Functionalized MoS2 nanosheet-capped periodic mesoporous organosilicas as a multifunctional platform for synergistic targeted chemo-photothermal therapy

The combination of different therapies into a single platform has attracted increasing attention as a potential synergistic tumor treatment. Herein, the fabrication of a novel folate targeted system for chemo-photothermal therapy by using thioether-bridged periodic mesoporous organosilica nanoparticles (PMOs) as a drug-loading vehicle is described. The novel targeted molecular bovine serum albumin-folic acid-modified MoS2 sheets (MoS2-PEI-BSA-FA) were successfully synthesized and characterized, and then utilized as a capping agent to block PMOs to control the drug release and to investigate their potential in near-infrared photothermal therapy. The resulting PMOs–DOX@MoS2–PEI-BSA-FA complexes had a uniform diameter (196 nm); high DOX loading capacity (185 mg/g PMOs-SH); excellent photothermal transformation ability; and good biocompatibility in physiological conditions. The PMOs–DOX@MoS2–PEI-BSA-FA exhibited pH-dependence and near infrared (NIR) laser irradiation-triggered DOX release. In vitro experimental results confirmed that the material exhibits excellent photothermal transfer ability, outstanding tumor killing efficiency and specificity to target tumor cells via an FA-receptor-mediated endocytosis process. The in vivo experiments further demonstrated that the platform for synergistic chemo-photothermal therapy could significantly inhibit tumor growth, which is superior to any monotherapy. Meanwhile, cytotoxicity assays and histological assessments show that the engineered PMOs@MoS2–PEI-BSA-FA have good biocompatibility, further inspiring potential biomedical applications. Overall, this work describes an excellent drug delivery system for chemo-photothermal synergistic targeted therapy having good drug release properties, which have great potential in cancer therapy

The Development Prospect of Chinese Rehabilitation Specialist Nurses under the Background of Aging

Objective: To explore the correlation between the supply-demand contradiction and development of rehabilitation nursing talents in China through the analysis of China's aging population. It provides ideas for the increasingly professional and regularization of rehabilitation nursing in China, and provides evidence-based suggestions for the employment of rehabilitation specialist nurses. Design: Review Article. Methods: Literature review. Finding: Due to the traditional concept of Chinese society and the low recognition of rehabilitation specialist nurses, the training institutions for rehabilitation specialist nurses are not perfect, and the education level of rehabilitation specialist nurses is uneven, making it difficult to meet the needs of Chinese rehabilitation nurses. Conclusion: Call on more nursing talents to participate in the construction of rehabilitation nursing in China.Explore the prospects for the development of rehabilitation specialist nurses around the world, take China as an example, and provide evidence-based advice for the employment of rehabilitation specialist nurses

l-Peptide functionalized dual-responsive nanoparticles for controlled paclitaxel release and enhanced apoptosis in breast cancer cells

Nanoparticles and macromolecular carriers have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by their enhanced permeability and retention effect. However, the therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, the design and development of novel l-peptide functionalized dual-responsive nanoparticles (l-CS-g-PNIPAM-PTX) for active targeting and effective treatment of GRP78-overexpressing human breast cancer in vitro and in vivo are reported. l-CS-g-PNIPAM-PTX NPs have a relative high drug loading (13.5%) and excellent encapsulation efficiency (74.3%) and an average diameter of 275 nm. The release of PTX is slow at pH 7.4 and 25 °C but greatly accelerated at pH 5.0 and 37 °C. MTT assays and confocal experiments showed that the l-CS-g-PNIPAM-PTX NPs possessed high targetability and antitumor activity toward GRP78 overexpressing MDA-MB-231 human breast cancer cells. As expected, l-CS-g-PNIPAM-PTX NPs could effectively treat mice bearing MDA-MB-231 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a high survival rate over an experimental period of 60 days. These results indicate that l-peptide-functionalized acid - and thermally activated - PTX prodrug NPs have a great potential for targeted chemotherapy in breast cancer.</p

What a Whole Slide Image Can Tell? Subtype-guided Masked Transformer for Pathological Image Captioning

Pathological captioning of Whole Slide Images (WSIs), though is essential in computer-aided pathological diagnosis, has rarely been studied due to the limitations in datasets and model training efficacy. In this paper, we propose a new paradigm Subtype-guided Masked Transformer (SGMT) for pathological captioning based on Transformers, which treats a WSI as a sequence of sparse patches and generates an overall caption sentence from the sequence. An accompanying subtype prediction is introduced into SGMT to guide the training process and enhance the captioning accuracy. We also present an Asymmetric Masked Mechansim approach to tackle the large size constraint of pathological image captioning, where the numbers of sequencing patches in SGMT are sampled differently in the training and inferring phases, respectively. Experiments on the PatchGastricADC22 dataset demonstrate that our approach effectively adapts to the task with a transformer-based model and achieves superior performance than traditional RNN-based methods. Our codes are to be made available for further research and development

Study of Highly Pixelated CdZnTe Detector for PET Applications

AbstractWe are investigating the feasibility of a high-resolution PET insert device based on a Cadmium Zinc Telluride (CdZnTe) detector with 350μm anode pixel pitch to be integrated into a conventional animal PET scanner to improve its image resolution to sub-500 micrometer range. In this work, we have used a simplified version of the future 2048-pixel CdZnTe planar detector with 250μm anode pixel size and 100μm gap. This simplified 9 anode pixel structure makes it possible to conduct experiments without a complete ASIC readout system (with 2048 channels) that is still under development. We characterized this CdZnTe detector by investigating it charge sharing, spatial resolution, and energy resolution. We imaged a Na-22 point source using the coincidence events between this 350μm pixelated CdZnTe detector and a lutetium oxyorthosilicate (LSO) based Siemens Inveon PET detector. The reconstructed PET image shows a resolution of 590μm full width at half maximum (FWHM) by using single-pixel events. When we included double-pixel charge sharing events in the image reconstruction, the image resolution was degraded to 655μm, but the sensitivity of the coincidence system increased 2.5 to 3 times

Effect of thermal treatment with methylolurea impregnated on poplar wood

The aim of this research was to study the physical and chemical performance of poplar wood treated by chemi-thermal modification. A thermal treatment was used to catalyze the effect of the methylolurea impregnated pre-treatment by curing the poplar wood at 160 °C under atmospheric conditions. The results showed that the thermal treatment played an important role in the chemical and mechanical performance. Such an approach not only can significantly reduce the hygroscopicity, but also can increase the bending strength and compressive strength parallel to grain. The positions of the XRD peaks did not change, which indicated that the structure of cellulose was not noticeably affected by the thermal treatment. The FT-IR analysis showed that the intensity of hydroxyl and carbonyl absorption peaks decreased significantly, which indicated that the NH-CH2-OH of methylolurea reacted with the wood carboxyl (C=O) and hydroxyl (-OH). The TGA showed that the thermal stability of treated wood improved. The SEM showed that the cell wall and vessels were filled with impregnated chemicals

Proteomic analysis of spinal cord tissue in a rat model of cancer-induced bone pain

BackgroundCancer-induced bone pain (CIBP) is a moderate to severe pain and seriously affects patients’ quality of life. Spinal cord plays critical roles in pain generation and maintenance. Identifying differentially expressed proteins (DEPs) in spinal cord is essential to elucidate the mechanisms of cancer pain.MethodsCIBP rat model was established by the intratibial inoculation of MRMT-1 cells. Positron emission tomography (PET) scan and transmission electron microscopy (TEM) were used to measure the stats of spinal cord in rats. Label free Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) were used to analyze the whole proteins from the lumbar spinal cord. Differentially expressed proteins (DEPs) were performed using Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and verified using Western blot and immunofluorescence assay.ResultsIn the current study, CIBP rats exhibited bone damage, spontaneous pain, mechanical hyperalgesia, and impaired motor ability. In spinal cord, an hypermetabolism and functional abnormality were revealed on CIBP rats. An increase of synaptic vesicles density in active zone and a disruption of mitochondrial structure in spinal cord of CIBP rats were observed. Meanwhile, 422 DEPs, consisting of 167 up-regulated and 255 down-regulated proteins, were identified among total 1539 proteins. GO enrichment analysis indicated that the DEPs were mainly involved in catabolic process, synaptic function, and enzymic activity. KEGG pathway enrichment analysis indicated a series of pathways, including nervous system disease, hormonal signaling pathways and amino acid metabolism, were involved. Expression change of synaptic and mitochondrial related protein, such as complexin 1 (CPLX1), synaptosomal-associated protein 25 (SNAP25), synaptotagmin 1 (SYT1), aldehyde dehydrogenase isoform 1B1 (ALDH1B1), Glycine amidinotransferase (GATM) and NADH:ubiquinone oxidoreductase subunit A11 (NDUFA11), were further validated using immunofluorescence and Western blot analysis.ConclusionThis study provides valuable information for understanding the mechanisms of CIBP, and supplies potential therapeutic targets for cancer pain

CAMKs support development of acute myeloid leukemia.

BACKGROUND: We recently identified the human leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse ortholog-paired Ig-like receptor (PirB) as receptors for several angiopoietin-like proteins (Angptls). We also demonstrated that PirB is important for the development of acute myeloid leukemia (AML), but exactly how an inhibitory receptor such as PirB can support cancer development is intriguing. RESULTS: Here, we showed that the activation of Ca (2+)/calmodulin-dependent protein kinases (CAMKs) is coupled with PirB signaling in AML cells. High expression of CAMKs is associated with a poor overall survival probability in patients with AML. Knockdown of CAMKI or CAMKIV decreased human acute leukemia development in vitro and in vivo. Mouse AML cells that are defective in PirB signaling had decreased activation of CAMKs, and the forced expression of CAMK partially rescued the PirB-defective phenotype in the MLL-AF9 AML mouse model. The inhibition of CAMK kinase activity or deletion of CAMKIV significantly slowed AML development and decreased the AML stem cell activity. We also found that CAMKIV acts through the phosphorylation of one of its well-known target (CREB) in AML cells. CONCLUSION: CAMKs are essential for the growth of human and mouse AML. The inhibition of CAMK signaling may become an effective strategy for treating leukemia