on DNA-engineered exosomes.

Cancer biomarkers are directly related to the development of cancers. Noninvasive identification of the location and expression levels of these biomarkers in live cancer cells offers great potential for accurate early-stage cancer diagnosis and cancer metastasis monitoring. Herein, we propose a DNA-engineered exosome (DNA-Exo) nanoplatform to image dual cancer biomarkers at the single-cell level, in which DNA probes were modified with the cholesterol group to facilely anchor on the exosomal membrane through hydrophobic interaction. Fluorophore-labeled DNA aptamer and hairpin probes targeting two kinds of cancer biomarkers of transmembrane glycoprotein mucin 1 (MUC1) and cytoplasmic microRNA-21 (miR-21), respectively, were employed for convenient dual-fluorescence imaging of cancer cells. The cellular uptake of DNA-Exos induced the specific recognition of MUC1 and miR-21, allowing the acquisition of the expression levels and spatial distributions of these two biomarkers in three tested cell lines. Our work demonstrated that the proposed DNA-Exos with designable functions have the capacity to visually discriminate different cell types based on the specific recognition of analytes.

Nanoplastics Disturb Nitrogen Removal in Constructed Wetlands: Responses of Microbes and Macrophytes.

Nanosized plastics (nanoplastics) releasing into the wastewater may pose a potential threat to biological nitrogen removal. Constructed wetland (CW), a wastewater treatment or shore buffer system, is an important sink of nanoplastics, while it is unclear how nitrogen removal in CWs occurs in response to nanoplastics. Here, we investigated the effects of polystyrene (PS) nanoplastics (0, 10, and 1000 µg/L) on nitrogen removal for 180 days in CWs. The results revealed that total nitrogen removal efficiency decreased by 29.5-40.6%. We found that PS penetrated the cell membrane and destroyed both membrane integrity and reactive oxygen species balance. Furthermore, PS inhibited microbial activity in vivo, including enzyme (ammonia monooxygenase, nitrate reductase, and nitrite reductase) activities and electron transport system activity (ETSA). These adverse effects, accompanied by a decline in the relative abundance of nitrifiers (e.g., Nitrosomonas and Nitrospira) and denitrifiers (e.g., Thauera and Zoogloea), directly accounted for the strong deterioration observed in nitrogen removal. The decline in leaf and root activities decreased nitrogen uptake by plants, which is an important factor of deterioration in nitrogen removal. Overall, our results imply that the presence of nanoplastics in the aquatic environment is a hidden danger to the global nitrogen cycle and should receive more attention.

Chronology of sodium channel mutations associated with pyrethroid resistance in Aedes aegypti.

Aedes aegypti is the primary mosquito vector of dengue, yellow fever, Zika and chikungunya. Current strategies to control Ae. aegypti rely heavily on insecticide interventions. Pyrethroids are a major class of insecticides used for mosquito control because of their fast acting, highly insecticidal activities and low mammalian toxicity. However, Ae. aegypti populations around the world have begun to develop resistance to pyrethroids. So far, more than a dozen mutations in the sodium channel gene have been reported to be associated with pyrethroid resistance in Ae. aegypti. Co-occurrence of resistance-associated mutations is common in pyrethroid-resistant Ae. aegypti populations. As global use of pyrethroids in mosquito control continues, new pyrethroid-resistant mutations keep emerging. In this microreview, we compile pyrethroid resistance-associated mutations in Ae. aegypti in a chronological order, as they were reported, and summarize findings from functional evaluation of these mutations in an in vitro sodium channel expression system. We hope that the information will be useful for tracing possible evolution of pyrethroid resistance in this important human disease vector, in addition to the development of methods for global monitoring and management of pyrethroid resistance in Ae. aegypti.

The expression of soluble functional α7-nicotinic acetylcholine receptors in E. coli and its high-affinity binding to neonicotinoid pesticides.

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels mediating fast cholinergic synaptic transmission in nervous system. In insects, nAChRs are the target sites for several naturally occurring and synthetic compounds, including the neonicotinoid insecticides. So far, one of the major strategies to explore the interaction of nAChR and ligands is based on the heterologous expression of nAChR, which is tough, and needs to be explored. In this study, we expressed and purified extracellular domain of rat a7 subunit (Rα7-ECD), the binding site of the ligands in E. coli and determined the interactions and kinetic constants of neonicotinoid insecticides with Rα7-ECD. The recombinant Rα7-ECD is water-soluble and appears to be correctly folded. The interactions of three neonicotinoid pesticides with Rα7-ECD were assessed by surface plasmon resonance (SPR) biosensor. The results revealed a fast association and fast disassociation binding mode of Rα7-ECD/pesticides complexes with the KD value of clothianidin (6.414E-9 M) > imidacloprid (9.030E-9 M) > acetamiprid (2.874E-6 M), respectively. This study demonstrated that the nAChR expressed from E. coli was functional, and SPR biosensor technology would be a good alternative for characterizing members of nAChR receptor family.

Characterization of Variable Region Genes and Discovery of Key Recognition Sites in the Complementarity Determining Regions of the Anti-Thiacloprid Monoclonal Antibody.

Sequence-defined recombinant antibodies (rAbs) have emerged as alternatives to hybridoma-secreted monoclonal antibodies (mAbs) for performing immunoassays. However, the polyploidy nature of hybridomas often leads to the coexistence of aberrant or non-specific functional variable region (VR) gene transcripts, which complicates the identification of correct VR sequences. Herein, we introduced the use of LC-MS/MS combined with next-generation sequencing to characterize VR sequences in an anti-thiacloprid mAb, which was produced by a hybridoma with genetic antibody diversity. The certainty of VR sequences was verified by the functional analysis based on the recombinant antibody (rAb) expressed by HEK293 mammalian cells. The performance of the rAb was similar to that of the parental mAb, with IC50 values of 0.73 and 0.46 µg/L as measured by ELISAs. Moreover, molecular docking analysis revealed that Ser52 (H-CDR2), Trp98, and Trp93 (L-CDR3) residues in the complementarity determining regions (CDRs) of the identified VR sequences predominantly contributed to thiacloprid-specific recognition through hydrogen bonds and the CH-π interaction. Through single-site-directed alanine mutagenesis, we found that Trp98 and Trp93 (L-CDR3) showed high affinity to thiacloprid, while Ser52 (H-CDR2) had an auxiliary effect on the specific binding. This study presents an efficient and reliable way to determine the key recognition sites of hapten-specific mAbs, facilitating the improvement of antibody properties.

[Therapeutic effect of cinnamaldehyde on ulcerative colitis in mice induced by dextran sulfate sodium with Candida albicans colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway].

To observe the efficacy of cinnamaldehyde on dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) with Can-dida albicans(Ca) colonization and its effect on dectin-1/TLRs/NF-κB signaling pathway in mice. C57 BL/6 mice were randomly divided into normal group, DSS group, DSS+Ca group, cinnamaldehyde group and mesalazine group. Mice in DSS+Ca group were given Ca(1×10~8 CFU per mouse) through intragastrical administration for 4 consecutive days and then distilled water with 3.0% DSS for 7 consecutive days. In cinnamaldehyde group and mesalazine group, in addition to the induction method of the DSS+Ca group, mice were given 75 mg·kg~(-1) cinnamaldehyde and 200 mg·kg~(-1) mesalazine accompanied with 3.0% DSS for 7 consecutive days, respectively. Mice in normal group and DSS group were correspondingly administered with distilled water. The general conditions of the mice were observed daily, the diseased activity index(DAI) score was calculated, and fungal loads of feces were detected by plate method. The mice were sacrificed on day 12, colon length was measured, colon mucosa damage index(CMDI) score was calculated, and histopathological analysis was carried out by HE staining. Anti-saccharomces cerevisiae antibody(ASCA) and ß-1,3-glucan in serum, and TNF-α, IL-1ß, IL-6, IL-8, IL-10 in serum and colon tissue were detected by ELISA. The contents of ß-1,3-glucan and macrophage infiltration in colon tissues were examined by immunofluorescence staining. The protein expressions of dectin-1, TLR2, TLR4 and NF-κB were detected by Western blot and immunohistochemistry staining. The results showed that cinnamaldehyde could significantly improve the general conditions of UC mice with Ca colonization, decrease DAI and histopathological scores, reduce intestinal mucosal congestion, erosion and colon shortening, decrease Ca load in mouse feces and tissues, down-regulate the contents of ASCA and ß-1,3-glucan in serum, reduce the contents of TNF-α, IL-1ß, IL-6, IL-8 and increase IL-10 in serum and colon tissues, inhibit macrophages infiltration and down-regulate the protein expression of dectin-1, TLR2, TLR4 and NF-κB in colon tissue. These results suggested that cinnamaldehyde had a therapeutic effect on UC mice with Ca colonization, which might be related to the inhibition of Ca proliferation, the regulation of dectin-1/TLRs/NF-κB signaling pathways and the coordination of the balance between pro-inflammatory and anti-inflammatory factors.

The Role of Circular RNAs in Cerebral Ischemic Diseases: Ischemic Stroke and Cerebral Ischemia/Reperfusion Injury.

Cerebral ischemic diseases including ischemic stroke and cerebral ischemia reperfusion injury can result in serious dysfunction of the brain, which leads to extremely high mortality and disability. There are no effective therapeutics for cerebral ischemic diseases to date. Circular RNAs are a kind of newly investigated noncoding RNAs. It is reported that circular RNAs are enriched in multiple organs, especially abundant in the brain, which indicates that circular RNAs may be involved in cerebral physiological and pathological processes. In this chapter, we will firstly review the pathophysiology, underlying mechanisms, and current treatments of cerebral ischemic diseases including ischemic stroke and cerebral ischemia/reperfusion injury. Secondly, the characteristics and function of circular RNAs will be outlined, and then we are going to introduce the roles circular RNAs play in human diseases. Finally, we will summarize the function of circular RNAs in cerebral ischemic diseases.

Action of six pyrethrins purified from the botanical insecticide pyrethrum on cockroach sodium channels expressed in Xenopus oocytes.

Pyrethrin I, pyrethrin II, cinerin I, cinerin II, jasmolin I and jasmolin II are six closely related insecticidal active esters, known as pyrethrins, found in the pyrethrum extract from the dry flowers of Tanacetum cinerariifolium. The chemical structures of the six compounds differ only in the terminal moieties at the acid and alcohol ends, but the compounds' in vivo toxicities are substantially different. Pyrethrins are lead compounds for pyrethroids, a large family of synthetic insecticides that alter nerve functions by prolonging the opening of voltage-gated sodium channels. However, data on the mechanism of action of natural pyrethrins are very limited. In this study, we examined the actions of all six pyrethrins on cockroach sodium channels expressed in Xenopus oocytes. Although the six compounds showed comparable potencies in inhibiting the inactivation of sodium channels, they had greatly variable potencies in inhibiting channel deactivation. Furthermore, unlike pyrethroids, the action of pyrethrins neither depend on nor were enhanced by repeated channel activation. We created a NavMs-based model of the cockroach sodium channel, in which pyrethrin II was docked at the pyrethroid receptor site 1 (PyR1), and proposed a rationale for the observed structure-activity relationship of the six pyrethrins. Our study sheds light on the molecular mechanism of pyrethrum action on sodium channels and reveled differences in the modes of action of the six bioactive constitutes of pyrethrum.

Lead isotope exchange between dissolved and fluvial particulate matter: a laboratory study from the Johor River estuary.

Atmospheric aerosols are the dominant source of Pb to the modern marine environment, and as a result, in most regions of the ocean the Pb isotopic composition of dissolved Pb in the surface ocean (and in corals) matches that of the regional aerosols. In the Singapore Strait, however, there is a large offset between seawater dissolved and coral Pb isotopes and that of the regional aerosols. We propose that this difference results from isotope exchange between dissolved Pb supplied by anthropogenic aerosol deposition and adsorbed natural crustal Pb on weathered particles delivered to the ocean by coastal rivers. To investigate this issue, Pb isotope exchange was assessed through a closed-system exchange experiment using estuarine waters collected at the Johor River mouth (which discharges to the Singapore Strait). During the experiment, a known amount of dissolved Pb with the isotopic composition of NBS-981 (206Pb/207Pb = 1.093) was spiked into the unfiltered Johor water (dissolved and particulate 206Pb/207Pb = 1.199) and the changing isotopic composition of the dissolved Pb was monitored. The mixing ratio of the estuarine and spike Pb should have produced a dissolved 206Pb/207Pb isotopic composition of 1.161, but within a week, the 206Pb/207Pb in the water increased to 1.190 and continued to increase to 1.197 during the next two months without significant changes of the dissolved Pb concentration. The kinetics of isotope exchange was assessed using a simple Kd model, which assumes multiple sub-reservoirs within the particulate matter with different exchange rate constants. The Kd model reproduced 56% of the observed Pb isotope variance. Both the closed-system experiment and field measurements imply that isotope exchange can be an important mechanism for controlling Pb and Pb isotopes in coastal waters. A similar process may occur for other trace elements.This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.