Targeted drug delivery is important in cancer therapy to decrease the systemic
toxicity resulting from nonspecific drug distribution and to enhance drug delivery
efficiency. We have developed an aptamer-based DNA dendritic nanostructure as a
multifunctional vehicle for targeted cancer cell imaging and drug delivery. The
multifunctional DNA dendrimer is constructed from functional Y-shaped building
blocks with predesigned base-pairing hybridization including fluorophores, targeting
DNA aptamers and intercalated anticancer drugs. With controllable step-by-step
self-assembly, the programmable DNA dendrimer has several appealing features,
including facile modular design, excellent biostability and biocompatibility, high
selectivity, strong binding affinity, good cell internalization efficiency, and high
drug loading capacity. Due to the unique structural features of DNA dendrimers,
multiple copies of aptamers can be incorporated into each dendrimer, generating a
multivalent aptamer-tethered nanostructure with enhanced binding affinity. A model
chemotherapeutic anticancer drug, doxorubicin, was delivered via these aptamer-based
DNA dendrimers and exerted a potent toxicity for target cancer cells (human T cell
acute lymphoblastic leukemia cell line) with low side effects for the non-target
cells (human Burkitt’s lymphoma cell line). This controllable aptamer-based
DNA dendrimer is a promising candidate for biomedical applications.
We aimed to investigate changes in pulmonary function and computed tomography (CT) findings in patients with coronavirus disease 2019 (COVID-19) during the recovery period. COVID-19 patients underwent symptom assessment, pulmonary function tests, and high-resolution chest CT 6 months after discharge from the hospital. Of the 54 patients enrolled, 31 and 23 were in the moderate and severe group, respectively. The main symptoms 6 months after discharge were fatigue and exertional dyspnea, experienced by 24.1% and 18.5% of patients, respectively, followed by smell and taste dysfunction (9.3%) and cough (5.6%). One patient dropped out of the pulmonary function tests. Of the remaining 54 patients, 41.5% had pulmonary dysfunction. Specifically, 7.5% presented with restrictive ventilatory dysfunction (forced vital capacity <80% of the predicted value), 18.9% presented with small airway dysfunction, and 32.1% presented with pulmonary diffusion impairment (diffusing capacity for carbon monoxide <80% of the predicted value). Of the 54 patients enrolled, six patients dropped out of the chest CT tests. Eleven of the remaining 48 patients presented with abnormal lung CT findings 6 months after discharge. Patients with residual lung lesions were more common in the severe group (52.6%) than in the moderate group (3.4%); a higher proportion of patients had involvement of both lungs (42.1% vs. 3.4%) in the severe group. The residual lung lesions were mainly ground-glass opacities (20.8%) and linear opacities (14.6%). Semiquantitative visual scoring of the CT findings revealed significantly higher scores in the left, right, and both lungs in the severe group than in the moderate group. COVID-19 patients 6 months after discharge mostly presented with fatigue and exertional dyspnea, and their pulmonary dysfunction was mostly characterized by pulmonary diffusion impairment. As revealed by chest CT, the severe group had a higher prevalence of residual lesions than the moderate group, and the residual lesions mostly manifested as ground-glass opacities and linear opacities.
Severe acute respiratory syndrome (SARS) is a new infectious disease with a global impact. Understanding its pathogenesis and developing specific diagnostic methods for its early diagnosis are crucial for the effective management and control of this disease. By using proteomic technology, truncated forms of alpha(1)-antitrypsin (TF-alpha(1)-AT) were found to increase significantly and consistently in sera of SARS patients compared to control subjects. The result showed a sensitivity of 100% for SARS patients and a specificity of 92.8% for controls. Furthermore, the levels of these proteins significantly correlated with certain clinico-pathological parameters. The dramatic increase in TF-alpha(1)-AT may be the result of degradation of alpha(1)-AT. As alpha(1)-AT plays an important role in the protection of lung function, its degradation may be an important factor in the pathogenesis of SARS. These findings indicate that increased TF-alpha(1)-AT may be therapeutically relevant, and may also be a useful biological marker for the diagnosis of SARS.
Here we report a simple all-nucleic-acid enzymefree catalyzed hairpin assembly assisted amplification strategy with quantum dots (QDs) as the nanoscale signal reporter for homogeneous visual and fluorescent detection of A549 lung cancer cells from clinical blood samples. This work was based on the phenomenon that CdTe QDs can selectively recognize Ag + and C-Ag + -C and by using mucin 1 as the circulating tumor cells (CTCs) marker and aptamer as the recognition probe. Under optimized conditions, the limits of detections as low as 0.15 fg/mL of mucin 1 and 3 cells/mL of A549 cells were achieved with fluorescence signals. A 1 fg/mL concentration of mucin 1 and 100 cells/mL of A549 can be distinguished by the naked eye. This method was used to quantitatively analyze CTCs in 51 clinical whole blood samples of patients with lung cancer. The levels of CTCs detected in clinical samples by this method were consistent with those obtained using the folate receptor-polymerase chain reaction clinical test kit and correlated with radiologic and pathological findings.
Photothermal
effects (PTEs) have been greatly concerned with the
fast development of new photothermal nanomaterials. Herein we propose
a photothermal immunoassay (PTIA) by taking mycotoxins (AFB1) as an example based on the PTEs of plasmonic Cu2–x
Se nanocrystals (NCs). By loading plasmonic Cu2–x
Se NCs into liposomes to form photothermal
soft nanoballs (ptSNBs), on which aptamer of AFB1 previously
assembled, a sandwich structure of AFB1 could be formed
with the aptamer on ptSNBs and capture antibody. The heat released
from the ptSNBs under NIR irradiation, owing to the plasmonic photothermal
light-to-heat conversion through photon–electron–phonon
coupling, makes the temperature of substrate solution increased, and
the increased temperature has a linear relationship with the AFB1 content. Owing to the large amounts of plasmonic Cu2–x
Se NCs in the ptSNBs, the PTEs get amplified, making
AFB1 higher than 1 ng/mL detectable in food even if with
a rough homemade immunothermometer. The proposal of PTIA opens a new
field of immunoassay including developing photothermal nanostructures,
new thermometers, PTIA theory, and so on.
By adapting reverse time migration (RTM) and demigration as the migration and modeling operators to maximize the crosscorrelation between the simulated and the acquired seismic data, we introduced a new practical least-squares RTM (LSRTM) scheme and derived a steepest descent method in seeking the optimal image. Through synthetic and real data experiments, we determined that the proposed LSRTM provided high-quality images with balanced amplitudes, improved focusing, and enhanced resolution. The method was also capable of removing free surface ghosts caused by towed streamer acquisition, filling the structures and reducing crosstalk noise associated with simultaneous shooting.
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