MicroRNAs have been proved to be the biomarker for early detection of pancreatic cancer and the precisely quantitation of the MicroRNA-10b in the blood samples even can distinguish pancreatic cancer ...from chronic pancreatitis (CP) and normal controls (NC). In this study, we developed a DSN-assisted dual-SERS biosensor for microRNA-10b in exosome and residual plasma of blood samples detection based on the Fe3O4 @Ag-DNA-Au@Ag@DTNB (SERS tag) conjugates. In presence of target microRNA, it can hybridized with the complementary DNA probes. DSN enzyme was then added to selectively cleaves the DNA probe of the DNA/microRNA duplex, SERS tags can be released from the Fe3O4@Ag and SERS intensity quenching can be triggered, the released microRNA can enter the cycle to decluster other DNA and SERS tags. Due to the dual-SERS enhancement of the Fe3O4@Ag-SERS tag conjugates and the recycling signal amplification, a detection limit of 1 aM with single-base recognition can be performed by one step. The target microRNA in plasma-derived exosome and residual supernatant plasma of blood samples from pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP) and normal controls (NC) were directly quantified and significant SERS signal distinction can be found among them. The precise quantitation, one-step and one-pot operation can ensure this assay a promising future for point-of-care cancer diagnosis technology.
•DSN-assisted SERS biosensor for exosomal microRNA detection has been designed.•Au@Ag@DTNB was designed as SERS tag and Fe3O4@Ag as magnetic SERS substrate.•A detection limit of 1 aM with single-base recognition can be realised by one-step.•Target microRNA in plasma-derived exosome of clinic samples was directly quantified.
Construction of photothermal therapy (PTT) at mild temperature through regulating heat shock proteins expression, autophagy level, free radical generation and organelle targeting, along with the ...combination of mild-temperature PTT with other treatment modalities to yield the remarkable superadditive effect.
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•The mild temperature threshold is firstly elucidated and the possible methods to decrease the mild temperature threshold are provided.•The representative examples that have been or possibly been used in constructing mild-temperature PTT system to combat cancer are systematically summarized.•The challenges and possible development for enhanced mild-temperature PTT are highlighted.
The last few years have witnessed explosive growth in the design and development of various photothermal agents (PTAs) to realize phtothermal therapy (PTT) for eradicating solid tumors. Nevertheless, the therapeutic efficacy of PTT is still restricted by several obstacles, especially the thermotolerance of tumors, which might potentially induce inflammatory disease, damage normal organs, or even lead to tumor recurrence. Exploitation of innovative strategies to enhance PTT at mild temperature is thus the key determinant toward successful clinical use of PTT. In this review, we dissect the cell death mechanism triggered by PTT at different temperature, indicating that enhancing apoptosis pathway is favorable for PTT at mild temperature. The recent advances in the construction of mild-temperature PTT through regulating heat shock proteins expression, autophagy level, free radical generation and organelle targeting to overcome tumor thermotolerance are susequently concluded, along with the excellent and representative examples of combining mild-temperature PTT with other therapies (i.e. photodynamic therapy, chemodynamic therapy, starvation therapy and gas therapy), which exhibits the remarkable superadditive effect. Furthermore, the key scientific and technical challenges for mild-temperature PTT are also discussed to accelerate clinical translation.
Levels of legacy brominated flame retardants (BFRs), including tetrabromobisphenol A (TBBPA), hexabromocyclododecane isomers (HBCDs) and polybrominated diphenyl ethers (PBDEs), and six currently used ...novel BFRs were determined in house dust and office dust collected from a community in Beijing, China. This is the first study where the three kinds of legacy BFRs and novel BFRs were all measured in dust samples from China. HPLC-MS/MS was used for the detection of TBBPA and HBCDs, and the other BFRs were tested on a GC-NCI/MS. Decabromodiphenyl ethane (DBDPE), PBDEs, HBCD and TBBPA were found to be the main BFRs in the dust samples, with median levels of 709, 241, 199 and 26.7ng/g dust, respectively. Due to the high density of electronic equipment used in offices, levels of BFRs in office dust were found to be higher than those in house dust. DBDPE, as a replacement of PBDEs, was the predominant BFR, and the median level of DBDPE was not only several orders of magnitude higher than that of other novel BFRs but also 3 to 27 times higher than that of the three legacy BFRs, indicating that the consumption pattern of BFRs in the Chinese market has shifted from PBDEs to PBDE alternatives. Median estimated daily intakes (EDIs) of BFRs through dust ingestion for adults (>20years) and toddlers (<2years) were in the range of 2.8×10−5–0.201ng/kg body weight (bw)/day and 5.7×10−4–2.52ng/kg bw/day, respectively. The body burden of BFRs for toddlers was far higher than that for adults; however, a comparison between EDIs and threshold values suggested that daily intakes of BFRs for both adults and toddlers were unlikely to raise significant health concerns.
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•BFRs were measured in house dust and office dust collected from Beijing, China.•Levels of DBDPE were higher than those of any other BFRs in this study.•The consumption pattern of BFRs in China may have shifted from PBDEs to non-PBDE BFRs.•The daily intake of BFRs is unlikely to raise significant health concerns.
Ammonia (NH3) is a promising energy carrier to store and transport renewable hydrogen (H2) that can be generated using, e.g., wind and solar energy. Direct combustion of NH3 is one of the possible ...methods to utilize the energy by the end users. To understand the combustion characteristics of NH3 as a fuel, the laminar burning velocities of NH3/air, NH3/H2/air, NH3/CO/air and NH3/CH4/air premixed flames were investigated experimentally using the heat flux method. Measurements are reported for a wide range of equivalence ratios and blending ratios. Kinetic modeling was also performed using available chemical kinetic mechanisms, namely the GRI-Mech 3.0, the Okafor et al. and the San Diego mechanisms. The experimental results for NH3/air flames agree well with the literature data and it is found that blending NH3 with H2 is the most effective manner to increase the burning velocity of NH3 based fuel mixtures. None of the kinetic mechanisms used can accurately predict most of the measured data. Sensitivity and reaction path analyses indicate that the oxidation of NH3 blended with the additive fuels considered can be understood as the parallel oxidation processes of the individual fuels, and that the source of discrepancy between the experimental and modeling results is related to the inaccuracy of the rate parameters of the N-containing reactions. In this regard, the present detailed and reliable experimental data is of special value for model development and validation.
The impacts of air pollution on public health have become a great concern worldwide. Ambient particulate matter (PM) is a major air pollution that comprises a heterogeneous mixture of different ...particle sizes and chemical components. The chemical composition and physicochemical properties of PM change with space and time, which may cause different impairments. However, the mechanisms of the adverse effects of PM on various systems have not been fully elucidated and systematically integrated. The Adverse Outcome Pathway (AOP) framework was used to comprehensively illustrate the molecular mechanism of adverse effects of PM and its components, so as to clarify the causal mechanistic relationships of PM-triggered toxicity on various systems. The main conclusions and new insights of the correlation between public health and PM were discussed, especially at low concentrations, which points out the direction for further research in the future. With the deepening of the study on its toxicity mechanism, it was found that PM can still induce adverse health effects with low-dose exposure. And the recommended Air Quality Guideline level of PM
was adjusted to 5 μg/m
by World Health Organization, which meant that deeper and more complex mechanisms needed to be explored. Traditionally, oxidative stress, inflammation, autophagy and apoptosis were considered the main mechanisms of harmful effects of PM. However, recent studies have identified several emerging mechanisms involved in the toxicity of PM, including pyroptosis, ferroptosis and epigenetic modifications. This review summarized the comprehensive evidence on the health effects of PM and the chemical components of it, as well as the combined toxicity of PM with other air pollutants. Based on the AOP Wiki and the mechanisms of PM-induced toxicity at different levels, we first constructed the PM-related AOP frameworks on various systems.
Decabromodiphenyl ether (BDE-209) and its substitute decabromodiphenyl ethane (DBDPE) are heavily used in various industrial products as flame retardant. They have been found to be persistent in the ...environment and have adverse health effects in humans. Although some former studies have reported toxic effects of BDE-209, the study of DBDPE's toxic effects is still in its infancy, and the effects of DBDPE on hepatotoxicity are also unclear. This study aimed to evaluate and compare the hepatotoxicity induced by BDE-209 and DBDPE using a rat model. Sprague-Dawley rats were administered DBDPE or BDE-209 (5, 50, 500 mg/kg bodyweight) intragastrically once a day for 28 days. Twenty-four hours after the end of treatment, the rats were sacrificed, and body liver weight, blood biochemical parameters, liver pathology, oxidative stress, inflammation, pregnane X receptor (PXR), constitutive androstane receptor (CAR), and changes in cytochrome P450 (CYP3A) enzymes were measured. Our results showed that both BDE-209 and DBDPE could cause liver morphological changes, induce oxidative stress, increase γ-glutamyl transferase and glucose levels in serum, and down-regulate PXR, CAR, and CYP3A expression. In addition, BDE-209 was found to increase liver weight and the ratio of liver/body weight, lead to elevated total bilirubin and indirect bilirubin levels in serum, and induce inflammation. The present study indicated that BDE-209 and DBDPE may interfere with normal metabolism in rats through oxidative stress and inflammation, which inhibit PXR and CAR to induce the expression of CYP3A enzymes, and finally produce hepatotoxic effects and cause liver damage in rats. Comparatively, our results show that the damage caused by BDE-209 was more serious than that caused by DBDPE.
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•Hepatotoxicity induced by BDE-209 and DBDPE in rats was studied and compared.•Both BDE-209 and DBDPE can cause liver damage whereas DBDPE is less toxic.•BDE-209 and DBDPE may interfere metabolism in rats through oxidative stress and inflammation.
The interfacial assembly of graphene oxide (GO) at the water/oil interface and its kinetics were systematically studied. GO nanosheets were found to segregate to the water/oil interface and interact ...with quaternized block copolymer chains by the peripheral carboxyl groups on the GO. If the interfacial area is decreased, then GO, assembled at and confined to the interface, jams and then buckles. An analysis of the kinetics of the assembly processes leads to the conclusion that the diffusion of GO to the interface is the rate-determining step. The morphology of the jammed GO film was investigated, and TEM images show that GO sheets form a mosaic or tile across the whole oil/water interface.
Health effects attributable to air pollution exposure in Chinese population have been least understood. The authors conducted a meta-analysis on 33 time-series and case-crossover studies conducted in ...China to assess mortality effects of short-term exposure to particulate matter with aerodynamic diameters less than 10 and 2.5μm (PM10 and PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO). Significant associations between air pollution exposure and increased mortality risks were observed in the pooled estimates for all pollutants of interest. In specific, each 10μg/m3 increase in PM2.5 was associated with a 0.38% (95% Confidence Interval, CI: 0.31, 0.45) increase in total mortality, a 0.51% (95% CI: 0.30, 0.73) in respiratory mortality, and a 0.44% (95% CI: 0.33, 0.54) in cardiovascular mortality. When current annual PM2.5 levels in mega-Chinese cities to be reduced to the WHO Air Quality Guideline (AQG) of 10μg/m3, mortality attributable to short-term exposure to PM2.5 could be reduced by 2.7%, 1.7%, 2.3%, and 6.2% in Beijing, Shanghai, Guangzhou and Xi'an, respectively. The authors recommend future studies on the nature of air pollution concentration and health effect relationships in Chinese population to support setting stringent air quality standards to improve public health.
► Understanding on the health effects attributable to air pollution exposure in Chinese population is limited. ► Significant mortality risks were found associated with increased acute exposure to air pollution in this study. ► Significant improvement in ambient air quality has substantial and measurable public health benefits. ► The exposure-response coefficients derived from long-term exposure to air pollution are urgently needed in China.
Supramolecular chemotherapy is aimed to employ supramolecular approach for regulating the cytotoxicity and improving the efficiency of antitumor drugs. In this paper, we demonstrated a new example of ...supramolecular chemotherapy by utilizing the clinical antitumor drug, oxaliplatin, which is the specific drug for colorectal cancer treatment. Cytotoxicity of oxaliplatin to the colorectal normal cell could be significantly decreased by host–guest complexation between oxaliplatin and cucurbit7uril (CB7). More importantly, oxaliplatin-CB7 exhibited cooperatively enhanced antitumor activity than oxaliplatin itself. On the one hand, the antitumor activity of oxaliplatin can reappear by competitive replacement of spermine from oxaliplatin-CB7; on the other hand, CB7 can consume the overexpressed spermine in tumor environments, which is essential for tumor cell growth. These two events can lead to the cooperatively enhanced antitumor performance. Supramolecular chemotherapy can be applied to treat with spermine-overexpressed tumors. It is highly anticipated that this strategy may be employed in many other clinical antitumor drugs, which opens a new horizon of supramolecular chemotherapy for potential applications in clinical antitumor treatments.
The detection of hepatocellular carcinoma (HCC) circulating tumor cells (CTCs) from a blood sample can be a very powerful noninvasive approach for the early detection and therapy of liver cancer. ...However, the extreme rarity of tumor cells in blood containing billions of other cells makes the capture and identification of CTCs with sufficient sensitivity and specificity a real challenge. Here, a magnetically assisted surface‐enhanced Raman scattering (SERS) biosensor for HCC CTC detection is reported for the first time. The biosensor consists of two basic elements: anti‐ASGPR antibody‐Fe3O4@Ag magnetic nanoparticles and anti‐GPC3 antibody‐Au@Ag@DTNB nanorods. According to the dual‐selectivity of the anti‐ASGPR and anti‐GPC3 antibodies and the dual‐enhancement SERS signal of the MNPs silver shell and the Au@Ag NRs SERS tags, a limit of detection of 1 cell mL−1 for HCC CTC in human peripheral blood samples with a linear relationship from 1 to 100 cells mL−1 can be obtained. The system shows good performance in real serum, which suggests it may be a promising tool for HCC clinical diagnosis.
Carcinoma cell detection: A magnetically assisted surface‐enhanced Raman scattering (SERS) biosensor for hepatocellular carcinoma (HCC) circulating tumor cells (CTC) detection is reported. The biosensor consists of anti‐ASGPR antibody‐Fe3O4@Ag magnetic nanoparticles and anti‐GPC3 antibody‐Au@Ag@DTNB nanorods. The system has dual selectivity of the anti‐ASGPR and anti‐GPC3 antibodies and a dual‐enhancement SERS signal of the MNPs silver shell and the Au@Ag NRs SERS tags.
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