Second near-infrared photothermal-amplified immunotherapy using photoactivatable composite nanostimulators.

BACKGROUND: The construction of a nanoimmune controlled-release system that spatiotemporally recognizes tumor lesions and stimulates the immune system response step by step is one of the most potent cancer treatment strategies for improving the sensitivity of immunotherapy response. RESULTS: Here, a composite nanostimulator (CNS) was constructed for the release of second near-infrared (NIR-II) photothermal-mediated immune agents, thereby achieving spatiotemporally controllable photothermal-synergized immunotherapy. CNS nanoparticles comprise thermosensitive liposomes as an outer shell and are internally loaded with a NIR-II photothermal agent, copper sulfide (CuS), toll-like receptor-9 (TLR-9) agonist, cytosine-phospho-guanine oligodeoxynucleotides, and programmed death-ligand 1 (PD-L1) inhibitors (JQ1). Following NIR-II photoirradiation, CuS enabled the rapid elevation of localized temperature, achieving tumor ablation and induction of immunogenic cell death (ICD) as well as disruption of the lipid shell, enabling the precise release of two immune-therapeutical drugs in the tumor region. Combining ICD, TLR-9 stimulation, and inhibited expression of PD-L1 allows the subsequent enhancement of dendritic cell maturation and increases infiltration of cytotoxic T lymphocytes, facilitating regional antitumor immune responses. CONCLUSION: CNS nanoparticle-mediated photothermal-synergized immunotherapy efficiently suppressed the growth of primary and distant tumors in two mouse models and prevented pulmonary metastasis. This study thus provides a novel sight into photo-controllably safe and efficient immunotherapy.

Mechanical and moisture barrier properties of corn distarch phosphate film influenced by modified microcry stalline corn straw cellulose.

BACKGROUND: In this paper, a novel modified microcrystalline corn straw cellulose (MMCSC) was prepared by ultrasonic/microwave-assisted treatment. Effective incorporation of MMCSC into corn distarch phosphate (CDP)-based composite films was investigated. RESULTS: As the proportion of MMCSC was increased, tensile strength increased initially before decreasing, and the elongation at break always decreased. The composite film of MMCSC20 showed the lowest water vapor permeability (2.917 × 10-7 g m-1 h-1 Pa-1 ). The measurement of surface color showed that by the increasing of the MMCSC proportion in composite films, the L* and b* values and the total color difference (ΔE* ) increased, while a* values decreased. Fourier transform infrared spectroscopy and X-ray diffraction analysis indicated that, with the incorporation of MMCSC, the stable structure of the films was enhanced through cross-linking and the crystallinity was increased. A scanning electron microscopy study revealed the surface microstructure of films (MMCSC0-MMCSC30) was smooth and homogeneous, and there was no distinct separation in the matrix of composite films. CONCLUSION: The incorporation of suitable MMCSC could improve the properties of composite films. The CDP-MMCSC films, which are completely biodegradable and environmental friendly, have a high potential to be used for food packaging. © 2018 Society of Chemical Industry.

Polymer-based hydrogels with local drug release for cancer immunotherapy.

Immunotherapy that boosts the body's immune system to treat local and distant metastatic tumors has offered a new treatment option for cancer. However, cancer immunotherapy via systemic administration of immunotherapeutic agents often has two major issues of limited immune responses and potential immune-related adverse events in the clinic. Hydrogels, a class of three-dimensional network biomaterials with unique porous structures can achieve local delivery of drugs into tumors to trigger the antitumor immunity, resulting in amplified immunotherapy at lower dosages. In this review, we summarize the recent development of polymer-based hydrogels as drug release systems for local delivery of various immunotherapeutic agents for cancer immunotherapy. The constructions of polymer-based hydrogels and their local delivery of various drugs in tumors to achieve sole immunotherapy, and chemotherapy-, and phototherapy-combinational immunotherapy are introduced. Furthermore, a brief conclusion is given and existing challenges and further perspectives of polymer-based hydrogels for cancer immunotherapy are discussed.

Near-infrared photothermal liposomal nanoantagonists for amplified cancer photodynamic therapy.

Photodynamic therapy (PDT) has been demonstrated to be a promising strategy for the treatment of cancer, while its therapeutic efficacy is often compromised due to excessive concentrations of glutathione (GSH) as a reactive oxygen species (ROS) scavenger in cancer cells. Herein, we report the development of near-infrared (NIR) photothermal liposomal nanoantagonists (PLNAs) for amplified PDT through through the reduction of intracellular GSH biosynthesis. Such PLNAs were constructed via encapsulating a photosensitizer, indocyanine green (ICG) and a GSH synthesis antagonist, l-buthionine sulfoximine (BSO) into a thermal responsive liposome. Under NIR laser irradiation at 808 nm, PLNAs generate mild heat via a ICG-mediated photothermal conversion effect, which leads to the destruction of thermal responsive liposomes for a controlled release of BSO in a tumor microenvironment, ultimately reducing GSH levels. This amplifies intracellular oxidative stresses and thus synergizes with PDT to afford an enhanced therapeutic efficacy. Both in vitro and in vivo data verify that PLNA-mediated phototherapy has an at least 2-fold higher efficacy in killing cancer cells and inhibiting tumor growth compared to sole PDT. This study thus demonstrates a NIR photothermal drug delivery nanosystem for amplified photomedicine.

Mechanical, barrier and antimicrobial properties of corn distarch phosphate/nanocrystalline cellulose films incorporated with Nisin and ε-polylysine.

Antimicrobial bio-nanocomposite films were prepared by incorporating nisin (0.25-0.5% W/W) and ε-polylysine (PL, 0.2% W/W) into corn distarch phosphate/nanocrystalline cellulose based films (CN) via casting method. Nisin and PL had significant effects on color parameters (L*, a*, b* and ∆E*) and improved the mechanical, barrier properties, thermal stability of the films. The CN bio-nanocomposite films incorporation the combination of nisin and PL had synergistic antimicrobial activity against Gram-positive bacteria (S. aureus) and Gram-negative bacteria (E. coli). Structural property assessment by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) revealed that a clear interaction between the hydroxyl groups of corn distarch phosphate and the amino groups of nisin and PL, leading to the microstructure of the CN bio-nanocomposite films with appropriate content of nisin and PL was more continuous and compact. These results indicate that the CN bio-nanocomposite films containing nisin and PL is a potential active packaging material with enhanced physicochemical properties in food industry.

The Effectiveness and Prognostic Factors of CT-Guided Radioactive I-125 Seed Implantation for the Treatment of Recurrent Head and Neck Cancer After External Beam Radiation Therapy.

PURPOSE: To analyze the efficacy and safety of radioactive I-125 seed implantation in the treatment of recurrent head and neck tumors after radiation therapy. METHODS AND MATERIALS: The data of 101 patients with recurrent head and neck cancer after radiation therapy who received computed tomography guided radioactive I-125 seed implantation were analyzed. The median previous cumulative external irradiation dose was 66 Gy, and the median dose to 90% of the target volume (D90) after operation was 117 Gy. The short-term efficacy was evaluated by Response Evaluation Criteria in Solid Tumors version 1.1, and the adverse event was evaluated by Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The 5-year local control rate was 26.6%, and the 5-year overall survival rate was 15.5%. Univariate analysis showed that factors related to local control rate included age, pathologic type, implantation site, lesion volume, and D90. The 5-year local control rate was 11.5% (2-year) if D90 was <120 Gy and 44.2% if D90 was ≥120 Gy (P = .001). Multivariate analysis showed that pathologic type, lesion volume, and D90 were independent factors related to local control (P = .002, 0, .014, respectively); Karnofsky performance status and lesion volume were independent factors associated with survival (P = .021 and 0, respectively). For the side effects, there were 26 cases of skin or mucosa ulceration (25.7%), 14 cases of pain (13.9%), and 2 cases of dry mouth (2%). The correlation between toxicity and dose had not been found. CONCLUSIONS: Radioactive I-125 seed implantation in the treatment of recurrent head and neck cancer after radiation therapy showed acceptable efficacy and safety. Nonsquamous carcinoma, small lesion volume, and high dose (D90) were correlated with better local control.

Facile and Versatile Strategy for Construction of Anti-Inflammatory and Antibacterial Surfaces with Polydopamine-Mediated Liposomes Releasing Dexamethasone and Minocycline for Potential Implant Applications.

Reducing early nonbacterial inflammation induced by implanted materials and infection resulting from bacterial contamination around the implant-abutment interface could greatly decrease implant failure rates, which would be of clinical significance. In this work, we presented a facile and versatile strategy for the construction of anti-inflammatory and antibacterial surfaces. Briefly, the surfaces of polystyrene culture plates were first coated with polydopamine and then decorated with dexamethasone plus minocycline-loaded liposomes (Dex/Mino liposomes), which was validated by contact angle goniometry, quartz crystal microbalance, and fluorescence microscopy. Dex/Mino liposomes were dispersed on functional surfaces and the drug release kinetics exhibited the sustained release of dexamethasone and minocycline. Our results demonstrated that the Dex/Mino liposome-modified surfaces had good biocompatibility. Additionally, liposomal dexamethasone reduced proinflammatory mediator expression (particularly IL-6 and TNF-α) in lipopolysaccharide-stimulated human gingival fibroblasts and human mesenchymal stem cells. Moreover, liposomal minocycline prevented the adhesion and proliferation of Porphyromonas gingivalis (Gram-negative bacteria) and Streptococcus mutans (Gram-positive bacteria). These findings demonstrate that an anti-inflammatory and antibacterial surface was developed, using dopamine as a medium and combining a liposomal delivery device, which has potential for use to reduce implant failure rates. Accordingly, the surface modification strategy presented could be useful in biofunctionalization of implant materials.

A clinical assessment of the Glidescope videolaryngoscope in nasotracheal intubation with general anesthesia.

STUDY OBJECTIVES: To evaluate the efficacy and safety of the Glidescope videolaryngoscope as a device to aid nasotracheal intubation, and to determine whether the GSVL provides a better laryngeal view in patients with difficult laryngoscopy compared with the Macintosh laryngoscope. DESIGN: Prospective, clinical study. SETTING: Two university hospitals. PATIENTS: 156 healthy adult ASA physical status I and II undergoing elective plastic and intraoral surgery with general anesthesia. INTERVENTIONS: After anesthesia induction with intravenous injection of fentanyl 2 microg/kg, propofol 2 mg/kg, and vecuronium 0.1 mg/kg, nasotracheal intubation was performed using GSVL. MEASUREMENTS: Preoperative airway measurements were taken to predict potential difficult airways. During nasotracheal intubation using GSVL, laryngeal views, times required for full visualization of glottis and successful intubation, difficulty encountered and auxiliary maneuvers adopted, and upper airway trauma were recorded. The laryngeal views obtained by GSVL and by Macintosh laryngoscope were compared. MAIN RESULTS: The laryngeal views obtained by GSVL in all patients were Cormack and Lehane (C&L) grades I and II, and the success rate of intubation using GSVL at one attempt was 98.1%. The times required for visualization of the glottis and successful intubation were 40.2 +/- 11.5 s and 52.7 +/- 12.3 seconds, respectively. Patients with C&L grade II needed more auxiliary maneuvers to achieve successful intubation than did those with C&L grade I (P < 0.001). In 36 patients with potential difficult airways, the frequency of difficult laryngoscopy (C&L grades III and IV) with the Macintosh laryngoscope (58.3%) was significantly higher than with the GSVL (0%, P < 0.05). The frequency of minor upper airway trauma was 4.5%. CONCLUSIONS: The GSVL is an effective device for nasotracheal intubation and may be incorporated easily into routine clinical practice. Compared with the Macintosh laryngoscope, the GSVL can provide an improved laryngeal view in the patient with difficult airway.

Effect of Incorporation Nanocrystalline Corn Straw Cellulose and Polyethylene Glycol on Properties of Biodegradable Films.

This work aimed to study the effect of nanocrystalline corn straw cellulose (NCSC) and polyethylene glycol (PEG) on the properties of biodegradable corn distarch phosphate (CDP) films. The mechanical properties and barrier properties were investigated. Meanwhile, the compatibility, crystallization, thermal stability, and morphological structure of the films were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (X-RD), thermogravimetric (TGA), and scanning electron microscopy (SEM). In contrast with the CDP films, incorporation of NCSC in the films improved their tensile strength (TS) significantly, and incorporation of PEG improved their elongation at break (EAB) significantly else. PEG, CDP, and NCSC (P-CDP/NCSC) blend films had the best barrier properties. The thermal stability of the films was increased by the incorporation of NCSC. X-RD showed that CDP and NCSC (CDP/NCSC) films had higher crystallinity. SEM revealed that all films had smooth surface, while the films presented a uniform network structure through the incorporation of NCSC.

[A retrospective clinical analysis of endodontic treatment of maxillary first molars].

PURPOSE: To evaluate the effect of root canal therapy (RCT) of maxillary first molars and the relevant influential factors. METHODS: A total of 170 maxillary first molars undergoing endodontic treatment were retrospectively studied. 100 molars were treated with vertical compaction technique (VCT) using warm gutta- percha under dental operating microscope (DOM), while 70 molars with traditional lateral compaction technique (LCT) under naked eyes. All patients were asked to revisit 5 years later and 5-year success rate was evaluated. Reversion 3.0.2 software package was used to analyze the data. RESULTS: The immediate high quality rates of RCT of VCT and LCT were 91% and 75.7%, respectively, which has significant difference (P<0.05). After 5 years, VCT kept high quality rate of RCT, while the high quality rate of RCT with LCT dropped from 75.7% to 68.6%. The 5-year clinical success rates of RCT with VCT and LCT were 98% and 81.4%, respectively; which had significant difference (P<0.05). CONCLUSIONS: VCT has excellent clinical effect in RCT of maxillary first molars. The use of DOM can increase the detection rate of the second mesiobuccal canal (MB2).

Cellobiose as a model system to reveal cellulose dissolution mechanism in acetate-based ionic liquids: Density functional theory study substantiated by NMR spectra.

Cellulose dissolution mechanism in acetate-based ionic liquids was systematically studied in Nuclear Magnetic Resonance (NMR) spectra and Density Functional Theory (DFT) methods by using cellobiose and 1-butyl-3-methylimidazolium acetate (BmimAc) as a model system. The solubility of cellulose in ionic liquid increased with temperature increase in the range of 90-140°C. NMR spectra suggested OAc(-) preferred to form stronger hydrogen bonds with hydrogen of hydroxyl in cellulose. Electrostatic potential method was employed to predict the most possible reaction sites and locate the most stable configuration. Atoms in molecules (AIM) theory was used to study the features of bonds at bond critical points and the variations of bond types. Simultaneously, noncovalent interactions were characterized and visualized by employing reduced density gradient analysis combined with Visual Molecular Dynamics (VMD) program. Natural bond orbital (NBO) theory was applied to study the noncovalent nature and characterize the orbital interactions between cellobiose and Bmim[OAc].

The Density of States and the Transport Effective Mass in a Highly Oriented Semiconducting Polymer: Electronic Delocalization in 1D.

The determination of the band structure along k parallel to the chain direction demonstrates significant electronic delocalization. The small effective mass [m* = 0.106mo ] is consistent with the high measured mobility.

Spontaneous periodontitis is associated with metabolic syndrome in rhesus monkeys.

OBJECTIVE: The present study was designed to investigate (1) whether the non-human primate would be an appropriate animal model for the study of spontaneous periodontitis and its association with metabolic syndrome (MetS), and (2) whether microRNAs (miRNAs) play roles in the co-development of metabolic disorders and periodontitis. DESIGN: Rhesus monkeys (aged 12-29 years) with or without MetS were analyzed for the prevalence of periodontitis. The potential mechanisms underlying the association between MetS and periodontitis were explored using miRNA profiling of the gingival tissues from the MetS monkey groups with or without periodontitis as well as the age-matched controls. RESULTS: Among the 57 rhesus monkeys examined, 18 were diagnosed with periodontitis according to the inclusion criteria, with an overall prevalence of 31.6%. Moreover, the prevalence of periodontitis was 8.3% in the control group, 18.2% in the at-risk group, and 44.1% in the MetS group. The C-reactive protein level was doubled in the MetS periodontitis group, compared to the non-periodontitis sub-groups. Most importantly, only 3 miRNAs were confirmed to be differentially expressed between the MetS periodontitis and non-periodontitis subgroups while other miRNAs showed similar expression profiles. CONCLUSIONS: The results indicate that the monkey with MetS is an ideal model for studies of spontaneous periodontitis and its association with MetS. miRNA profiling using this unique model showed that miRNAs play roles in the co-development of MetS and periodontitis.