Serum Adipocyte Fatty Acid–Binding Protein Levels Are Associated With Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Patients

OBJECTIVE—Adipocyte fatty acid–binding protein (A-FABP) is a major cytoplasmic protein in adipocytes and macrophages and is closely associated with metabolic syndrome, type 2 diabetes, and atherosclerosis. Here, we investigated whether A-FABP was associated with nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes

Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel

<p>Abstract</p> <p>Background</p> <p>We have studied the <it>in vitro </it>and <it>in vivo </it>utility of polyethylene glycol (PEG)-hydrogels for the development of an anticancer drug 5-fluorouracil (5-FU) delivery system.</p> <p>Methods</p> <p>A 5-FU-loaded PEG-hydrogel was implanted subcutaneously to evaluate the drug retention time and the anticancer effect. For the pharmacokinetic study, two groups of male rats were administered either an aqueous solution of 5-FU (control group)/or a 5-FU-loaded PEG-hydrogel (treated group) at a dose of 100 mg/kg. For the pharmacodynamic study, a human non-small-cell lung adenocarcinoma (NSCLC) cell line, A549 was inoculated to male nude mice with a cell density of 3 × 10⁶. Once tumors start growing, the mice were injected with 5-FU/or 5-FU-loaded PEG-hydrogel once a week for 4 weeks. The growth of the tumors was monitored by measuring the tumor volume and calculating the tumor inhibition rate (IR) over the duration of the study.</p> <p>Results</p> <p>In the pharmacokinetic study, the 5-FU-loaded PEG-hydrogel gave a mean residence time (MRT) of 8.0 h and the elimination half-life of 0.9 h; these values were 14- and 6-fold, respectively, longer than those for the free solution of 5-FU (p < 0.05). In the pharmacodynamic study, A549 tumor growth was significantly inhibited in the 5-FU-loaded PEG-hydrogel group in comparison to the untreated group beginning on Day 14 (p < 0.05-0.01). Moreover, the 5-FU-loaded PEG-hydrogel group had a significantly enhanced tumor IR (p < 0.05) compared to the free 5-FU drug treatment group.</p> <p>Conclusion</p> <p>We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.</p

Direct Observation of Cooperative Protein Structural Dynamics of Homodimeric Hemoglobin from 100 ps to 10 ms with Pump–Probe X-ray Solution Scattering

Proteins serve as molecular machines in performing their biological functions, but the detailed structural transitions are difficult to observe in their native aqueous environments in real time. For example, despite extensive studies, the solution-phase structures of the intermediates along the allosteric pathways for the transitions between the relaxed (R) and tense (T) forms have been elusive. In this work, we employed picosecond X-ray solution scattering and novel structural analysis to track the details of the structural dynamics of wild-type homodimeric hemoglobin (HbI) from the clam Scapharca inaequivalvis and its F97Y mutant over a wide time range from 100 ps to 56.2 ms. From kinetic analysis of the measured time-resolved X-ray solution scattering data, we identified three structurally distinct intermediates (I-1, I-2, and I-3) and their kinetic pathways common for both the wild type and the mutant. The data revealed that the singly liganded and unliganded forms of each intermediate share the same structure, providing direct evidence that the ligand photolysis of only a single subunit induces the same structural change as the complete photolysis of both subunits does. In addition, by applying novel structural analysis to the scattering data, we elucidated the detailed structural changes in the protein, including changes in the heme heme distance, the quaternary rotation angle of subunits, and interfacial water gain/loss. The earliest, R-like I-1 intermediate is generated within 100 ps and transforms to the R-like I-2 intermediate with a time constant of 3.2 +/- 0.2 ns. Subsequently, the late, T-like I-3 intermediate is formed via subunit rotation, a decrease in the heme-heme distance, and substantial gain of interfacial water and exhibits ligation-dependent formation kinetics with time constants of 730 +/- 120 ns for the fully photolyzed form and 5.6 +/- 0.8 mu s for the partially photolyzed form. For the mutant, the overall kinetics are accelerated, and the formation of the T-like I-3 intermediate involves interfacial water loss (instead of water entry) and lacks the contraction of the heme-heme distance, thus underscoring the dramatic effect of the F97Y mutation. The ability to keep track of the detailed movements of the protein in aqueous solution in real time provides new insights into the protein structural dynamics.1149sciescopu

Large-area Rb 87 Bose-Einstein condensate in a clipped-Gaussian optical dipole trap

© 2021 American Physical Society.We demonstrate a production of large-area Rb87 Bose-Einstein condensates (BECs) using a non-Gaussian optical dipole trap (ODT). The ODT is formed by focusing a symmetrically truncated Gaussian laser beam, and it is shown that the beam clipping causes the trap geometry to be elongated and flattened along the beam axis direction. In the clipped-Gaussian ODT, an elongated, highly oblate BEC of Rb87 is generated with a length and width of approximately 470 and 130μm, respectively, where the condensate healing length is estimated to be ζ≈0.25μm at the trap center. The ODT is characterized to have a quartic trapping potential along the beam axis and the atom density of the condensate is uniform within 10% over 1000ζ in the central region. Finally, we discuss the prospect of conducting vortex shedding experiments using the elongated condensate.11Nsciescopu

Vortex shedding frequency of a moving obstacle in a Bose-Einstein condensate

We experimentally investigate the periodic vortex shedding dynamics in a highly oblate Bose-Einstein condensate using a moving penetrable Gaussian obstacle. The shedding frequency f (v) is measured as a function of the obstacle velocity v and characterized by a linear relationship of f (v) = a(v - v (c)) with v (c) being the critical velocity. The proportionality constant a is linearly decreased with a decrease in the obstacle strength, whereas v (c) approaches the speed of sound. When the obstacle size increases, both a and v (c) are decreased. We discuss a possible association of a with the Strouhal number in the context of universal shedding dynamics of a superfluid. The critical vortex shedding is further investigated for an oscillating obstacle and found to be consistent with the measured f (v). When the obstacle&apos;s maximum velocity exceeds v (c) but its oscillation amplitude is not large enough to create a vortex dipole, we observe that vortices are generated in the low-density boundary region of the trapped condensate, which is attributed to the phonon emission from the oscillating obstacle.11Nsciescopu

Universal Early Coarsening of Quenched Bose Gases

© 2022 American Physical Society.We investigate the early coarsening dynamics of an atomic Bose gas quenched into a superfluid phase. Using a two-step quench protocol, we independently control the two cooling rates during and after passing through the critical region, respectively, and measure the number of quantum vortices spontaneously created in the system. The latter cooling rate regulates the temperature during the condensate growth, consequently controlling the early coarsening dynamics in the defect formation. We find that the defect number shows a scaling behavior with the latter cooling rate regardless of the initial cooling rate, indicating universal coarsening dynamics in the early stage of condensate growth. Our results demonstrate that early coarsening not only reduces the defect density, but also affects its scaling with the quench rate, which is beyond the Kibble-Zurek mechanism.11Nsciescopu

Dry Electrode-Based Body Fat Estimation System with Anthropometric Data for Use in a Wearable Device

The bioelectrical impedance analysis (BIA) method is widely used to predict percent body fat (PBF). However, it requires four to eight electrodes, and it takes a few minutes to accurately obtain the measurement results. In this study, we propose a faster and more accurate method that utilizes a small dry electrode-based wearable device, which predicts whole-body impedance using only upper-body impedance values. Such a small electrode-based device typically needs a long measurement time due to increased parasitic resistance, and its accuracy varies by measurement posture. To minimize these variations, we designed a sensing system that only utilizes contact with the wrist and index fingers. The measurement time was also reduced to five seconds by an effective parameter calibration network. Finally, we implemented a deep neural network-based algorithm to predict the PBF value by the measurement of the upper-body impedance and lower-body anthropometric data as auxiliary input features. The experiments were performed with 163 amateur athletes who exercised regularly. The performance of the proposed system was compared with those of two commercial systems that were designed to measure body composition using either a whole-body or upper-body impedance value. The results showed that the correlation coefficient ( r 2 ) value was improved by about 9%, and the standard error of estimate (SEE) was reduced by 28%

Quantification of purified endogenous miRNAs with high sensitivity and specificity

MicroRNAs (miRNAs) are short (19–24 nt) non-coding RNAs that suppress the expression of protein coding genes at the post-transcriptional level. Differential expression profiles of miRNAs across a range of diseases have emerged as powerful biomarkers, making a reliable yet rapid profiling technique for miRNAs potentially essential in clinics. Here, we report an amplification-free multi-color single-molecule imaging technique that can profile purified endogenous miRNAs with high sensitivity, specificity, and reliability. Compared to previously reported techniques, our technique can discriminate single base mismatches and single-nucleotide 3′-tailing with low false positive rates regardless of their positions on miRNA. By preloading probes in Thermus thermophilus Argonaute (TtAgo), miRNAs detection speed is accelerated by more than 20 times. Finally, by utilizing the well-conserved linearity between single-molecule spot numbers and the target miRNA concentrations, the absolute average copy numbers of endogenous miRNA species in a single cell can be estimated. Thus our technique, Ago-FISH (Argonaute-based Fluorescence In Situ Hybridization), provides a reliable way to accurately profile various endogenous miRNAs on a single miRNA sensing chip

Quantification of purified endogenous miRNAs with high sensitivity and specificity

MicroRNAs (miRNAs) are short (19–24 nt) non-coding RNAs that suppress the expression of protein coding genes at the post-transcriptional level. Differential expression profiles of miRNAs across a range of diseases have emerged as powerful biomarkers, making a reliable yet rapid profiling technique for miRNAs potentially essential in clinics. Here, we report an amplification-free multi-color single-molecule imaging technique that can profile purified endogenous miRNAs with high sensitivity, specificity, and reliability. Compared to previously reported techniques, our technique can discriminate single base mismatches and single-nucleotide 3′-tailing with low false positive rates regardless of their positions on miRNA. By preloading probes in Thermus thermophilus Argonaute (TtAgo), miRNAs detection speed is accelerated by more than 20 times. Finally, by utilizing the well-conserved linearity between single-molecule spot numbers and the target miRNA concentrations, the absolute average copy numbers of endogenous miRNA species in a single cell can be estimated. Thus our technique, Ago-FISH (Argonaute-based Fluorescence In Situ Hybridization), provides a reliable way to accurately profile various endogenous miRNAs on a single miRNA sensing chip