A light-activated polymer with excellent serum tolerance for intracellular protein delivery.

The design of efficient materials for intracellular protein delivery has attracted great interest in recent years; however, most current materials for this purpose are limited by poor serum stability due to the early release of cargoes triggered by abundant serum proteins. Here, we propose a light-activated crosslinking (LAC) strategy to prepare efficient polymers with excellent serum tolerance for intracellular protein delivery. A cationic dendrimer engineered with photoactivatable O-nitrobenzene moieties co-assembles with cargo proteins via ionic interactions, followed by light activation to yield aldehyde groups on the dendrimer and the formation of imine bonds with cargo proteins. The light-activated complexes show high stability in buffer and serum solutions, but dis-assemble under low pH conditions. As a result, the polymer successfully delivers cargo proteins green fluorescent protein and ß-galactosidase into cells with maintained bioactivity even in the presence of 50% serum. The LAC strategy proposed in this study provides a new insight to improve the serum stability of polymers for intracellular protein delivery.

A Method for Autonomous Generation of High-Precision Time Scales for Navigation Constellations.

The time maintenance accuracy of the navigation constellation determines the user positioning and timing performance. Especially in autonomous operation scenarios, the performance of navigation constellation maintenance time directly affects the duration of constellation autonomous navigation. Among them, the frequency stability of the atomic clock onboard the navigation satellite is a key factor. In order to further improve the stability of the navigation constellation time-frequency system, combined with the development of high-precision inter-satellite link measurement technology, the idea of constructing constellation-level synthetic atomic time has gradually become the development trend of major GNSS systems. This paper gives a navigation constellation time scale generation framework, and designs an improved Kalman plus weights (KPW) time scale algorithm and time-frequency steer algorithm that integrates genetic algorithms. Finally, a 30-day autonomous timekeeping simulation was carried out using the GPS precision clock data provided by CODE, when the sampling interval is 300 s, the Allan deviation of the output time scale is 5.73 × 10-14, a 71% improvement compared with the traditional KPW time scale algorithm; when the sampling interval is 1 day, the Allan deviation is 9.17 × 10-15; when the sampling interval is 1 × 106 s, the Allan deviation is 8.87 × 10-16, a 94% improvement compared with the traditional KPW time scale algorithm. The constellation-level high-precision time scale generation technology proposed in this paper can significantly improve the stability performance of navigation constellation autonomous timekeeping.

Boronate Building Blocks for Intracellular Protein Delivery.

Intracellular protein delivery plays a critical role in the development of biotherapeutics and biotechnologies, yet it is hampered by a number of factors including protein binding, cellular uptake, endosomal escape, and protein release. Boronate building blocks, which are frequently employed to create effective protein delivery systems, have shown significant promise in overcoming these limitations thanks to their versatile reactivities and stimuli-responsive property. Boronate ligands transport conjugated proteins into the cytosol via receptor-mediated endocytosis by forming reversible boronate disaster bonds with carbohydrates like sialic acid on the cell surface. Additionally, boronate modification gives cargo proteins extra binding sites for forming complexes with nanocarriers. After internalization, boronate-tagged proteins are released from their carriers in response to endolysosomal acidity, reactive oxygen species, and adenosine triphosphate, and sometimes transport into the nucleus via the importin α/ß pathway. Besides, boronate ligands are directly decorated on nanocarriers to enhance their binding affinity to native proteins via nitrogen-boron coordination. Owing to these promising features, various supramolecular and dynamic nanoassemblies are constructed based on boronate building blocks for efficient intracellular protein delivery.

Amphipathic poly-ß-peptides for intracellular protein delivery.

A series of amphipathic poly-ß-peptides are designed for intracellular protein delivery. The poly-ß-peptides with higher molecular weight and hydrophobic contents exhibit higher protein loading and superior delivery efficiency. The lead material efficiently delivers proteins into cells with reserved bioactivity.

Transition-Metal-Free Synthesis of Polyfunctional Triarylmethanes and 1,1-Diarylalkanes by Sequential Cross-Coupling of Benzal Diacetates with Organozinc Reagents.

A variety of functionalized triarylmethane and 1,1-diarylalkane derivatives were prepared via a transition-metal-free, one-pot and two-step procedure, involving the reaction of various benzal diacetates with organozinc reagents. A sequential cross-coupling is enabled by changing the solvent from THF to toluene, and a two-step SN 1-type mechanism was proposed and evidenced by experimental studies. The synthetic utility of the method is further demonstrated by the synthesis of several biologically relevant molecules, such as an anti-tuberculosis agent, an anti-breast cancer agent, a precursor of a sphingosine-1-phosphate (S1P) receptor modulator, and a FLAP inhibitor.

Chromium(II)-Catalyzed Diastereoselective and Chemoselective Csp2-Csp3 Cross-Couplings Using Organomagnesium Reagents.

A simple protocol for performing chromium-catalyzed highly diastereoselective alkylations of arylmagnesium halides with cyclohexyl iodides at ambient temperature has been developed. Furthermore, this ligand-free CrCl2 enables efficient electrophilic alkenylations of primary, secondary, and tetiary alkylmagnesium halides with readily available alkenyl acetates. Moreover, this chemoselective C-C coupling reaction with stereodefined alkenyl acetates proceeds in a stereoretentive fashion. A wide range of functional groups on alkyl iodides and alkenyl acetates are well tolerated, thus furnishing functionalized Csp2-Csp3 coupling products in good yields and high diastereoselectivity. Detailed mechanistic studies suggest that the in situ generated low-valent chromium(I) species might be the active catalyst for these Csp2-Csp3 cross-couplings.

Nanoparticle-Polymer Synergies in Nanocomposite Hydrogels: From Design to Application.

Hydrogels are an important class of soft materials with high water retention that exhibit intelligent and elastic properties and have promising applications in the fields of biomaterials, soft machines, and artificial tissue. However, the low mechanical strength and limited functions of traditional chemically cross-linked hydrogels restrict their further applications. Natural materials that consist of stiff and soft components exhibit high mechanical strength and functionality. Among artificial soft materials, nanocomposite hydrogels are analogous to these natural materials because of the synergistic effects of nanoparticle (NP) polymers in hydrogels construction. In this article, the structural design and properties of nanocomposite hydrogels are summarized. Furthermore, along with the development of nanocomposite hydrogel-based devices, the shaping and potential applications of hydrogel devices in recent years are highlighted. The influence of the interactions between NPs and polymers on the dispersion as well as the structural stability of nanocomposite hydrogels is discussed, and the novel stimuli-responsive properties induced by the synergies between functional NPs and polymeric networks are reviewed. Finally, recent progress in the preparation and applications of nanocomposite hydrogels is highlighted. Interest in this field is growing, and the future and prospects of nanocomposite hydrogels are also reviewed.