Toxicokinetics Explain Differential Freshwater Ecotoxicity of Nanoencapsulated Imidacloprid Compared to Its Conventional Active Ingredient.

Agricultural applications of nanotechnologies necessitate addressing safety concerns associated with nanopesticides, yet research has not adequately elucidated potential environmental risks between nanopesticides and their conventional counterparts. To address this gap, we investigated the risk of nanopesticides by comparing the ecotoxicity of nanoencapsulated imidacloprid (nano-IMI) with its active ingredient to nontarget freshwater organisms (embryonic Danio rerio, Daphnia magna, and Chironomus kiinensis). Nano-IMI elicited approximately 5 times higher toxicity than IMI to zebrafish embryos with and without chorion, while no significant difference was observed between the two invertebrates. Toxicokinetics further explained the differential toxicity patterns of the two IMI analogues. One-compartmental two-phase toxicokinetic modeling showed that nano-IMI exhibited significantly slower elimination and subsequently higher bioaccumulation potential than IMI in zebrafish embryos (dechorinated), while no disparity in toxicokinetics was observed between nano-IMI and IMI in D. magna and C. kiinensis. A two-compartmental toxicokinetic model successfully simulated the slow elimination of IMI from C. kiinensis and confirmed that both analogues of IMI reached toxicologically relevant targets at similar levels. Although nanopesticides exhibit comparable or elevated toxicity, future work is of utmost importance to properly understand the life cycle risks from production to end-of-life exposures, which helps establish optimal management measures before their widespread applications.

The m6A methylation and expression profiles of mouse neural stem cells after hypoxia/reoxygenation.

BACKGROUND: Ischemia-reperfusion injury to the central nervous system often causes severe complications. The activation of endogenous neural stem cells (NSCs) is considered a promising therapeutic strategy for nerve repair. However, the specific biological processes and molecular mechanisms of NSC activation remain unclear, and the role of N6-methyladenosine (m6A) methylation modification in this process has not been explored. METHODS: NSCs were subjected to hypoxia/reoxygenation (H/R) to simulate ischemia-reperfusion in vivo. m6A RNA methylation quantitative kit was used to measure the total RNA m6A methylation level. Quantitative real-time PCR was used to detect methyltransferase and demethylase mRNA expression levels. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were conducted for NSCs in control and H/R groups, and the sequencing results were analyzed using bioinformatics. Finally, the migration ability of NSCs was identified by wound healing assays, and the proliferative capacity of NSCs was assessed using the cell counting kit-8, EdU assays and cell spheroidization assays. RESULTS: Overall of m6A modification level and Mettl14 mRNA expression increased in NSCs after H/R treatment. The m6A methylation and expression profiles of mRNAs in NSCs after H/R are described for the first time. Through the joint analysis of MeRIP-seq and RNA-seq results, we verified the proliferation of NSCs after H/R, which was regulated by m6A methylation modification. Seven hub genes were identified to play key roles in the regulatory process. Knockdown of Mettl14 significantly inhibited the proliferation of NSCs. In addition, separate analysis of the MeRIP-seq results suggested that m6A methylation regulates cell migration and differentiation in ways other than affecting mRNA expression. Subsequent experiments confirmed the migration ability of NSCs was suppressed by knockdown of Mettl14. CONCLUSION: The biological behaviors of NSCs after H/R are closely related to m6A methylation of mRNAs, and Mettl14 was confirmed to be involved in cell proliferation and migration.

Toxicity and chemical characterization of shale gas wastewater discharged to the receiving water: Evidence from toxicity identification evaluation.

Flowback and produced water (FPW) generated from shale gas extraction is a complex mixture consisting of injected drilling fluid, deep formation water, and byproducts of downhole reactions. Limited knowledge is available regarding the impact of discharged FPW on surface water in China. With the development of shale gas exploitation, this emphasizes an urgent need for comprehensive assessments and stringent regulations to ensure the safe disposal of shale gas extraction-related wastewater. Herein, we explored potential impacts of treated shale gas wastewater discharged into a local river in southwest China through toxicity identification evaluation (TIE). Results revealed that organics and particulates significantly contributed to the overall toxicity of the treated FPW wastewater. Through target and suspect chemical analyses, various categories of organic contaminants were detected, including alkanes, aromatic hydrocarbons, biocides, phenols, and phthalates. Furthermore, non-target analysis uncovered the presence of surfactant-related contaminants in tissues of exposed organisms, but their contribution to the observed toxicity was unclear due to the lack of effect data for these compounds. Higher toxicity was found at the discharge point compared with upstream sites; however, the toxicity was rapidly mitigated due to dilution in the receiving river, posing little impact on downstream areas. Our study highlighted the importance of monitoring toxicity and water quality of FPW effluent even though dilution could be a viable approach when the water volume in the discharge was small.

Toxicity identification evaluation for hydraulic fracturing flowback and produced water during shale gas exploitation in China: Evidence from tissue residues and gene expression.

Hydraulic fracturing flowback and produced water (HF-FPW) from shale gas extraction processes is a highly complex medium with potential threats to the environment. Current research on ecological risks of FPW in China is limited, and the link between major components of FPW and their toxicological effects on freshwater organisms is largely unknown. By integrating chemical and biological analyses, toxicity identification evaluation (TIE) was used to reveal causality between toxicity and contaminants, potentially disentangling the complex toxicological nature of FPW. Here, FPW from different shale gas wells, treated FPW effluent, and a leachate from HF sludge were collected from southwest China, and TIE was applied to obtain a comprehensive toxicity evaluation in freshwater organisms. Our results showed that FPW from the same geographic zone could cause significantly different toxicity. Salinity, solid phase particulates, and organic contaminants were identified as the main contributors to the toxicity of FPW. In addition to water chemistry, internal alkanes, PAHs, and HF additives (e.g., biocides and surfactants) were quantified in exposed embryonic fish by target and non-target tissue analyses. The treated FPW failed to mitigate the toxicity associated with organic contaminants. Transcriptomic results illustrated that organic compounds induced toxicity pathways in FPW-exposed embryonic zebrafish. Similar zebrafish gene ontologies were affected between treated and untreated FPW, again confirming that sewage treatment did not effectively remove organic chemicals from FPW. Thus, zebrafish transcriptome analyses revealed organic toxicant-induced adverse outcome pathways and served as evidence for TIE confirmation in complex mixtures under data-poor scenarios.

miR-199a-5p from bone marrow mesenchymal stem cell exosomes promotes the proliferation of neural stem cells by targeting GSK-3ß.

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes are a promising therapeutic agent for human disease, but their effects on neural stem cells (NSCs) subject to spinal cord ischaemia-reperfusion injury (SCIRI) remain unknown. Here, we examine the impact of miR-199a-5p-enriched exosomes derived from BMSCs on NSC proliferation. We establish a rat model of aortic cross-clamping to induce SCIRI in vivo and a primary NSC model of oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate SCIRI in vitro. CCK8, EdU, and BrdU assays are performed to evaluate the proliferation of NSCs. Hematoxylin and eosin (H&E) staining is used to determine the number of surviving neurons. The Basso, Beattie, and Bresnahan (BBB) scale and inclined plane test (IPT) are used to evaluate hind limb motor function. DiO-labelled exosomes are efficiently internalized by NSCs and increase ectopic amounts of miR-199a-5p, which promotes the proliferation of NSCs. In contrast, exosomes derived from miR-199a-5p-depleted BMSCs exert fewer beneficial effects. MiR-199a-5p targets and negatively regulates glycogen synthase kinase 3ß (GSK-3ß) and increases nuclear ß-catenin and cyclin D1 levels. miR-199a-5p inhibition reduces the total number of EdU-positive NSCs after OGD/R, but the GSK-3ß inhibitor CHIR-99021 reverses this effect. In vivo, intrathecal injection of BMSC-derived exosomes increases the proliferation of endogenous spinal cord NSCs after SCIRI. In addition, more proliferating NSCs are found in rats intrathecally injected with exosomes overexpressing miR-199a-5p. In summary, miR-199a-5p in BMSC-derived exosomes promotes NSC proliferation via GSK-3ß/ß-catenin signaling.

miR-872-5p/FOXO3a/Wnt signaling feed-forward loop promotes proliferation of endogenous neural stem cells after spinal cord ischemia-reperfusion injury in rats.

The activation of endogenous neural stem cells (NSCs) is considered an important mechanism of neural repair after mechanical spinal cord injury; however, whether endogenous NSC proliferation can also occur after spinal cord ischemia-reperfusion injury (SCIRI) remains unclear. In this study, we aimed to verify the existence of endogenous NSC proliferation after SCIRI and explore the underlying molecular mechanism. NSC proliferation was observed after SCIRI in vivo and oxygen-glucose deprivation and reperfusion (OGD/R) in vitro, accompanied by a decrease in forkhead box protein O 3a (FOXO3a) expression. This downward trend was regulated by the increased expression of microRNA-872-5p (miR-872-5p). miR-872-5p affected NSC proliferation by targeting FOXO3a to increase the expression of ß-catenin and T-cell factor 4 (TCF4). In addition, TCF4 in turn acted as a transcription factor to increase the expression level of miR-872-5p, and knockdown of FOXO3a enhanced the binding of TCF4 to the miR-872-5p promoter. In conclusion, SCIRI in vivo and OGD/R in vitro stimulated the miR-872-5p/FOXO3a/ß-catenin-TCF4 pathway, thereby promoting NSC proliferation. At the same time, FOXO3a affected TCF4 transcription factor activity and miR-872-5p expression, forming a positive feedback loop that promotes NSC proliferation.

UV-dependent freshwater effect factor of nanoscale titanium dioxide for future life cycle assessment application.

Environmental impacts of nanoscale titanium dioxide (TiO2 ) should be assessed throughout the lifetime of nanoparticles (NPs) to improve the state of knowledge of the overall sustainability. Life cycle assessment (LCA) has been previously recognized as a promising approach to systematically evaluating environmental impacts of NPs. As a result of their unique nanospecific properties, characterization factors (CF) were previously used for compensating the release and potential impacts of TiO2 NPs. However, because TiO2 NPs are known to generate reactive oxygen species and elicit toxicity to freshwater organisms, the lack of adequate UV-dependent effect factors (EFs) remains a major shortcoming when addressing their life cycle impacts. To complement the LCA of TiO2 -NPs-enabled products under their specific applications, we recapitulated the freshwater toxicity of TiO2 NPs and then modeled in USEtox to determine trophic level EF ranges under UV and non-UV exposure conditions. Results indicate that EFs derived for non-UV exposure were 52 (42.9-65) potentially affected fraction (PAF) m3 /kg, and combined toxicity data derived EFs were 70.1 (55.6-90.5) PAF m3 /kg. When considering only the UV-induced exposure condition, the modeled EF increased to 500 (333-712) PAF m3 /kg. Our work highlights that case-dependent EFs should be considered and applied to reflect more realistic ecological impacts and illustrate comprehensive life cycle environmental impacts for nanoenabled products. Integr Environ Assess Manag 2023;19:578-585. © 2022 SETAC.

Augmented reality advertising and college students' interest in the extreme sports: Moderating role of innovation resistance and health consciousness.

Advertising and promotions are the most utilized types of augmented reality (AR) activations for marketers across all industries. The same is true for the sports industry. This form of augmented reality is meant to bring attention to the organization through a novel technology such as AR. Recently, a lack of interest among students in extreme sports has been attributed to a lack of professional advertising and marketing innovation. This situation requires the attention of researchers, and this study investigates the impact of augmented reality advertising on college students' interest in extreme sports, specifically in China. The article also investigates the moderating role of innovation resistance and health consciousness in the relationship between augmented reality advertising and college students' interest in extreme sports in China. Students actively participating in sports were selected using the purposive sampling technique, and AMOS was used for data analysis. According to the findings, augmented reality advertising positively correlates with interest in extreme sports. The findings also revealed that innovation resistance and health consciousness significantly moderated college students' interest in extreme sports and augmented reality advertising. This research assists regulators in developing regulations to increase interest in extreme sports through augmented reality advertising and innovation adoption.

Effect of combined epidural-general anesthesia on long-term survival of patients with colorectal cancer: a meta-analysis of cohort studies.

PURPOSE: This study aimed to analyze the long-term survival of patients with colorectal cancer after receiving combined epidural-general anesthesia (EGA) or general anesthesia (GA) alone. METHODS: The PubMed, MEDLINE, Web of Science, Cochrane Library, and Embase databases were used to search for cohort studies that explored the differences between the effects of EGA and GA on overall survival (OS) and recurrence-free survival (RFS) of patients with colorectal cancer. The hazard ratios (HRs) and their 95% confidence intervals (95%CIs) were used as indicators to evaluate the strength of the effects and were pooled. RESULTS: Nine studies were included in the meta-analysis. EGA improved the OS of patients with colorectal cancer compared with GA (HR = 0.904, 95%CI 0.871-0.938, P < 0.05). In the subgroup analysis, EGA was more protective for OS of patients with colon cancer than GA (HR = 0.840, 95%CI 0.732-0.963, P < 0.05), but not for OS of patients with rectal cancer (HR = 0.764, 95%CI 0.398-1.469, P > 0.05). Additionally, EGA could not further prolong RFS in patients with colorectal cancer (HR = 1.015, 95%CI 0.942-1.093, P > 0.05), which was the same in the subgroup analysis of patients with colon cancer (HR = 0.908, 95%CI 0.760-1.085, P > 0.05). CONCLUSION: EGA could improve the OS of patients with colorectal cancer, especially those with colon cancer, but it could not improve the OS in the subgroup of patients with rectal cancer. This difference may be due to the immune protective function of the parasympathetic nerve innervating the intestinal tubes above the splenic flexure retained by EGA. Additionally, although EGA has a protective effect on RFS in patients with colorectal cancer, the difference was not significant.  The design of this analysis is registered and displayed in the PROSPERO database (CRD42021274864).

Basal Nanosuit of Graphite for High-Energy Hybrid Li Batteries.

Lithium (Li) metal anode has attracted tremendous attention for its highest capacity (3860 mAh g-1). Herein, we report that the formation of dead Li can be effectively suppressed through Li plating on porous lithiated graphite lamina (PLGL). A lithiophilic carbon layer was decorated on the lithiophobic basal plane of porous graphite lamina (PGL) with an industry-scalable slurry-coating strategy. Moreover, the higher delithiation potential of PLGL will ensure the complete stripping of the plated Li before its delithiation, thus dramatically enhancing the average Coulombic efficiency (ACE) of Li plating/stripping to 98.5% at a high Li plating/stripping capacity of 2 mAh cm-2 (∼1100 mAh g-1) at 2 mA cm-2. Even at an ultrahigh current density of 4 mA cm-2 (with Li capacity of 4 mAh cm-2 (∼1900 mAh g-1)), the ACE could still be maintained at 96.2% in an ordinary carbonate electrolyte.

In-Plane Highly Dispersed Cu2O Nanoparticles for Seeded Lithium Deposition.

Uncontrollable dendrite growth is one of the major problems that hinders the application of lithium (Li) metal anode in rechargeable Li batteries. Achieving uniform Li deposition is the key to tackle this intractable problem. Herein, we report the highly dispersed Cu2O nanoparticles (NPs) in situ anchored on partially reduced graphene oxide via a low-temperature pyrolysis process could serve as seeds for the Li metal deposition. The lithiophilic nature of Cu2O NPs reduces the overpotential of Li nucleation and relieves the electrode polarization, enabling uniform Li nucleation and smooth plating, thus effectively eliminating dendritic and dead Li. As a result, the resulted Li metal electrodes deliver a high Coulombic efficiency of 95.6% after 140 cycles at a current density of 2 mA cm-2 and a prolonged lifespan (800 h at 1 mA cm-2) for the symmetrical cell.

Langmuir-Blodgett self-assembly of ultrathin graphene quantum dot films with modulated optical properties.

Multiple-color-emissive graphene quantum dots (GQDs) have great potential in diverse applications such as bioimaging, light emission, and photocatalysis. Growing interest in GQDs is largely focused on their macro-scale aggregations that could inherit the unique properties of individual dots. However, the lack of advanced fabrication methods limits the practical applications of GQDs. Here, we employed a Langmuir-Blodgett (LB) technique to fabricate ultrathin, high-quality GQD aggregated films with well-modulated optical properties in a wide range of wavelengths. Through the combination of a bottom-up synthesis of GQDs and the LB assembly method, uniform, closely packed, and ultra-thin GQD films can be self-assembled with a well-controlled thickness on different substrates. The photoluminescence (PL) spectra of ultra-thin GQD films have an obvious red-shift compared with isolated GQD solution. We then elucidate remarkably strong energy transfer in self-assembled GQDs. Furthermore, the ultra-thin GQD films exhibit a clear excitation-dependent PL that could almost cover the entire visible light. This convenient self-assembly method and systematic optical and physical studies of ultra-thin GQD films may provide a new direction for developing low-cost, GQD film-based light-emitting devices.

Fe3O4-Decorated Porous Graphene Interlayer for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are seriously restrained by the shuttling effect of intermediary products and their further reduction on the anode surface. Considerable researches have been devoted to overcoming these issues by introducing carbon-based materials as the sulfur host or interlayer in the Li-S systems. Herein, we constructed a multifunctional interlayer on a separator by inserting Fe3O4 nanoparticles (NPs) in a porous graphene (PG) film to immobilize polysulfides effectively. The porous structure of graphene was optimized by controlling the oxidation conditions for facilitating ion transfer. The polar Fe3O4 NPs were employed to trap sulfur species via strong chemical interaction. By exploiting the PG-Fe3O4 interlayer with optimal porous structure and component, the Li-S battery delivered a superior cycling performance and rate capability. The reversible discharge capacity could be maintained at 732 mAh g-1 after 500 cycles and 356 mAh g-1 after total 2000 cycles at 1 C with a final capacity retention of 49%. Moreover, a capacity of 589 mAh g-1 could also be maintained even at 2 C rate.

Evaluation of neutralizing efficacy of monoclonal antibodies specific for 2009 pandemic H1N1 influenza A virus in vitro and in vivo.

Pandemic influenza A virus (H1N1) 2009 poses a serious public-health challenge worldwide. To characterize the neutralizing epitopes of this virus, we generated a panel of eight monoclonal antibodies (mAbs) against the HA of the A/California/07/2009 virus. The antibodies were specific for the 2009 pdm H1N1 HA, as the antibodies displayed HA-specific ELISA, hemagglutination inhibition (HAI) and neutralization activity. One mAb (mAb12) showed significantly higher HAI and neutralizing titers than the other mAbs. We mapped the antigenic epitopes of the HA by characterizing escape mutants of a 2009 H1N1 vaccine strain (NYMC X-179A). The amino acid changes suggested that these eight mAbs recognized HA antigenic epitopes located in the Sa, Sb, Ca1 and Ca2 sites. Passive immunization with mAbs showed that mAb12 displayed more efficient neutralizing activity in vivo than the other mAbs. mAb12 was also found to be protective, both prophylactically and therapeutically, against a lethal viral challenge in mice. In addition, a single injection of 10 mg/kg mAb12 outperformed a 5-day course of treatment with oseltamivir (10 mg/kg/day by gavage) with respect to both prophylaxis and treatment of lethal viral infection. Taken together, our results showed that mouse-origin mAbs displayed neutralizing effectiveness in vitro and in vivo. One mAb in particular (mAb12) recognized an epitope within the Sb site and demonstrated outstanding neutralizing effectiveness.

NA proteins of influenza A viruses H1N1/2009, H5N1, and H9N2 show differential effects on infection initiation, virus release, and cell-cell fusion.

Two surface glycoproteins of influenza virus, haemagglutinin (HA) and neuraminidase (NA), play opposite roles in terms of their interaction with host sialic acid receptors. HA attaches to sialic acid on host cell surface receptors to initiate virus infection while NA removes these sialic acids to facilitate release of progeny virions. This functional opposition requires a balance. To explore what might happen when NA of an influenza virus was replaced by one from another isolate or subtype, in this study, we generated three recombinant influenza A viruses in the background of A/PR/8/34 (PR8) (H1N1) and with NA genes obtained respectively from the 2009 pandemic H1N1 virus, a highly pathogenic avian H5N1 virus, and a lowly pathogenic avian H9N2 virus. These recombinant viruses, rPR8-H1N1NA, rPR8-H5N1NA, and rPR8-H9N2NA, were shown to have similar growth kinetics in cells and pathogenicity in mice. However, much more rPR8-H5N1NA and PR8-wt virions were released from chicken erythrocytes than virions of rPR8-H1N1NA and rPR8-H9N2NA after 1 h. In addition, in MDCK cells, rPR8-H5N1NA and rPR8-H9N2NA infected a higher percentage of cells, and induced cell-cell fusion faster and more extensively than PR8-wt and rPR8-H1N1NA did in the early phase of infection. In conclusion, NA replacement in this study did not affect virus replication kinetics but had different effects on infection initiation, virus release and fusion of infected cells. These phenomena might be partially due to NA proteins' different specificity to α2-3/2-6-sialylated carbohydrate chains, but the exact mechanism remains to be explored.

Identification and characterization of RNA duplex unwinding and ATPase activities of an alphatetravirus superfamily 1 helicase.

Dendrolimus punctatus tetravirus (DpTV) belongs to the genus omegatetravirus of the Alphatetraviridae family. Sequence analysis predicts that DpTV replicase contains a putative helicase domain (Hel). However, the helicase activity in alphatetraviruses has never been formally determined. In this study, we determined that DpTV Hel is a functional RNA helicase belonging to superfamily-1 helicase with 5'-3' dsRNA unwinding directionality. Further characterization determined the length requirement of the 5' single-stranded tail on the RNA template and the optimal reaction conditions for the unwinding activity of DpTV Hel. Moreover, DpTV Hel also contains NTPase activity. The ATPase activity of DpTV Hel could be significantly stimulated by dsRNA, and dsRNA could partially rescue the ATPase activity abolishment caused by mutations. Our study is the first to identify an alphatetravirus RNA helicase and further characterize its dsRNA unwinding and NTPase activities in detail and should foster our understanding of DpTV and other alphatetraviruses.