Transcriptional networks of lung airway epithelial ciliogenesis

Motile cilia of the mammalian airway play an essential role in innate defense. The coordinated transcriptional regulation of cilial axoneme genes remains to be elucidated. Transcription factor FOXJ1 has been shown to be important in ciliogenesis; however, direct transactivation of cilia genes by FOXJ1 has not been reported. Using a combined bioinformatics and experimental approach, here, we show a transcriptional network for cilia gene expression. FOXJ1 can directly transactivate endogenous cilia genes such as ENKURIN, EFHC2, IFT57, RIBC2 and ROPN1L in human bronchial epithelial cells (HBEC). FOXJ1 transactivation is localized to the proximal end of the 5 flanking region of ENKURIN and EFHC2 promoters. However, FOXJ1 failed to transactivate HSPA1A and MNS1, two other cilia genes, indicating there are other transcription factor(s)involved in the ciliogenesis. Motif discovery analysis indicates ETS and RFX binding sites located in promoters of several cilia genes (IFT57, HSPA1A, MNS1, RIBC2 and ROPN1L). QRT-PCR indicates 5 of 27 human ETS transcription factors members (ETV1, ETV5, SPDEF, SPIC and ESE1) and 4 of 7 RFX transcription factors (RFX1, RFX2, RFX5 and RFXANK) are regulated coincidently with the differentiation of human bronchial epithelial cells and the appearance of cilia, suggesting these transcription factors are involved in gene regulations during lung airway epithelial ciliogenesis. ETS family members ESE1 and ETV1 both can transactivate endogenous EFHC2 and ENKURIN while SPIC represses EFHC2. An RFX family member RFX1 transactivates endogenous ENKURIN, HSPA1A, ROPN1L, and RFX5 transactivates EFHC2, HSPA1A and RIBC2. Furthermore, another transcription factor, GATA2, transactivates endogenous ENKURIN and EFHC2, and its transactivation also locates in the proximal end of the 5\u27 flanking region of ENKURIN and EFHC2 promoters. Our work defines a transcriptional network that regulates expression of cilia genes during airway epithelial differentiation and highlights the importance of multiple transcription factors in ciliogenesis

Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO) without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2) cells and human cervical cancer (HeLa) cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose) polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects

A bead sequence-driven deposition pattern evaluation criterion for lowering residual stresses in additive manufacturing

Deposition patterns can significantly influence the distribution and magnitude of residual stress in additively manufactured parts. Time-consuming thermal-mechanical simulations and costly experimental studies are often required to identify the optimal patterns. A simple and generic method to evaluate and optimize the deposition pattern for the purpose of minimizing residual stress is in urgent need. To overcome the shortcomings of the current practice, here we propose a novel pattern evaluation criterion. Starting from the discretization of the deposition pattern by a series of sequence numbers, we introduce two interconnected concepts. The first is called “equivalent bead sequence number” which can be physically interpreted as an index of the localized heat accumulation induced by the deposition process. Based on this point-wise “equivalent bead sequence number”, the second concept called “bead sequence number dispersion index” which can be considered as a representation of the global heat accumulation gradient, is proposed as a criterion for assessing the resulting residual stress. The temperature fields and residual stresses of a square part with six typical deposition patterns predicted by thermo-mechanical finite element simulations are used to develop and verify the proposed criterion. It is found that the “equivalent bead sequence number” of a given pattern is closely correlated to the distribution of the associated temperature and residual stress. More interestingly, both the highest equivalent and highest maximum principal residual stress of a pattern linearly increase with its corresponding value of “bead sequence number dispersion index”. Guided by this relation, two new patterns with lower residual stress are developed and evaluated. Among all the patterns considered, the so-called S pattern shows the lowest value of the “bead sequence number dispersion index” which corresponds to the lowest residual stress. The proposed sequence-driven approach provides a new candidate for real-time evaluation and optimization of the deposition pattern in additive manufacturing.publishedVersio

Effects of different doses of ropivacaine on postoperative analgesia, incidence of complications and stress factors in patients undergoing total knee arthroplasty

Purpose: To study the influence of various doses of ropivacaine (Ropi) on postoperative analgesia, incidence of complications and stress factors in patients undergoing total knee arthroplasty (TKA). Methods: One hundred and fifty (150) patients who received TKA treatment in Ganzhou Hospital of Traditional Chinese Medicine from January 2017 to January 2019 were randomly assigned to low-dose Ropi (0.15 %, group A), medium-dose Ropi (0.20 %, group B) and high-dose Ropi (0.30 %, group C), with 50 patients in each group. Changes in visual analogue scale (VAS) scores, MMSE scores, cognitive dysfunction, serum cortisol (Cor) and adverse reactions were determined before and after surgery. Results: Compared with group A, scores on rest visual analogue scale (RVAS) and passive visual analogue scale (PVAS) were significantly higher in low-dose and high-dose Ropi groups 24 and 48 h postoperatively (p < 0.05). Serum Cor levels in low-dose Ropi-treated patients were significantly lower than those in the other groups at 24 and 48 h after surgery (p < 0.05). The MMSE scores at 48 and 72 h after surgery were significantly higher in low-dose Ropi-treated patients than in the other 2 groups. The number of patients with cognitive impairment after surgery (POCD) was significantly higher in groups B and C than in A (p < 0.05). Conclusion: Low-dose Ropi exerts significant analgesic effect on elderly patients undergoing TKA, and improves their cognitive function without increasing stress response. Therefore, it should be further investigated on a larger scale for its potential as a candidate analgesic for patients after TKA

Discovery of An Active Intermediate-Mass Black Hole Candidate in the Barred Bulgeless Galaxy NGC 3319

We report the discovery of an active intermediate-mass black hole (IMBH) candidate in the center of nearby barred bulgeless galaxy $\rm NGC~3319$. The point X-ray source revealed by archival Chandra and XMM-Newton observations is spatially coincident with the optical and UV galactic nuclei from Hubble Space Telescope observations. The spectral energy distribution derived from the unresolved X-ray and UV-optical flux is comparable with active galactic nuclei (AGNs) rather than ultra-luminous X-ray sources, although its bolometric luminosity is only $3.6\times10^{40}~\rm erg~s^{-1}$. Assuming an Eddington ratio range between 0.001 and 1, the black hole mass (M_\rm{BH}) will be located at $3\times10^2-3\times10^5~M_{\odot}$, placing it in the so-called IMBH regime and could be the one of the lowest reported so far. Estimates from other approaches (e.g., fundamental plane, X-ray variability) also suggest M_\rm{BH}\lesssim10^5~M_{\odot}.Similar to other BHs in bulgeless galaxies, the discovered IMBH resides in a nuclear star cluster with mass of $\sim6\times10^6~M_{\odot}$. The detection of such a low-mass BH offers us an ideal chance to study the formation and early growth of SMBH seeds, which may result from the bar-driven inflow in late-type galaxies with a prominent bar such as $\rm NGC~3319$.Comment: ApJ accepted, 2 tables, 6 figure

An information-flow-based model with dissipation, saturation and direction for active pathway inference

<p>Abstract</p> <p>Background</p> <p>Biological systems process the genetic information and environmental signals through pathways. How to map the pathways systematically and efficiently from high-throughput genomic and proteomic data is a challenging open problem. Previous methods design different heuristics but do not describe explicitly the behaviours of the information flow.</p> <p>Results</p> <p>In this study, we propose new concepts of dissipation, saturation and direction to decipher the information flow behaviours in the pathways and thereby infer the biological pathways from a given source to its target. This model takes into account explicitly the common features of the information transmission and provides a general framework to model the biological pathways. It can incorporate different types of bio-molecular interactions to infer the signal transduction pathways and interpret the expression quantitative trait loci (eQTL) associations. The model is formulated as a linear programming problem and thus is solved efficiently. Experiments on the real data of yeast indicate that the reproduced pathways are highly consistent with the current knowledge.</p> <p>Conclusions</p> <p>Our model explicitly treats the biological pathways as information flows with dissipation, saturation and direction. The effective applications suggest that the three new concepts may be valid to describe the organization rules of biological pathways. The deduced linear programming should be a promising tool to infer the various biological pathways from the high-throughput data.</p