Ocular and Plasma Pharmacokinetics of Enavogliflozin Ophthalmic Solution in Preclinical Species.

An enavogliflozin ophthalmic solution (DWRX2008) is being developed to treat diabetic retinopathy and macular edema. This study evaluated the ocular distribution and plasma pharmacokinetics (PKs) of enavogliflozin in animal species. A sample of [14C] enavogliflozin was ocularly administered to two rabbits per time point at single doses of 600 µg/eye to evaluate ocular PK, which was evaluated using autoradiography until 48 h post-dose. Plasma concentrations after ocular administration in six rabbits, three rats, and three beagle dogs with single doses of 400 µg, 25 µg, and 100 µg, respectively, were investigated for 24 h. The retinal concentration of [14C] enavogliflozin reached Cmax at 2.0 h with an elimination half-life of 32.5 h, which remained above the IC50 value of sodium-dependent glucose transporter 2 until 24 h post-dose. In the plasma of rabbits, the fastest Tmax of 0.5 h and a 3.6 h half-life were observed among animal species. The relative bioavailability in rabbits after ocular administration was 3.4 compared to oral administration. Ocular administration of enavogliflozin could be a potential therapeutic route for diabetic retinal complications, based on relative bioavailability and effective delivery to the posterior ocular segment. DWRX2008 would be applicable to humans with favorable PK profiles and minimal systemic adverse effect.

An effective universal protocol for the extraction of fructooligosaccharide from the different agricultural byproducts.

Alternative bio-refinery technologies are required to promote the commercial utilization of plant biomass components. The fructooligosaccharide (FOS) obtained after hydrolysis of the hemicellulose fractions was mainly applied in the pharmaceutical and food industries. Agricultural bi-product is a rich constituent in dietary fibres, which have prebiotic effects on the intestinal microbiota and the host. Herein we explored the impact of FOS on microbiota modulation and the gut homeostasis effect. High fructooligosaccharide recovery was obtained using alkaline extraction techniques. The enzymatic method produced fructooligosaccharides with minor contamination from fructan and glucan components, although it had a low yield. But combining the alkaline and enzymatic process provides a higher yield ratio and purity of fructooligosaccharides. The structure of the fructooligosaccharide was confirmed, according to FTIR, 13C NMR, 1H NMR and 2D-NMR data. Our results could be applied to the development of efficient extraction of valuable products from agricultural materials using enzyme-mediated methods, which were found to be a cost-effective way to boost bio-refining value. Fructooligosaccharides with varying yields, purity, and structure can be obtained.

An integrated leachate bed reactor - anaerobic membrane bioreactor system (LBR-AnMBR) for food waste stabilization and biogas recovery.

This study developed an integrated LBR - AnMBR system for efficient stabilization and biogas recovery from food waste (FW) at room temperatures (21-22 °C). First, the leachate recirculation rate (4.4-13.2 L/h) was optimized to maximize hydrolysis and acidification yields. The maximum hydrolysis yield of 551 gSCOD/kg VSadded was achieved at recirculation rate of 13.2 L/h. The VFA concentrations in the FW leachate was as high as 12.5-16.0 g/L, resulting in a high acidification of 468 g CODVFA/kg VS. The solubilized FW was further stabilized by feeding the leachate to AnMBR. Different hydraulic (HRT) and solids retention times (SRT) were tested to achieve high COD removal and methane yields. High COD removal of 86 ± 3% was obtained in the AnMBR at HRT of 13 and SRT of 75 days. High biogas recovery of about 850 kWh per ton FWtreated was achieved along with high quality of AnMBR permeates containing low COD concentration but advantageously high concentration of nutrients (NH4+-N 317-403 mg/L, total phosphate 23-213 mg/L) without any particulates, which can be reused for landscape or liquid fertilizer.

Biohydrogen production and purification: Focusing on bioelectrochemical systems.

Innovative technologies on green hydrogen production become significant as the hydrogen economy has grown globally. Biohydrogen is one of green hydrogen production methods, and microbial electrochemical cells (MECs) can be key to biohydrogen provision. However, MECs are immature for biohydrogen technology due to several limitations including extracellular electron transfer (EET) engineering. Fundamental understanding of EET also needs more works to accelerate MEC commercialization. Interestingly, studies on biohydrogen gas purification are limited although biohydrogen gas mixture requires complex purification for use. To facilitate an MEC-based biohydrogen technology as the green hydrogen supply this review discussed EET kinetics, engineering of EET and direct interspecies electron transfer associated with hydrogen yield and the application of advanced molecular biology for improving EET kinetics. Finally, this article reviewed biohydrogen purification technologies to better understand purification and use appropriate for biohydrogen, focusing on membrane separation.

Dracocephalum moldavica Ethanol Extract Suppresses LPS-Induced Inflammatory Responses through Inhibition of the JNK/ERK/NF-κB Signaling Pathway and IL-6 Production in RAW 264.7 Macrophages and in Endotoxic-Treated Mice.

The excessive synthesis of interleukin-6 (IL-6) is related to cytokine storm in COVID-19 patients. Moreover, blocking IL-6 has been suggested as a treatment strategy for inflammatory diseases such as sepsis. Sepsis is a severe systemic inflammatory response syndrome with high mortality. In the present study, we investigated the anti-inflammatory and anti-septic effects and the underlying mechanisms of Dracocephalum moldavica ethanol extract (DMEE) on lipopolysaccharide (LPS)-induced inflammatory stimulation in RAW 264.7 macrophages along with septic mouse models. We found that DMEE suppressed the release of inflammatory mediators NO and PGE2 and inhibited both the mRNA and protein expression levels of iNOS and COX-2, respectively. In addition, DMEE reduced the release of proinflammatory cytokines, mainly IL-6 and IL-1ß, in RAW 264.7 cells by inhibiting the phosphorylation of JNK, ERK and p65. Furthermore, treatment with DMEE increased the survival rate and decreased the level of IL-6 in plasma in LPS-induced septic shock mice. Our findings suggest that DMEE elicits an anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophages and an anti-septic effect on septic mouse model through the inhibition of the ERK/JNK/NF-κB signaling cascades and production of IL-6.

Mentha arvensis Essential Oil Exerts Anti-Inflammatory in LPS-Stimulated Inflammatory Responses via Inhibition of ERK/NF-κB Signaling Pathway and Anti-Atopic Dermatitis-like Effects in 2,4-Dinitrochlorobezene-Induced BALB/c Mice.

The mechanism of atopic dermatitis (AD) is modulated by the release of cytokines and chemokines through the mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. Topical steroids are used to treat AD, but some people need safer anti-inflammatory drugs to avoid side effects. Mentha arvensis has been used as a herbal plant with medicinal properties, but its anti-inflammatory effects have not been elucidated in an AD model. In this study, we investigated the anti-inflammatory effects of M. arvensis essential oil (MAEO) and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and HaCaT cells (human epidermal keratinocyte). Additionally, we examined the ameliorating effects of the MAEO in a dinitrochlorobenzene (DNCB)-induced murine model of AD. We found, in both RAW 264.7 cells and HaCaT cells, MAEO inhibited LPS-stimulated inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 and proinflammatory cytokines, including IL-1ß and IL-6, due to the suppression of COX-2 and iNOS expression. In LPS-stimulated macrophages, we also observed that MAEO inhibited the phosphorylation of ERK and P65. Furthermore, MAEO treatment attenuated AD symptoms, including the dermatitis score, ear thickness, epidermal thickness and infiltration of mast cells, in a DNCB-induced animal model of AD. Overall, our findings suggest that MAEO exerts anti-inflammatory and anti-atopic dermatitis effects via inhibition of the ERK/NF-κB signaling pathway.

High-Intensity Warm-Up Increases Anaerobic Energy Contribution during 100-m Sprint.

This study aimed to evaluate the effects of warm-up intensity on energetic contribution and performance during a 100-m sprint. Ten young male sprinters performed 100-m sprints following both a high-intensity warm-up (HIW) and a low-intensity warm-up (LIW). Both the HIW and LIW were included in common baseline warm-ups and interventional warm-ups (eight 60-m runs, HIW; 60 to 95%, LIW; 40% alone). Blood lactate concentration [La-], time trial, and oxygen uptake (VO2) were measured. The different energy system contribution was calculated by using physiological variables. [La-1]Max following HIW was significantly higher than in LIW (11.86 ± 2.52 vs. 9.24 ± 1.61 mmol·L-1; p < 0.01, respectively). The 100-m sprint time trial was not significantly different between HIW and LIW (11.83 ± 0.57 vs. 12.10 ± 0.63 s; p > 0.05, respectively). The relative (%) phosphagen system contribution was higher in the HIW compared to the LIW (70 vs. 61%; p < 0.01, respectively). These results indicate that an HIW increases phosphagen and glycolytic system contributions as compared to an LIW for the 100-m sprint. Furthermore, an HIW prior to short-term intense exercise has no effect on a 100-m sprint time trial; however, it tends to improve times (decreased 100-m time trial; -0.27 s in HIW vs. LIW).

Quantum computation of dominant products in lithium-sulfur batteries.

Quantum chemistry simulations of some industrially relevant molecules are reported, employing variational quantum algorithms for near-term quantum devices. The energies and dipole moments are calculated along the dissociation curves for lithium hydride (LiH), hydrogen sulfide, lithium hydrogen sulfide, and lithium sulfide. In all cases, we focus on the breaking of a single bond to obtain information about the stability of the molecular species being investigated. We calculate energies and a variety of electrostatic properties of these molecules using classical simulators of quantum devices, with up to 21 qubits for lithium sulfide. Moreover, we calculate the ground-state energy and dipole moment along the dissociation pathway of LiH using IBM quantum devices. This is the first example, to the best of our knowledge, of dipole moment calculations being performed on quantum hardware.

The applicability of anaerobically treated domestic wastewater as a nutrient medium in hydroponic lettuce cultivation: Nitrogen toxicity and health risk assessment.

The applicability of anaerobic effluent (AE) from an anaerobic membrane bioreactor (AnMBR) treating domestic wastewater as a nutrient medium was evaluated through hydroponic cultivation of lettuce. The growth of lettuce plants on AE media was significantly inhibited to 31-40% in height and 36-48% in number of leaves compared to that on half-strength Hoagland solution (HHS) as a control. The primary cause of inhibition was nitrite toxicity as induced by partial nitrification. Therefore, the nitrification of AE as a pre-treatment step was adopted to prevent the toxicity of nitrite. The heights of lettuce grown on nitrified anaerobic effluent (NAE) and nitrified anaerobic effluent with 96 mg/L sulfate (NAES) were in the range of 11.4-11.5 cm and was comparable to that on control solution (11.4 cm). The potential health risk for heavy metals was insignificant based on health risk index (HRI < 1) and targeted hazardous quotient (THQ < 1). These results show that efficient crop production can be achieved with AE, but suitable pre-treatment steps should be followed.

Quantum simulation of electronic structure with a transcorrelated Hamiltonian: improved accuracy with a smaller footprint on the quantum computer.

Quantum simulations of electronic structure with a transformed Hamiltonian that includes some electron correlation effects are demonstrated. The transcorrelated Hamiltonian used in this work is efficiently constructed classically, at polynomial cost, by an approximate similarity transformation with an explicitly correlated two-body unitary operator. This Hamiltonian is Hermitian, includes no more than two-particle interactions, and is free of electron-electron singularities. We investigate the effect of such a transformed Hamiltonian on the accuracy and computational cost of quantum simulations by focusing on a widely used solver for the Schrödinger equation, namely the variational quantum eigensolver method, based on the unitary coupled cluster with singles and doubles (q-UCCSD) Ansatz. Nevertheless, the formalism presented here translates straightforwardly to other quantum algorithms for chemistry. Our results demonstrate that a transcorrelated Hamiltonian, paired with extremely compact bases, produces explicitly correlated energies comparable to those from much larger bases. For the chemical species studied here, explicitly correlated energies based on an underlying 6-31G basis had cc-pVTZ quality. The use of the very compact transcorrelated Hamiltonian reduces the number of CNOT gates required to achieve cc-pVTZ quality by up to two orders of magnitude, and the number of qubits by a factor of three.

Process optimization and energy analysis of vacuum degasifier systems for the simultaneous removal of dissolved methane and hydrogen sulfide from anaerobically treated wastewater.

The control of dissolved methane (CH4) and hydrogen sulfide (H2S) emissions in anaerobic effluents is essential for minimizing the environmental implications of greenhouse gases, odor, and carbon footprint, as well as for preventing energy loss in the form of unrecovered dissolved methane. This study assessed the feasibility of a vacuum degasifier for the removal of CH4 and H2S from staged anaerobic fluidized membrane bioreactor (SAF-MBR) effluent. The optimization results showed that the efficiency of the nozzle fitted degasifiers were superior to the media packed ones. In three-stage vacuum degasifiers at a -0.8 bar vacuum pressure, H2S removal was mostly pH dependent and 88% removal efficiency was achieved with an initial concentration of 13.6 mg/L. Methane removal was dependent primarily on the number of degasifier units, and approximately 94% efficiency was achieved in a three-stage degasifier. Energy balance analysis showed that energy production exceeded the system energy requirements with 0.05-0.07 kWh/m3 of surplus energy. These results provide deep insights into this new technology for simultaneous removal of dissolved CH4 and H2S, which can be referred for potential future applications.

Energy System Contributions and Physical Activity in Specific Age Groups during Exergames.

Exergames have been recommended as alternative ways to increase the health benefits of physical exercise. However, energy system contributions (phosphagen, glycolytic, and oxidative) of exergames in specific age groups remain unclear. The purpose of this study was to investigate the contributions of three energy systems and metabolic profiles in specific age groups during exergames. Seventy-four healthy males and females participated in this study (older adults, n = 26: Age of 75.4 ± 4.4 years, body mass of 59.4 ± 8.7 kg, height of 157.2 ± 8.6 cm; adults, n = 24: Age of 27.8 ± 3.3 years, body mass of 73.4 ± 17.8 kg, height of 170.9 ± 11.9 cm; and adolescents, n = 24: Age of 14 ± 0.8 years, body mass of 71.3 ± 11.5 kg, height of 173.3 ± 5.2 cm). To evaluate the demands of different energy systems, all participants engaged in exergames named Action-Racing. Exergames protocol comprised whole-body exercises such as standing, sitting, stopping, jumping, and arm swinging. During exergames, mean heart rate (HRmean), peak heart rate (HRpeak), mean oxygen uptake (VO2mean), peak oxygen uptake (VO2peak), peak lactate (Peak La-), difference in lactate (ΔLa-), phosphagen (WPCr), glycolytic (WLa-), oxidative (WAER), and total energy demands (WTotal) were analyzed. The contribution of the oxidative energy system was higher than that of the phosphagen or glycolytic energy system (65.9 ± 12% vs. 29.5 ± 11.1% or 4.6 ± 3.3%, both p < 0.001). The contributions of the total energy demands and oxidative system in older adults were significantly lower than those in adults and adolescents (72.1 ± 28 kJ, p = 0.028; 70.3 ± 24.1 kJ, p = 0.024, respectively). The oxidative energy system was predominantly used for exergames applied in the current study. In addition, total metabolic work in older adults was lower than that in adolescents and adults. This was due to a decrease in the oxidative energy system. For future studies, quantification of intensity and volume is needed to optimize exergames. Such an approach plays a crucial role in encouraging physical activity in limited spaces.

Design of Reconfigurable Time-to-Digital Converter Based on Cascaded Time Interpolators for Electrical Impedance Spectroscopy.

This paper presents a reconfigurable time-to-digital converter (TDC) used to quantize the phase of the impedance in electrical impedance spectroscopy (EIS). The TDC in the EIS system must handle a wide input-time range for analysis in the low-frequency range and have a high resolution for analysis in the high-frequency range. The proposed TDC adopts a coarse counter to support a wide input-time range and cascaded time interpolators to improve the time resolution in the high-frequency analysis without increasing the counting clock speed. When the same large interpolation factor is adopted, the cascaded time interpolators have shorter measurement time and smaller chip area than a single-stage time interpolator. A reconfigurable time interpolation factor is adopted to maintain the phase resolution with reasonable measurement time. The fabricated TDC has a peak-to-peak phase error of less than 0.72° over the input frequency range from 1 kHz to 512 kHz and the phase error of less than 2.70° when the range is extended to 2.048 MHz, which demonstrates a competitive performance when compared with previously reported designs.

Effects of sodium hypochlorite concentration on the methanogenic activity in an anaerobic fluidized membrane bioreactor.

The effect of membrane cleaning chemical, NaOCl on specific acetoclastic methanogenic activity (SAMA) of biomass in the anaerobic fluidized membrane bioreactors (AFMBRs) was assessed. Granular activated carbon (GAC) was used as a fluidizing media in the AFMBR to provide membrane scouring effect and surface for biofilm attachment. Effect of NaOCl on methane production was negligible for GAC with biofilm (bGAC) samples up to 150 mg NaOCl/g VSS, but was significant for the bulk liquid samples with noticeable lag period over 300 h even at the dosage of 50 mg NaOCl/g VSS. The toxicity of NaOCl on methane production was reduced in samples with virgin GAC (vGAC) by allowing 14 days of biomass buildup period prior to NaOCl addition, although the vGAC alone did not alleviate the toxicity. The results revealed that NaOCl concentrations beyond 100 mg/L within the reactor inhibited methanogenic activity and the effects were more pronounced on suspended biomass than the immobilized biomass on GAC.

Evaluation of Porcine Hybrid Bone Block for Bone Grafting in Dentistry.

BACKGROUND/AIM: The purpose of this study was to develop hybrid bone blocks using porcine-derived collagen and low crystalline porcine-derived hydroxyapatite to overcome the disadvantages of commonly used bone grafts in dentistry. MATERIALS AND METHODS: Collagen was added to hydroxyapatite particles to increase the spatial integration of particulate bone grafts. Physicochemical examination and in vivo tests were performed to analyze scaffold's characteristics and evaluate bone regeneration. RESULTS: Porcine hybrid bone block had an irregular and interconnecting macroporous structure that was adequate for bone regeneration and bone ingrowth, and showed a good space-occupying ability to become well positioned. In addition, it showed higher angiogenesis and biodegradability than Bio-Oss Collagen®, a commercialized bone graft used in dental clinics. CONCLUSION: Our results suggest that improved collagen hybrid bone block can be generated when porcine cancellous bone particles and collagen were reasonably mixed. This hybrid bone block was easy in handling had flexibility, good biodegradability and provided bone regeneration.

Interfacial chemical bonding-mediated ionic resistive switching.

In this paper, we present a unique resistive switching (RS) mechanism study of Pt/TiO2/Pt cell, one of the most widely studied RS system, by focusing on the role of interfacial bonding at the active TiO2-Pt interface, as opposed to a physico-chemical change within the RS film. This study was enabled by the use of a non-conventional scanning probe-based setup. The nanoscale cell is formed by bringing a Pt/TiO2-coated atomic force microscope tip into contact with a flat substrate coated with Pt. The study reveals that electrical resistance and interfacial bonding status are highly coupled together. An oxygen-mediated chemical bonding at the active interface between TiO2 and Pt is a necessary condition for a non-polar low-resistance state, and a reset switching process disconnects the chemical bonding. Bipolar switching mode did not involve the chemical bonding. The nature of chemical bonding at the TiO2-metal interface is further studied by density functional theory calculations.

Effects of FeCl3 addition on the operation of a staged anaerobic fluidized membrane bioreactor (SAF-MBR).

The effects on sulfur removal and membrane fouling resulting from FeCl(3) addition to an anaerobic fluidized membrane bioreactor (AFMBR) in a staged AFMBR (SAF-MBR) was investigated. Total sulfur removal in the SAF-MBR was 42-59% without FeCl(3) addition, but increased to 87-95% with FeCl(3) addition. Sulfide removal in the AFMBR increased to 90% with addition of FeCl(3) at a molar Fe(3+)/S ratio of 0.54 and to 95% when the ratio was increased to 0.95. Effluent sulfide concentration then decreased to 0.3-0.6 mg/L. Phosphate removals were only 19 and 37% with the above added FeCl(3) ratios, indicating that iron removed sulfide more readily than phosphate. Neither chemical oxygen demand nor biochemical oxygen demand removal efficiencies were affected by the addition of FeCl(3). When the AFMBR permeate became exposed to air, light brown particles were formed from effluent Fe(2+) oxidation to Fe(3+). FeCl(3) addition, while beneficial for sulfide removal, did increase the membrane fouling rate due to the deposition of inorganic precipitates in the membrane pores.

GPU-accelerated 3D mipmap for real-time visualization of ultrasound volume data.

Ultrasound volume rendering is an efficient method for visualizing the shape of fetuses in obstetrics and gynecology. However, in order to obtain high-quality ultrasound volume rendering, noise removal and coordinates conversion are essential prerequisites. Ultrasound data needs to undergo a noise filtering process; otherwise, artifacts and speckle noise cause quality degradation in the final images. Several two-dimensional (2D) noise filtering methods have been used to reduce this noise. However, these 2D filtering methods ignore relevant information in-between adjacent 2D-scanned images. Although three-dimensional (3D) noise filtering methods are used, they require more processing time than 2D-based methods. In addition, the sampling position in the ultrasonic volume rendering process has to be transformed between conical ultrasound coordinates and Cartesian coordinates. We propose a 3D-mipmap-based noise reduction method that uses graphics hardware, as a typical 3D mipmap requires less time to be generated and less storage capacity. In our method, we compare the density values of the corresponding points on consecutive mipmap levels and find the noise area using the difference in the density values. We also provide a noise detector for adaptively selecting the mipmap level using the difference of two mipmap levels. Our method can visualize 3D ultrasound data in real time with 3D noise filtering.

First-principles study of the nano-scaling effect on the electrochemical behavior in LiNi(0.5)Mn(1.5)O4.

Nano-scaling of electrode materials is often used in battery applications to enhance performance, particularly relating to rate capability. However, for the high-voltage spinel LiNi0.5Mn1.5O4 conflicting results have been reported on the benefits of nano-scaling. In this study, we present first-principles calculations to investigate the effect of nano-scaling on LiNi0.5Mn1.5O4, specifically focusing on the roles and coupling between surface stability, cation ordering and phase behavior. We calculate and compare the surface energy for the low index facets (100), (110), and (111), and find that the most stable facet is dependent on the cation ordering at the surface layer. In this context, we predict a spontaneous surface reconstruction in the cation-ordered structure which leads to a deviation from the perfect surface cation ordering and results in an enhanced accessibility to solid solution behavior as a function of Li content. Our results imply that nano-scaling will be more beneficial for the cation-ordered structure, as compared to the disordered structure where the solid solution region is already intrinsically accessible for a broad range of Li concentrations.

Li absorption and intercalation in single layer graphene and few layer graphene by first principles.

We present an exhaustive first-principles investigation of Li absorption and intercalation in single layer graphene and few layer graphene, as compared to bulk graphite. For single layer graphene, the cluster expansion method is used to systemically search for the lowest energy ionic configuration as a function of absorbed Li content. It is predicted that there exists no Li arrangement that stabilizes Li absorption on the surface of single layer graphene unless that surface includes defects. From this result follows that defect-poor single layer graphene exhibits significantly inferior capacity compared to bulk graphite. For few layer graphene, we calibrate a semiempirical potential to include the effect of van der Waals interactions, which is essential to account for the contribution of empty (no Li) gallery to the total energy. We identify and analyze the Li intercalation mechanisms in few layer graphene and map out the sequence in stable phases as we move from single layer graphene, through few layer, to bulk graphite.