An Intrinsic Photothermal Supramolecular Hydrogel with Robust Mechanical Strength and NIR-Responsive Shape Memory.

Near-infrared (NIR)-triggered shape memory hydrogels with promising mechanical strength hold immense potential in the field of biomedical applications and soft actuators. However, the optical and mechanical properties of currently reported hydrogels usually suffer from limited solubility and dispersion of commonly used photothermal additives in hydrogels, thus restricting their practical implementations. Here,, a set of NIR-responsive shape memory hydrogels synthesized by polyaddition of diisocyanate-terminated poly(ethylene glycol), imidazolidinyl urea (IU), and p-benzoquinone dioxime (BQDO) is reported. The introduction of IU, a hydrogen bond reinforcing factor, significantly enhances the mechanical properties of the hydrogels, allowing for their tunable ranges of the ultimate tensile strength (0.4-2.5 MPa), elongation at break (210-450%), and Young's modulus (190-850 kPa). The unique hydrogels exhibit an intrinsic photothermal effect because of the covalently incorporated photothermal moiety (BQDO), and the photothermal supramolecular hydrogel shows controllable shape memory capabilities characterized by rapid recovery speed and high recovery ratio (>90%). This design provides new possibilities for applying shape memory hydrogels in the field of soft actuators.

Dynamic Thermosetting Resins with Synergistic Enhanced Strength and Toughness through Combination with Rigid and Soft Microdomains.

Preparation of materials that possess highly strong and tough properties simultaneously is a great challenge. Thermosetting resins as a type of widely used polymeric materials without synergistic strength and toughness limit their applications in some special fields. In this report, an effective strategy to prepare thermosetting resins with synergistic strength and toughness, is presented. In this method, the soft and rigid microspheres with dynamic hemiaminal bonds are fabricated first, followed by hot-pressing to crosslink at the interfaces. Specifically, the rigid or soft microspheres are prepared via precipitation polymerization. After hot-pressing, the resulting rigid-soft blending materials exhibit superior strength and toughness, simultaneously. As compared with the precursor rigid or soft materials, the toughness of the rigid-soft blending films (RSBFs) is improved to 240% and 2100%, respectively, while the strength is comparable to the rigid precursor. As compared with the traditional crushing, blending, and hot-pressing of rigid or soft materials to get the nonuniform materials, the strength and toughness of the RSBFs are improved to 168% and 255%, respectively. This approach holds significant promise for the fabrication of polymer thermosets with a unique combination of strength and toughness.

Hard-Soft Thermoset Alloy with Enhanced Toughness, Impact-Resistance, and Electric Conductivity via Interpenetrated Dynamic Crosslinked Interface.

Polymer alloys (PAs) are mixtures of two or more types of polymers to enhance the properties of polymeric materials. However, thermosets with crosslinked structures are immiscible and cannot be prepared PAs. Herein, two immiscible covalent adaptable networks containing phenoxy carbamate bonds are explored as the typical polymeric materials to prepare the hard-soft thermoset alloy (HSTA) by the interpenetrated dynamic crosslinked interface (IDCI) to enhance the toughness. Specifically, two types of polyurethane covalent adaptable networks with either high stiffness (thermoset) or extensibility (elastomer) are prepared, respectively. The granules of thermoset and elastomer are mixed and hot-pressed to prepare the HSTA. The HSTA shows improved mechanical properties with a toughness of 22.8 MJ m-3 which is 14 times higher than that of hard thermoset. In addition, the HSTA shows excellent impact-resistance property after 1000 punctures. Moreover, the obtained HSTA via addition of carbon nanotubes can significantly decrease the electric resistance over six orders of magnitudes as compared to the blending method, which is due to the distribution of the carbon nanotubes at the interfaces of the two networks.

Highly Tough and Reliable Poly(Amic Acid) with Ballistic Impact-Resistance through Modulation of Hydrogen Bonding Interactions.

Poly(amic acid) (PAA) materials as the precursor of polyimide generally show remarkably poor mechanical properties, thus limiting their application as the engineering plastics. In this study, it is demonstrated that the mechanical properties of PAA materials can be improved significantly for tens of folds with breaking strength >50 MPa, Young's modulus >400 MPa, and elongation at break >300% by incorporation of 20% (mol%) poly(propylene glycol) (PPO) soft segments. The optimization for suitable hard-soft composition with 20% PPO and the existence of various hydrogen bonds with different binding energies can dissipate energies efficiently, which simultaneously improve the material strength and toughness. In addition, PAA82 films exhibit excellent tolerance toward cyclic stretch, and have the capability to resist various harsh conditions including solar radiation testing (1 sun), heat (85 °C), alkalinity (pH 10), and acidity (pH 4) over one month. Noted that PAA82 films can be laminated with Kapton films, which show excellent resistance to ultrahigh (200 °C) and ultralow temperature (-196 °C). The laminated film also exhibits bulletproof property with a thickness of 6 mm. The strategy via modulation of hard-soft compositions and hydrogen bonds in PAA materials shows great potentials to improve the mechanical properties of polymeric materials.

Highly Stretchable, Tough, Resilient, and Antifatigue Hydrogels Based on Multiple Hydrogen Bonding Interactions Formed by Phenylalanine Derivatives.

Noncovalent cross-linked hydrogels with promising mechanical properties are on demand for applications in tissue engineering, flexible electronics, and actuators. However, integrating excellent mechanical properties with facile preparation for the design of hydrogen bond cross-linked hydrogels is still challenging. In this work, an advanced hydrogel was prepared from acrylamide and N-acryloyl phenylalanine by one-pot free-radical copolymerization. Owing to hydrophobicity-assisted multiple hydrogen bonding interactions among phenylalanine derivatives, the hydrogels exhibited fascinating mechanical behaviors: tensile strength of 0.35 MPa, elongation at break of 2100%, tearing energy of 1134 J/m2, and compression strength of 3.56 MPa. The hydrogels also showed robust elasticity and fatigue resistance, and the compression strength did not show any decline, even after 100 successive cycles, as well as promising self-recovery property. In addition, the cytotoxicity test in vitro proved that the hydrogel showed good biocompatibility with normal human liver cells (LO2 cells). The excellent stretchability, robust elasticity, high toughness, fatigue resistance, and biocompatibility of the hydrogel demonstrated its vast potential in the biomedical field and flexible electronic devices.

Plasma-activated water: An alternative disinfectant for S protein inactivation to prevent SARS-CoV-2 infection.

SARS-CoV-2 is a highly contagious virus and is causing a global pandemic. SARS-CoV-2 infection depends on the recognition of and binding to the cellular receptor human angiotensin-converting enzyme 2 (hACE2) through the receptor-binding domain (RBD) of the spike protein, and disruption of this process can effectively inhibit SARS-CoV-2 invasion. Plasma-activated water efficiently inactivates bacteria and bacteriophages by causing damage to biological macromolecules, but its effect on coronavirus has not been reported. In this study, pseudoviruses with the SARS-CoV-2 S protein were used as a model, and plasma-activated water (PAW) effectively inhibited pseudovirus infection through S protein inactivation. The RBD was used to study the molecular details, and the RBD binding activity was inactivated by plasma-activated water through the RBD modification. The short-lived reactive species in the PAW, such as ONOO-, played crucial roles in this inactivation. Plasma-activated water after room-temperature storage of 30 days remained capable of significantly reducing the RBD binding with hACE2. Together, our findings provide evidence of a potent disinfection strategy to combat the epidemic caused by SARS-CoV-2.

Photoactivatable Prodrug-Backboned Polymeric Nanoparticles for Efficient Light-Controlled Gene Delivery and Synergistic Treatment of Platinum-Resistant Ovarian Cancer.

Combination of chemotherapy and gene therapy provides an effective strategy for cancer treatment. However, the lack of suitable codelivery systems with efficient endo/lysosomal escape and controllable drug release/gene unpacking is the major bottleneck for maximizing the combinational therapeutic efficacy. In this work, we developed a photoactivatable Pt(IV) prodrug-backboned polymeric nanoparticle system (CNPPtCP/si(c-fos)) for light-controlled si(c-fos) delivery and synergistic photoactivated chemotherapy (PACT) and RNA interference (RNAi) on platinum-resistant ovarian cancer (PROC). Upon blue-light irradiation (430 nm), CNPPtCP/si(c-fos) generates oxygen-independent N3• with mild oxidation energy for efficient endo/lysosomal escape through N3•-assisted photochemical internalization with less gene deactivation. Thereafter, along with Pt(IV) prodrug activation, CNPPtCP/si(c-fos) dissociates to release active Pt(II) and unpack si(c-fos) simultaneously. Both in vitro and in vivo results demonstrated that CNPPtCP/si(c-fos) displayed excellent synergistic therapeutic efficacy on PROC with low toxicity. This PACT prodrug-backboned polymeric nanoplatform may provide a promising gene/drug codelivery tactic for treatment of various hard-to-tackle cancers.

Visualizing Newly Synthesized RNA by Bioorthogonal Labeling-Primed DNA Amplification.

Monitoring RNA synthesis and spatial distribution can help to understand its role in physiology and diseases. However, visualizing newly synthesized RNA in single cells remains a great challenge. Here, we developed a bioorthogonal labeling-primed DNA amplification strategy to visualize newly synthesized RNA in single cells. The new bioorthogonal N6-allyladenosine nucleoside was prepared to metabolically label cellular newly synthesized RNAs. These allyl-functionalized RNAs then reacted with tetrazine-modified primers. These primers could initiate rolling circle amplification, producing tandem periodic long single DNA strands to capture hundreds of fluorescence probes for signal amplification. Using this method, we explored the subcellular distributions of newly synthesized RNAs. And we found that newly synthesized RNAs are spatially organized in a cell type-specific style with cell-to-cell heterogeneity.

Catalyst-Free One-Step Preparation of Self-Crosslinked pH-Responsive Vesicles.

The fabrication of block copolymer (BCP) vesicles with controlled membrane permeability and promising stability remains a considerable challenge. Herein, a new type of pH-responsive and self-crosslinked vesicle based on a hydrolytically hindered urea bond is reported. This kind of vesicle is formed by the self-assembly of a pH-responsive and hydrolytically self-crosslinkable copolymer poly(ethylene glycol)-block-poly[2-(3-(tert-butyl)-3-ethylureido)ethyl methacrylate-co-2-(diethylamino)ethyl methacrylate] (PEG-b-P(TBEU-co-DEA)). The BCP can be easily synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-(3-(tert-butyl)-3-ethylureido)ethyl methacrylate (TBEU) and 2-(diethylamino)ethyl methacrylate (DEA) using PEG-based macro-chain transfer agent. The copolymer could self-assemble into stable vesicles by the hydrophobic interaction and in situ cross-linking between amines and isocyanates after the hydrolysis of the hindered urea bonds without any catalyst. Dynamic light scattering (DLS) studies show that the vesicles exhibit enhanced stability against the dilution of organic solvent, and the size can be adjusted through the change of pH values. Moreover, the alkaline phosphatase-loaded vesicles can act as nano-reactor and enable free diffusion of small molecules into the vesicles, followed by the significantly improved fluorescence intensity of phosphate-caged fluorescein. This self-crosslinking and pH-sensitive vesicles may serve as a smart platform in controlled drug delivery and molecular reactor.

Serum Nuclease Susceptibility of mRNA Cargo in Condensed Polyplexes.

Messenger RNA (mRNA) is a biomolecule with a wide range of promising clinical applications. However, the unstable nature of mRNA and its susceptibility to degradation by ribonucleases (RNases) necessitate the use of specialized formulations for delivery. Polycations are an emerging class of synthetic carriers capable of packaging nucleic acids, and may serve as suitable RNase-resistant formulations for mRNA administration. Here, we explore the application of VIPER and sunflower polycations, two polycations previously synthesized by our group, for the delivery of mRNA in comparison to branched poly(ethylenimine); all three polycations have been shown to efficiently deliver plasmid DNA (pDNA) to cultured cells. Despite successful mRNA condensation and packaging, transfection studies reveal that these three polycations can only efficiently deliver mRNA under serum-free conditions, while pDNA delivery is achieved even in the presence of serum. RNase resistance studies confirm that nuclease degradation of mRNA cargo remains a significant barrier to mRNA delivery using these polycations. These results emphasize the need for additional strategies for nuclease protection of mRNA cargo beyond electrostatic complexation with polycation.

Injectable Enzymatically Cross-linked Hydrogels with Light-Controlled Degradation Profile.

An advanced hydrogel that features facile formation and injectability as well as light-controlled degradation profile is reported here. By modifying 4-arm poly(ethylene glycol) (4-arm PEG) with 2-nitrobenzyl (NB) and phenol, the 4-arm PEG precursor solutions could form enzymatically cross-linked hydrogels in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2 O2 ). The gelation time, mechanical strength, and porous structure could be simply tuned by the concentration of HRP and H2 O2 . Moreover, the hydrogels underwent controlled degradation under UV light irradiation via photo-cleavage reaction of the NB ester bond. The hydrogels exhibited negligible cytotoxicity toward mouse fibroblast L929 cells in vitro and can be manipulated through injection in vivo.

Tunable, Injectable Hydrogels Based on Peptide-Cross-Linked, Cyclized Polymer Nanoparticles for Neural Progenitor Cell Delivery.

A PEG-based cyclized vinyl polymer was synthesized via one-step RAFT polymerization and used as a precursor of injectable hydrogels. Dithiol linkers including laminin-derived peptides containing IKVAV and YIGSR sequences and DTT were used for gelation. Fast and adjustable gelation rate was achieved through nucleophile-initiated thiol-Michael reaction under physiological conditions. Low swelling ratio and moderate degradation rate of the formed hydrogels were observed. 3D encapsulation of neural progenitor cells in the synthetic hydrogel showed good cell viability over 8 days. The long-term cell survival and proliferation were promoted by the introduction of laminin-derived peptides. This hydrogel platform based on peptide-cross-linked, cyclized vinyl polymers can be used as a universal hydrogel template for 3D cell encapsulation.

Nano-Sized Sunflower Polycations As Effective Gene Transfer Vehicles.

The architecture of polycations plays an important role in both gene transfection efficiency and cytotoxicity. In this work, a new polymer, sunflower poly(2-dimethyl amino)ethyl methacrylate) (pDMAEMA), is prepared by atom transfer radical polymerization and employed as nucleic acid carriers compared to linear pDMAEMA homopolymer and comb pDMAEMA. The sunflower pDMAEMAs show higher IC50 , greater buffering capacity, and stronger binding capacity toward plasmid DNA than their linear and comb counterparts. In vitro transfection studies demonstrate that sunflower pDMAEMAs exhibit high transfection efficiency as well as relatively low cytotoxicity in complete growth medium. In vivo gene delivery by intraventricular injection to the brain shows that sunflower polymer delivers plasmid DNA more effectively than comb polymer. This study provides a new insight into the relationship between polymeric architecture and gene delivery capability, and as well as a useful means to design potent vectors for successful gene delivery.

Virus-Inspired Polymer for Efficient In†Vitro and In†Vivo Gene Delivery.

Clinical translation of nucleic acids drugs has been stunted by limited delivery options. Herein, we report a synthetic polymer designed to mimic viral mechanisms of delivery called VIPER (virus-inspired polymer for endosomal release). VIPER is composed of a polycation block for condensation of nucleic acids, and a pH-sensitive block for acid-triggered display of a lytic peptide to promote trafficking to the cell cytosol. VIPER shows superior efficiencies compared to commercial agents when delivering genes to multiple immortalized cell lines. Importantly, in murine models, VIPER facilitates effective gene transfer to solid tumors.

In vitro study of electroactive tetraaniline-containing thermosensitive hydrogels for cardiac tissue engineering.

Injectable hydrogels made of degradable biomaterials can function as both physical support and cell scaffold in preventing infarct expansion and promoting cardiac repair in myocardial infarction therapy. Here, we report in situ hydrogels consisting of thermosensitive PolyNIPAM-based copolymers and electroactive tetraaniline (TA). Studies showed that the addition of 2-methylene-1,3-dioxepane (MDO) provided the PolyNIPAM-based gel with biodegradability, and the introduction of tetraaniline endowed these copolymers with desirable electrical properties and antioxidant activities. The encapsulated H9c2 cells (rat cardiac myoblast) remained highly viable in the gel matrices. In vivo gel formation and histological analyses were performed in rats by subcutaneous injection and excellent biocompatibility was observed. Furthermore, the proliferation and intracellular calcium transients of H9c2 cells were also studied with (and without) electrical stimuli. Both in vitro and in vivo results demonstrated that electroactive hydrogel may be used as a promising injectable biomaterial for cardiac tissue engineering.

Impact of the digital economy on total factor energy efficiency: evidence from 268 Chinese cities.

Due to the advancement of digital technology, the digital economy has developed rapidly, profoundly changing human production and lifestyles, thereby promoting the dual digital transformation of the energy supply and demand sides and having a profound impact on energy utilization efficiency. Based on measuring the total factor energy efficiency (TFEE) of 268 cities in China from 2011 to 2019, we analyze the total and indirect effects of the digital economy on TFEE using a mediated effects model and examine the effects of urban heterogeneity from the perspectives of geographical location, city size, and resource endowment. The results show that the digital economy has a significant positive contribution to TFEE. In addition, the digital economy can promote TFEE through industrial structure upgrading, technological innovation, and environmental regulation. The test results of the subsample show that there is significant heterogeneity in the impact and mechanism of action of the digital economy on TFEE in different geographical locations, city sizes, and resource endowments. By understanding how the digital economy impacts TFEE, policymakers can formulate effective policies to simultaneously accelerate digital economy development and improve TFEE.

Hydrogen Bonds Reinforced Ionogels with High Sensitivity and Stable Autonomous Adhesion as Versatile Ionic Skins.

Flexible wearable sensors have demonstrated enormous potential in various fields such as human health monitoring, soft robotics, and motion detection. Among them, sensors based on ionogels have garnered significant attention due to their wide range of applications. However, the fabrication of ionogels with high sensitivity and stable autonomous adhesion remains a challenge, thereby limiting their potential applications. Herein, we present an advanced ionogel (PACG-MBAA) with exceptional performances based on multiple hydrogen bonds, which is fabricated through one-step radical polymerization of N-acryloylglycine (ACG) in 1-ethyl-3-methylimidazolium ethyl sulfate (EMIES) in the presence of N,N'-methylenebis(acrylamide) (MBAA). Compared with the ionogel (PAA-MBAA) formed by polymerization of acrylic acid (AA) in EMIES, the resulting ionogel exhibits tunable mechanical strength (35-130 kPa) and Young's modulus comparable to human skin (60-70 kPa) owing to the multiple hydrogen bonds formation. Importantly, they demonstrate stable autonomous adhesion to various substrates and good self-healing capabilities. Furthermore, the ionogel-based sensor shows high sensitivity (with a gauge factor up to 6.16 in the tensile range of 300-700%), enabling the detection of both gross and subtle movements in daily human activities. By integration of the International Morse code, the ionogel-based sensor enables the encryption, decryption, and transmission of information, thus expanding its application prospects.

Membrane-anchoring selenophene viologens for antibacterial photodynamic therapy against periodontitis via restoring subgingival flora and alleviating inflammation.

Antibacterial photodynamic therapy (aPDT) has emerged as a promising strategy for treating periodontitis. However, the weak binding of most photosensitizers to bacteria and the hypoxic environment of periodontal pockets severely hamper the therapeutic efficacy. Herein, two novel oxygen-independent photosensitizers are developed by introducing selenophene into viologens and modifying with hexane chains (HASeV) or quaternary ammonium chains (QASeV), which improve the adsorption to bacteria through anchoring to the negatively charged cell membrane. Notably, QASeV binds only to the bacterial surface of Porphyromonas gingivalis and Fusobacterium nucleatum due to electrostatic binding, but HASeV can insert into their membrane by strong hydrophobic interactions. Therefore, HASeV exhibits superior antimicrobial activity and more pronounced plaque biofilm disruption than QASeV when combined with light irradiation (MVL-210 photoreactor, 350-600 nm, 50 mW/cm2), and a better effect on reducing the diversity and restoring the structure of subgingival flora in periodontitis rat model was found through 16S rRNA gene sequencing analysis. The histological and Micro-CT analyses reveal that HASeV-based aPDT has a better therapeutic effect in reducing periodontal tissue inflammation and alveolar bone resorption. This work provides a new strategy for the development of viologen-based photosensitizers, which may be a favorable candidate for the aPDT against periodontitis.

Luminescent Perovskite-Cross-Linked Polymer with Low Shrinkage and Excellent Stability.

When organic cross-linked polymers are combined with metal halide perovskite nanocrystals (PNCs) for realizing luminescent perovskite-polymer display materials, the stability of PNCs is enhanced and their shrinkage is suppressed. This work presents a feasible strategy for preparing CsPbBr3 nanocrystals (NCs) within a polydicyclopentadiene (PDCPD) thermosetting cross-linked resin matrix simultaneously via a one-step reaction. The obtained PDCPD@PNCs composite exhibits narrow peak half-widths (15-20 nm), high light transmittance (80%), low curing volume shrinkage (1.4%), tunable tensile properties, excellent stability, and a photoluminescence quantum yield (PLQY) of 44.3%. The composite material exhibits long-term stability in water, acid, and base solutions for over 90 days, with the PL intensity being maintained at over 90%. Furthermore, the composite is highly resistant to polar organic solvents owing to the insolubility imparted by cross-linking. White LEDs (WLED) fabricated using the as-prepared composite demonstrate excellent potential as light sources in optical devices.

pH-responsive bioadhesive with robust and stable wet adhesion for gastric ulcer healing.

Development of bioadhesives that can be facilely delivered by endoscope and exhibit instant and robust adhesion with gastric tissues to promote gastric ulcer healing remains challenging. In this study, an advanced bioadhesive is prepared through free radical polymerization of ionized N-acryloyl phenylalanine (iAPA) and N-[tris (hydroxymethyl) methyl] acrylamide (THMA). The precursory polymer solution exhibits low viscosity with the capability for endoscope delivery, and the hydrophilic-hydrophobic transition of iAPA upon exposure to gastric acid can trigger gelation through phenyl groups assisted multiple hydrogen bonds formation and repel water molecules on tissue surface to establish favorable environment for interfacial interactions between THMA and functional groups on tissues. The in-situ formed hydrogel features excellent stability in acid environment (14 days) and exhibits firm wet adhesion to gastric tissue (33.4 kPa), which can efficiently protect the wound from the stimulation of gastric acid and pepsin. In vivo studies reveal that the bioadhesive can accelerate the healing of ulcers by inhibiting inflammation and promoting capillary formation in the acetic acid-induced gastric ulcer model in rats. Our work may provide an effective solution for the treatment of gastric ulcers clinically.