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Background and aims C-reactive protein (CRP) is a hepatocyte-produced marker of inflammation yet with undefined function in liver injury. We aimed to examine the role of CRP in acetaminophen-induced liver injury (AILI). Methods The effects of CRP in AILI were investigated using CRP knockout mice and rats combined with human CRP rescue. The mechanisms of CRP action were investigated in vitro and in mice with Fcγ receptor 2B knockout, C3 knockout, or hepatic expression of CRP mutants defective in complement interaction. The therapeutic potential of CRP was investigated by intraperitoneal administration at 2 or 6 hours post–AILI induction in wild-type mice. Results CRP knockout exacerbated AILI in mice and rats, which could be rescued by genetic knock-in, adeno-associated virus–mediated hepatic expression or direct administration of human CRP. Mechanistically, CRP does not act via its cellular receptor Fcγ receptor 2B to inhibit the early phase injury to hepatocytes induced by acetaminophen; instead, CRP acts via factor H to inhibit complement overactivation on already injured hepatocytes, thereby suppressing the late phase amplification of inflammation likely mediated by C3a-dependent actions of neutrophils. Importantly, CRP treatment effectively alleviated AILI with a significantly extended therapeutic time window than that of N-acetyl cysteine. Conclusion Our results thus identify CRP as a crucial checkpoint that limits destructive activation of complement in acute liver injury, and we argue that long-term suppression of CRP expression or function might increase the susceptibility to AILI.

Fully understanding the environmental implications of engineered nanomaterials is crucial for their safe and sustainable use. Cyanobacteria, as the pioneers of the planet earth, play important roles in global carbon and nitrogen cycling. Here, we evaluated the biological effects of molybdenum disulfide (MoS2) nanosheets on a N2-fixation cyanobacteria (Nostoc sphaeroides) by monitoring growth and metabolome changes. MoS2 nanosheets did not exert overt toxicity to Nostoc at the tested doses (0.1 and 1 mg/L). On the contrary, the intrinsic enzyme-like activities and semiconducting properties of MoS2 nanosheets promoted the metabolic processes of Nostoc, including enhancing CO2-fixation-related Calvin cycle metabolic pathway. Meanwhile, MoS2 boosted the production of a range of biochemicals, including sugars, fatty acids, amino acids, and other valuable end products. The altered carbon metabolism subsequently drove proportional changes in nitrogen metabolism in Nostoc. These intracellular metabolic changes could potentially alter global C and N cycles. The findings of this study shed light on the nature and underlying mechanisms of bio-nanoparticle interactions, and offer the prospect of utilization bio-nanomaterials for efficient CO2 sequestration and sustainable biochemical production.

Hypoxia exposure often cause the increases of pulmonary arterial pressure (PAP). Studies reported that mast cells (MCs) participate in pulmonary vascular remodeling and promote the formation of chronic pulmonary hypertension. Current studies mainly focus on the change of MCs under chronic hypoxia, but few studies on the regulatory role and mechanism of MCs under acute hypoxia. T herefore, present study investigated the dynamic change of MCs in lung tissues under acute hypoxia and the role of MCs activation in the increasement of PAP. In our study, we established an experimental rat model of acute hypobaric hypoxia using a hypobaric chamber (simulated altitude of 7,000 m) and pretreated with MCs degranulation inhibitor sodium cromoglycate (SCG) to study the MCs changes under acute hypoxic exposure. We found that acute hypobaric hypoxia contributed to the increased quantity, activity, and degranulation of MCs and SCG pretreatment showed attenuated PAP elevation under acute hypoxia. Our findings implied that there is a possible mechanism of acute hypoxia cause rapid recruitment of MCs, activation, and explosive degranulation to release Tryptase, Chymase, IL-6, His, 5-HT, and Ang II, which further contributed to pulmonary microvascular contraction and increase in PAP. This work extends the knowledge about MCs, providing a potential profile of MCs as an alternative treatment for high-altitude pulmonary edema (HAPE)-related increased pulmonary artery pressure.

The term “microplastics” (MPs) refers to fine plastics less than 5 mm in size and includes primary sources from the original production of small-sized particles and secondary sources from the degradation or fragmentation of large plastics. MPs have been widely detected in marine (estuaries, bays, coastal zones, deep seas, ocean waters and sediments), soils (farmlands, urban soils, wetlands, landfill and polar areas), freshwater (lakes, rivers, reservoirs, snow and ice, and sewage treatment plants) and sediments, atmosphere (outdoor and indoor airs), living organisms (plants, animals, microorganisms, human and pet faeces), and foods (table salts, drinking waters, beers, vegetables and pet foods). Besides, MPs could be acted as the vector for many environmental pollutants, pathogens and even antibiotic resistance genes (ARGs). Moreover, MPs can be taken up by various terrestrial and aquatic organisms and transfer along the food chain at various trophic levels. Thus, environmental MP pollution is becoming one of the most serious threats to the Earth’s surface ecosystems which has attracted serious concern and extensive research by many governments and the scientific community worldwide. Up to now, comprehensive studies and reports on the latest multidisciplinary research progress on microplastics in multiple environmental media remain limited. From the perspectives of earth sciences, chemistry, biology, and management, this article systematically reviews the research progress on the abundance, distribution and sources of microplastics in the waters, soils, atmosphere, sediments and organisms; the separation and analytical methods of microplastics in multiple environmental media; the migration and prediction of microplastics in terrestrial, marine and atmospheric environments; the surface changes and biofilm formation on microplastics and their adsorption characterization of environmental pollutants, pathogens and ARGs; the biological uptake, accumulation and ecological risks of MPs; the food chain transfer and health risks of MPs; the physico-chemical fragmentation and biodegradation of MPs in the environment and their risk reduction strategies and techniques. Finally, the key scientific issues and future research directions of environmental microplastics are also proposed in this review, such as methdology breakthroughs in separation and identification of submicron and nanoscale microplastics; comprehensive study on the distribution, migration, transport and flux of microplastics in environmental multi-media at cross-reginal and global scale; comprehensive monitoring, quantitative characterization and long-term evaluating the impacts of environmental microplastics on ecosystems; and the systematic assessment of human health risks of microplastics to different populations.

Sensory neurons are activated by physical and chemical stimuli, eliciting sensations such as temperature, touch, pain, and itch. From an evolutionary perspective, sensing danger is essential for organismal survival. Upon infection and injury, immune cells respond to pathogen/damage-associated molecular patterns (PAMPs/DAMPs) through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), and produce inflammatory mediators that activate sensory neurons through neuro–immune interactions. Sensory neurons also express TLRs and other PRRs that directly sense danger signals after injury or during infection, leading to pain, itch, or analgesia. In addition to slow-acting canonical TLR signaling, TLRs function uniquely in sensory neurons through non-canonical coupling to ion channels, enabling rapid modulation of neuronal activity. We discuss how sensory neurons utilize TLRs and other PRR pathways to detect danger signals in their environment.

Silica nanoparticles (SiO2-NP) are promising in nano-enabled agriculture due to their large surface area and biocompatible properties. Understanding the fundamental interaction between SiO2-NP and ...

Myocardial infarction (MI) is an acute coronary syndrome that refers to tissue infarction of the myocardium. This study aimed to investigate the effect of long intergenic non‐protein‐coding RNA (lincRNA) ATPase plasma membrane Ca2+ transporting 1 antisense RNA 1 (ATP2B1‐AS1) against MI by targeting nuclear factor‐kappa‐B inhibitor alpha (NFKBIA) and mediating the nuclear factor‐kappa‐B (NF‐κB) signalling pathway. An MI mouse model was established and idenepsied by cardiac function evaluation. It was determined that ATP2B1‐AS1 was highly expressed, while NFKBIA was poorly expressed and NF‐κB signalling pathway was activated in MI mice. Cardiomyocytes were extracted from mice and introduced with a series of mouse ATP2B1‐AS1 vector, NFKBIA vector, siRNA‐mouse ATP2B1‐AS1 and siRNA‐NFKBIA. The expression of NF‐κBp50, NF‐κBp65 and IKKβ was determined to idenepsy whether ATP2B1‐AS1 and NFKBIA affect the NF‐κB signalling pathway, the results of which suggested that ATP2B1‐AS1 down‐regulated the expression of NFKBIA and activated the NF‐κB signalling pathway in MI mice. Based on the data from assessment of cell viability, cell cycle, apoptosis and levels of inflammatory cytokines, either silencing of mouse ATP2B1‐AS1 or overexpression of NFKBIA was suggested to result in reduced cardiomyocyte apoptosis and expression of inflammatory cytokines, as well as enhanced cardiomyocyte viability. Our study provided evidence that mouse ATP2B1‐AS1 silencing may have the potency to protect against MI in mice through inhibiting cardiomyocyte apoptosis and inflammation, highlighting a great promise as a novel therapeutic target for MI.

Nanomaterials with enzyme-like activities (nanozyme) have shown potential to augment the inherent functions of plants, e.g. photosynthesis and stress resistance. Mechanistically understanding the interaction between plants and nanozymes is important. In this study, Mn3O4 NPs (1 and 5 mg per plant) with excellent antioxidant enzyme mimicking activities were synthesized and were foliarly applied to 3 week-old cucumber plants for 7 days. The response of plants to Mn3O4 NPs was determined at physiological and metabolic levels. Results showed that Mn3O4 NPs at 1 mg per plant significantly increased leaf photosynthetic pigment content, net photosynthesis, and biomass. Gas chromatography-mass spectrometry based metabolomics revealed that Mn3O4 NPs at 1 mg per plant altered the metabolomes in the cucumber leaves. A notable change was that both precursors (phenylalanine and tyrosine) and down-stream products (resveratrol, chlorogenic acid, dihydroxycinnamic acid, benzenetriol, hydroxybenzoic acid, trihydroxybenzene, quinic acid, and catechin) in shikimate and phenylpropanoid pathways were up-regulated in response to the Mn3O4 NPs, indicating the boosting of endogenous antioxidants. Mn3O4 NPs were then applied to 3 week-old cucumber plants subjected to salinity stress to test their performance to stress tolerance. Mn3O4 NPs at 1 mg per plant levels were found to successfully alleviate oxidative stress in cucumber plants allowing them to maintain their biomass. These results indicate that Mn3O4 NPs can boost endogenous antioxidant defenses in the plant, which may enable Mn3O4 NPs to be a promising nano-regulator helping to counter the undesirable effects of oxidative stress.

Gomphocerus sibiricus L., the dominant insect species in the alpine and subalpine grassland, overwinters with diapause at egg stage. In this study, cold tolerance and related cryoprotectants of G. sibiricus eggs were investigated. In particular, the supercooling point (SCP), water content, carbohydrates (trehalose, glucose, fructose, glycogen), polyols (glycerol, inositol, sorbitol), fat, and amino acids contents were evaluated at different developmental stages of G. sibiricus eggs collected under natural conditions. The SCPs of eggs were very low (-32.83 to -22.61°C) at mid-diapause. Water content gradually increased during development. The fructose, glycerol, and sorbitol contents were significantly higher in diapausing eggs than in early embryogenesis stage and post-diapause development stage. Glycogen content was high throughout the whole developmental period. The trehalose, glucose, and inositol contents were low during diapause compared to that in early embryogenesis stage and post-diapause development stage. There were no significant differences in the fat content of eggs among all development stages. The total amino acid contents in eggs in the early embryogenesis and at the start of diapause were higher than that in post-diapause eggs. The contents of Glu, Asp, Leu, Pro and Arg during diapause were significantly higher than those during post-diapause development. Results indicate that G. sibiricus eggs have a high supercooling capacity. Successful overwintering can be attributed to the accumulation of glycerol, fructose, sorbitol, and amino acids (Glu, Asp, Leu, Pro and Arg). These findings provide insight into the mechanisms underlying the adaptation of G. sibiricus to cold conditions.

Increasing CO2 levels are speculated to change the effects of engineered nanomaterials in soil and on plant growth. How plants will respond to a combination of elevated CO2 and nanomaterials stress has rarely been investigated, and the underlying mechanism remains largely unknown. Here, we conducted a field experiment to investigate the rice (Oryza sativa L. cv. IIyou) response to TiO2 nanoparticles (nano-TiO2, 0 and 200 mg kg-1) using a free-air CO2 enrichment system with different CO2 levels (ambient ∼370 μmol mol-1 and elevated ∼570 μmol mol-1). The results showed that elevated CO2 or nano-TiO2 alone did not significantly affect rice chlorophyll content and antioxidant enzyme activities. However, in the presence of nano-TiO2, elevated CO2 significantly enhanced the rice height, shoot biomass, and panicle biomass (by 9.4%, 12.8%, and 15.8%, respectively). Furthermore, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that genes involved in photosynthesis were up-regulated while most genes associated with secondary metabolite biosynthesis were down-regulated in combination-treated rice. This indicated that elevated CO2 and nano-TiO2 might stimulate rice growth by adjusting resource allocation between photosynthesis and metabolism. This study provides novel insights into rice responses to increasing contamination under climate change.

The widespread use of bisphenol S (BPS) as a bisphenol A substitute increases its potential of release into the aquatic environments. However, the degradation of BPS in aquatic systems is largely unknown, which will dictate its fate and toxicity. In this study, a bacterial consortium was enriched from river sediments and the dynamic changes of community structure during bacterial acclimation were studied. BPS degrading bacterial strains isolated from the consortium were identified by 16S rRNA analysis. The efficiency of the consortium and strains for BPS degradation were further evaluated. After 28 days of acclimation, the microbial diversity decreased significantly and four bacterial genera Hyphomicrobium, Pandoraea, Rhodococcus, and Cupriavidus with relative abundances of 5.1%-52.8% became dominant in the consortium. Total of two pure strains including Terrimonas pekingensis and Pseudomonas sp. were isolated from the consortium, using BPS as the sole carbon source. The consortium was highly efficient to degrade BPS, and 99% of BPS with an initial concentration of 50 mg/L was removed within 10 days at pH 7 and 30°C. In comparison with the consortium, a single strain cultures had lower BPS degradation efficiency. These findings indicate that BPS will degrade rapidly under aerobic conditions in river sediments and have implication for BPS-contaminated site remediation using the enriched consortium.

Calliptamus italicus L. is a major migratory pest that often causes serious agricultural losses in the desert/semi‐desert steppe of Central Asia. The present study aims to understand the physiological factors that affect migration of C. italicus by examining the relationships between flight capacity, energy accumulation, ovarian development and Juvenile hormone (JH) titre. The results show that flight capacity decreases with age, being greatest among 2‐day‐old males and lowest among 13‐day‐old locusts. There is no significant correlation between energy accumulation and flight capacity, although JH titre is negatively correlated with flight capacity. Energy accumulation and flight capacity first increases then decreases in 1–13‐day‐old females. Glycogen accumulation is significantly correlated with flight speed, and triglyceride accumulation is significantly correlated with flight distance, duration and speed. Changes in JH titre in 1–13‐day‐old females show double titre peaks, which are negatively correlated with flight capacity. Seven‐day‐old C. italicus have the highest glycogen and triglyceride accumulation, greatest flight capacity, grade II ovarian development and lowest JH titre. By contrast, 13‐day‐old C. italicus have the lowest triglyceride accumulation, lowest flight capacity, grade IV ovarian development and lowest JH titre. Taken together, these findings demonstrate that there is a trade‐off between ovarian development and flight capacity of C. italicus.

Critical for diverse biological processes, proteases represent one of the largest families of pharmaceutical targets. To inhibit pathogenic proteases with desired selectivity, monoclonal antibodies (mAbs) hold great promise as research tools and therapeutic agents. However, identification of mAbs with inhibitory functions is challenging because current antibody discovery methods rely on binding rather than inhibition. This study developed a highly efficient selection method for protease inhibitory mAbs by coexpressing 3 recombinant proteins in the periplasmic space of Escherichia coli—an antibody clone, a protease of interest, and a β-lactamase modified by insertion of a protease cleavable peptide sequence. During functional selection, inhibitory antibodies prevent the protease from cleaving the modified β-lactamase, thereby allowing the cell to survive in the presence of ampicillin. Using this method to select from synthetic human antibody libraries, we isolated panels of mAbs inhibiting 5 targets of 4 main protease classes: matrix metalloproteinases (MMP-14, a predominant target in metastasis; MMP-9, in neuropathic pain), β-secretase 1 (BACE-1, an aspartic protease in Alzheimer’s disease), cathepsin B (a cysteine protease in cancer), and Alp2 (a serine protease in aspergillosis). Notably, 37 of 41 identified binders were inhibitory. Isolated mAb inhibitors exhibited nanomolar potency, exclusive selectivity, excellent proteolytic stability, and desired biological functions. Particularly, anti-Alp2 Fab A4A1 had a binding affinity of 11 nM and inhibition potency of 14 nM, anti-BACE1 IgG B2B2 reduced amyloid beta (Aβ(40)) production by 80% in cellular assays, and IgG L13 inhibited MMP-9 but not MMP-2/-12/-14 and significantly relieved neuropathic pain development in mice.

Mechanical allodynia is a cardinal feature of pathological pain. Recent work has demonstrated the necessity of Aβ-low-threshold mechanoreceptors (Aβ-LTMRs) for mechanical allodynia-like behaviors in mice, but it remains unclear whether these neurons are sufficient to produce pain under pathological conditions. We generated a transgenic mouse in which channelrhodopsin-2 (ChR2) is conditionally expressed in vesicular glutamate transporter 1 (Vglut1) sensory neurons (Vglut1-ChR2), which is a heterogeneous population of large-sized sensory neurons with features consistent with Aβ-LTMRs. In naive male Vglut1-ChR2 mice, transdermal hindpaw photostimulation evoked withdrawal behaviors in an intensity- and frequency-dependent manner, which were abolished by local anesthetic and selective A-fiber blockade. Surprisingly, male Vglut1-ChR2 mice did not show significant differences in light-evoked behaviors or real-time aversion after nerve injury despite marked hypersensitivity to punctate mechanical stimuli. We conclude that optogenetic activation of cutaneous Vglut1-ChR2 neurons alone is not sufficient to produce pain-like behaviors in neuropathic mice. SIGNIFICANCE STATEMENT Mechanical allodynia, in which innocuous touch is perceived as pain, is a common feature of pathological pain. To test the contribution of low-threshold mechanoreceptors (LTMRs) to nerve-injury-induced mechanical allodynia, we generated and characterized a new transgenic mouse (Vglut1-ChR2) to optogenetically activate cutaneous vesicular glutamate transporter 1 (Vglut1)-positive LTMRs. Using this mouse, we found that light-evoked behaviors were unchanged by nerve injury, which suggests that activation of Vglut1-positive LTMRs alone is not sufficient to produce pain. The Vglut1-ChR2 mouse will be broadly useful for the study of touch, pain, and itch.

Calliptamus italicus L. is an important pest on the desert and semidesert steppes along the Sino-Kazakh border. To elucidate the molecular mechanism of its continuous outbreaks, we studied 11 different geographic populations of C. italicus to determine: 1) the complete sequences of the entire mitochondrial cytochrome oxidase subunit I (COI) and mitochondrial cytochrome oxidase subunit II (COII) genes, and 2) performed genetic diversity, differentiation, gene flow, and molecular variation analyses. Of the 11 populations, the Yining County (YNX) population had the highest haplotype diversity and Pi values. There are significant differences in Tajima’s D and Fu’s Fs (P < 0.05). The fixation index Fst values of the total C. italicus population were 0.03352, and its gene flow Nm values of the total C. italicus population were 15.32. Taken together, there were five main findings: 1) the current genetic differentiation of C. italicus arose within populations; 2) genetic exchange levels were high between geographical populations; 3) genetic variation level was low; 4) C. italicus populations likely expanded in recently, and 5) there was no significant correlation between genetic distance and geographic distance for any geographic population. Findings from this study indicate that frequent gene exchange between populations may enhance the adaptability of C. italicus along the Sino-Kazakh border, leading to frequent outbreaks.

Engineered nanoparticles (NPs) with activities that mimic antioxidant enzymes have good prospects in agriculture because they can increase photosynthesis and improve stress tolerance. Here, the interaction between cerium oxide NPs with spinach plants ( Spinacia oleracea) was investigated by integrating phenotypic and metabolomic analyses. Soil-grown, four-week-old spinach plants were foliar exposed for 3 weeks to CeO2 NPs at 0, 0.3, and 3 mg per plant. Phenotypic parameters (chlorophyll fluorescence, photosynthetic pigment contents, plant biomass, lipid peroxidation, and membrane permeability) were not affected. However, metabolomics analysis revealed that both doses of CeO2 NPs induced metabolic reprogramming in leaves and roots in a non-dose-dependent manner. The low dose of CeO2 NPs (0.3 mg per plant) induced stronger metabolic reprogramming in spinach leaves than high dose of CeO2 NPs. However, the high dose of CeO2 NPs triggered more metabolic changes in roots, compared to the low dose. Foliar spray of CeO2 NPs at 3 mg/plant induced marked down-regulation of a number of amino acids (threonine, tryptophan, l-cysteine, methionine, cycloleucine, aspartic acid, asparagine, tyrosine, and glutamic acid). In addition, Zn decreased by 44% and 54% in leaves and Ca decreased by 38% and 32% in roots under exposure to CeO2 NPs at 0.3 and 3 mg/plant, respectively. These results provide better understanding of the intrinsic phenotypic and metabolic changes imposed by CeO2 NPs in spinach plants.

Amyloid‐β peptides (Aβs) are generated in a membrane‐embedded state by sequential processing of amyloid precursor protein (APP). Although shedding of membrane‐embedded Aβ is essential for its secretion and neurotoxicity, the mechanism behind shedding regulation is not fully elucidated. Thus, we devised a Langmuir film balance‐based assay to uncover this mechanism. We found that Aβ shedding was enhanced under acidic pH conditions and in lipid compositions resembling raft microdomains, which are directly related to the microenvironment of Aβ generation. Furthermore, Aβ shedding efficiency was determined by the length of the C‐terminal membrane‐spanning region, whereas pH responsiveness appears to depend on the N‐terminal ectodomain. These findings indicate that Aβ shedding may be directly coupled to its generation and represents an unrecognized control mechanism regulating the fate of membrane‐embedded products of APP processing.

Bisphenol F (BPF) pollution in environment increased, but the studies on its fate and uptake in soil-earthworm systems were limited. Using 14C-tracers, environmental fate of BPF isomers in an oxic rice soil with/without earthworm Metaphire guillelmi was studied. After 59 days of incubation, mineralization increased in the order of 2,2'-BPF (18.7% ± 0.3% of the initial amount) < 2,4'-BPF (21.7% ± 0.2%) < 4,4'-BPF (26.9% ± 0.1%). About 70% was converted to bound residues (BRs) and most of the BRs resided in the humin fraction by physical entrapment and ester-linkages. M. guillelmi decreased the mineralization and BRs of 4,4'-BPF in soil, indicating that earthworm increased the ecological risk of 4,4'-BPF. About 5.2% ± 0.1% of the initial amount was accumulated in M. guillelmi and mostly in gut. Considerable amounts of the accumulated 4,4'-BPF were present as earthworm-bound residues (earthworm-BRs). The elimination of 4,4'-BPF from M. guillelmi was very slow, and there was still 96.2% of the initial accumulated radioactivity presented in earthworm after 5 days of depuration. The results of this study firstly provide the isomer - specific partitioning of three BPF isomers in an oxic soil and the uptake and depuration of 4,4'-BPF in earthworm during soil incubation.

The activity of e-waste recycling often causes the combined pollution of tetrabromobisphenol A (TBBPA) and cadmium (Cd) in soils. In this study, the effects of their co-existence on each other's fate, further reflecting the bioavailability, were analyzed in the presence of two ecologically different earthworm species, endogeic Metaphire guillelmi and epigeic Eisenia fetida. Mineralization of 14C-TBBPA combined with 10 mg Cd kg−1 was suppressed by the presence of M. guillelmi, whereas a facilitating effect was produced by the combination of 1 mg Cd kg−1 in the soil-E. fetida system after a 14-day exposure. The uptake of 14C-TBBPA by M. guillelmi (17% of initial amount) and by E. fetida (10%) dominantly contributed to significant (P 0.05) influence the accumulation and metabolism of TBBPA in the earthworms. Both earthworms accumulated only ~7% of Cd in soil, however, the bioavailable Cd determined by the diffusive gradients in thin films technique declined by ~46% in the presence of M. guillelmi, and a much smaller decrease was determined in the presence of E. fetida. Amendment of TBBPA at environmental levels did not alter the accumulation and subcellular distribution of Cd in both earthworms unless that at high doses. The results highlighted the importance of considering the difference of the earthworm species and the interaction of pollutants in soil-risk assessments of such combined contamination. Capsule M. guillelmi displayed greater effect on the fate of TBBPA and Cd co-existed in soils than E. fetida, while the accumulation, metabolism, or distribution of the two pollutants in earthworms did not significantly alter due to interactions between the two pollutants.

Sensory systems are shaped in postnatal life by the refinement of synaptic connections. In the dorsal horn of the spinal cord, sensory circuits undergo postnatal activity dependent reorganisation, including the retraction of primary afferent A-fibres from superficial to deeper laminae which is accompanied by decreases in cutaneous sensitivity. Here we show that microglia, the resident immune cells in the CNS, phagocytose A-fibre terminals in superficial laminae in the first weeks of life. Genetic perturbation of microglial engulfment at that time prevents the normal process of A-fibre retraction, resulting in increased sensitivity of dorsal horn cells to dynamic tactile cutaneous stimulation, and behavioural hypersensitivity to dynamic touch. Thus, functional microglia are necessary for normal postnatal development of dorsal horn sensory circuits. In the absence of microglial engulfment, superfluous A-fibre projections remain in the dorsal horn and the balance of sensory connectivity is disrupted, leading to lifelong hypersensitivity to dynamic touch.Impact statementMicroglia phagocytose superfluous A-fibres in the superficial spinal dorsal horn during normal development, the disruption of which leads to long term aberrant dynamic touch processing and behaviour.

GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37−/− mice. Notably, we found that ARU binds to GPR37 in macrophages and promotes phagocytosis and clearance of pathogens. Moreover, ablation of macrophages potentiated infection, sepsis, and their sequelae, whereas adoptive transfer of NPD1- or ARU-primed macrophages reduced infection, sepsis, and pain-like behaviors. Our findings reveal physiological actions of ARU in host cells by activating macrophages and suggest that GPR37 agonists may help to treat sepsis, bacterial infections, and malaria., GPR37 is expressed in macrophages, and has been implicated in resolution of inflammatory pain. Here the authors show that GPR37 can modulate sepsis in several animal models.

C-reactive protein (CRP) is a circulating marker of inflammation yet with ill-defined biological functions. This is partly due to the uncharacterized activities of endogenous CRP in mice, the major animal model used to define protein function. The hurdles for purification and characterization of mouse CRP are its low circulating levels and the lack of specific antibodies. To clear these hurdles, here we developed an efficient expression system by constructing recombinant Pichia pastoris cells for secretion of native conformation mouse CRP. The recombinant expression of mouse CRP in Escherichia coli failed to yield sufficient amount of native protein, reflecting the importance of post-translational modification of glycosylation in aiding proper folding. By contrast, sufficient amount of native mouse CRP was successfully purified from P. pastoris. Preliminary purification was performed by Nickel Chelating Sepharose Fast-Flow affinity chromatography with 6 × His tags attached to the protein. Subsequently, p-Aminophenyl Phosphoryl Choline Agarose resin affinity chromatography was used for tandem purification. The purified mouse CRP showed native pentamer and capabilities of PC binding. Moreover, the 6 × His tag provides a convenient tool for detecting the interactions of mouse CRP with ligands.

Type-I interferon (IFN-I) signaling is critical to maintaining antigen-presenting cell function for anti-tumor immunity. However, recent studies have suggested that IFN-I signaling may also contribute to more aggressive phenotypes, raising the possibility that IFN-I downstream signaling in cancer and myeloid cells may exert dichotomous functions.We analyzed the clinicopathologic correlation of cancer-specific IFN-I activation in 195 head and neck squamous cell carcinoma patients. We also characterized the immune impact of IFN-I receptor (IFNAR1)-deficiency in syngeneic tumor models using biochemistry, flow cytometry, and single-cell RNA-Seq. We stained HNSCC tissue microarrays with a sensitive IFN-I downstream signaling activation marker, MX1, and quantitated cancer cell-specific MX1 staining. Kaplan-Meier analysis revealed that MX1-high tumors exhibited worse survival, a phenotype that depends on the number of CD8+ intratumoral T-cells. We found that cancer-specific IFNAR1 engagement promotes cancer stemness and higher expression levels of suppressive immune checkpoint receptor ligands in cancer-derived exosomes. Notably, mice bearing Ifnar1-deficient tumors exhibited lower tumor burden, increased T-cell infiltration, reduced exhausted CD4+PD1high T-cells, and increased effector population CD8+IFN-γ+ T-cells. Then, we performed single-cell RNA-sequencing and discovered that cancer-specific IFN-I signaling not only restricts effector cells expansion but also dampens their functional fitness.The beneficial role of IFN-I activation is largely dependent on the myeloid compartment. Cancer-specific IFN-I receptor engagement promotes cancer stemness and the release of cancer-derived exosomes with high expression levels of immune checkpoint receptor ligands. Cancer-specific IFN-I activation is associated with poor immunogenicity and worse clinical outcomes in HNSCC.

Molybdenum disulfide (MoS2) is a transition metal dichalcogenides (TMDCs) material that is seeing rapidly increasing use. The wide range of applications will result in significant environmental release. Here, the impact of MoS2 nanosheets on rice and associated soil microbial communities was evaluated. Rice plants were grown for 4 weeks in a natural paddy soil amended with either 1T or 2H phase MoS2 nanosheets at 10 and 100 mg kg−1. The 1T MoS2 nanosheets have a significantly greater dissolution rate (58.9%) compared to 2H MoS2 (4.4%), indicating the instability of 1T MoS2 in environment. High dissolution rate resulted in a high Mo bioaccumulation in rice leaves (272 and 189 mg kg−1 under 1T and 2H exposure at 100 mg kg−1). However, this did not induce overt phytotoxicity, as indicated by a range of phenotypic or biochemical based determine endpoints, e.g., biomass, photosynthetic pigments, and malondialdehyde (MDA) content. Additionally, rice P uptake was significantly increased upon exposure to 1T and 2H MoS2 (10 mg kg−1). Gas chromatography-mass spectrometry (GC-MS) reveals that both phases of MoS2 in soil systematically enhanced the carbon and nitrogen related metabolic pathways in exposed plants. Soil 16S rRNA gene sequencing data show that soil microbial community structure was unchanged upon MoS2 exposure. However, both phases of MoS2 remarkably increased the relative abundance of N2-fixation cyanobacteria, and 2H MoS2 exposure increased a plant growth-promoting rhizobacteria-Bacillus. Overall, our results suggest that MoS2 nanosheets at tested doses did not exert negative impacts on rice plant and the associated soil microbial community.

C-reactive protein (CRP) is an established marker of rheumatoid arthritis (RA) but with ill-defined actions in the pathogenesis. Here, we show that CRP regulates the differentiation of osteoclasts, a central mediator of joint inflammation and bone erosion in RA, in a conformation- and receptor activator of NF-κB ligand (RANKL)-dependent manner. CRP in the native conformation is ineffective, whereas the monomeric conformation (mCRP) actively modulates osteoclast differentiation through NF-κB and phospholipase C signaling. Moreover, mCRP can bind RANKL, the major driver of osteoclast differentiation, and abrogate its activities. The binding and inhibition of RANKL are mediated by the cholesterol binding sequence (CBS) of mCRP. Corroborating the in vitro results, CRP knockout exacerbates LPS-induced bone resorption in mice. These results suggest that mCRP may be protective in joint inflammation by inhibiting pathological osteoclast differentiation and that the CBS peptide could be exploited as a potential RANKL inhibitor.

Plant-associated microorganisms play an important role in controlling heavy metal uptake and accumulation in aerial parts. The microbial community and its interaction with Cd accumulation by willow were assessed to explore the association of phytoextraction efficiency and rhizospheric microbial populations. Therefore, the rhizosphere microbial compositions of three willow genotypes grown in two Cd polluted sites were investigated, focusing on their interactions with phytoremediation potential. Principal coordinate analysis revealed a significant effect of genotype on the rhizosphere microbial communities. Distinct beneficial microorganisms, such as plant growth promoting bacteria (PGPB) and mycorrhizal fungi, were assembled in the rhizosphere of different willow genotypes. Linear mixed models showed that the relative abundance of PGPB was positively associated (p 0.01) with Cd accumulation, since these microbes significantly increased willow growth. The higher abundance of arbuscular mycorrhizal fungi in the rhizosphere of Salix × aureo-pendula CL 'J1011' at the Kejing site, showed a negative correlation with the Cd content, but a positive correlation with biomass. Conversely, mycorrhizal fungi, were more abundant in the rhizosphere of S. × jiangsuensis CL. 'J2345' and positively correlated with the Cd content in willow tissues. This study provides new insights into the distinctive microbial communities in rhizosphere of different willow genotypes, which may be consistent with the phytoremediation potential.

Tire crumb rubber (TCR) has been widely used in artificial turf fields, however, the potential environmental risk of TCR and the effect of sunlight exposure are scarcely studied. Here, we evaluated leachability of Zn and polycyclic aromatic hydrocarbons (PAHs) in four types of TCRs and acute toxicity of leachates to Daphnia magna. The results showed that all types of TCRs tested released Zn (0.20−1.3 μg/g) and PAHs (9.4−17 μg/g) but only two were lethal to D. magna (mortality 73%). Notably, ultraviolet (UV) irradiation induced TCR to generate acidic leachate (pH ~ 4.8), which contained 24- and 1.2-fold higher concentrations of Zn and PAHs and therefore was more toxic to D. magna than that in the absence of UV treatment. These findings demonstrate source-dependent toxicity of TCR and highlight the need to consider the effect of photoaging when evaluating the environmental risks of TCR.

With the intended application of engineered nanomaterials (ENMs) in agriculture, accurate assessment the effect of these ENMs on soil microbial communities is especially necessary. Here, maize plants were cultivated in soil amended by SiO2, TiO2, and Fe3O4 ENMs (100 mg kg−1 soil) for four weeks. The impact of ENMs on bacterial community structure of the rhizosphere soil was investigated by using high-throughput sequencing. In addition, metabolites of maize rhizosphere soil were quantified by gas chromatography-mass spectrometry (GC-MS) based metabolomics. We found that the disturbance of ENMs on soil microbes are in the follow of Fe3O4>TiO2>SiO2. Exposure of Fe3O4 ENMs significantly reduced the abundance of nitrogen-fixation related bacteria Bradyrhizobiaceae (from 2.94% to 2.40%) and iron-redox bacteria Sediminibacterium (from 2.15% to 2.07%). Additionally, Fe3O4 ENMs significantly increased populations of Nocardioides (from 1.63% to 1.77%), Chitinophaga sancti (from 1.12% to 2.08%), Pantoea (from 1.31% to 2.22%), Rhizobiumand (from 1.41% to 1.74%) and Burkholderia-Paraburkholderia (from 1.50% to 2.09%), which are associated with carbon cycling and plant growth promoting. This study provides a perspective on the response of rhizosphere microbial community and low molecular weight metabolites to ENMs exposure, providing a comprehensive understanding of the environmental risk of ENMs.

Pathologic roles for innate immunity in neurologic disorders are well-described, but protective aspects of the immune response are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induce inflammation. However, we found that Dectin-1 is protective in experimental autoimmune encephalomyelitis (EAE), while its canonical signaling mediator, Card9, promotes the disease. Notably, Dectin-1 does not respond to heat-killed Mycobacteria, an adjuvant to induce EAE. Myeloid cells mediate the protective function of Dectin-1 in EAE and upregulate gene expression of neuroprotective molecules, including Oncostatin M (Osm) through a non-canonical Card9-independent pathway, mediated by NFAT. Furthermore, we found that the Osm receptor (OsmR) functions specifically in astrocytes to reduce EAE severity. Our study revealed a new mechanism of protective myeloid-astrocyte crosstalk regulated by a non-canonical Dectin-1 pathway and identifies novel therapeutic targets for CNS autoimmunity.Graphical AbstractDectin-1 is a protective C-type lectin receptor (CLR) in experimental autoimmune encephalomyelitis (EAE)Dectin-1 promotes expression of Osm, a neuroprotective IL-6 family cytokine, in myeloid cellsOsmR signaling in astrocytes limits EAE progression and promotes remissionNon-canonical Card9-independent signaling drives a distinct Dectin-1-mediated transcriptional program to induce expression of Osm and other factors with protective or anti-inflammatory functions

Background: The association of genetically elevated levels of circulating C-reactive protein (CRP) with cancer risk has been extensively investigated in European populations; however, there are conflicting conclusions. The tri-allelic rs3091244 is a functionally validated genetic variant, and its allelic frequencies differ significantly between European and Asian populations. Here, we examined the association of rs3091244 with cancer risk in a Chinese population. Methods: rs3091244 was genotyped by Sanger sequencing in 4,971 cancer cases and 2,485 controls. The rs1205 and rs2794521 gene variants were also genotyped using TaqMan assays in subgroups. Results: No association was detected between the genotyped CRP variants and cancer risk, with or without distinguishing cancer types, suggesting that circulating CRP is not causally involved in tumorigenesis in Chinese populations.

Certain engineered nanoparticles (NPs) have unique properties that have exhibited significant potential for promoting photosynthesis and enhancing crop productivity. Understanding the fundamental interactions between NPs and plants is crucial for the sustainable development of nanoenabled agriculture. Leaf mesophyll protoplasts, which maintain similar physiological response and cellular activity as intact plants, were selected as a model system to study the impact of NPs on photosynthesis. The mesophyll protoplasts isolated from spinach were cultivated with different NMs (Fe, Mn3O4, SiO2, Ag, and MoS2) dosing at 50 mg/L for 2 h under illumination. The potential maximum quantum yield and adenosine triphosphate (ATP) production of mesophyll protoplasts were significantly increased by Mn3O4 and Fe NPs (23% and 43%, respectively), and were decreased by Ag and MoS2 NPs. The mechanism for the photosynthetic enhancement by Mn3O4 and Fe is to increase the photocurrent and electron transfer rate, as revealed by photoelectrochemical measurement. GC-MS based single cell type metabolomics reveal that NPs (Fe and MoS2) altered the metabolic profiles of mesophyll cells during 2 h of illumination period. Separately, the effect of NPs exposure on photosynthesis and biomass were also conducted at the whole plant level. A strong correlation was observed with protoplast data; plant biomass was significantly increased by Mn3O4 exposure (57%) but was decreased (24%) by treatment of Ag NPs. The use of mesophyll protoplasts can be a fast and reliable tool for screening NPs to enhance photosynthesis for potential nanofertilizer use. Importantly, inclusion of a metabolic analysis can provide mechanistic toxicity data to ensure the development "safer-by-design" nanoenabled platforms.

The rapid development of nanotechnology makes the environmental impact assessment a necessity to ensure the sustainable use of engineered nanomaterials. Here, silver nanoparticles (AgNPs) at 100 mg/kg were added to soils in the absence or presence of cucumber (Cucumis sativa) plants for 60 days. The response of the soil microbial community and associated soil metabolites was investigated by 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomics, respectively. The results show that AgNP exposure significantly increased the soil pH in both unplanted and cucumber-planted soils. The soil bacterial community structure was altered upon Ag exposure in both soils. Several functionally significant bacterial groups, which are associated with carbon, nitrogen, and phosphorus cycling, were compromised by AgNPs in both unplanted and cucumber-planted soils. Generally, plants played a limited role in mediating the impact of AgNPs on the bacterial community. Soil metabolomic analysis showed that AgNPs altered the metabolite profile in both unplanted and cucumber-planted soils. The significantly changed metabolites are involved in sugar and amino acid-related metabolic pathways, indicating the perturbation of C and N metabolism, which is consistent with the bacterial community structure results. In addition, several fatty acids were significantly decreased upon exposure to AgNPs in both unplanted and cucumber-planted soils, suggesting the possible oxidative stress imposed on microbial cell membranes. These results provide valuable information for understanding the biological and biochemical impact of AgNP exposure on both plant species and on soil microbial communities; such understanding is needed to understand the risk posed by these materials in the environment.

A mechanistic understanding of perfluorooctanoic acid (PFOA) toxicity to plants is essential for future risk assessment of PFOA in agricultural soil. In this study, soil-grown cucumber (Cucumis sativus) was exposed to 0, 0.2, and 5 mg/kg of PFOA for 60 days. At harvest, contaminant accumulation, cucumber biomass, photosynthesis profiles and metabolites were measured. Results showed that PFOA depressed cucumber biomass and accumulated highest in leaves. Photosynthesis analysis revealed that PFOA at both doses reduced the chlorophyll contents and net photosynthesis rate of cucumber leaves. Gas chromatography-mass spectrometry-based non-targeted metabolomics revealed that PFOA induced metabolic reprogramming in cucumber leaves, including up-regulation of phenols (at 0.2 and 5 mg/kg) and down-regulation of amino acids (at 5 mg/kg), indicating disrupted nitrogen and carbon metabolism. Results revealed how PFOA represses plant growth by down-regulating photosynthetic pigments and disturbing the metabolism of carbohydroxides, phenols and amino acids. These findings provide valuable information for understanding the molecular mechanisms involved in plant responses to PFOA-induced stress.

Summary: Chronic allergic itch is a common symptom affecting millions of people and animals, but its pathogenesis is not fully explained. Herein, we show that periostin, abundantly expressed in the skin of patients with atopic dermatitis (AD), induces itch in mice, dogs, and monkeys. We identify the integrin αVβ3 expressed on a subset of sensory neurons as the periostin receptor. Using pharmacological and genetic approaches, we inhibited the function of neuronal integrin αVβ3, which significantly reduces periostin-induced itch in mice. Furthermore, we show that the cytokine TSLP, the application of AD-causing MC903 (calcipotriol), and house dust mites all induce periostin secretion. Finally, we establish that the JAK/STAT pathway is a key regulator of periostin secretion in keratinocytes. Altogether, our results identify a TSLP-periostin reciprocal activation loop that links the skin to the spinal cord via peripheral sensory neurons, and we characterize the non-canonical functional role of an integrin in itch. : Mishra et al. demonstrate periostin-induced itch in mice, dogs, and monkeys and identify the integrin αVβ3 as the periostin neuronal receptor. They find that keratinocytes release periostin in response to TSLP, thus identifying a possible reciprocal vicious circle implicating the cytokine TSLP and periostin in chronic allergic itch. Keywords: atopic dermatitis, AD, chronic allergic itch, integrin, JAK/STAT, keratinocytes, NPPB, periostin, sensory neuron, TRPV1, TRPA1, TSLP

The skin serves as the interface between the body and the environment and plays a fundamental role in innate antimicrobial host immunity. Antiviral proteins are part of the innate host defense system and provide protection against viral pathogens. How breach of the skin barrier influences innate antiviral protein production remains largely unknown. Here, we identify and characterize the induction and regulation of antiviral proteins following skin injury. Transcriptional and phenotypic profiling of cutaneous wounds revealed that skin injury induces high levels of antiviral proteins in both mice and humans, and interleukin (IL)-27 was found to be necessary and sufficient to induce this pattern of expression. Notably, we here link the IL-27-mediated antiviral protein response to a neuro-immune axis. We herein identify how damage to the skin barrier elicits cutaneous nociceptive signaling to activate innate antiviral immune responses. Remarkably, pharmacology or genetic ablation of TRPV1-mediated nociception unveiled that TRPV1 signaling contributes significantly to the induction of antiviral proteins Oas2, Oasl2, and Isg15 via IL-27 in vivo, suggesting that nociception promotes skin antiviral competence through activation of antiviral signaling pathways upon wounding.

Cadmium (Cd) and tetrabromobisphenol A (TBBPA) are two ubiquitous pollutants in soils and are often found together at electronic waste recycling sites. In this study, their toxicity as well as the accumulation and subcellular partitioning of Cd were determined in two ecologically different earthworms Eisenia fetida and Metaphire guillelmi exposed for 14 days to Cd (1 mg kg−1) and TBBPA (10, 50, 100, and 500 mg kg−1) alone and in combination. In general, Cd-TBBPA co-exposure resulted in synergistic effects in terms of acute toxicity, growth inhibition, histopathological changes in body walls, and oxidative stress responses to earthworms, moreover, M. guillelmi showed higher sensitivity than E. fetida. Principal component analysis showed that the two earthworm species differed in their biomarker expression patterns. In addition, Cd accumulation was significantly (P

Inflammation is the body’s protective reaction to injury and infection. Pain is a hallmark of Inflammation and can be either protective or detrimental during acute or chronic phase. Macrophages play a chief role in the pathogenesis of pain and have bilateral communications with nociceptors, the specialized primary sensory neurons that sense pain. Macrophages “talk to” nociceptors by releasing pro-inflammatory mediators (e.g., pro-inflammatory cytokines) that induce pain via direct activation of nociceptors. Macrophages also “listen to” nociceptors, by which nociceptors secrete neuropeptides and chemokines which act on macrophages. Activation of toll-like receptors (TLRs) in nociceptors releases CCL2, activating macrophages and potentiating pathological pain. Emerging evidence also points to a pro-resolution role of macrophages in inflammation and pain. Macrophage GPR37 is activated by neuroprotectin D1, a specialized pro-resolving mediator (SPM) and resolves inflammatory pain via phagocytosis and production of IL-10 that inhibits nociceptors. Macrophage-nociceptor interactions are also mediated by microRNAs and microRNA-containing exosomes in chronic pain. Notably, extracellular microRNAs (e.g., let-7b and miR-711) can directly bind and activate nociceptors. Targeting macrophage-nociceptor interactions will help to control inflammation and pain.

Background Paranosema locustae Canning, 1953 (Microsporidia) provides effective control of grasshoppers. Horizontal transmission of P. locustae is known to occur, and evidence for the mechanism of this transmission via predatory natural enemies has been found. We conducted a 3-year laboratory and field study to assess the potential impact of feces from both grasshoppers Locusta migratoria L. and their natural enemies on the persistence of P. locustae. Results We found that P. locustae persisted among grasshopper populations in treated areas and in adjacent untreated areas for up to 2 years, and the density of grasshoppers decreased in both areas. We showed that healthy grasshoppers could be infected by eating food contaminated by feces from their natural enemies. Grasshopper predators retained a large number of spores acquired from eating grasshoppers infected with P. locustae. Spores in the feces of the main natural enemy, the beetle Pterostichus gebleri Dejean 1828, in the treated area showed clear viability. Conclusion These results demonstrate that predatory natural enemies are important vectors for this microsporidian disease, and suggest that sustainable transmission and continuing population suppression might be achieved by horizontal transmission via natural enemies, which should be maximized to increase the effectiveness of P. locustae. © 2018 Society of Chemical Industry.

The effects of metallic copper nanoparticles (nCu) in plants are not well understood. In this study, soil grown oregano (Origanum vulgare) was exposed for 60days to nCu and Cu microparticles (μCu) at 0-200mgCu/kg. At harvest, Cu accumulation, biomass production, nutrient composition, and Cu fractions in soil were measured. Except for μCu at 50mg/kg, both nCu and μCu increased root Cu (28.4-116.0%) and shoot Cu (83.0-163.0% and 225.4-652.5%, respectively), compared with control. Copper accumulation from μCu increased as the external μCu increased. nCu and μCu did not affect shoot length, malondialdehyde, or chlorophyll, but increased water content (6.9-12.5%) and reduced shoot biomass (21.6-58.5%), compared with control. In addition, at 50mg/kg, μCu decreased root biomass and length (48.6% and 20.5%, respectively) and water content (1.8% and 3.9% at 100 and 200mg/kg, respectively). All treatments modified root and shoot Ca, Fe, Mg, and Mn (p≤0.05). Additionally, all Cu treatments decreased starch (33.9-58.5%), total sugar (39.5-55.7%), and reducing sugar (13.6-33.9%) in leaves. Results showed that metallic Cu nanoparticles/microparticles affected agronomical and physiological parameters in oregano, which could impact human nutrition. However, smaller size particles do not necessarily imply greater toxicity.

Microplastics were reported to adsorb antibiotics and may modify their effects on soil systems. But there has been little research investigating how microplastics may affect the toxicities of antibiotics to microbes under future climate conditions. Here, we used a free-air CO2 enrichment system to investigate the responses of soil microbes to sulfamethazine (SMZ, 1 mg kg−1) in the presence of polystyrene microplastics (PS, 5 mg kg−1) at different CO2 concentrations (ambient at 380 ppm and elevated at 580 ppm). SMZ alone decreased bacterial diversity, negatively affected the bacterial structure and inter-relationships, and enriched the sulfonamide-resistance genes (sul1 and sul2) and class 1 integron (intl1). PS, at both CO2 conditions, showed little effect on soil bacteria but markedly alleviated SMZ’s adverse effects on bacterial diversity, composition and structure, and inhibited sul1 transmission by decreasing the intl1 abundance. Elevated CO2 had limited modification in SMZ’s disadvantages to microbial communities but markedly decreased the sul1 and sul2 abundance. Results indicated that increasing CO2 concentration or the presence of PS affected the responses of soil microbes to SMZ, providing new insights into the risk prediction of antibiotics under future climate conditions.

Large amounts of polystyrene (PS), one of the most widely used plastics in the world, end up in the environment through industrial discharge and littering, becoming one of the major components of plastic debris. Such plastics, especially the small-sized microplastics and nanoplastics, have received increasing concerns in terms of their potential environmental risks. Feasible approaches for the degradation of PS in waste materials and in the environment are highly desirable. Physicochemical pretreatments of PS may be applied to enhance biological degradation. In the present study, we synthesized 14C-labelled PS polymers, either uniformly labelled on the ring ([U-ring-14C]-PS) or labelled at the β-carbon position of the alkyl chain ([β-14C]-PS), and investigated the mineralisation of the 14C-PS polymers by the fungus Penicillium variabile CCF3219 as well as the effect of ozonation as a physico-chemical pre-treatment on the mineralisation by the fungi. Biodegradation of the 14C-PS polymers was studied in liquid medium (pH 7.5, without additional carbon substrate) with P. variabile for 16 weeks. During the incubation time, 14CO2 was captured to calculate the mineralisation of 14C-PS and the remaining polymers were analysed by means of scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectrometry and gel-permeation chromatography (GPC). The results showed that the fungi mineralised both labelled polymers, and that the [U-ring-14C]-PS with a lower molecular weight led to a higher mineralisation rate. Ozonation pre-treatment strongly enhanced mineralisation of [β-14C]-PS. SEM analysis showed that the surface of the ozonated [β-14C]-PS became uneven and rough after the incubation, indicating an attack on the polymer by P. variabile. FT-IR analysis showed that ozonation generated carbonyl groups on the [β-14C]-PS and the amount of the carbonyl groups decreased after incubation of the [β-14C]-PS with P. variabile. GPC analysis showed that the molecular weights of the ozonated [β-14C]-PS decreased after incubation. The present data suggest that ozonation pretreatment could be a potential approach for degradation of PS waste and remediation of PS-contaminated sites.

Tetrabromobisphenol A (TBBPA) is the world's most widely used brominated flame retardant but there is growing concern about its fate and toxicity in terrestrial organisms. In this study, two ecologically different earthworms, Metaphire guillelmi and Eisenia fetida, were exposed to soil spiked with 14C-labeled TBBPA for 21 days. M. guillelmi accumulated more TBBPA than E. fetida, evidenced by a 2.7-fold higher 14C-uptake rate and a 1.3-fold higher biota-soil accumulation factor. Considerable amounts of bound residues (up to 40% for M. guillelmi and 18% for E. fetida) formed rapidly in the bodies of both earthworms. 14C accumulated mostly in the gut of M. guillemi and in the skin of E. fetida, suggesting that its uptake by M. guillelmi was mainly via gut processes whereas in E. fetida epidermal adsorption predominated. The TBBPA transformation potential was greater in M. guillelmi than in E. fetida, since only 5% vs. 34% of extractable 14C remained as the parent compound after 21 days of exposure. Besides polar metabolites, the major metabolites in both earthworms were TBBPA mono- and dimethyl ethers (O-methylation products of TBBPA). Acute toxicity assessments using filter paper and natural soil tests showed that the methylation metabolites were much less toxic than the parent TBBPA to both earthworms. It indicated that earthworms used O-methylation to detoxify TBBPA, and M. guillelmi exhibited the higher detoxification ability than E. fetida. These results imply that if only the free parent compound TBBPA is measured, not only bioaccumulation may be underestimated but also its difference between earthworm species may be misestimated. The species-dependent fate of TBBPA may provide a better indicator of the differing sensitivities of earthworms to this environmental contaminant.

Concerns about the environmental safety of metal-based nanoparticles (MNPs) in aquatic ecosystems are increasing. Simultaneously, elevated atmospheric CO 2 levels are a serious problem worldwide, making it possible for the combined exposure of MNPs and elevated CO 2 to the ecosystem. Here we studied the toxicity of n ZnO to goldfish in a water-sediment ecosystem using open-top chambers flushed with ambient (400 ± 10 μL/L) or elevated (600 ± 10 μL/L) CO 2 for 30 days. We measured the content of Zn in suspension and fish, and analyzed physiological and biochemical changes in fish tissues. Results showed that elevated CO 2 increased the Zn content in suspension by reducing the pH value of water and consequently enhanced the bioavailability and toxicity of n ZnO. Elevated CO 2 led to higher accumulation of Zn in fish tissues (increased by 43.3%, 86.4% and 22.5% in liver, brain and muscle, respectively) when compared to ambient. Elevated CO 2 also intensified the oxidative damage to fish induced by n ZnO, resulting in higher ROS intensity, greater contents of MDA and MT and lower GSH content in liver and brain. Our results suggest that more studies in natural ecosystems are needed to better understand the fate and toxicity of nanoparticles in future CO 2 levels.

Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-α antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia (DRG) and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etanercept and in TNFR1/R2 DKO mice. Dry skin induced TNF-α expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-α/TNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be beneficial for chronic itch treatment.

Mounting evidence supports an important role of chemokines, produced by spinal cord astrocytes, in promoting central sensitization and chronic pain. In particular, CCL2 (C–C motif chemokine ligand 2) has been shown to enhance N-methyl-D-aspartate (NMDA)-induced currents in spinal outer lamina II (IIo) neurons. However, the exact molecular, synaptic, and cellular mechanisms by which CCL2 modulates central sensitization are still unclear. We found that spinal injection of the CCR2 antagonist RS504393 attenuated CCL2- and inflammation-induced hyperalgesia. Single-cell RT-PCR revealed CCR2 expression in excitatory vesicular glutamate transporter subtype 2-positive (VGLUT2+) neurons. CCL2 increased NMDA-induced currents in CCR2+/VGLUT2+ neurons in lamina IIo; it also enhanced the synaptic NMDA currents evoked by dorsal root stimulation; and furthermore, it increased the total and synaptic NMDA currents in somatostatin-expressing excitatory neurons. Finally, intrathecal RS504393 reversed the long-term potentiation evoked in the spinal cord by C-fiber stimulation. Our findings suggest that CCL2 directly modulates synaptic plasticity in CCR2-expressing excitatory neurons in spinal lamina IIo, and this underlies the generation of central sensitization in pathological pain.

Evidence suggests that CO2 modifies the behavior of nanomaterials. Thus, in a few decades, plants might be exposed to additional stress if atmospheric levels of CO2 and the environmental burden of nanomaterials increase at the current pace. Here, we used a full-size free-air CO2 enrichment (FACE) system in farm fields to investigate the effect of elevated CO2 levels on phytotoxicity and microbial toxicity of nTiO2 (0, 50, and 200 mg kg− 1) in a paddy soil system. Results show that nTiO2 did not induce visible signs of toxicity in rice plants cultivated at the ambient CO2 level (370 μmol mol− 1), but under the high CO2 concentration (570 μmol mol− 1) nTiO2 significantly reduced rice biomass by 17.9% and 22.1% at 50 mg kg− 1 and 200 mg kg− 1, respectively, and grain yield by 20.8% and 44.1% at 50 mg kg− 1 and 200 mg kg− 1, respectively. In addition, at the high CO2 concentration, nTiO2 at 200 mg kg− 1 increased accumulation of Ca, Mg, Mn, P, Zn, and Ti by 22.5%, 16.8%, 29.1%, 7.4%, 15.7% and 8.6%, respectively, but reduced fat and total sugar by 11.2% and 25.5%, respectively, in grains. Such conditions also changed the functional composition of soil microbial communities, alerting specific phyla of bacteria and the diversity and richness of protista. Overall, this study suggests that increases in CO2 levels would modify the effects of nTiO2 on the nutritional quality of crops and function of soil microbial communities, with unknown implications for future economics and human health.

Astrocytes are complex glial cells with numerous fine cellular processes that infiltrate the neuropil and interact with synapses. The mechanisms that control the establishment of astrocyte morphology are unknown, and it is unclear whether impairing astrocytic infiltration of the neuropil alters synaptic connectivity. Here we show that astrocyte morphogenesis in the mouse cortex depends on direct contact with neuronal processes and occurs in parallel with the growth and activity of synaptic circuits. The neuroligin family cell adhesion proteins NL1, NL2, and NL3, which are expressed by cortical astrocytes, control astrocyte morphogenesis through interactions with neuronal neurexins. Furthermore, in the absence of astrocytic NL2, the formation and function of cortical excitatory synapses are diminished, whereas inhibitory synaptic function is enhanced. Our findings highlight a previously undescribed mechanism of action for neuroligins and link astrocyte morphogenesis to synaptogenesis. Because neuroligin mutations have been implicated in various neurological disorders, these findings also point towards an astrocyte-based mechanism of neural pathology.

Multiple applications of metal oxide nanoparticles (MONPs) could result in their accumulation in soil, threatening higher terrestrial plants. Several reports have shown the effects of MONPs on plants. In this review, we analyze the most recent reports about the physiological and biochemical responses of plants to stress imposed by MONPs. Findings demonstrate that MONPs may be taken up and accumulated in plant tissues causing adverse or beneficial effects on seed germination, seedling elongation, photosynthesis, antioxidative stress response, agronomic, and yield characteristics. Given the importance of determining the potential risks of MONPs on crops and other terrestrial higher plants, research questions about field long-term conditions, transgenernational phytotoxicity, genotype specific sensitivity, and combined pollution problems should be considered.

Soil toxicological tests are commonly performed using Eisenia fetida as the standard earthworm species, but it is tolerant to a wide range of pollutants. Therefore, the inclusion of susceptible species is crucial for the accurate estimation of soil contamination. In this study, we examined the sensitivity to soil cadmium (Cd) of anecic Metaphire guillelmi and epigeic E. fetida by measuring multiple indexes of oxidative stress. Using subcellular partitioning analysis, we further elucidated the inherent mechanism underlying the species-specific sensitivity of the two earthworm species. Among the battery of biochemical indexes, reactive oxygen species and protein carbonyl groups served as sensitive biomarkers. According to their respective response thresholds, M. guillelmi was more sensitive than E. fetida and they differed in their dose-response relationships. In E. fetida, the activities of three antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST), exhibited a hormesis-like U-shaped dose-response relationship, while in M. guillelmi SOD, glutathione peroxidase (an analogue of CAT) and GST showed an inverted U-shaped relationship. The concentrations of Cd in the subcellular fractions and whole body of the earthworms well fit (R2>0.9) a saturation model versus bioavailable Cd concentrations determined by the diffusive gradients in thin films technique. Despite the lower accumulation capacity of M. guillelmi, the Cd-binding capacity (Cmax) of its subcellular heat-stable protein fraction, the so-called biologically detoxified metal pool, was 2.7 times lower than that of E. fetida, whereas the Cd binding affinity (logK) of its heat-denatured protein fraction, i.e. the metal-sensitive fraction, was 3.0 times higher, which accounted for the high susceptibility of M. guillelmi to soil Cd. Our results suggest that because of their sensitivity, as exemplified by M. guillelmi, native earthworm species should be taken into account in soil risk assessments to avoid underestimation of the toxicity of various pollutants.

Contamination of fine plastic particles (FPs), including micrometer to millimeter plastics (MPs) and nanometer plastics (NPs), in the environment has caught great concerns. FPs are strong adsorbents for hydrophobic toxic pollutants and may affect their fate and toxicity in the environment; however, such information is still rare. We studied joint toxicity of FPs with phenanthrene to Daphnia magna and effects of FPs on the environmental fate and bioaccumulation of 14C-phenanthrene in fresh water. Within the five sizes particles we tested (from 50 nm to 10 μm), 50-nm NPs showed significant toxicity and physical damage to D. magna. The joint toxicity of 50-nm NPs and phenanthrene to D. magna showed an additive effect. During a 14-days incubation, the presence of NPs significantly enhanced bioaccumulation of phenanthrene-derived residues in daphnid body and inhibited the dissipation and transformation of phenanthrene in the medium, while 10-μm MPs did not show significant effects on the bioaccumulation, dissipation, and transformation of phenanthrene. The differences may be attributed to higher adsorption of phenanthrene on 50-nm NPs than 10-μm MPs. Our findings underlined the high potential ecological risks of FPs, and suggested that NPs should be given more concerns, in terms of their interaction with hydrophobic pollutants in the environment.