Quantum Interference-Controlled Conductance Enhancement in Stacked Graphene-like Dimers.

Stacking interactions are of significant importance in the fields of chemistry, biology, and material optoelectronics because they determine the efficiency of charge transfer between molecules and their quantum states. Previous studies have proven that when two monomers are π-stacked in series to form a dimer, the electrical conductance of the dimer is significantly lower than that of the monomer. Here, we present a strong opposite case that when two anthanthrene monomers are π-stacked to form a dimer in a scanning tunneling microscopic break junction, the conductance increases by as much as 25 in comparison with a monomer, which originates from a room-temperature quantum interference. Remarkably, both theory and experiment consistently reveal that this effect can be reversed by changing the connectivity of external electrodes to the monomer core. These results demonstrate that synthetic control of connectivity to molecular cores can be combined with stacking interactions between their π systems to modify and optimize charge transfer between molecules, opening up a wide variety of potential applications ranging from organic optoelectronics and photovoltaics to nanoelectronics and single-molecule electronics.

Zoledronic acid mediated differential activation of NK cells in different organs of WT and Rag2-/- mice; stark differences between the bone marrow and gingivae.

We have previously shown that natural killer (NK) cells expand, and increase their function after interaction with cells that exhibit a number of different knock-down genes. We hypothesized that deletion or knockdown of a variety of key genes such as RAG may cause de-differentiation of the cells which could lead to increased NK expansion and function since we have shown previously that NK cells are activated and expanded by less differentiated cells. When comparing the function of NK cells from bone marrow (BM), spleen, pancreas, adipose tissue, and gingiva from WT mice to those from Rag2-/- mice, we observed a significant increase in IFN-γ secretion in all tissues of Rag2-/- mice versus in WT mice, with the exception of the gingivae in which similar levels were observed. After injecting WT mice with zoledronic acid (ZOL) and tooth extraction, immune cells from BM, spleen, and purified NK cells from spleen exhibited very high induction of IFN-γ and NK cell-mediated cytotoxicity with the exception of gingiva in which immune cells exhibited the opposite. In Rag2-/- mice, ZOL injection and tooth extraction stimulated IFN-γ secretion from BM immune cells but inhibited IFN-γ secretion from both spleen and gingivae. In both WT and Rag2-/- mice, immune cells from gingivae exhibited decreased IFN-γ secretion when activated, indicating significant regulation of immune cell function in the gingival microenvironment. However, even though significantly lower induction of IFN-γ was observed in both WT and Rag2-/- gingival cells after ZOL injection, ZOL mediated secretion of IFN-γ was still higher in the gingivae of WT mice when compared to those of Rag2-/- gingival cells. These results suggest an important role for IFN-γ in the pathogenesis of osteonecrosis lesions observed in post-tooth extraction jawbone.

Feeding and metabolism effects of three common microplastics on Tenebrio molitor L.

Mealworms from three different regions: Guangzhou, Tai'an and Shenzhen, were fed with three commonly used microplastics of polystyrene (PS), polyvinyl chloride (PVC) and low-density polyethylene (LDPE) for 1 month under favorable conditions, respectively. The survival rate and average weight of mealworms, the mass loss of microplastics and the production of frass were recorded every 4 days. Samples collected were characterized by X-ray diffraction, fourier transform infrared spectroscopy, thermogravimetric analyzer and gel permeation chromatography. The results showed that mealworms from Tai'an and Shenzhen could effectively metabolize the whole microplastics tested, while those from Guangzhou could only metabolize PS and LDPE. Besides, LDPE could be degraded by mealworms from Tai'an and Shenzhen, while those from Guangzhou showed no such capability, indicating that mealworms from different regions present different metabolism effects. Furthermore, PS and LDPE are more likely to be metabolized compared with PVC.

Effect of Low-intensity Pulsed Ultrasound on the Mandibular Remodeling Following Inferior Alveolar Nerve Transection.

Objective To investigate the effects of low-intensity pulsed ultrasound (LIPUS) on the mandibular remodeling following inferior alveolar nerve transection (IANX) and to optimize the parameters of LIPUS in the treatment of nerve injury. Methods IANX was performed in male Sprague-Dawley rats. Four weeks after IANX,the effect of daily LIPUS (from day 1) on the transected inferior alveolar nerve was examined in terms of sensitivity to mechanical stimulation. Moreover,histopathologic changes of mandibles were analyzed by micro-CT,HE staining,Masson trichrome staining,and immunohistochemical staining. Results LIPUS promoted the recovery of inferior alveolar nerve injury after transection. HE staining displayed the improvement of trabecular thickness and continuity. LIPUS with higher duty ratios had more obvious effect on bone remodeling. Conclusion LIPUS promotes the mandibular remodeling following IANX.

Evaluation of the efficacy of keratinized mucosa augmentation techniques around dental implants: a systematic review.

STATEMENT OF PROBLEM: The absence of periimplant keratinized mucosa is considered risky in patients with a predisposition to periodontitis or recession. Although various soft tissue augmentation techniques exist, dentists are seeking for more efficient approaches to augment periimplant keratinized mucosa. PURPOSE: The purpose of this systematic review was to evaluate the efficacy of the various techniques and biomaterials adopted in periimplant keratinized mucosa augmentation and whether one technique or biomaterial is superior. MATERIAL AND METHODS: A search in Medline-PubMed and the Cochrane Central Register of controlled trials was conducted. Randomized clinical trials, prospective cohort studies, clinical control studies, and case series from January 1, 1980, to December 31, 2013, with a follow-up of at least 6 months reporting changes on keratinized mucosa width were included. Several journals were hand-searched for related articles. The bibliographies of all publications selected for inclusion were also scanned. RESULTS: The screening of titles and abstracts resulted in 60 relevant publications. Six of them were finally included. Free gingival graft, connective tissue graft, acellular dermal matrix, and collagen matrix were used for keratinized mucosa augmentation. Because of heterogeneity of the studies, only descriptive analysis was performed. Improvements in keratinized mucosa width were reported in all studies. CONCLUSIONS: A definitive conclusion could not be achieved owing to the lack of well-designed studies and appropriate methods of studying soft tissue. The establishment of universal surgical guidelines and measurement systems is imperative in the future.

Digital PBL-CBL teaching method improves students' performance in learning complex implant cases in atrophic anterior maxilla.

Background: The clinical teaching of esthetic implant-supported restoration of the atrophic maxilla is challenging due to the complexity and unpredictability of bone and soft tissue augmentation. The traditional problem-based learning and case-based learning method (PBL-CBL method) with a full digital workflow (digital PBL-CBL method) provides the students a chance to view clinical cases in a more accurate and measurable way. The aim is to evaluate the effectiveness of the new digital PBL-CBL method in teaching complex implant cases in esthetic area. Materials & Methods: A full digital workflow of dental implant therapy was established for patients with severely atrophic anterior maxilla. The digital data of cases done in the new workflow was used as teaching materials in digital PBL-CBL teaching. Fifty-four postgraduate students were randomly selected and divided into three groups, including traditional PBL-CBL group (students taught in a PBL-CBL method with no digital cases), digital PBL-CBL group (students taught in a PBL-CBL method with full digital cases) and control group (students taught in didactic teacher-centered method). After training for three months, a study of the students' opinions on the corresponding teaching method was carried out through a feedback questionnaire. A theory test was used to evaluate students' mastery of knowledge about tissue augmentation and esthetic implant restoration. A case analysis was used to determine whether students could apply the knowledge to problem solving. Results: The digital PBL-CBL method resulted in a higher rate of satisfaction than the traditional PBL-CBL method and the didactic teacher-centered method in all items except for "This approach decreases extracurricular work". Case analysis scores of the digital PBL-CBL group were significantly higher than that of the traditional PBL-CBL group and the control group. For the theory test, the digital PBL-CBL group (61.00 ± 6.80) but not traditional PBL-CBL group (55.22 ± 9.86) obtained a significant higher score than the control group (45.11 ± 12.76), although no significant difference was found between the digital PBL-CBL group and the traditional PBL-CBL group. Conclusion: Compared with other methods, students taught with the digital PBL-CBL method showed higher satisfaction and better performance in acquisition of academic knowledge and ability in solving practical clinical problems. The digital PBL-CBL method provided a promising alternative for teaching complex implant cases at the anterior maxilla.

Preparation of curcumin-loaded liposomes and evaluation of their skin permeation and pharmacodynamics.

This study aimed to investigate the in vitro skin permeation and in vivo antineoplastic effect of curcumin by using liposomes as the transdermal drug-delivery system. Soybean phospholipids (SPC), egg yolk phospholipids (EPC), and hydrogenated soybean phospholipids (HSPC) were selected for the preparation of different kinds of phospholipids composed of curcumin-loaded liposomes: C-SPC-L (curcumin-loaded SPC liposomes), C-EPC-L (curcumin-loaded EPC liposomes), and C-HSPC-L (curcumin-loaded HSPC liposomes). The physical properties of different lipsomes were investigated as follows: photon correlation spectroscopy revealed that the average particle sizes of the three types of curcumin-loaded liposomes were 82.37 ± 2.19 nm (C-SPC-L), 83.13 ± 4.89 nm (C-EPC-L), and 92.42 ± 4.56 nm (C-HSPC-L), respectively. The encapsulation efficiency values were found to be 82.32 ± 3.91%, 81.59 ± 2.38%, and 80.77 ± 4.12%, respectively. An in vitro skin penetration study indicated that C-SPC-L most significantly promoted drug permeation and deposition followed by C-EPC-L, C-HSPC-L, and curcumin solution. Moreover, C-SPC-L displayed the greatest ability of all loaded liposomes to inhibit the growth of B16BL6 melanoma cells. Therefore, the C-SPC-L were chosen for further pharmacodynamic evaluation. A significant effect on antimelanoma activity was observed with C-SPC-L, as compared to treatment with curcumin solution in vivo. These results suggest that C-SPC-L would be a promising transdermal carrier for curcumin in cancer treatment.

Precise Design of Alginate Hydrogels Crosslinked with Microgels for Diabetic Wound Healing.

Alginate hydrogel has received great attention in diabetic wound healing. However, the limited tunability of the ionic crosslinking method prevents the delicate management of physical properties in response to diverse wound conditions. We addressed this issue by using a microgel particle (fabricated by zinc ions and coordinated through the complex of carboxymethyl chitosan and aldehyde hyaluronic acid) as a novel crosslinker. Then the cation was introduced as a second crosslinker to create a double crosslinked network. The method leads to the precise regulation of the hydrogel characters, including the biodegradation rate and the controlled release rate of the drug. As a result, the optimized hydrogels facilitated the live-cell infiltration in vitro and boosted the tissue regeneration of diabetic wounds in vivo. The results indicated that the addition of the microgel as a new crosslinker created flexibility during the construction of the alginate hydrogel, adapting for diverse applications during diabetic-induced wound therapy.

Zinc ions coordinated carboxymethyl chitosan-hyaluronic acid microgel for pulmonary drug delivery.

Microgel affords a porous and swollen microstructure for the establishment of pulmonary delivery system with sustained released properties. Here, we report a microgel (with the diameter around 4 µm) prepared with a precipitation method, synthesized by coordinating Zn2+ to the Schiff base cross-linked carboxymethyl chitosan and glycol split hyaluronate. The microgel has shown well swollen and pH sensitive behaviors, high safety and biocompatibility in vitro. Besides, the biomaterial could escape from macrophage phagocytosis, a key factor contribute to quick drug clearance in the lung after co-incubated with RAW 264.7 cells. In consist with this, the bovine serum albumin loaded in the microgel showed sustained release behavior in 24 h in vitro; meanwhile, the drug had a retention time up to 36 h in the lung and followed by clearance in ICR mice through pulmonary administration. Thus, our microgel platform provides a promising candidate for pulmonary drug delivery systems with controlled release rate.

Sensory denervation increases potential of bisphosphonates to induce osteonecrosis via disproportionate expression of calcitonin gene-related peptide and substance P.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of systematic administration of bisphosphonates (BPs). Sensory innervation is crucial for bone healing. We established inferior alveolar nerve injury (IANI) and inferior alveolar nerve transection (IANT) models characterized by disorganized periosteum, increased osteoclasts, and unbalanced neuropeptide expression. Zoledronate injection disrupted neuropeptide expression in the IANI and IANT models by decreasing calcitonin gene-related peptide (CGRP) and increasing substance P (SP); associated with this, BRONJ prevalence was significantly higher in the IANT model, followed by the IANI model and the sham control. CGRP treatment significantly reduced BRONJ occurrence, whereas SP administration had the opposite effect. In vitro, RAW 264.7 cells were treated with BPs and then CGRP and/or SP to study changes in zoledronate toxicity; combined application of CGRP and SP decreased zoledronate toxicity, whereas CGRP or SP applied alone showed no effects. These results demonstrate that sensory denervation facilitates the occurrence of BRONJ and that CGRP used therapeutically may prevent BRONJ progression, provided that SP is also present. Further studies are necessary to determine the optimal ratio of CGRP to SP for promoting bone healing and to uncover the mechanism by which CGRP and SP cooperate.

Application of problem-based learning and case-based learning integrated method in the teaching of maxillary sinus floor augmentation in implant dentistry.

BACKGROUND: Teaching of maxillary sinus floor augmentation (MSFA) is challenging for dental educators due to the varied sinus anatomy and high rate of complications. The method integrating problem-based learning and case-based learning (PBL-CBL method) may be more effective than the traditional teacher-centered method. The aim is to evaluate the efficacy of the PBL-CBL method in teaching MSFA. MATERIALS & METHODS: Ninety-two students who received training between 2015 and 2017 at the Department of Implant Dentistry were divided randomly into an experimental group and a control group. Students in the experimental group were trained using the PBL-CBL method, while those in the control group were trained using the traditional teacher-centered method. After three months of training, a survey of the students' opinions about the corresponding teaching method was carried out through a feedback questionnaire. A theory test was used to investigate the level of MSFA knowledge among the students. A case analysis was designed to test whether the students can apply the knowledge in solving new problems. RESULTS: Compared with the control method, the PBL-CBL method resulted in higher scores in both the theory test and the case analysis, and obtained a higher rate of satisfaction among the students. The difference in scores between the two methods were statistically significant (P < 0.01). CONCLUSION: The PBL-CBL method resulted in better results regarding acquisition of academic knowledge, ability in case analysis and student satisfaction compared with the teacher-centered method. It may be a promising mode for teaching complex surgical techniques in implant dentistry and other dental fields.

[Comparison of clinical effects of a modified socket shield technique and the conventional immediate implant placement].

OBJECTIVE: To compare the clinical effects of a modified socket shield technique (SST) and the conventional immediate implant placement in the esthetic zone. METHODS: Twenty-four patients with one hopeless upper incisor were consecutively enrolled in this study. All patients were scheduled for immediate implant placement. Twelve patients underwent a modified SST (experimental group) whereas the others underwent conventional procedures (control group). Radiographic and clinical data were obtained preoperatively, immediately after surgery, and 12 months after surgery. The success rate of the implants, the pink esthetic score (PES) and patient satisfaction were analyzed. Statistical analysis was conducted using SPSS 21.0 software. RESULTS: One year after operation, the success rate of the implants was 100% in both groups. The PES and patient satisfaction of the experimental group were significantly higher than those of the control group (P<0.05). The buccal bone plate resorbed less in the experimental group than in the control group (P<0.05). CONCLUSIONS: The modified SST is advantageous over the conventional immediate implant placement in terms of buccal bone and soft tissue maintenance.

Inferior alveolar nerve transection disturbs innate immune responses and bone healing after tooth extraction.

Coordination between the nervous and innate immune systems to maintain bone homeostasis is largely uncharacterized. The present study investigated the sensory-immune interaction in resting alveolar bone and healing socket by surgical sensory denervation. Bone histomorphometry and immunohistochemistry showed that sensory denervation resulted in moderate suppression of bone remodeling, with a proinflammatory milieu manifested by increased neutrophil recruitment and possible alternations in macrophage phenotypes along the resting bone surface. This denervation effect intensified when bone remodeling was triggered by tooth extraction, as revealed by disrupted temporospatial variations in macrophage subpopulations and neutrophil infiltration, which were closely associated with a dramatic decline in socket bone filling and residual ridge height. Antagonism of calcitonin gene-related peptide (CGRP) brought about similar antianabolic and proinflammatory effects as sensory denervation, suggesting that sensory nerves may monitor the bony milieu by CGRP. Depletion of macrophages, rather than neutrophils, ruled out CGRP effects, illustrating that macrophages were the primary immune mechanism that linked sensory innervation, innate immunity, and bone. The data support that sensory innervation is required for control of innate immune responses and maintenance of bone homeostasis. Sensory neuropeptides, such as CGRP, are a possible target for the development of proanabolic treatments in bone disease by modulating innate immune responses.

Rescue bisphosphonate treatment of alveolar bone improves extraction socket healing and reduces osteonecrosis in zoledronate-treated mice.

Bisphosphonate (BP)-related osteonecrosis of the jaw, previously known as BRONJ, now referred to more broadly as medication-related osteonecrosis of the jaw (MRONJ), is a morbid condition that represents a significant risk for oncology patients who have received high dose intravenous (IV) infusion of a potent nitrogen containing BP (N-BP) drug. At present, no clinical procedure is available to prevent or effectively treat MRONJ. Although the pathophysiological basis is not yet fully understood, legacy adsorbed N-BP in jawbone has been proposed to be associated with BRONJ by one or more mechanisms. We hypothesized that removal of the pre-adsorbed N-BP drug common to these pathological mechanisms from alveolar bone could be an effective preventative/therapeutic strategy. This study demonstrates that fluorescently labeled BP pre-adsorbed on the surface of murine maxillo-cranial bone in vivo can be displaced by subsequent application of other BPs. We previously described rodent BRONJ models involving the combination of N-BP treatment such as zoledronate (ZOL) and dental initiating factors such as tooth extraction. We further refined our mouse model by using gel food during the first 7 days of the tooth extraction wound healing period, which decreased confounding food pellet impaction problems in the open boney socket. This refined mouse model does not manifest BRONJ-like severe jawbone exposure, but development of osteonecrosis around the extraction socket and chronic gingival inflammation are clearly exhibited. In this study, we examined the effect of benign BP displacement of legacy N-BP on tooth extraction wound healing in the in vivo model. Systemic IV administration of a low potency BP (lpBP: defined as inactive at 100 µM in a standard protein anti-prenylation assay) did not significantly attenuate jawbone osteonecrosis. We then developed an intra-oral formulation of lpBP, which when injected into the gingiva adjacent to the tooth prior to extraction, dramatically reduced the osteocyte necrosis area. Furthermore, the tooth extraction wound healing pattern was normalized, as evidenced by timely closure of oral soft tissue without epithelial hyperplasia, significantly reduced gingival inflammation and increased new bone filling in the extraction socket. Our results are consistent with the hypothesis that local application of a rescue BP prior to dental surgery can decrease the amount of a legacy N-BP drug in proximate jawbone surfaces below the threshold that promotes osteocyte necrosis. This observation should provide a conceptual basis for a novel strategy to improve socket healing in patients treated with BPs while preserving therapeutic benefit from anti-resorptive N-BP drug in vertebral and appendicular bones.

Effects of Programmed Local Delivery from a Micro/Nano-Hierarchical Surface on Titanium Implant on Infection Clearance and Osteogenic Induction in an Infected Bone Defect.

The two major causes for implant failure are postoperative infection and poor osteogenesis. Initial period of osteointegration is regulated by immunocytes and osteogenic-related cells resulting in inflammatory response and tissue healing. The healing phase can be influenced by various environmental factors and biological cascade effect. To synthetically orchestrate bone-promoting factors on biomaterial surface, built is a dual delivery system coated on a titanium surface (abbreviated as AH-Sr-AgNPs). The results show that this programmed delivery system can release Ag+ and Sr2+ in a temporal-spatial manner to clear pathogens and activate preosteoblast differentiation partially through manipulating the polarization of macrophages. Both in vitro and in vivo assays show that AH-Sr-AgNPs-modified surface renders a microenvironment adverse for bacterial survival and favorable for macrophage polarization (M2), which further promotes the differentiation of preosteoblasts. Infected New Zealand rabbit femoral metaphysis defect model is used to confirm the osteogenic property of AH-Sr-AgNPs implants through micro-CT, histological, and histomorphometric analyses. These findings demonstrate that the programmed surface with dual delivery of Sr2+ and Ag+ has the potential of achieving an enhanced osteogenic outcome through favorable immunoregulation.

Age-dependent impact of inferior alveolar nerve transection on mandibular bone metabolism and the underlying mechanisms.

Aging is associated with peripheral nerve degradation and bone destruction. The aim of the study is to elucidate the influence of sensory denervation on bone metabolism in different age groups by establishing a modified unilateral inferior alveolar nerve transection (IANT) model. The rats, divided into young, middle-aged and aged group, were sacrificed at 1, 2, 4 and 8 weeks after right IANT. The histological changes of mandibles were analyzed by fluorescent double labeling, micro-CT, HE, TRAP and anti-CGRP immunohistochemical staining. Molecular mechanisms underlying the changes were analyzed by qPCR and western blot. Differences between the test and control side were evaluated by paired-samples t test. The Friedman test and separate Wilcoxon signed-rank tests were applied to analyze age-dependent difference. The impact of IANT was the most intensive in developing bone, the most persistent in full grown bone and the faintest in the aged bone. The role of IAN in keeping homeostasis was closely related to the anabolic effect of CGRP, which suppressed the number of osteoclasts through OPG/RANKL ratio and controlled growth factors expression like BMP2. This study contributes to a better understanding of the molecular mechanisms of CGRP in vivo and the relationship among sensory nerve, bone metabolism and aging.

In-Situ Onlay Grafting Combined with Titanium Mesh for Three-Dimensional Reconstruction of the Anterior Maxillary Ridge.

Reconstruction of anterior maxillary ridge defects involving both horizontal and vertical dimensions has always been a challenge. This case report proposes a novel approach to reconstruct labial bony walls with onlay bone blocks harvested in situ held by titanium mesh covered with concentrated growth factor. Favorable outcomes were shown because of better space maintenance and nutrition supply.