Villification of the intestinal epithelium is driven by Foxl1.

The primitive gut tube of mammals initially forms as a simple cylinder consisting of the endoderm-derived, pseudostratified epithelium and the mesoderm-derived surrounding mesenchyme. During mid-gestation a dramatic transformation occurs in which the epithelium is both restructured into its final cuboidal form and simultaneously folded and refolded to create intestinal villi and intervillus regions, the incipient crypts. Here we show that the mesenchymal winged helix transcription factor Foxl1, itself induced by epithelial hedgehog signaling, controls villification by activating BMP and PDGFRα as well as planar cell polarity genes in epithelial-adjacent telocyte progenitors, both directly and in a feed-forward loop with Foxo3.

Line-Features-Based Pose Estimation Method for the Disc Cutter Holder of Shield Machine.

To achieve automatic disc cutter replacement of shield machines, measuring the accurate pose of the disc cutter holder by machine vision is crucial. However, under polluted and restricted illumination conditions, achieving pose estimation by vision is a great challenge. This paper proposes a line-features-based pose estimation method for the disc cutter holder of the shield machine by using a monocular camera. For the blurring effect of rounded corners on the image edge, a rounded edge model is established to obtain edge points that better match the 3D model of the workpiece. To obtain the edge search box corresponding to each edge, a contour separation method based on an adaptive threshold region growing method is proposed. By preprocesses on the edge points of each edge, the efficiency and the accuracy of RANSAC linear fitting are improved. The experimental result shows that the proposed pose estimation method is highly reliable and can meet the measurement accuracy requirements in practical engineering applications.

Complete mitochondrial genome of Lepidotrigla alata (Osteichthyes: Triglidae) with phylogenetic consideration.

The complete mitochondrial genome of Lepidotrigla alata was sequenced in this study. The genome sequence is 16,512 bp in length, comprising 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and one control region. Overall base composition is 26.46% A, 25.05% T, 17.22% G, and 31.27% C. Phylogenetic analysis indicated that L. alata was close to L. guentheri and L. microptera, and each genus in the family Triglidae was monophyletic. This study can provide valuable information for future evolutionary studies on L. alata and Triglidae.

Pose Determination of the Disc Cutter Holder of Shield Machine Based on Monocular Vision.

The visual measurement system plays a vital role in the disc cutter changing robot of the shield machine, and its accuracy directly determines the success rate of the disc cutter grasping. However, the actual industrial environment with strong noise brings a great challenge to the pose measurement methods. The existing methods are difficult to meet the required accuracy of pose measurement based on machine vision under the disc cutter changing conditions. To solve this problem, we propose a monocular visual pose measurement method consisting of the high precision optimal solution to the PnP problem (OPnP) method and the highly robust distance matching (DM) method. First, the OPnP method is used to calculate the rough pose of the shield machine's cutter holder, and then the DM method is used to measure its pose accurately. Simulation results show that the proposed monocular measurement method has better accuracy and robustness than the several mainstream PnP methods. The experimental results also show that the maximum error of the proposed method is 0.28° in the direction of rotation and 0.32 mm in the direction of translation, which can meet the measurement accuracy requirement of the vision system of the disc cutter changing robot in practical engineering application.

Optimized scheme for paired transverse corrective forces in S-shaped scoliosis via ultrasound and application in Chêneau brace: a pilot study.

BACKGROUND: There is currently no consensus on the optimal positions of the transverse corrective forces (TCFs) for scoliosis braces. OBJECTIVES: This study aimed to explore an optimal scheme of placing paired TCF for S-shaped adolescent idiopathic scoliosis and its feasibility in Chêneau brace (CB) treatment. STUDY DESIGN: Cross-over feasibility pilot trial. METHODS: Ten S-shaped adolescent idiopathic scoliosis participants were invited to receive four tests with different paired TCF positions under ultrasound. The positions of the paired TCF were test 1: thoracic apical vertebra (AV), lumbar AV; test 2: 2 cm inferior to thoracic AV, lumbar AV; test 3: thoracic AV, 2 cm superior to lumbar AV; and test 4: 2 cm inferior to thoracic AV, 2 cm superior to lumbar AV. The test scheme with the highest mean in-force correction rate (IFCR) for the thoracic spinous process angle (SPA) was further applied in the CB fabrication of 4 additional participants. RESULTS: A significant higher mean IFCR of the thoracic SPA of 63.6% was found in test 2 (P < 0.001), which also contributed to its higher overall IFCR of the SPA of 64.6% (P = 0.001). Moreover, the mean in-brace correction rates for the thoracic and overall curves in CB were 46.4% and 51.8%, respectively. No adverse events were reported. CONCLUSIONS: Placing paired TCF at the lumbar AV and 2 cm inferior to the thoracic AV achieved better treatment efficacy than other schemes. The practical application of this scheme on the CB was feasible.

A Comparative Transcriptional Landscape of Two Castor Cultivars Obtained by Single-Molecule Sequencing Comparative Analysis.

Background and Objectives: Castor (Ricinus communis L.) is an important non-edible oilseed crop. Lm-type female strains and normal amphiprotic strains are important castor cultivars, and are mainly different in their inflorescence structures and leaf shapes. To better understand the mechanisms underlying these differences at the molecular level, we performed a comparative transcriptional analysis. Materials and Methods: Full-length transcriptome sequencing and short-read RNA sequencing were employed. Results: A total of 76,068 and 44,223 non-redundant transcripts were obtained from high-quality transcripts of Lm-type female strains and normal amphiprotic strains, respectively. In Lm-type female strains and normal amphiprotic strains, 51,613 and 20,152 alternative splicing events were found, respectively. There were 13,239 transcription factors identified from the full-length transcriptomes. Comparative analysis showed a great variety of gene expression of common and unique transcription factors between the two cultivars. Meanwhile, a functional analysis of the isoforms was conducted. The full-length sequences were used as a reference genome, and a short-read RNA sequencing analysis was performed to conduct differential gene analysis. Furthermore, the function of DEGs were performed to annotation analysis. Conclusion: The results revealed considerable differences and expression diversity between the two cultivars, well beyond what was reported in previous studies and likely reflecting the differences in architecture between these two cultivars.

MRISCs protect colonic stem cells from inflammatory damage.

Increasing evidence suggest functional roles of subepithelial mesenchymal niche cells in maintaining intestinal stem cells and in modulating the pathogenesis of various intestinal diseases in mammals. A recent study reported the discovery of a new population of stromal cells in mice termed MAP3K2-Regulated Intestinal Stromal Cells (MRISCs); these cells reside at the base of colonic crypt and function to protect colonic stem cells during colonic inflammation by expressing the Wnt agonist R-spondin1 (Rspo1).

The cellular niche for intestinal stem cells: a team effort.

The rapidly self-renewing epithelium in the mammalian intestine is maintained by multipotent intestinal stem cells (ISCs) located at the bottom of the intestinal crypt that are interspersed with Paneth cells in the small intestine and Paneth-like cells in the colon. The ISC compartment is also closely associated with a sub-epithelial compartment that contains multiple types of mesenchymal stromal cells. With the advances in single cell and gene editing technologies, rapid progress has been made for the identification and characterization of the cellular components of the niche microenvironment that is essential for self-renewal and differentiation of ISCs. It has become increasingly clear that a heterogeneous population of mesenchymal cells as well as the Paneth cells collectively provide multiple secreted niche signals to promote ISC self-renewal. Here we review and summarize recent advances in the regulation of ISCs with a main focus on the definition of niche cells that sustain ISCs.

Adaptive-Neuro-Fuzzy-Based Information Fusion for the Attitude Prediction of TBMs.

In a tunneling boring machine (TBM), to obtain the attitude in real time is very important for a driver. However, the current laser targeting system has a large delay before obtaining the attitude. So, an adaptive-neuro-fuzzy-based information fusion method is proposed to predict the attitude of a laser targeting system in real time. In the proposed method, a dual-rate information fusion is used to fuse the information of a laser targeting system and a two-axis inclinometer, and then obtain roll and pitch angles with a higher rate and provide a smoother attitude prediction. Considering that a measurement error exists, the adaptive neuro-fuzzy inference system (ANFIS) is proposed to model the measurement error, and then the ANFIS-based model is combined with the dual-rate information fusion to achieve high performance. Experimental results show the ANFIS-based information fusion can provide higher real-time performance and accuracy of the attitude prediction. Experimental results also verify that the ANFIS-based information fusion can solve the problem of the laser targeting system losing signals.

Robust internal model control of servo motor based on sliding mode control approach.

This paper proposes a robust internal model control (IMC) based on sliding mode control (SMC) approach for high-performance motion control of a servo motor subject to uncertainties and/or disturbances. The proposed control strategy considers not only the simplicity and intuition of the IMC-based controller for a prescribed tracking performance but also the effectiveness of the SMC scheme to guarantee the robustness of the servo system. Since the performance of the IMC-based controller can be analyzed via a SMC structure, a robust control law based on the SMC technique is introduced into the IMC scheme to decrease the sensitivity to uncertainties and enhance the resistance to disturbances. Moreover, the 2-degree-of-freedom IMC integrating the robust SMC scheme is developed to further improve the control performance. The stability is analyzed based on Lyapunov theory, and the theoretical results show that a prescribed transient tracking performance and a final tracking accuracy of the servo system can be guaranteed. Comparative simulations and experiments are investigated to verify the high performance nature of the proposed control strategy.

Reviewing Clinical Effectiveness of Active Training Strategies of Platform-Based Ankle Rehabilitation Robots.

Objective: This review aims to provide a systematical investigation of clinical effectiveness of active training strategies applied in platform-based ankle robots. Method: English-language studies published from Jan 1980 to Aug 2017 were searched from four databases using key words of "Ankle∗" AND "Robot∗" AND "Effect∗ OR Improv∗ OR Increas∗." Following an initial screening, three rounds of discrimination were successively conducted based on the title, the abstract, and the full paper. Result: A total of 21 studies were selected with 311 patients involved; of them, 13 studies applied a single group while another eight studies used different groups for comparison to verify the therapeutic effect. Virtual-reality (VR) game training was applied in 19 studies, while two studies used proprioceptive neuromuscular facilitation (PNF) training. Conclusion: Active training techniques delivered by platform ankle rehabilitation robots have been demonstrated with great potential for clinical applications. Training strategies are mostly combined with one another by considering rehabilitation schemes and motion ability of ankle joints. VR game environment has been commonly used with active ankle training. Bioelectrical signals integrated with VR game training can implement intelligent identification of movement intention and assessment. These further provide the foundation for advanced interactive training strategies that can lead to enhanced training safety and confidence for patients and better treatment efficacy.

A Feasibility Study of SSVEP-Based Passive Training on an Ankle Rehabilitation Robot.

OBJECTIVE: This study aims to establish a steady-state visual evoked potential- (SSVEP-) based passive training protocol on an ankle rehabilitation robot and validate its feasibility. METHOD: This paper combines SSVEP signals and the virtual reality circumstance through constructing information transmission loops between brains and ankle robots. The robot can judge motion intentions of subjects and trigger the training when subjects pay their attention on one of the four flickering circles. The virtual reality training circumstance provides real-time visual feedback of ankle rotation. RESULT: All five subjects succeeded in conducting ankle training based on the SSVEP-triggered training strategy following their motion intentions. The lowest success rate is 80%, and the highest one is 100%. The lowest information transfer rate (ITR) is 11.5 bits/min when the biggest one of the robots for this proposed training is set as 24 bits/min. CONCLUSION: The proposed training strategy is feasible and promising to be combined with a robot for ankle rehabilitation. Future work will focus on adopting more advanced data process techniques to improve the reliability of intention detection and investigating how patients respond to such a training strategy.

BMI1 and MEL18 Promote Colitis-Associated Cancer in Mice via REG3B and STAT3.

BACKGROUND & AIMS: Polycomb group proteins are epigenetic factors that silence gene expression; they are dysregulated in cancer cells and contribute to carcinogenesis by unclear mechanisms. We investigated whether BMI1 proto-oncogene, polycomb ring finger (BMI1), and polycomb group ring finger 2 (PCGF2, also called MEL18) are involved in the initiation and progression of colitis-associated cancer (CAC) in mice. METHODS: We generated mice containing floxed alleles of Bmi1 and/or Mel18 and/or Reg3b using the villin-Cre promoter (called Bmi1ΔIEC, Mel18ΔIEC, DKO, and TKO mice). We also disrupted Bmi1 and/or Mel18 specifically in intestinal epithelial cells (IECs) using the villin-CreERT2-inducible promoter. CAC was induced in cre-negative littermate mice (control) and mice with conditional disruption of Bmi1 and/or Mel18 by intraperitoneal injection of azoxymethane (AOM) followed by addition of dextran sulfate sodium (DSS) to drinking water. Colon tissues were collected from mice and analyzed by histology and immunoblots; IECs were isolated and used in cDNA microarray analyses. RESULTS: Following administration of AOM and DSS, DKO mice developed significantly fewer polyps than control, Bmi1ΔIEC, Mel18ΔIEC, Reg3bΔIEC, or TKO mice. Adenomas in the colons of DKO mice were low-grade dysplasias, whereas adenomas in control, Bmi1ΔIEC, Mel18ΔIEC, Reg3bΔIEC, or TKO mice were high-grade dysplasias with aggressive invasion of the muscularis mucosa. Disruption of Bmi1 and Mel18 (DKO mice) during late stages of carcinogenesis significantly reduced the numbers of large adenomas and the load of total adenomas, reduced proliferation, and increased apoptosis in colon tissues. IECs isolated from DKO mice after AOM and DSS administration had increased expression of Reg3b compared with control, Bmi1ΔIEC, or Mel18ΔIEC mice. Expression of REG3B was sufficient to inhibit cytokine-induced activation of STAT3 in IECs. The human REG3ß protein, the functional counterpart of mouse REG3B, inhibited STAT3 activity in human 293T cells, and its expression level in colorectal tumors correlated inversely with pSTAT3 level and survival times of patients. CONCLUSIONS: BMI1 and MEL18 contribute to the development of CAC in mice by promoting proliferation and reducing apoptosis via suppressing expression of Reg3b. REG3B negatively regulates cytokine-induced activation of STAT3 in colon epithelial cells. This pathway might be targeted in patients with colitis to reduce carcinogenesis.

Identification of olfactory receptor genes in the Japanese grenadier anchovy Coilia nasus.

Olfaction is essential for fish to detect odorant elements in the environment and plays a critical role in navigating, locating food and detecting predators. Olfactory function is produced by the olfactory transduction pathway and is activated by olfactory receptors (ORs) through the binding of odorant elements. Recently, four types of olfactory receptors have been identified in vertebrate olfactory epithelium, including main odorant receptors (MORs), vomeronasal type receptors (VRs), trace-amine associated receptors (TAARs) and formyl peptide receptors (FPRs). It has been hypothesized that migratory fish, which have the ability to perform spawning migration, use olfactory cues to return to natal rivers. Therefore, obtaining OR genes from migratory fish will provide a resource for the study of molecular mechanisms that underlie fish spawning migration behaviors. Previous studies of OR genes have mainly focused on genomic data, however little information has been gained at the transcript level. In this study, we identified the OR genes of an economically important commercial fish Coilia nasus through searching for olfactory epithelium transcriptomes. A total of 142 candidate MOR, 52 V2R/OlfC, 32 TAAR and two FPR putative genes were identified. In addition, through genomic analysis we identified several MOR genes containing introns, which is unusual for vertebrate MOR genes. The transcriptome-scale mining strategy proved to be fruitful in identifying large sets of OR genes from species whose genome information is unavailable. Our findings lay the foundation for further research into the possible molecular mechanisms underlying the spawning migration behavior in C. nasus.

A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors.

The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes-permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.

[Microdevice for the investigation of high-glucose induced lifespan and the protective effect of polydatin in C. elegans].

Caenorhabditis elegans (C. elegans) has been widely used as a model organism for biomedical research due to its sufficient homology with human at molecular or genomic level. In this work, we describe a microfluidic device not only to investigate the response of C. elegans including lifespan and oxidative stress, but also to evaluate the protective effect of polydatin induced by high-glucose condition. It was found that the mean lifespan of worms was significantly reduced and the oxidative stress protein GST-4 was increased in worms that are subjected to high glucose. However, a certain dose of polydatin could weaken the increased oxidative stress induced by high-glucose and extend the lifespan, indicating the protective effect of polydatin against the toxic of high-glucose. The established approach is simple to operate, easy for realtime imaging and multiparatemer evaluations in parallel, providing a potential platform for drug evaluation/screening in a high throughput format at single animal resolution.

Identification of a uniquely expanded V1R (ORA) gene family in the Japanese grenadier anchovy (Coilia nasus).

A number of studies have suggested that olfaction plays an important role in fish migration. Fish use several distinct families of olfactory receptors to detect environmental odorants, including MORs (main olfactory receptors), V1Rs (vomeronasal type-1 receptors), V2Rs (vomeronasal type-2 receptors), TAARs (trace amine-associated receptors), and FPRs (formyl peptide receptors). The V1Rs have been reported to detect pheromones, and a pheromone hypothesis for the spawning migration of anadromous fish has been proposed. Examining whether Coilia nasus relies on V1R-mediated olfaction for spawning migration is important for understanding the molecular basis of spawning migration behavior. Here, we explored the V1R gene family in anadromous C. nasus. Six V1R genes previously reported in other teleost fish were successfully identified. Interestingly, we detected the largest V1R repertoire in teleost fish from C. nasus and identified a species-specific expansion event of V1R3 gene that has previously been detected as single-copy genes in other teleost fish. The V1R loci were found to be populated with repetitive sequences, especially in the expanded V1R3 genes. Additionally, the divergence of V1R3 genetic structures in different populations of C. nasus indicates the copy number variation (CNV) in V1R3 gene among individuals of C. nasus. Most of the putative C. nasus V1R genes were expressed primarily in the olfactory epithelium, consistent with the role of the gene products as functional olfactory receptors. Significant differences in the expression levels of V1R genes were detected between the anadromous and non-anadromous C. nasus. This study represents a first step in the elucidation of the olfactory communication system of C. nasus at the molecular level. Our results indicate that some V1R genes may be involved in the spawning migration of C. nasus, and the study provides new insights into the spawning migration and genome evolution of C. nasus.

Modeling type 2 diabetes-like hyperglycemia in C. elegans on a microdevice.

Caenorhabditis elegans (C. elegans) has been widely used as a model organism for biomedical research due to its sufficient homology with mammals at the molecular and genomic levels. In this work, we describe a microfluidic assay to model type 2 diabetes-like hyperglycemia in C. elegans to examine several aspects of this disease on a microdevice. The microdevice is characterized by the integration of long-term worm culture, worm immobilization, and precise chemical stimuli in a single device, thus enabling the multi-parameter analysis of individual worms at a single-animal resolution. With this device, the lifespan, oxidative stress responses, and lipid metabolism of individual worms in response to different glucose concentrations were characterized. It was found that the mean lifespan of worms was significantly reduced by as much as 29.0% and 30.8% in worms that were subjected to 100 mM and 200 mM glucose, respectively. The expression of oxidative stress protein gst-4 was increased, and the expression of hsp-70 (heat shock protein) and skn-1 (redox sensitive transcription factor) genes was down-regulated in worms treated with a high level of glucose. Moreover, fat storage was markedly increased in the bodies of VS29 worms (vha-6p::GFP::dgat-2) that were exposed to the high-glucose condition. The established approach is not only suitable for further elucidation of the mechanism of metabolic disorders involved in diabetes and its complications, but also facilitates the evaluation of anti-diabetic drugs in a high-throughput manner.

A droplet microchip with substance exchange capability for the developmental study of C. elegans.

The nematode Caenorhabditis elegans (C. elegans) has been widely used as a multicellular organism in developmental research due to its simplicity, short lifecycle, and its relevance to human genetics and biology. Droplet microfluidics is an attractive platform for the study of C. elegans in integrated mode with flexibility at the single animal resolution. However, it is still challenging to conduct the developmental study of worms within droplets initiating at the L1 larval stage, due to the small size, active movement, and the difficulty in achieving effective substance exchange within the droplets. Here, we present a multifunctional droplet microchip to address these issues and demonstrate the usefulness of this device for investigating post-embryonic development in individual C. elegans initiating at the larval L1 stage. The key components of this device consist of multiple functional units that enable parallel worm loading, droplet formation/trapping, and worm encapsulation in parallel. In particular, it exhibits superior functions in encapsulating and trapping individual larval L1 worms into droplets in a controlled way. Continuous food addition and expulsion of waste by mixing the static worm-in-droplet with moving medium plugs allows for the long-term culture of worms under a variety of conditions. We used this device to investigate the development processes of C. elegans in transgenic strains with deletion and overexpression of the hypoxia-inducible factor (HIF-1), a highly conserved transcript factor in regulating an organism's response to hypoxia. This microdevice may be a useful tool for the high throughput analysis of individual worms starting at the larval stage, and facilitates the study of developmental worms in response to multiple drugs or environmental toxins.

De novo transcriptomes of olfactory epithelium reveal the genes and pathways for spawning migration in japanese grenadier anchovy (Coilia nasus).

BACKGROUND: Coilia nasus (Japanese grenadier anchovy) undergoes spawning migration from the ocean to fresh water inland. Previous studies have suggested that anadromous fish use olfactory cues to perform successful migration to spawn. However, limited genomic information is available for C. nasus. To understand the molecular mechanisms of spawning migration, it is essential to identify the genes and pathways involved in the migratory behavior of C. nasus. RESULTS: Using de novo transcriptome sequencing and assembly, we constructed two transcriptomes of the olfactory epithelium from wild anadromous and non-anadromous C. nasus. Over 178 million high-quality clean reads were generated using Illumina sequencing technology and assembled into 176,510 unigenes (mean length: 843 bp). About 51% (89,456) of the unigenes were functionally annotated using protein databases. Gene ontology analysis of the transcriptomes indicated gene enrichment not only in signal detection and transduction, but also in regulation and enzymatic activity. The potential genes and pathways involved in the migratory behavior were identified. In addition, simple sequence repeats and single nucleotide polymorphisms were analyzed to identify potential molecular markers. CONCLUSION: We, for the first time, obtained high-quality de novo transcriptomes of C. nasus using a high-throughput sequencing approach. Our study lays the foundation for further investigation of C. nasus spawning migration and genome evolution.