Monitoring of canonical BMP and Wnt activities during postnatal stages of mouse first molar root formation

Objective: This study aimed to explore the precise temporospatial distributions of bone morphogenetic protein (BMP) and Wnt signaling pathways during postnatal development of mammalian tooth roots after the termination of crown morphogenesis. Methodology: A total of two transgenic mouse lines, BRE-LacZ mice and BAT-gal mice, were undertaken. The mice were sacrificed on every postnatal (PN) day from PN 3d up to PN 21d. Then, the first lower molars were extracted, and the dissected mandibles were stained with 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside (X-gal) and fixed. Serial sections at 10 µm were prepared after decalcification, dehydration, and embedding in paraffin. Results: We observed BMP/Smads and Wnt/β-catenin signaling activities in the dental sac, dental pulp, and apical papilla with a certain degree of variation. The position of activation of the BMP/Smad signaling pathway was located more coronally in the early stage, which then gradually expanded as root elongation proceeded and was associated with blood vessels in the pulp and developing complex apical tissues in the later stage. However, Wnt/β-catenin signaling was highly concentrated in the mesenchyme below the cusps in the early stage, gradually expanded to regions around the root in the transition/root stage, and then disappeared entirely in the later stage. Conclusions: These results further confirmed the participation of both BMP and Wnt canonical signaling pathways in tooth root development, as well as formed the basis for future studies on how precisely integrated signaling pathways regulate root morphogenesis and regeneration

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

A comparison of the effect of different nickel⁃titanium instruments combined with ultrasonic irrigation on root canal preparation

Objective To compare the removal efficiency and the amounts of apically extruded debris using Twist⁃ ed File (TF), Twisted File Adaptive (TFA), ProTaper, and ProTaper Next combined with ultrasonic irrigation and to pro⁃ vide an experimental basis for the selection of root canal instrumentation in the clinic. Methods Forty mandibular pre⁃ molars were randomly divided into 4 groups (n＝10 teeth per group). The canals were cut using a Twisted File, Twisted File Adaptive, ProTaper, or ProTaper Next nickel⁃titanium instrument. The canals were irrigated with ultrasonic irriga⁃ tion. The apically extruded debris were collected in preweighted Eppendorf tubes. The amount of dental tissue removed and extruded debris were assessed with an electronic balance. Results The amount of tooth tissue removed in groups A, B, C and D was 20.5 ± 2.0 mg, 17.8 ± 4.2 mg, 20.8 ± 3.9 mg and 16.5 ± 2.2 mg, respectively. Combined with ultra⁃ sonic irrigation, the Twisted File and ProTaper had a better removal efficiency than the ProTaper Next(P < 0.05). There was no significant difference in the amount of extruded debris (χ2＝4.057, P＝0.255) among four groups. Conclusion The Twisted File and ProTaper had a better removal efficiency than the ProTaper Next combined with ultrasonic irriga⁃tion. There was no significant difference in the amount of extruded debris using four Nickel⁃titanium instruments com⁃ bined with ultrasonic irrigation

Bacterial diversity and community structure of supragingival plaques in adults with dental health or caries revealed by 16S pyrosequencing

Dental caries has a polymicrobial etiology within the complex oral microbial ecosystem. However, the overall diversity and structure of supragingival plaque microbiota in adult dental health and caries are not well understood. Here, 160 supragingival plaque samples from patients with dental health and different severities of dental caries were collected for bacterial genomic DNA extraction, pyrosequencing by amplification of the 16S rDNA V1–V3 hypervariable regions, and bioinformatic analysis. High-quality sequences (2,261,700) clustered into 10,365 operational taxonomic units (OTUs; 97% identity), representing 453 independent species belonging to 122 genera, 66 families, 34 orders, 21 classes, and 12 phyla. All groups shared 7522 OTUs, indicating the presence of a core plaque microbiome. Smooth rarefaction curves were suggestive of plaque microbial diversity. α diversity analysis showed that healthy plaque microbial diversity exceeded that of dental caries, with the diversity decreasing gradually with the severity of caries. The dominant phyla of plaque microbiota included Bacteroidetes, Actinobacteria, Proteobacteria, Firmicutes, Fusobacteria, and TM7. The dominant genera included Capnocytophaga, Prevotella, Actinomyces, Corynebacterium, Neisseria, Streptococcus, Rothia, and Leptotrichia. β diversity analysis showed that the plaque microbial community structure was similar in all groups and that group members were relatively constant, only showing differences in abundance. Analysis of composition differences identified 10 health-related and 21 caries-related genera. Key genera (27) that potentially contributed to plaque microbiota distributions between groups were identified. Finally, co-occurrence network analysis and function prediction were performed. Treatment strategies directed toward modulating microbial interactions and their functional output should be further developed

Genome-wide analysis of acid tolerance genes of Enterococcus faecalis with RNA-seq and Tn-seq

Abstract Enterococcus faecalis, a formidable nosocomial and community-acquired opportunistic pathogen, can persist a wide range of extreme environments, including low pH and nutrient deficiency. Clarifying the survival mechanism of E. faecalis in low-pH conditions is the key to combating the infectious diseases caused by E. faecalis. In this study, we combined transcriptome profiling (RNA-seq) and transposon insertion sequencing (TIS) to comprehensively understand the genes that confer these features on E. faecalis. The metadata showed that genes whose products are involved in cation transportation and amino acid biosynthesis were predominantly differentially expressed under acid conditions. The products of genes such as opp1C and copY reduced the hydrion concentration in the cell, whereas those of gldA2, gnd2, ubiD, and ubiD2 mainly participated in amino metabolism, increasing matters to neutralize excess acid. These, together with the folE and hexB genes, which are involved in mismatch repair, form a network of E. faecalis genes necessary for its survival under acid conditions

Human Dental Pulp Stem Cells via the NF-&#954;B Pathway

Background/Aims: Odontogenic differentiation of human dental pulp stem cells (HDPSCs) is regulated by multiple factors and signaling molecules. However, their regulatory mechanisms are not completely understood. In this study, we investigated the role of Zinc finger and BTB domain-containing 20 (ZBTB20) in odontoblastic differentiation of HDPSCs. Methods: HDPSCs were obtained from human third molars and ZBTB20 expression was examined by qRT-PCR and western blot. Their osteo/odontogenic differentiation and the involvement of NF-&#954;B pathway were subsequently investigated. Results: The expression of ZBTB20 is upregulated in a time-dependent manner during odontogenic differentiation of hDPSCs. Inhibition of ZBTB20 reduced osteogenic medium (OM)-induced odontogenic differentiation, reflected in decreased alkaline phosphatase (ALP) activity, mineralized nodule formation and mRNA expression of odonto/osteogenic marker genes. In contrast, overexpression of ZBTB20 enhanced ALP activity, mineralization and the expression of differentiation marker genes. Furthermore, the expression of I&#954;Ba was increased by ZBTB20 silencing in HDPSCs, whereas ZBTB20 overexpression decreased I&#954;Ba and enhanced nuclear NF-&#954;B p65. Inhibition of the NF-&#954;B pathway significantly suppressed the odontogenic differentiation of HDPSCs induced by ZBTB20. Conclusion: This study shows for the first time that ZBTB20 plays an important role during odontoblastic differentiation of HDPSCs and may have clinical implications for regenerative endodontics

Advancement of platelet-inspired nanomedicine

Human platelets play important roles in several physiologic and pathologic processes. Any defects in platelet number and function can lead to a variety of bleeding complications; platelet transfusions are commonly used to improve platelet count and hemostatic function in these cases. However, transfusions are complicated by the short storage life of donated platelets and contamination risks. Synthetic platelet substitutes can render efficient hemostasis while allowing advantages of large-scale preparation, minimum contamination risk via effective sterilization, longer shelf-life, no need for blood type matching, and reduced risks of biologic or pathologic side effects. Recent efforts in synthetic platelet design have additionally focused on applications including hemostasis, drug delivery, and targeted delivery of cancer therapeutics. In the present review, we summarize the advancement of platelet-inspired nanomedicine for artificial blood component, tumor research, and treatment of thrombi