A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1.

The E3 ligase HERC4 is overexpressed in human breast cancer and its expression levels correlated with the prognosis of breast cancer patients. However, the roles of HERC4 in mammary tumorigenesis remain unclear. Here we demonstrate that the knockdown of HERC4 in human breast cancer cells dramatically suppressed their proliferation, survival, migration, and tumor growth in vivo, while the overexpression of HERC4 promoted their aggressive tumorigenic activities. HERC4 is a new E3 ligase for the tumor suppressor LATS1 and destabilizes LATS1 by promoting the ubiquitination of LATS1. miRNA-136-5p and miRNA-1285-5p, expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, are directly involved in suppressing the expression of HERC4. In summary, we discover a miRNA-HERC4-LATS1 pathway that plays important roles in the pathogenesis of breast cancer and represents new therapeutic targets for human breast cancer

Effects of pool size and spacing on burning rate and flame height of two square heptane pool fires

The interaction of multiple pool fires might lead to higher burning rate and flame height than single pool fire, raising the possibility of fire ignition and flame spread and increasing the risks to people, buildings and environment. To quantify the burning rate and flame height of multiple pool fires from the view of physical mechanism, this paper presents an experimental study on two identical square pool fires. Heptane was used as fuel. The pool size and spacing were varied. Results showed that both the burning rate and flame height change non-monotonically with spacing. From the view of air entrainment, a correlation for the flame height of two pool fires is developed involving pool size, spacing and the flame height of zero spacing. The comparison with experimental results shows that the developed correlation is suitable for two heptane or propane fires. A theoretical study based on energy balance at one of the pool surfaces is performed to evaluate the burning rate of two fires, which is finally expressed as a function of pool size, spacing, burning rate and the flame height of single fire. The proposed model is validated using the experimental and literature data, which presents a reasonable reliability

Functional Role of Cyclin-Dependent Kinase 5 in the Regulation of Melanogenesis and Epidermal Structure

The mammalian integumentary system plays important roles in body homeostasis, and dysfunction of melanogenesis or epidermal development may lead to a variety of skin diseases, including melanoma. Skin pigmentation in humans and coat color in fleece-producing animals are regulated by many genes. Among them, microphthalmia-associated transcription factor (MITF) and paired-box 3 (PAX3) are at the top of the cascade and regulate activities of many important melanogenic enzymes. Here, we report for the first time that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of MITF and PAX3. Cdk5 knockdown in mice causes a lightened coat color, a polarized distribution of melanin and hyperproliferation of basal keratinocytes. Reduced expression of Keratin 10 (K10) resulting from Cdk5knockdown may be responsible for an abnormal epidermal structure. In contrast, overexpression of Cdk5 in sheep (Ovis aries) only produces brown patches on a white background, with no other observable abnormalities. Collectively, our findings show that Cdk5 has an important functional role in the regulation of melanin production and transportation and in normal development of the integumentary system

Chinese medicine PaBing-II protects human iPSC-derived dopaminergic neurons from oxidative stress

BackgroundPaBing-II Formula (PB-II) is a traditional Chinese medicine for treating Parkinson’s disease (PD). However, owing to the complexity of PB-II and the difficulty in obtaining human dopaminergic neurons (DAn), the mechanism of action of PB-II in PD treatment remains unclear. The aim of this study was to investigate the mechanisms underlying the therapeutic benefits of PB-II in patients with PD.MethodshiPSCs derived DAn were treated with H2O2 to construct the DAn oxidative damage model. SwissTargetPrediction was employed to predict the potential targets of the main compounds in serum after PB-II treatment. Metascape was used to analyze the pathways. Sprague-Dawley rats were used to construct the 6-hydroxydopamine (6-OHDA)-induced PD model, and the duration of administration was four weeks. RNA sequencing was used for Transcriptome analysis to find the signal pathways related to neuronal damage. The associated inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). We identified PB-II as an Nrf2 activator using antioxidant-responsive element luciferase assay in MDA-MB-231 cells.ResultsIn vitro experiments showed that the treatment of PB-II-treated serum increased the percentage of TH+ cells, decreased inflammation and the apoptosis, reduced cellular reactive oxygen species, and upregulated the expression of Nrf2 and its downstream genes. Pathway analysis of the RNA-seq data of samples before and after the treatment with PB-II-treated serum identified neuron-associated pathways. In vivo experiments demonstrated that PB-II treatment of PD rat model could activate the Nrf2 signaling pathway, protect the midbrain DAn, and improve the symptoms in PD rats.ConclusionPB-II significantly protects DAn from inflammation and oxidative stress via Nrf2 pathway activation. These findings elucidate the roles of PB-II in PD treatment and demonstrate the application of hiPSC-derived DAn in research of Chinese medicine

Supplementary figure: Types of circRNA

Supplementary figure: Types of circRNA in Identification of CircRNA-miRNA-mRNA Network in Myometrial Contractile Activity during Labor.</p

Experimental investigation on influence of smoke venting velocity and vent height on mechanical smoke exhaust efficiency

A set of burning experiments were conducted to investigate the influence of smoke vent height and exhausting velocity on mechanical smoke exhausting efficiency. Results have shown that the smoke exhausting process becomes more efficient due to the increased smoke vent height and the decreased exhausting velocity, which eliminate the plug-holing issue with fewer disturbances on the smoke layer interface. For each certain exhausting velocity, there is a critical value of distance between the vent and the bottom of the smoke layer. When the distance is less than the critical value, the smoke exhausting is inefficient, and the efficiency decreases sharply as the distance decreases. Contrarily, when the distance is greater than the critical value, a good efficiency can be acquired and the exhausted smoke increased relatively slowly as the distance increases. A critical Froude number, proposed by Hinkley to predict the onset of plug-holing effect in gravity venting systems, was validated in the experiments. However, the experimental results indicate that in the tests without the plug-holing, the fresh air entrained due to smoke exhausting is up to 48% of the mechanical exhausting rate

Incompatibility as a Resource for Programmable Quantum Instruments

Quantum instruments represent the most general type of quantum measurement, as they incorporate processes with both classical and quantum outputs. In many scenarios, it may be desirable to have some “on-demand” device that is capable of implementing one of many possible instruments whenever the experimenter desires. We refer to such objects as programmable instrument devices (PIDs), and this paper studies PIDs from a resource-theoretic perspective. A physically important class of PIDs are those that do not require quantum memories to implement, and these are naturally “free” in this resource theory. Additionally, these free objects correspond precisely to the class of unsteerable channel assemblages in the study of channel steering. The traditional notion of measurement incompatibility emerges as a resource in this theory since any PID controlling an incompatible family of instruments requires a quantum memory to build. We identify an incompatibility preorder between PIDs based on whether one can be transformed into another using processes that do not require additional quantum memories. Necessary and sufficient conditions are derived for when such transformations are possible based on how well certain guessing games can be played using a given PID. Ultimately our results provide an operational characterization of incompatibility, and they offer semi-device-independent tests for incompatibility in the most general types of quantum instruments

Incompatibility as a resource for programmable quantum instruments

Quantum instruments represent the most general type of quantum measurement, as they incorporate processes with both classical and quantum outputs. In many scenarios, it may be desirable to have some "on-demand" device that is capable of implementing one of many possible instruments whenever the experimenter desires. We refer to such objects as programmable instrument devices (PIDs), and this paper studies PIDs from a resource-theoretic perspective. A physically important class of PIDs are those that do not require quantum memory to implement, and these are naturally "free" in this resource theory. The traditional notion of measurement incompatibility emerges as a resource in this theory since any PID controlling an incompatible family of instruments requires quantum memory to build. We identify an incompatibility partial ordering of PIDs based on whether one can be transformed into another using processes that do not require additional quantum memory. Necessary and sufficient conditions are derived for when such transformations are possible based on how well certain guessing games can be played using a given PID. Ultimately our results provide an operational characterization of incompatibility, and they offer device-independent tests for incompatibility in the most general types of quantum instruments. Since channel steerability is equivalent to PID incompatibility, this work can also be seen as a resource theory of channel steering.Comment: 18 pages, 8 figure