Upconversion nanoparticles-based
photodynamic nanotheranostic agents
(UCNPs-PDT) have received great interest due to improved tissue penetration,
weak autofluorescence, and low biotoxicity. However, conventional
UCNPs-PDT are often limited by low energy transfer efficiency from
UCNPs to photosensitizer (PS) molecules and insufficient generation
and limited diffusion distance of reactive oxygen species (ROSs).
Herein, an “all in one” nanotheranostic agent has been
developed which has multicolor sandwich-structured UCNPs (SWUCNPs)
as the core, a thin silica layer with a mitochondria-targeted group
for loading dual PS as the medium layer, and polyethylene glycol–folic
acid (PEG-FA) chains as the outer layer. Multicolor SWUCNPs simultaneously
achieve two-photon fluorescence imaging and serve as energy donor
for dual PS molecules. The thin luminescence layer and silica layer
control most UCNPs activators and PS molecules in the effective energy
transfer distance to guarantee a high energy transfer efficiency.
Via FA-mediated endocytosis, the nanotheranostic agent is selectively
endocytosed by cancer cells, is released from the endosome/lysosome,
targets the mitochondria, and in situ produces ROSs under excitation
from NIR, leading to significant mitochondria-mediated cell apoptosis.
Furthermore, the established nanotheranostic agent shows tumor targetability,
increased generation of ROSs, high PDT efficacy, significant cell
apoptosis, minimal systemic cytotoxicity, and efficacious in vivo
tumor inhibition.
Multiple body donation programs have been established throughout China over the last 20 years, but these programs remain challenged by an insufficient supply of cadavers for medical education. The commemoration of body donors is a feature of many successful programs, and adopting this practice throughout the country could be an important element of raising public awareness and encouraging body donation among the public. The present study aimed to investigate public views on the commemoration of whole‐body donors and postdonation services in China by analyzing the factors that influence participants' willingness to donate. A survey was conducted using convenience sampling with a non‐probability sampling method, and data were analyzed using chi‐square and post hoc multiple comparisons tests. A total of 1,800 questionnaires were distributed, 1,717 were returned, and 1,605 were considered valid. Of the respondents, 20.87% were willing to donate, and 64.80% thought that it is necessary to commemorate donors. The results of multiple comparisons demonstrated that the elderly and those with a higher educational level were more willing to donate than participants in other groups. Education was also found to influence views on donation memorial activities, and the chi‐square test revealed that conducting commemorations and improving postdonation services can promote the establishment of successful donor programs in China and improve the social acceptance of body donation.
Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15,581 lung adenocarcinoma (AD) cases, 8,350 squamous cell carcinoma (SqCC) cases, and 27,355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3,064 credible risk variants for NSCLC, which were overrepresented in enhancerlike and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER=1.95, P=0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Hydrophobic modification of Bletilla striata polysaccharide (BSP) was performed by grafting fatty acids to BSP backbone and then characterized on their physicochemical properties. All neutral derivatives were able to self-assemble into spherical particles within the size range of 250-400 nm, their size and critical micelle concentration decreased with increasing hydrophobicity and substitution degree of the fatty acids. Also, the BSP-stearic acid conjugates showed a preferable performance on hemolysis test and cytotoxicity analysis on HepG2 cells, which suggested their potential application as a drug delivery vector.
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