Multifunctional Biodegradable Conductive Hydrogel Regulating Microenvironment for Stem Cell Therapy Enhances the Nerve Tissue Repair.

The nerve guidance conduits incorporated with stem cells, which can differentiate into the Schwann cells (SCs) to facilitate myelination, shows great promise for repairing the severe peripheral nerve injury. The innovation of advanced hydrogel materials encapsulating stem cells, is highly demanded for generating supportive scaffolds and adaptive microenvironment for nerve regeneration. Herein, this work demonstrates a novel strategy in regulating regenerative microenvironment for peripheral nerve repair with a biodegradable conductive hydrogel scaffold, which can offer multifunctional capabilities in immune regulation, enhancing angiogenesis, driving SCs differentiation, and promoting axon regrowth. The biodegradable conductive hydrogel is constructed by incorporation of polydopamine-modified silicon phosphorus (SiP@PDA) nanosheets into a mixture of methacryloyl gelatin and decellularized extracellular matrix (GelMA/ECM). The biomimetic electrical microenvironment performs an efficacious strategy to facilitate macrophage polarization toward a pro-healing phenotype (M2), meanwhile the conductive hydrogel supports vascularization in regenerated tissue through sustained Si element release. Furthermore, the MSCs 3D-cultured in GelMA/ECM-SiP@PDA conductive hydrogel exhibits significantly increased expression of genes associated with SC-like cell differentiation, thus facilitating the myelination and axonal regeneration. Collectively, both the in vitro and in vivo studies demonstrates that the rationally designed biodegradable multifunctional hydrogel significantly enhances nerve tissues repair.

Mild Photothermal-Stimulation Based on Injectable and Photocurable Hydrogels Orchestrates Immunomodulation and Osteogenesis for High-Performance Bone Regeneration.

A photoactivated bone scaffold integrated with minimally invasive implantation and mild thermal-stimulation capability shows great promise in the repair and regeneration of irregularly damaged bone tissues. Developing multifunctional photothermal biomaterials that can simultaneously serve as both controllable thermal stimulators and biodegradable engineering scaffolds for integrated immunomodulation, infection therapy, and impaired bone repair remains an enormous challenge. Herein, an injectable and photocurable hydrogel therapeutic platform (AMAD/MP) based on alginate methacrylate, alginate-graft-dopamine, and polydopamine (PDA)-functionalized Ti3C2 MXene (MXene@PDA) nanosheets is rationally designed for near-infrared (NIR)-mediated bone regeneration synergistic immunomodulation, osteogenesis, and bacterial elimination. The optimized AMAD/MP hydrogel exhibits favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro. The proper immune microenvironment provided by AMAD/MP could further modulate the balance of M1/M2 phenotypes of macrophages, thereby suppressing reactive oxygen species-induced inflammatory status. Significantly, this multifunctional hydrogel platform with mild thermal stimulation efficiently attenuates local immune reactions and further promotes new bone formation without the addition of exogenous cells, cytokines, or growth factors. This work highlights the potential application of an advanced multifunctional hydrogel providing photoactivated on-demand thermal cues for bone tissue engineering and regenerative medicine.

Effects of microplastics on the phytoremediation of Cd, Pb, and Zn contaminated soils by Solanum photeinocarpum and Lantana camara.

Microplastics are emerging pollutants and have become a global environmental issue. The impacts of microplastics on the phytoremediation of heavy metal-contaminated soils are unclear. A pot experiment was conducted to investigate the effects of four additions (0, 0.1%, 0.5%, and 1% w·w-1) of polyethylene (PE) and cadmium (Cd), lead (Pb), and zinc (Zn) contaminated soil on the growth and heavy metal accumulation of two hyperaccumulators (Solanum photeinocarpum and Lantana camara). PE significantly decreased the pH and activities of dehydrogenase and phosphatase in soil, while it increased the bioavailability of Cd and Pb in soil. Peroxidase (POD), catalase (CAT), and malondialdehyde (MDA) activity in the plant leaves were all considerably increased by PE. PE had no discernible impact on plant height, but it did significantly impede root growth. PE affected the morphological contents of heavy metals in soils and plants, while it did not alter their proportions. PE increased the content of heavy metals in the shoots and roots of the two plants by 8.01-38.32% and 12.24-46.28%, respectively. However, PE significantly reduced the Cd extraction amount in plant shoots, while it significantly increased the Zn extraction amount in the plant roots of S. photeinocarpum. For L. camara, a lower addition (0.1%) of PE inhibited the extraction amount of Pb and Zn in the plant shoots, but a higher addition (0.5% and 1%) of PE stimulated the Pb extraction amount in the plant roots and the Zn extraction amount in the plant shoots. Our results indicated that PE microplastics have negative effects on the soil environment, plant growth, and the phytoremediation efficiency of Cd and Pb. These findings contribute to a better knowledge of the interaction effects of microplastics and heavy metal-contaminated soils.

MRI monitoring of transplanted neonatal porcine islets labeled with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles in a mouse model.

Islet transplantation is a potential treatment option for certain patients with type 1 diabetes; however, it still faces barriers to widespread use, including the lack of tools to monitor islet grafts post-transplantation. This study investigates whether labeling neonatal porcine islets (NPI) with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) affects their function, and whether this nanoparticle can be utilized to monitor NPI xenografts with magnetic resonance imaging (MRI) in a mouse model. In vitro, PVP-SPIO-labeled NPI in an agarose gel was visualized clearly by MRI. PVP-SPIO-labeled islets were then transplanted under the kidney capsules of immunodeficient nondiabetic and diabetic mice. All diabetic mice that received transplantation of PVP-SPIO-labeled islets reached normoglycemia. Grafts appeared as hypo-intense areas on MRI and were distinguishable from the surrounding tissues. Following injection of spleen cells from immunocompetent mice, normoglycemic recipient mice became diabetic and islet grafts showed an increase in volume, accompanied by a mixed signal on MRI. Overall, this study demonstrates that PVP-SPIO did not affect the function of NPI that PVP-SPIO-labeled islets were easily seen on MRI, and changes in MRI signals following rejection suggest a potential use of PVP-SPIO-labeled islets to monitor graft viability.

The genomic architectures of tumour-adjacent tissues, plasma and saliva reveal evolutionary underpinnings of relapse in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is characterised by a dismal prognosis; nonetheless, limited studies have unveiled the mechanisms underlying HNSCC relapse. METHODS: Next-generation sequencing was performed to identify the somatic mutations in 188 matched samples, including primary tumours, tumour-adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. The evolutionary relationship between TATs and tumours were analysed. The dynamic changes of tumour- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis. RESULTS: Alterations were detected in 27 out of 27 and 19 out of 26 tumours and TATs, respectively. TP53 was the most prevalently mutated gene in TATs. Some TATs shared mutations with primary tumours, while some other TATs were evolutionarily unrelated to tumours. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and are indicative of worse survival (hazard ratio = 14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies and were indicative of disease relapse. CONCLUSIONS: TATs might undergo the processes of premalignant transformation, tumorigenesis and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where the tumour originated or gaining private mutations independent of primary tumours. Detection of tumour- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use.

Plasmonic SERS Biosensor Based on Multibranched Gold Nanoparticles Embedded in Polydimethylsiloxane for Quantification of Hematin in Human Erythrocytes.

This work reports a plasmonic surface-enhanced Raman scattering (SERS) biosensor that allows for quantitative analysis of hematin in erythrocytes without the need of separating it from hemoglobin (Hb). The biosensor exploits the tunable localized surface plasmon resonance (LSPR) characteristics of multibranched gold nanoparticles (M-AuNPs) and the strong plasmon coupling between an Au thin film and a flexible substrate consisting of M-AuNPs embedded in polydimethylsiloxane (PDMS) (i.e., M-AuNP-embedded PDMS substrate). In the assay, the hematin (or hematin-containing erythrocyte hemolysate) was deposited on Au film surface and covered with M-AuNP-embedded PDMS. Strong SERS signals were generated under excitation at 785 nm; the signals were sensitive to hematin concentration but not to several common coexisting biological substances. The intensities of the SERS signal (at 1623 cm-1) displayed a wide linear range using hematin concentrations in a range of at least ∼1.5 nM-1.1 µM; the limit of detection (LOD) was ∼0.03 ± 0.01 nM at a signal/noise (S/N) of 3. This assay is simple and sensitive without tedious separation procedures, thereby saving time and enhancing efficiency. This biosensor can be used to determine hematin concentration in human erythrocyte cytosols giving concentrations of ∼18.5 ± 4.5 (by averaging eight samples) and 51.5 ± 6.2 µM (by averaging three samples) for healthy and sickle erythrocytes, respectively, making it a potential application in clinical detection.

Targeted Delivery of Curcumin Rescues Endoplasmic Reticulum-Retained Mutant NOX2 Protein and Avoids Leukocyte Apoptosis.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by defects in the leukocyte NADP oxidase. We previously reported that sarcoplasmic/endoplasmic reticulum calcium pump (SERCA) inhibitors could be used to rescue mutant H338Y-gp91phox protein of a particular type of CGD with a CybbC1024T mutation, leading to endoplasmic reticulum (ER) retention of the mutant protein. In this study, we developed a novel mouse model with the CybbC1024T mutation on a Cybb knockout background and investigated the therapeutic effects of ER-targeted delivery of the SERCA inhibitor, curcumin, with poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs). We found that PLGA encapsulation improved the efficacy of curcumin as a SERCA inhibitor to induce ER calcium release. ER-targeting curcumin-loaded PLGA NPs reduced and delayed extracellular calcium entry and protected the cells from mitochondrial damage and apoptosis. In vivo studies showed that ER-targeting curcumin-loaded PLGA NPs treatment enhanced neutrophil gp91phox expression, ROS production and peritoneal bacterial clearance ability of the CybbC1024T transgenic Cybb -/- mice. Our findings indicate that ER-targeted delivery of curcumin not only rescues ER-retained H338Y-gp91phox protein, and hence leukocyte function, but also enhances the bioavailability and reduces cytotoxicity. Modulation of ER function by using organelle-targeted NPs may be a promising strategy to improve the therapeutic potential of curcumin as a treatment for CGD.

Organic-Inorganic Nanocomposite Film for High-Performance Stretchable Resistive Memory Device.

A compatible organic/inorganic nanocomposite film for a stretchable resistive memory device with high performance is demonstrated using poly(4-vinylpyridine)-block-poly(propyl methacrylate) (P4VP-b-PPMA) with zinc oxide (ZnO) nanoparticle. The PPMA soft segment is designed for reducing the rigidity of the active layer, while the P4VP block serves as a charge-trapping component to induce conductive filament and also a compatible moiety for inorganic nanoparticles through hydrogen bonding. The experimental results show that the P4VP-b-PPMA-based electrical memory device exhibits write-once-read-many-times memory behavior and an excellent ON/OFF current ratio of over 105 with a stable turn-on voltage (Vset ) around -2.0 V and stable memory behavior upon stretching up to 60% strain. On the other hand, P4VP-b-PPMA/ZnO nanocomposite film switches the memory characteristic to the dynamic random access memory behavior. The stretchable memory device prepared from the nanocomposite film can have a stretching durability over 40% strain and up to 1000 times cycling stretch-relaxation test. This work demonstrates a new strategy using nanocomposite films with tunable electrical characteristics and enhanced mechanical properties for stretchable electrical devices.

Heterochronic truncation of odontogenesis in theropod dinosaurs provides insight into the macroevolution of avian beaks.

Beaks are innovative structures characterizing numerous tetrapod lineages, including birds, but little is known about how developmental processes influenced the macroevolution of these important structures. Here we provide evidence of ontogenetic vestigialization of alveoli in two lineages of theropod dinosaurs and show that these are transitional phenotypes in the evolution of beaks. One of the smallest known caenagnathid oviraptorosaurs and a small specimen of the Early Cretaceous bird Sapeornis both possess shallow, empty vestiges of dentary alveoli. In both individuals, the system of vestiges connects via foramina with a dorsally closed canal homologous to alveoli. Similar morphologies are present in Limusaurus, a beaked theropod that becomes edentulous during ontogeny; and an analysis of neontological and paleontological evidence shows that ontogenetic reduction of the dentition is a relatively common phenomenon in vertebrate evolution. Based on these lines of evidence, we propose that progressively earlier postnatal and embryonic truncation of odontogenesis corresponds with expansion of rostral keratin associated with the caruncle, and these progenesis and peramorphosis heterochronies combine to drive the evolution of edentulous beaks in nonavian theropods and birds. Following initial apomorphic expansion of rostral keratinized epithelia in perinatal toothed theropods, beaks appear to inhibit odontogenesis as they grow postnatally, resulting in a sequence of common morphologies. This sequence is shifted earlier in development through phylogeny until dentition is absent at hatching, and odontogenesis is inhibited by beak formation in ovo.

Amino-Functionalized Nitrogen-Doped Graphene-Quantum-Dot-Based Nanomaterials with Nitrogen and Amino-Functionalized Group Content Dependence for Highly Efficient Two-Photon Bioimaging.

We fabricated nanomaterials comprising amino-functionalized and nitrogen-doped graphene quantum dots (amino-N-GQDs) and investigated their photostability and intrinsic luminescence in the near-infrared spectrum to determine their suitability as contrast agents in two-photon imaging (TPI). We observed that amino-N-GQDs with a higher amount of bonded nitrogen and amino-functionalized groups (6.2%) exhibited superior two-photon properties to those with a lower amount of such nitrogen and groups (4.9%). These materials were conjugated with polymers containing sulfur (polystyrene sulfonate, PSS) and nitrogen atoms (polyethylenimine, PEI), forming amino-N-GQD-PSS-PEI specimens (amino-N-GQD-polymers). The polymers exhibited a high quantum yield, remarkable stability, and notable two-photon properties and generated no reactive oxygen species, rendering them excellent two-photon contrast agents for bioimaging. An antiepidermal growth factor receptor (AbEGFR) was used for labeling to increase specificity. Two-photon imaging (TPI) of amino-N-GQD (6.2%)-polymer-AbEGFR-treated A431 cancer cells revealed remarkable brightness, intensity, and signal-to-noise ratios for each observation at a two-photon excitation power of 16.9 nJ pixel-1 under 30 scans and a three-dimensional (3D) depth of 105 µm, indicating that amino-N-GQD (6.2%)-polymer-AbEGFR-treated cells can achieve two-photon luminescence with 71 times less power required for two-photon autofluorescence (1322.8 nJ pixel-1 with 500 scans) of similar intensity. This economy can minimize photodamage to cells, rendering amino-N-GQD-polymers suitable for noninvasive 3D bioimaging.

Sodium-fluoride PET-CT for the non-invasive evaluation of coronary plaques in symptomatic patients with coronary artery disease: a cross-correlation study with intravascular ultrasound.

OBJECTIVES: The aim of this study was to evaluate the 18F-sodium fluoride (18F-NaF) coronary uptake compared to coronary intravascular ultrasound (IVUS) in patients with symptomatic coronary artery disease. BACKGROUND: 18F-NaF PET enables the assessment of vascular osteogenesis by interaction with surface hydroxyapatite, while IVUS enables both identification and quantification of intra-plaque components. METHODS: Forty-four patients with symptomatic coronary artery disease were included in this prospective controlled trial, 32 of them (30 patients with unstable angina and 2 patients with stable angina), representing the final study cohort, got additional IVUS. All patients underwent cardiac 18F-NaF PET/CT and IVUS within 2 days. 18F-NaF maximum tissue-to-blood ratios (TBRmax) were calculated for 69 coronary plaques and correlated with IVUS plaque classification. RESULTS: Significantly increased 18F-NaF uptake ratios were observed in fibrocalcific lesions (meanTBRmax = 1.42 ± 0.28), thin-cap atheroma with spotty calcifications (meanTBRmax = 1.32 ± 0.23), and thick-cap mixed atheroma (meanTBRmax = 1.28 ± 0.38), while fibrotic plaques showed no increased uptake (meanTBRmax = 0.96 ± 0.18). The 18F-NaF uptake ratio was consistently higher in atherosclerotic lesions with severe calcification (meanTBRmax = 1.34 ± 0.22). The regional 18F-NaF uptake was most likely localized in the border region of intensive calcification. Coronary lesions with positive 18F-NaF uptake showed some increased high-risk anatomical features on IVUS in comparison to 18F-NaF negative plaques. It included a significant severe plaque burden (70.1 ± 13.8 vs. 61.0 ± 13.8, p = 0.01) and positive remodeling index (1.03 ± 0.08 vs. 0.99 ± 0.07, p = 0.05), as well as a higher percentage of necrotic tissue (37.6 ± 13.3 vs. 29.3 ± 15.7, p = 0.02) in positive 18F-NaF lesions. CONCLUSIONS: 18F-NaF coronary uptake may provide a molecular insight for the characterization of coronary atherosclerotic lesions. Specific regional uptake is needed to be determined by histology.

Graphene oxide conjugated with polymers: a study of culture condition to determine whether a bacterial growth stimulant or an antimicrobial agent?

BACKGROUND: The results showed that the deciding factor is the culture medium in which the bacteria and the graphene oxide (GO) are incubated at the initial manipulation step. These findings allow better use of GO and GO-based materials more and be able to clearly apply them in the field of biomedical nanotechnology. RESULTS: To study the use of GO sheets applied in the field of biomedical nanotechnology, this study determines whether GO-based materials [GO, GO-polyoxyalkyleneamine (POAA), and GO-chitosan] stimulate or inhibit bacterial growth in detail. It is found that it depends on whether the bacteria and GO-based materials are incubated with a nutrient at the initial step. This is a critical factor for the fortune of bacteria. GO stimulates bacterial growth and microbial proliferation for Gram-negative and Gram-positive bacteria and might also provide augmented surface attachment for both types of bacteria. When an external barrier that is composed of GO-based materials forms around the surface of the bacteria, it suppresses nutrients that are essential to microbial growth and simultaneously produces oxidative stress, which causes bacteria to die, regardless of whether they have an outer-membrane-Gram-negative-bacteria or lack an outer-membrane-Gram-positive-bacteria, even for high concentrations of biocompatible GO-POAA. The results also show that these GO-based materials are capable of inducing reactive oxygen species (ROS)-dependent oxidative stress on bacteria. Besides, GO-based materials may act as a biofilm, so it is hypothesized that they suppress the toxicity of low-dose chitosan. CONCLUSION: Graphene oxide is not an antimicrobial material but it is a general growth enhancer that can act as a biofilm to enhance bacterial attachment and proliferation. However, GO-based materials are capable of inducing ROS-dependent oxidative stress on bacteria. The applications of GO-based materials can clearly be used in antimicrobial surface coatings, surface-attached stem cells for orthopedics, antifouling for biocides and microbial fuel cells and microbial electro-synthesis.

Preparation and characterization of laser-melted Mg-Sn-Zn alloys for biomedical application.

The rapid degradation rate of Magnesium (Mg) alloy limits its biomedical application even though it possesses outstanding biological performance and biomechanical compatibility. In this study, a combined method of laser rapid melting and alloying Zinc (Zn) was proposed to decrease the degradation rate of Mg-Sn alloy. The microstructure, degradation behaviors and mechanical properties of the laser-melted Mg-5Sn-xZn (x = 0, 2, 4, 6 and 8 wt.%) alloys were investigated. The results indicated that the grain size of the alloys decreased with increasing Zn content, due to the increased number of nucleation particles formed in the process of solidification. Moreover, the laser-melted Mg-Sn alloys possessed finer grains compared with traditional as-cast and as-rolled Mg-Sn alloys. The degradation rate of the alloys decreased with increasing Zn content (0-4 wt.%), which was ascribed to the grain refinement and the formation of Zn(OH)2 protective layer. However, the degradation rate increased as the Zn content further increased (4-8 wt.%), which was caused by the galvanic corrosion between the Mg matrix and the generated Mg7Zn3 phase. Besides, Zn also increased the hardness of the alloys owing to the grain refinement strengthening and solid solution strengthening.

Sox2 marks epithelial competence to generate teeth in mammals and reptiles.

Tooth renewal is initiated from epithelium associated with existing teeth. The development of new teeth requires dental epithelial cells that have competence for tooth formation, but specific marker genes for these cells have not been identified. Here, we analyzed expression patterns of the transcription factor Sox2 in two different modes of successional tooth formation: tooth replacement and serial addition of primary teeth. We observed specific Sox2 expression in the dental lamina that gives rise to successional teeth in mammals with one round of tooth replacement as well as in reptiles with continuous tooth replacement. Sox2 was also expressed in the dental lamina during serial addition of mammalian molars, and genetic lineage tracing indicated that Sox2(+) cells of the first molar give rise to the epithelial cell lineages of the second and third molars. Moreover, conditional deletion of Sox2 resulted in hyperplastic epithelium in the forming posterior molars. Our results indicate that the Sox2(+) dental epithelium has competence for successional tooth formation and that Sox2 regulates the progenitor state of dental epithelial cells. The findings imply that the function of Sox2 has been conserved during evolution and that tooth replacement and serial addition of primary teeth represent variations of the same developmental process. The expression patterns of Sox2 support the hypothesis that dormant capacity for continuous tooth renewal exists in mammals.

A Formulation Study of 5-Aminolevulinic Encapsulated in DPPC Liposomes in Melanoma Treatment.

Photodynamic therapy (PDT) is a widely used technique for epithelial skin cancer treatment. 5-aminolevulinic acid (5-ALA) is a drug currently used for PDT and is a hydrophilic molecule at its physiological pH, and this limits its capacity to cross the stratum corneum of skin. Since skin penetration is a key factor in the efficacy of topical 5-ALA-mediated PDT, numerous strategies have been proposed to improve skin penetration. Yet this problem is still ongoing. The results of a previous study showed a low rate of 5-ALA encapsulated in liposomes (5.7%) that were 400 nm in size. In the present study, we used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes as vehicles and tested their delivery efficacy of 5-ALA-medicated PDT both in vitro and in vivo. Our data shows that 5-ALA encapsulated in 0.1 or 0.5% DPPC liposomes (5-ALA/DPPC) had a better encapsulated rate (15~16%) and were smaller in size (84~89 nm). We found the 5-ALA/DPPC formulation reduced cell viability, mitochondria membrane potential, and enhanced intracellular ROS accumulation as compared to 5-ALA alone in melanoma cells. Furthermore, the 5-ALA/DPPC formulation also had better skin penetration ability as compared to the 5-ALA in our ex vivo data by assaying 5-ALA converted into protoporphyrin IX (PpIX) in the skin of the mice that were experimented on. In melanoma xenograft models, 5-ALA/DPPC enhanced PpIX accumulation only in tumor tissue but not normal skin. In conclusion, we found DPPC liposomes to be good carriers for 5-ALA delivery and believe that they may prove useful in 5-ALA-mediated PDT in the future.

Urchin-Like Amorphous Ni2B Alloys: Efficient Antibacterial Materials and Catalysts for Hydrous Hydrazine Decomposition to Produce H2.

Urchin-like amorphous Ni2B alloys were successfully prepared for the first time from a mixture of Ni(NH3)6(2+) and polyvinyl alcohol (PVA) via a solution plasma process (SPP). The as-synthesized samples were characterized by X-ray powder diffraction (XRD), inductively coupled plasma atomic emission spectrometry (ICP-AES) X-ray photoelectron spectroscopy (XPS), scanning transmission electron microscopy (STEM), selected-area electron diffraction patterns (SAED) and nitrogen adsorption-desorption isotherms. In the performance test, the obtained Ni-B urchins showed great antibacterial activities, comparable with those of amikacin and kanamycin, especially towards Pseudomonas aeruginosa (P. aeruginosa). Meanwhile, the magnetic properties of Ni-B urchins are enhanced in comparison with those of conventional Ni-B. During hydrous hydrazine (N2H4) decomposition, the dehydrogenation performance of Ni-B urchins is superior to those of Raney Ni and conventional Ni-B. The enhanced catalytic performance of Ni-B urchins is attributed to their high surface area of active species nickel and the enhanced intrinsic activity resulting from their unique structure.

Specialized stem cell niche enables repetitive renewal of alligator teeth.

Reptiles and fish have robust regenerative powers for tooth renewal. However, extant mammals can either renew their teeth one time (diphyodont dentition) or not at all (monophyodont dentition). Humans replace their milk teeth with permanent teeth and then lose their ability for tooth renewal. Here, we study tooth renewal in a crocodilian model, the American alligator, which has well-organized teeth similar to mammals but can still undergo life-long renewal. Each alligator tooth is a complex family unit composed of the functional tooth, successional tooth, and dental lamina. Using multiple mitotic labeling, we map putative stem cells to the distal enlarged bulge of the dental lamina that contains quiescent odontogenic progenitors that can be activated during physiological exfoliation or artificial extraction. Tooth cycle initiation correlates with ß-catenin activation and soluble frizzled-related protein 1 disappearance in the bulge. The dermal niche adjacent to the dermal lamina dynamically expresses neural cell adhesion molecule, tenascin-C, and other molecules. Furthermore, in development, asymmetric ß-catenin localization leads to the formation of a heterochronous and complex tooth family unit configuration. Understanding how these signaling molecules interact in tooth development in this model may help us to learn how to stimulate growth of adult teeth in mammals.

Using double occlusion checking system and Bi-digital O-Ring Test to determine the vertical dimension of occlusion for maxillofacial prosthodontics for patients with long-term pathophysiological condition.

Common practice of establishing occlusal vertical dimension by adopting traditional method for patients with long-term pathological conditions has left the results much less than desired, since the degree of pathological condition for each patient varies from one patient to another, and traditional methods to determine vertical dimension are mostly intended for normal patients. Ideally, the occlusal vertical dimension should be dictated by, and conformed to patient's comfort range for the physiological accommodation to each patient's condition. This article describes a method of a double checking system for occlusion determination by increasing vertical dimension of occlusion (VDO) by 1/2 mm each week to find the most comfort zone and beyond for patient, and then to gradually decrease ½ mm of the VDO each week to the original VDO to double check the comfort zone for the patient. During the process, Bi-Digital O-Ring Test was employed to corroborate, to determine, and to individualize the occlusal vertical dimension for patients with pathological abnormalities. Traditional methods of vertical dimension determination were merely used as a guiding reference in our treatment of those patients. Patient's comfort and discomfort were carefully recorded, compared and studied before the denture prosthesis was fabricated.

Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results.

Bisphosphonates are recommended in patients with osteolytic lesions secondary to multiple myeloma. We report on the safety of bisphosphonate therapy with long-term follow-up in the Medical Research Council Myeloma IX study. Patients with newly diagnosed multiple myeloma were randomised to zoledronic acid (ZOL; 4 mg intravenously every 21-28 d) or clodronate (CLO; 1600 mg/d orally) plus chemotherapy. Among 1960 patients (5.9-year median follow-up), both bisphosphonates were well tolerated. Acute renal failure events were similar between groups (ZOL 5.2% vs. CLO 5.8% at 2 years; incidence plateaued thereafter). The overall incidence of confirmed osteonecrosis of the jaw (ONJ) was low, but higher with ZOL (ZOL 3.7% vs. CLO 0.5%; P < 0.0001). ONJ events were generally low grade and most occurred between 8 and 30 months (median time to ONJ, 23.7 months). Among 10 patients with ONJ recovery data, four patients in the ZOL group completely recovered, two patients improved, and three patients experienced no improvement; one CLO patient experienced no improvement. Dental surgery or trauma preceded ONJ in six ZOL patients. The incidence of renal adverse events was similar for ZOL and CLO. ONJ incidence remained low and was lower with CLO compared to ZOL. We have seen no further ONJ cases to date.

To choose the proper antibiotic regimen between the old and new antimicrobial agents and to determine the optimum dosage with Bi-Digital O-Ring Test.

Bi-Digital O-Ring Test (BDORT) can be used for various purposes for medical and dental diagnosis as well as for treatment purposes by determining the type of medication and the dosage for a patient. In case of infection, BDORT is a fast and non-invasive way to decide what kind of antibiotic and the dosage to be given to patient. If a patient already has been on a certain antibiotic for days, the clinician could use BDORT with diode (with arrow signs of the diode pointing to the patient) to test the same drug. Otherwise without diode, if BDORT result is negative, it could either mean the negative result might be due to resonance phenomenon or it may be because the antibiotic is ineffective. Either way, if O-Ring would be open during testing, the clinician should gradually increase or decrease the dosage of antibiotic to find out if BDORT result begins to become positive. In great majority of cases involving less effective old generation antibiotics, it is usually due to resistant microbia that require increasing dosage of antibiotic to make it become more effective. If increasing dosage would make O-Ring close, then the increased dosage would be effective to the patient. If the result is negative, the clinician should consider switching to another antibiotic regimen that may be tested positive with BDORT. Old generation antibiotics have not necessarily lost usefulness or lack efficacy on those new emerging resistant bacteria. Clinicians may just need to increase the dosage of those older generation antibiotics to make them more effective. In fact, with so many antibiotic-resisting strains of bacteria, clinician often face dilemma whether to switch to newer generation of antibiotics or just to increase the dosage of the older generation of antibiotics that a patient has been taking. When testing antibiotic of penicillin-related medication including amoxicillin, the thymus tablet (bovine source) should also be used for the testing after initially testing without it. Such a double checking system will avoid the false signal from BDORT about the drugs of penicillin family.