Cholinium Pyridinolate Ionic Pair-Catalyzed Fixation of CO2 into Cyclic Carbonates.

A halide-free ionic pair organocatalyst was proposed for the cycloaddition of CO2 into epoxide reactions. Cholinium pyridinolate ionic pairs with three different substitution positions were designed. Under conditions of temperature of 120 °C, pressure of 1 MPa CO2, and catalyst loading of 5 mol %, the optimal catalyst cholinium 4-pyridinolate ([Ch]+[4-OP]-) was employed. After a reaction time of 12 h, styrene oxide was successfully converted into the corresponding cyclic carbonate, and its selectivity was improved to 90%. A series of terminal epoxides were converted into cyclic carbonates within 12 h, with yields ranging from 80 to 99%. The proposed mechanism was verified by 1H NMR and 13C NMR titrations. Cholinium cations act as a hydrogen bond donor to activate epoxides, and pyridinolate anions combine with carbon dioxide to form intermediate carbonate anions that attack epoxides as nucleophiles and lead to ring opening. In summary, a halide-free ionic pair organocatalyst was designed and the catalytic mechanism in the cycloaddition of CO2 into epoxides reactions was proposed.

Facilitating safe and sustained submucosal lift through an endoscopically injectable shear-thinning carboxymethyl starch sodium hydrogel.

Traditional submucosal filling materials frequently show insufficient lifting height and duration during clinical procedures. Here, the anionic polysaccharide polymer sodium carboxymethyl starch and cationic Laponite to prepare a hydrogel with excellent shear-thinning ability through physical cross-linking, so that it can achieve continuous improvement of the mucosal cushion through endoscopic injection. The results showed that the hydrogel (56.54 kPa) had a lower injection pressure compared to MucoUp (68.56 kPa). The height of submucosal lifting height produced by hydrogel was higher than MucoUp, and the height maintenance ability after 2 h was 3.20 times that of MucoUp. At the same time, the hydrogel also showed satisfactory degradability and biosafety, completely degrading within 200 h. The hemolysis rate is as low as 0.76 %, and the cell survival rate > 80 %. Subcutaneous implantation experiments confirmed that the hydrogel showed no obvious systemic toxicity. Animal experiments clearly demonstrated the in vivo feasibility of using hydrogels for submucosal uplift. Furthermore, successful endoscopic submucosal dissection was executed on a live pig stomach, affirming the capacity of hydrogel to safely and effectively facilitate submucosal dissection and mitigate adverse events, such as bleeding. These results indicate that shear-thinning hydrogels have a wide range applications as submucosal injection materials.

An ECM-mimicking assembled gelatin/hyaluronic acid hydrogel with antibacterial and radical scavenging functions for accelerating open wound healing.

A multifunctional hydrogel dressing with hemostatic, antibacterial, and reactive oxygen species (ROS)-removing properties is highly desirable for the clinical treatment of open wounds. Although many wound dressings have been prepared, the modification of polymers is often involved in the preparation process, and the uncertainty of biological safety and stability of modified polymers hinders the clinical application of products. In this study, inspired by the composition and crosslinking pattern of extracellular matrix (ECM), a deeply ECM-mimicking multifunctional hydrogel dressing is created. Tannic acid (TA) and poly-ϵ-lysine (EPL) are added into a gelatin/hyaluronic acid (Gel/HA) matrix, and a stable hydrogel is formed due to the formation of the triple helix bundles of gelatin and hydrogen bonds between polymers. The introduction of TA and EPL endows the ECM-mimicking hydrogel with stable rheological properties, as well as antibacterial and hemostatic functions. The as-produced hydrogels have suitable swelling ratio, enzyme degradability, and good biocompatibility. In addition, it also shows a significant ability to eliminate ROS, which is confirmed by the elimination of 2,2-diphenyl-1-picrylhydrazyl free radical. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed ECM-mimicking Gel/HA hydrogels have a prominent effect on ECM formation and promotion of wound closure. Taken together, these findings suggest that the multifunctional hydrogels deeply mimicking the ECM are promising candidates for the clinical treatment of open wounds.

A click chemistry-mediated all-peptide cell printing hydrogel platform for diabetic wound healing.

High glucose-induced vascular endothelial injury is a major pathological factor involved in non-healing diabetic wounds. To interrupt this pathological process, we design an all-peptide printable hydrogel platform based on highly efficient and precise one-step click chemistry of thiolated γ-polyglutamic acid, glycidyl methacrylate-conjugated γ-polyglutamic acid, and thiolated arginine-glycine-aspartate sequences. Vascular endothelial growth factor 165-overexpressed human umbilical vein endothelial cells are printed using this platform, hence fabricating a living material with high cell viability and precise cell spatial distribution control. This cell-laden hydrogel platform accelerates the diabetic wound healing of rats based on the unabated vascular endothelial growth factor 165 release, which promotes angiogenesis and alleviates damages on vascular endothelial mitochondria, thereby reducing tissue hypoxia, downregulating inflammation, and facilitating extracellular matrix remodeling. Together, this study offers a promising strategy for fabricating tissue-friendly, high-efficient, and accurate 3D printed all-peptide hydrogel platform for cell delivery and self-renewable growth factor therapy.

Versatile Injectable Carboxymethyl Chitosan Hydrogel for Immediate Hemostasis, Robust Tissue Adhesion Barrier, and Antibacterial Applications.

Iatrogenic ulcers resulting from endoscopic submucosal dissection surgery remain a significant clinical concern due to the risk of uncontrolled bleeding. Herein, we have developed an injectable shear-thinning hydrogel cross-linked through electrostatic interactions and hydrogen bonding. The hydrogel underwent comprehensive characterization, focusing on rheological behavior, injectability, microstructure, film-forming capability, adhesion, swelling behavior, degradation kinetics, antibacterial efficacy, hemostatic performance, and biocompatibility. The incorporation of poly(vinyl alcohol) notably enhanced the internal structural stability and injection pressure, while the Laponite content influenced self-healing ability, modulus, and viscosity. Additionally, the hydrogel exhibited pH sensitivity, appropriate degradation, and swelling rates and displayed favorable film-forming and adhesion properties. Notably, it demonstrated excellent resistance against Escherichia coli and Staphylococcus aureus, highlighting its potential to create an optimal wound environment. In vivo studies further confirmed the hydrogel's exceptional hemostatic performance, positioning it as an optimal material for endoscopic submucosal dissection (ESD) surgery. Moreover, cell experiments and hemolysis tests revealed high biocompatibility, supporting their potential to facilitate the healing of iatrogenic ulcers post-ESD surgery. In conclusion, our hydrogels hold great promise as endoscopic treatment materials for ESD-induced ulcers given their outstanding properties.

Recent Progress and Future Prospects of Anions O-site Doped Perovskite Oxides in Electrocatalysis for Various Electrochemical Systems.

With the rapid development of novel energy conversion and storage technologies, there is a growing demand for enhanced performance in a wide range of electrocatalysts. Perovskite oxides (ABO3 ) have caused widespread concerns due to their excellent electrocatalytic properties, low cost, stable and reliable performance. In recent years, the research on anion O-site doping of perovskite oxides has been a cynosure, which is considered as a promising route for enhancing performance. However, a systematic review summarizing the research progress of anion-doped perovskite oxides is still lacking. Therefore, this review mainly introduces the elements and strategies of various common anions doped at O-site of perovskite oxides, analyzes their influence on the physical and chemical properties of perovskites, and separately concludes their applications in electrocatalysis. This review will provide ideas and prospects for the development of subsequent anion doping strategies for high performance perovskite oxides.

Boosting the Electrocatalytic Activity of Pr0.5Ba0.5FeO3-δ via Ni Doping in Symmetric Solid Oxide Electrolysis Cells.

Symmetric solid oxide electrolysis cells (SSOECs) have garnered significant scientific interest due to their simplified cell architecture, robust operational reliability, and cost-effectiveness, for which a highly electrocatalytically active electrode is the decisive main factor. This work evaluates the electrochemical performance of Ni-doped Pr0.5Ba0.5FeO3-δ (PBF) perovskite materials, with a focus on Pr0.5Ba0.5Fe0.8Ni0.2O3-δ (PBFN). The experimental findings herein prove the exceptional electrocatalytic ability of PBFN in facilitating the oxygen evolution and carbon dioxide reduction reaction, surpassing the electrochemical performance of PBF. In addition, the PBFN symmetric cell has excellent performance for CO2 electrolysis, and the cell has a low polarization resistance value of 0.1 Ω·cm2. Moreover, it achieves an impressive current density value of 1.118 A·cm-2 under operating conditions of 2.0 V and 800 °C, which is superior to those of the PBF symmetric cell and the PBFN asymmetric cell. It also has a good structural and performance stability. These results imply a bright development prospect of PBFN as electrodes for SSOECs.

Laponite stabilized endogenous antibacterial hydrogel as wet-tissue adhesive.

Clinical adhesives for suture-less wound closure remain the problem of poor biocompatibility, weak adhesive strength, and no endogenous antibacterial ability. Here, we designed a novel antibacterial hydrogel (CP-Lap hydrogel) consisting of chitosan and ε-polylysine after being modified with gallic acid (pyrogallol structure). The hydrogel was crosslinked by glutaraldehyde and Laponite via Schiff base and dynamic Laponite-pyrogallol interaction, free from heavy metal and oxidants. Given its dual crosslinking feature, the CP-Lap hydrogel exhibited adequate mechanical strength (150-240 kPa) and demonstrated swelling and degradation resistance. For a typical lap shear test with pigskin, the apparent adhesion strength of the CP-Lap hydrogel could be enhanced to ∼30 kPa benefiting from the O2 blocking effect provided by nanoconfinement space between Laponite. In addition, the hydrogel showed effective antibacterial properties and excellent biocompatibility. The results indicated that this hydrogel has great potential for wound-closing bioadhesives to avoid chronic infections and further harm.

Chlorhexidine-loaded polysulfobetaine/keratin hydrogels with antioxidant and antibacterial activity for infected wound healing.

Multifunctional hydrogel dressings are promising for wound healing. In the study, chlorhexidine(CHX) loaded double network hydrogels were prepared by free radical polymerization of sulfobetaine and oxidative self-crosslinking of reduced keratin. The introduced keratin and CHX endowed hydrogels with cytocompatibility, antioxidant capability as well as enhanced antibacterial activity due to the antifouling property of polysulfobetaine. These hydrogels exhibited acidity, glutathione(GSH), and trypsin triple-responsive release behaviors, resulting in the accelerated release of CHX under wound microenvironments. Intriguingly, the freeze-drying hydrogels could be ground to powders and sprinkled on the irregular wound bed, followed by absorbing wound fluid to reform hydrogel in situ. These xerogel powders were more convenient for sterilization, formulation, and storage. Further, these xerogel powders could be rejected after being mixed with an appropriate amount of water. In vivo infected wound healing confirmed that the xerogel powder dressing significantly promoted collagen deposition and reduced inflammation, thereby accelerating the closure and regeneration of skin wounds. Taken together, these degradable xerogel powders have great potential applications for wound healing.

Achieving Net-Zero Emissions with Solid Oxide Electrolysis Cells: The Power-to-X Approach.

Replacing fossil fuels with renewable energy sources is a crucial step for mitigating global warming. However, the intermittent nature of the most prevalent renewable sources, such as solar and wind, poses a significant challenge to their widespread deployment. One potential solution for renewable sources of storage is power-to-X, which involves the production of chemicals from electricity using solid oxide electrolysis cells. This process offers a flexible and efficient means of energy storage. This Perspective offers an overview of the characteristics, capabilities, and fundamental mechanisms of solid oxide electrolysis cells. It also examines the latest research progress and explores the prospects and challenges in this field.

Combining Panel-Based Next-Generation Sequencing and Exome Sequencing for Genetic Liver Diseases.

OBJECTIVES: To determine how advanced genetic analysis methods may help in clinical diagnosis. STUDY DESIGN: We report a combined genetic diagnosis approach for patients with clinical suspicion of genetic liver diseases in a tertiary referral center, using tools either tier 1: Sanger sequencing on SLC2SA13, ATP8B1, ABCB11, ABCB4, and JAG1 genes, tier 2: panel-based next generation sequencing (NGS), or tier 3: whole-exome sequencing (WES) analysis. RESULTS: In a total of 374 patients undergoing genetic analysis, 175 patients received tier 1 Sanger sequencing based on phenotypic suspicion, and pathogenic variants were identified in 38 patients (21.7%). Tier 2 included 216 patients (39 of tier 1-negative patients) who received panel-based NGS, and pathogenic variants were identified in 60 (27.8%). In tier 3, 41 patients received WES analysis, and 20 (48.8%) obtained genetic diagnosis. Pathogenic variants were detected in 6 of 19 (31.6%) who tested negative in tier 2, and a greater detection rate in 14 of 22 (63.6%) patients with deteriorating/multiorgan disease receiving one-step WES (P = .041). The overall disease spectrum is comprised of 35 genetic defects; 90% of genes belong to the functional categories of small molecule metabolism, ciliopathy, bile duct development, and membrane transport. Only 13 (37%) genetic diseases were detected in more than 2 families. A hypothetical approach using a small panel-based NGS can serve as the first tier with diagnostic yield of 27.8% (98/352). CONCLUSIONS: NGS based genetic test using a combined panel-WES approach is efficient for the diagnosis of the highly diverse genetic liver diseases.

Conductive Hydrogel Patches with High Elasticity and Fatigue Resistance for Cardiac Microenvironment Remodeling.

Remodeling the conductive zone to assist normal myocardial contraction and relaxation during myocardial fibrosis has become the primary concern of myocardial infarction (MI) regeneration. Herein, we report an unbreakable and self-recoverable hyaluronic acid conductive cardiac patch for MI treatment, which can maintain structural integrity under mechanical load and integrate mechanical and electrical conduction and biological cues to restore cardiac electrical conduction and diastolic contraction function. Using the free carboxyl groups and aldehyde groups in the hydrogel system, excellent adhesion properties are achieved in the interface between the myocardial patch and the tissue, which can be closely integrated with the rabbit myocardial tissue, reducing the need for suture. Interestingly, the hydrogel patch exhibits sensitive conductivity (ΔR/R0 ≈ 2.5) for 100 cycles and mechanical stability for 500 continuous loading cycles without collapse, which allows the patch to withstand mechanical damage caused by sustained contraction and relaxation of the myocardial tissue. Moreover, considering the oxidative stress state caused by excessive ROS in the MI area, we incorporated Rg1 into the hydrogel to improve the abnormal myocardial microenvironment, which achieved more than 80% free radicalscavenging efficiency in the local infarcted region and promoted myocardial reconstruction. Overall, these Rg1-loaded conductive hydrogels with highly elastic fatigue resistance have great potential in restoring the abnormal electrical conduction pathway and promoting the myocardial microenvironment, thereby repairing the heart and improving the cardiac function.

A multicenter, prospective, randomized controlled trial of intracranial hemorrhage risk of intensive statin therapy in patients with acute ischemic stroke combined with cerebral microbleeds (CHRISTMAS): Study protocol.

Background: Low serum levels of major lipid markers have been proved to be significantly associated with increased risks of hemorrhagic stroke (HS) and cerebral microbleeds (CMBs). However, there is no lipid modification guideline telling us how to maintain a balance between the prevention of ischemic stroke recurrence and the prevention of hemorrhagic events, especially in patients with acute ischemic stroke (AIS) and CMBs. Aim: The Intracranial Hemorrhage Risk of Intensive Statin Therapy in Patients with Acute Ischemic Stroke combined with Cerebral Microbleeds (CHRISTMAS) trial evaluates the risk of intracranial hemorrhage (i.e., HS and CMBs) of high-dose statin therapy in patients with AIS combined with CMBs. Methods and design: This is an investigator-initiated, multicenter, prospective, randomized controlled clinical trial design. Up to 344 eligible patients will be consecutively randomized to receive high-dose or low-dose atorvastatin in 1:1 ratio in 5 stroke centers in China. Outcomes: CHRISTMAS trial has co-primary outcomes, namely, hemorrhage risk: the incidence of HS and the changes in degree of CMBs until the end of 36-month follow-up. Discussion: The primary hypothesis of this study is that an excessive reduction in serum lipid levels by an intensive statin therapy in AIS patients with CMBs can increase the risk of intracranial hemorrhage. This study will shed light on new clinical decisions regarding the long-term serum lipid management in these patients with dilemma in clinical practice. Clinical trial registration: Clinicaltrials.gov, identifier: NCT05589454.

A mini review of the recent progress of electrode materials for low-temperature solid oxide fuel cells.

Lowering the operating temperature (450-650 °C) of solid oxide fuel cells (SOFCs) faces the intrinsic challenge of sluggish electrode reaction kinetics in the low temperature (LT) range. To accelerate the electrode reaction rate, many efforts have been put into the optimization of electrode composition and morphology. In this review, we have summarized recent developments of LT-SOFC electrodes, including anode and cathode materials. For anode performance improvement, the internal structure design, fine anode structure, reforming layer addition, and in situ exsolution techniques are introduced and their related functionalities are also explained, respectively. While for the cathode, we focus on the perovskite-type materials because of their superior catalytic performance and relatively good stability. The optimization of perovskite composition, including A site alkali or alkali-earth metal doping and B site variable-valence transition metal doping, is discussed in detail based on their effects on oxygen reduction reaction (ORR). Besides, nanostructure assembly and 3D morphology design are also recent hotspots for cathode research. Finally, we also propose several research directions in this field, hoping to provide guidelines for future research.

Enzyme-regulated NO programmed to release from hydrogel-forming microneedles with endogenous/photodynamic synergistic antibacterial for diabetic wound healing.

The infection-prone wound pathology microenvironment leads to ulceration and difficult healing of diabetic wounds, which seriously affects the quality of survival of patients. In this study, natural polymer materials gelatin and polylysine were used as substrates. By introducing iron/tannic acid (FeIIITA) composite nanoparticles with excellent photothermal properties into the system, the glutamine residues of gelatin were crosslinked with the primary ammonia of polylysine by glutamine aminotransferase. A nanocomposite hydrogel with excellent antibacterial ability and NO production was constructed it was used to improve the clinical problems of diabetes wounds that were difficult to vascularize and easy to be infected. Under the premise of maintaining its structural stability, the hydrogel can be customized to meet the needs of different mechanical strengths by adjusting the ratios to match different diabetic wounds. Meanwhile, the photothermal effect of FeIIITA nanoparticles can synergize with the endogenous antibacterial ability of polylysine to improve the antibacterial efficacy of hydrogels. The potential of hydrogel to promote intracellular NO production was confirmed by fluorescent staining. Microneedle patches prepared from hydrogel can be applied to diabetic wounds, which can achieve NO deep release. Its anti-inflammatory and angiogenic abilities are also useful in achieving effective healing of diabetic wounds.

Injectable shear-thinning sodium alginate hydrogels with sustained submucosal lift for endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is one of the most effective approaches for the minimally invasive treatment of early gastrointestinal cancers. Submucosal injections help safely and successfully remove lesions during ESD by elevating the mucosa and separating the submucosal muscle layer. Herein, we report dynamic injectable sodium alginate hydrogels (ISAHs) with shear-thinning for ESD surgery, which were easily fabricated by the sulfhydryl group of GSH-modified sodium alginate (SA-GSH) reacting with the aldehyde group of oxidized sodium alginate (OSA) at room temperature. ISAHs have advantageous self-healing abilities and antioxidant activity. Additionally, according to an in vitro test on porcine colorectal submucosal lifting, the submucosal elevation heights created by ISAHs were 13 % -18 % greater than those created by commercial ESD solutions (0.4 w/v% sodium hyaluronate). These properties and biocompatibility were confirmed in vitro and in vivo experiments. ISAHs will hopefully become a novel submucosal injectable hydrogel to assist ESD surgery.

Injectable polylysine and dextran hydrogels with robust antibacterial and ROS-scavenging activity for wound healing.

Cutaneous wound management remains a major concern due to uncontrolled inflammation and bacterial infection in clinical care. A desirable hydrogel dressing with antibacterial and antioxidative properties can drive wound healing by inhibiting infection and inflammation. Herein, a multifunctional hydrogel based on polylysine-graft-cysteine (EPL-SH)/oxidized dextran (ODex) was fabricated for promoting skin tissue regeneration. The engineered hydrogel possessed versatile properties including tunable gelation time (60-300 s), typical rheological behavior, suitable swelling and degradation progress, injectable and self-healing ability. The unique hydrogels also displayed promising tissue adhesiveness, high cell affinity, excellent antioxidant and antimicrobial activity. Furthermore, the in vivo full-thickness skin defect experiment demonstrated the simple-to-implement injectable hydrogels could significantly promoting wound healing by improving the collagen deposition and angiogenesis. The manufacture of our multifunctional hydrogels dressing affords a new strategy for improving efficacy of cutaneous wound treatment.

Upregulation of miRNA-26a Enhances the Apoptosis of Cerebral Neurons by Targeting EphA2 and Inhibiting the MAPK Pathway.

Neural tube defects (NTDs) constitute the second most common congenital malformation of the central nervous system. The pathogenesis of NTDs is not entirely clear. In recent years, microRNAs (miRNAs) have become a hot spot in genetic and developmental biology research. The present study aimed to explore the potential role of miRNA-26a in NTDs and the underlying pathogenesis thereof. First, we found significantly increased miRNA-26a expression in fetuses with NTDs (p < 0.0001), which significantly downregulated EphA2 and ERK1 mRNA and protein expression levels in fetuses with NTDs compared to normal controls (p < 0.01). In addition, a dual-luciferase reporter assay showed that miR-26a negatively regulated EphA2 by directly binding with the 3'-untranslated region of EphA2. Second, the upregulation of miRNA-26a expression increased caspase 3 and 9 protein expression levels (p < 0.01) and decreased EphA2 mRNA and protein expression levels (p < 0.01), as well as ERK1 and SRF protein expression levels (p < 0.01) in mouse neural stem cells (NE-4C) and human astroblastoma cells (U87MG). Furthermore, the upregulation of miRNA-26a inhibited cell proliferation and enhanced apoptosis of NE-4C and U87MG cells (p < 0.05). Similar results were observed with the MAPK inhibitor PD98059 (p < 0.01). These results suggest that miR-26a targets EphA2, modulates phosphorylation of the MAPK/ERK (MEK) pathway, regulates SRF, and participates in regulating nervous cell proliferation and apoptosis. Dysregulation of the aforementioned mechanism may be involved in the pathogenesis of NTDs.

Adaptive injectable carboxymethyl cellulose/poly (γ-glutamic acid) hydrogels promote wound healing.

The clinical acceleration of skin autogenous healing remains a great challenge, especially in the early stage after injury. In this work, a novel directly injectable hydrogel with high self-adaptability is designed as a provisional matrix to close the apposition of wound edges, using carboxymethyl cellulose and poly (γ-glutamic acid) through Schiff-base reaction. Benefiting from the dynamic covalent cross-linking structure, the functional biodegradable hydrogels are easy to prepare (gel time 5-180 s), demonstrating adequate mechanical strength (40-120 kPa), anti-fatigue abilities, and rapid self-healing (5-10 min at skin defect). Furthermore, the hydrogels exhibit biocompatibility and proliferation-promoting activity with murine fibroblasts. In the full-thickness dermal animal models, it significantly promoted collagen deposition, skin-function restoration, and VEGF expression. This hydrogel shows potential as a dressing available for skin regeneration during the healing of dermal injuries.

Changes in structures and digestibility of amylose-oleic acid complexes following microwave heat-moisture treatment.

Amylose-oleic acid complexes (AOA) were exposed to microwave heat-moisture treatment (M-HMT) with different moisture content (MC), and the variations in structures and digestibility were investigated. M-HMT caused the dissociation of helical structures and destruction of short-range molecular order of AOA. Meanwhile, the molecules of amylose and oleic acid rearranged and more amylose-oleic acid complexes were formed during M-HMT, the complexing index of AOA was increased from 25.41 % to 41.20 % when treating at 35 % MC. Moreover, the relative content of single helix increased with increasing MC, resulting in higher V-type relative crystallinity. With ≥30 % MC, the treated complexes showed greater thermostability than that of original AOA. The treatment increased the enzymatic digestibility of AOA, and sample treated with 35 % MC had the highest resistant starch content of 82.33 %, which was 17.96 % higher than that of native AOA. The improved enzyme resistance should be correlated to increased molecular interplay and formation of amylose-oleic acid complexes.