Reversal of pancreatic desmoplasia by a tumour stroma-targeted nitric oxide nanogel overcomes TRAIL resistance in pancreatic tumours.

OBJECTIVE: Stromal barriers, such as the abundant desmoplastic stroma that is characteristic of pancreatic ductal adenocarcinoma (PDAC), can block the delivery and decrease the tumour-penetrating ability of therapeutics such as tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), which can selectively induce cancer cell apoptosis. This study aimed to develop a TRAIL-based nanotherapy that not only eliminated the extracellular matrix barrier to increase TRAIL delivery into tumours but also blocked antiapoptotic mechanisms to overcome TRAIL resistance in PDAC. DESIGN: Nitric oxide (NO) plays a role in preventing tissue desmoplasia and could thus be delivered to disrupt the stromal barrier and improve TRAIL delivery in PDAC. We applied an in vitro-in vivo combinatorial phage display technique to identify novel peptide ligands to target the desmoplastic stroma in both murine and human orthotopic PDAC. We then constructed a stroma-targeted nanogel modified with phage display-identified tumour stroma-targeting peptides to co-deliver NO and TRAIL to PDAC and examined the anticancer effect in three-dimensional spheroid cultures in vitro and in orthotopic PDAC models in vivo. RESULTS: The delivery of NO to the PDAC tumour stroma resulted in reprogramming of activated pancreatic stellate cells, alleviation of tumour desmoplasia and downregulation of antiapoptotic BCL-2 protein expression, thereby facilitating tumour penetration by TRAIL and substantially enhancing the antitumour efficacy of TRAIL therapy. CONCLUSION: The co-delivery of TRAIL and NO by a stroma-targeted nanogel that remodels the fibrotic tumour microenvironment and suppresses tumour growth has the potential to be translated into a safe and promising treatment for PDAC.

Identification of Salivary Biomarkers for Oral Cancer Detection with Untargeted and Targeted Quantitative Proteomics Approaches.

Oral cavity squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. In Taiwan, OSCC is the fifth leading cause of cancer-related mortality and leads to 2800 deaths per year. The poor outcome of OSCC patients is principally ascribed to the fact that this disease is often advanced at the time of diagnosis, suggesting that early detection of OSCC is urgently needed. Analysis of cancer-related body fluids is one promising approach to identify biomarker candidates of cancers. To identify OSCC biomarkers, salivary proteomes of OSCC patients, individuals with oral potentially malignant disorders (OPMDs), and healthy volunteers were comparatively profiled with isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry (MS). The salivary levels of 67 and 18 proteins in the OSCC group are elevated and decreased compared with that in the noncancerous group (OPMD and healthy groups), respectively. The candidate biomarkers were further selected using the multiple reaction monitoring (MRM)-MS and validated with the immunoassays. More importantly, the higher salivary level of three proteins, complement factor H (CFH), fibrinogen alpha chain (FGA), and alpha-1-antitrypsin (SERPINA1) was correlated with advanced stages of OSCC. Our results indicate that analysis of salivary proteome is a feasible strategy for biomarker discovery, and the three proteins are potential salivary markers for OSCC diagnosis.

Mouse Models of Human Gastric Cancer Subtypes With Stomach-Specific CreERT2-Mediated Pathway Alterations.

BACKGROUND & AIMS: Patterns of genetic alterations characterize different molecular subtypes of human gastric cancer. We aimed to establish mouse models of these subtypes. METHODS: We searched databases to identify genes with unique expression in the stomach epithelium, resulting in the identification of Anxa10. We generated mice with tamoxifen-inducible Cre recombinase (CreERT2) in the Anxa10 gene locus. We created 3 mouse models with alterations in pathways that characterize the chromosomal instability (CIN) and the genomically stable (GS) subtypes of human gastric cancer: Anxa10-CreERT2;KrasG12D/+;Tp53R172H/+;Smad4fl/f (CIN mice), Anxa10-CreERT2;Cdh1fl/fl;KrasG12D/+;Smad4fl/fl (GS-TGBF mice), and Anxa10-CreERT2;Cdh1fl/fl;KrasG12D/+;Apcfl/fl (GS-Wnt mice). We analyzed tumors that developed in these mice by histology for cell types and metastatic potential. We derived organoids from the tumors and tested their response to chemotherapeutic agents and the epithelial growth factor receptor signaling pathway inhibitor trametinib. RESULTS: The gastric tumors from the CIN mice had an invasive phenotype and formed liver and lung metastases. The tumor cells had a glandular morphology, similar to human intestinal-type gastric cancer. The gastric tumors from the GS-TGFB mice were poorly differentiated with diffuse morphology and signet ring cells, resembling human diffuse-type gastric cancer. Cells from these tumors were invasive, and mice developed peritoneal carcinomatosis and lung metastases. GS-Wnt mice developed adenomatous tooth-like gastric cancer. Organoids derived from tumors of GS-TGBF and GS-Wnt mice were more resistant to docetaxel, whereas organoids from the CIN tumors were more resistant to trametinib. CONCLUSIONS: Using a stomach-specific CreERT2 system, we created mice that develop tumors with morphologic similarities to subtypes of human gastric cancer. These tumors have different patterns of local growth, metastasis, and response to therapeutic agents. They can be used to study different subtypes of human gastric cancer.

Study of the enantioselectivity and recognition mechanism of sulfhydryl-compound-functionalized gold nanochannel membranes.

Two new chiral membranes were prepared by modification of gold nanochannel membranes with D-penicillamine and N-acetyl-L-cysteine and were characterized by scanning electron microscopy and X-ray photoelectron spectroscopy. The effects of key factors such as the gold deposition time, the pH, and the concentration of sodium dihydrogen phosphate on the separation factor are discussed. Chiral resolution of amino acid enantiomers by the chiral membranes was investigated. The experimental results show that the D-penicillamine-modified membrane has good enantioselectivity toward tyrosine and phenylalanine enantiomers, whereas the N-acetyl-L-cysteine-modified membrane has good enantioselectivity toward tyrosine and tryptophan enantiomers. Furthermore, the chiral recognition mechanism was studied by density functional theory. The calculation results indicate that the basic chiral recognition system of D-penicillamine complexes involves only one chiral selector and one selected enantiomer, whereas that of N-acetyl-L-cysteine complexes involves two chiral selectors and one selected enantiomer. Finally, the NH3+ group of D-penicillamine is proved to play an important role in enhancing interactions between complexes and improving enantioselectivity. Graphical abstract Enantioselective interactions between amino acid enantiomers and sulfhydryl-compound-functionalized gold nanochannel membranes.

Development of a Multiplexed Assay for Oral Cancer Candidate Biomarkers Using Peptide Immunoaffinity Enrichment and Targeted Mass Spectrometry.

Oral cancer is one of the most common cancers worldwide, and there are currently no biomarkers approved for aiding its management. Although many potential oral cancer biomarkers have been discovered, very few have been verified in body fluid specimens in parallel to evaluate their clinical utility. The lack of appropriate multiplexed assays for chosen targets represents one of the bottlenecks to achieving this goal. In the present study, we develop a peptide immunoaffinity enrichment-coupled multiple reaction monitoring-mass spectrometry (SISCAPA-MRM) assay for verifying multiple reported oral cancer biomarkers in saliva. We successfully produced 363 clones of mouse anti-peptide monoclonal antibodies (mAbs) against 36 of 49 selected targets, and characterized useful mAbs against 24 targets in terms of their binding affinity for peptide antigens and immuno-capture ability. Comparative analyses revealed that an equilibrium dissociation constant (KD ) cut-off value < 2.82 × 10-9 m could identify most clones with an immuno-capture recovery rate >5%. Using these mAbs, we assembled a 24-plex SISCAPA-MRM assay and optimized assay conditions in a 25-µg saliva matrix background. This multiplexed assay showed reasonable precision (median coefficient of variation, 7.16 to 32.09%), with lower limits of quantitation (LLOQ) of <10, 10-50, and >50 ng/ml for 14, 7 and 3 targets, respectively. When applied to a model saliva sample pooled from oral cancer patients, this assay could detect 19 targets at higher salivary levels than their LLOQs. Finally, we demonstrated the utility of this assay for quantification of multiple targets in individual saliva samples (20 healthy donors and 21 oral cancer patients), showing that levels of six targets were significantly altered in cancer compared with the control group. We propose that this assay could be used in future studies to compare the clinical utility of multiple oral cancer biomarker candidates in a large cohort of saliva samples.

Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan.

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

Suppressing Antibacterial Resistance: Chemical Binding of Monolayer Quaternary Ammonium Salts to Polymethyl Methacrylate in an Aqueous Solution and its Clinical Efficacy.

Antibacterial resistance (ABR) poses an enormous threat to human health. ABR mainly develops due to bacteria being constantly exposed to diluted levels of disinfectants. Here, we propose a method for suppressing ABR through the chemical binding of disinfectants to polymethyl methacrylate (PMMA) device surfaces in solutions of 5%, 10%, and 20% disinfectant concentrations. PMMA discs were fabricated from a commercial orthodontic acrylic resin system (Ortho-Jet) and quaternary ammonium salts (QAS), 3-(trimethoxysilyl)-propyldimethyloctadecyl ammonium chloride (42% in methanol), were used as the disinfectant. The PMMA surfaces were activated in 3 M sulfuric acid at 80 °C for 5 h for the esterification of hydrolyzed QAS to PMMA. Fourier transform infrared difference spectra confirmed that the carboxy-terminated PMMA was chemically bound to the QAS. In vitro cell viability tests using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays revealed that 5%QAS-c-PMMA was more biocompatible than 10%QAS-c-PMMA and 20%QAS-c-PMMA. The results of antibacterial tests and clinical trials demonstrated the excellent antibacterial power of 5%QAS-c-PMMA. This method is the first solution-based approach to successfully avoid disinfectant leakage and subsequent ABR, as revealed by mass spectrometry studies of the solution obtained by agitating the disinfectant-bound PMMA for 28 days.

Enantioselective permeations of amino acids through L-proline-modified gold nanochannel membrane: an experimental and theoretical study.

L-Proline-modified gold nanochannel membrane (L-Pro-GNM) was prepared and applied for the enantioselective permeations of amino acid enantiomers including tyrosine (Tyr), tryptophan (Trp) and phenylalanine (Phe). Experimental results show that L-Pro-GNM has enantioselectivities for Tyr and Phe enantiomers. Furthermore, the chiral recognition mechanism was studied by density functional theory (DFT) and reduced density gradient (RDG). DFT computational results illustrate that the fundamental chiral recognition system contains two chiral selectors and one selectand, which can be used to evaluate the enantioselective efficiencies of other chiral compounds and the enantioselective ability of other potential amino acid-modified GNM. Finally, graphs obtained by RDG using Multiwfn show helpful visual interactions between the chiral selector and selectand. Results indicate that the electrostatic interaction and hydrogen bonding are responsible for the binding of the chiral selector and selectand, and the larger binding energy shows larger van der Waals interactions.

Development of hybrid scaffolds with biodegradable polymer composites and bioactive hydrogels for bone tissue engineering.

The development of treatments for critical-sized bone defects has been considered an important topic in the biomedical field because of the high demand for transplantable bone grafts. Following the concept of tissue engineering, implantation of biocompatible porous scaffolds carrying cells and regulating factors is the most efficient strategy to stimulate clinical bone regeneration. With the advancement in the development of 3D-printing techniques, scaffolds with highly controllable architectures can be fabricated to further improve healing efficacies. However, challenges such as the limited biocompatibility of resin materials and poor cell-carrying capacities still exist in the application of current scaffolds. In this study, a novel biodegradable polymer, poly (ethylene glycol)-co-poly (glycerol sebacate) acrylate (PEGSA), was synthesized and blended with hydroxyapatite (HAP) nanoparticles to produce osteoinductive and photocurable resins for 3D printing. The composites were optimized and applied in the fabrication of gyroid scaffolds with biomimetic characteristics and high permeability, followed by the combination of bioactive hydrogels containing Wharton's jelly-derived mesenchymal stem cells (WJMSC) to increase the efficiency of cell delivery. The promotion of osteogenesis from 3D-printed scaffolds was confirmed in-vivo while the hybrid scaffolds were proven to be great platforms for WJMSC culture and differentiation in-vitro. These results indicate that the proposed hybrid systems, combining osteoinductive 3D-printed scaffolds and cell-laden hydrogels, have great potential for bone tissue engineering and are expected to be applied in the treatment of bone defects based on active tissue regeneration.

An Environmental-Inert and Highly Self-Healable Elastomer Obtained via Double-Terminal Aromatic Disulfide Design and Zwitterionic Crosslinked Network for Use as a Triboelectric Nanogenerator.

Due to the ongoing development of portable/mobile electronics, sources to power have received widespread attention. Compared to chemical batteries as power sources, triboelectric nanogenerators (TENGs) possess lots of advantages, including the ability to harvest energy via human motions, flexible structures, environment-friendliness, and long-life characteristics. Although many self-healable TENGs are reported, the achievement of a muscle-like elasticity and the ability to recover from inevitable damage under extreme conditions (such as a high/low temperature and/or humidity) remain a challenge. Herein, a "double-terminal aromatic disulfide" on a structure with zwitterions as branched chains is reported to engineer the high-efficient self-healable elastomer for application in a flexible TENG. The as-designed material exhibits a repeatable elastic recovery (at 250% elongation) and a self-healing efficiency with an ultimate tensile stress of 96% over 2 h, representing an improvement on previously reported disulfide-based elastomers. The elastomer can autonomously recover by 50% even at a subzero temperature of -30 °C within 24 h. The elastomer-based TENG, as a self-driven sensor for detecting human behavior, is demonstrated to exhibit stable outputs and self-healing in the temperature range of -30 to 60 °C, and so is expected to promote the development of self-powered electronics for next-generation human-machine communications.

Protocol for fabricating electroless nickel immersion gold strain sensors on nitrile butadiene rubber gloves for wearable electronics.

This protocol describes the fabrication of patterned conductive gold films on nitrile butadiene rubber (NBR) gloves for wearable strain sensors using electroless nickel immersion gold (ENIG) plating, a solution-based metallization technique. The resulting NBR/ENIG films are strain sensitive; resistance measurements of a patterned sensing array can be used to map human hand motions. This protocol also describes challenges related to the ENIG process and troubleshooting steps to achieve conformal gold films for strain sensing over a large working range. For complete details on the use and execution of this protocol, please refer to Mechael et al. (2021).

Carboxylated cellulose nanocrystals with chiral nematic property from cotton by dicarboxylic acid hydrolysis.

Carboxylated cellulose nanocrystals (CNCs) were produced from cotton linter using a mixture of a dicarboxylic acid (maleic acid or succinic acid) and its corresponding anhydride with or without catalyst in acetic acid as solvent. The low solubilities of these dicarboxylic acids can ease chemical recovery and decrease environmental impact (especailly maleic acid is a U.S. FDA approved indirect food additive (21CFR175-177)) and capital costs compared with the conventional concentrated sulfuric acid hydrolysis for producing CNCs. The dicarboxylic-acid-produced CNCs (DC-CNCs) contained surface carboxyl groups of approximately 0.5 mmol/g, with ranges of dimensions of 50-150 nm in diameter and 50-700 nm in length. Birefringence was observed in the DC-CNC suspensions above critical concentrations. However, fingerprint texture was only observed in the DC-CNC suspensions produced with catalyst p-toluenesulfonic acid. Scanning electron microscopy images of the cross section of DC-CNC films revealed a periodic ordered multilayer structure. DC-CNCs were also produced using recycled dicarboxylic acids.

Pulmonary surfactants affinity Pluronic-hybridized liposomes enhance the treatment of drug-resistant lung cancer.

For a long time, the incidence and mortality of lung cancer have ranked first among all kinds of cancers, of which the major type is non-small cell lung cancer (NSCLC). Until now, chemotherapy and radiotherapy are still the first choice for patients with advanced or metastatic NSCLC. However, the emergence of multi-drug resistance (MDR) always leads to the failure of chemotherapy and increases cancer-related mortality. In this study, we prepared a Pluronic-hybridized paclitaxel-loaded liposome (PPL), which was used in combination with ambroxol (Ax) to not only resensitize drug-resistant tumor cells, but also increase the preparation retention in the lung. On the one hand, Ax induced the production of pulmonary surfactants (PS) and responsively improved the accumulation of pulmonary surfactants affinity liposomes whose skeleton was exogenous pulmonary surfactant phospholipids DPPC, because of the specific affinity of phospholipids related to pulmonary surfactant proteins. On the other hand, drug-resistant tumor cells were resensitized due to the inhibition of autophagy by Ax and the reduced expression of the drug-resistant protein P-glycoprotein (P-gp) by Pluronic P105. Therefore, we concluded that the combination of PPL and Ax achieved excellent killing tumor effects through multi-path and multi-strategy, having great application prospects in the future.

Dual-functional antibiofilm polymer composite for biodegradable medical devices.

Urinary tract infections (UTI) represent one of the most common problem within the urological disorders, and it is mainly caused by biofilm formation which leads to bacterial infection. Anti-adhesion and antibacterial agents are two primary mechanisms to prevent biofilm formation; however, current strategies are insufficiently effective. In this study, we developed an effective antibiofilm biodegradable polymer with high biocompatibility. Here we embedded silver nanoparticles (AgNPs) in poly(glycerol sebacate) acrylate (PGSA) followed by superhydrophilic modification on the polymer surfaces. The modified surfaces were characterized using SEM, AFM and contact angle measurements. This anti-adhesive surface prevented the adhesion of E. coli and limited the biofilm coverage percentage to less than 3% in 24 h. In the in vitro degradation, the long-term antibiofilm performance was evaluated in Nowatzki-Stoodley artificial urine (NSAU). The surface modified AgNPs embedded PGSA (sPGSA-AgNPs) was able to effectively inhibit the formation of biofilm by reducing the biofilm coverage to less than 0.01%, and it also showed low cytotoxicity with human bladder carcinoma cell. With the effective antibiofilm, biocompatibility and biodegradability, it is possible to be applied in urological devices to ameliorate the situation of UTIs.

Pulmonary-Affinity Paclitaxel Polymer Micelles in Response to Biological Functions of Ambroxol Enhance Therapeutic Effect on Lung Cancer.

PURPOSE: Cancer chemotherapy effect has been largely limited by cell autophagy and little drug accumulation at the action sites. Herein, we designed an intelligent strategy involving paclitaxel (PTX) polymer micelles in response to biological functions of ambroxol (Ax). The amphiphilic polymers polyethyleneglycol-polylactic acid (PEG-PLA) and Pluronic P105 were selected as nanocarriers to encapsulate PTX to form into lung affinity PEG-PLA/P105/PTX micelles. Ax which can up-regulate the secretion of pulmonary surfactant (PS) and inhibit autophagy was hired to change the microenvironment of the lung, thereby promoting the lung accumulation and increasing cell-killing sensitivity of the micelles. METHODS: The physical and chemical properties of the micelles were characterized including size, morphology, critical micellar concentration (CMC) and in vitro drug release behavior. The therapeutic effects of the combination regimen were characterized both in vitro and in vivo including study on Ax in promoting the secretion of pulmonary surfactant, in vitro cytotoxicity, cellular uptake, Western blotting, in vivo biodistribution, in vivo pharmacokinetics and in vivo antitumor efficacy. RESULTS: The PEG-PLA/P105/PTX micelles showed a particle size of 16.7 ± 0.5 nm, a nearly round shape, small CMC and sustained drug release property. Moreover, the in vitro results indicated that Ax could increase PS and LC3 protein secretion and enhance the cytotoxicity of PEG-PLA/P105/PTX micelles toward A549 cells. The in vivo results indicated that the combination therapeutic regimen could promote the micelles to distribute in lung and enhance the therapeutic effect on lung cancer. CONCLUSION: This multifunctional approach of modulating the tumor microenvironment to enhance drug transportation and cell-killing sensitivity in the action sites might offer a new avenue for effective lung cancer treatment.

Fluorescence Probes Exhibit Photoinduced Structural Planarization: Sensing In Vitro and In Vivo Microscopic Dynamics of Viscosity Free from Polarity Interference.

We demonstrate the construction of wavelength λ-ratiometric images that allow visualizing the distribution of microscopic dynamics within living cells and tissues by using the newly developed principle of fluorescence response. The bent-to-planar motion in the excited state of incorporated fluorescence probes leads to elongation of the π-delocalization, resulting in microviscosity-dependent but polarity-insensitive interplay between well-separated blue and red bands in emission spectra. This allows constructing the exceptionally contrasted images of cellular dynamics. Moreover, the application of probes with increased affinity toward biological membranes allowed detecting the differences in dynamics between the plasma membrane and intracellular membrane structures. Such λ-ratiometric microviscosity imaging was extended for mapping the living tissues and observing their inflammation-dependent changes.

Leukocyte-mimicking Pluronic-lipid nanovesicle hybrids inhibit the growth and metastasis of breast cancer.

Breast cancer is a severe threat to the health of women, and the metastasis of tumor cells leads to high mortality in female patients. Evidence shows that leukocytes are recruited by breast tumors through adhesion to inflammatory endothelial cells as well as tumor cells. Moreover, it is known that Pluronic P123 is effective in the reduction of matrix metalloproteinases (MMPs), which play a key role in the degradation of the extracellular matrix (ECM), therefore helping tumor cells to escape from the primary site. Inspired by these mechanisms, we established a leukocyte-mimicking Pluronic-lipid nanovesicle hybrid (LPL) through integrating the membrane proteins extracted from leukocytes with membrane-like vesicles, with Pluronic P123 hybridized in the lipid bilayer, while paclitaxel (PTX) was selected as the model drug. The hybrid vesicles were perfectly incorporated with the leukocyte membrane proteins, and no disruption to the lipid membrane was caused by P123, with the bio-targeting ability of leukocytes and the MMP-9-downregulation effect of P123 fully preserved in LPL. LPL exhibited enhanced cellular uptake and anti-metastasis efficacy in in vitro assays, while significant tumor targeting capabilities were also found through biodistribution assays. Moreover, the in vivo therapeutic effects of PTX-loaded LPL (PTX-LPL) were observed, with an 80.84% inhibition rate of tumor growth and a 10.62% metastatic rate of tumor foci in lung tissue. Furthermore, the amounts of MMP-9 and neutrophils in the tumor as well as in the lung were greatly reduced with PTX-LPL. In summary, LPL may have potential applications in metastatic breast cancer therapy.

Enhanced organic-inorganic heterojunction of polypyrrole@Bi2WO6: Fabrication and application for sensitive photoelectrochemical immunoassay of creatine kinase-MB.

In this report, enhanced organic-inorganic heterojunction of polypyrrole@Bi2WO6 was fabricated and applied for sensitive photoelectrochemical (PEC) immunoassay of creatine kinase-MB (CK-MB). Specifically, heterostructured polypyrrole@Bi2WO6 photoelectrode was prepared and sandwich immunorecognition were integrated for the CK-MB immunoassay. In the detection, with the aid of alkaline phosphate (ALP)-induced biocatalytic precipitation (BCP), the precipitation-dependent suppression of the photocurrent can be recorded due to the impediment of the interfacial mass and electron transfer. On the basis of target-controlled BCP formation, a novel PEC immunoassay could be developed for the sensitive and specific CK-MB detection. This work manifested the great potential of polypyrrole@Bi2WO6 heterojunction as a novel platform for PEC bioanalysis development and also a PEC method for CK-MB detection. This work is expected to stimulate more interest in the design and implementation of numerous other organic-inorganic heterojunction for advanced PEC bioanalysis development.

A carbohydrate mimetic peptide modified size-shrinkable micelle nanocluster for anti-tumor targeting and penetrating drug delivery.

PURPOSE: To deliver the chemotherapeutics through the nanoparticles, the delivery system should accumulate at the tumor site first and then penetrate through the interstitium into the interior. The specific tumor-targeting pathway mediated via the receptor-ligand binding could achieve the desirable accumulation of nanoparticles, and the nanoparticles with smaller sizes were required for penetration. METHODS AND MATERIALS: We constructed a size-shrinkable nanocluster modified with a tumor-targeting motif IF-7 (IF-7-MNC) based on a pH-sensitive framework which could be disintegrated in an acid environment to release the micelles aggregated inside. The micelles were constructed by amphiphilic block copolymers PEG-PLA to encapsulate paclitaxel (PTX), while the cross-linked framework consisting of TPGS-PEI was used as a net to gather and release micelles. This nanoplatform could specifically bind with the tumor receptor Annexin A1 through the ligand IF-7 and then shrunk into small micelles with a desirable size for penetration. CONCLUSION: IF-7-MNC of 112.27±6.81 nm could shrink into micelles in PBS (0.01 M, pH 5.0) with sizes of 14.89±0.32 nm. The cellular-uptake results showed that IF-7-MNC could be significantly internalized by A549 cells and HUVEC cells, while the penetration of IF-7-MNC could be more prominent into the 3D-tumor spheroids compared with that of MNC. The biodistribution results displayed that the fluorescence of IF-7-MNC in the tumor site at 24 hrs was 4.5-fold stronger than that of MNC. The results of anti-tumor growth demonstrated that IF-7-MNC was more favorable for the tumor therapy than MNC, where the inhibitory rate of tumor growth was 88.29% in the PTX-loaded IF-7-MNC (IF-7-PMNC) treated group, significantly greater than PMNC treatment group (p<0.05).

USP6 gene rearrangement differentiates primary paranasal sinus solid aneurysmal bone cyst from other giant cell-rich lesions: report of a rare case.

Aneurysmal bone cysts (ABCs) mostly occur in the metaphysis of long bones. Primary paranasal ABCs are extremely rare, and most reported cases reveal typical histopathological features including cystic space with fibrous septa and hemorrhage. Solid-variant ABCs or solid ABCs lacking cyst formation may be histologically indistinguishable from giant cell reparative granulomas, giant cell tumor of bone, and brown tumor. Here we report the case of a 24-year-old woman with a paranasal mass diagnosed as USP6-rearranged solid ABC, mimicking giant cell reparative granuloma, giant cell tumor of bone, and brown tumor. For paranasal sinus bone or soft tissue tumors containing numerous giant cells, molecular analysis including the USP6 gene may serve as a useful diagnostic tool to distinguish solid ABCs from other giant cell-rich lesions.