Biomineralization stimulated peri-titanium implants prepared by selective laser melting

AbstractTitanium implants prepared by selective laser melting (SLM), a method of additive manufacturing, were subjected to implantation in beagle dogs for two and four weeks. Argon ion beam-polished cross sections of the implants after in vivo tests were characterized by scanning electron microscope (SEM) to evaluate the bone–implant interface and the early peri-implant biomineralization with sufficiently improved resolution. Two bone mineralization mechanisms were disclosed. As early as two weeks after implantation, a layer of new bone was found to form directly on the implant surface and bone in-growth was also observed. Osseointegration was found to establish partly at the tip of the implants. After healing for four weeks it was found that osseointegration was established around the entire tip of the implants, whereas only partly at the third thread region of the implants. The experimental evidences observed reveal that an inherent highly porous surface of the titanium implants generated by selective laser melting is favorable for new bone apposition

Effects of Plasma-Activated Water on Skin Wound Healing in Mice

Cold atmospheric plasma (CAP) has been widely used in biomedicine during the last two decades. While direct plasma treatment has been reported to promote wound healing, its application can be uneven and inconvenient. In this study, we first activated water with a portable dielectric barrier discharge plasma device and evaluated the inactivation effect of plasma-activated water (PAW) on several kinds of bacteria that commonly infect wounds. The results show that PAW can effectively inactivate these bacteria. Then, we activated tap water and examined the efficacy of PAW on wound healing in a mouse model of full-thickness skin wounds. We found that wound healing in mice treated with PAW was significantly faster compared with the control group. Histological analysis of the skin tissue of mice wounds showed a significant reduction in the number of inflammatory cells in the PAW treatment group. To identify the possible mechanism by which PAW promotes wound healing, we analyzed changes in the profiles of wound bacteria after PAW treatment. The results show that PAW can significantly reduce the abundance of wound bacteria in the treatment group. The results of biochemical blood tests and histological analysis of major internal organs in the mice show that PAW had no obvious side effects. Taken together, these results indicate that PAW may be a new and effective method for promoting wound healing without side effects

Senescence: novel insight into DLX3 mutations leading to enhanced bone formation in Tricho-Dento-Osseous syndrome

The homeodomain transcription factor distal-less homeobox 3 gene (DLX3) is required for hair, tooth and skeletal development. DLX3 mutations have been found to be responsible for Tricho-Dento-Osseous (TDO) syndrome, characterized by kinky hair, thin-pitted enamel and increased bone density. Here we show that the DLX3 mutation (c.533 A>G; Q178R) attenuates osteogenic potential and senescence of bone mesenchymal stem cells (BMSCs) isolated from a TDO patient, providing a molecular explanation for abnormal increased bone density. Both DLX3 mutations (c.533 A>G and c.571_574delGGGG) delayed cellular senescence when they were introduced into pre-osteoblastic cells MC3T3-E1. Furthermore, the attenuated skeletal aging and bone loss in DLX3 (Q178R) transgenic mice not only reconfirmed that DLX3 mutation (Q178R) delayed cellular senescence, but also prevented aging-mediated bone loss. Taken together, these results indicate that DLX3 mutations act as a loss of function in senescence. The delayed senescence of BMSCs leads to increased bone formation by compensating decreased osteogenic potentials with more generations and extended functional lifespan. Our findings in the rare human genetic disease unravel a novel mechanism of DLX3 involving the senescence regulation of bone formation

Mutations in WNT10B Are Identified in Individuals with Oligodontia

Supplemental Data Supplemental Data include six figures and three tables and can be found with this article online at http://dx.doi.org/10.1016/j.ajhg.2016.05.012. Supplemental Data Document S1. Figures S1–S6 and Tables S1–S3 Download Document S2. Article plus Supplemental Data Download Web Resources Allen Brain Atlas, http://www.brain-map.org/ Eurexpress, http://www.eurexpress.org/ee/ ExAC Browser, http://exac.broadinstitute.org/ GEO Profiles, http://www.ncbi.nlm.nih.gov/geoprofiles HGMD, http://www.biobase-international.com/product/hgmd MutationTaster, http://www.mutationtaster.org/ OMIM, http://www.omim.org RefSeq, http://www.ncbi.nlm.nih.gov/refseq/ Tooth agenesis is one of the most common developmental anomalies in humans. Oligodontia, a severe form of tooth agenesis, is genetically and phenotypically a heterogeneous condition. Although significant efforts have been made, the genetic etiology of dental agenesis remains largely unknown. In the present study, we performed whole-exome sequencing to identify the causative mutations in Chinese families in whom oligodontia segregates with dominant inheritance. We detected a heterozygous missense mutation (c.632G>A [p.Arg211Gln]) in WNT10B in all affected family members. By Sanger sequencing a cohort of 145 unrelated individuals with non-syndromic oligodontia, we identified three additional mutations (c.569C>G [p.Pro190Arg], c.786G>A [p.Trp262∗], and c.851T>G [p.Phe284Cys]). Interestingly, analysis of genotype-phenotype correlations revealed that mutations in WNT10B affect the development of permanent dentition, particularly the lateral incisors. Furthermore, a functional assay demonstrated that each of these mutants could not normally enhance the canonical Wnt signaling in HEPG2 epithelial cells, in which activity of the TOPFlash luciferase reporter was measured. Notably, these mutant WNT10B ligands could not efficiently induce endothelial differentiation of dental pulp stem cells. Our findings provide the identification of autosomal-dominant WNT10B mutations in individuals with oligodontia, which increases the spectrum of congenital tooth agenesis and suggests attenuated Wnt signaling in endothelial differentiation of dental pulp stem cells

5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding

Funding Information: The investigators were supported by grants from the NIH (R01DK114279, R01DK109934, and R21NS108091 to QT; R01ES027544 and R01DK111436 to ZS; R00DK107008 to PX; R01DK109194 and R56DK109194 to QW; P01DK113954, R01DK115761, R01DK117281, and R01DK125480 to YX; R01DK120858 to QT and YX; K01DK119471 to CW; and P20GM135002 to YH), USDA/CRIS (51000-064-01 S to YX and QW), American Diabetes Association (1-17-PDF-138 to YH, 7-13-JF-61 to QW, and 1-15-BS-184 to QT), American Heart Association awards (16POST27260254 to CW), the Pew Charitable Trust awards to QW (0026188), Baylor Collaborative Faculty Research Investment Program grants to QW, the Faculty Start-up grants from USDA/ ARS to QW, the Biotechnology and Biological Sciences Research Council (BB/ K001418/1 and BB/NO17838/1 to LKH), and the Medical Research Council (MC/PC/ 15077 to LKH). QW is the Pew Scholar of Biomedical Sciences and the Kavli Scholar. The anxiety tests (e.g., open-field test, light–dark test, and elevated plus maze test) were performed in the Mouse Neurobehavior Core, Baylor College of Medicine, which was supported by National Institutes of Health Grant No. P30HD024064. The Ad-iN/ WED virus was kindly provided by Dr. Martin Myers (University of Michigan). The AAV9-CBA-DIO-WGA-zsGreen virus was kindly provided by Dr. Richard Palmiter (University of Washington).Peer reviewedPublisher PD

Orbital-Dependent Electron Correlation in Double-Layer Nickelate La3Ni2O7

The latest discovery of high temperature superconductivity near 80K in La3Ni2O7 under high pressure has attracted much attention. Many proposals are put forth to understand the origin of superconductivity. The determination of electronic structures is a prerequisite to establish theories to understand superconductivity in nickelates but is still lacking. Here we report our direct measurement of the electronic structures of La3Ni2O7 by high-resolution angle-resolved photoemmission spectroscopy. The Fermi surface and band structures of La3Ni2O7 are observed and compared with the band structure calculations. A flat band is formed from the Ni-3dz2 orbitals around the zone corner which is 50meV below the Fermi level. Strong electron correlations are revealed which are orbital- and momentum-dependent. Our observations will provide key information to understand the origin of high temperature superconductivity in La3Ni2O7.Comment: 18 pages, 4 figure

Pharmacokinetics/pharmacodynamics of polymyxin B in patients with bloodstream infection caused by carbapenem-resistant Klebsiella pneumoniae

Introduction: Polymyxin B is a last-line therapy for carbapenem-resistant microorganisms. However, a lack of clinical pharmacokinetic/pharmacodynamic (PK/PD) data has substantially hindered dose optimization and breakpoint setting.Methods: A prospective, multi-center clinical trial was undertaken with polymyxin B [2.5 mg/kg loading dose (3-h infusion), 1.25 mg/kg/12 h maintenance dose (2-h infusion)] for treatment of carbapenem-resistant K. pneumoniae (CRKP) bloodstream infections (BSI). Safety, clinical and microbiological efficacy were evaluated. A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to determine the concentrations of polymyxin B in blood samples. Population pharmacokinetic (PK) modeling and Monte Carlo simulations were conducted to examine the susceptibility breakpoint for polymyxin B against BSI caused by CRKP.Results: Nine patients were enrolled and evaluated for safety. Neurotoxicity (5/9), nephrotoxicity (5/9), and hyperpigmentation (1/9) were recorded. Blood cultures were negative within 3 days of commencing therapy in all 8 patients evaluated for microbiological efficacy, and clinical cure or improvement occurred in 6 of 8 patients. Cmax and Cmin following the loading dose were 5.53 ± 1.80 and 1.62 ± 0.41 mg/L, respectively. With maintenance dosing, AUCss,24 h was 79.6 ± 25.0 mg h/L and Css,avg 3.35 ± 1.06 mg/L. Monte Carlo simulations indicated that a 1 mg/kg/12-hourly maintenance dose could achieve >90% probability of target attainment (PTA) for isolates with minimum inhibitory concentration (MIC) ≤1 mg/L. PTA dropped substantially for MICs ≥2 mg/L, even with a maximally recommended daily dose of 1.5 mg/kg/12-hourly.Conclusion: This is the first clinical PK/PD study evaluating polymyxin B for BSI. These results will assist to optimize polymyxin B therapy and establish its breakpoints for CRKP BSI

Genome Expression Profile Analysis of the Immature Maize Embryo during Dedifferentiation

Maize is one of the most important cereal crops worldwide and one of the primary targets of genetic manipulation, which provides an excellent way to promote its production. However, the obvious difference of the dedifferentiation frequency of immature maize embryo among various genotypes indicates that its genetic transformation is dependence on genotype and immature embryo-derived undifferentiated cells. To identify important genes and metabolic pathways involved in forming of embryo-derived embryonic calli, in this study, DGE (differential gene expression) analysis was performed on stages I, II, and III of maize inbred line 18-599R and corresponding control during the process of immature embryo dedifferentiation. A total of ∼21 million cDNA tags were sequenced, and 4,849,453, 5,076,030, 4,931,339, and 5,130,573 clean tags were obtained in the libraries of the samples and the control, respectively. In comparison with the control, 251, 324 and 313 differentially expressed genes (DEGs) were identified in the three stages with more than five folds, respectively. Interestingly, it is revealed that all the DEGs are related to metabolism, cellular process, and signaling and information storage and processing functions. Particularly, the genes involved in amino acid and carbohydrate transport and metabolism, cell wall/membrane/envelope biogenesis and signal transduction mechanism have been significantly changed during the dedifferentiation. To our best knowledge, this study is the first genome-wide effort to investigate the transcriptional changes in dedifferentiation immature maize embryos and the identified DEGs can serve as a basis for further functional characterization