Sulfonated Perylene as Three-in-One STING Agonist for Cancer Chemo-Immunotherapy.

Activation of stimulator of interferon genes (STING) by cyclic dinucleotides (CDNs) has been considered as a powerful immunotherapy strategy. While promising, the clinical translation of CDNs is still overwhelmed by its limited biostability and the resulting systemic immunotoxicity. Being differentiating from current application of exogenous CDNs to address these challenges, we herein developed one perylene STING agonist PDIC-NS, which not only promotes the production of endogenous CDNs but also inhibits its hydrolysis. More significantly, PDIC-NS can well reach lung-selective enrichment, and thus mitigates the systemic immunotoxicity upon intravenous administration. As a result, PDIC-NS had realized remarkable in vivo antitumor activity, and backward verified on STING knock out mice. Overall, this study states that PDIC-NS can function as three-in-one small-molecule STING agonist characterized by promoting the content and biostability of endogenous CDNs as well as possessing good tissue specificity, and hence presents an innovative strategy and platform for tumor chemo-immunotherapy.

Electroactive biocake layer-driven advanced removal of dissolved organic matter at membrane interface of anaerobic electrochemical membrane bioreactor.

The bio-cake layer is one of the most negative effects during water and wastewater filtration, but its potential behoof of biodegradation is poorly understood. In this study, we activated and reconstructed the bio-cake by using the carbon nanotube membrane (25 cm2 area, 17 LMH flux) as the anode in an anaerobic membrane bioreactor (AnMBR), and investigated its positive role in advanced removal of dissolved organic matter from up-flow anaerobic sludge bed unit (3 L/d) when treating synthetic municipal wastewater. At the anodic membrane interface, the enhanced biodegradation was proved to dominate the DOM reduction (contribution >40%), controlling the effluent COD as low as 19.2 ± 2.5 mg/L. Bio-cake characterizations suggested that the positive potential induced electroactive improvement, cell viability boost, and metabolic optimization. Metatranscriptomic analyses revealed that anode respiratory out-compete methanogenesis, forwarding a synergetic metabolism between enriched fermenters like Proteiniphilum sp. and exoelectrogens like Geobacter sp. Thus, electroactive bio-cake not only accelerated the decomposition of inside foulants to maintain the high flux, but also efficiently intercepted flow-through DOM due to reduced mass-transfer limitations and enhanced metabolic activity. An ordered, non-clogging, and potentially functional "cell filter" was established to achieve a win-win situation between fouling control and effluent improvement, which is promising to upgrade the AnMBR technology for maximizing the sustainable regeneration in future wastewater treatment.

LDH-Based "Smart" Films for Corrosion Sensing and Protection.

In a "smart" corrosion-protective coating system, both the active anti-corrosion and the early corrosion detection of underlying metals are highly required. It is practical significant to develop materials that possess self-detecting of the early local corrosion and self-healing of coating defects simultaneously. The organic compound 8-hydroxyquinoline (8HQ) is an effective inhibitor and a fluorescent sensor probe for corrosion of aluminum alloy. Therefore, a layer double hydroxide (LDH) nanocontainer film loaded with the 8HQ was developed for the active corrosion protection purpose of aluminum alloy AA2024. In corrosive environments, the 8HQ are released from LDH film to inhibit the corrosion process, leading to the loss of the complexation with Al3+ ions in LDH laminates, thus turning off fluorescence. Results show that the LDH film loaded with 8HQ composites can improve the anti-corrosion performance of the film by releasing corrosion inhibitors on demand. Simultaneously, due to the complexation of 8HQ and Al3+ ions, the LDH film is fluorescent at the initial stage under ultraviolet light, and then becomes non-fluorescent at the corrosion sites, indicating the corrosion evolution process of the coating. The 8HQ-loaded LDH film with self-healing and self-detecting dual functions provides promising opportunities for the effective corrosion protection of aluminum alloy due to its "smart" and multifunctional properties.

Stepwise Crystalline Structural Transformation in 0D Hybrid Antimony Halides with Triplet Turn-on and Color-Adjustable Luminescence Switching.

Intelligent stimuli-responsive fluorescence materials are extremely pivotal for fabricating luminescent turn-on switching in solid-state photonic integration technology, but it remains a challenging objective for typical 3-dimensional (3D) perovskite nanocrystals. Herein, by fine-tuning the accumulation modes of metal halide components to dynamically control the carrier characteristics, a novel triple-mode photoluminescence (PL) switching was realized in 0D metal halide through stepwise single-crystal to single-crystal (SC-SC) transformation. Specifically, a family of 0D hybrid antimony halides was designed to exhibit three distinct types of PL performance including nonluminescent [Ph3EtP]2Sb2Cl8 (1), yellow-emissive [Ph3EtP]2SbCl5·EtOH (2), and red-emissive [Ph3EtP]2SbCl5 (3). Upon stimulus of ethanol, 1 was successfully converted to 2 through SC-SC transformation with enhanced PL quantum yield from ~0% to 91.50% acting as "turn-on" luminescent switching. Meanwhile, reversible SC-SC and luminescence transformation between 2 and 3 can be also achieved in the ethanol impregnation-heating process as luminescence vapochromism switching. As a consequence, a new triple-model turn-on and color-adjustable luminescent switching of off-onI-onII was realized in 0D hybrid halides. Simultaneously, wide advanced applications were also achieved in anti-counterfeiting, information security, and optical logic gates. This novel photon engineering strategy is expected to deepen the understanding of dynamic PL switching mechanism and guide development of new smart luminescence materials in cutting-edge optical switchable device.

Salinity determines performance, functional populations, and microbial ecology in consortia attenuating organohalide pollutants.

Organohalide pollutants are prevalent in coastal regions due to extensive intervention by anthropogenic activities, threatening public health and ecosystems. Gradients in salinity are a natural feature of coasts, but their impacts on the environmental fate of organohalides and the underlying microbial communities remain poorly understood. Here we report the effects of salinity on microbial reductive dechlorination of tetrachloroethene (PCE) and polychlorinated biphenyls (PCBs) in consortia derived from distinct environments (freshwater and marine sediments). Marine-derived microcosms exhibited higher halotolerance during PCE and PCB dechlorination, and a halotolerant dechlorinating culture was enriched from these microcosms. The organohalide-respiring bacteria (OHRB) responsible for PCE and PCB dechlorination in marine microcosms shifted from Dehalococcoides to Dehalobium when salinity increased. Broadly, lower microbial diversity, simpler co-occurrence networks, and more deterministic microbial community assemblages were observed under higher salinity. Separately, we observed that inhibition of dechlorination by high salinity could be attributed to suppressed viability of Dehalococcoides rather than reduced provision of substrates by syntrophic microorganisms. Additionally, the high activity of PCE dechlorinating reductive dehalogenases (RDases) in in vitro tests under high salinity suggests that high salinity likely disrupted cellular components other than RDases in Dehalococcoides. Genomic analyses indicated that the capability of Dehalobium to perform dehalogenation under high salinity was likely owing to the presence of genes associated with halotolerance in its genomes. Collectively, these mechanistic and ecological insights contribute to understanding the fate and bioremediation of organohalide pollutants in environments with changing salinity.

SmCIP7, a COP1 interactive protein, positively regulates anthocyanin accumulation and fruit size in eggplant.

In higher plants, COP1 (Constitutively Photomorphogenic 1) acts as a central regulator of light-signaling networks and globally conditions the target proteins via the ubiquitin-proteasome pathway. However, the function of COP1-interacting proteins in light-regulated fruit coloration and development remains unknown in Solanaceous plants. Here, a COP1-interacting protein-encoding gene, SmCIP7, expressed specifically in the eggplant (Solanum melongena L.) fruit, was isolated. Gene-specific silencing of SmCIP7 using RNA interference (RNAi) significantly altered fruit coloration, fruit size, flesh browning, and seed yield. SmCIP7-RNAi fruits showed evident repression of the accumulation of anthocyanins and chlorophyll, indicating functional similarities between SmCIP7 and AtCIP7. However, the reduced fruit size and seed yield indicated SmCIP7 had evolved a distinctly new function. With the comprehensive application of HPLC-MS, RNA-seq, qRT-PCR, Y2H, BiFC, LCI, and dual-luciferase reporter system (DLR™), it was found that SmCIP7, a COP1 interactive protein in light signaling promoted anthocyanin accumulation, probably by regulating the transcription of SmTT8. Additionally, the drastic up-regulation of SmYABBY1, a homologous gene of SlFAS, might account for the strongly retarded fruit growth in SmCIP7-RNAi eggplant. Altogether, this study proved that SmCIP7 is an essential regulatory gene to modulate fruit coloration and development, serving as a key gene locus in eggplant molecular breeding.

Duplex Coating Combing Vanadate-Intercalated Layered Double Hydroxide and Ce-Doped Sol-Gel Layers on Aluminum Alloy for Active Corrosion Protection.

In this study, a duplex coating system (LDH-V/SG-Ce) of vanadate-intercalated layered double hydroxide (LDH) and Ce-doped sol-gel (SG) layers was developed for the purpose of active corrosion protection of the aluminum alloy AA2024. ZnAl-LDH film was grown in situ on the surface of an aluminum alloy using a hydrothermal method and intercalated with V2O74- anions as corrosion inhibitors, and sealed with a Ce (III)-doped silane coating using a sol-gel technique. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses were used to analyze the microstructure, surface functional groups and structure of the LDH-V/SG-Ce film. The uniform and compact silane layer was covered both in the pores and on top of the LDH film. The results of glow discharge optical emission spectroscopy (GDOES) indicated that V2O74- and Ce (III) ions were loaded in the LDH layer and silane film, respectively. The potentiodynamic polarization results showed that the corrosion current density of the bilayer system in the presence of corrosion inhibitors was reduced to 1.92 × 10-8 A/cm2. Electrochemical impedance spectroscopy (EIS) results showed that the LDH-V/SG-Ce duplex coating could provide effective protection for the aluminum alloy after being exposed to a corrosive solution for 14 days.

Inorganic versus organic fertilizers: How do they lead to methylmercury accumulation in rice grains.

Both inorganic and organic fertilizers are widely used to increase rice yield. However, these fertilizers are also found to aggravate mercury methylation and methylmercury (MeHg) accumulation in paddy fields. The aim of this study was to reveal the mechanisms of inorganic and organic fertilizers on MeHg accumulation in rice grains, which are not yet well understood. Potting cultures were conducted in which different fertilizers were applied to a paddy soil. The results showed that both inorganic and organic fertilizers increased MeHg concentrations rather than biological accumulation factors (BAFs) of MeHg in mature rice grains. Inorganic fertilizers, especially nitrogen fertilizer, enhanced the bioavailability of mercury and the relative amount Hg-methylating microbes and therefore intensified mercury methylation in paddy soil and MeHg accumulation in rice grains. Unlike inorganic fertilizers, organic matter (OM) in organic fertilizers was the main reason for the increase of MeHg concentrations in rice grains, and it also could immobilize Hg in soil when it was deeply degraded. The enhancement of MeHg concentrations in rice grains induced by inorganic fertilizers (5.18-41.69%) was significantly (p < 0.05) lower than that induced by organic fertilizers (80.49-106.86%). Inorganic fertilizers led to a larger increase (50.39-99.28%) in thousand-kernel weight than MeHg concentrations (5.18-41.69%), resulting in a dilution of MeHg concentrations in mature rice grains. Given the improvement of soil properties by organic fertilizer, increasing the proportion of inorganic fertilizer application may be a better option to alleviate MeHg accumulation in rice grains and guarantee the rice yield in the agricultural production.

Anthocyanins identification and transcriptional regulation of anthocyanin biosynthesis in purple Brassica napus.

KEY MESSAGE: The main anthocyanin components were identified, and the transcriptional regulation pattern of anthocyanin related genes in leaves and stem bark was elucidated in a purple B. napus. Brassica napus is one of the most important oil crops planted worldwide, and developing varieties of dual-purpose for oil and vegetable is beneficial to improve economic benefits. Anthocyanins are a class of secondary metabolites that not only make plants present beautiful colors, but have a variety of important physiological functions and biological activities. Therefore, increasing the accumulation of anthocyanin in vegetative organs can improve vegetable value of rapeseed. However, anthocyanin enriched varieties in vegetative organs are rare, and there are few studies on category identification and accumulation mechanism of anthocyanin, which limits the utilization of anthocyanins in B. napus. In this study, 157 anthocyanin biosynthesis related genes (ABGs) were identified in B. napus genome by homology comparison and collinearity analysis of genes related to anthocyanin synthesis and regulation in Arabidopsis. Moreover, five anthocyanins were identified in the stem bark and leaves of the purple B. napus PR01 by high performance liquid chromatography-mass spectrometry (HPLC-MS), and the expression characteristics of ABGs in the leaves and stem bark of PR01 were analyzed and compared with the green cultivar ZS11 by RNA-Seq. Combining further weighted gene co-expression network analysis (WGCNA), the up-regulation of transcript factors BnaA07. PAP2 and BnaC06. PAP2 were identified as the key to the up-regulation of most of anthocyanin synthesis genes that promoted anthocyanin accumulation in PR01. This study is helpful to understand the transcriptional regulation of anthocyanin biosynthesis in B. napus and provides the theoretical basis for breeding novel varieties of dual-purpose for oil and vegetable.

Dehalogenation of Polybrominated Diphenyl Ethers and Polychlorinated Biphenyls Catalyzed by a Reductive Dehalogenase in Dehalococcoides mccartyi Strain MB.

Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are notorious persistent organic pollutants. However, few organohalide-respiring bacteria that harbor reductive dehalogenases (RDases) capable of dehalogenating these pollutants have been identified. Here, we report reductive dehalogenation of penta-BDEs and PCBs byDehalococcoides mccartyi strain MB. The PCE-pregrown cultures of strain MB debrominated 86.6 ± 7.4% penta-BDEs to di- to tetra-BDEs within 5 days. Similarly, extensive dechlorination of Aroclor1260 and Aroclor1254 was observed in the PCE-pregrown cultures of strain MB, with the average chlorine per PCB decreasing from 6.40 ± 0.02 and 5.40 ± 0.03 to 5.98 ± 0.11 and 5.19 ± 0.07 within 14 days, respectively; para-substituents were preferentially dechlorinated from PCBs. Moreover, strain MB showed distinct enantioselective dechlorination of different chiral PCB congeners. Dehalogenation activity and cell growth were maintained during the successive transfer of cultures when amended with penta-BDEs as the sole electron acceptors but not when amended with only PCBs, suggesting metabolic and co-metabolic dehalogenation of these compounds, respectively. Transcriptional analysis, proteomic profiling, and in vitro activity assays indicated that MbrA was involved in dehalogenating PCE, PCBs, and PBDEs. Interestingly, resequencing of mbrA in strain MB identified three nonsynonymous mutations within the nucleotide sequence, although the consequences of which remain unknown. The substrate versatility of MbrA enabled strain MB to dechlorinate PCBs in the presence of either penta-BDEs or PCE, suggesting that co-metabolic dehalogenation initiated by multifunctional RDases may contribute to PCB attenuation at sites contaminated with multiple organohalide pollutants.

Offshore Marine Sediment Microbiota Respire Structurally Distinct Organohalide Pollutants.

Marine sediments are a major sink of organohalide pollutants, but the potential for offshore marine microbiota to transform these pollutants remains underexplored. Here, we report dehalogenation of diverse organohalide pollutants by offshore marine microbiota. Dechlorination of polychlorinated biphenyls (PCBs) was observed in four marine sediment microcosms, which was positively correlated with in situ PCB contamination. Three distinct enrichment cultures were enriched from these PCB-dechlorinating microcosms using tetrachloroethene (PCE) as the sole organohalide. All enrichment cultures also dehalogenated polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A (TBBPA), and 2,4,6-trichlorophenol (2,4,6-TCP). Particularly, two enrichments completely debrominated penta-BDEs, the first observation of complete debromination of penta-BDEs in marine cultures. Multiple Dehalococcoides and uncultivated Dehalococcoidia were identified in the initial sediment microcosms, but only Dehalococcoides was dominant in all enrichments. Transcription of a gene encoding a PcbA5-like reductive dehalogenase (RDase) was observed during dehalogenation of different organohalides in each enrichment culture. When induced by a single organohalide substrate, the PcbA5-like RDase dehalogenated all tested organohalides (PCE, PCBs, PBDEs, TBBPA, and 2,4,6-TCP) in in vitro tests, suggesting its involvement in dehalogenation of structurally distinct organohalides. Our results demonstrate the versatile dehalogenation capacity of marine Dehalococcoidia and contribute to a better understanding of the fate of these pollutants in marine systems.

Differentiating Closely Affiliated Dehalococcoides Lineages by a Novel Genetic Marker Identified via Computational Pangenome Analysis.

As a group, the genus Dehalococcoides dehalogenates a wide range of organohalide pollutants, but the range of organohalide compounds that can be utilized for reductive dehalogenation differs among Dehalococcoides strains. Dehalococcoides lineages cannot be reliably disambiguated in mixed communities using typical phylogenetic markers, which often confounds bioremediation efforts. Here, we describe a computational approach to identify Dehalococcoides genetic markers with improved discriminatory resolution. Screening core genes from the Dehalococcoides pangenome for degree of similarity and frequency of 100% identity found a candidate genetic marker encoding a bacterial neuraminidase repeat (BNR)-containing protein of unknown function. This gene exhibits the fewest completely identical amino acid sequences and has among the lowest average amino acid sequence identity in the core pangenome. Primers targeting BNR could effectively discriminate between 40 available BNR sequences (in silico) and 10 different Dehalococcoides isolates (in vitro). Amplicon sequencing of BNR fragments generated from 22 subsurface soil samples revealed a total of 109 amplicon sequence variants, suggesting a high diversity of Dehalococcoides distributed in the environment. Therefore, the BNR gene can serve as an alternative genetic marker to differentiate strains of Dehalococcoides in complicated microbial communities. IMPORTANCE The challenge of discriminating between phylogenetically similar but functionally distinct bacterial lineages is particularly relevant to the development of technologies seeking to exploit the metabolic or physiological characteristics of specific members of bacterial genera. A computational approach was developed to expedite screening of potential genetic markers among phylogenetically affiliated bacteria. Using this approach, a gene encoding a bacterial neuraminidase repeat (BNR)-containing protein of unknown function was selected and evaluated as a genetic marker to differentiate strains of Dehalococcoides, an environmentally relevant genus of bacteria whose members can transform and detoxify a range of halogenated organic solvents and persistent organic pollutants, in complex microbial communities to demonstrate the validity of the approach. Moreover, many apparently phylogenetically distinct, currently uncharacterized Dehalococcoides were detected in environmental samples derived from contaminated sites.

Aminophosphate precursors for the synthesis of near-unity emitting InP quantum dots and their application in liver cancer diagnosis.

InP quantum dots (QDs) are a promising and environment-friendly alternative to Cd-based QDs for in vitro diagnostics and bioimaging applications. However, their poor fluorescence and stability severely limit their biological applications. Herein, we synthesize bright (∼100%) and stable InP-based core/shell QDs by using cost-effective and low-toxic phosphorus source, and then aqueous InP QDs are prepared with quantum yield over 80% by shell engineering. The immunoassay of alpha-fetoprotein can be detected in the widest analytical range of 1-1000 ng ml-1 and the limit of detection of 0.58 ng ml-1 by using those InP QDs-based fluorescent probes, making it the best-performing heavy metal-free detection reported so far, comparable to state-of-the-art Cd-QDs-based probes. Furthermore, the high-quality aqueous InP QDs exhibit excellent performance in specific labeling of liver cancer cells and in vivo tumor-targeted imaging of live mice. Overall, the present work demonstrates the great potential of novel high-quality Cd-free InP QDs in cancer diagnosis and image-guided surgery.

Evaluation of the Biological Activity of Folic Acid-Modified Paclitaxel-Loaded Gold Nanoparticles.

PURPOSE: Gold nanoparticles (AuNPs) with good physical and biological properties are often used in medicine, diagnostics, food, and similar industries. This paper explored an AuNPs drug delivery system that had good target selectivity for folate-receptor overexpressing cells to induce apoptosis. METHODS: A novel drug delivery system, Au@MPA-PEG-FA-PTX, was developed carrying paclitaxel (PTX) on folic acid (FA) and polyethylene glycol (PEG)-modified AuNPs. The nanomaterial was characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and ultraviolet-visible spectroscopy (UV-Vis). Also, the biological activity of the AuNPs drug delivery system was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HL-7702, Hela, SMMC-7721, and HCT-116 cells. Furthermore, apoptotic activity using annexin V-FITC, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels was estimated by flow cytometry and fluorescence microscopy. RESULTS: Au@MPA-PEG-FA-PTX exhibited a distinct core-shell structure with a controllable size of 28±1 nm. Also, the AuNPs maintained good dispersion and spherical shape uniformity before and after modification. The MTT assay revealed good antitumor activity of the Au@MPA-PEG-FA-PTX against the Hela, SMMC-7721, and HCT-116 cells, while Au@MPA-PEG-FA-PTX produced better pharmacological effects than PTX in isolation. Further mechanistic investigation revealed that effective internalization of AuNPs by folate-receptor overexpressing cancer cells induced cell apoptosis through excessive production of intracellular ROS. CONCLUSION: The AuNPs drug delivery system showed good target selectivity for folate-receptor overexpressing cancer cells to induce target cell-specific apoptosis. These AuNPs may have great potential as theranostic agents such as in cancer.

Mesoporous silica nanoparticles loaded with fluorescent coumarin-5-fluorouracil conjugates as mitochondrial-targeting theranostic probes for tumor cells.

In this study, a nanodrug carrier (mesoporous silica nanoparticle (MSN)-SS-cysteamine hydrochloride (CS)-hyaluronic acid (HA)) for targeted drug delivery was prepared using MSNs, in which HA was used as a targeting ligand and blocking agent to control drug release. Coumarin is a fluorescent molecule that targets mitochondria. Two conjugates (XDS-DJ and 5-FUA-4C-XDS) were synthesized by chemically coupling nitrogen mustard and 5-fluorouracil with coumarin, which was further loaded into MSN-SS-CS-HA nanocarriers. MTT analysis demonstrated that the nanocomposite MSN-SS-CS@5-FUA-4C-XDS/HA displayed stronger cytotoxicity toward HCT-116 cells than HeLa or QSG-7701 cells. Furthermore, MSN-SS-CS@5-FUA-4C-XDS/HA was able to target the mitochondria of HCT-116 cells, causing decreased mitochondrial membrane potential and excessive production of reactive oxygen species. These results indicate that MSN-SS-CS@5-FUA-4C-XDS/HA has the potential to be a nanodrug delivery system for the treatment of colon cancer.

Acceleration of polychlorinated biphenyls remediation in soil via sewage sludge amendment.

Bioremediation of polychlorinated biphenyls (PCBs) is impeded by difficulties in massively cultivating bioinoculant. Meanwhile, sewage sludge is rich in pollutant-degrading microorganisms and nutrients, drawing our attention to investigate their potential to be used as a supplement for bioremediation of PCBs. Here we reported extensive microbial reductive dechlorination of PCBs by waste activated sludge (WAS) and digestion sludge (DS), which were identified to harbor multiple putative organohalide-respiring bacteria (i.e., Dehalococcoides, Dehalogenimonas, Dehalobacter, and uncultivated Dehalococcoidia) and PCB reductive dehalogenase genes (i.e., pcbA4 and pcbA5). Consequently, amendment of 1-20% (w/w) fresh WAS/DS enhanced the attenuation of PCBs by 126-544% in a soil microcosm compared with the control soil, with the fastest dechlorination of PCBs being achieved when spiked with 20% fresh WAS. Notably, dechlorination pathways of PCBs were also changed by sludge amendment. Microbial and physicochemical analyses revealed that the enhanced dechlorination of PCBs by sludge amendment was largely attributed to the synergistic effects of sludge-derived nutrients, PCB-dechlorinating bacteria, and stimulated growth of beneficial microorganisms (e.g., fermenters). Finally, risk assessment of heavy metals suggests low potential ecological risks of sludge amendment in soil. Collectively, our study demonstrates that sewage sludge amendment could be an efficient, cost-effective and environment-friendly approach for in situ bioremediation of PCBs.

Insights into the Occurrence, Fate, and Impacts of Halogenated Flame Retardants in Municipal Wastewater Treatment Plants.

Halogenated flame retardants (HFRs) have been extensively used in various consumer products and many are classified as persistent organic pollutants due to their resistance to degradation, bioaccumulation potential and toxicity. HFRs have been widely detected in the municipal wastewater and wastewater treatment solids in wastewater treatment plants (WWTPs), the discharge and agricultural application of which represent a primary source of environmental HFRs contamination. This review seeks to provide a current overview on the occurrence, fate, and impacts of HFRs in WWTPs around the globe. We first summarize studies recording the occurrence of representative HFRs in wastewater and wastewater treatment solids, revealing temporal and geographical trends in HFRs distribution. Then, the efficiency and mechanism of HFRs removal by biosorption, which is known to be the primary process for HFRs removal from wastewater, during biological wastewater treatment processes, are discussed. Transformation of HFRs via abiotic and biotic processes in laboratory tests and full-scale WWTPs is reviewed with particular emphasis on the transformation pathways and functional microorganisms responsible for HFRs biotransformation. Finally, the potential impacts of HFRs on reactor performance (i.e., nitrogen removal and methanogenesis) and microbiome in bioreactors are discussed. This review aims to advance our understanding of the fate and impacts of HFRs in WWTPs and shed light on important questions warranting further investigation.

Hyaluronic Acid-Modified and Doxorubicin-Loaded Gold Nanoparticles and Evaluation of Their Bioactivity.

Functionalized gold nanoparticles (AuNPs) have been successfully used in many fields as a result of having low cytotoxicity, good biocompatibility, excellent optical properties, and their ability to target cancer cells. Here, we synthesized AuNP carriers that were modified by hyaluronic acid (HA), polyethylene glycol (PEG), and adipic dihydrazide (ADH). The antitumor drug doxorubicin (Dox) was loaded into AuNP carriers and attached chemically. The Au nanocomposite AuNPs@MPA-PEG-HA-ADH-Dox was able to disperse uniformly in aqueous solution, with a diameter of 15 nm. The results of a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that AuNP carriers displayed very little toxicity toward cells in high doses, although the antitumor properties of Au nanocomposites were significantly enhanced. Cellular uptake experiments demonstrated that AuNPs modified with hyaluronic acid were more readily ingested by HepG2 and HCT-116 cells, as they have a large number of CD44 receptors. A series of experiments measuring apoptosis such as Rh123 and annexin V-FITC staining, and analysis of mitochondrial membrane potential (MMP) analysis, indicated that apoptosis played a role in the inhibition of cell proliferation by AuNPs@MPA-PEG-HA-ADH-Dox. Excessive production of reactive oxygen species (ROS) was the principal mechanism by which the Au nanocomposites inhibited cell proliferation, leading to apoptosis. Thus, the Au nanocomposites, which allowed cell imaging in real-time and induced apoptosis in specific cell types, represent theragnostic agents with potential for future clinical applications in bowel cancer.

Influence of excessive exercise on immunity, metabolism, and gut microbial diversity in an overtraining mice model.

The purpose of this study was to evaluate the negative influence of excessive exercise on immunity, substance and energy metabolism as well as gut microbiota in mice. Firstly, an overtraining model of Male Kunming mice was established by high-intensity swimming exercise for 4 weeks. Then, a series of evaluation indicators, including the routine blood analysis, immune organ coefficient, digestive enzymes, and aquaporins expression levels of small intestine and colon tissue, histological examinations of liver, spleen, small intestine, and colon, were determined based on this model. Furthermore, 16S rRNA gene sequencing was also employed to measure the microbial composition in gut. The results found that immune parameters, substance and energy metabolism of all mice was altered and disturbed after high-intensity swimming for 4 weeks, led to an atrophy of thymus and spleen as well as abnormal structural changes in liver when compared to non-swimming mice. Besides, excessive swimming mice had lower microbial diversity compared to non-swimming mice. However, there was no significant difference in gut microbial taxa between the two groups. The data indicated that excessive exercise exhibits negative impacts on immunity, substance and energy metabolism as well as gut microbial diversity.

Anti-hepatitis B virus activity of α-DDB-FNCG, a novel nucleoside-biphenyldicarboxylate compound in vitro and in vivo.

A novel codrug, α-DDB-FNCG, was synthesized through coupling of α-biphenyl dimethyl dicarboxylate (α-DDB) and the nucleoside analogue FNCG, via an ester bond. The anti-HBV activity and hepatoprotective effects of this compound were investigated both in vitro and in vivo. In HBV-transfected HepG2.2.15 cell line, the secretion of HBsAg and HBeAg as well as the levels of extracellular and intracellular viral DNA were determined by ELISA and real-time fluorescent quantitative Polymerase Chain Reaction (FQ-PCR), respectively. In DHBV-infected ducks, the viral DNA levels in serum and liver were determined by FQ-PCR. In addition, the levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in both serum and liver were also examined. The improvement of ducks' livers was evaluated by histopathological analysis. It has been demonstrated that α-DDB-FNCG could suppress the levels of HBV antigens and viral DNA in a time- and dose-dependent manner in the HepG2.2.15 cell line. Furthermore, this codrug could also significantly inhibit the viral DNA replication and reduce the ALT and AST levels in both serum and liver of DHBV-infected ducks, with improved hepatocellular architecture in drug-treated ducks. In short, these results suggest that α-DDB-FNCG could be a promising candidate for further development of new anti-HBV agents with hepatoprotective effects.