Emerging evidence indicates that the long noncoding RNAs extensively participate in cancer progression. Nevertheless, the molecular pathogenesis of how these lncRNAs regulate tumorigenesis has not been fully elucidated especially in hepatocellular carcinoma (HCC). Here, we sought to define the role of a novel lncRNA named lncRNA-NEF in modulating epithelial to mesenchymal transition (EMT) in HCC. It was found that the lncRNA-NEF was transcriptionally activated by EMT suppressor FOXA2 and frequently downregulated in HCC cell lines as well as clinical specimens. Although enhanced expression of lncRNA-NEF did not affect tumor cell growth, ectopic expression of lncRNA-NEF significantly suppressed EMT program and cell migration. Animal studies validated that lncRNA-NEF alleviated in vivo tumor metastasis and protected mice from tumor-induced mortality. Interestingly, we verified that lncRNA-NEF acted as a novel activator of its neighbor gene FOXA2, which formed a positive feedback loop. Subsequent studies revealed that lncRNA-NEF physically interacted with β-catenin to increase the binding of GSK3β with β-catenin and therefore promoted the inhibitory phosphorylation of β-catenin, leading to the suppression on Wnt/β-catenin signaling and activation of FOXA2 expression. Hence, our findings illustrated a novel feedback loop including FOXA2 and its neighboring gene lncRNA-NEF, which might provide mechanistic insights into the metastatic progress of HCC.

The ultrasonic cardiac output monitor (USCOM) is a noninvasive transcutaneous continuous wave Doppler method for assessing hemodynamics. There are no published reference ranges for normal values in adults (aged 18–60 years) for this device. This study aimed to (1) measure cardiovascular indices using USCOM in healthy adults aged 18–60 years; (2) combine these data with those for healthy children (aged 0–12), adolescents (aged 12–18), and the elderly (aged over 60) from our previously published studies in order to present normal ranges for all ages, and (3) establish normal ranges of USCOM‐derived variables according to both weight and age. This was a population‐based cross‐sectional observational study of healthy Chinese subjects aged 0.5–89 years in Hong Kong. USCOM scans were performed on all subjects, to produce measurements including stroke volume, cardiac output, and systemic vascular resistance. Data from previously published studies (children, adolescents, and the elderly) were included. Normal ranges were defined as lying between the 2.5th and 97.5th percentiles. A total of 2218 subjects were studied (mean age = 16.4, range = 0.5–89; 52% male). From previous studies, 1197 children (aged 0–12, 55% male), 590 adolescents (aged 12–18, 49% male), and 77 elderly (aged 60–89, 55% male) were included. New data were collected from 354 adults aged 18–60 (47% male). Normal ranges are presented according to age and weight. We present comprehensive normal ranges for hemodynamic parameters obtained with USCOM in healthy subjects of all ages from infancy to the elderly.

In order to define the extent to which retinotopic order in the optic pathways may contribute to fiber segregation at the chiasm or to the formation of central maps, the arrangement of fibers in the optic nerve and tract of rat embryos, on embryonic days 16.5 and 18.5, has been studied by placing a small granule of DiI in one of the four quadrants of the retina and tracing the filled fibers through transverse sections of the retinofugal pathway with confocal microscopy. There is a distinct quadrant-specific order in the optic stalk immediately behind the eye, with fibers from the ventral nasal, dorsal nasal, dorsal temporal, and ventral temporal retina arranged sequentially across the rostrocaudal axis of the cross section of the stalk. However, this distinct order is not maintained very far. There is a gradual increase in the degree of overlap between fibers from the different quadrants as the fibers pass towards the chiasm. The dorsal groups of fibers intermingle extensively along almost the entire length of the stalk, but the fibers from ventral sectors remain separate until they reach the prechiasmatic region, where the ventral temporal and the ventral nasal fibers spread throughout the rostrocaudal extent of the stalk and the chiasm. The initial quadrant-specific order is completely lost at the chiasm. However, beyond the optic chiasm, the fibers are reorganized into another distinct order. In the optic tract, there is a segregation of dorsal from ventral fibers, but the nasal and temporal groups remain intermingled. The results of this study indicate that the earliest fibers in the developing optic tract are arranged according to topographical rules that differ from those obtaining behind the eye. Since all topographical order is lost between these two levels, there must be an active sorting mechanism in the region where the chiasm joins the tract. Possibly this mechanism is related to the development of the dorsoventral axis of the topographic maps in the central visual targets.

Bacterial flagellar switching between counterclockwise and clockwise directions is mediated by the coupling of the chemotactic system and the motor switch complex. The conformational changes of FliG are closely associated with this switching mechanism. We present two crystal structures of FliG(MC) from Helicobacter pylori, each showing distinct domain orientations from previously solved structures. A 180° rotation of the charged ridge-containing C-terminal subdomain FliG(Cα1-6) that is prompted by the rotational freedom of Met245 psi and Phe246 phi at the MFXF motif was revealed. Studies on the swarming and swimming behavior of Escherichia coli mutants further identified the importance of the ₂₄₅MFXF₂₄₈ motif and a highly conserved residue, Asn216, in motor switching. Additionally, multiple conformations of FliG(Cα1-6) were demonstrated by intramolecular cysteine crosslinking. The conformational flexibility of FliGc leads us to propose a model that accounts for the symmetrical torque generation process and for the dynamics of the motor.

This large study presents normal values for cardiovascular indices in children using the Ultrasonic Cardiac Output Monitor with good interobserver reliability.

Background: Function of Dhrs3 and importance of the upstream metabolism of retinoic acid are not well understood in early embryonic development. Results: Dhrs3 attenuates retinoic acid synthesis and is required for embryonic patterning. Conclusion: dhrs3 is involved in maintaining balance of retinoic acid signaling and therefore regulates body axis formation. Significance: This is the first functional study of Xenopus dhrs3 in embryonic development.

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Objectives: Access block refers to the delay caused for patients in gaining access to in-patient beds after being admitted. It is almost always associated with emergency department overcrowding. This study aimed to identify evidence-based strategies that can be followed in emergency departments and hospital settings to alleviate the problem of access block and emergency department overcrowding; and to explore the applicability of these solutions in Hong Kong.Data sources: A systematic literature review was performed by searching the following databases: CINAHL, Cochrane Database of Systematic Reviews, EMBASE, MEDLINE (OVID), NHS Evidence, Scopus, and PubMed. Study selection:The search terms used were "emergency department, access block, overcrowding". The inclusion criteria were full-text articles, studies, economic evaluations, reviews, editorials, and commentaries. The exclusion criteria were studies not based in the emergency departments or hospitals, and abstracts.