Regulation of hepatocyte phospholipid peroxidation signaling by a Chinese patent medicine against psychological stress-induced liver injury.

BACKGROUND: Psychological stress is associated with various diseases including liver dysfunction, yet effective intervention strategies remain lacking due to the unrevealed pathogenesis mechanism. PURPOSE: This study aims to explore the relevance between BMAL1-controlled circadian rhythms and lipoxygenase 15 (ALOX15)-mediated phospholipids peroxidation in psychological stress-induced liver injury, and to investigate whether hepatocyte phospholipid peroxidation signaling is involved in the hepatoprotective effects of a Chinese patent medicine, Pien Tze Huang (PZH). METHODS: Restraint stress models were established to investigate the underlying molecular mechanisms of psychological stress-induced liver injury and the hepatoprotective effects of PZH. Redox lipidomics based on liquid chromatography-tandem mass spectrometry was applied for lipid profiling. RESULTS: The present study discovered that acute restraint stress could induce liver injury. Notably, lipidomic analysis confirmed that phospholipid peroxidation was accumulated in the livers of stressed mice. Additionally, the essential core circadian clock gene Brain and Muscle Arnt-like Protein-1 (Bmal1) was altered in stressed mice. Circadian disruption in mice, as well as BMAL1-overexpression in human HepaRG cells, also appeared to have a significant increase in phospholipid peroxidation, suggesting that stress-induced liver injury is closely related to circadian rhythm and phospholipid peroxidation. Subsequently, arachidonate 15-lipoxygenase (ALOX15), a critical enzyme that contributed to phospholipid peroxidation, was screened as a potential regulatory target of BMAL1. Mechanistically, BMAL1 promoted ALOX15 expression via direct binding to an E-box-like motif in the promoter. Finally, this study revealed that PZH treatment significantly relieved pathological symptoms of psychological stress-induced liver injury with a potential mechanism of alleviating ALOX15-mediated phospholipid peroxidation. CONCLUSION: Our findings illustrate the critical role of BMAL1-triggered phospholipid peroxidation in psychological stress-induced liver injury and provide new insight into treating psychological stress-associated liver diseases by TCM intervention.

DEAD-box helicase 1 inhibited CD8+ T cell antitumor activity by inducing PD-L1 expression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) does not respond well to current treatments, even immune checkpoint inhibitors. PD-L1 (programmed cell death ligand 1 or CD274 molecule)-mediated immune escape of tumor cells may be a key factor affecting the efficacy of immune checkpoint inhibitor (ICI) therapy. However, the regulatory mechanisms of PD-L1 expression and immune escape require further exploration. Here, we observed that DDX1 (DEAD-box helicase 1) was overexpressed in HCC tissues and associated with poor prognosis in patients with HCC. Additionally, DDX1 expression correlated negatively with CD8+ T cell frequency. DDX1 overexpression significantly increased interferon gamma (IFN-γ)-mediated PD-L1 expression in HCC cell lines. DDX1 overexpression decreased IFN-γ and granzyme B production in CD8+ T cells and inhibited CD8+ T cell cytotoxic function in vitro and in vivo. In conclusion, DDX1 plays an essential role in developing the immune escape microenvironment, rendering it a potential predictor of ICI therapy efficacy in HCC.

Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.

Ab initio studies of counterion effects in molecular quantum-dot cellular automata.

Molecular quantum-dot cellular automata (QCA) is a low-power computing paradigm that may offer ultra-high device densities and THz-speed switching at room temperature. A single mixed-valence (MV) molecule acts as an elementary QCA device known as a cell. Cells coupled locally via the electrostatic field form logic circuits. However, previously-synthesized ionic MV molecular cells are affected by randomly-located, nearby neutralizing counterions that can bias device states or change device characteristics, causing incorrect computational results. This ab initio study explores how non-biasing counterions affect individual molecular cells. Additionally, we model two novel neutral, zwitterionic MV QCA molecules designed to avoid biasing and other undesirable counterionic effects. The location of the neutralizing counterion is controlled by integrating one counterion into each cell at a well-defined, non-biasing location. Each zwitterionic QCA candidate molecule presented here has a fixed, integrated counterion, which neutralizes the mobile charges used to encode the device state.

Scutellaria baicalensis: a promising natural source of antiviral compounds for the treatment of viral diseases.

Viruses, the smallest microorganisms, continue to present an escalating threat to human health, being the leading cause of mortality worldwide. Over the decades, although significant progress has been made in the development of therapies and vaccines against viral diseases, the need for effective antiviral interventions remains urgent. This urgency stems from the lack of effective vaccines, the severe side effects associated with current drugs, and the emergence of drug-resistant viral strains. Natural plants, particularly traditionally-used herbs, are often considered an excellent source of medicinal drugs with potent antiviral efficacy, as well as a substantial safety profile. Scutellaria baicalensis, a traditional Chinese medicine, has garnered considerable attention due to its extensive investigation across diverse therapeutic areas and its demonstrated efficacy in both preclinical and clinical trials. In this review, we mainly focused on the potential antiviral activities of ingredients in Scutellaria baicalensis, shedding light on their underlying mechanisms of action and therapeutic applications in the treatment of viral infections.

Mechanism of Xiezhuo Huayu Yiqi Tongluo Formula in the Treatment of Uric Acid Nephropathy Based on Network Pharmacology, Molecular Docking, and In Vivo Experiments.

Background: Xiezhuo Huayu Yiqi Tongluo Formula (XHYTF) consists of 14 Chinese herbal medicines. In this study, we investigated the potential mechanism of XHYTF in the treatment of uric acid nephropathy (UAN) through network pharmacology, molecular docking, and in vivo methods. Methods: Using various pharmacological databases and analysis platforms, information on the active ingredients and targets of Chinese herbal medicine was collected, and UAN disease targets were retrieved using OMIM, Gene Cards, and NCBI. Then common target proteins were integrated. A Drug-Component-Target (D-C-T) map was constructed to screen core compounds and build a protein-protein interaction (PPI) network. Further, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for common targets, and a Drug-Component-Target-Pathway (D-C-T-P) network diagram was constructed. The molecular docking simulation was performed to verify the binding affinity between core components and hub targets. Subsequently, the UAN rat model was established, followed by the collection of serum and renal tissues. The expression levels of indicators in the serum were determined using an enzyme-linked immunosorbent assay. The pathological changes of renal tissues were detected using H & E staining and Masson staining. The expression of related proteins in renal tissue was detected by western blot. Results: In the study, 216 active ingredients and 439 targets in XHYTF were screened, and 868 targets were identified as being related to UAN. Among them, 115 were common targets. Based on the D-C-T network, quercetin, luteolin, ß-sitosterol, and stigmasterol were observed to be the key active ingredients of XHYTF that were effective against UAN. The analysis of the PPI network revealed TNF, IL6, AKT1, PPARG, and IL1ß as the 5 key targets. GO enrichment analysis revealed that the pathways were mainly concentrated in cell killing, regulation of signaling receptor activity, and other activities. Subsequently, KEGG pathway analysis revealed that multiple signaling pathways, including the HIF-1, PI3K-Akt, IL-17, and other signaling pathways, were closely related to the action of XHYTF. All 5 key targets were confirmed to interact with all core active ingredients. In vivo experiments indicated that XHYTF significantly reduced blood uric acid and creatinine levels, alleviated inflammatory cell infiltration in kidney tissues, reduced the levels of serum inflammatory factors such as TNF-α and IL1ß, and ameliorated renal fibrosis in rats with UAN. Finally, western blot revealed decreased levels of PI3K and AKT1 proteins in the kidney, which confirmed the hypothesis. Conclusion: Collectively, our observations demonstrated that XHYTF significantly protects kidney function, including alleviation of inflammation and renal fibrosis via multiple pathways. This study provided novel insights into the treatment of UAN using traditional Chinese medicines.

Reduced graphene oxide accelerates the dissipation of 14C-Triclosan in paddy soil via adsorption interactions.

Reduced graphene oxide (RGO) is one of common carbon nanomaterials, which is widely used in various fields. Triclosan is an antimicrobial agent added in pharmaceuticals and personal care products. Extensive release of RGO and triclosan has posed potential risks to humans and the environment. The impact of RGO on the fate of triclosan in paddy soil is poorly known. 14C-Triclosan was employed in the present study to determine its distribution, degradation and mineralization in paddy soil mixed with RGO. Compared with the control, RGO (500 mg kg-1) significantly inhibited the mineralization of 14C-triclosan, and reduced its extractability by 6.5%. The bound residues of triclosan in RGO-contaminated soil (100 and 500 mg kg-1) were 2.9-13.3% greater than that of the control at 112 d. RGO also accelerated the dissipation of triclosan, and its degradation products in both treatments and controls were tentatively identified via 14C-labeling method and LC-Q-TOF-MS analysis. The concentrations of the major metabolites (methyl-triclosan and dechlorinated dimer) were inversely related with the concentrations of RGO. RGO at 50 mg kg-1 or lower had a negligible effect on the degradation of triclosan in paddy soil. Triclosan was strongly adsorbed onto RGO-contaminated soil, which may play a vital role in the fate of triclosan in RGO-contaminated paddy soil. Interestingly, RGO had little effect on triclosan-degrading bacteria via soil microbial community analysis. This study helps understand the effects of RGO on the transformation of triclosan in paddy soil, which is of significance to evaluate the environmental risk of triclosan in RGO-contaminated soil.

Designing boron-cluster-centered zwitterionic Y-shaped clocked QCA molecules.

Quantum-dot cellular automata (QCA) is a nanoscale, transistor-less device technology. A single molecule may provide an elementary QCA device known as a cell. Molecular redox centers function as quantum dots, and the configuration of mobile charge on the dots encodes device states useful for classical computing. Molecular QCA may support ultra-high device densities and THz-scale switching speeds at room temperature. An applied electric field may be used to clock molecular QCA, providing power gain to boost weakened signals, as well as quasi-adiabatic device operation for minimal power dissipation in QCA devices and circuits. A zwitterionic, Y-shaped, three-dot molecule may function as a field-clocked QCA cell. We focus on the design of a counterion built into the center of the cell.Ab initiocomputations demonstrate that choice of counterion determines the number of mobile charges for encoding the device state on the three quantum dots. We useB5H52-orB4CH5-as the central counterionic linker for two different Y-shaped, three-dot QCA molecules. While both molecules support the desired device states, the number of trapped charges in the counterion determines the number of mobile holes on the molecular quantum dots. This, in turn, determines whether the device state is encoded by a hole or an electron. This choice of encoding determines how the molecular QCA cell responds to a clocking field. The two counterions studied here lead to two QCA molecules with opposite responses to the clock, similar to the complementary responses of PMOS and NMOS transistors to gated voltage control.

Nucleosome-Omics: A Perspective on the Epigenetic Code and 3D Genome Landscape.

Genetic information is loaded on chromatin, which involves DNA sequence arrangement and the epigenetic landscape. The epigenetic information including DNA methylation, nucleosome positioning, histone modification, 3D chromatin conformation, and so on, has a crucial impact on gene transcriptional regulation. Out of them, nucleosomes, as basal chromatin structural units, play an important central role in epigenetic code. With the discovery of nucleosomes, various nucleosome-level technologies have been developed and applied, pushing epigenetics to a new climax. As the underlying methodology, next-generation sequencing technology has emerged and allowed scientists to understand the epigenetic landscape at a genome-wide level. Combining with NGS, nucleosome-omics (or nucleosomics) provides a fresh perspective on the epigenetic code and 3D genome landscape. Here, we summarized and discussed research progress in technology development and application of nucleosome-omics. We foresee the future directions of epigenetic development at the nucleosome level.

Injectable conductive and angiogenic hydrogels for chronic diabetic wound treatment.

Chronic diabetic wounds are lack of angiogenesis and susceptible to bacterial infections due to their high sugar microenvironment, making them difficult to heal. Here, a conductive and intrinsically antibacterial hydrogel with pH responsiveness has been developed. This hydrogel has good mechanical properties, self-healing ability and biocompatibility, and can smartly release the pro-angiogenic drug, deferoxamine. Application of the hydrogel promotes the proliferation and migration of endothelial cells and enhances vascularization by upregulating the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor. The hydrogel dressing combined with electrical stimulation improves angiogenesis and significantly accelerates the healing of infected diabetic wounds, which would lead to a promising therapeutic strategy.

Distinct uptake and accumulation profiles of triclosan in youdonger (Brassica campestris subsp. Chinensis var. communis) under two planting systems: Evidence from 14C tracing techniques.

Triclosan is a widely used biocide against microorganisms and is ubiquitously distributed in the environment. Triclosan can be accumulated into plants from soil and hydroponic media. However, little information is currently available on the comparative fate of triclosan in plants under soil and hydroponics cultivation conditions and factors governing uptake. Therefore, this study was designed to comparatively elucidate the uptake mechanism of 14C-triclosan in youdonger (Brassica campestris subsp. Chinensis var. communis) grown under different soils and hydroponics and clarify dominant uptake factors. Results showed that 77.2% of 14C were accumulated in youdonger grown in a hydroponic system, while only 1.24%-2.33% were accumulated in the two soil-planting systems. In addition, the bioconcentration factor (BCF) of 14C-triclosan in soil-plant systems was approximately 400-fold smaller than that in the hydroponics. In the soil-planting system, a strong linear correlation was found between concentrations of triclosan in soil pore water and youdonger plant (R2 > 0.85, p < 0.01) at different incubation times. Therefore, triclosan in pore water might be a good indicator to estimate its accumulation in plants and is significantly affected by soil pH, clay, and organic matter contents. The estimated average dietary intakes of triclosan for youdonger grown in hydroponic and soil-planting systems were estimated to be 1.31 ng day-1 kg-1 and 0.05-0.12 ng day-1 kg-1, respectively, much lower than the acceptable dietary intakes of triclosan (83 µg day-1 kg-1), indicating no significant human health risks from youdonger consumption. This study provided insights into uptake routes of triclosan into youdonger plants from both soil and hydroponic systems, bioavailability of triclosan in different soils, and further assessment of human exposure to triclosan from youdonger.

Single-cell omics: A new direction for functional genetic research in human diseases and animal models.

Over the past decade, with the development of high-throughput single-cell sequencing technology, single-cell omics has been emerged as a powerful tool to understand the molecular basis of cellular mechanisms and refine our knowledge of diverse cell states. They can reveal the heterogeneity at different genetic layers and elucidate their associations by multiple omics analysis, providing a more comprehensive genetic map of biological regulatory networks. In the post-GWAS era, the molecular biological mechanisms influencing human diseases will be further elucidated by single-cell omics. This review mainly summarizes the development and trend of single-cell omics. This involves single-cell omics technologies, single-cell multi-omics technologies, multiple omics data integration methods, applications in various human organs and diseases, classic laboratory cell lines, and animal disease models. The review will reveal some perspectives for elucidating human diseases and constructing animal models.

Intrinsic Antibacterial and Conductive Hydrogels Based on the Distinct Bactericidal Effect of Polyaniline for Infected Chronic Wound Healing.

Most chronic wounds suffer from infections, and their treatment is challenging. The usage of antibiotics may lead to bacterial resistance and adverse side effects. Positively charged substances have shown promise, but their applications are usually limited by certain cytotoxicity or complex synthesis. Doped polyaniline that carries a high density of positive charges would be a promising candidate due to its good biocompatibility and easy availability, but its interaction with bacteria has not been elucidated. Herein, the distinct bactericidal effect of polyaniline against Gram-positive bacteria has been verified. The antibacterial activity may result from the specific interaction with lipoteichoic acid to destroy the Gram-positive bacterial cell wall. Polyaniline and a macromolecular dopant (sulfonated hyaluronic acid) are used to construct a flexible hydrogel with skin-mimic electrical conductivity. The in vivo results demonstrate that electrical stimulation (ES) through this hydrogel is superior to ES via separated electrodes (the ES strategy used clinically) for promoting infected chronic wound healing.

Conductive dual hydrogen bonding hydrogels for the electrical stimulation of infected chronic wounds.

Electrical stimulation (ES) via rigid electrodes near the wound is one of the promising approaches for chronic wound treatment, but it is unable to stimulate the whole wound area and treat infected wounds. In this study, a tough conductive hydrogel was prepared by the copolymerization of N-acryloyl glycinamide (NAGA) with quaternized chitosan-g-polyaniline (QCSP). The hydrogel showed a similar conductivity to the human skin and robust mechanical properties due to the dual hydrogen bonding motifs. The grafted polyaniline segments and functionalized quaternary ammonium groups showed intense antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus biofilms. The in vivo assay in diabetic rats proves that the ES via the conductive hydrogel was more effective in promoting the healing of infected wounds than the conventional ES via rigid electrodes. Due to the excellent flexibility and antibacterial properties, this conductive hydrogel shows great promise for infected chronic wound treatment.

Synthesis and Characterization of Salinomycin-Loaded High-Density Lipoprotein and Its Effects on Cervical Cancer Cells and Cervical Cancer Stem Cells.

BACKGROUND: Cervical cancer stem cells (CCSCs), a small part of tumor population, are one of the important reasons for metastasis and recurrence of cervical cancer. Targeting CCSCs may be an effective way to eliminate tumors. Salinomycin (Sal) has been proved to be an effective anticancer drug in many studies, especially for cancer stem cells (CSCs). However, the cytotoxicity of salinomycin limits its further research as an anticancer drug. High-density lipoprotein (HDL) nanoparticles are an excellent drug carrier, which can reduce the toxicity of Sal, have a certain targeting effect and improve the clinical benefit of Sal. METHODS: Salinomycin-loaded high-density lipoprotein (S-HDL) was synthesized and characterized by various analytical techniques. CD44highCD24low CCSCs were isolated from HeLa cells by magnetic separation. The uptake of HDL nanoparticles was observed by laser confocal microscopy, and the effect of S-HDL on the proliferation of CCCs and CCSCs was detected by cell viability analysis. Genome-wide analysis was used to analyze the effects of S-HDL on the biological processes of CCCs and then cell apoptosis, cell cycle and cell migration were selected for verification. RESULTS: S-HDL had a particle size of 38.98 ± 1.78 nm and an encapsulation efficiency of 50.73 ± 4.29%. Cell uptake analysis showed that HDL nanoparticles could enhance the drug uptake of CCCs and CCSCs and may target CCCs and CCSCs. In cell viability analysis, CCCs and CCSCs showed high sensitivity to S-HDL. S-HDL can more efficiently prevent CCSCs from developing tumorspheres than Sal in tumorsphere formation study. S-HDL had stronger ability to induce cell cycle arrest, promote cell apoptosis and inhibit cell migration compared with free Sal, which was consistent with the results of Genome Wide analysis. CONCLUSION: S-HDL can effectively target and eliminate CCCs and CCSCs, which is a potential drug for the treatment of cervical cancer.

Soft-hard hybrid covalent-network polymer sponges with super resilience, recoverable energy dissipation and fatigue resistance under large deformation.

Energy absorption or dissipation ability has been widely developed in tough hydrogels and 3D nano-structured sponges for a variety of applications. However, fully recoverable energy dissipation and fatigue resistance under large deformation is still challenging yet highly desirable. Polymer network with homogeneous chemical crosslinking structures is an efficient way to construct hydrogels with high resilience and fatigue resistance. Unfortunately, such polymer network usually has poor energy dissipation capability. In this paper, we propose a new approach to build the ability of fully recoverable energy dissipation into covalent-crosslink polymer network by integrating soft and hard chains in a uniform crosslinking network and present the one-pot synthesis method for constructing corresponding polymer sponges by low-temperature phase-separation photopolymerization. The application of such polymer sponges as a tissue engineering scaffold, fabricated by using cyclic acetal units and PEG based monomers in particular is demonstrated. For the first time, we show the feasibility of building a synthetic scaffold with the characteristics of high porosity, super compressibility and resilience, fast recovery, completely recoverable energy dissipation, high fatigue resistance, biodegradability and biocompatibility. Such a scaffold is promising in tissue engineering especially in load-bearing applications.

Translocation and metabolism of imidacloprid in cabbage: Application of 14C-labelling and LC-QTOF-MS.

Imidacloprid (IMI) is a widely used neonicotinoid insecticide effective against sucking and some chewing insects. Translocation and metabolism of IMI in plants are related to food safety. In this study, 14C-labeled IMI was used to investigate its translocation, transformation, radioactive IMI metabolites and possible metabolic pathways in cabbage. The amount of IMI accumulated in the edible part of cabbage accounted for 80.3-95.4% of the applied amounts by foliar application. There was a tendency to transport from edible parts to inedible parts. The proportions of extractable IMI decreased gradually from 92.4% to 83.0% in edible parts, greater than that in inedible parts over the experiment (0-19 days), while the bound residues showed an opposite trend. The half-life of IMI was determined as 33.0 and 63.0 days in the edible parts and whole plant, respectively. Five radioactive components including the parent IMI were detected by HPLC-LSC. The relative content of M1 was less than 0.01 mg kg-1, which was not required to identify according to the metabolic scheme proposed by the US Environmental Protection Agency. The metabolites N-nitro(1-6-chloro-3-pyridylmethyl)-4,5-dihydroxyimidazol-2-imine (M2), N-nitro(1-6-chloro-3-pyridylmethyl)-4/5-hydroxyimidazole-2-imine (M3) and 1/3-(1-6-chloro-3-pyridylmethyl)-2,4-imidazodione (M4) were identified by LC-QTOF-MS. The primary metabolism of IMI in cabbage included hydrolysis and oxidation. The residue level and daily intake values of IMI in cabbage were estimated to be 0.033-0.078 mg kg-1 and 9.56-20.01 ng d-1 kg-1, respectively, which were far below the maximum residue level and allowable daily intake values.

Novel insights into stress-induced susceptibility to influenza: corticosterone impacts interferon-ß responses by Mfn2-mediated ubiquitin degradation of MAVS.

Although stress has been known to increase the susceptibility of pathogen infection, the underlying mechanism remains elusive. In this study, we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus (H1N1) and obviously aggravated lung inflammation. Corticosterone (CORT), a main type of glucocorticoids in rodents, was secreted in the plasma of stressed mice. We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling (MAVS) protein-transduced IFN-ß production without affecting its mRNA level, while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice. Mechanistically, the effect of CORT was mediated by proteasome-dependent degradation of MAVS, thereby resulting in the impediment of MAVS-transduced IFN-ß generation in vivo and in vitro. Furthermore, RNA-seq assay results indicated the involvement of Mitofusin 2 (Mfn2) in this process. Gain- and loss-of-function experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS. Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2 (HR1), MAVS (C-terminal/TM) and SYVN1 (TM). Collectively, our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a 'fine tuning' of antiviral innate immunity in response to influenza infection under stress.

Uptake, translocation and accumulation of the fungicide benzene kresoxim-methyl in Chinese flowering cabbage (Brassica campastris var. parachinensis) and water spinach (Ipomoea aquatica).

Benzene kresoxim-methyl (BKM) is an important methoxyacrylate-based strobilurin fungicide widely used against various phytopathogenic fungi in crops. Uptake, translocation and accumulation of BKM in vegetables remain unknown. This study was designed to investigate uptake, translocation, and accumulation of 14C-BKM and/or its potential metabolites in Chinese flowering cabbage and water spinach. 14C-BKM can be gradually taken up to reach a maximum of 44.4% of the applied amount by Chinese flowering cabbage and 34.6% by water spinach at 32 d after application. The 14CO2 fractions released from the hydroponic plant system reached 37.8% for cabbage and 45.8% for water spinach, respectively. Concentrations of 14C in leaves, stems and roots all gradually increased as vegetables growing, with relative 44.9% (cabbage) and 26.8% (water spinach) of translocated from roots to edible leaves. In addition, 14C in leaves was mainly accumulated in the bottom leaves, which was visualized by quantitative radioautographic imaging. The bioconcentration factor of 14C ranged from 7.1 to 38.2 mL g-1 for the cabbage and from 8.6 to 24.6 mL g-1 for the water spinach. The translocation factor of BKM ranged from 0.10 to 2.04 for the cabbage and 0.10-0.46 for the water spinach throughout the whole cultivation period, indicating that the cabbage is easier to translocate BKM from roots to leaves and stems than water spinach. In addition, the daily human exposure values of BKM in both vegetables were much lower than the limited dose of 0.15 mg day-1. The results help assess potential accumulation of BMK in vegetables and potential risk.