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Zn2+is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+pool from which mitochondrial Zn2+is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+levels for normal mitochondrial structure and functions.

Arginine catabolism involves enzyme-dependent reactions in both mitochondria and the cytosol, defects in which may lead to hyperargininemia, a devastating developmental disorder. It is largely unknown if defective arginine catabolism has any effects on mitochondria. Here we report that normal arginine catabolism is essential for mitochondrial homeostasis in Caenorhabditiselegans. Mutations of the arginase gene argn-1lead to abnormal mitochondrial enlargement and reduced adenosine triphosphate (ATP) production in C. eleganshypodermal cells. ARGN-1 localizes to mitochondria and its loss causes arginine accumulation, which disrupts mitochondrial dynamics. Heterologous expression of human ARG1 or ARG2 rescued the mitochondrial defects of argn-1mutants. Importantly, genetic inactivation of the mitochondrial basic amino acid transporter SLC-25A29 or the mitochondrial glutamate transporter SLC-25A18.1 fully suppressed the mitochondrial defects caused by argn-1mutations. These findings suggest that mitochondrial damage probably contributes to the pathogenesis of hyperargininemia and provide clues for developing therapeutic treatments for hyperargininemia.

The competition between SO2and elemental mercury (Hg0) for active sites was an important factor for suppressing the Hg0oxidation properties of catalysts. There were obvious differences in properties of basicity and acidity between SO2and Hg0. Raising the SO2resistance via adjusting the basicity and acidity sites of catalysts was promising for reducing the competition between SO2and Hg0. This study aimed to form multiple active sites with different basicities via Cu, Fe, Mn, and Sn doping. The results indicated that Cu doping had the best modification performance. Five percent CuO doping could significantly improve the SO2resistance of CuO(5)-CeO2(5)-WO3(9)/TiO2and increase the mercury oxidation efficiency (MOE) from 54.7 to 85.5% in the condition (6% O2, 100 ppm NO, 100 ppm NH3, and 100 ppm SO2). CO2temperature-programmed desorption analysis showed that CuO(5)-CeO2(5)-WO3(9)/TiO2exhibited weak basic sites (CeO2), medium-strong basic sites (Cu–O–Ce), and strong basic sites (CuO). Therefore, the CuO in the Ce–O–Cu structure was prioritized for the reaction with acid gas SO2and protected CeO2from SO2poisoning. This study prepared a highly SO2-resistant catalyst for Hg0oxidation. This research and development will be conducive for use in Hg0oxidation in actual coal-fired flue gases.

The accurate detection of tumorous methylglyoxal (MGO) and its detoxifier glyoxalase 1 (GLO1) in living systems is critical for understanding their roles in tumor initiation and progression. To date, the in situ fluorescence detection of endogenous MGO and GLO1 in tumor has not been reported. Herein we developed a near-infrared (NIR) fluorescent probe MEBTDto specifically detect tumorous MGO. Compared with previously reported MGO fluorescent probes, MEBTDexhibits several distinct advantages, including NIR emission, high selectivity with an MGO detection limit of 18 nM, and a 131-fold off-on ratio. The probe could sense GLO1 activity and monitor the therapeutic effect of GLO1 inhibitors by imaging tumorous MGO in a both a real-time and in situ manner, demonstrating that the biological effect of GLO1 inhibitors is dependent on the GLO1 activity. Furthermore, MEBTDenables the visualization of tumorous MGO induced by GLO1 inhibitors in vivo. To the best of our knowledge, MEBTDis the first NIR fluorescent probe for specifically imaging tumorous MGO in living animals, indicating the promising potential for tumor diagnosis and therapeutic evaluation.

Photodynamic therapy (PDT) has emerged as an efficient cancer treatment method with minimal invasiveness. However, the majority of current photosensitizers (PSs) display severe dark toxicity and low tumor specificity due to their “always-on” photoactivity in blood circulation. To address this concern, we herein report a series of acid-activatable PSs for ultrasensitive PDT of triple-negative breast tumors. These set of novel PSs are synthesized by covalently modifying tetrakis(4-carboxyphenyl)porphyrin (TCPP) with a variety of tertiary amines for acidity-activatable fluorescence imaging and reactive oxygen species (ROS) generation. The resultant TCPP derivatives are grafted with a poly(ethylene glycol) (PEG) chain viaa matrix metalloproteinase-2 (MMP-2)-liable peptide spacer and chelated with Mn2+for magnetic resonance imaging (MRI) capability. The PEGylated TCPP derivatives are amphiphilic and self-assemble into micellar nanoparticles to elongate blood circulation and for tumor-specific PDT. We further demonstrate that the PEGylated TCPP nanoparticles could serve as a nanoplatform to deliver the anticancer drug doxorubicin (DOX) and perform fluorescence image-guided combinatorial PDT and chemotherapy, which efficiently suppress the growth of 4T1 breast tumors and lung metastases in a mouse model. These acid-activatable PS-incorporated nanoparticles might provide a versatile platform for precise PDT and combinatorial breast cancer therapy.

Brucellosis is a worldwide zoonosis caused by Brucellaspecies and represents a serious threat to both human and animal health. Omp25 is an important immunogenic and protective antigen in Brucellaspecies; however, the functional mechanism of Omp25 in macrophages has not yet been elucidated. Here, we constructed a Brucella melitensis omp25deletion mutant (M5-90-Δomp25) and performed microRNA (miRNA) profiling of infected RAW264.7 cells. Eight differentially expressed miRNAs (mmu-miR-146a-5p, mmu-miR-155-5p, mmu-miR-3473a, mmu-miR-149-3p, mmu-miR-671-5p, mmu-miR-1224-5p, mmu-miR-1895, and mmu-miR-5126) were identified, with quantitative real-time PCR (qRT-PCR) analysis confirming the up-regulation of mmu-miR-146-a-5pand mmu-miR-155-5pand down-regulation of mmu-miR-149-3pand mmu-miR-5126. mRNA profiling of B. melitensisM5-90-Δomp25-infected RAW264.7 cells identified 967 differentially expressed genes (DEGs) (fold change ≥ 2). Among these, we focused on genes that were predicted by TargetScan, miRanda, and PicTar to be the potential targets of the differentially expressed miRNAs. The results suggested that 17 separate genes are potentially targeted by mmu-miR-149-3p, with one of these genes, Tbr1, also targeted by mmu-miR-5126. qRT-PCR analysis confirmed the up-regulation of nine of the predicted target genes. Our findings provide important information about the functional molecules in host cells, including miRNA and their target genes, affected by Omp25 from Brucella. This information is particularly valuable for the prophylaxis and treatment of brucellosis.

To accurately monitor the variations of lysosomal nitric oxide (NO) under physiological condition remains a great challenge for understanding the biological function of NO. Herein, we developed a new chemotype probe, namely, MBTD, for acid-promoted and far-red fluorescence imaging of lysosomal NO in vitro and ex vivo. MBTD was rationally designed by incorporating o-phenylenediamino (OPD) moiety into the donor–acceptor–donor (D-A-D) type fluorophore based on a dual intramolecular charge transfer (ICT) mechanism. Compared to previously reported OPD-based NO probes, MBTD displays several distinct advantages including large stroke shift, huge on–off ratio with minimal autofluorescence, and high NO specificity. Particularly, MBTD exhibits an acid-promoted response to NO with high acid tolerance, which greatly improves the spatial resolution to lysosomal NO by excluding the background noise from other nonacidic organelles. Furthermore, MBTD displayed much longer-lived and more stable fluorescence emission in comparison with the commercialized NO probe. MBTD was employed for ratiometric examination of the exogenous or endogenous NO of macrophages. More importantly, MBTD was able to detect the variation of lysosomal NO level in an acute liver injury mouse model ex vivo, implying the potential of MBTD for real-time monitoring the therapeutic efficacy of drug candidates for the treatment of acute liver injury. MBTD as a novel type of NO probe might open a new avenue for precisely sensing lysosomal NO-related pathological and therapeutic process.

Innate recognition of Brucellaspp. is a key step in the activation of inflammation. CD14 binds PAMPs and is involved in LPS-induced pro-inflammatory cytokine release. Previously we showed that knock down of CD14 in RAW264.7 macrophages disrupted Brucella–host interactions. However, its effect on the macrophage microRNA (miRNA) expression profile, especially after stimulation by Brucellainfection, is still unclear. To identify miRNAs involved in the macrophage response to Brucellainfection, we performed miRNA expression profiling of CD14 knock-down RAW264.7 (224.3) macrophages infected with Brucella melitensis, and demonstrated, for the first time, that CD14 knock down significantly up-regulated the expression of mmu-miR-199a-3p and mmu-miR-183-5p in these conditions. These miRNAs have a well-characterized association with the target genes involved in immune response, inflammatory response, innate immune response, apoptosis processes, anti-apoptosis, cytokine production and cytokine-mediated signaling pathways. Among the 104 inflammation-related candidate target genes of mmu-miR-199a-3p and mmu-miR-183-5p in the 224.3+B. melitensisgroup cells, the expression of the Cbl-b, a potential target of mmu-miR-199a-3p, was confirmed to be down-regulated using qRT-PCR and Western blot analysis. Our findings suggest that CD14 functions in the Brucella–host interaction may be through altered miRNA expression, and regulation of Cbl-b proteins.

Mercury, as a global pollutant, has significant impacts on the environment and human health. The current state of atmospheric mercury emissions, pollution and control in China is comprehensively reviewed in this paper. With about 500–800 t of anthropogenic mercury emissions, China contributes 25%–40% to the global mercury emissions. The dominant mercury emission sources in China are coal combustion, non-ferrous metal smelting, cement production and iron and steel production. The mercury emissions from natural sources in China are equivalent to the anthropogenic mercury emissions. The atmospheric mercury concentration in China is about 2–10 times the background level of North Hemisphere. The mercury deposition fluxes in remote areas in China are usually in the range of 10–50 μg·m−2·yr−1. To reduce mercury emissions, legislations have been enacted for power plants, non-ferrous metal smelters and waste incinerators. Currently mercury contented in the flue gas is mainly removed through existing air pollution control devices for sulfur dioxide, nitrogen oxides, and particles. Dedicated mercury control technologies are required in the future to further mitigate the mercury emissions in China.

A straightforward strategy for assembling polymeric dimers from amphiphilic nanoparticles is reported. Amphiphilic polymeric nanoparticles with a mixed‐shell of PEO/P2VN blocks and a flexible core of PAA blocks are fabricated by a non‐covalent crosslinking method. Uniform polymeric dimers are efficiently and simply obtained via hydrophobic interactions under optimized conditions in selective solvent. The steric hindrance generated by reorganization of hydrophilic polymer brushes during the interparticle association is critical for morphological selectivity in the assembly. General applicability offers the possibility to organize functional NPs into superstructures with well‐defined geometry and association numbers.

Swine hepatitis E (SHE) is a new type of zoonotic infectious disease caused by swine hepatitis E virus (SHEV). Open reading frame 3 (ORF3) is a key regulatory and virulent protein of SHEV. Circular RNAs (circRNAs) are a special kind of non-coding RNA molecule, which has a closed ring structure. In this study, to identify the circRNA profile in host cells affected by SHEV ORF3, adenovirus ADV4-ORF3 mediated the overexpression of ORF3 in HepG2 cells, whole genome sequencing was used to investigate the differentially expressed circRNAs, GO and KEGG were performed to enrichment analyze of differentially expressed circRNA-hosting gene, and Targetscan and miRanda softwares were used to analyze the interaction between circRNA and miRNA. The results showed adenovirus successfully mediated the overexpression of ORF3 in HepG2 cells, 1,105 up-regulation circRNAs and 1,556 down-regulation circRNAs were identified in ADV4-ORF3 infection group compared with the control. GO function enrichment analysis of differentially expressed circRNAs-hosting genes classified three main categories (cellular component, biological process and molecular function). KEGG pathway enrichment analysis scatter plot showed the pathway term of top20. The circRNAs with top10 number of BS sites for qRT-PCR validation were selected to confirmed, the results indicated that the up-regulated hsa_circ_0001423 and hsa_circ_0006404, and down-regulated of hsa_circ_0004833 and hsa_circ_0007444 were consistent with the sequencing data. Our findings first preliminarily found that ORF3 protein may affect triglyceride activation (GO:0006642) and riboflavin metabolism (ko00740) in HepG2 cells, which provides a scientific basis for further elucidating the effect of ORF3 on host lipid metabolism and the mechanism of SHEV infection.