Dual-targeting multifunctional hyaluronic acid ligand-capped gold nanorods with enhanced endo-lysosomal escape ability for synergetic photodynamic-photothermal therapy of cancer.

Au nanorods (AuNRs) have attracted considerable interest as drug delivery systems because of their enhanced cell internalization and stronger drug-loading ability. In addition, the incorporation of photodynamic therapy (PDT) and photothermal therapy (PTT) into one nanosystem presents great promise to defect multiple drawbacks in cancer therapy. Herein, we fabricated a multifunctional and dual-targeting nanoplatform based on hyaluronic acid-grafted-(mPEG/triethylenetetramine-conjugated-lipoic acid/tetra(4-carboxyphenyl)porphyrin/folic acid) polymer ligand capped AuNRs (AuNRs@HA-g-(mPEG/Teta-co-(LA/TCPP/FA)) for combined photodynamic-photothermal therapy of cancer. The prepared nanoparticles displayed high TCPP loading capacity and excellent stability in different biological media. Furthermore, AuNRs@HA-g-(mPEG/Teta-co-(LA/TCPP/FA)) not only could produce a localized hyperthermia to conduct PTT, but also generate cytotoxic singlet oxygen (1 O2 ) to perform PDT under laser irradiation. Confocal imaging results disclosed that this nanoparticle endowing the specific function of polymeric ligand could enhance cellular uptake, accelerate endo/lysosomal escape, as well as produce higher reactive oxygen species. Importantly, this combination therapy strategy could also induce higher anticancer potential than PDT or PTT only against MCF-7 tumor cells in vitro. Therefore, this work presented an AuNRs-based therapeutic nanoplatform with great potential in dual-targeting and photo-induced combination therapy of cancer.

Modulating tumour vascular normalisation using triptolide-loaded NGR-functionalized liposomes for enhanced cancer radiotherapy.

Radiotherapy is an effective therapy in tumour treatment. However, the characteristics of the tumour microenvironment, including hypoxia, low pH, and interstitial fluid pressure bring about radioresistance. To improve the anti-tumour effect of radiotherapy, it has been demonstrated that antiangiogenic therapy can be employed to repair the structural and functional defects of tumour angiogenic vessels, thereby preventing radioresistance or poor therapeutic drug delivery. In this study, we prepared triptolide (TP)-loaded Asn-Gly-Arg (NGR) peptide conjugated mPEG2000-DSPE-targeted liposomes (NGR-PEG-TP-LPs) to induce tumour blood vessel normalisation, to the end of increasing the sensitivity of tumour cells to radiotherapy. Further, to quantify the tumour vessel normalisation window, the structure and functionality of tumour blood vessels post NGR-PEG-TP-LPs treatment were evaluated. Thereafter, the anti-tumour effect of radiotherapy following these treatments was evaluated using HCT116 xenograft-bearing mouse models based on the tumour vessel normalisation period window. The results obtained showed that NGR-PEG-TP-LPs could modulate tumour vascular normalisation to increase the oxygen content of the tumour microenvironment and enhance the efficacy of radiotherapy. Further, liver and kidney toxicity tests indicated that NGR-PEG-TP-LPs are safe for application in cancer treatment.

Fluoropolymer: A Review on Its Emulsion Preparation and Wettability to Solid-Liquid Interface.

In the preparation of a superamphiphobic surface, the most basic method is to reduce the surface free energy of the interface. The C-F bond has a very low surface free energy, which can significantly change the wettability of the solid-liquid interface and make it a hydrophobic or oleophobic, or even superamphiphobic surface. Based on the analysis of a large number of research articles, the preparation and application progress in fluoropolymer emulsion were summarized. After that, some corresponding thoughts were put forward combined with our professional characteristics. According to recent research, the status of the fluoropolymer emulsion preparation system was analyzed. In addition, all related aspects of fluoropolymer emulsion were systematically classified in varying degrees. Furthermore, the interaction between fluoropolymer structure and properties, especially the interaction with nanomaterials, was also explored. The aim of this review is to try to attract more scholars' attention to fluorocarbon interfacial materials. It is expected that it will make a certain theoretical and practical significance in the preparation and application of fluoropolymer.

A Salivary Odorant-Binding Protein Mediates Nilaparvata lugens Feeding and Host Plant Phytohormone Suppression.

Odorant-binding proteins (OBPs) typically act as transporters of odor molecules and play an important role in insect host location. Here, we identified an OBP in brown planthopper (BPH) Nilaparvata lugens salivary glands via transcriptome sequencing. Real-time quantitative PCR and Western blotting analysis results showed that NlugOBP11 was highly expressed in salivary glands and secreted into rice plant during feeding, suggesting that it assists in BPH feeding on rice. Functional analysis in N. lugens saliva revealed that silencing this gene by RNA interference decreased the BPH stylet performance in the phloem of rice plants, reduced sap sucking, and ultimately led to insect death. Moreover, overexpression of NlugOBP11 in rice protoplasts or Nicotiana benthamiana leaves inhibited the production of defense-related signaling molecule salicylic acid in rice plant. The results demonstrate that NlugOBP11 is not only essential for BPH feeding, but also acts as an effector that inhibits plant defense.

Liposome-Encapsulated Zoledronate Favors Tumor Vascular Normalization and Enhances Anticancer Efficacy of Cisplatin.

The aim of this study was to examine the effectiveness of alanine-proline-arginine-proline-glycine (APRPG) peptide-conjugated PEGylated cationic liposomes-encapsulated zoledronic acid (ZOL) (APRPG-PEG-ZOL-CLPs) in achieving vascular normalization. Cisplatin (diamminedichloroplatinum, DDP) was used to improve anticancer efficacy. The present study showed that APRPG-PEG-ZOL-CLPs increased anticancer efficacy, which was regarded as vascular normalization. Our results demonstrated that the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were evidently repressed by APRPG-PEG-ZOL-CLPs. Moreover, APRPG-PEG-ZOL-CLPs could decrease vessel density, as well as hypoxia-inducible factor 1α (HIF-1α), and increase thrombospondin 1 (TSP-1) expression of tumors. Therefore, the anticancer efficacy of APRPG-PEG-ZOL-CLPs combined with DDP was superior to that of PEG-ZOL-CLP or ZOL treatment combined with DDP schemes, as demonstrated by the obviously evident reduction in tumor volume. These results indicated that APRPG-PEG-ZOL-CLPs were most effective in normalizing tumor vasculature to elevate the therapeutic effect of antitumor drugs.

A tumor-targeted and enzyme-responsive gold nanorod-based nanoplatform with facilitated endo-lysosomal escape for synergetic photothermal therapy and protein therapy.

To tackle the obstacles related to tumor targeting and overcome the limitations of single treatment models, we have developed a nanoplatform that is both tumor-targeted and enzyme-responsive. This nanoplatform integrates photothermal gold nanorods (AuNRs) and protein drugs into a single system. This nanosystem, known as AuNRs@HA-mPEG-Deta-LA, was fabricated by modifying gold nanorods (AuNRs) with a polymeric ligand called hyaluronic acid-grafted-(mPEG/diethylenetriamine-conjugated-lipoic acid). The purpose of this fabrication was to load cytochrome c (CC) and utilize it for the synergetic protein-photothermal therapy of cancer. The resulting nanoplatform exhibited a high efficiency in loading proteins and demonstrated excellent stability in different biological environments. Additionally, CC-loaded AuNRs@HA-mPEG-Deta-LA not only enabled localized hyperthermia for photothermal therapy (PTT) with laser irradiation but also facilitated the release of CC under the action of hyaluronidase, an enzyme known to be overexpressed in tumor cells. The confocal imaging results demonstrated that the presence of a specific polymeric ligand on this nanoparticle enhances the internalization of CD44-positive cancer cells, accelerates endo/lysosomal escape, and facilitates the controlled release of CC within the cells. Furthermore, the results of the MTT assay also showed that AuNRs@HA-mPEG-Deta-LA as a protein nanocarrier demonstrated excellent biocompatibility. Importantly, this synergistic therapeutic strategy effectively induced apoptosis in A549 cancer cells by increasing the intracellular concentration of CC and utilizing the photothermal conversion of AuNRs, which was observed to be more effective compared to using only protein therapy or PTT. Therefore, this study showcased a nanoplatform based on AuNRs that has great potential for tumor-targeted protein delivery in combination with PTT in cancer treatment.

[Microplastics in the stomach and intestine of pelagic squid: A case study of Dosidicus gigas in open sea of Peru]. / å¤§æ´‹æ€§å¤´è¶³ç±»èƒƒå’Œè‚ é“ä¸­çš„å¾®å¡‘æ–™­­ä»¥ç§˜é²å¤–海茎柔鱼为例.

Microplastic (MP) ingestion by marine animals has been well documented, but less being known about pelagic squid. Jumbo squid Dosidicus gigas supports the world's largest cephalopod fishery and plays an important ecological role in the Eastern Pacific Ocean. In this study, D. gigas taken from the open sea of the Peruvian Exclusive Economic Zone were selected as research objects. We estimated the abundance and characteristics of MPs in the stomach and intestine of D. gigas and investigated the differences between tissues and sexes. Similar abundance and characteristics of MPs were observed in the same tissue of females and males. However, the stomach had a higher abundance of MPs with larger size than the intestine, while the MP abundance by stomach wet weight was lower than that of the intestine. The MPs were predominantly fiber-shaped, with blue or black color. The most frequent polymers were high-density cellophane and polyacrylic acid. These polymers could sink into deeper sea layers and were available for D. gigas living there during the daytime. Our findings revealed the distribution pattern of MPs in the waters of the Peruvian fishing ground. This study could improve our understanding of the MP contamination level in pelagic squid, and have implications for evaluating the ecological effects of MP on cephalopods.

A pipeline inspection robot for navigating tubular environments in the sub-centimeter scale.

In complex systems like aircraft engines and oil refinery machines, pipeline inspection is an essential task for ensuring safety. Here, we proposed a type of smart material-driven pipeline inspection robot (weight, 2.2 grams; length, 47 millimeters; diameter, <10 millimeters) that could fit into pipes with sub-centimeter diameters and different curvatures. We adopted high-power density, long-life dielectric elastomer actuators as artificial muscles and smart composite microstructure-based, high-efficiency anchoring units as transmissions. Fast assembling of components using magnets with an adjustable number of units was used to fit varying pipeline geometries. We analyzed the dynamic characteristics of the robots by considering soft material's unique properties like viscoelasticity and dynamic vibrations and tuned the activation voltage's frequency and phase accordingly. Powered by tethered cables from outside the pipe, our peristaltic pipeline robot achieved rapid motions horizontally and vertically (horizontal: 1.19 body lengths per second, vertical: 1.08 body lengths per second) in a subcentimeter-sized pipe (diameter, 9.8 millimeters). Besides, it was capable of moving in pipes with varying geometries (diameter-changing pipe, L-shaped pipe, S-shaped pipe, or spiral-shaped pipe), filled media (air or oil), and materials (glass, metal, or carbon fiber). To demonstrate its capability for pipeline inspection, we installed a miniature camera on its front and controlled the robot manually from outside. The robot successfully finished an inspection task at different speeds.

Candesartan treatment enhances liposome penetration and anti-tumor effect via depletion of tumor stroma and normalization of tumor vessel.

The poor penetration of nanoparticles in solid tumors has been a critical factor limiting the clinical benefits of nanomedicine. Therefore, we depleted the dense extracellular matrix (ECM) and normalized tumor vessels to enhance drug delivery and therapeutic efficacy. We used candesartan as an angiotensin system inhibitor, which reduced ECM content and facilitated "vascular normalization" by targeting the angiotensin-signaling axis, resulting in improved anti-cancer therapeutic effects. We also combined candesartan with PEGylated liposome-encapsulated zoledronic acid (ZOL) (PEG-ZOL-LPs) to assess how this affected anti-tumor therapy. Our findings indicated that the migration of 4T1 mouse breast cancer cells was inhibited by candesartan. Moreover, the ECM depletion (including collagen I and hyaluronan) by candesartan was achieved through the downregulation of TGF-ß1 in vitro, consistent with in vivo results. Furthermore, treatment groups that received candesartan also had significantly decreased tumor vessel permeability and proportions of circulating endothelial progenitor cells (CEPCs) in the serum, which resulted in normalization of tumor vasculature and improved delivery of PEG-ZOL-LPs. Finally, the positive effect candesartan in terms of tumor growth was found not to have an impact of the efficacy of the PEG-ZOL-LPs treatment. This unexpected lack of effect of candesartan on the performance of PEG-ZOL-LPs would be due to dynamics of the effect of both treatments. It might be possible that a different protocol of administration could lead to a synergistic effect. Graphical abstract The schematic illustration showed that candesartan favored depletion of tumor stroma and tumor vascular normalization to improve the anti-cancer efficacy of PEG-ZOL-LPs.

Combination of metronomic administration and target delivery strategies to improve the anti-angiogenic and anti-tumor effects of triptolide.

The metronomic administration of a low-dose cytotoxic agent with no prolonged drug-free breaks is an anti-angiogenic cancer treatment method. The use of nano-formulations in this manner enhances anti-tumor efficacy and reduces toxicity by inhibiting angiogenic activity, reduces adverse effects, and changes the biodistribution of TP in the body, steering TP away from potentially endangering healthy tissues. The present study uses liposomes and Asn-Gly-Arg (NGR) peptide conjugated aminopeptidase N(APN)-targeted liposomes for triptolide (TP), as a model for the investigation of targeted metronomic administration and subsequent effects on the toxicity profile and efficacy of the chemotherapeutic agent. Metronomic NGR-PEG-TP-LPs have been found to have enhanced anti-tumor activity, a phenomenon that is attributed to an increase in angiogenic inhibition properties. In vitro experiments demonstrate that the viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) are obviously suppressed in comparison with that of other treatment groups. In vivo experiments also demonstrate that the anti-tumor efficacy of targeted metronomic administration is superior to that of liposome-administered treatments given at maximum tolerated dose (MTD) schemes, as is evidenced by markedly decreased tumor volume, vessel density, and the volume of circulating endothelial progenitor cells (CEPCs) in serum. Moreover, we observed that the metronomic administration of NGR-PEG-TP-LPs could elevate thrombospondin-1 (TSP-1) expression in tumors, a finding that is consistent with the promotion of TSP-1 secretion specifically from HUVECs. Additionally, metronomic NGR-PEG-TP-LPs have minimal drug-associated toxicity (weight loss, hepatotoxicity and nephrotoxicity in mice). Our research demonstrates the significance of targeted metronomic administration using liposomes for anti-angiogenic cancer therapy.

Biochemical and genetic characteristics of Cronobacter sakazakii biofilm formation.

Cronobacter sakazakii is a wide-spread opportunistic foodborne pathogen that can form biofilms on a number of different substances, creating food safety risk. However, there is little information about biofilm characteristics for this species. In this study, biofilm formation of 14 foodborne C. sakazakii strains was examined. Transposon mutants of the strain (IQCC10423), the isolate with the greatest biofilm activity, were prepared. A total of 12 mutants were developed with >40% reduction in biofilm formation ability. Eight of these mutants were successfully sequenced with genes putatively identified for: biofilm formation, fundamental cellular processes, phage tail complete protein and uncertain functional protein. The morphology of the biofilm showed that the wild type strain formed a thick biofilm and mutants formed less extracellular polymeric substances (EPSs). Raman spectroscopy was employed to confirm less biofilm formation by different bacterial mutants and demonstrate a similar chemical composition, but different contents of EPS. Wild type biofilms contained a high level of carotenoids, with the distribution of carotenoids mapped using confocal Raman imaging. We demonstrate that various selective functional genes are responsible for the forming ability of C. sakazakii biofilms, which may have the potential to cause risks to food safety.

Duplicated zebrafish co-orthologs of parathyroid hormone-related peptide (PTHrP, Pthlh) play different roles in craniofacial skeletogenesis.

In mammals, parathyroid hormone-related peptide (PTHrP, alias PTH-like hormone (Pthlh)) acts as a paracrine hormone that regulates the patterning of cartilage, bone, teeth, pancreas, and thymus. Beyond mammals, however, little is known about the molecular genetic mechanisms by which Pthlh regulates early development. To evaluate conserved pathways of craniofacial skeletogenesis, we isolated two Pthlh co-orthologs from the zebrafish (Danio rerio) and investigated their structural, phylogenetic, and syntenic relationships, expression, and function. Results showed that pthlh duplicates originated in the teleost genome duplication. Zebrafish pthlha and pthlhb were maternally expressed and showed overlapping and distinct zygotic expression patterns during skeletal development that mirrored mammalian expression domains. To explore the regulation of duplicated pthlh genes, we studied their expression patterns in mutants and found that both sox9a and sox9b are upstream of pthlha in arch and fin bud cartilages, but only sox9b is upstream of pthlha in the pancreas. Morpholino antisense knockdown showed that pthlha regulates both sox9a and sox9b in the pharyngeal arches but not in the brain or otic vesicles and that pthlhb does not regulate either sox9 gene, which is likely related to its highly degraded nuclear localization signal. Knockdown of pthlha but not pthlhb caused runx2b overexpression in craniofacial cartilages and premature bone mineralization. We conclude that in normal cartilage development, sox9 upregulates pthlh, which downregulates runx2, and that the duplicated nature of all three of these genes in zebrafish creates a network of regulation by different co-orthologs in different tissues.

Heparin-chitosan-coated acellular bone matrix enhances perfusion of blood and vascularization in bone tissue engineering scaffolds.

Currently, the main hurdle in the tissue engineering field is how to provide sufficient blood supply to grafted tissue substitutes in the early post-transplanted period. For three-dimensional, cell-dense, thick tissues to survive after transplantation, treatments are required for hypoxia, nutrient insufficiency, and the accumulation of waste products. In this study, a biomacromolecular layer-by-layer coating process of chitosan/heparin onto a decellularized extracellular bone matrix was designed to accelerate the blood perfusion and re-endothelialization process. The results of in vitro measurements of the activated partial thromboplastin time supported the theory that the combination of chitosan and heparin could bring both anticoagulation and hemocompatibility to the scaffold. A rabbit bone defect model was established for further evaluation of the application of this kind of surface-modified scaffold in vivo. The final results of computed tomography (CT) perfusion imaging and histological examination proved that this facile coating approach could significantly promote blood perfusion and re-endothelialization in the early post-transplanted period compared with an acellular bone matrix due to its much-improved anticoagulation property.

Magnetic poly(PEGMA-MAA) nanoparticles: photochemical preparation and potential application in drug delivery.

Poly(PEGMA-MAA)-coated superparamagnetic nanoparticles were synthesized by in situ photochemical polymerization in magnetite aqueous suspension under UV irradiation. The magnetic poly(PEGMA-MAA) nanoparticles were characterized by Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), photo correlation spectroscopy (PCS) and vibration sample magnetometry (VSM), respectively. The results indicated that the magnetic poly(PEGMA-MAA) nanoparticles were of regularly spherical shape and remained monodisperse. The average size measured in aqueous media was 96.4 nm, which was much bigger than that in dry state, the nanoparticles behaved superparamagnetic with saturated magnetization of 64.8 emu/g, the zeta potential was -18.3 mV at physiological pH 7.2, and the magnetic poly(PEGMA-MAA) nanoparticles had a high stability in vitro. A typical anti-inflammatory drug, ibuprofen, was used for drug loading, and the release behavior of ibuprofen in a simulated body fluid (SBF, pH 7.4) was studied. The results indicated that these novel magnetic nanoparticles had a high drug-loading capacity and favorable release properties for ibuprofen. The magnetic poly(PEGMA-MAA) nanoparticles are very promising for application in drug delivery.

Matrix metalloproteinase and its inhibitor in temporomandibular joint osteoarthrosis after indirect trauma in young goats.

Our aim was to examine the change in expression of matrix metalloproteinases (MMP-13), matrix metalloproteinases-3 (MMP-3), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the articular cartilage of goats with experimentally-induced osteoarthrosis of the temporomandibular joint (TMJ) at various times. Osteoarthrosis was induced in 20 goats in the bilateral TMJ and 5 goats acted as controls. There were 5 goats in each group, and a group was killed at 7 days, and 1, 3, and 6 months postoperatively. The samples were collected, and the joints evaluated histologically. Immunofluorescence was used to detect the presence of MMPs and TIMP-1 in the articular disc and condylar cartilage. The ultrastructure of the articular disc and condylar surface at 1 month was examined with scanning electron microscopy (SEM). Osteoarthrosis of the TMJ progressed gradually over time. MMP-13, MMP-3, and TIMP-1 were expressed strongly in the TMJ soon after injury; MMP-13 became gradually weakened, and MMP-3 strengthened later. None of these were expressed in the normal condyle. After a month the surface of the arthrotic condyle was uneven, and the underlying collagen fibrils were exposed in irregular fissures on the surface. The secretion of TIMP-1 was related closely to the changes of MMPs during osteoarthrosis of the TMJ. The unbalanced ratio between them caused degradation of the matrix of the cartilage and might be the cause of osteoarthrosis of the TMJ.