Targeted photodynamic therapy (PDT) in head/neck cancer patients with a conjugate of the anti‐epidermal growth factor receptor (EGFR) antibody, Cetuximab and a phthalocyanine photosensitizer IR700DX ...is under way, but the exact mechanisms of action are still not fully understood. In this study, the EGFR‐overexpressing human head/neck OSC‐19‐luc2‐cGFP tumor with transfected GFP gene was used in a skin‐fold window chamber model in BALB/c nude mice. The uptake and localization of the conjugate in the tumor and its surrounding normal tissues were studied by an intravital confocal laser scanning microscopy with image analyses. The tumor was also irradiated with 690 nm laser light 24 h after conjugate administration. The vascular and tumor responses were examined by morphological evaluation and immunohistochemistry (IHC). The amount of conjugate in the tumor peaked at 24–48 h after injection. Image analyses of colocalization correlation parameters demonstrated a high fraction of the conjugate IR700DX colocalized in the GFP‐expressing tumor cells. PDT‐treated tumors showed extensive necrotic/apoptotic destruction with little vascular damage, while IHC showed no HIF‐1α expression and decreased EGFR and Ki67 expression with activated caspase‐3 overexpression, indicating a direct killing of tumor cells through both necrotic and apoptotic cell death.
The EGFR overexpressing human head and neck OSC‐19‐luc2‐cGFP tumor with transfected GFP gene was used in a skin‐fold window chamber model in BALB/c nude mice. The tumor localization of the anti‐EGFR cetuximab–IR700DX conjugate was studied by an intravital confocal laser scanning microscopy at 24 h after intravenous injection. The tumor in the window chamber was then irradiated with 690 nm laser light (100 J cm−2 at 50 mW cm−2). The conjugate localizes selectively in tumor cells resulting in necrosis and apoptosis after light exposure.
Described by the fractional Schrödinger equation (FSE) with the parabolic potential, the periodic evolution of the astigmatic chirped symmetric Pearcey Gaussian vortex beams (SPGVBs) is exhibited ...numerically and some interesting behaviors are found. The beams show stable oscillation and autofocus effect periodically during the propagation for a larger Lévy index (0 < α ≤ 2). With the augment of the α, the focal intensity is enhanced and the focal length becomes shorter when 0 < α ≤ 1. However, for a larger α, the autofocusing effect gets weaker, and the focal length monotonously reduces, when 1 < α ≤ 2. Moreover, the symmetry of the intensity distribution, the shape of the light spot and the focal length of the beams can be controlled by the second-order chirped factor, the potential depth, as well as the order of the topological charge. Finally, the Poynting vector and the angular momentum of the beams prove the autofocusing and diffraction behaviors. These unique properties open more opportunities of developing applications to optical switch and optical manipulation.
Bactericera cockerelli has recently become a major concern because of its direct feeding and vectoring of bacterial diseases in many solanaceous crops. The repellency of four biorational ...insecticides, MOI-201 (a Chinese medicine plant extract), Requiem (a plant extract of
Chenopodium ambrosioides), BugOil (a mixture of four plant essential oils), and SunSpray oil (a mineral oil), to
B.
cockerelli adults was tested on tomato. In a no-choice test, all the insecticides had significant repellency to adults and deterred oviposition as compared with untreated controls. Of the four insecticides, the two oils showed a stronger repellency to adults and deterred oviposition more strongly than Requiem or MOI-201. In a choice test, all insecticides had significant repellency to adults and deterred oviposition compared to untreated controls. Of the four tested insecticides, <1 adults and no eggs were found on the leaves treated with SunSpray Oil, BugOil or Requiem 3 d after treatment. The repellency rates of these three insecticides were 77.2–95.4%. MOI-201 also repelled adults significantly and deterred oviposition compared to untreated controls even though it was the least effective insecticide among the four evaluated. In conclusion, all four insecticides tested showed significant repellency to
B. cockerelli adults and deterred oviposition, especially the two oils. The overall repellency to potato psyllid adults can be arranged in a descending order of SunSpray oil > BugOil > Requiem > MOI-201. These insecticides could be used in integrated pest management programs targeted against the potato psyllid on solanaceous crops.
Targeted photodynamic therapy (PDT) has the potential to improve the therapeutic effect of PDT due to significantly better tumor responses and less normal tissue damage. Here we investigated if the ...efficacy of epidermal growth factor receptor (EGFR) targeted PDT using cetuximab-IRDye700DX is fluence rate dependent. Cell survival after treatment with different fluence rates was investigated in three cell lines. Singlet oxygen formation was investigated using the singlet oxygen quencher sodium azide and singlet oxygen sensor green (SOSG). The long-term response (to 90 days) of solid OSC-19-luc2-cGFP tumors in mice was determined after illumination with 20, 50, or 150 mW·cm
. Reflectance and fluorescence spectroscopy were used to monitor therapy. Singlet oxygen was formed during illumination as shown by the increase in SOSG fluorescence and the decreased response in the presence of sodium azide. Significantly more cell death and more cures were observed after reducing the fluence rate from 150 mW·cm
to 20 mW·cm
both in-vitro and in-vivo. Photobleaching of IRDye700DX increased with lower fluence rates and correlated with efficacy. The response in EGFR targeted PDT is strongly dependent on fluence rate used. The effectiveness of targeted PDT is, like PDT, dependent on the generation of singlet oxygen and thus the availability of intracellular oxygen.
It has attracted much attention worldwide that the application of artificial intelligence (AI) in primary screening and clinical diagnosis and treatment of eye diseases. In recent years, this ...technology has also been widely used in various grass-roots eye disease management, effectively improving the current situation of weak eye disease diagnosis ability and shortage of human resources in primary medical institutions. At present, there is no reference standard or guideline for the management mode, implementation content and management method of vision health management based on this technology, which are in urgent need of standardization. The article described the work mode exploration of AI-assisted grass-roots visual health management in Shanghai and shared practical experience. The aim is to provide reference for other provinces in China to carry out relevant work.
Pure, 5% Ti-doped and 10% Ti-doped WO
3
thin films were prepared by the radio frequency magnetron sputtering and characterised by a SEM, an electrochemical workstation and an UV-VIS-NIR ...spectrophotometer. Research results showed that Ti doping had no apparent influence on the surface morphology and optical band gap. It could also be found that the addition of Ti has little interference with the electrochromic property of WO
3
in both bleached and coloured states at initial cycles from electrochemical and optical test results, while there were apparent differences in the optical transmittance and inserted and extracted charge with increasing cycles. This is attributed that Ti-doped WO
3
thin films allow facile ion interaction/extraction and have less ion residues, which can stabilise the electrochemical cycling performance. Furthermore, the data we have obtained indicate that 5% Ti-doped WO
3
film has the best electrochromic property.
Summary
Recent evidence suggests that persistence of Helicobacter pylori can be explained, at least in part, by the failure of macrophages to kill bacteria. The fate of type 1 H. pylori strain LC11, ...which expresses the cag pathogenicity island (PAI) and the vacuolating cytotoxin, and type 2 strain LC20, which lacks both these virulence factors, was determined following infection of the murine macrophage cell line RAW 264.7 or the human macrophage‐like cell line THP‐1. Helicobacter pylori strain LC11 displayed enhanced survival in macrophages in comparison with strain LC20 (4.0 ± 0.2 versus 2.1 ± 0.6 log CFU ml−1, P < 0.01) at 24 h. Phagosomes containing strain LC11 showed reduced co‐localization with LysoTracker Red, higher levels of expression of the early endosome marker EEA1 expression and lower expression of the late endosome/lysosome marker LAMP1 relative to internalized strain LC20, both at 2 h and 24 h. These findings indicate that, in contrast to strain LC20, strain LC11 resides in a compartment with early endosome properties and does not fuse with lysosomes. In addition, phagosomes containing LC11 recruited and retained a higher percentage of TACO (coronin 1) protein in comparison with phagosomes containing strain LC20. Furthermore, IFN‐γ stimulation facilitated maturation of phagosomes containing strain LC11 in association with the release of TACO and a reduction in bacterial survival. We have demonstrated through the use of isogenic cagA‐, cagE‐/picB‐ and vacA‐ mutant strains, that VacA plays a significant role in the interruption of the phagosome maturation. Taken together, these results indicate that, following phagocytosis, H. pylori strains expressing the vacuolating cytotoxin arrest phagosome maturation in association with the retention of TACO.
Endoplasmic reticulum stress(ERS)was used as the research emphasis to further investigate the mechanisms of apoptosis of FLT3-ITD-mutated leukemia cells and decreased expression of FLT3-ITD mutated ...protein induced by all-trans retinoic acid(ATRA).
FLT3-ITD-mutated leukemia cell lines(MV4-11 and MOLM13)were treated with ATRA. Flow cytometry was conducted to assess cell apoptosis. Real-time fluorescent quantitative PCR(RT-qPCR)and Western blot were used to detect the expression of ERS-related and autophagy-related genes and protein, respectively.
A low-dose ATRA further increased FLT3-ITD cells and ERS levels. ATRA acted on the ERS-related PERK/eif2ɑ signaling pathway and continued to increase the ERS of FLT3-ITD cells, resulting in an upregulation of apoptotic gene CHOP expression. After the treatment with ATRA, FLT3-ITD protein in FLT3-ITD cells was decreased. Of the two main ERS-related protein degradation pathways, ER-associated degradation(ERAD)and ER-activated autophagy(ERAA), the expression of ERAD-relat
Anaplastic thyroid cancer is an extremely aggressive disease resistant to radioiodine treatment because of loss of sodium iodide symporter (NIS) expression. To enhance prognosis of this fatal cancer, ...we validated the preclinical efficacy of measles virus (MV)-NIS, the vaccine strain of the oncolytic MV (MV-Edm), modified to include the NIS gene. Western blotting analysis confirmed that a panel of eight anaplastic thyroid cancer (ATC)-derived cell lines do not express NIS protein, but do express CD46, the MV receptor. In vitro cell death assays and in vivo xenograft studies demonstrate the oncolytic efficacy of MV-NIS in BHT-101 and KTC-3, ATC-derived cell lines. Radioactive iodine uptake along with single-photon emission computed tomography (SPECT)-computed tomography imaging of KTC-3 xenografts after (99)Tc(m) administration confirmed NIS expression in vitro and in vivo, respectively, after virus treatment. Adjuvant administration of RAI, to MV-NIS-treated KTC-3 tumors showed a trend for increased tumor cell killing. As current treatment for ATC is only palliative, and MV-NIS is currently Food and Drug Administration approved for human clinical trials in myeloma, our data indicate that targeting ATC with MV-NIS could prove to be a novel therapeutic strategy for effective treatment of iodine-resistant ATC and will expedite its testing in clinical trials for this aggressive disease.
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