Experimental Study of Heat Transfer for Supercritical Carbon Dioxide with Upward Flow in Vertical Tube

In this study heat transfer of supercritical carbon dioxide in vertical tube with 10 mm of inner diameter and 1800 mm of length was investigated experimentally. The initial temperature of tube wall was set to 150 and 200°C. The system pressures of supercritical carbon dioxide are 1100, 1500 and 2000 psi, respectively. The experimental results show that the heat transfer coefficient and heat transfer rate increase with Reynolds number. The maximum heat transfer coefficient and heat transfer rate was occurred in 1500 psi of system pressure. The heat transfer coefficient for 150°C is higher than that of 200°C resulted from effect of specific heat

NPRL-Z-1, as a New Topoisomerase II Poison, Induces Cell Apoptosis and ROS Generation in Human Renal Carcinoma Cells

NPRL-Z-1 is a 4β-[(4″-benzamido)-amino]-4′-O-demethyl-epipodophyllotoxin derivative. Previous reports have shown that NPRL-Z-1 possesses anticancer activity. Here NPRL-Z-1 displayed cytotoxic effects against four human cancer cell lines (HCT 116, A549, ACHN, and A498) and exhibited potent activity in A498 human renal carcinoma cells, with an IC50 value of 2.38 µM via the MTT assay. We also found that NPRL-Z-1 induced cell cycle arrest in G1-phase and detected DNA double-strand breaks in A498 cells. NPRL-Z-1 induced ataxia telangiectasia-mutated (ATM) protein kinase phosphorylation at serine 1981, leading to the activation of DNA damage signaling pathways, including Chk2, histone H2AX, and p53/p21. By ICE assay, the data suggested that NPRL-Z-1 acted on and stabilized the topoisomerase II (TOP2)–DNA complex, leading to TOP2cc formation. NPRL-Z-1-induced DNA damage signaling and apoptotic death was also reversed by TOP2α or TOP2β knockdown. In addition, NPRL-Z-1 inhibited the Akt signaling pathway and induced reactive oxygen species (ROS) generation. These results demonstrated that NPRL-Z-1 appeared to be a novel TOP2 poison and ROS generator. Thus, NPRL-Z-1 may present a significant potential anticancer candidate against renal carcinoma

Anti-apoptotic and anti-fibrotic efficacy of exercise training in hypertensive hearts: A systematic review

BackgroundThis review aims to summarize the antiapoptotic, pro-survival, and antifibrotic effects of exercise training in hypertensive hearts.MethodsKeyword searches were conducted in PubMed, Web of Science, and Scopus in May 2021. Research published in English on the effects of exercise training on the apoptosis, survival, and fibrosis pathways in hypertension was included. The CAMARADES checklist was used to determine the quality of the studies. Two reviewers independently implemented predesigned protocols for the search and selection of studies, the assessment of study quality, and the evaluation of the strength of evidence.ResultsEleven studies were included after selection. The duration of the exercise training ranged from 5 to 27 weeks. Nine studies showed that exercise training improved cardiac survival rates by increasing IGF-1, IGF-1 receptor, p-PI3K, Bcl-2, HSP 72, and p-Akt. Furthermore, 10 studies showed that exercise training reduced apoptotic pathways by downregulating Bid, t-Bid, Bad, Bak, Bax, TNF, and FADD. Finally, two studies reported the modification and subsequent improvement of physiological characteristics of fibrosis and decreased MAPK p38 and PTEN levels by exercise training in the left ventricle of the heart.ConclusionsThe findings of the review showed that exercise training could improve cardiac survival rates and attenuate cardiac apoptotic and fibrotic pathways in hypertension, suggesting that exercise training could act as a therapeutic approach to prevent hypertension-induced cardiac apoptosis and fibrosis.Systematic Review Registrationhttps://www.crd.york.ac.uk, identifier: CRD42021254118

Gene Transfer of Pro-opiomelanocortin Prohormone Suppressed the Growth and Metastasis of Melanoma: Involvement of ␣-Melanocyte-Stimulating Hormone-Mediated Inhibition of the Nuclear Factor B/Cyclooxygenase-2 Pathway

ABSTRACT Pro-opiomelanocortin (POMC) is a prohormone of various neuropeptides, including corticotropin, ␣-melanocyte-stimulating hormone (␣-MSH), and ␤-endorphin (␤-EP) . POMC neuropeptides are potent inflammation inhibitors and immunosuppressants and may exert opposite influences during tumorigenesis. However, the role of POMC expression in carcinogenesis remains elusive. We evaluated the antineoplastic potential of POMC gene delivery in a syngenic B16-F10 melanoma model. Adenovirus-mediated POMC gene delivery in B16-F10 cells increased the release of POMC neuropeptides in cultured media, which differentially regulated the secretion of pro-and anti-inflammatory cytokines in lymphocytes. POMC gene transfer significantly reduced the anchorage-independent growth of melanoma cells. Moreover, pre-or post-treatment with POMC gene delivery effectively retarded the melanoma growth in mice. Intravenous injection of POMC-transduced B16-F10 cells resulted in reduced foci formation in lung by 60 to 70% of control. The reduced metastasis of POMC-transduced B16-F10 cells could be attributed to their attenuated migratory and adhesive capabilities. POMC gene delivery reduced the cyclooxygenase-2 (COX-2) expression and prostaglandin (PG) E 2 synthesis in melanoma cells and tumor tissues. In addition, application of NS-398, a selective COX-2 inhibitor, mimicked the antineoplastic functions of POMC gene transfer in melanoma. The POMC-mediated COX-2 down-regulation was correlated with its inhibition of nuclear factor B (NFB) activities. Exogenous supply of ␣-MSH inhibited NFB activities, whereas application of the ␣-MSH antagonist growth hormone-releasing peptide-6 (GHRP-6) abolished the POMC-induced inhibition of NFB activities and melanoma growth in mice. In summary, POMC gene delivery suppresses melanoma via ␣-MSH-induced inhibition of NFB/COX-2 pathway, thereby constituting a novel therapy for melanoma. POMC is a multifunctional polycistronic gene located on human chromosome 2p23.3. POMC is a 31 kDa prohormone that is processed into various neuropeptides, including corticotropin, melanotropins (␣-, ␤-, and ␥-MSH), lipotropins, and ␤-endorphin (␤-EP

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Correlation of Immunological and Molecular Profiles with Response to Crizotinib in Alveolar Soft Part Sarcoma: An Exploratory Study Related to the EORTC 90101 “CREATE” Trial

Alveolar soft part sarcoma (ASPS) is a rare subtype of soft tissue sarcoma characterized by an unbalanced translocation, resulting in ASPSCR1-TFE3 fusion that transcriptionally upregulates MET expression. The European Organization for Research and Treatment of Cancer (EORTC) 90101 “CREATE” phase II trial evaluated the MET inhibitor crizotinib in ASPS patients, achieving only limited antitumor activity. We performed a comprehensive molecular analysis of ASPS tissue samples collected in this trial to identify potential biomarkers correlating with treatment outcome. A tissue microarray containing 47 ASPS cases was used for the characterization of the tumor microenvironment using multiplex immunofluorescence. DNA isolated from 34 available tumor samples was analyzed to detect recurrent gene copy number alterations (CNAs) and mutations by low-coverage whole-genome sequencing and whole-exome sequencing. Pathway enrichment analysis was used to identify diseased-associated pathways in ASPS sarcomagenesis. Kaplan–Meier estimates, Cox regression, and the Fisher’s exact test were used to correlate histopathological and molecular findings with clinical data related to crizotinib treatment, aiming to identify potential factors associated with patient outcome. Tumor microenvironment characterization showed the presence of PD-L1 and CTLA-4 in 10 and 2 tumors, respectively, and the absence of PD-1 in all specimens. Apart from CD68, other immunological markers were rarely expressed, suggesting a low level of tumor-infiltrating lymphocytes in ASPS. By CNA analysis, we detected a number of broad and focal alterations. The most common alteration was the loss of chromosomal region 1p36.32 in 44% of cases. The loss of chromosomal regions 1p36.32, 1p33, 1p22.2, and 8p was associated with shorter progression-free survival. Using whole-exome sequencing, 13 cancer-associated genes were found to be mutated in at least three cases. Pathway enrichment analysis identified genetic alterations in NOTCH signaling, chromatin organization, and SUMOylation pathways. NOTCH4 intracellular domain dysregulation was associated with poor outcome, while inactivation of the beta-catenin/TCF complex correlated with improved outcome in patients receiving crizotinib. ASPS is characterized by molecular heterogeneity. We identify genetic aberrations potentially predictive of treatment outcome during crizotinib therapy and provide additional insights into the biology of ASPS, paving the way to improve treatment approaches for this extremely rare malignancy

Theoretical Study on the Exciton Binding Energy from Density Functional Theory Methods

束縛能的定義是把束縛的電子電洞對變成自由電荷所需要的能量，束縛能對於有機光電材料和裝置來說，是一個影響表現好壞的因素，然而，對於現在運用密度泛函理論(Density Functional Theory)的量子計算是不是可以信賴是一個很重要的議題，在本研究中，我們分成兩部份去討論。 我們用9種常用的密度泛函理論方法和參考方法(CCSD)去計算121個小分子的束縛能，把9種密度泛函理論方法和參考方法比較找出最精準的方法，這些方法包括LSDA、PBE、M06L、B3LYP、ωB97、ωB97X、ωB97X-D、M06-HF、M06-2X，他們的平均絕對誤差依序為ωB97X 是0.38 eV、ωB97是0.39 eV、ωB97X-D是0.40 eV、M06-2X是0.48 eV、B3LYP是0.53 eV、M06L是0.57 eV、PBE和LSDA是0.66 eV、M06-HF是0.80 eV，在本研究中還有計算其他的光電性質，例如：frontier orbitals和HOMO-LUMO gap，比較所有光電性質的計算結果，ωB97是最精準的，所以我們預期ωB97是有潛力去預測更複雜分子的束縛能。 根據前面的結果，顯示ωB97方法可能可以預測有機半導體材料的束縛能，另一方面，Pabitra K. Nayak暗示B3LYP方法也可以預測有機半導體材料的束縛能，所以我們計算了19個有機半導體材料的adiabatic ionization potential, adiabatic electron affinity and vertical optical gap，並把ωB97和B3LYP計算結果和實驗值做比較，這證明了ωB97和B3LYP是有能力預測有機半導體材料的束縛能，所以我們預期ωB97和B3LYP有能力預測出新設計的光電裝置材料的束縛能。The exciton binding energy, the energy required to separate an excited electron-hole pair to free charge carriers, is one of the key performance factors of organic photoactive materials and devices. However, it is questionable whether modern quantum mechanical calculations based on the density functional theory (DFT) can provide reliable predictions for this physical quantity. In this study, we use two parts to discuss it. we compared the results from 9 common DFT methods, including LDA, PBE, M06L, B3LTP, ωB97, ωB97X, ωB97X-D, M06-HF, M06-2X, to the benchmark method, CCSD, for 121 small to medium sized molecules. The mean absolute errors in the exciton binding energy are found to be 0.38 eV from ωB97X, 0.39 from ωB97X, 0.40 eV from ωB97X-D, 0.48 eV from M06-2X, 0.53 eV from B3LYP, 0.57 eV from M06L, 0.66 eV from PBE and LSDA, and 0.80 eV from M06-HF. The ωB97-methods are also found to be accurate for many other optoelectronic properties such as the energy of frontier orbitals and the HOMO-LUMO gap. Our results indicate that the ωB97-method has the potential of predicting the exciton binding energy for more complex systems. From previous work, our results show ωB97 method is possible to estimate the exciton binding energy of molecular organic semiconductors. On the other hand, Pabitra K. Nayak implies B3LYP is possible to estimate the exciton binding energy of molecular organic semiconductors. We compared adiabatic ionization potential, adiabatic electron affinity and vertical optical gap from ωB97 and B3LYP methods to experimental values for 19 molecular organic semiconductors. It verifies ωB97 and B3LYP methods have good prediction for molecular organic semiconductors. Our results indicate that the ωB97 and B3LYP methods have the potential to predict the exciton binding energy for designing new organic optoelectronic materials