Dirichlet Process Mixture Models with Shrinkage Prior

We propose Dirichlet process mixture (DPM) models for prediction and cluster-wise variable selection, based on three choices of shrinkage baseline prior distributions for the linear regression coefficients, namely, conditional Laplace prior, Horseshoe prior and Normal-Gamma prior. We show in a simulation study that each of the three proposed DPM models tends to outperform the standard DPM model based on the non-shrinkage normal prior, in terms of predictive, variable selection, and clustering accuracy. This is especially true for the Horseshoe model and when the number of covariates exceeds the within-cluster sample size. Real data sets are analyzed to illustrate the proposed modeling methodology, where all proposed DPM models again attained better predictive accuracy

Exploring the potential of polypeptide–polypeptoide hybrid nanogels for mucosal delivery

Amphiphilic nanoparticles with high drug loading capacity and mucus penetration properties are attractive for the delivery of potent hydrophobic drugs across the mucosal barrier in tumor therapy. In this study we report a facile strategy towards biocompatible and tumour microenvironment responsive nanogels, capable of controlling the mucosal delivery and release of a model dye. Polypeptide–polypeptoide hybrid nanogels were obtained by the chain extension of corona-forming poly(sarcosine) with N-carboxyanhydrides (NCA) of phenylalanine and cystine as a core crosslinker. The nanogels exhibited a suitable size range of around 100 nm and a spherical morphology as monitored by dynamic light scattering (DLS), transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). They further showed a reduction-responsive behaviour through the cleavage of the cystine disulfide core crosslinks by glutathione at concentrations present in the intracellular environment as well as a lack of cytotoxicity against both cancerous and non-cancerous cell lines. Lead nanogels facilitated an enhanced transport of a model hydrophobic dye across artificial mucus compared to the dye alone with a reduction sensitive release in the presence of glutathione. This work provides a facile strategy for the synthesis of responsive nanomedicines in anti-cancer therapy where mucosal barriers have to be overcome. </p

Solvothermal-Etching Process Induced Ti-Doped Fe₂O₃ Thin Film with Low Turn-On Voltage for Water Splitting

In this work, a thinning process of hematite film accompanied by simultaneous titanium (Ti) doping has been demonstrated. Ti⁴⁺ ion was incorporated into ultrathin Fe₂O₃ film by solvothermally etching a hematite film fabricated on titanium nanorod array substrate. As a consequence, the onset potential (<i>V</i>_on) of oxygen evolution reaction for final ultrathin Ti-doped Fe₂O₃ film shifted toward cathodic substantially, a very low <i>V</i>_on of 0.48 V_RHE was realized, approximately 0.53 V cathodic shift of the hematite film. Working mechanisms were investigated from both kinetic and thermodynamic ways. The ultrathin Ti-doped Fe₂O₃ film exhibited reduced Tafel slope and higher generated photovoltage than the pristine Fe₂O₃ electrode. Moreover, the highly doped Fe₂O₃ resulted in significant reduction of charge-transfer resistance at the Fe₂O₃∥electrolyte interface. The drastic cathodic-shift <i>V</i>_on is believed to be a result of combined factors including thermodynamic contribution, improved surface reaction kinetics, as well as facilitated charge transfer across bulk and interface

Ligand-Exchange Assisted Formation of Au/TiO₂ Schottky Contact for Visible-Light Photocatalysis

Plasmonic noble metal nanoparticles have emerged as a promising material in sensitizing wide-bandgap semiconductors for visible-light photocatalysis. Conventional methods in constructing such heterocatalysts suffer from either poor control over the size of the metal nanoparticles or inefficient charge transfer through the metal/semiconductor interface, which limit their photocatalytic activity. To solve this problem, in this work we construct Au/TiO₂ photocatalysts by depositing presynthesized colloidal Au nanoparticles with well-controlled sizes to TiO₂ nanocrystals and then removing capping ligands on the Au surface through a delicately designed ligand-exchange method, which leads to close Au/TiO₂ Schottky contact after a mild annealing process. Benefiting from this unique synthesis strategy, the obtained photocatalysts show superior activity to conventionally prepared photocatalysts in dye decomposition and water-reduction hydrogen production under visible-light illumination. This study not only opens up new opportunities in designing photoactive materials with high stability and enhanced performance for solar energy conversion but also provides a potential solution for the well-recognized challenge in cleaning capping ligands from the surface of colloidal catalyst nanoparticles

Recent advances of tumor microenvironment-responsive nanomedicines-energized combined phototherapy of cancers

Photodynamic therapy (PDT) has emerged as a powerful tumor treatment tool due to its advantages including minimal invasiveness, high selectivity and thus dampened side effects. On the other side, the efficacy of PDT is severely frustrated by the limited oxygen level in tumors, thus promoting its combination with other therapies, particularly photothermal therapy (PTT) for bolstered tumor treatment outcomes. Meanwhile, nanomedicines that could respond to various stimuli in the tumor microenvironment (TME) provide tremendous benefits for combined phototherapy with efficient hypoxia relief, tailorable drug release and activation, improved cellular uptake and intratumoral penetration of nanocarriers, etc. In this review, we will introduce the merits of combining PTT with PDT, summarize the recent important progress of combined phototherapies and their combinations with the dominant tumor treatment regimen, chemotherapy based on smart nanomedicines sensitive to various TME stimuli with a focus on their sophisticated designs, and discuss the challenges and future developments of nanomedicine-mediated combined phototherapies. </p

Steerable Microneedles Enabling Deep Delivery of Photosensitizers and CRISPR/Cas9 Systems for Effective Combination Cancer Therapy

Although gene therapy has shown prospects in treating triple-negative breast cancer, it is insufficient to treat such a malignant tumor. Herein, nanoparticles (NPs)-embedded dissolving microneedles (IR780-PL/pFBXO44@MNs) with steerable and flectional property were developed to achieve the codelivery of FBXO44-targeted CRISPR/Cas9 plasmids (pFBXO44) and hydrophobic photosensitizers. For improved NP penetration in tumor tissue, collagenase@MNs were preapplied to degrade the tumor matrix. Under light irradiation, IR780 exhibited remarkable phototherapy, while the escape efficiency of NPs from lysosomes was improved. pFBXO44 was subsequently released in tumor cell cytoplasm via reducing the disulfide bonds of NPs, which could specifically knock out the FBXO44 gene to inhibit the migration and invasion of tumor cells. As a result, tumor cells were eradicated, and lung metastasis was effectively suppressed. This micelle-incorporated microneedle platform broadens the potential of combining gene editing and photo synergistic cancer therapy

Recent advances of tumor microenvironment-responsive nanomedicines-energized combined phototherapy of cancers

Photodynamic therapy (PDT) has emerged as a powerful tumor treatment tool due to its advantages including minimal invasiveness, high selectivity and thus dampened side effects. On the other side, the efficacy of PDT is severely frustrated by the limited oxygen level in tumors, thus promoting its combination with other therapies, particularly photothermal therapy (PTT) for bolstered tumor treatment outcomes. Meanwhile, nanomedicines that could respond to various stimuli in the tumor microenvironment (TME) provide tremendous benefits for combined phototherapy with efficient hypoxia relief, tailorable drug release and activation, improved cellular uptake and intratumoral penetration of nanocarriers, etc. In this review, we will introduce the merits of combining PTT with PDT, summarize the recent important progress of combined phototherapies and their combinations with the dominant tumor treatment regimen, chemotherapy based on smart nanomedicines sensitive to various TME stimuli with a focus on their sophisticated designs, and discuss the challenges and future developments of nanomedicine-mediated combined phototherapies. </p

Nanoconfined β‑Sheets Mechanically Reinforce the Supra-Biomolecular Network of Robust Squid Sucker Ring Teeth

The predatory efficiency of squid and cuttlefish (superorder Decapodiformes) is enhanced by robust Sucker Ring Teeth (SRT) that perform grappling functions during prey capture. Here, we show that SRT are composed entirely of related structural “suckerin” proteins whose modular designs enable the formation of nanoconfined β-sheet-reinforced polymer networks. Thirty-seven previously undiscovered suckerins were identified from transcriptomes assembled from three distantly related decapodiform cephalopods. Similarity in modular sequence design and exon–intron architecture suggests that suckerins are encoded by a multigene family. Phylogenetic analysis supports this view, revealing that suckerin genes originated in a common ancestor ∼350 MYa and indicating that nanoconfined β-sheet reinforcement is an ancient strategy to create robust bulk biomaterials. X-ray diffraction, nanomechanical, and micro-Raman spectroscopy measurements confirm that the modular design of the suckerins facilitates the formation of β-sheets of precise nanoscale dimensions and enables their assembly into structurally robust supramolecular networks stabilized by cooperative hydrogen bonding. The suckerin gene family has likely played a key role in the evolutionary success of decapodiform cephalopods and provides a large molecular toolbox for biomimetic materials engineering

Biomimetic Production of Silk-Like Recombinant Squid Sucker Ring Teeth Proteins

The sucker ring teeth (SRT) of Humboldt squid exhibit mechanical properties that rival those of robust engineered synthetic polymers. Remarkably, these properties are achieved without a mineral phase or covalent cross-links. Instead, SRT are exclusively made of silk-like proteins called “suckerins”, which assemble into nanoconfined β-sheet reinforced supramolecular networks. In this study, three streamlined strategies for full-length recombinant suckerin protein production and purification were developed. Recombinant suckerin exhibited high solubility and colloidal stability in aqueous-based solvents. In addition, the colloidal suspensions exhibited a concentration-dependent conformational switch, from random coil to β-sheet enriched structures. Our results demonstrate that recombinant suckerin can be produced in a facile manner in E. coli and processed from mild aqueous solutions into materials enriched in β-sheets. We suggest that recombinant suckerin-based materials offer potential for a range of biomedical and engineering applications