Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their ...sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very longchain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.
This paper examines the Efficient Market Hypothesis (EMH) in crude oil amid the “financialization of commodity markets” and the “fracking revolution”. It applies the generalized spectral derivative ...test (Hong and Lee 2005) on both West Texas Intermediate and Brent spot and futures markets, alongside a stochastic dominance test (Linton et al., 2005) to investigate arbitrage opportunities across markets and benchmarks. The findings indicate that financialization has made each market more efficient but also created more arbitrage opportunities in spot‐futures markets at both benchmarks. The fracking revolution has fragmented oil markets but had little impact on EMH in individual markets or across markets.
It remains controversial whether targeting tumour vasculature can improve radiotherapeutic efficacy. We report that radiation-induced endothelial-to-mesenchymal transition (EndMT) leads to tumour ...vasculature with abnormal SMA
NG2
pericyte recruitment during tumour regrowth after radiotherapy. Trp53 (but not Tgfbr2) deletion in endothelial cells (ECs) inhibited radiation-induced EndMT, reducing tumour regrowth and metastases with a high CD44v6
cancer-stem-cell (CSC) content after radiotherapy. Osteopontin, an EndMT-related angiocrine factor suppressed by EC-Trp53 deletion, stimulated proliferation in dormant CD44v6
cells in severely hypoxic regions after radiation. Radiation-induced EndMT significantly regulated tumour-associated macrophage (TAM) polarization. CXCR4 upregulation in radioresistant tumour ECs was highly associated with SDF-1
TAM recruitment and M2 polarization of TAMs, which was suppressed by Trp53 deletion. These EndMT-related phenomena were also observed in irradiated human lung cancer tissues. Our findings suggest that targeting tumour EndMT might enhance radiotherapy efficacy by inhibiting the re-activation of dormant hypoxic CSCs and promoting anti-tumour immune responses.
The modified International Standard Classification of Occupations (ISCO) has been used empirically to report or investigate working conditions or worker status. We used principal component analysis ...and k-means clustering to analyze the working population based on 67 occupational characteristics among 23,060 workers from the fourth Korean Working Conditions Survey in 2014. The three-cluster approach classified workers into major groups 1–4 (managers, professionals, technicians, and clerical support workers), 5–6 (service, sales, agricultural, forestry, and fishery workers), and 7–9 (crafts, trades, machine operators, assemblers, and elementary occupations) based on the ISCO-08. The results of the current study suggest a well-defined clustered occupational classification that can be used to report or investigate workers.
Medical big data: promise and challenges Lee, Choong Ho; Yoon, Hyung-Jin
Kidney research and clinical practice,
03/2017, Letnik:
36, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The concept of big data, commonly characterized by volume, variety, velocity, and veracity, goes far beyond the data type and includes the aspects of data analysis, such as hypothesis-generating, ...rather than hypothesis-testing. Big data focuses on temporal stability of the association, rather than on causal relationship and underlying probability distribution assumptions are frequently not required. Medical big data as material to be analyzed has various features that are not only distinct from big data of other disciplines, but also distinct from traditional clinical epidemiology. Big data technology has many areas of application in healthcare, such as predictive modeling and clinical decision support, disease or safety surveillance, public health, and research. Big data analytics frequently exploits analytic methods developed in data mining, including classification, clustering, and regression. Medical big data analyses are complicated by many technical issues, such as missing values, curse of dimensionality, and bias control, and share the inherent limitations of observation study, namely the inability to test causality resulting from residual confounding and reverse causation. Recently, propensity score analysis and instrumental variable analysis have been introduced to overcome these limitations, and they have accomplished a great deal. Many challenges, such as the absence of evidence of practical benefits of big data, methodological issues including legal and ethical issues, and clinical integration and utility issues, must be overcome to realize the promise of medical big data as the fuel of a continuous learning healthcare system that will improve patient outcome and reduce waste in areas including nephrology.
For the demonstration of remote‐controllable actuators, a dendronized polymer (denpol) is newly designed and successfully synthesized by ring‐opening metathesis polymerization of azobenzene‐based ...macromonomers. The incorporation of azobenzene mesogens into the denpols helps to construct finely tuned hierarchical superstructures with anisotropic physical properties and reversible photoisomerization. The polynorbornene backbones and azobenzene side chains in the uniaxially oriented films are aligned perpendicularly and parallel to the layer normal, respectively. Based on photoreversible actuation experiments combined with diffraction results, direct relationships between the chemical structures, hierarchical superstructures, and their corresponding photomechanical behaviors are proposed. Smart denpols possess great potential for practical applications in photoresponsive switches.
To demonstrate remote‐controllable actuators, a polynorbornene with dendronized azobenzene chromophores is synthesized by ring‐opening metathesis polymerization.
Objective
Helicobacter pylori
(HP) is known to play an important role in the development of gastric cancer (GC). The aim of this study was to analyze the effect of HP eradication on the survival rate ...and cancer recurrence in patients who underwent subtotal gastrectomy for GC.
Design
Totally 1,031 patients diagnosed with gastric adenocarcinoma who received surgical treatment at the Seoul National University Bundang Hospital from 2003 to 2017 and positive for HP infection were analyzed. The overall and GC-related survival according to HP eradication were compared; risk factors for GC-specific death and cancer recurrence were analyzed, and propensity score matching (PSM) was performed.
Results
Statistically significant benefits of overall and GC-specific survival were observed in the eradicated group compared to the non-eradicated group (
P
< 0.001), and these benefits were maintained after PSM (
P
< 0.001) in both of early and advance stage. In Cox proportional hazards multivariate analyses, cancer stage (stage II, adjusted hazard ratio aHR = 9.33,
P
< 0.001; stage III or IV, aHR = 26.17,
P
< 0.001), and HP positivity (aHR = 3.41,
P
= 0.001) were independent risk factors for GC-specific death; cancer stage (cancer stage II, aHR = 7.08,
P
< 0.001; cancer stage III or IV, aHR = 19.64,
P
< 0.001) and HP positivity (aHR = 2.70;
P
= 0.005) were independent risk factors for cancer recurrence.
Conclusion
Our results suggest that HP needed to be conducted more intensively in patients who are surgically treated for GC, regardless of cancer stage.
The color distributions of globular clusters (GCs) in individual early-type galaxies show great diversity in their morphology. Based on the conventional "linear" relationship between the colors and ...metallicities of GCs, the GC metallicity distributions inferred from colors and in turn their formation histories, should be as diverse as they appear. In contrast, here we show that an alternative scenario rooted in the "nonlinear" nature of the metallicity-to-color transformation points to a simpler and more coherent picture. Our simulations of the color distributions for ∼80 GC systems in early-type galaxies from the ACS Virgo and Fornax Cluster Surveys suggest that the majority (∼70%) of early-type galaxies have old (∼13 Gyr) and coeval GCs. Their variety in the color distribution morphology stems mainly from one parameter, the mean metallicity of a GC system. Furthermore, the color distributions of the remaining (∼30%) GC systems are also explained by the nonlinearity scenario, assuming additional young or intermediate-age GCs with a number fraction of ∼20% of underlying old GCs. Our results reinforce the nonlinearity explanation for the GC color bimodality and provide a new perspective on early-type galaxy formation in the cluster environment, such as the Virgo and Fornax galaxy clusters.
Endothelial-to-mesenchymal transition (EndMT) involves the phenotypic conversion of endothelial-to-mesenchymal cells, and was first discovered in association with embryonic heart development. EndMT ...can regulate various processes, such as tissue fibrosis and cancer. Recent findings have shown that EndMT is related to resistance to cancer therapy, such as chemotherapy, antiangiogenic therapy, and radiation therapy. Based on the known effects of EndMT on the cardiac toxicity of anticancer therapy and tissue damage of radiation therapy, we propose that EndMT can be targeted as a strategy for overcoming tumor resistance while reducing complications, such as tissue damage. In this review, we discuss EndMT and its roles in damaging cardiac and lung tissues, as well as EndMT-related effects on tumor vasculature and resistance in anticancer therapy. Modulating EndMT in radioresistant tumors and radiation-induced tissue fibrosis can especially increase the efficacy of radiation therapy. In addition, we review the role of hypoxia and reactive oxygen species as the main stimulating factors of tissue damage due to vascular damage and EndMT. We consider drugs that may be clinically useful for regulating EndMT in various diseases. Finally, we argue the importance of EndMT as a therapeutic target in anticancer therapy for reducing tissue damage.
In eukaryotic cells, mitochondria are closely tethered to the endoplasmic reticulum (ER) at sites called mitochondria‐associated ER membranes (MAMs). Ca2+ ion and phospholipid transfer occurs at MAMs ...to support diverse cellular functions. Unlike those in yeast, the protein complexes involved in phospholipid transfer at MAMs in humans have not been identified. Here, we determine the crystal structure of the tetratricopeptide repeat domain of PTPIP51 (PTPIP51_TPR), a mitochondrial protein that interacts with the ER‐anchored VAPB protein at MAMs. The structure of PTPIP51_TPR shows an archetypal TPR fold, and an electron density map corresponding to an unidentified lipid‐like molecule probably derived from the protein expression host is found in the structure. We reveal functions of PTPIP51 in phospholipid binding/transfer, particularly of phosphatidic acid, in vitro. Depletion of PTPIP51 in cells reduces the mitochondrial cardiolipin level. Additionally, we confirm that the PTPIP51–VAPB interaction is mediated by the FFAT‐like motif of PTPIP51 and the MSP domain of VAPB. Our findings suggest that PTPIP51 is a phospholipid transfer protein with a MAM‐tethering function.
SYNOPSIS
The crystal structure and biochemical analyses of PTPIP51, a mitochondrial protein localized at the mitochondria‐associated ER membrane (MAM), revealed its phospholipid binding and transfer activity.
The crystal structure of the TPR domain of PTPIP51 at 1.45 Å resolution revealed the presence of a lipid‐like serpentine electron density.
PTPIP51 has phospholipid (especially phosphatidic acid) binding and transfer functions in vitro.
Mitochondrial cardiolipin levels are affected by PTPIP51.
The crystal structure and biochemical analyses of PTPIP51, a mitochondrial protein localized at the mitochondria‐associated ER membrane (MAM), revealed its phospholipid binding and transfer activity.
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