Correction: Ren et al. Injectable and Antioxidative HT/QGA Hydrogel for Potential Application in Wound Healing. Gels 2021, 7, 204.

In the original publication [...].

Tetrahomo corona[4]arene-based spirophanes: synthesis, structure, and properties.

In contrast to a plethora of macrocyclic and cage compounds, spirophanes have remained largely unexplored. We report herein the construction, structure and properties of unprecedented tetrahomo corona[4]arene-based ditopic and tritopic macrocycles of spiro structures. Synthesis was conveniently achieved by means of an efficient SNAr reaction from simple and commercially available starting materials. Racemic samples were resolved into enantiopure chiral tetrahomo i-corona[4]arenes, spirophanes and bispirophanes which show interesting chiroptical properties. The acquired electron-deficient macrocyclic compounds were found to adopt unique conformational structures and to form distinct complexes with TTF in the solid state. Our study provides a new opportunity to develop multitopic macrocycles of different topologies which have potential applications in supramolecular chemistry.

Metagenomic and Genomic Sequences from a Methanogenic Benzene-Degrading Consortium.

Draft and complete metagenome assembled genomes (MAGs) were created from multiple metagenomic assemblies of DGG-B, a strictly anaerobic, stable mixed microbial consortium that degrades benzene completely to methane and CO2. Our objective was to obtain closed genome sequences of benzene-fermenting bacteria to enable the elucidation of their elusive anaerobic benzene degradation pathway.

"Candidatus Nealsonbacteria" Are Likely Biomass Recycling Ectosymbionts of Methanogenic Archaea in a Stable Benzene-Degrading Enrichment Culture.

The Candidate Phyla Radiation (CPR), also referred to as superphylum Patescibacteria, is a very large group of bacteria with no pure culture representatives discovered by 16S rRNA sequencing or genome-resolved metagenomic analyses of environmental samples. Within the CPR, candidate phylum Parcubacteria, previously referred to as OD1, is prevalent in anoxic sediments and groundwater. Previously, we had identified a specific member of the Parcubacteria (referred to as DGGOD1a) as an important member of a methanogenic benzene-degrading consortium. Phylogenetic analyses herein place DGGOD1a within the clade "Candidatus Nealsonbacteria." Because of its persistence over many years, we hypothesized that "Ca. Nealsonbacteria" DGGOD1a must play an important role in sustaining anaerobic benzene metabolism in the consortium. To try to identify its growth substrate, we amended the culture with a variety of defined compounds (pyruvate, acetate, hydrogen, DNA, and phospholipid), as well as crude culture lysate and three subfractions thereof. We observed the greatest (10-fold) increase in the absolute abundance of "Ca. Nealsonbacteria" DGGOD1a only when the consortium was amended with crude cell lysate. These results implicate "Ca. Nealsonbacteria" in biomass recycling. Fluorescence in situ hybridization and cryogenic transmission electron microscope images revealed that "Ca. Nealsonbacteria" DGGOD1a cells were attached to larger archaeal Methanothrix cells. This apparent epibiont lifestyle was supported by metabolic predictions from a manually curated complete genome. This is one of the first examples of bacterial-archaeal episymbiosis and may be a feature of other "Ca. Nealsonbacteria" found in anoxic environments. IMPORTANCE An anaerobic microbial enrichment culture was used to study members of candidate phyla that are difficult to grow in the lab. We were able to visualize tiny "Candidatus Nealsonbacteria" cells attached to a large Methanothrix cell, revealing a novel episymbiosis.

Multifunctional hydrogel with reactive oxygen species scavenging and photothermal antibacterial activity accelerates infected diabetic wound healing.

Management of diabetic wound has long been a clinical challenge due to pathological microenvironment of excessive inflammation, persistent hyperglycemia, and biofilm infection caused by overdue reactive oxygen species (ROS) production and defective blood vessels. Herein, a multifunctional hydrogel with ROS scavenging and photothermal antibacterial activity based on oxidized dextran (Odex), gallic acid-grafted gelatin (GAG) and Ferric ion, named OGF, was developed for treatment of infected wound in a diabetic mouse. This hydrogel was double-crosslinked by the dynamically Schiff-base bonds formed between aldehyde groups in Odex and amino groups in GAG and the metal coordination bonds formed between Ferric ion and polyphenol groups or carboxyl groups in GAG, which endowed the resulted OGF hydrogel with well injectable, self-healing and adhesive properties. Due to the high-efficiency photothermal effect of Ferric ion/polyphenol chelate, this hydrogel killed Staphylococcus aureus and Escherichia coli rapidly and completely within 3.5 min under near-infrared light radiation. Furthermore, this composed hydrogel presented good antioxidation, hemostasis and biocompatibility. It also remarkably accelerated the complete re­epithelialization of Staphylococcus aureus­infected wound in diabetic mice within 18 days by eliminating infection, mitigating oxidative stress and inflammation, and facilitating angiogenesis. Therefore, the proposed multifunctional hydrogel exerts a great potential for translation in the clinical management of diabetic wounds. STATEMENT OF SIGNIFICANCE: High reactive oxygen species (ROS) levels and vascular defects in diabetic wounds can lead to excessive inflammation, persistent hyperglycemia, biofilm infection and other pathological microenvironments, which can further develop to the chronic wounds. In this study, we designed a multifunctional hydrogel with ROS-scavenging ability and photothermal antibacterial activity for the treatment of infected diabetic wound. As expected, this multifunctional hydrogel dressing highly accelerated the complete re­epithelialization of Staphylococcus aureus­infected wound in diabetic mouse by eliminating infection, mitigating oxidative stress and inflammation, as well as facilitating angiogenesis. This work provides a promising therapeutic strategy for infected diabetic wound by inhibition of oxidative stress and biofilm infection.

Transient Oxygen Exposure Causes Profound and Lasting Changes to a Benzene-Degrading Methanogenic Community.

We investigated the impact of oxygen on a strictly anaerobic, methanogenic benzene-degrading enrichment culture derived decades ago from oil-contaminated sediment. The culture includes a benzene fermenter from Deltaproteobacteria candidate clade Sva0485 (referred to as ORM2) and methanogenic archaea. A one-time injection of 0.1 mL air , simulating a small leak into 30 mL batch culture bottle, had no measurable impact on benzene degradation rates, although retrospectively, a tiny enrichment of aerobic taxa was detected. A subsequent 100 times larger injection of air stalled methanogenesis and caused drastic perturbation of the microbial community. A benzene-degrading Pseudomonas became highly enriched and consumed all available oxygen. Anaerobic benzene-degrading ORM2 cell numbers plummeted during this time; re-growth and associated recovery of methanogenic benzene degradation took almost 1 year. These results highlight the oxygen sensitivity of this methanogenic culture and confirm that the mechanism for anaerobic biotransformation of benzene is independent of oxygen, fundamentally different from established aerobic pathways, and is carried out by distinct microbial communities. The study also highlights the importance of including microbial decay in characterizing and modeling mixed microbial communities.

Facile preparation of PVA hydrogels with adhesive, self-healing, antimicrobial, and on-demand removable capabilities for rapid hemostasis.

Multifunctional and smart hydrogel-based hemostatic materials are of great significance in the field of medical care. In this paper, a facile method for the preparation of self-healing, adhesive and on-demand removable PBO hydrogels was established with a simple mixture of polyvinyl alcohol (PVA), borax and oligomeric procyanidin (OPC). In this hydrogel system, borax and OPC were used as dynamic crosslinkers to connect the PVA macromolecules through reversible borate ester bonds and hydrogen bonds, resulting in hydrogels that possess good self-healing and adhesive abilities. Furthermore, the PBO hydrogel displayed excellent antimicrobial activity against Escherichia coli and Staphylococcus aureus. In addition, thanks to the adhesive property of the hydrogel and the inherent hemostatic activity of OPC, this hydrogel showed rapid hemostasis performance as concluded from the in vivo experiments of mouse liver incision, tail amputation and femoral artery models. Benefitting from the fast degradation in water, this hydrogel could be easily removed on-demand within 10 min. Therefore, this well-designed PBO hydrogel offers an important prospect as a rapid hemostatic dressing.

Facile preparation of antibacterial hydrogel with multi-functions based on carboxymethyl chitosan and oligomeric procyanidin.

Hydrogel-based antibacterial materials with multi-functions are of great significance for healthcare. Herein, a facile and one-step method was developed to fabricate an injectable hydrogel (named CMCS/OPC hydrogel) based on carboxymethyl chitosan (CMCS) and oligomeric procyanidin (OPC). In this hydrogel system, OPC serves as the dynamic crosslinker to bridge CMCS macromolecules mainly through dynamical hydrogen bonds, which endows this hydrogel with excellent injectable, self-healing, and adhesive abilities. In addition, due to the inherent antibacterial properties of CMCS and OPC, this hydrogel shows excellent antibacterial activity. Therefore, the well-designed CMCS/OPC hydrogel has great prospects as an antibacterial material in the biomedical field.

Injectable and reactive oxygen species-scavenging gelatin hydrogel promotes neural repair in experimental traumatic brain injury.

Oxidative stress caused by the overexpression of reactive oxygen species (ROS) plays an important role in the pathogenesis of traumatic brain injury (TBI). Accumulation of ROS can lead to cell death, neurodegeneration, and neurological deficit. Therefore, the design and application of functional materials with ROS scavenging ability is of great significance for neural repair. Herein, an injectable and antioxidant hydrogel was developed for TBI treatment based on the Schiff base reaction of gallic acid-conjugated gelatin (GGA) and oxidized dextran (Odex). The resulting GGA/Odex hydrogel could effectively scavenge DPPH and ABTS radicals, as well as protect cells from the oxidative damage in vitro. Moreover, GGA/Odex hydrogel possessed well biocompatible features. In a moderate TBI mouse model, in situ implantation of GGA6Odex hydrogel efficiently facilitated neurogenesis and promoted the motor, learning and memory abilities. Also, this composite hydrogel suppressed oxidative stress and inflammation via the activation of Nrf2/HO-1 pathway and the regulating of inflammatory factors secretion and macrophage/microglia polarization. Therefore, this injectable and ROS-scavenging GGA6Odex hydrogel is a promising biomaterial for tissue regenerative medicine, including TBI and other tissue repair relevant to raised ROS circumstance.

Injectable Self-Healing Adhesive Chitosan Hydrogel with Antioxidative, Antibacterial, and Hemostatic Activities for Rapid Hemostasis and Skin Wound Healing.

Engineered wound dressing materials with excellent injectability, self-healing ability, tissue-adhesiveness, especially the ones possessing potential therapeutic effects have great practical significance in healthcare. Herein, an injectable quaternary ammonium chitosan (QCS)/tannic acid (TA) hydrogel based on QCS and TA was designed and fabricated by facile mixing of the two ingredients under physiological conditions. In this system, hydrogels were mainly cross-linked by dynamic ionic bonds and hydrogen bonds between QCS and TA, which endows the hydrogel with excellent injectable, self-healing, and adhesive properties. Benefitting from the inherent antioxidative, antibacterial, and hemostatic abilities of TA and QCS, this hydrogel showed superior reactive oxygen species scavenging activity, broad-spectrum antibacterial ability, as well as rapid hemostatic capability. Moreover, the QCS/TA2.5 hydrogel (containing 2.5% TA) exhibited excellent biocompatibility. The in vivo experiments also showed that QCS/TA2.5 hydrogel dressing not only rapidly stopped the bleeding of arterial and deep incompressible wounds in mouse tail amputation, femoral artery hemorrhage, and liver incision models but also significantly accelerated wound healing in a full-thickness skin wound model. For the great potentials listed above, this multifunctional QCS/TA2.5 hydrogel offers a promising network as a dressing material for both rapid hemostasis and skin wound repair.

In situ forming and biocompatible hyaluronic acid hydrogel with reactive oxygen species-scavenging activity to improve traumatic brain injury repair by suppressing oxidative stress and neuroinflammation.

The efficacy of neural repair and regeneration strategies for traumatic brain injury (TBI) treatment is greatly hampered by the harsh brain lesion microenvironment including oxidative stress and hyper-inflammatory response. Functionalized hydrogel with the capability of oxidative stress suppression and neuroinflammation inhibition will greatly contribute to the repairment of TBI. Herein, antioxidant gallic acid-grafted hyaluronic acid (HGA) was combined with hyaluronic acid-tyramine (HT) polymer to develop an injectable hydrogel by dual-enzymatically crosslinking method. The resulting HT/HGA hydrogel is biocompatible and possesses effective scavenging activity against DPPH and hydroxyl radicals. Meanwhile, this hydrogel improved cell viability and reduced intracellular reactive oxygen species (ROS) production under H2O2 insult. The in vivo study showed that in situ injection of HT/HGA hydrogel significantly reduced malondialdehyde (MDA) production and increased glutathione (GSH) expression in lesion area after treatment for 3 or 21 days, which might be associated with the activation of Nrf2/HO-1 pathway. Furthermore, this hydrogel promoted the microglia polarization to M2 (Arg1) phenotype, it also decreased the level of proinflammatory factors including TNF-α and IL-6 and increased anti-inflammatory factor expression of IL-4. Finally, blood-brain barrier (BBB) was protected, neurogenesis in hippocampus was promoted, and the motor, learning and memory ability was enhanced. Therefore, this injectable, biocompatible, and antioxidant hydrogel exhibits a huge potential for treating TBI and allows us to recognize the great value of this novel biomaterial for remodeling brain structure and function.

Functionalized injectable hyaluronic acid hydrogel with antioxidative and photothermal antibacterial activity for infected wound healing.

Infected wound healing has always been a challenge in clinic. Effective and economic wound dressings with combined antibacterial activity and pro-healing function are highly desirable, especially in the context of infected wounds. An obvious advantage of antibacterial wound dressing is to avoid the overuse of antibiotics and the occurrence of drug resistance. Herein, an injectable hyaluronic acid hydrogel with antioxidative and photothermal antibacterial activity as a functional dressing was prepared, characterized and evaluated in an experimental infected wound model. This hydrogel was developed by loading graphene oxide (GO) in a natural polymer network consisting of hyaluronic acid grafted with tyramine (HT) and gelatin grafted with gallic acid (GGA). The HT/GGA/GO hydrogels have a porous cross-linked network structure and demonstrate a good stability, biocompatibility, antioxidant, hemostatic and photothermal antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, in vivo studies have shown that HT1/GGA2/GO0.1 hydrogel dressing combined with photothermal therapy can effectively prevent early infection and accelerate wound healing. These results indicated this functionalized injectable hydrogel HT1/GGA2/GO0.1 has a great potential in wound dressing application.

Elucidating the Synergistic Effect of Multiple Chinese Herbal Prescriptions in the Treatment of Post-stroke Neurological Damage.

Background: Traditional Chinese medicine (TCM) has been widely used in the treatment of human diseases. However, the synergistic effects of multiple TCM prescriptions in the treatment of stroke have not been thoroughly studied. Objective of the study: This study aimed to reveal the mechanisms underlying the synergistic effects of these TCM prescriptions in stroke treatment and identify the active compounds. Methods: Herbs and compounds in the Di-Tan Decoction (DTD), Xue-Fu Zhu-Yu Decoction (XFZYD), and Xiao-Xu-Ming Decoction (XXMD) were acquired from the TCMSP database. SEA, HitPick, and TargetNet web servers were used for target prediction. The compound-target (C-T) networks of three prescriptions were constructed and then filtered using the collaborative filtering algorithm. We combined KEGG enrichment analysis, molecular docking, and network analysis approaches to identify active compounds, followed by verification of these compounds with an oxygen-glucose deprivation and reoxygenation (OGD/R) model. Results: The filtered DTD network contained 39 compounds and 534 targets, the filtered XFZYD network contained 40 compounds and 508 targets, and the filtered XXMD network contained 55 compounds and 599 targets. The filtered C-T networks retained approximately 80% of the biological functions of the original networks. Based on the enriched pathways, molecular docking, and network analysis results, we constructed a complex network containing 3 prescriptions, 14 botanical drugs, 26 compounds, 13 targets, and 5 pathways. By calculating the synergy score, we identified the top 5 candidate compounds. The experimental results showed that quercetin, baicalin, and ginsenoside Rg1 independently and synergistically increased cell viability. Conclusion: By integrating pharmacological and chemoinformatic approaches, our study provides a new method for identifying the effective synergistic compounds of TCM prescriptions. The filtered compounds and their synergistic effects on stroke require further research.

Injectable hyaluronic acid hydrogel loaded with BMSC and NGF for traumatic brain injury treatment.

Injectable hydrogel has the advantage to fill the defective area and thereby shows promise as therapeutic implant or cell/drug delivery vehicle for tissue repair. In this study, an injectable hyaluronic acid hydrogel in situ dual-enzymatically cross-linked by galactose oxidase (GalOx) and horseradish peroxidase (HRP) was synthesized and optimized, and the therapeutic effect of this hydrogel encapsulated with bone mesenchymal stem cells (BMSC) and nerve growth factors (NGF) for traumatic brain injury (TBI) mice was investigated. Results from in vitro experiments showed that either tyramine-modified hyaluronic acid hydrogels (HT) or NGF loaded HT hydrogels (HT/NGF) possessed good biocompatibility. More importantly, the HT hydrogels loaded with BMSC and NGF could facilitate the survival and proliferation of endogenous neural cells probably by neurotrophic factors release and neuroinflammation regulation, and consequently improved the neurological function recovery and accelerated the repair process in a C57BL/6 TBI mice model. All these findings highlight that this injectable, BMSC and NGF-laden HT hydrogel has enormous potential for TBI and other tissue repair therapy.

One-Step Synthesis of Multifunctional Chitosan Hydrogel for Full-Thickness Wound Closure and Healing.

Multifunctional hydrogel as a sealant or wound dressing with high adhesiveness and excellent antibacterial activity is highly desirable in clinical applications. In this contribution, one-step synthetic hydrogel based on quaternized chitosan (QCS), tannic acid (TA), and ferric iron (Fe(III)) is developed for skin incision closure and Staphylococcus aureus (S. aureus)-infected wound healing. In this hydrogel system, the ionic bonds and hydrogen bonds between QCS and TA form the main backbone of hydrogel, the metal coordination bonds between TA and Fe(III) (catechol-Fe) endow hydrogel with excellent adhesiveness and (near-infrared light) NIR-responsive photothermal property, and these multiple dynamic physical crosslinks enable QCS/TA/Fe hydrogel with flexible self-healing ability and injectability. Moreover, QCS/TA/Fe hydrogel possesses superior antioxidant, anti-inflammatory, hemostasis, and biocompatibility. Also, it is safe for vital organs. The data from the mouse skin incision model and infected full-thickness skin wound model presented the high wound closure effectiveness and acceleration of the wound healing process by this multifunctional hydrogel, highlighting its great potential in wound management.

A simple and successful treatment for rupture and defect of the posterior third superior sagittal sinus caused by open depressed skull fracture: A case report / 中华创伤杂志(英文版)

It is extremely dangerous to treat the posterior third of the superior sagittal sinus (PTSSS) surgically, since it is usually not completely ligated. In this report, the authors described the case of a 27-year-old man with a ruptured and defective PTSSS caused by an open depressed skull fracture, which was treated by ligation of the PTSSS and the patient achieved a positive recovery. The patient's occiput was hit by a height-limiting rod and was in a mild coma. A CT scan showed an open depressed skull fracture overlying the PTSSS and a diffuse brain swelling. He underwent emergency surgery. When the skull fragments were removed, a 4 cm segment of the superior sagittal sinus (SSS) and the adjacent dura mater were removed together with bone fragments. Haemorrhage occurred and blood pressure dropped. We completed the operation by ligating the severed ends of the fractured sagittal sinus. One month after the operation, apart from visual field defects, he recovered well. In our opinion, in primary hospitals, when patients with severely injured PTSSS cannot sustain a long-time and complicated operation, e.g., the bypass using venous graft, and face life-threatening conditions, ligation of the PTSSS is another option, which may unexpectedly achieve good results.

Injectable and Antioxidative HT/QGA Hydrogel for Potential Application in Wound Healing.

Hydrogels have gained a niche in the market as wound dressings due to their high water content and plasticity. However, traditional hydrogel wound dressings are difficult to fully adapt to irregular-shaped wound areas. Additionally, excessive reactive oxygen species (ROS) accumulated in the damaged area impede the wound healing process. Therefore, hydrogels with injectable and antioxidant properties offer promising qualities for wound healing, but their design and development remain challenges. In this study, HT/QGA (tyramine-grafted hyaluronic acid/gallic acid-grafted quaternized chitosan) hydrogels with injectable and antioxidant properties were prepared and characterized. This hydrogel exhibited excellent injectability, favorable antioxidant activity, and good biocompatibility. Moreover, we evaluated the therapeutic effect of HT/QGA hydrogel in a full-thickness skin injury model. These results suggested that HT/QGA hydrogel may offer a great potential application in wound healing.