Targeting TRAF3 signaling protects against hepatic ischemia/reperfusions injury.

BACKGROUND & AIMS: The hallmarks of hepatic ischemia/reperfusion (I/R) injury, a common clinical problem that occurs during liver surgical procedures, include severe cell death and inflammatory responses that contribute to early graft failure and a higher incidence of organ rejection. Unfortunately, effective therapeutic strategies are limited. Tumor necrosis factor receptor (TNFR)-associated factor (TRAF) 3 transduces apoptosis and/or inflammation-related signaling pathways to regulate cell survival and cytokine production. However, the role of TRAF3 in hepatic I/R-induced liver damage remains unknown. METHODS: Hepatocyte- or myeloid cell-specific TRAF3 knockdown or transgenic mice were subjected to an I/R model in vivo, and in vitro experiments were performed by treating primary hepatocytes from these mice with hypoxia/reoxygenation stimulation. The function of TRAF3 in I/R-induced liver damage and the potential underlying mechanisms were investigated through various phenotypic analyses and biological approaches. RESULTS: Hepatocyte-specific, but not myeloid cell-specific, TRAF3 deficiency reduced cell death, inflammatory cell infiltration, and cytokine production in both in vivo and in vitro hepatic I/R models, whereas hepatic TRAF3 overexpression resulted in the opposite effects. Mechanistically, TRAF3 directly binds to TAK1, which enhances the activation of the downstream NF-κB and JNK pathways. Importantly, inhibition of TAK1 almost completely reversed the TRAF3 overexpression-mediated exacerbation of I/R injury. CONCLUSIONS: TRAF3 is a novel hepatic I/R mediator that promotes liver damage and inflammation via TAK1-dependent activation of the JNK and NF-κB pathways. Inhibition of hepatic TRAF3 may represent a promising approach to protect the liver against I/R injury-related diseases.

[Multivariate factors analysis on length of stay in Lushan earthquake victims].

OBJECTIVE: To clarify the factors associate with the length of stay (LOS) in Lushan Earthquake victims. METHODS: We retrospectively analyzed the medical information of 263 traumatic patients admitted to West China Hospital, Sichuan University after the Lushan Earthquake. Ten variables extracted for the analysis, including gender, age, injuried time, multiple injury, infection, comorbidities, Injury Severity Score (ISS), Revised Trauma Score (RTS) CRAMS score, and Prehospital Index (PHI). Univariable analysis using multiple stepwise regression analysis was performed to identify the factors associated with extended LOS. RESULTS: Infection, ISS score, and Pre-hospital Time were associated with extended LOS, and infection was the most weighted factor. The regression equation is: LOS (h) = 498.36 + 671.41 x Infection + 43.87 x ISS score - 5.12 x Pre-hospital Time. CONCLUSION: This study demonstrated that trauma patients with infections and high ISS scores were at increased risk for extended LOS and pre-hospital time decreased the risk.

Benzaldehyde-tethered fluorous tags for cytosolic delivery of bioactive peptides.

Development of intracellular delivery systems for bioactive peptides remains challenging. Herein, we report a facile strategy to address this issue by conjugating peptides with benzaldehyde-tethered fluorous tags to generate dynamic peptide amphiphiles via a hydrazone bond for efficient cytosolic delivery. Those dynamic peptide fluoroamphiphiles could self-assemble into nanoparticles that readily cross the cell membrane. Using this strategy, several bioactive peptides were efficiently internalized by cancer cells and released into the cytosol to exert their biological functions, which showed much higher efficacies than non-fluorous lipids and cell penetrating peptide decorated peptides. Moreover, the fluorous tagged proapoptotic peptide was able to efficiently inhibit tumor growth in vivo. This report provides a new family of fluorous tags based on benzaldehyde for efficient cytosolic peptide delivery.

Robust and multifunctional natural polyphenolic composites for water remediation.

The scarcity of clean water has become a global environmental problem which constrains the development of public health, economy, and sustainability. In recent years, natural polyphenols have drawn increasing interests as promising platforms towards diverse water remediation composites and devices, owing to their abundant and renewable resource in nature, highly active surface chemistry, and multifunctionality. This review aims to summarize the most recent advances and highlights of natural polyphenol-based composite materials (e.g., nanofibers, membranes, particles, and hydrogels) for water remediation, by focusing on their structural and functional features, as well as their diversified applications including membrane filtration, solar distillation, adsorption, advanced oxidation processes, and disinfection. Finally, the future challenges in this field are also prospected. It is anticipated that this review will provide new opportunities towards the future development of natural polyphenols and other kinds of naturally occurring molecules in water purification applications.

Half-Dose Anticoagulation for Venous Thromboembolism and Phlegmasia Cerulea Dolens in a Patient With Recurrent Subdural Hematoma.

Anticoagulation for venous thromboembolism (VTE) in patients with recurrent subdural hematoma (SDH) is challenging. It becomes even more challenging when the patient develops phlegmasia cerulea dolens (PCD). We present a 66-year-old female with a recent history of recurrent SDH who received half-dose heparin therapy for VTE and PCD. The patient had improvement of dyspnea and resolution of PCD after two days of treatment. She was discharged with half-dose enoxaparin. At her one-month follow-up, there was no evidence of new SDH or progression of VTE. Half-dose anticoagulation therapy should be considered in patients with recurrent SDH when anticoagulation is inevitable.

Superabsorbent poly(acrylic acid) and antioxidant poly(ester amide) hybrid hydrogel for enhanced wound healing.

Wound healing dressing is increasingly needed in clinical owing to the large quantity of skin damage annually. Excessive reactive oxygen species (ROS) produced through internal or external environmental influences can lead to lipid peroxidation, protein denaturation, and even DNA damage, and ultimately have harmful effects on cells. Aiming to sufficiently contact with the wound microenvironment and scavenge ROS, superabsorbent poly (acrylic acid) and antioxidant poly (ester amide) (PAA/PEA) hybrid hydrogel has been developed to enhance wound healing. The physical and chemical properties of hybrid hydrogels were studied by Fourier-transform infrared (FTIR) absorption spectrum, compression, swelling, degradation, etc. Besides, the antioxidant properties of hybrid hydrogels can be investigated through the free radical scavenging experiment, and corresponding antioxidant indicators have been tested at the cellular level. Hybrid hydrogel scaffolds supported the proliferation of human umbilical vein endothelial cells and fibroblasts, as well as accelerated angiogenesis and skin regeneration in wounds. The healing properties of wounds in vivo were further assessed on mouse skin wounds. Results showed that PAA/PEA hybrid hydrogel scaffolds significantly accelerated the wound healing process through enhancing granulation formation and re-epithelialization. In summary, these superabsorbent and antioxidative hybrid hydrogels could be served as an excellent wound dressing for full-thickness wound healing.

Self-Assembly of Poly(Janus particle)s into Unimolecular and Oligomeric Spherical Micelles.

Using shape-persistent Janus particles to construct poly(Janus particle)s and studying their self-assembly behaviors are of great interest, but remain largely unexplored. In this work, we reported a type of amphiphiles constructed by the ring-opening metathesis polymerization of nonspherical molecular Janus particles (APOSS-BPOSS), called poly(Janus particle)s (poly(APOSS-BPOSS)n, n = 12, 17, 22, and 35, and Mn = 35-100 kg/mol). Unlike traditional bottlebrush polymers consisting of flexible side chains, these poly(Janus particles) consist of rigid hydrophilic and hydrophobic polyhedral oligomeric silsesquioxane (POSS) cages as side chains. Interestingly, instead of maintaining an expected extended chain conformation, they could also collapse and then self-assemble to form unconventional unimolecular or oligomeric spherical micelles in solutions with a feature size smaller than 7 nm. More importantly, unlike traditional amphiphilic polymer brushes that could form unimolecular micelles at a relatively high degree of polymerization by self-assembly, these poly(Janus particles)s could accomplish self-assembly at a quite low degree of polymerization because of their unique chemical structure and molecular topology. The formation of unimolecular and oligomeric micelles was also further confirmed by dissipative particle dynamics simulations. This study of introducing the POSS-based poly(Janus particle)s as a class of shape amphiphiles will provide a model system for generating unimolecular and oligomeric micellar nanostructures through solution self-assembly.

Polydopamine antibacterial materials.

Recently, the development of polydopamine (PDA) has demonstrated numerous excellent performances in free radical scavenging, UV shielding, photothermal conversion, and biocompatibility. These unique properties enable PDA to be widely used as efficient antibacterial materials for various applications. Accordingly, PDA antibacterial materials mainly include free-standing PDA materials and PDA-based composite materials. In this review, an overview of PDA antibacterial materials is provided to summarize these two types of antibacterial materials in detail, including the fabrication strategies and antibacterial mechanisms. The future development and challenges of PDA in this field are also presented. It is hoped that this review will provide an insight into the future development of antibacterial functional materials based on PDA.

Biomimetic Gelatin Methacrylate/Nano Fish Bone Hybrid Hydrogel for Bone Regeneration via Osteoimmunomodulation.

The consideration of osteoimmunomodulatory activity is crucial to determine the in vivo fate of the bone biomaterials. Herein, we proposed a biomimetic gelatin methacrylate/nano fish bone hybrid hydrogel to systematically investigate its potential for bone regeneration. The results showed that nano fish bone incorporation could not only enhance the mechanical performance of hybrid hydrogel but also modulate the immune microenvironment to further promote bone regeneration. This nano fish bone-based hybrid hydrogel would provide a promising option for developing advanced bone biomaterials with osteoimmunomodulatory activities.

Polydopamine free radical scavengers.

Polydopamine (PDA) is the most typical kind of synthetic melanin, which possesses interesting properties such as antioxidation, photoprotection, metal chelation, and energy dissipation. Over the past few years, PDA has been successfully synthesized via polymerization methods and has demonstrated excellent free radical scavenging ability. The related applications have been rapidly expanded to include sunscreens, anti-inflammatory treatment, and composite material fabrication. Despite great progress, the comprehensive mechanisms of its free radical scavenging behaviors are not fully understood. This article strives to summarize the possible mechanisms, established antioxidant regulation methods and the related biomedical applications of PDA free radical scavengers. We believe this paper can provide insight into the current PDA scavenging systems and offer inspiration towards the design of new melanin-inspired scavengers with a broad range of biomedical applications.

Integrated POSS-dendrimer nanohybrid materials: current status and future perspective.

Polyhedral oligomeric silsesquioxane (POSS)-dendrimer hybrid materials have attracted great interest in the past ten years. The integration of inorganic POSS and organic dendrimer blocks in a single-phase material offers numerous possibilities to access desirable mechanical, optical, and biomedical properties for various applications. In this review article, we describe several kinds of POSS-dendrimer hybrid materials (POSS as the core, surface functionality, repeating unit of dendrimers and the POSS-dendron conjugates) with an emphasis on their synthetic strategies, tunable macroscopic properties, and potential applications. Moreover, the current trends, challenges and future directions of POSS-dendrimer hybrid materials are elaborated.

[Comparison of the performance of three prehospital trauma scores in evaluation of injury severity among Lushan earthquake victims].

OBJECTIVE: To investigate the performance of revised trauma score (RTS), CRAMS score (circulation, respiration, abdomen, motor and speech) and prehospital index (PHI) on evaluation of injury severity in earthquake victims. METHODS: Data of victims admitted to West China Hospital of Sichuan University during the Lushan earthquake from April 20th, 2013, to April 27th were retrospectively analyzed. The clinical information at admission was recorded, and the injury severity score (ISS), RTS, CRAMS and PHI were calculated. The optimal cut-off values were looked for, the comparability between the three scores and ISS score were figured out by receiver operator characteristic curve (ROC curve), and the correlation between ISS and three scores was analyzed by linear regression analysis. RESULTS: There was a total of 263 victims included in the study. ISS ≥ 16 was found in 86 cases, and ISS<16 in 177 victims, and there were significant statistic differences in male ratio (67.4% vs. 50.8%, χ² = 6.477, P=0.011), RTS score [7.55 (0.29) vs. 7.84 (0), U=6 825, P=0.013] and CRAMS scores [8 (1) vs. 9 (1), U=3 977, P=0.000] between two groups. It was showed by ROC curve analysis that the area under the ROC curve (AUC) of RTS, CRAMS and PHI was 0.547 (P=0.220), 0.734 (P=0.000) and 0.544 (P=0.250), and the Youden indexes of the three scores were 0.093, 0.443, and 0.119, respectively. Moreover, the best cut-off values of them were 4.9, 9.5 and 3.5. Linear regression analysis showed that RTS and CRAMS score showed negative correlation with ISS score (r1=-0.139, P1=0.024; r2=-0.413, P2=0.000), while PHI showed no relationship with it (r=0.071, P=0.250). CONCLUSIONS: Of these three scoring systems, CRAMS has the best correlation with ISS, and it can be used in the prompt assessment of trauma severity in earthquake victims.