TiO2 nanoparticles (NPs) are extensively used in various applications, highlighting the importance of ongoing research into their effects. This work belongs among rare whole-body inhalation studies investigating the effects of TiO2 NPs on mice. Unlike previous studies, the concentration of TiO2 NPs in the inhalation chamber (130.8 μg/m3) was significantly lower. This 11-week study on mice confirmed in vivo the presence of TiO2 NPs in lung macrophages and type II pneumocytes including their intracellular localization by using the electron microscopy and the state-of-the-art methods detecting NPs' chemical identity/crystal structure, such as the energy-dispersed X-ray spectroscopy (EDX), cathodoluminescence (CL), and detailed diffraction pattern analysis using powder nanobeam diffraction (PNBD). For the first time in inhalation study in vivo, the alterations in erythrocyte morphology with evidence of echinocytes and stomatocytes, accompanied by iron accumulation in spleen, liver, and kidney, are reported following NP's exposure. Together with the histopathological evidence of hyperaemia in the spleen and kidney, and haemosiderin presence in the spleen, the finding of NPs containing iron might suggest the increased decomposition of damaged erythrocytes. The detection of TiO2 NPs on erythrocytes through CL analysis confirmed their potential systemic availability. On the contrary, TiO2 NPs were not confirmed in other organs (spleen, liver, and kidney); Ti was detected only in the kidney near the detection limit.

• MeSH
• Administration, Inhalation MeSH
• Erythrocytes * drug effects   pathology   MeSH
• Inhalation Exposure * adverse effects   MeSH
• Metal Nanoparticles * toxicity   MeSH
• Mice MeSH
• Nanoparticles * toxicity   MeSH
• Lung * drug effects   metabolism   pathology   MeSH
• Toxicity Tests, Subchronic MeSH
• Titanium * toxicity   pharmacokinetics   administration & dosage   MeSH
• Tissue Distribution MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND AND OBJECTIVE: Capturing the population variability of bone properties is of paramount importance to biomedical engineering. The aim of the present paper is to describe variability and correlations in bone mineral density with a spatial random field inferred from routine computed tomography data. METHODS: Random fields were simulated by transforming pairwise uncorrelated Gaussian random variables into correlated variables through the spectral decomposition of an age-detrended correlation matrix. The validity of the random field model was demonstrated in the spatiotemporal analysis of bone mineral density. The similarity between the computed tomography samples and those generated via random fields was analyzed with the energy distance metric. RESULTS: The random field of bone mineral density was found to be approximately Gaussian/slightly left-skewed/strongly right-skewed at various locations. However, average bone density could be simulated well with the proposed Gaussian random field for which the energy distance, i.e., a measure that quantifies discrepancies between two distribution functions, is convergent with respect to the number of correlation eigenpairs. CONCLUSIONS: The proposed random field model allows the enhancement of computational biomechanical models with variability in bone mineral density, which could increase the usability of the model and provides a step forward in in-silico medicine.

• MeSH
• Bone and Bones * MeSH
• Bone Density * MeSH
• Tomography, X-Ray Computed MeSH
• Publication type
• Journal Article MeSH

Decarbonization of the power sector is one of the most important efforts to meet the climate mitigation targets under the Paris Agreement. China's power sector is of global importance, accounting for ∼25% of global electricity production in 2015. The carbon intensity of China's electricity is still much higher than the global average, but the country has made important strides toward a low-carbon transition based on two main pillars: improvement of energy efficiency and decreasing the share of fossil fuels. By applying a decoupling indicator, our study shows that 21 provinces achieved a "relative decoupling" of carbon emissions and electricity production and the remaining nine provinces achieved "absolute decoupling" between 2005 and 2015. We updated China's emission factors based on the most recent data by also considering the quality of imported coal and compared our results with the widely used Intergovernmental Panel on Climate Change coefficients to show the sensitivity of results and the potential error. Our decomposition analysis shows that improvement of energy efficiency was the dominant driver for decarbonization of 16 provincial power sectors, while the access to low-carbon electricity and substitution of natural gas for coal and oil further accelerated their decarbonization.

• MeSH
• Electricity MeSH
• Carbon Dioxide analysis   MeSH
• Coal MeSH
• Carbon analysis   MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• China MeSH

In this work, the binding mechanism of new Polyketide Synthase 13 (Pks13) inhibitors has been studied through molecular dynamics simulation and free energy calculations. The drug Tam1 and its analogs, belonging to the benzofuran class, were submitted to 100 ns simulations, and according to the results obtained for root mean square deviation, all the simulations converged from approximately 30 ns. For the analysis of backbone flotation, the root mean square fluctuations were plotted for the Cα atoms; analysis revealed that the greatest fluctuation occurred in the residues that are part of the protein lid domain. The binding free energy value (ΔGbind) obtained for the Tam16 lead molecule was of -51.43 kcal/mol. When comparing this result with the ΔGbind values for the remaining analogs, the drug Tam16 was found to be the highest ranked: this result is in agreement with the experimental results obtained by Aggarwal and collaborators, where it was verified that the IC50 for Tam16 is the smallest necessary to inhibit the Pks13 (IC50 = 0.19 μM). The energy decomposition analysis suggested that the residues which most interact with inhibitors are: Ser1636, Tyr1637, Asn1640, Ala1667, Phe1670, and Tyr1674, from which the greatest energy contribution to Phe1670 was particularly notable. For the lead molecule Tam16, a hydrogen bond with the hydroxyl of the phenol not observed in the other analogs induced a more stable molecular structure. Aggarwal and colleagues reported this hydrogen bonding as being responsible for the stability of the molecule, optimizing its physic-chemical, toxicological, and pharmacokinetic properties.

• MeSH
• Amino Acids MeSH
• Antitubercular Agents chemistry   pharmacology   MeSH
• Bacterial Proteins antagonists & inhibitors   chemistry   MeSH
• Benzofurans chemistry   pharmacology   MeSH
• Protein Conformation MeSH
• Molecular Structure MeSH
• Drug Discovery MeSH
• Polyketide Synthases antagonists & inhibitors   chemistry   MeSH
• Molecular Dynamics Simulation * MeSH
• Molecular Docking Simulation * MeSH
• Protein Binding MeSH
• Binding Sites MeSH
• Hydrogen Bonding MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH

BACKGROUND/AIM: The aim of this study was to evaluate the possibility to discriminate the blood clot from tumorous tissue in the assessment of transitional cell carcinoma (TCC), when CT data are used only from single-phase dual-energy CT (DECT). MATERIALS AND METHODS: A total of 18 patients were included into the retrospective analysis of the prospectively collected data (the average age was 67.3 years, range=62-79 years, 12 males, 6 females). DECT was performed in all patients after intravenous administration of the iodinated contrast material. DECT analysis using three-material decomposition algorithm was used to discriminate blood and enhancing tumorous tissue. In all patients, TCC was detected and subsequently kidney surgery or endoscopy was performed within the next two weeks. The findings were compared with DECT results. RESULTS: In our cohort of patients we found 9 TCC of the renal pelvis or ureter and 7 TCC of the urinary bladder. The accuracy of the TCC detection was 94% (17/18). The presence of coagulated blood within the urinary collecting system together with a tumor was detected in 7 CT examinations. The blood coagulum without a confirmed malignant tumor was found in one case with false positive DECT finding. In other 6 cases bleeding was confirmed during surgery or endoscopy (accuracy 87%). CONCLUSION: The dual-energy data analysis enables discrimination of a blood clot from tumorous tissue. It helps in detection of UCC in cases when the excretion potential of the kidneys is decreased due to fulfillment of the collecting system with blood clots.

• MeSH
• Algorithms MeSH
• Iodine analysis   MeSH
• Carcinoma, Transitional Cell diagnosis   diagnostic imaging   pathology   MeSH
• Contrast Media MeSH
• Kidney pathology   surgery   MeSH
• Middle Aged MeSH
• Humans MeSH
• Urinary Bladder pathology   surgery   MeSH
• Biomarkers, Tumor analysis   MeSH
• Tomography, X-Ray Computed methods   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Thrombosis diagnosis   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The exposure of human cells to oxidative stress leads to the oxidation of biomolecules such as lipids, proteins and nuclei acids. In this study, the oxidation of lipids, proteins and DNA was studied after the addition of hydrogen peroxide and Fenton reagent to cell suspension containing human leukemic monocyte lymphoma cell line U937. EPR spin-trapping data showed that the addition of hydrogen peroxide to the cell suspension formed hydroxyl radical via Fenton reaction mediated by endogenous metals. The malondialdehyde HPLC analysis showed no lipid peroxidation after the addition of hydrogen peroxide, whereas the Fenton reagent caused significant lipid peroxidation. The formation of protein carbonyls monitored by dot blot immunoassay and the DNA fragmentation measured by comet assay occurred after the addition of both hydrogen peroxide and Fenton reagent. Oxidative damage of biomolecules leads to the formation of singlet oxygen as conformed by EPR spin-trapping spectroscopy and the green fluorescence of singlet oxygen sensor green detected by confocal laser scanning microscopy. It is proposed here that singlet oxygen is formed by the decomposition of high-energy intermediates such as dioxetane or tetroxide formed by oxidative damage of biomolecules.

• MeSH
• Electron Spin Resonance Spectroscopy MeSH
• Hydroxyl Radical toxicity   MeSH
• Protein Carbonylation drug effects   MeSH
• Comet Assay MeSH
• Microscopy, Confocal MeSH
• Leukemia metabolism   pathology   MeSH
• Humans MeSH
• Malondialdehyde analysis   MeSH
• Cell Line, Tumor MeSH
• Oxidative Stress drug effects   MeSH
• Hydrogen Peroxide toxicity   MeSH
• Lipid Peroxidation drug effects   MeSH
• Singlet Oxygen metabolism   MeSH
• Cell Survival drug effects   MeSH
• Chromatography, High Pressure Liquid MeSH
• Iron toxicity   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

A quantum mechanics (QM)-based scoring function has been applied to complexes of cyclin-dependent kinase 2 (CDK2) and thirty-one pyrazolo[1,5-a]pyrimidine-based inhibitors and their bioisosteres. A hybrid three-layer QM/MM setup (DFT-D/PM6-D3H4X/AMBER in generalized Born solvent) was used here for the first time as an extension of our previous full QM and SQM/MM (SQM means semiempirical QM) approaches. Two approaches to obtain the structures of the CDK2/inhibitor complexes were examined: i) building the modifications from one X-ray structure available coupled with a conformational search and ii) docking the compounds into CDK2. The QM-based scoring entailed a QM/SQM/MM optimization followed by calculations of the binding scores which were subsequently correlated with the experimental binding free energies. The correlation for the building protocol was good (r(2) = 0.64, predictive index = 0.81), whereas the docking approach failed. A decomposition of the interaction energies to ligand fragments enabled us to rationalize the differences in the binding affinities. In conclusion, we have developed and refined a QM-based scoring protocol and successfully applied it to reproduce the binding affinities in congeneric series of CDK2 inhibitors and to rationalize their potency. We thus propose that such a tool can be used in computer-aided rational drug design.

• MeSH
• Cyclin-Dependent Kinase 2 antagonists & inhibitors   chemistry   metabolism   MeSH
• Quantum Theory MeSH
• Humans MeSH
• Pyrazoles chemistry   pharmacology   MeSH
• Pyrimidines chemistry   pharmacology   MeSH
• Molecular Dynamics Simulation MeSH
• Molecular Docking Simulation MeSH
• Thermodynamics MeSH
• Protein Binding MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Cíl. Posoudit stupeň korelace výsledků chemické analýzy urolitiázy pomocí výpočetní tomografie s duální energií záření (DECT) s laboratorní chemickou analýzou konkrementů a zhodnotit přínos metody DECT pro klinickou praxi. Metoda. Celkem 67 pacientů bylo vyšetřeno pomocí DECT s požadavkem na chemickou analýzu již známé či suspektní urolitiázy. K analýze chemického složení konkrementů pomocí DECT jsme využili simultánní expozici 140 kV a 80 kV. Získaná data byla analyzována pomocí programu Syngo Dual Energy Siemens v modulu Kidney Stones. U 30 pacientů byl následně proveden urologický výkon s extrakcí litiázy a jejím chemickým rozborem. V tomto souboru jsme pak korelovali výslednou chemickou skladbu urolitiázy získanou oběma metodami. Výsledky. V souboru 30 pacientů se podařilo prokázat u konkrementů velikosti nad 3 mm 100% senzitivitu a 100% specificitu DECT analýzy. V případě velmi drobné urolitiázy (tj. pod 3 mm) je přesnost detekce 100%, ale schopnost diferenciace na jednotlivé typy urolitiázy snížená na 97 %. Závěr. Metoda DECT analýzy urolitiázy vykazuje u konkrementů nad velikost 3 mm 100% shodu výsledků v porovnání s chemickou laboratorní analýzou močových konkrementů a má tedy velký přínos pro klinickou praxi, zejména v možnosti včasného zahájení vhodného terapeutického postupu.

Aim. To assess the degree of correlation between the results of chemical analysis of urolithiasis using dual energy computed tomography (DECT) with laboratory chemical analysis of stone, and to evaluate the contribution of this method to clinical practice. Method. Total 67 patients underwent DECT in order to performe the chemical analysis of already known or suspected urolithiasis. To analyze the chemical composition of the stone using DECT, we used the simultaneous exposure to 140 kV and 80 kV. The obtained data were analyzed using software Syngo Siemens Dual Energy in program "Kidney Stones". The method of the analysis was based on a material decomposition algorithm. In 30 patients, the extraction ofthe stone followed and the chemical and crystalograpic analysis was made. The results of virtual chemical analysis and laboratory findings were compared. Results. In the stones greater than 3 mm, sensitivity and specificity reached 100% using DECT analysis. In the case of very small stone disease (ie. less than 3 mm), the detection reached 100% accuracy, but the ability to differentiate the correct type of stone disease decreased to 97 %. Conclusion. DECT analysis of urolithiasis shows the stones of size 3 mm with 100% match results in comparison with laboratory chemical analysis of urinary stones and therefore has great benefit for clinical practice, especially early in choosing the appropriate therapeutic procedure.

• Keywords
• chemická dekompozice tří materiálů, výpočetní tomografie s duální energií záření,
• MeSH
• Algorithms MeSH
• Chemistry, Analytic MeSH
• Diagnostic Techniques, Urological instrumentation   utilization   MeSH
• Financing, Organized MeSH
• Furosemide diagnostic use   MeSH
• Contrast Media diagnostic use   MeSH
• Kidney Calculi diagnosis   etiology   chemistry   MeSH
• Humans MeSH
• Tomography, X-Ray Computed methods   instrumentation   utilization   MeSH
• Radiography, Dual-Energy Scanned Projection methods   instrumentation   utilization   MeSH
• Statistics as Topic MeSH
• Ultrasonography methods   utilization   MeSH
• Urolithiasis diagnosis   etiology   MeSH
• Outcome and Process Assessment, Health Care MeSH
• Check Tag
• Humans MeSH

Cíl. Zhodnotit možnosti posouzení viability tkáně slinivky analýzou dat CT provedeného skenováním duální energií záření X (DECT). Materiál a metoda. U 16 nemocných (průměrný věk 53,2 let, rozpětí 42-75, 9 mužů, 7 žen) s těžkou akutní pankreatitidou byla provedena analýza dat z DECT zobrazení břicha, použit byl soft warový experimentální modul Syngo-DualEnergy (Siemens, Forchheim, Německo). Vyšetření byla provedena v portální fázi nástřiku po podání 100 ml jódové kontrastní látky s koncentrací 400 mgI/ml průtokem 4 ml/s na dvouzdrojovém CT přístroji (Definition, Siemens, Forchheim, Německo) s použitím akvizice dat s napětím 140 KV soustavou A a 80 kV soustavou B; oba systémy simultánně využívaly kolimaci 2× (32 × 0,6 mm). Na mapách distribuce jódu byly zhodnoceny oblasti pankreatu s výpadkem perfuze, které byly označeny jako nekrotické a vyhledávána byla prokrvácená tkáň na mapách virtuálního nativního zobrazení. Nálezy byly porovnány s vývojem onemocnění při zobrazení provedeným konvenční technikou MDCT s kolimací 2× (32 × 0,6 mm) rovněž v portální fázi nástřiku k.l. Výsledky. Mortalita v souboru byla 18,8 % (3/16), u dvou z nemocných byly nalezeny nekrózy s rozsahem více než 2/3 pankreatu a s ložisky hemoragie, u jedné ze zemřelých nekróza téměř celé žlázy. Jen u třech nemocných nebyly nalezeny významnější odchylky v sycení pankreatu. U ostatních nemocných byl rozsah nekrózy pankreatu v rozpětí do 2/3 jejího objemu, v dalším vývoji byl zaznamenán těžký průběh pankreatitidy s rozvojem pseudocyst a nekróz peripankreatického tuku. Závěr. Virtuální nativní zobrazení a analýza map distribuce jódu při DECT je slibnou metodou predikce vývoje pankreatitidy včetně prognózy nemocného, dále je významným prostředkem snížení radiační zátěže vynecháním nativního či dvoufázového CT vyšetření pankreatu.

Aim. The aim of this study is to evaluate the possibility of application of the CT acquisition with dual energy X-radiation (DECT) for assessment of the viability of the pancreatic tissue in patients with a severe form of acute pancreatitis. Material and method. 16 patients were prospectively enrolled in the study (the average age was 53.2, age range of 34-75, 9 males, 7 females). The patients underwent CT due to clinical signs of severe, acute pancreatitis. All the CT examinations were performed in the dual-energy regimen (DE) using data acquisition with the voltage of 140 kV in the A system and 80 kV in the B system from the dome of the diaphragm to the symphysis. The examinations were performed aft er the intravenous application of 100 ml of iodinated contrast material with the concentration 400 milligrams of iodine per milliliter. The analysis of material decomposition allowed obtaining virtual non-contrast images (VNC) and maps of iodine distribution (IDM). The findings on post-contrast conventional images were compared with the presence of deficit of iodine distribution within pancreas and the presence of increased density on virtual non-contrast images. The prognostic values of necrosis more than two thirds of pancreas and presence of bleeding were tested according to the survival. Results. Virtual-non-contrast images of valuable quality were obtained in all cases. The assessment of iodine distribution maps provided to change the stage of acute pancreatitis in three cases in comparison to the assessment of conventional post-contrast images. The most important factor involving the fatal prognosis was necrosis more than two thirds of pancreas found on iodine distribution map, it reached sensitivity, specificity, negative and positive predictive value of 100%. Conclusion. Dual-energy CT with the analysis of iodine distribution allows assessing the viability of the pancreas with the high accuracy in patients with severe acute pancreatitis.

• MeSH
• Pancreatitis, Acute Necrotizing diagnosis   pathology   MeSH
• Financing, Organized MeSH
• Gastrointestinal Hemorrhage diagnosis   complications   MeSH
• Iodine diagnostic use   MeSH
• Contrast Media MeSH
• Humans MeSH
• Necrosis diagnosis   complications   MeSH
• Pancreas physiopathology   pathology   MeSH
• Tomography, X-Ray Computed methods   instrumentation   utilization   MeSH
• Prospective Studies MeSH
• Tomography, Spiral Computed methods   instrumentation   utilization   MeSH
• Outcome and Process Assessment, Health Care methods   trends   utilization   MeSH
• Check Tag
• Humans MeSH

Cíl. Zhodnotit zkušenosti s CT vyšetřením srdce duální energií záření X (DECT). Materiál a metoda. Bylo provedeno 40 CT srdce (29 mužů, 11 žen) s použitím dvouzdrojového CT přístroje v režimu expozice dvojí energie záření X (systém A ? 140 a systém B ? 100 kV). Průměrný věk v souboru byl 58,3 v rozpětí 48?81 let. CCTA byla inidikována z důvodu podezření na koronární nemoc (27×) nebo se jednalo o kontrolní vyšetření u nemocných po operaci aortokoronárních bypassů (13×). Pro perfuzní analýzu byl využit algoritmus dekompozice tří materiálů s generováním map distribuce jódu z obrazů 140 a 100 kV s časovým rozlišením 330 ms a s šíří obrazu 1,5 mm. U 20 nemocných byla porovnána perfuzní analýza DECTs perfuzním zobrazením myokardu magnetickou rezonancí a zobrazením pozdního sycení myokardu. Výsledky. Dostatečné zobrazení perfuze bylo získáno u 88 % nemocných, hodnotitelný angiogram u všech nemocných. Při porovnání s perfuzním zobrazením myokardu magneticku rezonancí bylo dosaženo shody v nálezu u 85 % nemocných. Závěr. DECT je slibnou metodou ke zhodnocení stavu koronárních tepen a perfuzního objemu myokardu z dat jediného vyšetření.

Aim. To evaluate the experience with the dual-energy cardiac CT (DECT). Material and method. Forty examinations (29 males, 11 females, mean age 58.3 ranging 48? 81 year) using dual-energy CT on dual-source system operating in dual energy mode were performed in suspected coronary arterial disease (27×) and in patients who underwent aortocoronary bypass graft surgery (13×). Based on the two sets of images (140 kV and 100 kV) images of 1.5 mm thickness, 330 ms of temporal, the three-material-decomposition algorithm was used to create maps of iodine distribution and these maps were used in myocardial perfusion analysis. Perfusion analysis using DECT was compared with perfusion and delayed enhancement magnetic resonance imaging in 20 patients. Results. Sufficient perfusion imaging was obtained in 88% of patients; assessable angiogram of coronaries was reconstructed in all patients. Comparing the perfusion analyses, the same finding was found both on DECT and MRI in 85% of patients. Conclusion. DECT of the heart is the promising imaging method including the imaging of coronary anatomy and myocardial perfusion obtained from a single data acquisition.

• MeSH
• Financing, Organized MeSH
• Contrast Media MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   utilization   MeSH
• Myocardium MeSH
• Perfusion MeSH
• Tomography, X-Ray Computed methods   instrumentation   utilization   MeSH
• Image Processing, Computer-Assisted methods   utilization   MeSH
• Prospective Studies MeSH
• Heart physiology   physiopathology   MeSH
• Check Tag
• Humans MeSH