Polyplex Micelle with pH-Responsive PEG Detachment and Functional Tetraphenylene Incorporation to Promote Systemic Gene Expression.

Tetraphenylene (TPE), characterized as a lipophilic and aggregation-induced-emissive fluorophore, was used to incorporate into an electrostatic self-assembled polyethylenimine-poly(ethylene glycol) (PEI-PEG)/plasmid DNA (pDNA) complexed micelle. The hydrophobic character of TPE appeared to drive a higher degree of condensation of the pDNA payload, which consequently resulted in not only strengthened colloidal stability of the constructed polyplex micelle but also improved biocompatibility by virtue of the elevated PEG crowdedness owing to the TPE-induced collapse of pDNA. These beneficial consequences potentially permitted a larger number of polyplex micelles to be internalized into the cells. PEG segments were designed to enable selective detachment from polyplex micelles in acidic milieu, e.g., the tumor microenvironment, and intracellular endosome compartment, based on the strategic arrangement of acid-responsive cleavable linkage between PEG and PEI. Upon PEG detachment, the exposure of cationic PEI/TPE polyplex was allowed to directly interact with the cell membrane, endosome membrane, and charged intracellular species, thus promoting cell internalization, endosome escape, and the release of the pDNA payload. Of note, this association of cationic PEI/TPE polyplex with the endosomal membrane could be further facilitated with the aid of lipophilic TPE, thereby eliciting pronounced destabilization potency to the endosome membrane and exerting an endosomal escape function. Eventually, the proposed system of these facile strategies, including responsive PEG detachment and functional TPE incorporation, was proven to provide efficient gene expression in the targeted tumors with an appreciable safety profile via systemic administration.

A ratiometric fluorescent probe for sensing hydrogen peroxide based on a hemicyanine-naphthol fluorophore.

The synthesis, properties and applications of a water-soluble boronate-functioned hemicyanine-naphthol hybrid as a novel ratiometric fluorescent sensor for hydrogen peroxide are presented. The dye displayed remarkable a colour change from pale orange (λ(em) = 590 nm) to pink (λ(em) = 690 nm) in the presence of H2O2, which could be rationalized by the chemoselective H2O2-mediated transformation of arylboronate to phenolate with high selectivity and a fast response (within 2 min). A good linear relationship (R(2) = 0.9951) was obtained with the H2O2 concentration ranging from 0 to 25 µM, with a limit of detection of 0.09 µM according to the signal-to-noise ratio (S/N = 3). The advantages of this fluorophore include easy modification, excellent aqueous solubility and superior photostability, and it has been applied to the detection of trace amounts of hydrogen peroxide in water samples.

A single backbone amide modification method to achieve single site-specific chemical protein conjugation.

Efficient and precise chemical protein modification methods are highly sought after in biotechnology. However, chemically distinguishing a single site within a large protein is challenging. This study introduces a Copper Assisted Sequence-specific Conjugation Tag (CAST) method, enabling rapid (second order rate 8.1 M-1s-1) and site-specific chemical modification of the protein backbone with pinpoint accuracy. The versatility of this method is demonstrated through the preparation of antibody-drug conjugates, showcasing high plasma stability and potent efficacy in both in vitro and in vivo settings. Thus, CAST emerges as an efficient and quantitative approach for attaching payloads to large, native proteins.

Copper assisted sequence-specific chemical protein conjugation at a single backbone amide.

Direct, site-specific methods of protein functionalization are highly desirable for biotechnology. However, such methods are challenging due to the difficulty of chemically differentiating a single site within a large protein. Herein, we propose "metal binding targeting" strategy and develop a Copper Assisted Sequence-specific conjugation Tag (CAST) method to achieve rapid (second order rate 8.1 M-1 s-1), site-specific protein backbone chemical modification with pinpoint accuracy. We demonstrate the versatility of CAST conjugation by preparing various on-demand modified recombinant proteins, including a homogeneous antibody-drug conjugate with high plasma stability and potent efficacy in vitro and in vivo. Thus, CAST provides an efficient and quantitative method to site-specifically attach payloads on large, native proteins.

Synthesis and Photocatalytic Sterilization Performance of SA/TiO2.

The photocatalyst sorbic acid (SA)/titanium dioxide (TiO2) was successfully synthesized by sol-gel method and characterized. The composite exhibited regularly spherical particles with the size of 50 nm and the specific surface area of 90.3 m2 g-1, furthermore, it showed mesoporous structure and significantly improved dispersion. SA was grafted on TiO2 surface by -COOTi and TiO2 existed as pure anatase phase in the composite. The addition of SA made the band gap of TiO2 increased from 3.03 to 3.35 eV, which indicting that the composite exhibited a strong response to the ultraviolet light. The optimum preparation parameters of the catalyst were as follows: n(Ti):n(SA) = 1:0.05, ethanol 60 mL, glacial acetic acid 40 mL, hydrothermal temperature 180 °C, hydrothermal time 12 h. The composite could reach the 4.31 log reduction of E. coli, with the optimum catalyst dosage of 0.7 g L-1, irradiated by UV light for 60 min. SA/TiO2 was an environmentally friendly, non-toxic and safe sterilized nanocomposite material appropriate for future bactericidal applications, providing a new way to effectively increase the dispersion of TiO2 particles to achieve superior photocatalytic sterilization efficiency.

Deep Subspace Clustering.

In this article, we propose a deep extension of sparse subspace clustering, termed deep subspace clustering with L1-norm (DSC-L1). Regularized by the unit sphere distribution assumption for the learned deep features, DSC-L1 can infer a new data affinity matrix by simultaneously satisfying the sparsity principle of SSC and the nonlinearity given by neural networks. One of the appealing advantages brought by DSC-L1 is that when original real-world data do not meet the class-specific linear subspace distribution assumption, DSC-L1 can employ neural networks to make the assumption valid with its nonlinear transformations. Moreover, we prove that our neural network could sufficiently approximate the minimizer under mild conditions. To the best of our knowledge, this could be one of the first deep-learning-based subspace clustering methods. Extensive experiments are conducted on four real-world data sets to show that the proposed method is significantly superior to 17 existing methods for subspace clustering on handcrafted features and raw data.

Arylation of benzyl amines with aromatic nitriles.

In the past years, the activations of aromatic nitriles for radical arylations under photoirradiation have been developed. We here report the first example of radical arylations using aromatic nitriles without the assistance of photoirradiation. Importantly, with this method, the direct arylation of C(sp3)-H in benzyl amines provided a practical method for the synthesis of diarylmethylamines without the use of precious transition metal catalysts.

Photoinduced, Copper-Promoted Regio- and Stereoselective Decarboxylative Alkylation of α,ß-Unsaturated Acids with Alkyl Iodides.

The first example of UV light-induced, copper-catalyzed regio- and stereoselective decarboxylative coupling of α,ß-unsaturated acids with alkyl iodides was reported. Under standard conditions, the 1°, 2°, and 3° alkyl iodides proceeded smoothly with the E-selective alkenes obtained in uniformly good yields and high stereoselectivities.

A ratiometric strategy to detect hydrogen sulfide with a gold nanoclusters based fluorescent probe.

The emergence of ratiometric fluorescent probes have offered more convincing results to the bioanalytical field of research. In particular, using nanoparticles as scaffolds for the construction of ratiometric systems has received increasing attention. In this work, a novel design strategy was implemented for ratiometric sensing of hydrogen sulfide (H2S), in which bovine serum albumin templated gold nanoclusters (BSA-AuNCs) was served as the internal reference fluorophore and HSip-1, a azamacrocyclic Cu(2+) complex based fluorescent probe toward H2S, acted as both the signal indicator and specific recognition element. Under single wavelength excitation, the nanohybrid probe HSip-1@AuNC emitted dual fluorescence at 519 and 632nm, coming from HSip-1 and AuNCs respectively. The effective fluorescence response of organic dye to H2S and constant fluorescence of AuNCs enabled the proposed HSip-1@AuNC to achieve the ratiometric measurement with a dynamic linear range of 7-100µM and a detection limit of 0.73µM. This probe also possesses high selectivity, stability against pH change and continuously light illumination. In addition, we provided HSip-1@AuNC as a valuable tool to analyze sulfides in serum samples and perfect recoveries verified its potential in biological applications.

[Preparation of ß-In2S3 and Catalytic Degradation of Oxytetracycline Under Solar Light Irradiation].

The preparation of beta-In2S3 nanomaterial was carried out by reacting In (NO3)3 with thioacetamide through hydrothermal process at 120 degrees C for 12 h. The size and morphology of In2S3 were characterized by the scanning electron microscope (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) while the degradation efficiency was evaluated by the photocatalytic degradation of oxytetracycline under natural sunlight. The results revealed that beta-In2S3 nanoparticles are made up of nanosheets with a length of 15-30 nm and with high efficient catalytic performance, in which more than 98% of the initial oxytetracycline (30 mg x L(-1)) was degraded in 4 h. Furthermore, the prepared pG-In2 S3 can be recycled and kept efficient catalytic performance above 85% even after reusing for four times, which reflected the good stability and relative photocatalytic activity of In2S3.