Modulating signaling pathways including Wnt and Hippo can induce cardiomyocyte proliferation in vivo. Applying these signaling modulators to human induced pluripotent stem cell-derived cardiomyocytes ...(hiPSC-CMs) in vitro can expand CMs modestly (<5-fold). Here, we demonstrate massive expansion of hiPSC-CMs in vitro (i.e., 100- to 250-fold) by glycogen synthase kinase-3β (GSK-3β) inhibition using CHIR99021 and concurrent removal of cell-cell contact. We show that GSK-3β inhibition suppresses CM maturation, while contact removal prevents CMs from cell cycle exit. Remarkably, contact removal enabled 10 to 25 times greater expansion beyond GSK-3β inhibition alone. Mechanistically, persistent CM proliferation required both LEF/TCF activity and AKT phosphorylation but was independent from yes-associated protein (YAP) signaling. Engineered heart tissues from expanded hiPSC-CMs showed comparable contractility to those from unexpanded hiPSC-CMs, demonstrating uncompromised cellular functionality after expansion. In summary, we uncovered a molecular interplay that enables massive hiPSC-CM expansion for large-scale drug screening and tissue engineering applications.
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•GSK-3β inhibition-mediated hiPSC-cardiomyocyte proliferation is cell density dependent•GSK-3β inhibition with reduced cell-cell contact massively expands hiPSC-cardiomyocytes•LEF/TCF activity inhibits hiPSC-cardiomyocyte maturation without promoting cell cycling•Long-term expansion does not alter cardiomyocyte contractile function
Deriving a large number of hiPSC-cardiomyocytes would be beneficial for large-scale tissue engineering and drug screening applications. Buikema et al. show that GSK-3β inhibition combined with removal of cell-cell contact enables massive expansion of hiPSC-cardiomyocytes with comparable function to non-expanded cells.
Summary
Background
Whether 10‐day or 14‐day sequential therapy is superior to 14‐day triple therapy in the first‐line treatment of Helicobacter pylori remains controversial.
Aim
To compare the ...efficacy of 10‐day or 14‐day sequential therapy vs. 14‐day triple therapy.
Methods
Randomised controlled trials (RCTs) comparing 10‐day or 14‐day sequential therapy and 14‐day triple therapy as first‐line treatment in adults were searched from the PubMed and Cochrane databases from 2000 to October 2015. s from international annual conferences were also searched. The primary and secondary outcomes were the eradication rate according to the intention‐to‐treat analysis and adverse effects, respectively.
Results
Of the 109 articles identified, 13 RCTs including 2749 patients in the sequential therapy group and 2424 patients in the 14‐day triple therapy group were eligible. Overall, sequential therapy for 10 or 14 days was not significantly superior to 14‐day triple therapy Risk ratio (RR) 1.04, 95% confidence interval (CI) 0.99–1.08, P = 0.145. However, there was significant heterogeneity (I2 = 57.6%, P = 0.005). In the subgroup analysis of four trials, we found that 14‐day sequential therapy was significantly more effective than 14‐day triple therapy (RR: 1.09, 95% CI: 1.04–1.16, P = 0.002), and there was no significant heterogeneity (I2 = 0%, P = 0.624) in this comparison. Sequential therapy given for 10 days was not superior to 14‐day triple therapy (RR: 1.03, 95% CI: 0.98–1.09, P = 0.207). There was no significant difference in the risk of adverse effects.
Conclusion
Sequential therapy given for 14 days, but not 10 days, was more effective than 14‐day triple therapy as first‐line treatment.
Aim To test ex vivo the efficiency of laser‐activated irrigation in removing dentine debris from the apical part of the root canal and to visualize in vitro the fluid dynamics during the activation ...of the irrigant by laser, using high‐speed imaging at a relevant timescale.
Methodology Root canals with a standardized groove in one canal wall filled with dentine debris were irrigated with syringe irrigation, ultrasonically or laser‐activated irrigation (LAI) using 2% sodium hypochlorite as irrigant. The quantity of dentine debris after irrigation was determined. Visualization of the fluid dynamics during activation was achieved using a high‐speed camera and a glass model.
Results Laser‐activated irrigation was significantly more effective in removing dentine debris from the apical part of the root canal than passive ultrasonic irrigation or hand irrigation when the irrigant was activated for 20 s.
Conclusions The in vitro recordings suggest that streaming, caused by the collapse of the laser‐induced bubble, is the main cleaning mechanism of LAI.
Thulium iron garnet (TmIG) films with perpendicular magnetic anisotropy (PMA) were grown on gadolinium gallium garnet (GGG) (111) substrates by off-axis sputtering. High-resolution synchrotron ...radiation X-ray diffraction studies and spherical aberration-corrected scanning transmission electron microscope (Cs-corrected STEM) images showed the excellent crystallinity of the films and their sharp interface with GGG. Damping constant of TmIG thin film was determined to be 0.0133 by frequency-dependent ferromagnetic resonance (FMR) measurements. The saturation magnetization (M
) and the coercive field (H
) were obtained systematically as a function of the longitudinal distance (L) between the sputtering target and the substrate. A 170% enhancement of PMA field (H
) was achieved by tuning the film composition to increase the tensile strain. Moreover, current-induced magnetization switching on a Pt/TmIG structure was demonstrated with an ultra-low critical current density (j
) of 2.5 × 10
A/cm
, an order of magnitude smaller than the previously reported value. We were able to tune M
, H
and H
to obtain an ultra-low j
of switching the magnetization, showing the great potential of sputtered TmIG films for spintronics.
Aim To evaluate ex vivo the incidence of defects in root dentine before and after root canal preparation and filling.
Methodology Eighty extracted mandibular premolars were divided equally in four ...groups. Group 1 was left unprepared. All other root canals were prepared using Gates Glidden drills and System GT files up to size‐40, 0.06 taper at the working length. Group 2 was not filled while the canals of the other groups were filled with gutta‐percha and AH26, either with a master cone and passive insertion of secondary gutta percha points (group 3) or lateral compaction (group 4). Roots were then sectioned horizontally 3, 6, and 9 mm from the apex and observed under a microscope. The presence of dentinal defects (fractures, craze lines or incomplete cracks) was noted and the differences between the groups were analysed with the Fisher’s exact test.
Results No defects were observed in the roots with unprepared canals. The overall difference between the groups was significant (P < 0.05). Canal preparation alone created significantly more defects than unprepared canals (P < 0.05). The total number of defects after lateral compaction was significantly larger than after noncompaction canal filling.
Conclusion Root canal preparation and filling of extracted teeth created dentine defects such as fractures, craze lines and incomplete cracks.
To detect illegal copies of copyrighted images, recent copy detection methods mostly rely on the bag-of-visual-words (BOW) model, in which local features are quantized into visual words for image ...matching. However, both the limited discriminability of local features and the BOW quantization errors will lead to many false local matches, which make it hard to distinguish similar images from copies. Geometric consistency verification is a popular technology for reducing the false matches, but it neglects global context information of local features and thus cannot solve this problem well. To address this problem, this paper proposes a global context verification scheme to filter false matches for copy detection. More specifically, after obtaining initial scale invariant feature transform (SIFT) matches between images based on the BOW quantization, the overlapping region-based global context descriptor (OR-GCD) is proposed for the verification of these matches to filter false matches. The OR-GCD not only encodes relatively rich global context information of SIFT features but also has good robustness and efficiency. Thus, it allows an effective and efficient verification. Furthermore, a fast image similarity measurement based on random verification is proposed to efficiently implement copy detection. In addition, we also extend the proposed method for partial-duplicate image detection. Extensive experiments demonstrate that our method achieves higher accuracy than the state-of-the-art methods, and has comparable efficiency to the baseline method based on the BOW quantization.
Cadmium-enrichment of farmland soil greatly threatens the sustainable use of soil resources and the safe cultivation of grain. This review paper briefly introduces the status of farmland soil as well ...as grain, which are both often polluted by cadmium (Cd) in China, and illustrates the major sources of Cd contaminants in farmland soil. In order to meet soil environmental quality standards and farmland environmental quality evaluation standards for edible agricultural products, Cd-enriched farmland soil is frequently remediated with the following prevailing techniques: dig and fill, electro-kinetic remediation, chemical elution, stabilisation and solidification, phytoremediation, field management and combined remediation. Most remediation techniques are still at the stage of small-scale trial experiments in China and few techniques are assessed in field trials. After comparing the technical and economical applicability among different Cd-enriched farmland soil remediation techniques, a novel ecological and hydraulic remediation technique has been proposed, which integrated the advantages of chemical elution, solidification and stabilisation, phytoremediation and field management. The ecological and hydraulic remediation concept is based on existing irrigation and drainage facilities, ecological ditches (ponds) and agronomic measures, which mainly detoxify the Cd-enriched soil during the interim period of crop cultivation, and guarantee the grain safety during its growth period. This technique may shift the challenge from soil to water treatment, and thus greatly enhances the remediation efficiency and shortens the remediation duration. Moreover, the proposed ecological and hydraulic remediation method matches well with the practical choice of cultivation while remediation for Cd-enriched soil in China, which has negligible impacts on the normal crop cultivation process, and thus shows great potential for large area applications.
Concept of ecological and hydraulic remediation regarding farmland soil enriched by cadmium in China. Display omitted
•In China, cadmium is the most important metal in farmland soil contamination.•Review: electro-kinetic; elution; solidification & stabilisation; phytoremediation.•Soil remediation while cultivation is most practical for cadmium management.•Integration: chemical elution; solidification & stabilisation; phytoremediation.•Ecological and hydraulic remediation is promising in detoxifying soil cadmium.
AIMS: The aim of this study was to characterize anaerobic ammonium oxidation (anammox) community in sediments of the Dongjiang River, a drinking water source of Hong Kong. METHODS AND RESULTS: The ...diversity and distribution of the anammox community were investigated based on a comparative analyses of 16S rRNA and hydrazine oxidation (hzo) genes of anammox bacteria. Candidatus Brocadia and two new anammox bacterial clusters were detected based on phylogenetic analysis of 16S rRNA genes. In contrast, the targeting of hzo genes indicated the presence of only Candidatus Jettenia with four different clusters. It was found that the sequence diversities of hzo genes were higher than those of the 16S rRNA genes. The abundance of anammox bacteria varied significantly among the sediment samples based on qPCR. Pearson correlation analysis indicated that nitrite concentration was the key factor influencing the abundance of anammox bacteria. The redundance analysis (RDA) confirmed that the combination of the contents of nitrite and nitrate, and the ratio of total nitrogen vs total carbon (TN/TC) had significant impact on the anammox bacterial community structure. CONCLUSIONS: The results revealed that the diverse anammox bacteria were present in sediments of the Dongjiang River, and the community structures were associated with varied environmental factors caused by urban pollutant invasion. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report about the distribution of anammox bacterial community in sediments of the Dongjiang River, which provides helpful information of anammox niche specificity and influencing factors in the river ecosystem.
Embryonic gene expression intricately reflects anatomical context, developmental stage, and cell type. To address whether the precise spatial origins of cardiac cells can be deduced solely from their ...transcriptional profiles, we established a genome-wide expression database from 118, 949, and 1,166 single murine heart cells at embryonic day 8.5 (e8.5), e9.5, and e10.5, respectively. We segregated these cells by type using unsupervised bioinformatics analysis and identified chamber-specific genes. Using a random forest algorithm, we reconstructed the spatial origin of single e9.5 and e10.5 cardiomyocytes with 92.0% ± 3.2% and 91.2% ± 2.8% accuracy, respectively (99.4% ± 1.0% and 99.1% ± 1.1% if a ±1 zone margin is permitted) and predicted the second heart field distribution of Isl-1-lineage descendants. When applied to Nkx2-5−/− cardiomyocytes from murine e9.5 hearts, we showed their transcriptional alteration and lack of ventricular phenotype. Our database and zone classification algorithm will enable the discovery of novel mechanisms in early cardiac development and disease.
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•Single-cell RNA-seq uncovers chamber-specific genes in the embryonic mouse heart•Machine learning can infer anatomical context from single-cell transcriptional data•Nkx2-5−/− embryonic mouse cardiomyocytes lack a ventricular transcriptional profile•Embryonic ventricular myocardium display trabecular-compact expression gradients
Cardiogenesis is orchestrated by cell-type- and chamber-specific transcription. Li et al. collected 2,233 single-cell RNA-seq samples from embryonic mouse hearts. This data resource uncovers anatomical patterns of gene expression that enable the deduction of a single-cell sample's anatomical origin, providing insight into developmental perturbations in congenital heart defect models.
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