Improvement of Heterojunction Nanomaterials Photoelectrochemical Properties by Sol-Gel Synthesis and Hydrothermal Reaction.

The ZnO nanorod arrays (NRs)/CuAlO2 laminar crystal thin films (LFs)/Ni heterojunctions with delafossite structure were prepared by sol-gel synthesis for LFs and hydrothermal for NRs. X-ray diffraction analysis demonstrates the typical delafossite structure CuAlO2 and pure ZnO of R¯3m space group. Compared with a traditional CuAlO2/Ni laminar films (LFs) nanostructure, the photocurrent of this heterojunction nanostructure is significantly increased. Note that a significant blue-shift of the absorption edge and a favorable forward current to reverse current ratio at applied voltages of -0.75 to +2 V were observed in this heterojunction with the increase of Zn2+ ion concentration in the hydrothermal reaction. Moreover, the photoelectrochemical characteristics recorded under AM 1.5 illumination with 100 mW/cm2 light intensity at 0 V (vs. Ag/AgCl), while the highest photocurrent density arrive at 3.59 mA/cm2. This study demonstrates that heterojuction nanostructure, which is easily adapted to other chemical systems, is a promising technique for improving photoelectro-chemical properties of low-cost solar cells.

Cationic lioposomes with folic acid as targeting ligand for gene delivery.

In our previous Letter, we have carried out the synthesis of a novel DDCTMA cationic lipid which was formulated with DOPE for gene delivery. Herein, we used folic acid (FA) as targeting ligand and cholesterol (Chol) as helper lipid instead of DOPE for enhancing the stability of the liposomes. These liposomes were characterized by dynamic laser scattering (DLS), transmission electron microscopy (TEM) and agarose gel electrophoresis assays of pDNA binding affinity. The lipoplexes were prepared by using different weight ratios of DDCTMA/Chol (1:1, 2:1, 3:1, 4:1) liposomes and different concentrations of FA (50-200µg/mL) combining with pDNA. The transfection efficiencies of the lipoplexes were evaluated using pGFP-N2 and pGL3 plasmid DNA against NCI-H460 cells in vitro. Among them, the optimum gene transfection efficiency with DDCTMA/Chol (3:1)/FA (100µg/mL) was obtained. The results showed that FA could improve the gene transfection efficiencies of DDCTMA/Chol cationic liposome. Our results also convincingly demonstrated FA (100µg/mL)-coated DDCTMA/Chol (3:1) cationic liposome could serve as a promising candidate for the gene delivery.

SpindlesTracker: An Automatic and Low-Cost Labeled Workflow for Spindle Analysis.

Quantitative analysis of spindle dynamics in mitosis through fluorescence microscopy requires tracking spindle elongation in noisy image sequences. Deterministic methods, which use typical microtubule detection and tracking methods, perform poorly in the sophisticated background of spindles. In addition, the expensive data labeling cost also limits the application of machine learning in this field. Here we present a fully automatic and low-cost labeled workflow that efficiently analyzes the dynamic spindle mechanism of time-lapse images, called SpindlesTracker. In this workflow, we design a network named YOLOX-SP which can accurately detect the location and endpoint of each spindle under box-level data supervision. We then optimize the algorithm SORT and MCP for spindle's tracking and skeletonization. As there was no publicly available dataset, we annotated a S.pombe dataset that was entirely acquired from the real world for both training and evaluation. Extensive experiments demonstrate that SpindlesTracker achieves excellent performance in all aspects, while reducing label costs by 60%. Specifically, it achieves 84.1% mAP in spindle detection and over 90% accuracy in endpoint detection. Furthermore, the improved algorithm enhances tracking accuracy by 1.3% and tracking precision by 6.5%. Statistical results also indicate that the mean error of spindle length is within 1 µm. In summary, SpindlesTracker holds significant implications for the study of mitotic dynamic mechanisms and can be readily extended to the analysis of other filamentous objects. The code and the dataset are both released on GitHub.

Ultramorphological Comparison of Proboscis and Associated Sensilla of Scotogramma trifolii and Protoschinia scutosa (Lepidoptera: Noctuidae).

The proboscis is an important feeding organ for the glossatan moths, mainly adapted to the flower and non-flower visiting habits. The clover cutworm, Scotogramma trifolii Rottemberg, and the spotted clover moth, Protoschinia scutosa (Denis & Schiffermuller), are serious polyphagous pests, attacking numerous vegetables and crops, resulting in huge economic losses. However, the feeding behavior and mechanisms of the adult stage remain unsatisfactorily explored. In this study, the proboscis morphology of S. trifolii and P. scutosa are described in detail using scanning electron microscopy, with the aim of investigating the morphological differences and feeding behavior of these two species. The proboscises of S. trifolii and P. scutosa are similar in morphology and structure and are divided into three zones (Zone 1-3) based on the morphological changes of the dorsal legulae. Three sensillum types are located on the proboscises of both species, sensilla chaetica, sensilla basiconica, and sensilla styloconica. Significant differences were observed in the length of the proboscis and each zone between these two species, as well as in sensilla size and number. Based on the morphology of the proboscis and associated sensilla, S. trifolii and P. scutosa are potential flower visitors, which was also reinforced by the pollen observed at the proboscis tip. These results will strengthen our understanding of the structure of the proboscis related to the feeding behavior of Noctuidae.

CT Radiomics Model for Discriminating the Risk Stratification of Gastrointestinal Stromal Tumors: A Multi-Class Classification and Multi-Center Study.

OBJECTIVE: To establish and verify a computed tomography (CT)-based multi-class prediction model for discriminating the risk stratification of gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS: A total of 381 patients with GISTs were confirmed by surgery and pathology. Information on 213 patients were obtained from one hospital and used as training cohort, whereas the details of 168 patients were collected from two other hospitals and used as independent validation cohort. Regions of interest on CT images of arterial and venous phases were drawn, radiomics features were extracted, and dimensionality reduction processing was performed. Using a one-vs-rest method, a Random Forest-based GISTs risk three-class prediction model was established, and the receiver operating characteristic curve (ROC) was used to evaluate the performance of the multi-class classification model, and the generalization ability was verified using external data. RESULTS: The training cohort included 96 very low-risk and low-risk, 60 intermediate-risk and 57 high-risk patients. External validation cohort included 82 very low-risk and low-risk, 48 intermediate-risk and 38 high-risk patients. The GISTs risk three-class radiomics model had a macro/micro average area under the curve (AUC) of 0.84 and an accuracy of 0.78 in the training cohort. It had a stable performance in the external validation cohort, with a macro/micro average AUC of 0.83 and an accuracy of 0.80. CONCLUSION: CT radiomics can discriminate GISTs risk stratification. The performance of the three-class radiomics prediction model is good, and its generalization ability has also been verified in the external validation cohort, indicating its potential to assist stratified and accurate treatment of GISTs in the clinic.

Sensilla of the antenna and proboscis of Athetis lepigone (Möschler) (Lepidoptera: Noctuidae).

Sensory structures on the antennae and mouthparts of insects are associated with various activities, such as host location, feeding, attracting a mate, and identifying a suitable oviposition site. Athetis lepigone (Möschler) is an important polyphagous Eurasian pest with more than 30 species of host plants. The larvae target bud leaves, prop roots, and tender stems of many agricultural crops, but the feeding habits of the adults remain poorly known. Aiming to understand the feeding behavior of the species, we investigated the fine morphology of its antennae and proboscis using scanning electron microscopy. The antennae of both sexes are filiform, and bear eight types of sensilla: Böhm's bristles, sensilla squamiformia, trichodea, chaetica, basiconica, coeloconica, styloconica, and auricillica. Sensilla trichodea are the most abundant among these sensillum types. The proboscis consists of two elongated, interlocked maxillary galeae that enclose the food canal by dorsal and ventral legulae. The external galeal surface is covered with numerous triangular microtrichia on Zone 1 and abundant blunt microbumps on Zone 2. The surface of the food canal bears closely connected and smooth semicircular ridges, gradually tapering toward the proboscis tip. Three types of sensilla are noticeable on the proboscis: sensilla trichodea, basiconica, and styloconica. We briefly discuss the putative functional significance of the antennal and proboscis sensilla and, based on the specific structural modifications of the proboscis, predict a flower-visiting habit for A. lepigone.

Co-delivery of paclitaxel and anti-VEGF siRNA by tripeptide lipid nanoparticle to enhance the anti-tumor activity for lung cancer therapy.

The combination of chemotherapeutic drug paclitaxel (PTX) and VEGF siRNA could inhibit cancer development with synergistic efficacy. However, efficient and safe delivery systems with high encapsulation efficiency of PTX and a long-time release of drugs are urgently needed. In this study, novel nanoparticles (PTX/siRNA/FALS) were constructed by using tripeptide lipid (L), sucrose laurate (S), and folate-PEG2000-DSPE (FA) to co-deliver PTX and siRNA. The cancer cell targeting nanoparticle carrier (PTX/siRNA/FALS) showed anticipated PTX encapsulation efficiency, siRNA retardation ability, improved cell uptake and sustained and controlled drug release. It led to significant anti-tumor activity in vitro and in vivo by efficient inhibition of VEGF expression and induction of cancer cell apoptosis. Importantly, the biocompatibility of the carriers and low dosage of PTX required for effective therapy greatly reduced the toxicity to mice. The targeting nanoparticles show potential as an effective co-delivery platform for RNAi and chemotherapy drugs, aiming to improve the efficacy of cancer therapy.

Toxicological exploration of peptide-based cationic liposomes in siRNA delivery.

The toxicology of cationic liposomes was explored to advance clinical trials of liposome-mediated gene therapy through the analysis of a peptide cationic liposome with DOTAP as a positive control. We first investigated the delivery of luciferase siRNA by several peptide liposomes in mice bearing lung cancer A549 cell xenografts. Of these, a cationic liposome (CDO14) was selected for further investigation. CDO14 efficiently mediated IGF-1R-siRNA delivery and inhibited the growth of the A549 cell xenografts. The in vivo toxicity and toxicological mechanisms of the selected liposome were evaluated to assess its potential utility for gene delivery. Specifically, the effects of CDO14 on mouse body weight, hematology, urine, serum biochemical indices, and histopathology were measured in acute toxicity and subchronic toxicity tests. CDO14 showed limited toxicological effects at low dosages although it induced pulmonary inflammation and liver injury at higher dosages. The toxicity of CDO14 was lower than that of DOTAP, and the toxicity of CDO14 did not change when complexed with siRNA. The pulmonary inflammation induced by CDO14 occurred via expressional up-regulation of the pro-inflammatory cytokines TNF-α and IL-6, and expressional down-regulation of the anti-inflammatory cytokine IL-10. Liver injury induced by CDO14 was mediated by the JAK2-STAT3 signaling pathway. Lastly, CDO14 did not affect the expression of apoptosis-related proteins in normal liver cells, suggesting that it did not induce apoptosis of normal cells. The toxicological results demonstrate that peptide-based headgroups in lipids are superior to those with quaternary ammonium headgroups that are used as gene vectors for cancer therapy.

Zwitterionic pH-responsive hyaluronic acid polymer micelles for delivery of doxorubicin.

As zwitterionic polymers show great promise in drug delivery, hyaluronic acid (HA) was deacetylated and grafted with dodecylamine to prepare a pH-sensitive zwitterionic polymer dHAD used as a carrier for antitumor drugs. The polymer was negatively charged at pH 7.4 and became positive at pH 6.2. In vitro delivery of DOX against MCF-7 cells showed that the blank micelle dHAD had low cytotoxicity and the dHAD-DOX micelles could greatly prohibit the growth of the MCF-7 cells. In addition, the dHAD-DOX micelles had higher cellular uptake, indicating that the micelles were rapidly internalized into the cells via CD44 receptor-mediated endocytosis. The in vivo delivery of DOX to tumor-bearing mice confirmed that the dHAD-DOX micelles greatly inhibited the tumor growth and significantly reduced systemic toxicity of DOX. These results demonstrated that biocompatible pH-responsive zwitterionic dHAD micelles are promising carriers for the delivery of DOX.

Cancer Treatment with Liposomes Based Drugs and Genes Co-delivery Systems.

There are several mechanisms by which cancer cells develop resistance to treatments, including increasing anti-apoptosis, increasing drug efflux, inducing angiogenesis, enhancing DNA repair and altering cell cycle checkpoints. The drugs are hard to reach curative effects due to these resistance mechanisms. It has been suggested that liposomes based co-delivery systems, which can deliver drugs and genes to the same tumor cells and exhibit synergistic anti-cancer effects, could be used to overcome the resistance of cancer cells. As the co-delivery systems could simultaneously block two or more pathways, this might promote the death of cancer cells by sensitizing cells to death stimuli. This article provides a brief review on the liposomes based co-delivery systems to overcome cancer resistance by the synergistic effects of drugs and genes. Particularly, the synergistic effects of combinatorial anticancer drugs and genes in various cancer models employing multifunctional liposomes based co-delivery systems have been discussed. This review also gives new insights into the challenges of liposomes based co-delivery systems in the field of cancer therapy, by which we hope to provide some suggestions on the development of liposomes based co-delivery systems.

Grafting chitosan with polyethylenimine in an ionic liquid for efficient gene delivery.

Modifying chitosan (CS) with polyethylenimine (PEI) grafts is an effective way to improve its gene transfection performance. However, it is still a challenge to conduct the grafting with fine control and high efficiency, particularly for the modification of water-insoluble CS. Herein, a novel method to graft CS with PEI (1.8 kDa, PEI-1.8) was developed by using ionic liquid 1-butyl-3-methyl imidazolium acetate ([BMIM]Ac) as a reaction solvent, water-insoluble CS as a reaction substrate and 1,1-carbonyldiimidazole (CDI) as a linking agent. The grafting reaction was greatly accelerated and the reaction time was largely shortened to 4 h by taking advantages of the good solubility of CS, the enhanced nucleophilicity of amino groups and the preferential stability of the activated complexes in the ionic liquid. The chitosan-graft-polyethylenimine (CS-g-PEI) products were characterized by 1H NMR, FTIR and GPC. PEI-1.8 was quantitatively grafted to CS through urea linkages, and the grafting degree (GD) was conveniently tuned by varying the molar ratios of PEI-1.8 to D-glucosamine units of CS in the range of 9.0 × 10(-3) to 9.0 × 10(-2). Compared with CS, the synthesized CS-g-PEI copolymers showed higher pDNA-binding affinity, which increased with the GD as shown in Agarose gel electrophoresis. The dynamic light scattering (DLS) experiment demonstrated that the CS-g-PEI/pDNA polyplexes had suitable particle sizes and proper ζ-potentials for cell transfection. The CS-g-PEI copolymer with a medium GD of 4.5% conferred the best gene transfection, with the efficiency 44 times of CS and 38 times of PEI-1.8 in HEp-2 cells. The cytotoxicity of CS-g-PEI was tested and found nearly as low as that of CS and much lower than that of PEI.

[Expression of small breast epithelial mucin mRNA in peripheral blood of breast cancer patients and its clinical significance].

BACKGROUND & OBJECTIVE: The major cause of death in breast cancer patients is distant metastasis. This study was to explore the expression and significance of small breast epithelial mucin (SBEM) mRNA, the specific marker of breast cancer, in peripheral blood of breast cancer patients. METHODS: Expression of SBEM mRNA in peripheral blood samples from 67 breast cancer patients, 16 benign breast disease patients, and 20 healthy volunteers was detected by nested reverse transcription-polymerase chain reaction (nested RT-PCR). RESULTS: SBEM mRNA was not detected in healthy volunteers and benign breast disease patients. Positive rate of SBEM mRNA was 50.7% (34/67) in breast cancer patients. Positive rate of SBEM mRNA was 25.0% (2/8) in stage I patients, 45.8% (11/24) in stage II patients, 43.8% (7/16) in stage III patients, and 73.7% (14/19) in stage IV patients, respectively. Positive rate of SBEM mRNA was significantly higher in stage IV patients than in stages I, II, and III patients (P0.05). The expression of SBEM mRNA in peripheral blood was not correlated with patient's age, primary tumor size, pathologic type, and estrogen or progestin receptor status (P0.05). CONCLUSION: SBEM mRNA is specifically expressed in peripheral blood of breast cancer patients, and may be a marker of micrometastasis of breast cancer.