Isolation of TTF-1 Positive Circulating Tumor Cells for Single-Cell Sequencing by Using an Automatic Platform Based on Microfluidic Devices.

Single-cell sequencing provides promising information in tumor evolution and heterogeneity. Even with the recent advances in circulating tumor cell (CTC) technologies, it remains a big challenge to precisely and effectively isolate CTCs for downstream analysis. The Cell RevealTM system integrates an automatic CTC enrichment and staining machine, an AI-assisted automatic CTC scanning and identification system, and an automatic cell picking machine for CTC isolation. H1975 cell line was used for the spiking test. The identification of CTCs and the isolation of target CTCs for genetic sequencing were performed from the peripheral blood of three cancer patients, including two with lung cancer and one with both lung cancer and thyroid cancer. The spiking test revealed a mean recovery rate of 81.81% even with extremely low spiking cell counts with a linear relationship between the spiked cell counts and the recovered cell counts (Y = 0.7241 × X + 19.76, R2 = 0.9984). The three cancer patients had significantly higher TTF-1+ CTCs than healthy volunteers. All target CTCs were successfully isolated by the Cell Picker machine for a subsequent genetic analysis. Six tumor-associated mutations in four genes were detected. The present study reveals the Cell RevealTM platform can precisely identify and isolate target CTCs and then successfully perform single-cell sequencing by using commercially available genetic devices.

Hydrophilic Sulfonated 2,9-Diamide-1,10-phenanthroline Endowed with a Highly Effective Ligand for Separation of Americium(III) from Europium(III): Extraction, Spectroscopy, and Density Functional Theory Calculations.

The design and development of a water-soluble heterocyclic ligand are believed to be an alternative way for improving the separation efficiency of actinides from lanthanides. Herein, we designed and synthesized a novel hydrophilic multidentate ligand: disulfonated N,N'-diphenyl-2,9-diamide-1,10-phenanthroline (DS-Ph-DAPhen) with soft and hard donor atoms, as a masking agent in aqueous solutions for Am(III) separation. The combination of N,N,N',N'-tetraoctyldiglycolamide in kerosene and DS-Ph-DAPhen in aqueous phases could separate Am(III) from Eu(III) across a range of nitric acid concentrations with very high selectivity. The coordination behaviors of Eu(III) with DS-Ph-DAPhen in aqueous solutions were studied by UV-vis titration, electrospray ionization mass spectrometry, and Fourier transform infrared spectra. The results indicated that Eu(III) ions could form both 1:1 and 1:2 complexes with the DS-Ph-DAPhen ligand in aqueous solution. Density functional theory calculation suggests that there are more covalent characters for Am-N bonds than that for Eu-N bonds in the complexes, which supports the better selectivity of the DS-Ph-DAPhen ligand toward Am(III) over Eu(III). This work demonstrates a feasible alternative approach to separating trivalent actinides from lanthanides with high selectivity.

Way to Enforce Selectivity via Steric Hindrance: Improvement of Am(III)/Eu(III) Solvent Extraction by Loaded Diphosphonic Acid Esters.

Hybrid donor extractants are a promising class of compounds for the separation of trivalent actinides and lanthanides. Here, we investigated a series of sterically loaded diphosphonate ligands based on bipyridine (BiPy-PO-iPr and BiPy-PO-cHex) and phenanthroline (Phen-PO-iPr and Phen-PO-cHex). We studied their complex formation with nitrates of trivalent f-elements in solvent extraction systems (Am and Eu) and homogeneous acetonitrile solutions (Nd, Eu, and Lu). Phenanthroline extractants demonstrated the highest efficiency and selectivity [SF(Am/Eu) up to 14] toward Am(III) extraction from nitric acid solutions among all of the studied diphosphonates of N-heterocycles. The binding constants established by UV-vis titration also indicated stronger binding of sterically impaired diphosphonates compared to the primary substituted diphosphonates. NMR titration and slope analysis during solvent extraction showed the formation of 2:1 complexes at high concentrations (>10-3 mol/L) for phenanthroline-based ligands. According to UV-vis titrations at low concentrations (10-5-10-6 mol/L), the phenanthroline-based ligands formed 1:1 complexes. Bipyridine-based ligands formed 1:1 complexes regardless of the ligand concentration. Luminescence titrations revealed that the quantum yields of the complexes with Eu(III) were 81 ± 8% (BiPy-PO-iPr) and 93 ± 9% (Phen-PO-iPr). Single crystals of the structures [Lu(µ2,κ4-(iPrO)2P(O)Phen(O)2(OiPr))(NO3)2]2 and Eu(Phen-PO-iPr)(NO3)3 were obtained by chemical synthesis with the Phen-PO-iPr ligand. X-ray diffraction studies revealed a closer contact of the f-element with the aromatic N atoms in the case of sterically loaded P═O ligands compared with sterically deficient ligands. Density functional theory calculations allowed us to rationalize the observed selectivity trends in terms of the bond length, Mayer bond order, and preorganization energy.

Does plain radiography still have a role in cases of fish bone ingestion in emergency rooms? A retrospective analysis.

BACKGROUND: Fish bones are the most common aerodigestive foreign bodies found in adults. Most cases of fish bone impaction improve after primary management by emergency physicians with a mirror laryngoscopy using a tongue depressor, before otolaryngologists perform a fiberoptic nasendoscopy. A computed tomography scan usually follows to determine the next step. Studies have recently been concerned about overdoses of radiation from computed tomography. However, clear algorithms remain unavailable for fish bone ingestion management to date. METHODS: A retrospective review was conducted on 180 patients who visited the emergency department with complaints of fish bone impaction between January 2017 and January 2019. RESULTS: A total of 81.6% of patients with fish bone impaction got symptomatic relief after primary management by emergency physicians and otolaryngologists. Out of 180 patients, 33 (18.3%) needed an endoscopic procedure due to persistent symptoms. Only one (0.56%) required an operation due to perforation. In the group failing primary management, the plain radiography of eight patients showed a positive finding and an esophagogastroscopy was done to remove the fish bones. CONCLUSION: Lateral neck radiography is still beneficial to patients with fish bone ingestion failure from primary management. Positive lateral soft tissue radiography in cases with persistent symptoms post primary management may directly suggest esophagogastroscopy without confirmation from a computed tomography, unless complications are suspected. For patients aged below 40, following up on their conditions after post management radiography shows negative results may increase their safety.

Ambient air particulates and Hg(p) concentrations and dry depositions estimations, distributions for various particles sizes ranges.

Ambient air TSP concentrations, dry deposition fluxes and particulate-bound mercury (Hg(p)) concentrations were measured and analyzed at a complex (traffic, residential and commercial) site. Zhang and He's model[1] was used to predict the dry deposition fluxes of ambient air particulates and Hg(p) at this complex site. The results revealed that October had the highest mean particulate concentration and lowest Hp(p) concentration and dry deposition flux. The mean calculated dry deposition fluxes of PM2.5 and PM2.5-10 accounted for 1%-2% and 0.06%-5% of the average total calculated dry deposition particle flux, respectively. The average calculated particle dry depositions flux of PM10+, accounted for 93%-99% of the average total calculated dry depositions particle flux. Finally, the model of Zhang and He underestimated the ambient air dry depositions fluxes of both particulates and Hg(p) for all particles sizes (PM2.5, PM2.5-10, PM10+) at the mixed site in this study. Better results concerning the dry deposition fluxes of pollutants were obtained as the particles size increased.

Particulates and particulates-bound mercury (Hg(p)) sizes (PM18, PM10, PM2.5, PM1, PM<1) distributions study by using MOUDI sampler at a complex sampling site.

The objectives of this study were to measure ambient air particles concentrations of different particulates sizes ranges (PM18, PM10, PM2.5, PM1, PM<1) at a complex (traffic, residential and commercial) site. Besides, particulates-bound mercury (Hg(p)) concentrations for various particulates sizes (PM18, PM10, PM2.5, PM1, PM<1) at mixed site were also studied. Finally, ambient air particulates and Hg(p) size distributions were also described at this complex sampling site. The results showed that the average PM18, PM10, PM2.5, PM1, PM<1 concentrations were 48.83, 41.78, 35.41, 19.89, and 11.86 µg/m3, respectively. And the average ambient air particulates-bound mercury (Hg(p)) which attached on PM18, PM10, PM2.5, PM1, PM<1 particles concentrations were 0.0838, 0.0867, 0.0790, 0.0546, and 0.0373 ng/m3, respectively, in the summer season. In addition, the average ambient air Hg(p) which attached on PM18, PM10, PM2.5, PM1, PM<1 particles concentrations were 0.0175, 0.0144, 0.0120, 0.0092, and 0.0057 ng/m3, respectively, in the autumn season. Finally, the average ambient air Hg(p) which attached on PM18, PM10, PM2.5, PM1, PM<1 particles concentrations were 0.0070, 0.0053, 0.0038, 0.0026, and 0.0014 ng/m3, respectively, in the winter season. And July has the average highest PM18 and PM10 concentrations. As for PM2.5, PM1 and PM<1 particulates, the average highest particulates concentrations all occurred in November. In addition, the highest average Hg(p) in PM18, PM10, PM2.5, PM1, and PM<1 concentrations all occurred in July. Moreover, the average particles and particulates-bound mercury m.m.d. values were ranged from 1.0 to 1.8 and 0.7 to 2.0 µm from July to December of 2018, respectively, at this mixed sampling site. As for monthly ambient air particles sizes distributions, the results further showed that the main peaks for July, September, and December all occurred in the sizes of 10-18 µm. The main peaks for October and November all occurred in the sizes of 2.5-10 µm. As for monthly Hg(p) sizes distributions, the results further showed that the main peaks for July occurred in the size of 0.3-1 µm. The main peak for September occurred in the size of 1-2.5 µm. The main peaks for October to December all occurred in the size of 10-18 µm. The above finding further concluded that the particulates-bound mercury (Hg(p)) was tended to be associated with the large particles sizes mode during the winter season. Finally, this study further shows that the Taichung Thermal Power Plant was responsible for the main emission source of Hg(p) especially in summer season of Central Taiwan.

Infected aneurysm of the thoracic aorta probably caused by Bacillus cereus: a case report.

BACKGROUND: An infected aneurysm of the thoracic aorta is a rare clinical condition with significant morbidity and mortality. Patients with fast-growing aortic aneurysms show a high incidence of rupture. Gram-positive organisms, such as the Staphylococcus and Enterococcus species, are the most common cause of infection. CASE PRESENTATION: A 91-year-old man presented at our facility with high grade fever and tachypnea, which he had experienced for the previous two days. He had a history of end-stage renal disease and had been undergoing regular chest computed tomography (CT) follow-up for a left lower lung nodule. CT imaging with intravenous contrast media showed a thoracic aortic aneurysm with hemothorax. Rupture of the aneurysm was suspected. CT imaging performed a year ago showed a normal aorta. Blood samples showed a Bacillus cereus infection. The patient was successfully treated for a mycotic aortic aneurysm secondary to Bacillus cereus bacteremia. CONCLUSIONS: Here, we report a rare of an infected aneurysm of the thoracic aorta probably caused by Bacillus cereus. Although infected aneurysms have been described well before, an aneurysm infected with Bacillus cereus is rare. Bacillus cereus, a gram-positive spore-building bacterium, can produce biofilms, which attach to catheters. It has recently emerged as a new organism that can cause serious infection.

Uncovering the impact of 'capsule' shaped amine-type ligands on Am(iii)/Eu(iii) separation.

Separation of trivalent actinides (An(iii)) and lanthanides (Ln(iii)) in spent nuclear fuel reprocessing is extremely challenging mainly owing to their similar chemical properties. Two amine-type reagents, tetrakis(2-pyridyl-methyl)-1,2-ethylenediamine (TPEN) and its hydrophobic derivative N,N,N',N'-tetrakis((4-butoxypyridin-2-yl)methyl)-ethylenediamine (TBPEN), have been identified to possess a selectivity for Am(iii) over Eu(iii). In this work, the structures, bonding nature, and thermodynamic behaviors of the Am(iii) and Eu(iii) complexes with these two ligands have been systematically studied via scalar relativistic density functional theory (DFT) calculations. According to Mayer bond order and the quantum theory of atoms in molecules (QTAIM) analyses, interactions between the ligands and metal cations exhibit some degree of covalent character with relatively more covalency for Am(iii) complexes. In comparison with TPEN, TBPEN has better extractability but worse separation ability for Am(iii) and Eu(iii). Four nitrogen atoms in pyridine moieties may be responsible for the different extraction abilities of TPEN and TBPEN, while two nitrogen atoms in amine chains of these ligands appear to play more important roles in the separation of Am(iii)/Eu(iii). These different extraction behaviors may be attributed to the longer and thinner 'capsule' shaped TBPEN ligand compared to TPEN. Our study might provide new insights into understanding the selectivity of the amine-type ligands toward minor actinides, and pave the way for designing new TPEN derivatives for extraction and separation of An(iii)/Ln(iii).

Understanding Am3+/Cm3+ separation with H4TPAEN and its hydrophilic derivatives: a quantum chemical study.

Am3+/Cm3+ separation is an extremely hard but important task in nuclear waste treatment. In this study, Am and Cm complexes formed with a back-extraction agent N,N,N',N'-tetrakis[(6-carboxypyridin-2-yl)methyl]ethylene-diamine (H4TPAEN) and its two derivatives with hydrophilic substituents (methoxy and morpholine groups) were investigated using the density functional theory (DFT). The optimized geometrical structures indicated that the Am3+ cation matched better with the cavities of the three studied ligands than Cm3+, and the Am3+ cations were located deeper in the cavities of the ligands. The bond order and quantum theory of atoms in molecules (QTAIM) analyses suggested that ionic interactions dominated An-N and An-O (An = Cm and Am) bonds. However, weak and different extents of partial covalency could also be found in the Am-N and Cm-N bonds. The O donor atoms in the carboxylate groups preferably coordinated with Cm3+ rather than Am3+, whereas the N atoms preferred Am3+. Therefore, the Am3+/Cm3+ selectivity of H4TPAEN and its two hydrophilic derivatives may be ascribed to the competition between the An-N and An-O interactions and the few dissimilarities in their geometrical structures. Based on our calculations, the methoxy and morpholine groups in the two derivatives can serve as electron-donating groups and enhance the strength of the An-NPY bonds (NPY denotes the nitrogen atom of pyridine ring). When compared with the Am-complex, the Cm-complex exhibited significant strength effect, resulting in the relatively lower Am3+/Cm3+ separation ability of the H4TPAEN's hydrophilic derivatives.

Theoretical unraveling of the separation of trivalent Am and Eu ions by phosphine oxide ligands with different central heterocyclic moieties.

The treatment of nuclear spent fuels, especially the separation of minor actinides, is an imperative task for the healthy development of the nuclear industry. Up to now, it still remains a worldwide challenge to separate trivalent An3+ from Ln3+ because of their similar chemical properties. Therefore, investigating the mechanism behind the selective extraction of An3+ by theoretical methods is necessary. In this work, three phosphine oxide ligands with the same side structures but different bridging frameworks, Ph2PyPO, Ph2BipyPO and Ph2PhenPO, were investigated theoretically, and compared with each other using relativistic density functional theory. The results of QTAIM and MBO suggest that the Am-N bonds in the studied complexes have more covalent character than those in the Eu-N bonds, whereas the PDOS analysis indicates that more overlap exists between Am-5f and the Ph2PyPO's N-2p orbital than between Am-5f and Ph2BipyPO's N-2p, and Am-5f and Ph2PhenPO's N-2p orbital. However, the studied ligands all possess stronger affinities towards Am3+ than Eu3+, which partly results in the Am3+ selectivity towards Eu3+ in these three ligands. The calculated reaction free energy can reproduce the Am/Eu separation ability difference of three ligands well. This work offers some useful information for An/Ln separation of phosphine oxide ligands, and may help to design more efficient An3+/Ln3+ separation ligands.

Pyridine-di-phosphonates as chelators for trivalent f-elements: kinetics, thermodynamic and interfacial study of Am(III)/Eu(III) solvent extraction.

The fractionation of high-level radioactive waste from nuclear power plants simplifies the handling of its components, and facilitates the reduction of radiotoxic effects on the environment. The search and study of new ligands for solvent extraction, as one of the methods in fractionation, remains a complex and important research task. In this work, four pyridine diphosphonate ligands were synthesized. These ligands are part of the class of the N,O-donor extractants, which are selective towards Am(III). The separation factor SF(Am/Eu) for the best extractant reached values up to 10. The influence of the substituents on the efficiency of extraction and complexation of trivalent f-elements, the kinetics of extraction, and the behavior of the ligand at the interface were described. The effect of nitric acid concentration on the extraction was shown. The stoichiometry of the complexes was determined by slope analysis in solvent extraction experiment and verified by spectrophotometric titration in acetonitrile. Liquid tension experiments with a pendant drop method revealed the interfacial properties of the ligands in "F-3 solvent/H2O" and "F-3 solvent/HNO3" systems. The relationship between the surface activity and the ligand structure was shown. Studies of the extraction kinetics were performed in a modified Lewis cell. The effect of the ligand structure on the extraction rate was shown. The DFT calculation with the B3LYP density functional was used to explain the extraction properties of the ligands, including selectivity. The calculation of the pre-organization energy of the ligands explained the kinetics and extraction patterns for the studied series.

Enhancing the Am3+/Cm3+ separation ability by weakening the binding affinity of N donor atoms: a comparative theoretical study of N, O combined extractants.

Mutual separation of trivalent americium (Am3+) and curium (Cm3+) ions through liquid-liquid extraction is challenging due to the similarity in their chemical properties. Three N, O combined extractants 2,6-pyridinedicarboxylic acid di(N-ethyl-4-fluoroanilide) (Et(pFPh)DPA), diphenyl(2-pyridyl)phosphine oxide (Ph2PyPO), and alkyldiamide amine with 2-ethylhexylalkyl chains (ADAAM(EH)) have been identified to exhibit selectivity for Am3+ over Cm3+. In this work, the structures, bonding nature, and thermodynamic behaviors of a series of representative Am- and Cm-complexes with these ligands have been systematically investigated using density functional theory (DFT) calculations. Based on our calculations, the ONO angle formed by three donor atoms of the ligand in the Am-complex is slightly larger than that in its Cm-analogue. The studied ligands show their preference toward Am3+ by opening their "mouths" slightly wider. According to the Mayer bond order and the quantum theory of atoms in molecules (QTAIM) analyses, the interactions between the O donor atoms of these ligands and Am3+ and Cm3+ ions show some weak partial covalent character, and compared to the Am-O bond, there is relatively more covalency in the Cm-O bond in the corresponding complex. However, opposite results can be found in the Am-N and Cm-N bonding for the first two ligands. Particularly, for the better separation ligand ADAAM(EH), the Am-N and Cm-N interactions are extremely weak and no covalent character exists in the bonding. Nevertheless, the difference between the very weak Am-N and Cm-N interactions still leads to a better performance of ADAAM(EH). Based on the comparison of these ligands, we can find that weakening the binding ability of N atoms in the ligand may increase the difference between the Am-N and Cm-N interactions, thus enhancing the Am3+/Cm3+ separation ability of the ligand. Our study might provide new insights into understanding the selectivity of these three N, O combined ligands toward minor actinides and pave the way for designing efficient Am3+/Cm3+ extraction and separation ligands.

Theoretical studies on the synergistic extraction of Am3+ and Eu3+ with CMPO-HDEHP and CMPO-HEH[EHP] systems.

In recent years, there has been a trend to use synergistic systems of neutral and acidic extractants into a single-solvent formulation to achieve Ln3+/An3+ extraction and separation via simplified processing schemes. In this study, geometrical structures, bonding nature, and thermodynamic stabilities of a series of possible extraction complexes of Am3+ and Eu3+ with two neutral-acid synergistic systems (CMPO-HDEHP and CMPO-HEH[EHP]) were theoretically studied using scalar-relativistic density functional theory (DFT). It is found that hydrogen bonds between neutral and acid ligands may greatly influence the Eu3+/Am3+ extraction and separation performance of the two synergistic systems. According to natural bond orbital (NBO) and energy decomposition analyses (EDA), the phosphoryl oxygen atoms of HDEHP or HEH[EHP] have higher affinity for Eu3+ and Am3+ than those of the CMPO ligand. Since weak but different extents of covalency exist in Eu- and Am-complexes, Eu3+/Am3+ separation via these two systems may be attributed to the different compositions of interactions between the metal ions and ligands. Thermodynamic analysis shows that the neutral complexes ML(NO3)2 (M = Eu and Am; L = [CMPO-DEHP]- and [CMPO-EH[EHP]]-) appear to be the most probable species in the complexation process.

Remote Control and Smart Phone Display -- Human Body Loading by ECG Instrumentation.

Electrical instrumentation is now a real-time phenomenon and an active part of smart phone trends. Modern electronic devices and controllers can be seen everywhere. Personal information detectors provide timely and effective medical care. In previous times, personnel electronic devices, such as the smart phone, i-watch, and e-clothes were diffi cult to link. Nowadays, it's a good time to prevent a health tragedy in certain people. This study tries to focus on discussing the remote control and smart phone display topic, through ECG instrumentation from e-clothes to prevent the human body from taking excessive exercise. Besides, the research also built a database in a remote server, where it stored historical ECG records. Through the model, a real sport (running) case study and system validation was proposed. Humans have a possibility to optimize their sporting style. The e-clothes can send GPS signals to a remote server. The system would then track the routes taken and monitor human body loading. Future research suggests that mass human trials or more mathematical hybrid model designs should take place.

Comparative theoretical study of the structures and stabilities of four typical gadolinium carboxylates in different scintillator solvents.

The structural properties and stabilities of four typical gadolinium carboxylates (Gd-CBX) in toluene, linear alkyl benzene (LAB), and phenyl xylyl ethane (PXE) solvents were theoretically studied using density functional theory (DFT/B3LYP with the basis sets 6-311G(d) and MWB54) and the polarizable continuum model (PCM). The average Gd-ligand interaction energies (E int, corrected for dispersion) and the values of the energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital (ΔHL) for the gadolinium complexes were calculated to compare the relative stabilities of the four Gd-CBX molecules in the three liquid scintillator solvents. According to the calculations, the values of E int and ΔHL for Gd-CBX in LAB are larger than the corresponding values in PXE and toluene. Gd-CBX may therefore be more compatible with LAB than with PXE and toluene. It was also found that, in the three scintillator solvents, the stabilities of the four Gd-CBX molecules increase in the order Gd-2EHA < Gd-2MVA < Gd-pivalate < Gd-TMHA.

Theoretical study of structure and stability of small gadolinium carboxylate complexes in liquid scintillator solvents.

The structural properties of three small gadolinium carboxylate complexes in three liquid scintillator solvents (pseudocumene, linear alkylbenzene, and phenyl xylylethane) were theoretically investigated using density functional theory (B3LYP/LC-RECP) and polarizable continuum model (PCM). The average interaction energy between gadolinium atom and carboxylate ligand (E(int)) and the energy difference of the highest singly occupied molecular orbital and lowest unoccupied molecular orbital (Δ(SL)) were calculated to evaluate and compare the relative stability of these complexes in solvents. The calculation results show that the larger (with a longer alkyl chain) gadolinium carboxylate complex has greater stability than the smaller one, while these gadolinium carboxylates in linear alkylbenzene were found to have greater stability than those in the other two solvents.