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2,4,6-Trichlorophenol (2,4,6-TCP) is extensively consumed in industrial production and may cause environmental damages. The effect of halide ions on the decomposition of 2,4,6-TCP has often been overlooked. In this study, the bromide ion was found to have a stronger negative impact on 2,4,6-TCP degradation than chloride ion in the O3 system, and led to the formation of adsorbable organic halogens (AOX). Kinetic modeling demonstrated that the concentration of various radicals was largely depended on the solution pH, and stronger basicity not only contributed to the mineralization of 2,4,6-TCP, but also inhibited the formation of halogenated by-products. Combining the intermediate identification and quantum chemical calculation, the degradation pathways of 2,4,6-TCP during ozone oxidation process were proposed. The toxicity test and ECOSAR simulation demonstrated that the acute toxicity of some 2,4,6-TCP degradation intermediates was relatively higher than their parent compound. With high concentrations of halide ions, the ozone-treated solution showed greater toxicity than the originator 2,4,6-TCP solution. These results illustrate that the ozone treatment of the halide-containing wastewater may cause potential ecological hazards and its application needs to be more cautious.

Lesion mimic mutants (LMMs) are ideal materials for studying programmed cell death and defense response in plants. Here we report investigations on two LMMs (msl-1 and msl-2) from the indica rice cultivar JG30 treated by ethyl methyl sulfone. Both of the mutants showed similar mosaic spot lesions at seedling stage, but they displayed different phenotypes along with development of the plants. At tillering stage, larger orange spots appeared on leaves of msl-2, while only small reddish-brown spots exhibit on leaves of msl-1. At heading stage, the msl-2 plants were completely dead, while the msl-1 plants were still alive even if showed apparent premature senility. For both the mutants, the mosaic spot lesion formation was induced by light; DAB and trypan blue staining showed a large amount of hydrogen peroxide accumulated at the lesion sites, accompanied by a large number of cell death. Consequently, reactive oxygen species were enriched in leaves of the mutants; SOD and CAT activities in the scavenging enzyme system were decreased compared with the wild type. In addition, degraded chloroplasts, decreased photosynthetic pigment content, down-regulated expression of genes associated with chloroplast synthesis/photosynthesis and up-regulated expression of genes related to senescence were detected in the mutants, but the abnormality of msl-2 was more serious than that of msl-1 in general. Genetic analysis and map-based cloning revealed that the lesion mimic and premature senescence traits of both the mutants were controlled by recessive mutated alleles of the SL (Sekiguchi lesion) gene, which encodes the CYP71P1 protein belonging to cytochrome P450 monooxygenase family. The difference of mutation sites and mutation types (SNP-caused single amino acid change and SNP-caused early termination of translation) led to the different phenotypes in severity between msl-1 and msl-2. Taken together, this work revealed that the CYP71P1 is involved in regulation of both premature senescence and cell death in rice, and its different mutation sites and mutation types could cause different phenotypes in terms of severity.

Antibiotics have raised significant concern as emerging pollutants for their increasing consumption, persistent input, and potential threat to ecological environment. Due to low concentrations and various types in coastal water, simultaneous quantification of all kinds of antibiotics is time-consuming and costly. In order to make antibiotic regular monitoring in coastal water possible, identifying the priority antibiotics in the environment is essential. Here, a method for screening the priority antibiotics in coastal water was proposed, considering individual antibiotic concentration, the positive correlation between individual and total antibiotic concentration, the detection frequency, and obvious ecological risk. Taking coastal water of the East China Sea as an example, on a list of 77 target antibiotics, 7 (SMX, TMP, SCP, SMP, CNX, ATM, and ETM) and 4 (SMX, SCP, SMP, and CNX) antibiotics were selected to be the priority antibiotics in 2017 and 2018, respectively. Furthermore, the 4 priority antibiotics in 2018 were all involved in the 7 priority antibiotics in 2017. The sum of the priority antibiotic concentrations accounted for 0.8% and 23.2% of total antibiotic concentrations, and the sum of their RQ accounted for 69.2% and 66.8% of total RQ values in 2017 and 2018, respectively. Among the above 7 priority antibiotics, ATM is mainly used in human clinical, SMX, SCP, and SMP are mainly consumed in veterinary medicine, TMP, CNX, and ETM are commonly used for humans and animals. The proposed method might provide an important reference for the monitoring and management of antibiotic pollution in coastal water.

Metabolic programs are crucial for T reg cell stability and function. Yu et al. report that TRAF3IP3 acts as a pivotal regulator in controlling metabolic fitness to maintain T reg cell stability and function at the lysosome., Metabolic programs are crucial for regulatory T (T reg) cell stability and function, but the underlying mechanisms that regulate T reg cell metabolism are elusive. Here, we report that lysosomal TRAF3IP3 acts as a pivotal regulator in the maintenance of T reg cell metabolic fitness. T reg–specific deletion of Traf3ip3 impairs T reg cell function, causing the development of inflammatory disorders and stronger antitumor T cell responses in mice. Excessive mechanistic target of rapamycin complex 1 (mTORC1)–mediated hyper-glycolytic metabolism is responsible for the instability of TRAF3IP3-deficient T reg cells. Mechanistically, TRAF3IP3 restricts mTORC1 signaling by recruiting the serine-threonine phosphatase catalytic subunit (PP2Ac) to the lysosome, thereby facilitating the interaction of PP2Ac with the mTORC1 component Raptor. Our results define TRAF3IP3 as a metabolic regulator in T reg cell stability and function and suggest a lysosome-specific mTORC1 signaling mechanism that regulates T reg cell metabolism., Graphical Abstract

The distribution of 77 antibiotics in the coastal water and sediment from 3 bays of the East China Sea was investigated. There were 43 and 25 antibiotics detected with total concentrations of 30.8–2106.1 ng/L and 2.2–99.9 ng/g in water and sediment, respectively. Approximately 83.0% and 85.4% of the individual antibiotic concentrations were lower than 5.0 ng/L in water and 1.0 ng/g in sediment. Clindamycin (1.2–1507.9 ng/L, mean 183.8 ng/L) and erythromycin (ND–45.2 ng/g, mean 3.4 ng/g) were the most abundant in water and sediment, respectively. Ecological risk assessment revealed that the joint toxicity was enhanced when multiple antibiotics were present simultaneously. A decrease in the total antibiotic concentration and the ecological risk in water was observed from nearshore to offshore. Three antibiotics (sulfamethoxypyridazine, sulfamethoxazole and cinoxacin) were selected to be prioritized based on ecological risks for antibiotics monitoring and management of the coastal water in the East China Sea.

Our ex vivo and in vivo studies demonstrate a molecular pathway for exercise-induced learning enhancement., Physical exercise improves learning and memory, but little in vivo evidence has been provided to illustrate the molecular mechanisms. Here, we show that chronic treadmill exercise activates the mechanistic target of rapamycin (mTOR) pathway in mouse motor cortex. Both ex vivo and in vivo recordings suggest that mTOR activation leads to potentiated postsynaptic excitation and enhanced neuronal activity of layer 5 pyramidal neurons after exercise, in association with increased oligodendrogenesis and axonal myelination. Exercise training also increases dendritic spine formation and motor learning. Together, exercise activates mTOR pathway, which is necessary for spinogenesis, neuronal activation, and axonal myelination leading to improved motor learning. This model provides new insights for neural network adaptations through exercises and supports the intervention of cognitive deficits using exercise training.

Minimal hepatic encephalopathy (MHE) is characterized as cognitive deficits including memory and learning dysfunctions after liver injuries or hepatic diseases. Our understandings of neurological mechanisms of MHE-associated cognitive syndromes, however, are far from complete. In the current study we generated a mouse MHE model by repetitive administrations of thioacetamide (TAA), which induced hyperammonemia plus elevated proinflammatory cytokines in both the general circulation and motor cortex. MHE mice presented prominent motor learning deficits, which were associated with excess dendritic spine pruning in the motor cortex under 2-photon in vivo microscopy. The pharmaceutical blockade of glucocorticoid receptor or suppression of its biosynthesis further rescued motor learning deficits and synaptic protein loss. Moreover, MHE mice presented microglial activation, which can be alleviated after glucocorticoid pathway inhibition. In sum, our data demonstrates corticosterone-induced microglial activation, synaptic over-pruning and motor learning impairments in MHE, providing new insights for MHE pathogenesis and potential targets of clinical interventions.

Autistic spectral disorder (ASD) is a prevalent neurodevelopmental disease that affects multiple brain regions. Both clinical and animal studies have revealed the possible involvement of the cerebellum in ASD pathology. In this study, we generated a rodent ASD model through a single prenatal administration of valproic acid (VPA) into pregnant mice, followed by cerebellar morphological and functional studies of the offspring. Behavioral studies showed that VPA exposure led to retardation of critical motor reflexes in juveniles and impaired learning in a tone-conditioned complex motor task in adults. These behavioral phenotypes were associated with premature migration and excess apoptosis of the granular cell (GC) precursor in the cerebellar cortex during the early postnatal period, and the decreased cell density and impaired dendritic arborization of the Purkinje neurons. On acute cerebellar slices, suppressed synaptic transmission of the Purkinje cells were reported in the VPA-treated mice. In summary, converging evidence from anatomical, electrophysiological and behavioral abnormalities in the VPA-treated mice suggest cerebellar pathology in ASD and indicate the potential values of motor dysfunction in the early diagnosis of ASD.

Viral infection causes host cells to produce type I IFNs, which play a critical role in viral clearance. IFN regulatory factor (IRF) 7 is the master regulator of type I IFN-dependent immune responses. In this article, we report that N-Myc and STATs interactor (Nmi), a Sendai virus–inducible protein, interacted with IRF7 and inhibited virus-triggered type I IFN production. The overexpression of Nmi inhibited the Sendai virus–triggered induction of type I IFNs, whereas the knockdown of Nmi promoted IFN production. Furthermore, the enhanced production of IFNs resulting from Nmi knockdown was sufficient to protect cells from infection by vesicular stomatitis virus. In addition, Nmi was found to promote the K48-linked ubiquitination of IRF7 and the proteasome-dependent degradation of this protein. Finally, an impairment of antiviral responses is also detectable in Nmi-transgenic mice. These findings suggest that Nmi is a negative regulator of the virus-triggered induction of type I IFNs that targets IRF7.

Perforin is a pore-forming protein engaged mainly in mediating target T cell death and is employed by cytotoxic T lymphocytes (CTLs) and natural killer cells. However, whether it also plays a role in conventional CD4(+) T cell function remains unclear. Here we report that in perforin-deficient (PKO) mice, CD4(+) T cells are hyperproliferative in response to T cell receptor (TCR) stimulation. This feature of hyperproliferation is accompanied by the enhancement both in cell division and in IL-2 secretion. It seems that the perforin deficiency does not influence T cell development in thymus spleen and lymph node. In vivo, perforin deficiency results in increased antigen-specific T cell proliferation and antibody production. Furthermore, PKO mice are more susceptible to experimental autoimmune uveitis. To address the molecular mechanism, we found that after TCR stimulation, CD4(+) T cells from PKO mice display an increased intracellular calcium flux and subsequently enhance activation of transcription factor NFAT1. Our results indicate that perforin plays a negative role in regulating CD4(+) T cell activation and immune response by affecting TCR-dependent Ca(2+) signaling.