The effects of food on the pharmacokinetics of mycophenolate mofetil in healthy horses.

Additional immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses. The aim of this study was to evaluate the pharmacokinetics of a single dose of MMF in healthy horses in the fed vs. fasted state. Six healthy Standardbred mares were administered MMF 10 mg/kg by a nasogastric (NG) tube in a fed and fasted state. A six-day washout period was performed between the two doses. No statistically significant differences in mycophenolic acid (MPA) concentrations were seen at any time point apart from 8 h, when plasma metabolite concentrations were significantly higher in the fasted state compared to the fed state (p = .038). Evidence of enterohepatic recirculation was seen only in the fasted state; this did not yield clinical differences in horses administered a single-dose administration but may be significant in horses receiving long-term MMF treatment.

Fabrication of Highly Thermally Resistant and Self-Healing Polysiloxane Elastomers by Constructing Covalent and Reversible Networks.

The fabrication of self-healing elastomers with high thermal stability for use in extreme thermal conditions such as aerospace remains a major challenge. A strategy for preparing self-healing elastomers with stable covalent bonds and dynamic metal-ligand coordination interactions as crosslinking sites in polydimethylsiloxane (PDMS) is proposed. The added Fe (III) not only serves as the dynamic crosslinking point at room temperature which is crucial for self-healing performance, but also plays a role as free radical scavenging agent at high temperatures. The results show that the PDMS elastomers possessed an initial thermal degradation temperature over 380 °C and a room temperature self-healing efficiency as high as 65.7%. Moreover, the char residue at 800 °C of PDMS elastomer reaches 7.19% in nitrogen atmosphere, and up to 14.02% in air atmosphere by doping a small amount (i.e., 0.3 wt%) of Fe (III), which is remarkable for the self-healing elastomers that contain weak and dynamic bonds with relatively poor thermal stability. This study provides an insight into designing self-healing PDMS-based materials that can be targeted for use as high-temperature thermal protection coatings.

MR microneurography of human peripheral fascicles using a clinical 3T MR scanner.

BACKGROUND AND PURPOSE: Knowledge of nerve fascicular structures is essential for managing peripheral nerve disorders. This study aimed to investigate the feasibility of z-axis high-resolution magnetic resonance (MR) microneurography (zH-MRMN) in displaying the three-dimensional structures of tibial nerve fascicles in vivo using a 3T MR scanner. MATERIALS AND METHODS: Twelve volunteers underwent z-axis conventional-resolution MR microneurography (zC-MRMN) and zH-MRMN of tibial nerves. The visibility scores of the nerve fascicles (VSNFs) on axial zC-MRMN images and axial zH-MRMN multiplanar reformation (MPR) images were compared. The nerve fascicle appearances on the longitudinal zH-MRMN MPR images were described. RESULTS: In the nerve segments whose long axes were perpendicular to the imaging planes of both zC-MRMN and zH-MRMN, the VSNFs were not significantly different between the axial images of the two modalities (P = 0.083). In the nerve segments whose long axes were not perpendicular to the imaging planes of zC-MRMN, the VSNFs on the axial zC-MRMN images were significantly lower than those on the axial zH-MRMN MPR images that were angled perpendicular to the long axis of the tibial nerve (P < 0.001). CONCLUSIONS: The longitudinal zH-MRMN MPR images clearly displayed the changing features of the intraneural fascicles as well as the gross morphology of the tibial nerves. zH-MRMN can clearly delineate the topography of the tibial nerve fascicles in vivo through use of a 3T MR scanner.

Actein antagonizes colorectal cancer through blocking PI3K/Akt pathways by downregulating IMPDH2.

Actein, a triterpene glycoside, isolated from rhizomes of Cimicifuga foetida, was reported to exhibit anticancer effects in vitro and in vivo. However, the effects of actein on colorectal cancer (CRC) remains unclear. As one of the most popular cancers all over the world, CRC ranked third place in both men and women. Recently, we investigated the potential anti-CRC effects of actein and its mechanisms. The Cell counting kit-8 cell proliferation assays, cell cycle detection, apoptosis detection, reactive oxygen species and mitochondrial membrane potential evaluation, western blot, as well as SW480 xenograft mice model were conducted to illustrate the mechanisms of action on anti-CRC effects of actein. Actein could significantly inhibit the human CRC cell lines SW480 and HT-29 proliferation, whereas less antiproliferation effects were found in normal colorectal cell lines HCoEpiC and FHC. Administration of actein resulted in G1 phase cell cycle arrest in both SW480 and HT-29 cells. Moreover, mitochondria-mediated apoptosis was also observed after treatment with actein in SW480 and HT-29 cell lines. Further investigation of mechanisms of action on actein-mediated anti-CRC proliferation effects indicated that the phosphoinositide 3-kinases (PI3K)/Akt pathways were involved. Actein significantly downregulated the phosphorylation of key molecules in PI3K/Akt pathways, including mTOR, glycogen synthesis kinase 3ß (GSK-3ß), as well as FOXO1. In addition, inosine 5'-monophosphate dehydrogenase type II (IMPDH2) was also observed decreasing in both SW480 and HT-29 cell lines after actein treatment, suggesting that actein may inhibit the PI3K/Akt pathways by decreasing IMPDH2. Finally, our SW480 xenograft model verified the anti-CRC effects and the safety of actein in vivo. Our findings suggest actein is worthy of further investigation as a novel drug candidate for the treatment of CRC.

A Mussel-Inspired Persistent ROS-Scavenging, Electroactive, and Osteoinductive Scaffold Based on Electrochemical-Driven In Situ Nanoassembly.

Conductive polymers are promising for bone regeneration because they can regulate cell behavior through electrical stimulation; moreover, they are antioxidative agents that can be used to protect cells and tissues from damage originating from reactive oxygen species (ROS). However, conductive polymers lack affinity to cells and osteoinductivity, which limits their application in tissue engineering. Herein, an electroactive, cell affinitive, persistent ROS-scavenging, and osteoinductive porous Ti scaffold is prepared by the on-surface in situ assembly of a polypyrrole-polydopamine-hydroxyapatite (PPy-PDA-HA) film through a layer-by-layer pulse electrodeposition (LBL-PED) method. During LBL-PED, the PPy-PDA nanoparticles (NPs) and HA NPs are in situ synthesized and uniformly coated on a porous scaffold from inside to outside. PDA is entangled with and doped into PPy to enhance the ROS scavenging rate of the scaffold and realize repeatable, efficient ROS scavenging over a long period of time. HA and electrical stimulation synergistically promote osteogenic cell differentiation on PPy-PDA-HA films. Ultimately, the PPy-PDA-HA porous scaffold provides excellent bone regeneration through the synergistic effects of electroactivity, cell affinity, and antioxidative activity of the PPy-PDA NPs and the osteoinductivity of HA NPs. This study provides a new strategy for functionalizing porous scaffolds that show great promise as implants for tissue regeneration.

Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury.

INTRODUCTION: Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. METHODS: Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. RESULTS: Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. DISCUSSION: Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018.

An efficient supramolecular adsorbent for co-adsorption of dyes and metal ions from wastewater and its application in self-healing materials.

Herein, a novel type of two-component supramolecular adsorbent, 2-OA, was developed based on non-covalent interactions using tetrazolyl derivative with octadecylamine (OA) and fully characterized using a number of structural and spectral techniques. The self-assembled 2-OA gels displayed remarkable stimuli-responsiveness as well as shape-persistent and self-healing properties. In addition, it was found that the adsorbent 2-OA was able to remove dyes (10 kinds of cationic and anionic dyes) and metal ions (Cu2+ and Fe2+) simultaneously from wastewater owing to synergistic electrostatic attraction, hydrogen-bonding, and hydrophobic and coordination interactions. It also exhibited excellent co-adsorption capability to dye mixtures and binary mixtures of dyes and metal ions. In particular, the dye/metal-loaded adsorbents could be obtained easily from the aqueous phase, and recycling of the adsorbents could thus be achieved. These results suggest that the supramolecular gel 2-OA not only has great potential application in wastewater treatment but also provides a strategy for the development of intriguing self-healing materials.

Examining the Mechanism of Treatment for Primary Dysmenorrhea with Wenjing Huoxue Decoction Based on Transcriptomics, Metabolomics, and Network Pharmacology.

BACKGROUND: Wenjing Huoxue Decoction (WJHXD) is a traditional treatment for primary dysmenorrhea (PD) that can quickly relieve various symptoms caused by PD. Previous clinical studies have shown that WJHXD has better long-term efficacy than ibuprofen in the treatment of PD and can reverse the disorder of T cell subsets. OBJECTIVE: To investigate the effect of WJHXD on serum-related factors in the treatment of PD, including the identification of key targets, pathways, and active ingredients. METHODS: In order to study the effects of the WJHXD intervention in Parkinson's Disease (PD) rats, we used transcriptomics and metabolomics methods to examine the differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs). We also utilized network pharmacology to predict the target and effective route of WJHXD in treating PD. Finally, we employed molecular docking (MD) technology to confirm the placement of important targets and metabolites. RESULTS: WJHXD has been found to be effective in prolonging the onset time and decreasing the number of writhing episodes in PD rats after oxytocin injection. It has also been observed to reduce the levels of PGF2, COX-2, AVP, and PGE2 in the serum of PD rats to different degrees. Transcriptomics analysis has revealed that the core targets of WJHXD include KRT1, KRT16, CCL5, F2, NOS2, RAC2, and others, while the core pathways are Calcium signaling and cAMP signaling. The Estrogen signaling pathway was found to be downregulated in PD rats compared to normal uterine tissue, but WJHXD was able to up-regulate the pathway. A combined transcriptomics and metabolomics analysis suggested that WJHXD may be involved in eight metabolism-related pathways, with the most reliable ones being mucin-type O-glycan biosynthesis and glycolysis or gluconeogenesis. MD has shown that Hydroxyisocaproic acid may bind to important targets such as SLC6A4, PTGER3, IGFBP3, and IGF2. CONCLUSION: In WJHXD, the most targeted herbs were Corydalis rhizoma, licorice, and Myrrha. The most targeted active ingredients include quercetin, 3'-Hydroxy-4'-O-methylglabridin, shinpterocarpin, and isorhamnetin. Potential targets include PTGS2, NOS2, AR, SCN5A, and GAS6. Analysis revealed 72 highly reliable relationships between group A and B DEGs and DEMs, with 23 positive correlations and 49 negative correlations among them. A combined analysis of transcriptomics, metabolomics, and network pharmacology was used to identify possible targets, pathways, and active ingredients of WJHXD in PD treatment, and the correlation between DEGs and DEMs was investigated. However, further research is required to confirm the relationship between active ingredients, targets, and metabolites.

In Situ Ceramization of Nanoscale Interface Enables Aerogel with Thermal Protection at 1950 °C.

Conventional carbon fiber felt-reinforced aerogel composites are often used as lightweight thermal protection systems (TPSs) for aerospace craft. However, due to their poor oxidation resistance, they have gradually failed to handle increasingly harsh thermal environments. In this work, a nanoscale composite coating interface of SiC-ZrC ceramic precursor is first constructed on the fiber surface. Subsequently, using the coated fiber felt as a three-dimensional skeleton and through polymerization-induced phase separation, an aerogel composite with excellent thermal protection in extreme thermal environments is prepared. Owing to the in situ ceramization of this nanoscale interface at ultrahigh temperatures, the back temperature of the 12 mm thick aerogel is only 147 °C after exposure to an oxyacetylene flame at 1950 °C for 70 s. Meanwhile, the central region of the aerogel recedes by only 7%. Not only does this work provide a way to enhance aerogels by constructing a self-ceramizable nanoscale interface it is also expected that the developed aerogel composite can be applied in the ultrahigh-temperature thermal protection of future aerospace craft.

Hierarchical Composite with Self-Adaptive Anisotropic Deformation for Thermal Protection System.

Rigid thermal protection materials such as ultra-high-temperature ceramics are desirable for applications in aerospace vehicles, but few materials can currently satisfy the emerging high-temperature sealing requirements for dynamic gaps created by the mismatch of the thermal expansion of different protection layers. Here, we design and fabricate a flexible biomimetic anisotropic deformation composite by multilayer cocuring onto fiber fabrics. It displays superior anisotropic deformation, whose longitudinal expansion ratio is 48 times greater than the transverse expansion ratio at specific temperatures. Furthermore, the ordered carbon structure created by transition-metal-catalyzed graphitization and the C/Si synergistic effect resulting from the combination of biomimetic fiber fabrics and SR enable the in situ formation of a high-temperature-resistant SiC crystalline phase within the char layer, ultimately resulting in exceptional thermal protection properties. By constructing hollow structures in situ, the back temperature of the composite, which is only 4.33 mm thick, is stabilized at 140 °C under the condition of continuous butane flame ablation (1300 °C) for 420 s. Multilayer structure and flexible features can facilitate large-scale preparation and arbitrary cutting and bending, adapted to different thermal protection areas.

Promotive role of eukaryotic translation initiation factor 4A isoform 3 in ovarian cancer cell growth and aerobic glycolysis through the pyruvate dehydrogenase kinase 4 signaling.

Ovarian cancer (OC) represents one of the most detrimental gynecological malignancies. RNA-binding protein eukaryotic translation initiation factor 4A isoform 3 (EIF4A3) is well-regarded as a definitive oncogene that contributes to the development of multiple malignant tumors. This study sought to elucidate the molecular mechanism of EIF4A3 in OC growth and aerobic glycolysis by regulation of pyruvate dehydrogenase kinase 4 (PDK4) mRNA stability. We determined the EIF4A3 and PDK4 expression levels in OC cell lines and normal ovarian epithelial cells, and subsequently evaluated the cell viability and colony formation by cell counting kit-8 and colony formation assays. The degree of cell aerobic glycolysis was evaluated by measurements of lactic acid production, glucose intake, adenosine triphosphate level, extracellular oxygen consumption, and protein levels of pyruvate kinase isozymes M2 and hexokinase-2. Afterwards, we verified the binding of EIF4A3 and PDK4 mRNA via RNA immunoprecipitation, and determined the mRNA stability after actinomycin D treatment. Finally, a series of rescue experiments was performed with pcDNA3.1-PDK4. EIF4A3 and PDK4 were upregulated in OC cells. Silencing EIF4A3 obstructed cell proliferation and aerobic glycolysis, while the same was annulled by EIF4A3 overexpression. Mechanically, EIF4A3 could bind to PDK4 mRNA to stabilize its mRNA and upregulate its protein levels. PDK4 overexpression inverted the inhibitory role of silencing EIF4A3 in proliferation and aerobic glycolysis. Overall, our findings highlighted that EIF4A3 induced OC progression by stabilizing PDK4 mRNA.

Epigenetic regulation and therapeutic strategies in ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease, and is characterized by the diffuse inflammation and ulceration in the colon and rectum mucosa, even extending to the caecum. Epigenetic modifications, including DNA methylations, histone modifications and non-coding RNAs, are implicated in the differentiation, maturation, and functional modulation of multiple immune and non-immune cell types, and are influenced and altered in various chronic inflammatory diseases, including UC. Here we review the relevant studies revealing the differential epigenetic features in UC, and summarize the current knowledge about the immunopathogenesis of UC through epigenetic regulation and inflammatory signaling networks, regarding DNA methylation, histone modification, miRNAs and lncRNAs. We also discuss the epigenetic-associated therapeutic strategies for the alleviation and treatment of UC, which will provide insights to intervene in the immunopathological process of UC in view of epigenetic regulation.

Improving the Ablation Properties of Liquid Silicone Rubber Composites by Incorporating Hexaphenoxycyclotriphosphonitrile.

The ablative properties of epoxy-modified vinyl silicone rubber (EMVSR) composites containing hexaphenoxycyclotriphosphonitrile (HPCTP) have been systematically studied. The strength of the ablation char layer was greatly enhanced with the addition of HPCTP, which induced the formation of a more complete, denser, and thicker char during oxyacetylene ablation tests. Moreover, the HPCTP-containing EMVSR composites demonstrated lower thermal conductivity and pyrolysis rate when compared with those without HPTCP. At the same time, the thermal insulation properties of HPCTP-filled composites were improved under low heat flow ablation scenarios. The reduction of graphitic carbon content, the formation of phosphate-like crystals as well as the increase of SiC content contributed to strengthening the char layer, which was critical for improving the ablation properties. The optimum char layer strength and thermal insulation properties were achieved when the content of HPCTP was 15 phr, whereas an optimum ablation resistance was achieved at 25 phr HPCTP. This suggests that HPCTP-modified EMVSR composites can be used for thermal protection purposes, especially in the fields of aerospace and aeronautics.

Flexible Thermal Protection Polymeric Materials with Self-Sensing and Self-Adaptation Deformation Abilities.

Based on the strategy of killing two birds with one stone, we introduce thermally expandable microspheres into a silicone rubber matrix to fabricate temperature-responsive controllable deformation materials, which exhibit intelligent deformation properties as well as enhanced thermal protection performance, for dynamic thermal protection in the next-generation morphing aircrafts. The formation of hollow structures endows the material with intelligent thermal management ability and makes the thermal conductivity controllable, meeting the requirements of rapid deformation and excellent thermal insulation. The dimensions of the material adaptively expand with increasing temperature, and a constant 50N force can be provided to ensure reliable sealing. Moreover, benefiting from the synergistic effect of the hollow structure and zinc borate in the ceramization process of the silicone rubber, the 10 mm thick material can reduce the temperature from 2000 to 63 °C, and the mass ablation rate is only 4.8 mg/s. To broaden the application of our material, a sensor with a sandwich structure composed of different functional layers is designed. It is pleasantly surprising to observe that the sensor can provide real-time remote warning of fire and overheating sites with a response time as short as 1 s. This synergistic strategy opens a new possibility to fabricate intelligent thermal protection materials.

A single-cell atlas depicting the cellular and molecular features in human anterior cruciate ligamental degeneration: A single cell combined spatial transcriptomics study.

Background: To systematically identify cell types in the human ligament, investigate how ligamental cell identities, functions, and interactions participated in the process of ligamental degeneration, and explore the changes of ligamental microenvironment homeostasis in the disease progression. Methods: Using single-cell RNA sequencing and spatial RNA sequencing of approximately 49,356 cells, we created a comprehensive cell atlas of healthy and degenerated human anterior cruciate ligaments. We explored the variations of the cell subtypes' spatial distributions and the different processes involved in the disease progression, linked them with the ligamental degeneration process using computational analysis, and verified findings with immunohistochemical and immunofluorescent staining. Results: We identified new fibroblast subgroups that contributed to the disease, mapped out their spatial distribution in the tissue and revealed two dynamic trajectories in the process of the degenerative process. We compared the cellular interactions between different tissue states and identified important signaling pathways that may contribute to the disease. Conclusions: This cell atlas provides the molecular foundation for investigating how ligamental cell identities, biochemical functions, and interactions contributed to the ligamental degeneration process. The discoveries revealed the pathogenesis of ligamental degeneration at the single-cell and spatial level, which is characterized by extracellular matrix remodeling. Our results provide new insights into the control of ligamental degeneration and potential clues to developing novel diagnostic and therapeutic strategies. Funding: This study was funded by the National Natural Science Foundation of China (81972123, 82172508, 82372490) and 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301).

Pharmacokinetics and tolerability of multiple-day oral dosing of mycophenolate mofetil in healthy horses.

BACKGROUND: Additional efficacious immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses. HYPOTHESIS/OBJECTIVES: To evaluate the pharmacokinetics (PK) of multiple-day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen. ANIMALS: Six healthy Standardbred mares. METHODS: Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough samples collected every 24 hours, immediately before morning drug administration. Noncompartmental PK analyses were performed to determine primary PK parameters, followed by calculation of geometric means and coefficients of variation. A CBC, serum biochemical profile, physical examination, and fecal scoring were used to assess dose tolerability. RESULTS: Seven days of treatment resulted in a mycophenolic acid (MPA) area under the curve (AUC0-12 ) of 12 594 h × ng/mL (8567-19 488 h × ng/mL) and terminal half-life (T1/2 ) of 11.3 hours (7.5-15.9 hours), yielding minor metabolite accumulation in all horses treated. Salmonellosis was detected in the feces of 2 horses by Day 7, and all horses developed myelosuppression, hyperbilirubinemia, hyporexia, decreased gastrointestinal motility, and decreased fecal output by the seventh day of treatment. CONCLUSION AND CLINICAL IMPORTANCE: Administration of MMF at 10 mg/kg PO q12h resulted in hematologic and clinical toxicity within 1 week of treatment. A decreased MMF dose, frequency, or both is needed to avoid colic. Drug monitoring should include frequent hemograms, serum biochemical profiles, and strict biosecurity protocols.

A Metal-Organic Framework-Incorporated Hydrogel for Delivery of Immunomodulatory Neobavaisoflavone to Promote Cartilage Regeneration in Osteoarthritis.

The treatment of osteoarthritis (OA)-related cartilage defects is a great clinical challenge due to the complex pathogenesis of OA and poor self-repair ability of cartilage tissue. Combining local and long-term anti-inflammatory therapies to promote cartilage repair is an effective method to treat OA. In this study, a zinc-organic framework-incorporated extracellular matrix (ECM)-mimicking hydrogel platform was constructed for the inflammatory microenvironment-responsive delivery of neobavaisoflavone (NBIF) to promote cartilage regeneration in OA. The NBIF was encapsulated in situ in zeolitic imidazolate frameworks (ZIF-8 MOFs). The NBIF@ZIF-8 MOFs were decorated with polydopamine and incorporated into a methacrylate gelatin/hyaluronic acid hybrid network to form the NBIF@ZIF-8/PHG hydrogel. The hydrogel featured excellent cell/tissue affinity, providing a favorable microenvironment for recruiting cells and cytokines to the defect sites. The hydrogel enabled the on-demand NBIF released in response to a weakly acidic microenvironment at the injured joint site to resolve inflammatory responses during the early stages of OA. Consequently, the cooperativity of the loaded NBIF and hydrogel synergistically modulated the immune response and assisted in cartilage defect repair. In summary, the NBIF@ZIF-8/PHG hydrogel delivery platform represents an effective treatment strategy for OA-related cartilage defects and may attract attentions for applications in other inflammatory diseases.

A decellularized nerve matrix scaffold inhibits neuroma formation in the stumps of transected peripheral nerve after peripheral nerve injury.

Traumatic painful neuroma is an intractable clinical disease characterized by improper extracellular matrix (ECM) deposition around the injury site. Studies have shown that the microstructure of natural nerves provides a suitable microenvironment for the nerve end to avoid abnormal hyperplasia and neuroma formation. In this study, we used a decellularized nerve matrix scaffold (DNM-S) to prevent against the formation of painful neuroma after sciatic nerve transection in rats. Our results showed that the DNM-S effectively reduced abnormal deposition of ECM, guided the regeneration and orderly arrangement of axon, and decreased the density of regenerated axons. The epineurium-perilemma barrier prevented the invasion of vascular muscular scar tissue, greatly reduced the invasion of α-smooth muscle actin-positive myofibroblasts into nerve stumps, effectively inhibited scar formation, which guided nerve stumps to gradually transform into a benign tissue and reduced pain and autotomy behaviors in animals. These findings suggest that DNM-S-optimized neuroma microenvironment by ECM remodeling may be a promising strategy to prevent painful traumatic neuromas.

Infant Skin Friendly Adhesive Hydrogel Patch Activated at Body Temperature for Bioelectronics Securing and Diabetic Wound Healing.

Adhesive-caused injury is a great threat for infants with premature skin or diabetic patients with fragile skin because extra-strong adhesion might incur pain, inflammation, and exacerbate trauma upon removal. Herein, we present a skin-friendly adhesive hydrogel patch based on protein-polyphenol complexation strategy, which leads to a thermoresponsive network sensitive to body temperature. The adhesion of the hydrogel is smartly activated after contacting with warm skin, whereas the painless detachment is easily realized by placing an ice bag on the surface of the hydrogel. The hydrogel exhibits an immunomodulatory performance that prevents irritation and allergic reactions during long-period contact with the skin. Thus, the hydrogel patch works as a conformable and nonirritating interface to guarantee nondestructively securing bioelectronics on infant skin for healthcare. Furthermore, the hydrogel patch provides gentle adhesion to wounded skin and provides a favorable environment to speed up the healing process for managing diabetic wounds.

Boosting the anti-poisoning ability of palladium towards electrocatalytic formic acid oxidation via polyphosphide chemistry.

In this work, we reported a novel polyphosphide strategy for the synthesis of phosphorus doped Pd (P-Pd) using red phosphorus as the starting material at quasi-ambient conditions. Polyphophide anions, as the key reaction intermediates, served as the reducing agent and phosphorus source to modulate the surface electronic structure of Pd. The P-Pd obtained exhibited topmost CO tolerance and electrocatalytic activity to formic acid oxidation among the state-of-arts reports. The mass activity and turnover frequency of P-Pd reached 4413 mA mg-1Pd and 16.04 s-1 at 0.8 V, which were 23.7 and 6.4 times that of commercial Pd/C respectively. After 1000 repeated cycles, 82% initial activity was reserved. Combined with the electrochemical analysis and the density functional theory calculation, the boosted electrochemical performances can be attributed to the size and electronic effects induced by the P doping, which increase the surface actives sites, inhibit the adsorption of CO and change the reaction pathway to favorable CO2 route. A full cell was also assembled to demonstrate the practical potential of the P-Pd, which showed a maximum power density of 21.56 mW cm-2. This polyphophide-based reaction route provides a new strategy for the preparation of efficient and durable phosphorus doped alloys for electrocatalysis.