Dual-mode aptasensor based on P-CeO2NR@Mxene and exonuclease I-assisted target recycling for malachite green detection.

Malachite green (MG) has been illicitly employed in aquaculture as a parasiticide, however, its teratogenic and carcinogenic effects pose a significant human health threat. Herein, a dual-mode colorimetric and electrochemical aptasensor was fabricated for MG detection, capitalizing on the robust catalytic and peroxidase-like activity of P-CeO2NR@Mxene and good capture efficiency of a tetrahedral DNA nanostructure (TDN) designed with multiple aptamers (m-TDN). P-CeO2NR@Mxene-modified complementary DNA (cDNA) served as both colorimetric and electrochemical probe. m-TDN was attached to AuE to capture MG and P-CeO2NR@Mxene/cDNA. The superior aptamer and MG binding to cDNA regulated signals and enabled precise MG quantification. The further introduced Exo I enabled aptamer hydrolysis, releasing MG for further binding rounds, allowing target recycling amplification. Under the optimal conditions, the aptasensor reached an impressively low detection limit 95.4 pM in colorimetric mode and 83.6 fM in electrochemical mode. We believe this dual-mode approach holds promise for veterinary drug residue detection.

Rational Design of a Robust G-Quadruplex Aptamer as an Inhibitor to Alleviate Listeria monocytogenes Infection.

Listeria monocytogenes (LM) is one of the most invasive foodborne pathogens that cause listeriosis, making it imperative to explore novel inhibiting strategies for alleviating its infection. The adhesion and invasion of LM within host cells are partly orchestrated by an invasin protein internalin A (InlA), which facilitates bacterial passage by interacting with the host cell E-cadherin (E-Cad). Hence, in this work, we proposed an aptamer blocking strategy by binding to the region on InlA that directly mediated E-Cad receptor engagement, thereby alleviating LM infection. An aptamer GA8 with a robust G-quadruplex (G4) structural feature was designed through truncation and base mutation from the original aptamer A8. The molecular docking and dynamics analysis showed that the InlA/aptamer GA8 binding interface was highly overlapping with the natural InlA/E-Cad binding interface, which confirmed that GA8 can tightly and stably bind InlA and block more distinct epitopes on InlA that involved the interaction with E-Cad. On the cellular level, it was confirmed that GA8 effectively blocked LM adhesion with an inhibition rate of 78%. Overall, the robust G4 aptamer-mediated design provides a new direction for the development of inhibitors against other wide-ranging and emerging pathogens.

A prospective study of radical external beam radiotherapy versus external beam radiotherapy combined with intraluminal brachytherapy for primary esophageal cancer.

PURPOSE: This study compared the efficacy and side effects of external beam radiotherapy (EBRT) + intraluminal brachytherapy (IBT) with EBRT alone in patients with primary thoracic esophageal cancer. MATERIALS AND METHODS: Between 2013 and 2020, 64 patients with primary thoracic esophageal cancer without surgery received radiotherapy. Thirty-two patients received EBRT + IBT. EBRT dose was 50 Gy, 2 Gy/f, 5 times a week, and IBT dose was 10 Gy, 5 Gy/f, once a week. Thirty-two patients received EBRT alone, and the total dose was 60 Gy. The median followup was 19 months. RESULTS: The local control rates (LCR) of EBRT + IBT and EBRT alone group at 1, 2, and 3 years after treatment were 88% and 72%, 53% and 22%, 25%, and 9%, respectively. The overall survival (OS) of the EBRT + IBT and EBRT alone group at 3 years after treatment were 38% and 9%. The 3-year local recurrence-free survival (LRFS) rates of EBRT + IBT and EBRT alone group were 25% and 9%. Univariate analysis showed that EBRT + IBT could be the prognostic factor improving OS (p = 0.04), and tumor located in the mid-thoracic region exhibited a poorer prognosis on LRFS (p = 0.03). Grade 3 or higher acute side effects included two cases of dysphagia and three cases of bone marrow suppression. Severe late side effects included three cases of fistula, three cases of radiation pneumonia, and five cases of stenosis requiring treatment. CONCLUSIONS: Compared with EBRT alone, EBRT + IBT is an effective treatment modality for T1∼3NanyM0 primary thoracic esophageal cancer with good local control. It can prolong the survival time of patients and has acceptable toxicity.

Microfluidic nitrogen-assisted nanoelectrospray emitter: A monolithic interface for accurate mass measurements based on a single nozzle.

Nitrogen-assisted nanoelectrospray emitter (NANE) was developed to achieve accurate mass-to-charge ratio (m/z) measurements with a single monolithic nozzle. Deposition patterns of generated electrosprays from NANE confirmed their wrapped configurations. Additionally, the intensity of the sample ion and its ratio relative to a reference ion was inclined to focus on the central region of the spray; this trend further supported the existence of wrapped configurations. Further, the proposed NANE was fabricated from poly-(dimethylsiloxane) (PDMS) with octadecyltrichlorosilane modification to restrain the dissolution of PDMS monomers. Assist nitrogen flows were introduced to improve the ionization of reference ions. Moreover, the NANE could regulate the distribution of reference ions by microfluidic three dimensional hydrodynamic focusing. By regulating the distribution of reference ions, the ionization depression was reduced to some degree, and an improved sensitivity was accomplished compared with the mixing of sample and reference solutions. Achieved relative errors of m/z were between 0.2-4.5ppm and 5.2-9.2ppm for ten organic molecules and four biological macromolecules, respectively. Acceptable linear ranges were obtained in quantifications for rhodamine B and emamectin benzoate. Finally, the NANE was compatible with broad infusion rates (from 50nLmin-1 to 15µLmin-1) and solutions of different compositions (from 100% methanol to 100% water). Considering the comprehensive application of PDMS in microfluidics, the proposed NANE could be used as a compact and monolithic interface to achieve accurate m/z measurements.

Three-dimensional hydrodynamic focusing microfluidic emitter: a strategy to inhibit sample ion expansion in nanoelectrospray ionization.

A microfluidic emitter based on three-dimensional hydrodynamic focusing was developed to generate a wrapped charged aerosol plume, in which the distribution of the sample ion in the nanoelectrospray could be regulated. Deposition patterns of the wrapped spray from the proposed three-dimensional hydrodynamic focusing nanoelectrospray emitter (3D HFNE) were collected under different conditions to ensure the wrapped configuration. Moreover, sample ion intensities as well as their ratios to a focusing background ion were studied as a function of different displacements from the center of the wrapped electrospray to confirm the inhibition of ion expansion. Furthermore, the proposed 3D HFNE indicated improved sensitivities compared with a reported nanoelectropray emitter as well as its commercial ESI counterpart, and this demonstrated its capacity for determining samples with low concentrations and infusion rates. In addition, the proposed 3D HFNE was compatible with various sample flow compositions (from 100% methanol to 100% water) and a broad infusion rate range (from 10 nL min(-1) to 15 µL min(-1)). Finally, its stability and durability were indicated to be acceptable for various determinations. Therefore, the 3D HFNE is a potential option to achieve on-line nanoelectrospray MS determinations using microfluidics with conventional mass spectrometers, considering its low cost and user-friendly properties.