Ultrasensitive Imaging Assay of Multiple Mycotoxins Using Cobalt DNA-Inorganic Hybrid Superstructure with High Chemiluminescence Catalytic Property.

A multiplex assay of mycotoxins in food and medicine is urgently needed and challenging due to synergistic hazards of trace mycotoxins and a lack of sensitive and user-friendly detection approaches. Herein, a cobalt DNA-inorganic hybrid superstructure (Co@DS) was developed through isothermal rolling circle amplification (RCA) for an ultrasensitive chemiluminescence (CL) imaging assay of multiple mycotoxins. Cobalt ions were enriched in the RCA product, endowing the Co@DS with a high CL catalytic property. Experimental studies elucidated the formation and CL catalytic mechanism of Co@DS. Co@DS was facilely integrated with biotinylated DNA to function as a universal platform and combined with a disposable immunosensor array chip. After a competitive immunoassay and biotin-avidin recognition, the CL signals of luminol and hydrogen peroxide, catalyzed by Co@DS captured on each testing zone of the array chip, were imaged simultaneously. Target mycotoxins can be quantitated by CL intensities. To validate the concept, the CL imaging approach was employed for joint determination of aflatoxin B1, ochratoxins A, and zearalenone. Under optimal conditions, it showed advantages including simple sample pretreatment, acceptable throughput, high accuracy, minimal sample consumption, broad linear ranges, and detection limits as low as 0.75, 0.62, and 0.61 pg mL-1, respectively. Furthermore, the approach was applied in analyzing real coix seed samples, showcasing excellent performance in effectively distinguishing qualified and contaminated medicine, revealing the great potential in managing the complex issue of mycotoxins cocontamination in food and medicine.

Phosphorylation of Li-Rich Mn-Based Layered Oxides for Anion Redox and Structural Stability.

Li-rich Mn-based layered oxides are proposed to be candidates for high-energy Li-ion batteries. However, their large-scale production is still hampered by poor rate capability and severe voltage decay. It was mainly attributed to the irreversible oxygen loss, which induces transition metal ion migration, electrolyte consumption, and structural evolution. Herein, we propose an effective strategy of phosphorylation, in which the phosphate ion is induced to remove the surface labile oxygen. It urges the Li2MnO3 component to transform to the spinel-like structure and promotes the anionic redox process, thus facilitating lithium-ion diffusion and improving structural stability. As a result, the Li2MnO3 component is more prone to be activated, with the capacity increased by 18% in comparison with the pristine one. It also exhibits a superior capacity retention of 86.1% after 150 extended cycles and better rate performance delivering a capacity of 148.1 mA h g-1 even at 10 C. The effective phosphorylation opens a new way to tune anion redox chemistry and obtain structurally stable materials.

Programmable T-Junction Structure-Assisted CRISPR/Cas12a Electrochemiluminescence Biosensor for Detection of Sa-16S rDNA.

Herein, a strand displacement amplification (SDA)-assisted CRISPR/Cas12a (LbCpf1) electrochemiluminescence (ECL) biosensor was fabricated for ultrasensitive identification of Staphylococcus aureus (Sa)-16S rDNA. A porphyrinic Zr metal-organic framework (MOF) (PCN-224) nanomaterial was prepared as the coreactant accelerator, which promoted the conversion of S2O82- and SO4*-, thus enhancing the reaction with CdS quantum dots (QDs) and amplifying the ECL emission signal. Meanwhile, with the presence of Sa-16S rDNA, the auxiliary probes and primers stimulated the SDA reaction under the action of Klenow fragment (3'-5' exo-) and Nt. BbvCI specifically recognized Sa-16S rDNA to form a defective T-junction structure and generated second primers to initiate the cycles. Such a structure transformed the input signal (Sa-16S rDNA) into substantial single-stranded DNA products (SP) through SDA. SP acted as activators and activated arbitrary side chain cleavage of CRISPR/Cas12a (trans-cleavage) and further realized effective annihilation of ECL signals. This ECL platform demonstrated desirable assay performance for Sa-16S rDNA with a wide response range of 1 fM to 10 nM, and the limit of detection was 0.437 fM (S/N = 3), showing good sensitivity and specificity. Therefore, the method not only expanded the applications of CRISPR/Cas12a but also opened up a novel strategy for clinical diagnosis.

Targeting BET proteins inhibited the growth of non-small cell lung carcinoma through downregulation of Met expression.

Hepatocyte growth factor receptor (HGFR or Met) upregulation has been proven to play important roles in non-small cell lung carcinoma (NSCLC). Interestingly, chemoresistance against epidermal growth factor receptor (EGFR) inhibitors including erlotinib and gefitinib was also related to Met. Targeting bromodomain and extra terminal domain (BET) proteins, especially BRD4, has shown inhibitory effects on lung cancer, but the mechanism is unclear. Herein, we found that JQ1 (BET inhibitor) suppressed NSCLC cell growth, reduced the Met expression, and contributed to inactivation of PI3K/Akt and MAPK/ERK pathways. Moreover, another BET protein inhibitor I-BET151, or BRD4 depletion, also inhibited NSCLC cell growth and downregulated Met. JQ1 inhibited HGF-induced cell growth and Met/PI3K/Akt activation, also inhibited A549 tumor growth in xenograft mouse models, in parallel with Met downregulation. Moreover, JQ1 inhibited the growth of paired erlotinib-sensitive and resistant HCC827 cells in parallel with Met downregulation and PI3K/Akt signaling inactivation. JQ1 also exerted inhibitory influences on the growth of erlotinib-sensitive and resistant HCC827 tumors in xenograft mouse models. These results suggested that targeting BET proteins inhibited NSCLC via downregulating Met and inactivating PI3K/AKT pathway. Our findings reveal a novel mechanism of BET proteins implicated in NSCLC progression with Met taken into consideration.

Nanomaterials pollutant's emission influencing outdoor recreation in China: Analytical strategies proceeding to sustainable environment.

The global demand for bioenergy and nanomaterial utilization has significantly contributed to their source depletion. The impact of outdoor pollutant emissions on residents' health, behavior, physical activity, and sleeping behavior is much less explored. Producing biofuels from organic waste has the potential to unite budget-friendliness and long-term sustainability. Primary biofuels are produced specifically to mitigate environmental problems, and secondary biofuels are produced specifically to mitigate other environmental problems. The high level of pollutants ina certain area can severely restrict human activities and ultimately influence their whole life. The study aims to empirically evaluate the influence of nanomaterials pollutants emissions influencing outdoor recreation in China because its economy is based on fast-paced industrialization and urbanization. Various datasets were collected, including domestic and international tourists from the annual statistics for 2011-2020 from the National Bureau of Statistics of China. Ten years of annual METAR data of visibility (VR), temperature (T), relative humidity (Demirhan), and wind speed (WS) from 30 metrological stations at international airports. Annual average AOD (Aerosol's Optical Depth), O3 (Ozone), CO (Carbon Monoxide), SO4 (Sulphate), and PM2.5 (Particulate Matter) satellite imageries from 2011 to 2020 were obtained from NASA's official portal. The overall picture of satellite observations of pollutants over China describes that the highest level of AOD was observed in regions with greater population concentration than in other areas. We computed a statistical summary, correlation matrix, and Autoregressive Distributed Lag (ARDL) approach. Certain analyses were performed, like Unrestricted Error Correction Models (UECM) and Restricted Error Correction Model (RECM)), bound tests for cointegration, and multiplier estimations for short-term and long-term impacts. UECM and RECM models produced R2 > 0.90 with good F statistics and a p-value of <0.05. A bounds F-test for no cointegration on the ARDL model was performed, and the results show that the p-value = 1e-06 and F = 8.516 with alternative hypothesis = Possible cointegration. Bounds t-test for no cointegration was also performed on UECM model and the results show that t = -2.9066, Lower-bound I(0) = -3.43, Upper-bound I(1) = -5.37, p-value = 0.6138 and alternative hypothesis = Possible cointegration. The study's findings may help Chinese policymakers and stakeholders design effective information strategies to combat air pollution. Effective measures can help alleviate this devastating air quality factor, thus benefiting the tourism industry and enhancing the local inhabitants' welfare.

Photoelectrochemical biosensor based on CdS quantum dots anchored h-BN nanosheets and tripodal DNA walker for sensitive detection of miRNA-141.

Herein, a high-sensitivity photoelectrochemical (PEC) biosensor was developed based on CdS quantum dots (QDs) sensitized porous hexagonal boron nitride (h-BN) nanosheets (NSs) and the multiple sites tripodal DNA walker (TDW) formed by catalytic hairpin assembly (CHA). Noticeably, the porous structure of h-BN NSs gives it a lasting gift of large specific surface areas and extensive active reaction sites, which makes it possible to be employed as photoelectric substrate material. The h-BN/CdS QDs composite material promotes the transmission of photogenerated electrons and holes, the outstanding photoelectric conversion efficiency. Meanwhile, the CHA-formed TDWs triggered by miRNA-141 moved on track strand-functionalized electrode, so that a large number of alkaline phosphatase (ALP) was immobilized on the electrode surface and further in situ catalyzed ascorbic acid 2-phosphate (AAP) to produce ascorbic acid (AA) as the electron donor. As the result of the decisive influence of electron donor on PEC biosensor, the sensitive detection of miRNA-141 was realized. The proposed PEC biosensor displayed an excellent linear relationship ranging from 1 fM to 100 nM with a detection limit of 0.73 fM, providing a powerful strategy for early clinical diagnosis and biomedical research.

Photoswitchable CRISPR/Cas12a-Amplified and Co3O4@Au Nanoemitter Based Triple-Amplified Diagnostic Electrochemiluminescence Biosensor for Detection of miRNA-141.

In this work, a CRISPR/Cas12a initiated switchable ternary electrochemiluminescence (ECL) biosensor combined with a Co3O4@Au nanoemitter is presented for the in vitro monitoring of miRNA-141. Benefiting from the advantages of high-throughput cargo payload capability and superconductivity, three-dimensional reduced graphene oxide (3D-rGO) was designated as an introductory conducting stratum of a paper working electrode (PWE). With the collaborative participation of Co3O4@Au NPs, the transmutation of TPrA in the Ru(bpy)32+/TPrA system can be riotously expedited into exorbitant free radical ions TPrA•, which provoked the exaggeration of the ECL signal. Moreover, the programmable enzyme-free hybrid chain reaction (HCR) amplifier on the PWE surface accurately anchored the assembly of nucleic acid tandem and accomplished the secondary recursion of the signal. Impressively, the multifunctional CRISPR/Cas12a with nonspecific cis/trans-splitting decomposition manipulated the photoswitch of the "on-off" signal state that avoided the false-positive diagnosis. The presented multistrategy cooperative biosensor demonstrated extraordinary sensitivity and specificity, with a low detection limit of 3.3 fM (S/N = 3) in the concentration scope from 10 fM to 100 nM, which fully corresponded to the expectation. Overall, this innovative methodology paved a generous avenue for evaluating multifarious biotransformations and provided a tremendous impetus to the development of real-time diagnosis and clinical detection of other biomarkers.

Dual-Engine Powered Paper Photoelectrochemical Platform Based on 3D DNA Nanomachine-Mediated CRISPR/Cas12a for Detection of Multiple miRNAs.

This work proposed a novel double-engine powered paper photoelectrochemical (PEC) biosensor based on an anode-cathode cooperative amplification strategy and various signal enhancement mechanisms, which realized the monitoring of multiple miRNAs (such as miRNA-141 and miRNA-21). Specifically, C3N4 quantum dots (QDs) sensitized ZnO nanostars and BiOI nanospheres simultaneously to construct a composite photoelectric layer that amplified the original photocurrent of the photoanode and photocathode, respectively. Through the independent design and partition of a flexible paper chip to functionalize injection holes and electrode areas, the bipolar combination completed the secondary upgrade of signals, which also provided biological reaction sites for multitarget detection. With the synergistic participation of a three-dimensional (3D) DNA nanomachine and programmable CRISPR/Cas12a shearing tool, C3N4 QDs lost their attachment away from the electrode surface to quench the signal. Moreover, electrode zoning significantly reduced the spatial cross talk of related substances for multitarget detection, while the universal trans-cleavage capability of CRISPR/Cas12a simplified the operation. The designed PEC biosensor revealed excellent linear ranges for detection of miRNA-141 and miRNA-21, for which the detection limits were 5.5 and 3.4 fM, respectively. With prominent selectivity and sensitivity, the platform established an effective approach for trace multitarget monitoring in clinical applications, and its numerous pioneering attempts owned favorable reference values.

BET inhibitors combined with chemotherapy synergistically inhibit the growth of NSCLC cells.

The bromodomain and extra­terminal domain (BET) family proteins are essential epigenetic regulators in lung cancer. However, BET inhibitors have not had the anticipated therapeutic efficacy. Combined treatment using BET inhibitors along with other drugs had favorable therapeutic effects but the underlying molecular mechanisms remain elusive. The aim of the present study was to investigate the antineoplastic effects and mechanisms of a combination of a BET inhibitor and paclitaxel or cisplatin in non­small cell lung cancer (NSCLC). By using the online Kaplan­Meier plotter, it was revealed that increased mRNA levels of several BET protein­coding genes were associated with poor prognosis in NSCLC. SRB assay results revealed that pharmaceutical or genetic targeting of BET proteins suppressed the growth of NSCLC cells. Inhibition of BET protein expression, in combination with the use of chemotherapeutic drugs such as paclitaxel and cisplatin, further restrained NSCLC cell growth in a synergistic manner. Mechanistically, this combination of suppression of BET expression and chemotherapeutic treatment blocked NSCLC cell growth by inhibiting autophagy and promoting apoptosis, which were revealed by both western blot and ELISA results. The present findings revealed a new rationale for using a combination of BET inhibitors with chemotherapy in NSCLC treatment.

A general route of fluoride coating on the cyclability regularity of high-voltage NCM cathodes.

The effect of fluoride coatings, an effective approach to suppress HF corrosion, on the cycling stability of NCM523 cathodes is systematically studied. It is the first study to reveal that fluoride coatings significantly restrain interfacial reactions when, simultaneously, the fluoride suspension possesses an appropriate pH (near 4.0) and there is a small cation ionic radius.

Accurate Control of Initial Coulombic Efficiency for Lithium-rich Manganese-based Layered Oxides by Surface Multicomponent Integration.

Low initial Coulombic efficiency (ICE) is an obstacle for practical application of Li-rich Mn-based layered oxides (LLOs), which is closely related with the irreversible oxygen evolution owing to the overoxidized reaction of surface labile oxygen. Here we report a NH4 F-assisted surface multicomponent integration technology to accurately control the ICE, by which oxygen vacancies, spinel-layered coherent structure, and F-doping are skillfully integrated on the surface of treated LLOs microspheres. Though the regulation on the removed amount of labile oxygen by surface integrated structure, the ICE of LLOs cathodes can adjust from starting value to 100 %. X-ray absorption spectroscopy, refined X-ray diffraction, and scanning transmission electron microscopy show that the removed labile oxygen mainly comes from Li2 MnO3 -like structure. Even operating at a high cut-off voltage of 5 V, the capacity retention of integrated sample at 200 mA g-1 is still larger than 98 % after 100 cycles.

AEG-1 promotes the growth of gastric cancer through the upregulation of eIF4E expression.

Background: AEG-1 has been proven to be tumor enhancer in gastric cancer. However, its mechanism has not yet been fully clarified. Methods: Gain-of-function and loss-of-function experiments were conducted to determine the role of eIF4E in AEG-1-induced growth of gastric cancer cells and xenografts of a nude mouse model. Western blot analysis and SRB assay were used to determine the protein expression levels and survival cell numbers. Results: Silencing the expression of AEG-1 inhibited the growth of gastric cancer cells in parallel with a decreased eIF4E and cyclin D1 expression; however, the overexpression of AEG-1 promoted cell growth and increased eIF4E and cyclin D1 expression. Moreover, the overexpression of eIF4E partially reversed the AEG-1 silencing-induced reduction of cyclin D1 and the inhibition of cell growth. An eIF4E knockdown also partially reversed the AEG-1 overexpression-induced upregulation of cyclin D1 and cell growth. Notably, manipulating the expression of eIF4E did not affect the expression of AEG-1. Finally, the silencing of AEG-1 expression inhibited the growth of SGC-7901 xenografts in parallel with the downregulation of eIF4E and cyclin D1 expression in the nude mouse model. Conclusion: AEG-1 promoted the growth of gastric cancer through upregulation of eIF4E/cyclin D1 signaling pathway.

Glibenclamide Targets Sulfonylurea Receptor 1 to Inhibit p70S6K Activity and Upregulate KLF4 Expression to Suppress Non-Small Cell Lung Carcinoma.

Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of ATP-sensitive potassium channels (KATP channels) and the receptor of antidiabetic drugs, such as glibenclamide, which induce insulin secretion in pancreatic ß cells. However, the expression and role of SUR1 in cancer are unknown. In this study, we found that SUR1 expression was elevated in human non-small cell lung carcinoma (NSCLC) tissues and cell lines. SUR1 silencing suppressed the growth of NSCLC cells, while SUR1 overexpression promoted cell growth. Targeting SUR1 with glibenclamide suppressed cell growth, cell-cycle progression, epithelial-mesenchymal transition (EMT), and cell migration. Moreover, SUR1 directly interacted with p70S6K and upregulated p70S6K phosphorylation and activity. In addition, glibenclamide inhibited p70S6K, and overexpression of p70S6K partially reversed the growth-inhibiting effect of glibenclamide. Furthermore, glibenclamide upregulated the expression of the tumor suppressor Krüppel-like factor 4 (KLF4), and silencing KLF4 partially reversed the inhibitory effect of glibenclamide on cell growth, EMT, and migration. We found that SUR1 targeted p70S6K to downregulate KLF4 expression by enhancing DNA-methyltransferase 1-mediated methylation of the KLF4 promoter. Finally, in xenograft mouse models, SUR1 expression silencing or glibenclamide treatment inhibited the growth of A549 tumors, downregulated p70S6K activity, and upregulated KLF4 expression. These findings suggested that SUR1 expression was elevated in some NSCLC tissues and functioned as a tumor enhancer. Targeting SUR1 with glibenclamide inhibited NSCLC through downregulation of p70S6K activity and subsequent upregulation of the expression of the tumor suppressor gene KLF4 SUR1 can be developed as a new target for cancer therapy and glibenclamide has potential anticancer effects.

[Effect of Cu-Ce/γ-Al2O3 catalyst on bio-oil production by hydrothermal deoxygenation of stearic acid].

In order to improve the hydrothermal deoxygenation of organic acids as well as to reduce the cost, we prepared a Cu-Ce/γ-Al2O3 catalyst to study the hydrothermal deoxygenation of stearic acid in the absence of H2. The Brunauer-Emmett-Teller surface area and X-ray diffraction pattern suggest that both CuO and CeO2 exist in the Cu-Ce/γ-Al2O3 catalyst. The crystals of Cu-Ce/γ-Al2O3 were more stable compared with those of the Cu/γ-Al2O3 catalyst after 12 h of hydrothermal liquefaction at 300℃, thereby indicating a better thermal stability of the former. The presence of Cu-Ce/γ-Al2O3 catalyst could greatly improve the conversion of stearic acid (94.71%) and the yield of hydrocarbon (81.41%). A preliminary analysis of the mechanism suggests that decarboxylation is the main step in the deoxygenation during the hydrothermal liquefaction of stearic acid. The addition of Cu/γ-Al2O3 and Cu-Ce/γ-Al2O3 decreased the yield of n-heptadecane and increased the yield of n-octadecane. Besides, the yields of n-paraffins increased drastically from 0.45% to 49.72% along the series from n-nonane to n-hexadecane. Thus, the cracking reactions could be improved in the presence of Cu-Ce/γ-Al2O3, suggesting that it is an efficient deoxygenation catalyst in the hydrothermal liquefaction of organic acid. In addition, the Cu-Ce/γ-Al2O3 catalyst could help in removing the carbonyl groups, and this effectively reduced the amounts of aldehydes and ketones in the bio-oil.