Random laser as a potential tool for the determination of the scattering coefficient

The determination of the optical properties of a turbid medium is a major topic in the field of optics. Generally, they comprise the parameters µ_a, µ_s, g and n. There is, however, a lack of techniques for the direct determination of the scattering coefficient µ_s. This study, therefore, proposes the random laser (RL) as a tool to directly measure µ_s - and not μs′. Evidence is found that it is possible to determine µ_s in the diffusive regime by means of the RL. Based on these findings, a local model of the RL is developed and presented in this study.     

Optical coherence tomography can assess skeletal muscle tissue from mouse models of muscular dystrophy by parametric imaging of the attenuation coefficient

We present the assessment of ex vivo mouse muscle tissue by quantitative parametric imaging of the near-infrared attenuation coefficient µ_t using optical coherence tomography. The resulting values of the local total attenuation coefficient µ_t (mean ± standard error) from necrotic lesions in the dystrophic skeletal muscle tissue of mdx mice are higher (9.6 ± 0.3 mm⁻¹) than regions from the same tissue containing only necrotic myofibers (7.0 ± 0.6 mm⁻¹), and significantly higher than values from intact myofibers, whether from an adjacent region of the same sample (4.8 ± 0.3 mm⁻¹) or from healthy tissue of the wild-type C57 mouse (3.9 ± 0.2 mm⁻¹) used as a control. Our results suggest that the attenuation coefficient could be used as a quantitative means to identify necrotic lesions and assess skeletal muscle tissue in mouse models of human Duchenne muscular dystrophy.OCIS codes: (110.4500) Optical coherence tomography, (170.6935) Tissue characterization, (100.2960) Image analysis, (290.1350) Backscattering     

Three-dimensional printed optical phantoms with customized absorption and scattering properties

Three-dimensional (3D) printing offers the promise of fabricating optical phantoms with arbitrary geometry, but commercially available thermoplastics provide only a small range of physiologically relevant absorption (µ_a) and reduced scattering (µ_s`) values. Here we demonstrate customizable acrylonitrile butadiene styrene (ABS) filaments for dual extrusion 3D printing of tissue mimicking optical phantoms. µ<sub>a</sub> and µ<sub>s</sub>` values were adjusted by incorporating nigrosin and titanium dioxide (TiO₂) in the filament extrusion process. A wide range of physiologically relevant optical properties was demonstrated with an average repeatability within 11.5% for µ_a and 7.71% for µ_s`. Additionally, a mouse-simulating phantom, which mimicked both the geometry and optical properties of a hairless mouse with an implanted xenograft tumor, was printed using dual extrusion methods. 3D printed tumor optical properties matched the live tumor with less than 3% error at a wavelength of 659 nm. 3D printing with user defined optical properties may provide a viable method for durable optically diffusive phantoms for instrument characterization and calibration.OCIS codes: (170.5280) Photon migration, (110.0113) Imaging through turbid media, (110.7050) Turbid media, (160.4670) Optical materials     

α-Glucosidase inhibitors from Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit: molecular docking and interaction mechanism of flavonols with different B-ring hydroxylations

Inhibition of α-glucosidase alleviates postprandial high glycemic levels in diabetic or prediabetic population. In Chinese bayberry fruit, myricetin, quercetin and kaempferol are main flavonols, which differ only in their hydroxylation on the B-ring. Kaempferol (4′-OH) showed high IC₅₀ (65.36 ± 0.27 μmol L⁻¹) against α-glucosidase, while quercetin (3′,4′-OH) exhibited stronger inhibition (46.91 ± 0.54 μmol L⁻¹) and myricetin (3′,4′,5′-OH) possessed the strongest inhibitory activity (33.20 ± 0.43 μmol L⁻¹). Molecular docking analysis illustrated that these flavonols could insert to the active cavity of α-glucosidase. Adjacent hydroxyl groups at B-ring of myricetin and quercetin positively contributed to form hydrogen bonds that were important to the stability of flavonol–enzyme complex, while kaempferol had no adjacent hydroxyl groups. Such observation was further validated by molecular dynamics simulations, and in good consistency with in vitro kinetic analysis and fluorescence spectroscopy analysis. Among three flavonols tested, myricetin possessed the strongest inhibition effects on α-glucosidase with the lowest dissociation constant (K_i = 15.56 μmol L⁻¹) of myricetin-α-glucosidase, largest fluorescence quenching constant (K_sv) of (14.26 ± 0.03) × 10⁴ L mol⁻¹ and highest binding constant (K_a) of (1.38 ± 0.03) × 10⁵ L mol⁻¹ at 298 K with the enzyme. Bio-Layer Interferometry (BLI) and circular dichroism (CD) analysis further confirmed that myricetin had high affinity to α-glucosidase and induced conformational changes of enzyme. Therefore, myricetin, quercetin and kaempferol are all excellent dietary α-glucosidase inhibitors and their inhibitory activities are enhanced by increasing number of hydroxyl groups on B-ring.

Inhibition of α-glucosidase alleviates postprandial high glycemic levels in diabetic or prediabetic population.     

Efficiency of Incorporation and Chain Termination Determines the Inhibition Potency of 2′-Modified Nucleotide Analogs against Hepatitis C Virus Polymerase

Ribonucleotide analog inhibitors of the RNA-dependent RNA polymerase of hepatitis C virus (HCV) represent one of the most exciting recent developments in HCV antiviral therapy. Although it is well established that these molecules cause chain termination by competing at the triphosphate level with natural nucleotides for incorporation into elongating RNA, strategies to rationally optimize antiviral potency based on enzyme kinetics remain elusive. In this study, we used the isolated HCV polymerase elongation complex to determine the pre-steady-state kinetics of incorporation of 2′F-2′C-Me-UTP, the active metabolite of the anti-HCV drug sofosbuvir. 2′F-2′C-Me-UTP was efficiently incorporated by HCV polymerase with apparent K_d (equilibrium constant) and k_pol (rate of nucleotide incorporation at saturating nucleotide concentration) values of 113 ± 28 μM and 0.67 ± 0.05 s⁻¹, respectively, giving an overall substrate efficiency (k_pol/K_d) of 0.0059 ± 0.0015 μM⁻¹ s⁻¹. We also measured the substrate efficiency of other UTP analogs and found that substitutions at the 2′ position on the ribose can greatly affect their level of incorporation, with a rank order of OH > F > NH₂ > F-C-Me > C-Me > N₃ > ara. However, the efficiency of chain termination following the incorporation of UMP analogs followed a different order, with only 2′F-2′C-Me-, 2′C-Me-, and 2′ara-UTP causing complete and immediate chain termination. The chain termination profile of the 2′-modified nucleotides explains the apparent lack of correlation observed across all molecules between substrate efficiency at the single-nucleotide level and their overall inhibition potency. To our knowledge, these results provide the first attempt to use pre-steady-state kinetics to uncover the mechanism of action of 2′-modified NTP analogs against HCV polymerase.     

Realistic dielectric response of high temperature sintered ZnO ceramic: a microscopic and spectroscopic approach

High temperature sintering (1200–1400 °C) has been performed on ZnO ceramics. An X-ray Absorption Fine Structure (XAFS) study shows that high sintering temperature introduces a constant amount of V_O and V_Zn defects without any significant effect on the crystal or electronic structure of Wurtzite ZnO. The combined effects of grain boundaries and voids are considered responsible for the apparent colossal dielectric constant (ε′) > 10⁴ at low frequency (∼10² Hz) for all the sintered ZnO ceramics. The superior contact among grains of the ZnO-1200 sample enhances both the interfacial and orientational polarization of the Zn²⁺–V_O dipoles, which results in the increase of low and high frequency dielectric constants (ε′) and the corresponding dielectric loss (tan δ) also increases. On the other hand, high temperature sintering of ZnO at 1300 °C and 1400 °C introduces voids at the expense of reduced grain and grain boundary contact areas, thus affecting both the interfacial and orientational polarization with corresponding reduction of dielectric constant (ε′) and dielectric loss. Orientational polarizations due to Zn²⁺–V_O dipoles are suggested to remain fixed and it is the microstructure which controls the dielectric properties of high temperature sintered ZnO ceramics.

Superior grain contacts of ZnO-1200 samples enhance low and high frequency dielectric constants (ε′) and dielectric loss (tan δ).     

Evaluation of diastolic function by three-dimensional volume tracking of the mitral annulus with cardiovascular magnetic resonance: comparison with tissue Doppler imaging

Background

Measurement of mitral annulus (MA) dynamics is an important component of the evaluation of left ventricular (LV) diastolic function; MA velocities are commonly measured using tissue Doppler imaging (TDI). This study aimed to examine the clinical potential of a semi-automated cardiovascular magnetic resonance (CMR) technique for quantifying global LV diastolic function, using 3D volume tracking of the MA with conventional cine-CMR images.

Methods

124 consecutive patients with normal ejection fraction underwent both clinically indicated transthoracic echocardiography (TTE) and CMR within 2 months. Interpolated 3D reconstruction of the MA over time was performed with semi-automated atrioventricular junction (AVJ) tracking in long-axis cine-CMR images, producing an MA sweep volume over the cardiac cycle. CMR-based diastolic function was evaluated, using the following parameters: peak volume sweep rates in early diastole (PSR_E) and atrial systole (PSR_A), PSR_E/PSR_A ratio, deceleration time of sweep volume (DT_SV), and 50% diastolic sweep volume recovery time (DSVRT₅₀); these were compared with TTE diastolic measurements.

Results

Patients with TTE-based diastolic dysfunction (n = 62) showed significantly different normalized MA sweep volume profiles compared to those with TTE-based normal diastolic function (n = 62), including a lower PSR_E (5.25 ± 1.38 s⁻¹ vs. 7.72 ± 1.7 s⁻¹), a higher PSR_A (6.56 ± 1.99 s⁻¹ vs. 4.67 ± 1.38 s⁻¹), a lower PSR_E/PSR_A ratio (0.9 ± 0.44 vs. 1.82 ± 0.69), a longer DT_SV (144 ± 55 ms vs. 96 ± 37 ms), and a longer DSVRT₅₀ (25.0 ± 11.0% vs. 15.6 ± 4.0%) (all p < 0.05). CMR diastolic parameters were independent predictors of TTE-based diastolic dysfunction after adjusting for left ventricular hypertrophy, hypertension, and coronary artery disease. Good correlations were observed between CMR PSR_E/PSR_A and early-to-late diastolic annular velocity ratios (e′/a′) measured by TDI (r = 0.756 to 0.828, p < 0.001).

Conclusions

3D MA sweep volumes generated by semi-automated AVJ tracking in routinely acquired CMR images yielded diastolic parameters that were effective in identifying patients with diastolic dysfunction when correlated with TTE-based variables.     

Multiorgan insulin sensitivity in lean and obese subjects

OBJECTIVE

To provide a comprehensive assessment of multiorgan insulin sensitivity in lean and obese subjects with normal glucose tolerance.

RESEARCH DESIGN AND METHODS

The hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracer infusions was performed in 40 obese (BMI 36.2 ± 0.6 kg/m², mean ± SEM) and 26 lean (22.5 ± 0.3 kg/m²) subjects with normal glucose tolerance. Insulin was infused at different rates to achieve low, medium, and high physiological plasma concentrations.

RESULTS

In obese subjects, palmitate and glucose R_a in plasma decreased with increasing plasma insulin concentrations. The decrease in endogenous glucose R_a was greater during low-, medium-, and high-dose insulin infusions (69 ± 2, 74 ± 2, and 90 ± 2%) than the suppression of palmitate R_a (52 ± 4, 68 ± 1, and 79 ± 1%). Insulin-mediated increase in glucose disposal ranged from 24 ± 5% at low to 253 ± 19% at high physiological insulin concentrations. The suppression of palmitate R_a and glucose R_a were greater in lean than obese subjects during low-dose insulin infusion but were the same in both groups during high-dose insulin infusion, whereas stimulation of glucose R_d was greater in lean than obese subjects across the entire physiological range of plasma insulin.

CONCLUSIONS

Endogenous glucose production and adipose tissue lipolytic rate are both very sensitive to small increases in circulating insulin, whereas stimulation of muscle glucose uptake is minimal until high physiological plasma insulin concentrations are reached. Hyperinsulinemia within the normal physiological range can compensate for both liver and adipose tissue insulin resistance, but not skeletal muscle insulin resistance, in obese people who have normal glucose tolerance.Obesity is associated with a constellation of metabolic alterations that are risk factors for coronary heart disease, including diabetes, dyslipidemia, and nonalcoholic fatty liver disease (1). It is likely that insulin resistance in specific organ systems, namely adipose tissue, liver, and skeletal muscle, is involved in the pathogenesis of these metabolic abnormalities (2,3). The effect of insulin resistance on daily glucose and free fatty acid (FFA) metabolism in obese people who do not have diabetes is unclear, however, because it is possible that hyperinsulinemia associated with obesity can overcome the defect in insulin action and normalize metabolic function. In fact, data from large studies have demonstrated that basal plasma glucose and FFA concentrations in obese people are not different than those in lean subjects (4). Accordingly, it is possible that many obese people have multiorgan insulin resistance and are at increased risk for development of metabolic diseases even when basal glucose and FFA concentrations are normal.The assessment of insulin action is complex because insulin has multiple metabolic functions that differ across organ systems and require different doses of insulin to achieve maximal effects (5). A multistage hyperinsulinemic-euglycemic clamp procedure (HECP), conducted in conjunction with isotopically labeled tracer infusions to measure substrate kinetics, can be used to determine simultaneously insulin action in the liver (suppression of glucose R_a into plasma), muscle (stimulation of glucose R_d from plasma), and adipose tissue (suppression of adipose tissue triglyceride lipolysis; i.e., glycerol and palmitate R_a into plasma).The primary purpose of the current study was to further understand the potential insulin-related metabolic dysfunction associated with obesity by providing a comprehensive assessment of multiorgan insulin sensitivity across a physiological range of plasma insulin concentrations in lean and obese subjects through the use of a multistage HECP in conjunction with stable isotopically labeled glucose, palmitate, and glycerol tracer infusions. Only subjects who had normal fasting plasma glucose concentrations and who did not have impaired glucose tolerance or diabetes were included in this study to eliminate the potential confounding influences of basal hyperglycemia and diabetes therapy on the assessment of insulin action. Most obese people do not have impaired glucose tolerance or diabetes, so our group represents the majority of the obese population (4). We hypothesized that hepatic glucose production and adipose tissue lipolytic rate are much more sensitive to insulin than is muscle glucose uptake. Basal hyperinsulinemia and physiological increases in plasma insulin concentration in obese subjects with normal glucose tolerance should therefore be able to overcome insulin resistance in the liver and adipose tissue but not skeletal muscle, resulting in normal rates of endogenous glucose production (EGP) and lipolysis but not glucose disposal.     

Extraction of tissue optical property and blood flow from speckle contrast diffuse correlation tomography (scDCT) measurements

Measurement of blood flow in tissue provides vital information for the diagnosis and therapeutic monitoring of various vascular diseases. A noncontact, camera-based, near-infrared speckle contrast diffuse correlation tomography (scDCT) technique has been recently developed for 3D imaging of blood flow index (αD_B) distributions in deep tissues up to a centimeter. A limitation with the continuous-wave scDCT measurement of blood flow is the assumption of constant and homogenous tissue absorption coefficient (μ_a). The present study took the advantage of rapid, high-density, noncontact scDCT measurements of both light intensities and diffuse speckle contrast at multiple source-detector distances and developed two-step fitting algorithms for extracting both μ_a and αD_B. The new algorithms were tested in tissue-simulating phantoms with known optical properties and human forearms. Measurement results were compared against established near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) techniques. The accuracies of our new fitting algorithms with scDCT measurements in phantoms (up to 16% errors) and forearms (up to 23% errors) are comparable to relevant study results (up to 25% errors). Knowledge of μ_a not only improved the accuracy in calculating αD_B but also provided the potential for quantifying tissue blood oxygenation via spectral measurements. A multiple-wavelength scDCT system with new algorithms is currently developing to fit multi-wavelength and multi-distance data for 3D imaging of both blood flow and oxygenation distributions in deep tissues.     

Development of a combined broadband near-infrared and diffusion correlation system for monitoring cerebral blood flow and oxidative metabolism in preterm infants

Neonatal neuromonitoring is a major clinical focus of near-infrared spectroscopy (NIRS) and there is an increasing interest in measuring cerebral blood flow (CBF) and oxidative metabolism (CMRO₂) in addition to the classic tissue oxygenation saturation (StO₂). The purpose of this study was to assess the ability of broadband NIRS combined with diffusion correlation spectroscopy (DCS) to measured changes in StO₂, CBF and CMRO₂ in preterm infants undergoing pharmaceutical treatment of patent ductus arteriosus. CBF was measured by both DCS and contrast-enhanced NIRS for comparison. No significant difference in the treatment-induced CBF decrease was found between DCS (27.9 ± 2.2%) and NIRS (26.5 ± 4.3%). A reduction in StO₂ (70.5 ± 2.4% to 63.7 ± 2.9%) was measured by broadband NIRS, reflecting the increase in oxygen extraction required to maintain CMRO₂. This study demonstrates the applicability of broadband NIRS combined with DCS for neuromonitoring in this patient population.OCIS codes: (170.3660) Light propagation in tissues, (170.3880) Medical and biological imaging, (170.6510) Spectroscopy, tissue diagnostics     

Effect of Bi-substitution into the A-site of multiferroic La0.8Ca0.2FeO3 on structural,electrical and dielectric properties

(La_0.8Ca_0.2)_1−xBi_xFeO₃ (x = 0.00, 0.05, 0.10, 0.15 and 0.20) (LCBFO) multiferroic compounds have been prepared by the sol–gel method and calcined at 800 °C. X-ray diffraction results have shown that all samples crystallise in the orthorhombic structure with the Pnma space group. Electrical and dielectric characterizations of the synthesized materials have been performed using complex impedance spectroscopy techniques in the frequency range from 100 Hz to 1 MHz and in a temperature range from 170 to 300 K. The ac-conductivity spectra have been analysed using Jonscher''s power law σ(ω) = σ_dc + Aω^s, where the power law exponent (s) increases with the temperature. The imaginary part of the complex impedance (Z′′) was found to be frequency dependent and shows relaxation peaks that move towards higher frequencies with the increase of the temperature. The relaxation activation energy deduced from the Z′′ vs. frequency plots was similar to the conduction activation energy obtained from the conductivity. Hence, the relaxation process and the conduction mechanism may be attributed to the same type of charge carriers. The Nyquist plots (Z′′ vs. Z′) at different temperatures revealed the appearance of two semi-circular arcs corresponding to grain and grain boundary contributions.

(La_0.8Ca_0.2)_1−xBi_xFeO₃ (x = 0.00, 0.05, 0.10, 0.15 and 0.20) (LCBFO) multiferroic compounds have been prepared by the sol–gel method and calcined at 800 °C.     

Machine learning for real-time optical property recovery in interstitial photodynamic therapy: a stimulation-based study

With the continued development of non-toxic photosensitizer drugs, interstitial photodynamic therapy (iPDT) is showing more favorable outcomes in recent clinical trials. IPDT planning is crucial to further increase the treatment efficacy. However, it remains a major challenge to generate a high-quality, patient-specific plan due to uncertainty in tissue optical properties (OPs), µ_a and µ_s. These parameters govern how light propagates inside tissues, and any deviation from the planning-assumed values during treatment could significantly affect the treatment outcome. In this work, we increase the robustness of iPDT against OP variations by using machine learning models to recover the patient-specific OPs from light dosimetry measurements and then re-optimizing the diffusers’ optical powers to adapt to these OPs in real time. Simulations on virtual brain tumor models show that reoptimizing the power allocation with the recovered OPs significantly reduces uncertainty in the predicted light dosimetry for all tissues involved.     

Imprinting Status of GαS,NESP55, and XLαs in Cell Cultures Derived from Human Embryonic Germ Cells: GNAS Imprinting in Human Embryonic Germ Cells

GNAS is a complex gene that through use of alternative first exons encodes signaling proteins Gα_s and XLαs plus neurosecretory protein NESP55. Tissue‐specific expression of these proteins is regulated through reciprocal genomic imprinting in fully differentiated and developed tissue. Mutations in GNAS account for several human disorders, including McCune‐Albright syndrome and Albright hereditary osteodystrophy, and further knowledge of GNAS imprinting may provide insights into variable phenotypes of these disorders. We therefore analyzed expression of Gα_s, NESP55, and XLαs prior to tissue differentiation in cell cultures derived from human primordia germ cells. We found that the expression of Gα_s was biallelic (maternal allele: 52.6%± 2.5%; paternal allele: 47.2%± 2.5%; p= 0.07), whereas NESP55 was expressed preferentially from the maternal allele (maternal allele: 81.9%± 10%; paternal allele: 18.1%± 10%; p= 0.002) and XLαs was preferentially expressed from the paternal allele (maternal allele: 2.7%± 0.3%; paternal allele: 97.3%± 0.3%; p= 0.007). These results demonstrate that imprinting of NESP55 occurs very early in development, although complete imprinting appears to take place later than 5–11 weeks postfertilization, and that imprinting of XLαs occurs very early postfertilization. By contrast, mprinting of Gα_s most likely occurs after 11 weeks postfertilization and after tissue differentiation.     

Effects of Antiviral Drugs on Organic Anion Transport in Human Placental BeWo Cells

Placental drug transfer is important for achieving better pharmacotherapy in pregnant women and in fetuses. In the present study, we examined the effects of anti-hepatitis C virus (HCV) and anti-HIV drugs on organic anion transport in human placental BeWo cells. The cellular uptake of two fluorescence organic anions, 8-(2-[fluoresceinyl]aminoethylthio)adenosine-3′,5′-cyclic monophosphate (8-FcAMP) and fluorescein, was temperature and concentration dependent. The Michaelis constant (K_m) and the maximum uptake rate (V_max) for 8-FcAMP transport in BeWo cells were estimated to be 6.45 ± 0.75 μM and 25.55 ± 5.93 pmol/mg protein/10 min, respectively. The K_m and V_max values for fluorescein uptake were estimated to be 31.2 ± 11.8 μM and 510.9 ± 90.6 pmol/mg protein/10 min, respectively. Several known substrates of organic anion transporters in human placenta, including atorvastatin, glibenclamide, estrone-3-sulfate, and rifampin, inhibited cellular uptake of 8-FcAMP and fluorescein in BeWo cells. Transport of 8-FcAMP and fluorescein was inhibited by the antiviral drugs boceprevir, telaprevir, elvitegravir, and maraviroc. These findings suggest that some antiviral drugs are sufficiently potent to influence placental drug transfer and cause drug-drug interactions.     

3,3′-Diiodothyronine Production, a Major Pathway of Peripheral Iodothyronine Metabolism in Man

3,3′-Diiodothyronine (3,3′-T₂) has been detected in human serum and in thyroglobulin. However, no quantitative assessment of its clearance rate (CR), production rate (PR), or of the importance of extrathyroidal sources of 3,3′-T₂ relative to direct thyroidal secretion is yet available. This study examines these parameters in seven euthyroid subjects, and in eight athyreotic subjects (H) eumetabolic due to thyroxine therapy (HT₄) (n = 5) or triiodothyronine replacement (HT₃) (n = 3). A highly specific radioimmunoassay for the measurement of 3,3′-T₂ in whole serum was developed. Serum 3,3′-T₂ concentrations were (mean ± SD) 6.0±1.0 ng/100 ml in 13 normal subjects, 9.0±4.6 ng/100 ml in 25 hyperthyroid patients, and 2.7±1.1 ng/100 ml in 17 hypothyroid patients. The values in each of the latter two groups were significantly different from normal. 3,3′-T₂ was detected regularly in normal concentrations in 11 hypothyroid patients eumetabolic by treatment with synthetic T₄, in 10 eumetabolic patients suffering from nonthyroidal systemic illness, and in 2 subjects with elevated serum T₄-binding globulin. The 3,3′-T₂ CR was assessed from data acquired from the ¹²⁵I-3,3′-T₂ constant infusion technique. The 3,3′-T₂ PR was calculated from CR and serum concentration of 3,3′-T₂ determined by radio-immunoassay. In the HT₄ subjects the 3,3′-T₂ CR averaged 840±377 liters/day and 3,3′-T₂ PR 33.9±12.5 μg/day. These results were not significantly different from those in the control group: 3,3′-T₂ CR 628±218 liters/day and 3,3′-T₂ PR 39.8±19.8 μg/day (all corrected to 70 kg body wt). In addition to 3,3′-T₂ PR, T₃, and reverse triiodothyronine (rT₃) PR were determined in three of the HT₄ subjects. In each case studied, the 3,3′-T₂ PR was close to the combined triiodothyronine (T₃ + rT₃) PR. The mean molar ratio of T₂ PR/(T₃ + rT₃) PR was 1.08±0.10. The results obtained in the HT₄ subjects indicate that the production of 3,3′-T₂ is a major route of T₄ metabolism. The combined studies of 3,3′-T₂, T₃ and rT₃ PR in the HT₄ subjects indicate that both T₃ and rT₃ are major precursors of 3,3′-T₂. In the HT₃ subjects, the conversion of T₃ to 3,3′-T₂, determined as the molar ratio of 3,3′-T₂ PR to T₃ PR, ranged from 0.36 to 0.92, providing further evidence that T₃ is a precursor of 3,3′-T₂. From the close agreement between the mean values for 3,3′-T₂ PR in the euthyroid and HT₄ group it is concluded that most, if not all of the 3,3′-T₂ produced in normal humans is derived by extrathyroidal conversion from T₃ and rT₃.     

A series of four novel alkaline earth metal–organic frameworks constructed of Ca(ii), Sr(ii), Ba(ii) ions and tetrahedral MTB linker: structural diversity,stability study and low/high-pressure gas adsorption properties

A series of four novel microporous alkaline earth metal–organic frameworks (AE-MOFs) containing methanetetrabenzoate linker (MTB) with composition {[Ca₄(μ₈-MTB)₂]·2DMF·4H₂O}_n (UPJS-6), {[Ca₄(μ₄-O)(μ₈-MTB)_3/2(H₂O)₄]·4DMF·4H₂O}_n (UPJS-7), {[Sr₃(μ₇-MTB)_3/2]·4DMF·7H₂O}_n (UPJS-8) and {[Ba₃(μ₇-MTB)_3/2(H₂O)₆]·2DMF·4H₂O}_n (UPJS-9) (UPJS = University of Pavol Jozef Safarik) have been successfully prepared and characterized. The framework stability and thermal robustness of prepared materials were investigated using thermogravimetric analysis (TGA) and high-energy powder X-ray diffraction (HE-PXRD). MOFs were tested as adsorbents for different gases at various pressures and temperatures. Nitrogen and argon adsorption showed that the activated samples have moderate BET surface areas: 103 m² g⁻¹ (N₂)/126 m² g⁻¹ (Ar) for UPJS-7′′, 320 m² g⁻¹ (N₂)/358 m² g⁻¹ (Ar) for UPJS-9′′ and UPJS-8′′ adsorbs only a limited amount of N₂ and Ar. It should be noted that all prepared compounds adsorb carbon dioxide with storage capacities ranging from 3.9 to 2.4 wt% at 20 °C and 1 atm, and 16.4–13.5 wt% at 30 °C and 20 bar. Methane adsorption isotherms show no adsorption at low pressures and with increasing pressure the storage capacity increases to 4.0–2.9 wt% of CH₄ at 30 °C and 20 bar. Compounds displayed the highest hydrogen uptake of 3.7–1.8 wt% at −196 °C and 800 Torr among MTB containing MOFs.

Four novel microporous alkaline earth metal–organic frameworks (AE-MOFs) containing methanetetrabenzoate linker (MTB): UPJS-6, UPJS-7, UPJS-8 and UPJS-9 have been successfully prepared, characterized and tested as adsorbents for different gases.     

Pharmacokinetics and Distribution over the Blood-Brain Barrier of Zalcitabine (2′,3′-Dideoxycytidine) and BEA005 (2′,3′-Dideoxy-3′-Hydroxymethylcytidine) in Rats, Studied by Microdialysis

Microdialysis was applied to sample the unbound drug concentration in the extracellular fluid in brain and muscle of rats given zalcitabine (2′,3′-dideoxycytidine; n = 4) or BEA005 (2′,3′-dideoxy-3′-hydroxymethylcytidine; n = 4) (50 mg/kg of body weight given subcutaneously). Zalcitabine and BEA005 were analyzed by high-pressure liquid chromatography with UV detection. The maximum concentration of zalcitabine in the dialysate (C_max) was 31.4 ± 5.1 μM (mean ± standard error of the mean) for the brain and 238.3 ± 48.1 μM for muscle. The time to C_max was found to be from 30 to 45 min for the brain and from 15 to 30 min for muscle. Zalcitabine was eliminated from the brain and muscle with half-lives 1.28 ± 0.64 and 0.85 ± 0.13 h, respectively. The ratio of the area under the concentration-time curve (AUC) (from 0 to 180 min) for the brain and the AUC for muscle (AUC ratio) was 0.191 ± 0.037. The concentrations of BEA005 attained in the brain and muscle were lower than those of zalcitabine, with C_maxs of 5.7 ± 1.4 μM in the brain and 61.3 ± 12.0 μM in the muscle. The peak concentration in the brain was attained 50 to 70 min after injection, and that in muscle was achieved 30 to 50 min after injection. The half-lives of BEA005 in the brain and muscle were 5.51 ± 1.45 and 0.64 ± 0.06 h, respectively. The AUC ratio (from 0 to 180 min) between brain and muscle was 0.162 ± 0.026. The log octanol/water partition coefficients were found to be −1.19 ± 0.04 and −1.47 ± 0.01 for zalcitabine and BEA005, respectively. The degrees of plasma protein binding of zalcitabine (11% ± 4%) and BEA005 (18% ± 2%) were measured by microdialysis in vitro. The differences between zalcitabine and BEA005 with respect to the AUC ratio (P = 0.481), half-life in muscle (P = 0.279), and level of protein binding (P = 0.174) were not statistically significant. The differences were statistically significant in the case of the half-life in the brain (P = 0.032), clearance (P = 0.046), volume of distribution (P = 0.027) in muscle, and octanol/water partition coefficient (P = 0.019).     

Solvent-tuned magnetic exchange interactions in Dy2 systems ligated by a μ-phenolato heptadentate Schiff base

A series of binuclear dysprosium compounds, namely, [Dy(api)]₂ (1), [Dy(api)]₂·2CH₂Cl₂ (2), [Dy(Clapi)]₂·2C₄H₈O (3), and [Dy(Clapi)]₂·2C₃H₆O (4) (H₃api = 2-(2-hydroxyphenyl)-1,3-bis[4-(2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazoline; H₃Clapi = 2-(2′-hydroxy-5′-chlorophenyl)-1,3-bis[3′-aza-4′-(2′′-hydroxy-5′′-chlorophenyl)prop-4′-en-1′-yl]-1,3-imidazolidine), have been isolated by the reactions of salen-type ligands H₃api/H₃Clapi with DyCl₃·6H₂O in different solvent systems. Structural analysis reveals that each salen-type ligand provides a heptadentate coordination pocket (N₄O₃) to encapsulate a Dy^III ion and all of the Dy^III centers in 1–4 adopt a distorted square antiprism geometry with D_4d symmetry. Magnetic studies showed that compound 1 did not exhibit single-molecule magnetic (SMMs) behavior. With the introduction of different lattice solvents, compounds 2–4 showed filed-induced slow magnetic relaxation with barriers U_eff of 18.2 K (2), 28.0 K (3) and 16.4 K (4), respectively. Ab initio calculations were employed to interpret the magnetization behavior of 1–4. The combination of experimental and theoretical data reveal the importance of the weak exchange interaction between the Dy^III ions in the observation of slow magnetic relaxation, and a relaxation mechanism has been developed to rationalize the observed difference in the U_eff values. The different lattice solvents influence Dy–O–Dy bond angles and thus alter the torsion of the square antiprism geometry, consequently resulting in distinct magnetic interactions and the magnetic behavior.

Solvent-tuning changes the magnetic exchange interaction and results in different magnetic relaxation dynamics in Dy₂ systems ligated by a μ-phenolato heptadentate Schiff base.     

Synthesis,crystal structures,and luminescent properties of Zn(ii), Cd(ii), Eu(iii) complexes and detection of Fe(iii) ions based on a diacylhydrazone Schiff base

Acylhydrazone Schiff bases are rich in N and O atoms to coordinate with metal ions to form multidentate complexes. In this study, a novel diacylhydrazone Schiff base (N′¹E,N′⁴E)-N′¹,N′⁴-bis(2-hydroxy-5-nitrobenzylidene)succinohydrazide (H₄L) was synthesized from the condensation of nitrosalicylaldehyde and succinic dihydrazide. The interactions of H₄L with common monovalent, divalent and trivalent metal ions were investigated by ultraviolet spectroscopy and fluorescence spectroscopy. The results showed that H₄L had no obvious effect on the monovalent metal ions (Li⁺, Na⁺, K⁺), but reacted with most divalent and trivalent metal ions, and showed single selectivity in the fluorescence recognition of Fe³⁺ ions. More importantly, three kinds of binuclear molecular structures, [Zn₂(H₂L)₂]·5DMF (Zn-L), [Cd₂(H₂L)₂]·DMF·H₂O (Cd-L) and [Eu₂(H₂L)₃]·6DMSO (Eu-L), have been studied to further illustrate the interaction mode of diacylhydrazone Schiff base and metal ions. In addition, the optical properties of these crystallized complexes have been studied in DMF solution.

Acylhydrazone Schiff bases are rich in N and O atoms to coordinate with metal ions to form multidentate complexes.     

Nitro/Nitrosyl-Ruthenium Complexes Are Potent and Selective Anti-Trypanosoma cruzi Agents Causing Autophagy and Necrotic Parasite Death

cis-[RuCl(NO₂)(dppb)(5,5′-mebipy)] (complex 1), cis-[Ru(NO₂)₂(dppb)(5,5′-mebipy)] (complex 2), ct-[RuCl(NO)(dppb)(5,5′-mebipy)](PF₆)₂ (complex 3), and cc-[RuCl(NO)(dppb)(5,5′-mebipy)](PF₆)₂ (complex 4), where 5,5′-mebipy is 5,5′-dimethyl-2,2′-bipyridine and dppb is 1,4-bis(diphenylphosphino)butane, were synthesized and characterized. The structure of complex 2 was determined by X-ray crystallography. These complexes exhibited a higher anti-Trypanosoma cruzi activity than benznidazole, the current antiparasitic drug. Complex 3 was the most potent, displaying a 50% effective concentration (EC₅₀) of 2.1 ± 0.6 μM against trypomastigotes and a 50% inhibitory concentration (IC₅₀) of 1.3 ± 0.2 μM against amastigotes, while it displayed a 50% cytotoxic concentration (CC₅₀) of 51.4 ± 0.2 μM in macrophages. It was observed that the nitrosyl complex 3, but not its analog lacking the nitrosyl group, releases nitric oxide into parasite cells. This release has a diminished effect on the trypanosomal protease cruzain but induces substantial parasite autophagy, which is followed by a series of irreversible morphological impairments to the parasites and finally results in cell death by necrosis. In infected mice, orally administered complex 3 (five times at a dose of 75 μmol/kg of body weight) reduced blood parasitemia and increased the survival rate of the mice. Combination index analysis of complex 3 indicated that its in vitro activity against trypomastigotes is synergic with benznidazole. In addition, drug combination enhanced efficacy in infected mice, suggesting that ruthenium-nitrosyl complexes are potential constituents for drug combinations.