Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptotic cell death in a variety of tumor cells without significant cytotoxicity on normal cells. However, many cancer cells with apoptotic defects are resistant to treatment with TRAIL alone, limiting its potential as an anticancer therapeutic. Here, we report on the tumoricidal activity of a human single-chain fragment variable, HW1, which specifically binds to TRAIL receptor 2 (TR2) without competing with TRAIL for the binding. HW1 treatment as a single agent induces autophagic cell death in a variety of both TRAIL-sensitive and TRAIL-resistant cancer cells, but exhibits much less cytotoxicity on normal cells. The HW1-induced autophagic cell death was inhibited by an autophagy inhibitor, 3-methyladenine, or by RNA interference knockdown of Beclin-1 and Atg7. We also show that the HW1-mediated autophagic cell death occurs predominantly via the c-Jun NH 2 -terminal kinase pathway in a caspase-independent manner. Analysis of the death-inducing signaling complex induced by HW1 binding to TR2 exhibits the recruitment of TNF receptor-associated death domain and TNF receptorassociated factor 2, but not Fas-associated death domain, caspase-8, or receptor-interacting protein, which is distinct from that induced by TRAIL. Our results reveal a novel TR2-mediated signaling pathway triggering autophagic cell death and provides a new strategy for the elimination of cancer cells, including TRAIL-resistant tumors, through nonapoptotic cell death. [Cancer Res 2007;67(15):7327-34]

Two-dimensional (2D) nanomaterials, such as graphene-based materials and transition metal dichalcogenide (TMD) nanosheets, are promising materials for biomedical applications owing to their remarkable cytocompatibility and physicochemical properties. On the basis of their potent antibacterial properties, 2D materials have potential as antibacterial films, wherein the 2D nanosheets are immobilized on the surface and the bacteria may contact with the basal planes of 2D nanosheets dominantly rather than contact with the sharp edges of nanosheets. To address these points, in this study, we prepared an effective antibacterial surface consisting of representative 2D materials, i.e., graphene oxide (GO) and molybdenum disulfide (MoS), formed into nanosheets on a transparent substrate for real device applications. The antimicrobial properties of the GO-MoS nanocomposite surface toward the Gram-negative bacteria Escherichia coli were investigated, and the GO-MoS nanocomposite exhibited enhanced antimicrobial effects with increased glutathione oxidation capacity and partial conductivity. Furthermore, direct imaging of continuous morphological destruction in the individual bacterial cells having contacts with the GO-MoS nanocomposite surface was characterized by holotomographic (HT) microscopy, which could be used to detect the refractive index (RI) distribution of each voxel in bacterial cell and reconstruct the three-dimensional (3D) mapping images of bacteria. In this regard, the decreases in both the volume (67.2%) and the dry mass (78.8%) of bacterial cells that came in contact with the surface for 80 min were quantitatively measured, and releasing of intracellular components mediated by membrane and oxidative stress was observed. Our findings provided new insights into the antibacterial properties of 2D nanocomposite film with label-free tracing of bacterial cell which improve our understanding of antimicrobial activities and opened a window for the 2D nanocomposite as a practical antibacterial film in biomedical applications.

Background: Scoring systems integrating possible prognostic factors and predicting rotator cuff healing after surgical repair could provide valuable information for clinical practice. Purpose: To determine the prognostic factors predictive of rotator cuff healing after surgical repair and to integrate these factors into a scoring system. Study Design: Case-control study; Level of evidence, 3. Methods: The authors reviewed the records of 603 patients who, at least 12 months after primary rotator cuff repair by a single surgeon, had magnetic resonance imaging or computed tomographic arthrography to assess repair integrity. The mean age at the time of surgery was 60 years (range, 39-81 years), and 378 patients were women (62.7%). Previous known or suggested factors affecting cuff integrity were analyzed through univariate and multivariate analyses. Factors identified in the multivariate analysis were integrated in a scoring system based on odds ratios (ORs). Results: The overall healing failure rate was 24%. The following independent risk factors were identified in the multivariate analysis: age .70 years at the time of surgery (P = .003, OR = 2.71), size of the tear in anteroposterior dimension (P = .033, OR = 1.94) and retraction (P = .000, OR = 4.56), fatty infiltration of infraspinatus exceeding grade 2 (P = .001, OR = 2.91), low bone mineral density (T score-2.5, P = .04, OR = 1.95), and high level of work activity (P = .036, OR = 2.18). A 15-point scoring system comprised the following: 4 points for retraction; 3 points for fatty infiltration of infraspinatus; and 2 points for anteroposterior tear size, age, bone mineral density, and work activity, weighted according to multivariate analysis ORs. Patients with 4 points had a 6.0% healing failure rate, and those with 5 and 10 points had 55.2% and 86.2% healing failure rates, respectively. Conclusion: A numerical scoring system including significant clinical and radiological factors was designed to predict healing of the rotator cuff after surgical repair. This scoring system helped predict the adequacy of the repair and assist in deciding the appropriate treatment options.

The most important finding of this study was the potential for a new biological supplement to enhance rotator cuff healing-a continuing challenge.

Graphene produced by chemical vapor deposition (CVD) has attracted great interest as a transparent conducting material, due to its extraordinary characteristics such as flexibility, optical transparency, and high conductivity, especially in next-generation displays. Graphene-based novel electrodes have the potential to satisfy the important factors for high-performance flexible organic light-emitting diodes (OLEDs) in terms of sheet resistance, transmittance, work function, and surface roughness. In this study, flexible and transparent graphene electrode architecture is proposed by adopting a selective defect healing technique for CVD-grown graphene, which results in several benefits that produce high-performance devices with excellent stabilities. The proposed architecture, which has a multi-layer graphene structure treated by a layer-by-layer healing process, exhibits significant improvement in sheet resistance with high optical transparency. For improving the charge transport property and mechanical robustness, various defect sites of the CVD-grown graphene are successfully decorated with gold nanoparticles through a simple electroplating (EP) method. Further, a graphene-based OLED device that integrates the proposed electrode architecture on flexible substrates is demonstrated. Therefore, this architecture provides a new strategy to fabricate graphene electrode in OLEDs, extending graphene's immense potential as an advanced conductor toward high-performance, flexible, and transparent displays.

Two-dimensional transition metal dichalcogenides (TMDs) are promising materials for a range of applications owing to their intriguing properties including the excellent electrical performance and biocompatibility. Strikingly, 1T-phase TMDs have attracted significant interest based on their metallic properties with octahedral metal coordination where the phase transition can occur from the semiconducting 2H-phase to metallic 1T-phase by chemical intercalation-induced exfoliation process. In this regard, 1T-phase TMDs have great potential in antibacterial agents in terms of effective charge transfer between the bacterial membrane and TMD nanosheets while their biological interactions have been underexplored. To bridge this gap, we herein investigate the antibacterial activities of various 1T-phase TMDs including molybdenum disulfide (MoS2), tungsten disulfide (WS2), and molybdenum diselenide (MoSe2) toward Gram-negative bacteria Escherichia coli that exhibit the reduction of bacterial viability caused by the production of reactive oxygen species, oxidation of glutathione and other chemical functionalities. The effective antibacterial capacity of metallic 1T-phase TMDs is observed and their bactericidal mechanisms are investigated in terms of their electrical conductivity and chemical oxidation property that induce the charge transfer from bacterial membrane to TMDs leading to the continuous disruption of bacteria and loss of cellular components. Furthermore, we demonstrated the transparent antibacterial films consisting of 1T-phase TMDs in which TMD nanosheets are immobilized on the surfaces and their basal planes play an important role in antibacterial actions for practical biomedical applications. Thus, our findings provide new insights into the great potential of 1T-phase TMDs as promising building blocks for antibacterial surfaces and contribute to the widespread use of 1T-phase TMDs for practical biomedical applications.

DL-PDT with MAL shows clinically good responses to inflammatory lesions and is well tolerated in patients with moderate to severe acne.

The bark of Rhus verniciflua Stokes (RVS) has been used to treat cancer in Korean herbal medicine. When we screened for PD-1 and CTLA-4 immune checkpoint inhibitors (PD-1/PD-L1 CTLA-4/CD80) from around 800 herbal extracts using competitive Enzyme-Linked Immunosorbent Assay (ELISA), we found that RVS blocked both the PD-1/PD-L1 and the CTLA-4/CD80 interactions. To identify the active compounds from RVS, we performed bioactivity-guided fractionation, and the ethyl acetate (EtOAc) fraction of RVS proved to be the most effective at blocking the PD-1/PD-L1 and CTLA-4/CD80 interactions. In addition, we isolated and identified 20 major compounds in the EtOAc fraction of RVS and then examined the blocking effects of these 20 compounds on PD-1/PD-L1 and CTLA-4/CD80. Among them, four compounds [eriodictyol (7) > fisetin (9) > quercetin (18) > liquiritigenin (13)] blocked the interaction of PD-1/PD-L1 on competitive ELISA. In addition, four different compounds [protocatechuic acid (2) > caffeic acid (19) > taxifolin (5) > butin (6)] blocked the interaction of CTLA-4/CD80. Our findings suggest that RVS and its components could be used as a potential immune checkpoint inhibitor blockade and could be developed for immuno-oncological therapeutics.