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Density estimation plays a fundamental role in many areas of statistics and machine learning. Parametric, nonparametric, and semiparametric density estimation methods have been proposed in the literature. Semiparametric density models are flexible in incorporating domain knowledge and uncertainty regarding the shape of the density function. Existing literature on semiparametric density models is scattered and lacks a systematic framework. In this article, we consider a unified framework based on reproducing kernel Hilbert space for modeling, estimation, computation, and theory. We propose general semiparametric density models for both a single sample and multiple samples which include many existing semiparametric density models as special cases. We develop penalized likelihood based estimation methods and computational methods under different situations. We establish joint consistency and derive convergence rates of the proposed estimators for both finite dimensional Euclidean parameters and an infinite-dimensional functional parameter. We validate our estimation methods empirically through simulations and an application. for this article are available online. [ABSTRACT FROM AUTHOR]

This paper deals with a conjecture posed by Abbas Salemi in 2011 (Banach J. Math. Anal.), claiming that for the spectrum of every bounded linear operator on a separable Hilbert space there exists an estimable total decomposition. We partially solve this problem, in the sense that, for the normal operator, there exists an estimable decomposition, under approximately unitary equivalence. [ABSTRACT FROM AUTHOR]

Despite being highly recognized as an antitumor candidate due to its high potency in binding to DNA topoisomerase I and inhibiting of DNA relegation, full clinical application of camptothecin is unfortunately hampered by its poor solubility in aqueous medium and by the adverse effects caused by its hydrolyzed product under physiological conditions. In an attempt to increase its effective solubility, nanomicelles formed through self-assembly of copolymers by polymer-drug conjugate or by physical envelopment have recently been established to improve the efficacy of many drugs. This review provides the most up-to-date information available relating novel nanomicelles technology to the improvement and realization of the full potential of camptothecin. In particular, physicochemical and biological properties of camptothecin and its derivatives, the controlled factors of micelle formation, the techniques of drug encapsulation, and the structure-properties of nanomicelles are elucidated and discussed. Undoubtedly, polymer nanomicelle carriers can be selectively delivered to tumors via the enhanced permeability and retention effect. Moreover, micelles with smart functions such as stimulus-responsive and specific drug targeting may enhance the activity of potent bioactive compounds, facilitating their clinical applications. [ABSTRACT FROM PUBLISHER]

α-Chymotrypsin immobilized on super paramagnetic nanogels covered with carboxyl groups, exhibited high stereoselectivity in kinetic resolution of racemic phenylalanine in toluene/water biphasic system, and even improved reusability over its parent free enzyme. The results also showed that the addition of ionic liquid to water phase could enhance the stereoselectivity of the immobilized enzyme to a certain extent while the conversion yield decreased. The long-term stability allows the supported enzyme with nano-scaled dimension to use in continuous chiral resolution reaction, which opens a new horizon for enzymatic chiral resolution in large-scale production. [ABSTRACT FROM AUTHOR]

Interpenetrating polymer networks (IPN) coating were synthesized from castor oil-based polyurethane (PU), methyl acrylate (MA), and coated onto the surface of regenerated cellulose (RC) film to obtain biodegradable water-resistant films. The tensile strength (σb), water resistance (R), water vapor permeability (P) percent light transmittance (T) and biodegradation rate of the coated films cured at 80°C for 5 minutes changed with the content of methyl acrylate in the coating. The introduction of methyl acrylate can enhance the water resistance, but reduce the biodegradation rate of the films. The most excellent values such as σb, 444 kg cm-2 in wet state, R, 0.59, P, 3.2 × 10-2 mg cm-2 day-1 were obtained at 30 wt% methyl acrylate in the coating. The interfacial bonding of the coated film was investigated with infrared spectroscopy (IR), ultraviolet spectroscopy (UV), transmission electron microscopy (TEM), electron probe microanalysis (EPMA), and differential thermal analysis (DTA). The results showed that the coated films exist strong interfacial bonding caused by covalent and hydrogen bonds between the RC film and the coating. Furthermore, while there was formation of IPN in the coating, the PU prepolymer in the coating penetrated into the RC film and crosslinked with the cellulose formed another semi-IPN. [ABSTRACT FROM AUTHOR]

H2O2 and temperature dual-responsive supramolecular micelles were prepared from β-cyclodextrin-poly(N-isopropylacrylamide) (β-CD-PNIPAM) star polymer and ferrocene-modified polyethylene glycol (Fc-mPEG) due to the host–guest recognitions between cyclodextrin and ferrocene. The micelles with the size of about 100 nm were comprised of hydrophobic PNIPAM as the core and hydrophilic mPEG as the shell at the temperature above LCST. The supramolecular micelles exhibited reversible temperature and redox on–off switch feature. The hydrophobic micelles core and cavity of β-CD can effectively encapsulate doxorubicin (DOX) with the drug-loading content of 37.23% and entrapment efficiency of 74.45%. The drug-loaded micelles exhibited higher anti-cancer activity than free drugs. The ferrocene group was oxidized into ferrocene ions when H2O2 was added, resulting in the dissociation of supramolecular micelles and acceleration of drug release. Release kinetics of DOX conforms to oxidation controlled mechanism with H2O2 and Fickian diffusion-controlled mechanism with temperature. [ABSTRACT FROM AUTHOR]

A novel pH-sensitive polymeric prodrug of camptothecin (CPT) by polymerizing γ-camptothecin-glutamate N-carboxyanhydride (Glu (CPT)-NCA) on boronate ester-linked poly (ethyleneglycol) (PEG) directly via the amine-initiated ring open polymerization (ROP) has been developed. The resulting amphiphilic prodrug (mPEG-BC-PGluCPT) could self-assemble into nanoparticles and encapsulate doxorubicin (Dox) simultaneously in aqueous solution for dual-drug delivery. The formation of polymeric prodrug micelles (mPEG-BC@PGluCPT) was confirmed by the measurements of critical aggregation concentration (CAC), particle size, and morphology observations. The mPEG-BC@PGluCPT micelles were colloidally stable in solutions for two weeks. Polymeric prodrug micelles mPEG-BC@PGluCPT and Dox-loaded micelles mPEG-BC@PGluCPT⋅Dox showed sustained drug release profiles over 48 h. As expected, drug release was accelerated by the decreasement of pH value from 7.4 to 6.0, which demonstrated pH-dependent manner of drug release. Additionally, it was found that cellular uptake of mPEG-BC@PGluCPT⋅Dox micelles on HepG2 cells was higher than that on HL-7702 cells, especially in culture medium at pH 6.0. The enhanced cellular uptake of mPEG-BC@PGluCPT⋅Dox micelles under acidic condition on HepG2 cells resulted in the higher cytotoxicity of mPEG-BC@PGluCPT⋅Dox micelles at acidic pH than that at pH 7.4. [ABSTRACT FROM PUBLISHER]

The objective of this study was to prepare the CHS-mPEG/CHS-dFdC nanoformulation could be administrated through intravenous injection in nude mice. Particularly, CHS-mPEG was selected to co-assemble with CHS-dFdC to improve the prodrug concentration and enhance the stability of nanoformulation. The nanoformulation could be prepared by codissolution–coprecipitation. All of the nanoformulations kept stable in PBS at 4 °C or simulative human plasma at 37 °C. As molar ratios of CHS-mPEG1900/CHS-dFdC increased from 0.1/1 to 2/1, the weight concentration of CHS-dFdC increased from 2.5 to 15 mg/mL. It was found the optimal CHS-mPEG1900/CHS-dFdC nanoformulation displayed controlled drug release in simulative lysosome condition. The amount of released dFdC reached up to 90% within 10 h. It also exhibited enhanced cellular uptake ability, 7-folds higher than that of dFdC during 2.5 h incubation. And it showed superior cytotoxicity resulted from the enhanced cellular uptake ability on BxPC-3 cells. [ABSTRACT FROM PUBLISHER]

T cell Ig mucin-3 (Tim-3), an immune checkpoint inhibitor, shows therapeutic potential. However, the molecular mechanism by which Tim-3 regulates immune responses remains to be determined. In particular, very little is known about how Tim-3 works in innate immune cells. Here, we demonstrated that Tim-3 is involved in the development of tumor-promoting M2 macrophages in colon cancer. Manipulation of the Tim-3 pathway significantly affected the polarization status of intestinal macrophages and the progression of colon cancer. The Tim-3 signaling pathway in macrophages was explored using microarray, co-immunoprecipitation, gene mutation, and high-content analysis. For the first time, we demonstrated that Tim-3 polarizes macrophages by directly binding to STAT1 via residue Y256 and Y263 in its intracellular tail and inhibiting the STAT1-miR-155-SOCS1 signaling axis. We also identified a new signaling adaptor of Tim-3 in macrophages, and, by modulating the Tim-3 pathway, demonstrated the feasibility of altering macrophage polarization as a potential tool for treating this kind of disease. [ABSTRACT FROM PUBLISHER]