Iron-catalyzed benzylic C-H thiolation via photoinduced ligand-to-metal charge-transfer.

Here, we describe an iron-catalyzed benzylic C-H thiolation of alkylarenes via photoinduced ligand-to-metal charge-transfer. The protocol features operational simplicity, mild reaction conditions, and the use of FeCl3 as catalyst and thiols/disulfides as sulfur sources, which enables the transformation of diverse benzylic C-H bonds into C-S bonds with a high efficiency.

Electrochemiluminescence aptasensing method for ultrasensitive determination of lipopolysaccharide based on CRISPR-Cas12a accessory cleavage activity.

In this study, an ultrasensitive electrochemiluminescence (ECL) aptasensing method was developed for lipopolysaccharide (LPS) determination based on CRISPR-Cas12a accessory cleavage activity. Tris (2,2'-bipyridine) dichlororuthenium (II) (Ru(bpy)32+) was adsorbed on the surface of a glassy carbon electrode (GCE) coated with a mixture of gold nanoparticles (AuNPs) and Nafion film via electrostatic interaction. The obtained ECL platform (Ru(bpy)32+/AuNP/Nafion/GCE) exhibited strong ECL emission. Thiol-functionalized single-stranded DNA (ssDNA) was modified with a ferrocenyl (Fc) group and autonomously assembled on the ECL platform of Ru(bpy)32+/AuNP/Nafion/GCE via thiol-gold bonding, resulting in the quenching of ECL emission. After hybridization of the LPS aptamer strand (AS) with its partial complementary strand (CS), the formed double-stranded DNA (dsDNA) could activate CRISPR-Cas12a to indiscriminately cleave ssDNA-Fc on the surface of Ru(bpy)32+/AuNP/Nafion/GCE, resulting in recovery of the ECL intensity of Ru(bpy)32+ due to the increasing distance between Fc and the electrode surface. The combination of LPS and AS suppressed the formation of dsDNA, inhibited the activation of CRISPR-Cas12a, and prevented further cleavage of ssDNA-Fc. This mechanism aided in upholding the integrity of ssDNA-Fc on the surface of the electrode and was combined with ECL quenching induced by the target. The ECL intensity decreased linearly as the concentration of LPS increased from 1 to 50,000 pg/mL and followed a logarithmic relationship. This method exhibited a remarkably low detection limit of 0.24 pg/mL, which meets the requirement for low-concentration detection of LPS in the human body. The proposed method demonstrates the capacity of CRISPR-Cas12a to perform non-specific cutting of single-stranded DNA and transform the resultant cutting substances into changes in the ECL signal. By amalgamating this approach with the distinct identification abilities of LPS and its aptamers, a simple, responsive, and discriminatory LPS assay was established that holds immense significance for clinical diagnosis.

C-Doped LiVO3 Honeycombs Derived from the Biomass Template Strategy for Superior Lithium Storage.

LiVO3 as a prospective anode for lithium-ion batteries has drawn considerable focus based on its superior ion transfer capability and relatively elevated specific capacity. Nevertheless, the inherent low electrical conductivity and sluggish reaction kinetics hindered its commercial application. Herein, C-doped LiVO3 honeycombs (C-doped LiVO3 HCs) are designed via introducing low-cost and scalable biomass carbon as a template, and the influence of the structure on the lithium storage property is systematically studied. The prepared C-doped LiVO3 HC electrode delivers a high reversible capacity of 743.7 mA h g-1 at 0.5 A g-1 after 400 cycles and superior high-rate performance with an average discharge capacity of 420.8 mA h g-1 even at 5.0 A g-1. The remarkable comprehensive electrochemical performance is attributed to the high electrical conductivity caused by carbon doping and rapid ion transport triggered by the honeycomb structure. This work may offer a rational design on both the hierarchical structure and doping engineering of future battery electrodes.

Washing-Free Electrochemiluminescence Biosensor for the Simultaneous Determination of N6 Methyladenosines Incorporating a Tri-Double Resolution Strategy.

We propose a novel washing-free electrochemiluminescence (ECL) biosensor for the simultaneous detection of two types of N6 methyladenosines-RNAs (m6A-RNAs), which are potential cancer biomarkers, on the basis of binding-induced DNA strand displacement (BINSD). The biosensor integrated a tri-double resolution strategy that combined spatial and potential resolution, hybridization and antibody recognition, and ECL luminescence and quenching. The biosensor was fabricated by separately immobilizing two ECL reagents (gold nanoparticles/g-C3N4 nanosheets and ruthenium bipyridine derivative/gold nanoparticles/Nafion) and the capture DNA probe on the two sections of glassy carbon electrode. As a proof of concept, m6A-Let-7a-5p and m6A-miR-17-5p were chosen as model analytes, while m6A antibody-DNA3/ferrocene-DNA4/ferrocene-DNA5 was designed as an m6A-binding probe and DNA6/DNA7 was designed as a hybridization probe with DNA3 to release the quenching probes ferrocene-DNA4/ferrocene-DNA5. The recognition process led to the quenching of the ECL signals from both probes via BINSD. The proposed biosensor has the advantage of being washing-free. The ECL methods using the fabricated ECL biosensor with the designed probes exhibited a low detection limit of 0.03 pM for two m6A-RNAs and high selectivity. This work reveals that this strategy is promising for developing an ECL method for the simultaneous detection of two m6A-RNAs. The proposed strategy could be expanded to develop the analytical methods for the simultaneous detection of other RNA modifications by changing the antibody and hybridization probe sequences.

An injectable and active hydrogel induces mutually enhanced mild magnetic hyperthermia and ferroptosis.

Magnetic hyperthermia therapy (MHT) is a promising new modality to deal with solid tumors, yet the low magnetic-heat conversion efficacy, magnetic resonance imaging (MRI) artifacts, easy leakage of magnetic nanoparticles, and thermal resistance are the main obstacles to expand its clinical applications. Herein, a synergistic strategy based on a novel injectable magnetic and ferroptotic hydrogel is proposed to overcome these bottlenecks and boost the antitumor efficacy of MHT. The injectable hydrogel (AAGel) exhibiting a sol-gel transition upon heating is made of arachidonic acid (AA)-modified amphiphilic copolymers. Ferrimagnetic Zn0.4Fe2.6O4 nanocubes with high-efficiency hysteresis loss mechanism are synthesized and co-loaded into AAGel with RSL3, a potent ferroptotic inducer. This system maintains the temperature-responsive sol-gel transition, and provides the capacity of multiple MHT and achieves accurate heating after a single injection owing to the firm anchoring and uniform dispersion of nanocubes in the gel matrix. The high magnetic-heat conversion efficacy of nanocubes coupled with the application of echo limiting effect avoids the MRI artifacts during MHT. Besides the function of magnetic heating, Zn0.4Fe2.6O4 nanocubes combined with multiple MHT can sustain supply of redox-active iron to generate reactive oxygen species and lipid peroxides and accelerate the release of RLS3 from AAGel, thus enhancing the antitumor efficacy of ferroptosis. In turn, the reinforced ferroptosis can alleviate the MHT-triggered thermal resistance of tumors by impairment of the protective heat shock protein 70. The synergy strategy achieves the complete elimination of CT-26 tumors in mice without causing local tumor recurrence and other severe side effects.

3D-Printed Porous Scaffolds of Hydrogels Modified with TGF-ß1 Binding Peptides to Promote In Vivo Cartilage Regeneration and Animal Gait Restoration.

The treatment of cartilage injury and osteoarthritis has been a classic problem for many years. The idea of in situ tissue regeneration paves a way for osteochondral repair in vivo. Herein, a hydrogel scaffold linked with bioactive peptides that can selectively adsorb transforming growth factor ß1 (TGF-ß1) was hypothesized to not only afford cell ingrowth space but also induce the endogenous TGF-ß1 recruitment for chondrogenesis promotion. In this study, bilayered porous scaffolds with gelatin methacryloyl (GelMA) hydrogels as a matrix were constructed via three-dimensional (3D) printing, of which the upper layer was covalently bound with bioactive peptides that can adsorb TGF-ß1 for cartilage repair and the lower layer was blended with hydroxyapatite for subchondral regeneration. The scaffolds showed promising therapeutic efficacy proved by cartilage and osteogenic induction in vitro and osteochondral repair of rats in vivo. In particular, the animal gait behavior was recovered after the in situ tissue regeneration, and the corresponding gait analysis demonstrated the promotion of tissue regeneration induced by the porous hydrogels with the binding peptides.

An injectable hemostatic PEG-based hydrogel with on-demand dissolution features for emergency care.

Uncontrolled bleeding from internal noncompressible wounds is a major cause of prehospital death in military personnel and civilian populations. An ideal hemostatic sealant for emergency care should quickly control blood loss and be removed without debridement for the follow-up treatment in the operating room, yet the lack of suitable materials to meet both requirements is the bottleneck. Herein, we suggest an injectable and dissolvable hydrogel sealant for hemorrhage management of noncompressible wounds. To this end, a 4-arm poly(ethylene glycol) (PEG) crosslinker modified with thioester linkages and terminated with aldehyde groups is designed and synthesized, and to modulate the gel properties and make it suitable as a hemostatic sealant, a mixed amino component composed of poly(ethylene imine) and adipic dihydrazide is employed to react with the PEG crosslinker to form the adhesive and elastic sealant for the first time. The aldehyde groups provide the adhesion to the tissues, and the amino component affords the procoagulant ability. More importantly, the thioester moieties allow the on-demand dissolution of sealant via a thiol-thioester exchange reaction upon exposure to an exogenous thiolate solution. In the rat femoral artery puncture and liver injury models, the administration of the hydrogel sealant dramatically reduces blood loss, and its subsequent removal does not induce rebleeding. Consequently, this hydrogel sealant with the unique feature of on-demand dissolution can not only efficiently control bleeding in emergent scenarios, but also allow non-traumatic re-exposure of wounds during subsequent surgical care. STATEMENT OF SIGNIFICANCE: Sealants, adhesives or hemostatic dressings currently used in emergency situations not only require manual pressure to control bleeding, but also face removal by cutting and mechanical debridement to enable eventual surgical treatment. In this study, we design and develop an injectable and adhesive hydrogel sealant with good procoagulant capacity and on-demand dissolution feature. The application of the hydrogel sealant substantially reduces bleeding from internal noncompressible wounds without the need for direct pressure, and demonstrates for the first time that its controlled removal without debridement does not cause rebleeding. Considering that there are currently no commercial wound sealant systems with the feature of on-demand dissolution, the hydrogel sealant developed by us is expected to address an unmet clinical need.

NIR Light-Triggered Quantitative Pulsed Drug Release.

Quantitative drug release is important for improving therapeutic efficiency and avoiding side effects. While using long-term delivery system for repeated therapies, it is indispensable but challenging to accurately control the drug dosing. Here, a photocleavable prodrug loaded hydrogel is proposed for near infrared (NIR) light-triggered quantitative pulsed drug release. IR783, a commercially available NIR fluorescent dye, is conjugated with methyl honokiol (mHNK) to give a photocleavable IR783-mHNK prodrug. Injectable glycol chitosan (GC) hydrogel is chosen as a reservoir, in which IR783-mHNK can be efficiently loaded via electrostatic and hydrophobic interactions. Upon 680 nm light-emitting diode (LED) light irradiation, IR783-mHNK cleaves and mHNK is released. Notably, it is found that IR783-mHNK presents synchronous photocleavage-fluorescence bleaching phenomenon. The released amount of mHNK is visible by measuring the residual fluorescent intensity of hydrogel. Quantitative drug release is achieved by controlling irradiation duration and the drug release process is visible by fluorescence imaging. The prodrug-loaded hydrogel shows good stability, minimum leakage and efficient light responsibility both in vitro and in vivo. After light triggering, monitorable quantitative mHNK release and on-demand sleep-promotiing effect are verified in mice without toxicities.

Biological sealing and integration of a fibrinogen-modified titanium alloy with soft and hard tissues in a rat model.

Percutaneous or transcutaneous devices are important and unique, and the corresponding biological sealing at the skin-implant interface is the key to their long-term success. Herein, we investigated the surface modification to enhance biological sealing, using a metal sheet and screw bonded by biomacromolecule fibrinogen mediated via pre-deposited synthetic macromolecule polydopamine (PDA) as a demonstration. We examined the effects of a Ti-6Al-4V titanium alloy modified with fibrinogen (Ti-Fg), PDA (Ti-PDA) or their combination (Ti-PDA-Fg) on the biological sealing and integration with skin and bone tissues. Human epidermal keratinocytes (HaCaT), human foreskin fibroblasts (HFF) and preosteoblasts (MC3T3-E1), which are closely related to percutaneous implants, exhibited better adhesion and spreading on all the three modified sheets compared with the unmodified alloy. After three-week subcutaneous implantation in Sprague-Dawley (SD) rats, the Ti-PDA-Fg sheets could significantly attenuate the soft tissue response and promote angiogenesis compared with other groups. Furthermore, in the model of percutaneous tibial implantation in SD rats, the Ti-PDA-Fg screws dramatically inhibited epithelial downgrowth and promoted new bone formation. Hence, the covalent immobilization of fibrinogen through the precoating of PDA is promising for enhanced biological sealing and osseointegration of metal implants with soft and hard tissues, which is critical for an orthopedic percutaneous medical device.

PEG-based thermosensitive and biodegradable hydrogels.

Injectable thermosensitive hydrogels are free-flowing polymer solutions at low or room temperature, making them easy to encapsulate the therapeutic payload or cells via simply mixing. Upon injection into the body, in situ forming hydrogels triggered by body temperature can act as drug-releasing reservoirs or cell-growing scaffolds. Finally, the hydrogels are eliminated from the administration sites after they accomplish their missions as depots or scaffolds. This review outlines the recent progress of poly(ethylene glycol) (PEG)-based biodegradable thermosensitive hydrogels, especially those composed of PEG-polyester copolymers, PEG-polypeptide copolymers and poly(organophosphazene)s. The material design, performance regulation, thermogelation and degradation mechanisms, and corresponding applications in the biomedical field are summarized and discussed. A perspective on the future thermosensitive hydrogels is also highlighted. STATEMENT OF SIGNIFICANCE: Thermosensitive hydrogels undergoing reversible sol-to-gel phase transitions in response to temperature variations are a class of promising biomaterials that can serve as minimally invasive injectable systems for various biomedical applications. Hydrophilic PEG is a main component in the design and fabrication of thermoresponsive hydrogels due to its excellent biocompatibility. By incorporating hydrophobic segments, such as polyesters and polypeptides, into PEG-based systems, biodegradable and thermosensitive hydrogels with adjustable properties in vitro and in vivo have been developed and have recently become a research hotspot of biomaterials. The summary and discussion on molecular design, performance regulation, thermogelation and degradation mechanisms, and biomedical applications of PEG-based thermosensitive hydrogels may offer a demonstration of blueprint for designing new thermogelling systems and expanding their application scope.

Cell-Free Bilayered Porous Scaffolds for Osteochondral Regeneration Fabricated by Continuous 3D-Printing Using Nascent Physical Hydrogel as Ink.

Cartilage is difficult to self-repair and it is more challenging to repair an osteochondral defects concerning both cartilage and subchondral bone. Herein, it is hypothesized that a bilayered porous scaffold composed of a biomimetic gelatin hydrogel may, despite no external seeding cells, induce osteochondral regeneration in vivo after being implanted into mammal joints. This idea is confirmed based on the successful continuous 3D-printing of the bilayered scaffolds combined with the sol-gel transition of the aqueous solution of a gelatin derivative (physical gelation) and photocrosslinking of the gelatin methacryloyl (gelMA) macromonomers (chemical gelation). At the direct printing step, a nascent physical hydrogel is extruded, taking advantage of non-Newtonian and thermoresponsive rheological properties of this 3D-printing ink. In particular, a series of crosslinked gelMA (GelMA) and GelMA-hydroxyapatite bilayered hydrogel scaffolds are fabricated to evaluate the influence of the spacing of 3D-printed filaments on osteochondral regeneration in a rabbit model. The moderately spaced scaffolds output excellent regeneration of cartilage with cartilaginous lacunae and formation of subchondral bone. Thus, tricky rheological behaviors of soft matter can be employed to improve 3D-printing, and the bilayered hybrid scaffold resulting from the continuous 3D-printing is promising as a biomaterial to regenerate articular cartilage.

An injectable thermosensitive hydrogel loaded with an ancient natural drug colchicine for myocardial repair after infarction.

Localized administration of anti-inflammatory agents benefits patients after myocardial infarction (MI) by repressing/modulating inflammatory response of the MI region and thus accelerating repair of the impaired tissues. Colchicine (Col), an ancient natural drug, has excellent anti-inflammatory effects; however, its utilization is strictly limited due to its severe systemic toxicity and narrow therapeutic window. In this study, we developed an intramyocardial delivery system of Col using an injectable, thermosensitive poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) polymer hydrogel as the vehicle for the treatment of MI while minimizing its systemic toxicity. The aqueous PLGA-PEG-PLGA solution loaded with Col (Col@Gel) underwent a sol-gel transition at 35 °C and maintained a gel state at body temperature. Col was released from the Col@Gel in an initial burst followed by a sustained release manner for over 8 days. The in vitro cell tests showed that the Col@Gel system significantly inhibited macrophage proliferation and migration. In a mouse model of MI, a single intramyocardial administration of the Col@Gel effectively alleviated cardiac inflammation, inhibited myocardial apoptosis and fibrosis, improved cardiac function and structure, and increased mouse survival without inducing severe systemic toxicity, which was observed following intraperitoneal administration of Col solution. These results suggested that the Col@Gel system is a reliable drug delivery system for the sustained local release of Col and has great potential as an anti-inflammatory therapy for the treat of MI.

[Sprouting ecology of woody plants: a research review].

Sprouting is an efficient regeneration means of woody plants to regain their biomass loss after disturbances. This paper reviewed the biological characteristics of sprouting, and its consequences on woody plants individual life history, dynamics of population and community, and biogeography. Many achievements have been obtained on the researches of sprouting strategy and its relationships with disturbances, but less is known about the ecological significances of sprouting, and especially, its effects on the structure and dynamics of woody plants population and community. As in China, both the basic and the applied research of sprouting ecology and vegetation restoration should be strengthened.