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Double bituminous surface treatment (DBST) has been a widely utilized pavement maintenance material due to its capability to restore the surface roughness of existing pavement and provide a layer of protection against weathering, aging, and moisture. However, DBST is highly prone to aggregate loss at an early stage, which is a very common problem experienced by surface treatment. Therefore, to lessen the aggregate loss and prolong the service life of DBST, fiber additive can be incorporated to strengthen the adhesion between the asphalt emulsion and aggregates. This study investigated the performance of glass fiber-reinforced polymer-modified DBST against aggregate loss by conducting laboratory tests using typical DBST as the benchmark of the test results. Four laboratory tests were chosen to represent different loading applications on the surface of the pavement: the bitumen bond strength (BBS) test, the sweep test, the Hamburg wheel-track test (HWT test), and a one-third-scale model mobile load simulator (MMLS3) model. Furthermore, the curing time of the asphalt emulsion was considered in the BBS test and sweep test. Based on all results from the conducted laboratory tests, polymer-modified DBST with glass fiber reinforcement presented an increased resistance to aggregate loss compared with typical DBST. Moreover, it was found that a longer curing time of the asphalt emulsion, whether it was typical or modified, strengthened the surface treatment's resistance to aggregate loss. [ABSTRACT FROM AUTHOR]

Conventional treatments for allergic rhinitis (AR) exhibit insufficiency and long-term use-related side effects. Considering the reported anti-inflammatory and immunoregulatory effects of Bojungikgi-tang (BJIGT), we aimed to assess its efficacy on persistent AR (PAR). Patients with PAR were randomly assigned in a 1:1:1 ratio into high-dose BJIGT, standard-dose BJIGT, and placebo groups, followed by 1-week run-in and 4-week treatment periods. The primary outcome included the mean change in Total Nasal Symptom Score (TNSS), with secondary outcomes encompassing the Korean Allergic Rhinitis-Specific Quality of Life Questionnaire, biomarkers, overall assessment, TNSS by AR pattern identification, and the Sasang constitution. The mean TNSS change was more improved in the BJIGT group than in the placebo group; however, no statistically significant differences were observed. Additional interaction effect analysis revealed a statistically significant improvement in the high-dose BJIGT group compared with the placebo group from weeks 1–2 to weeks 3–4. Regarding secondary outcomes, the BJIGT group exhibited similar or improved results compared with the placebo group, showing no statistically significant differences. No serious adverse effects or clinically significant changes in safety assessments were observed. Given that this study validated clinical improvement and safety, it serves as potential groundwork for pertinent future studies. [ABSTRACT FROM AUTHOR]

This study addresses the imperative for enhancing asphalt mixtures tailored for rural pavements, focusing on optimizing RAP mixtures with styrene–butadiene–styrene (SBS)-modified asphalt binders incorporating petroleum resin and oil. Through systematic investigation, the study examines the impact of varying RAP content (25% and 50%) and two SBS-modified asphalt binder types (Type 1 and Type 2) on mechanical properties and sustainability. Laboratory tests reveal that the mix of 25% RAP + 75% Type 1 exhibits exceptional flexibility, evidenced by a high ductility value of 880 mm at 25 °C, enhancing pavement resilience. Conversely, the 50% RAP + 50% Type 2 mixture displays vulnerability to fatigue cracking, while 25% RAP + 75% Type 1 demonstrates superior resistance, with a fatigue vulnerability value of 1524 kPa. The Hamburg Wheel Tracking test highlights the influence of RAP content on rut depth, with the mix of 50% RAP + 50% Type 1 achieving the lowest rutting at 3.9 mm. Overlay test results show the mix of 25% RAP + 75% Type 2's resilience, with the lowest load reduction at 64.5%, while the mix of 50% RAP + 50% Type 1 exhibits substantial load reduction at 82.1%. Field tests unveil differences in pavement bearing capacities, with the mix of 25% RAP + 75% Type 2 demonstrating a remarkable elastic modulus of 58.5 MPa, indicating heightened bearing capacity. The investigation underscores the significant role of SBS-modified asphalt binders with incorporated petroleum resin and oil in enhancing fatigue resistance for sustainable rural pavements. [ABSTRACT FROM AUTHOR]

Cambodia's transportation sector has exhibited tremendous growth in the past decades together with its economic advancement. However, these improvements are only focused on the national and provincial roads, leaving the rural roads underdeveloped. A large percentage of the rural roads in Cambodia are unpaved while those paved roads are in deteriorated condition, making these rural roads prone to structural failure when subjected to heavy truck traffic and massive rainfall. Therefore, an innovative pavement material shall be used in the construction and rehabilitation of Cambodian rural roads. In this study, a composite pavement testbed consisting of a roller compacted cement (RCC) base layer and a modified double bituminous surface treatment (DBST), namely multi-layered bituminous surface treatment (MAST), was constructed in Cambodia and its performance was evaluated. To have a point of comparison, the testbed was divided into three sections with varying combinations of surface and base layer: (1) MAST surface with an RCC base, (2) MAST surface with an aggregate base, and (3) DBST surface with an aggregate base. Initially, a visual inspection was conducted to investigate the surface condition of the testbed. To assess the structural capacity, a light-falling weight deflectometer device was used. Meanwhile, the surface roughness was evaluated through the sand patch test. Lastly, the pass-by test was performed to quantify the noise level of the pavement. Based on the results, the proposed composite pavement performed significantly superior to the typical pavement in Cambodia, which is the third section. In summary, the composite pavement with MAST as the surface layer and RCC as the base layer was observed to be suitable for heavy truck traffic loading and the environmental conditions of Cambodia. [ABSTRACT FROM AUTHOR]

Considering the characteristics of coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS), we compared the clinical course and outcomes of patients with ARDS who received venovenous extracorporeal membrane oxygenation (VV ECMO) based on the etiology of ARDS. This retrospective single-center study included adult patients with severe ARDS necessitating VV ECMO during the COVID-19 pandemic. Among 45 patients who received VV ECMO, 21 presented with COVID-19. COVID-19 patients exhibited lower sequential organ failure assessment scores (9 [8–12.75] versus 8 [4–11.5], p = 0.033) but longer duration of VV ECMO support (10.5 days [3.25–29.25] versus 28 days [10.5–70.5] p = 0.018), which was accompanied by an weaning off rate from VV ECMO in 12/24 (50%) versus 12/21 (57.1%) and 28-day mortality in 9/24 [37.5%] versus 2/21 [9.5%] in non-COVID-19 and COVID-19 patients (p = 0.767, p = 0.040), respectively. Finally, in the adjusted Cox regression model for hospital mortality, the hazard ratio of COVID-19 was not significant (hazard ratio 0.350, 95% confidence interval 0.110–1.115, p = 0.076). Although the VV ECMO period was longer, COVID-19 did not significantly impact ECMO weaning off and mortality rates. Nonetheless, judicious patient selections based on risk factors should be followed. [ABSTRACT FROM AUTHOR]

We present a simple yet effective pipeline for absolute three-dimensional (3D) human pose estimation from two-dimensional (2D) joint keypoints, namely, the 2D-to-3D human pose lifting problem. Our method comprises two simple baseline networks, a 3D conversion function, and a correction network. The former two networks predict the root distance and the root-relative joint distance simultaneously. Given the input and predicted distances, the 3D conversion function recovers the absolute 3D pose, and the correction network reduces 3D pose noise caused by input uncertainties. Furthermore, to cope with input noise implicitly, we adopt a Siamese architecture that enforces the consistency of features between two training inputs, i.e., ground truth 2D joint keypoints and detected 2D joint keypoints. Finally, we experimentally validate the advantages of the proposed method and demonstrate its competitive performance over state-of-the-art absolute 2D-to-3D pose-lifting methods. [ABSTRACT FROM AUTHOR]

Cadmium (Cd), a harmful heavy metal, can lead to various pulmonary diseases, including chronic obstructive pulmonary disease (COPD), by inducing cytotoxicity and disturbing redox homeostasis. The aim of the present study was to investigate Cd-mediated cytotoxicity using human lung fibroblasts and the therapeutic potential of 3,3′-diindolylmethane (DIM). Cadmium significantly reduced the cell viability of human embryonic lung (HEL299) cells accompanied by enhanced oxidative stress as evidenced by the increased expression of autophagy-related proteins such as LC3B and p62. However, treatment with DIM significantly suppressed autophagic cell death in Cd-induced HEL299 fibroblasts. In addition, DIM induced antioxidant enzyme activity and decreased intracellular reactive oxygen species (ROS) levels in Cd-damaged HEL299 cells. This study suggests that DIM effectively suppressed Cd-induced lung fibroblast cell death through the upregulation of antioxidant systems and represents a potential agent for the prevention of various diseases related to Cd exposure. [ABSTRACT FROM AUTHOR]

Phosphate concentrations change continuously throughout hospitalization; however, it is unclear which available phosphate measures are most clinically important for predicting hospital mortality. Therefore, we investigated phosphate concentrations in association with hospital mortality following admission to the intensive care unit. We retrospectively enrolled all adult patients receiving mechanical ventilation. Phosphate concentrations were divided into three categories: initially measured phosphate (iP); maximum–minimum phosphate values (ΔP); and phosphate arithmetic average (Pmean). In total, 175 patients were enrolled. The hospital mortality rate was 32.6%, and the most common primary diagnosis was respiratory failure. In multivariable logistic regression analyses, the odds ratios for hospital mortality in association with ΔP and Pmean values were 1.56 and 2.13, respectively (p < 0.0001). According to the obtained receiver operating characteristic curve, ΔP (0.75) and Pmean (0.72) each showed a fair predictive power for hospital mortality. In evaluating relative risks, we found that higher concentrations of Pmean and ΔP were each associated with a higher hospital mortality. ΔP and Pmean values were significantly associated with hospital mortality in critically ill patients, compared to iP. These findings showed that throughout hospitalization, it is important to reduce phosphate level fluctuations and maintain appropriate phosphate concentrations through consistent monitoring and corrections. [ABSTRACT FROM AUTHOR]

In this paper, performance analysis of the cross-eye jamming effect under mechanical defects is dealt with. By using a numerical analysis-based approach, the performance analysis method proposed in this paper is closer to the not approximated empirical mean square difference (MSD) than the first-order Taylor approximation-based performance analysis method and the second-order Taylor approximation-based performance analysis method proposed in previous studies. In other words, the effects of amplitude ratio perturbation and phase difference perturbation on performance degradation are quantitatively analyzed. Note that the numerical integration is adopted to derive an analytic expression of the MSD. [ABSTRACT FROM AUTHOR]

Accurate circuit simulation reflecting physical and electrical stress is of importance in indium gallium zinc oxide (IGZO)-based flexible electronics. In particular, appropriate modeling of threshold voltage (VT) changes in different bias and bending conditions is required for reliability-aware simulation in both device and circuit levels. Here, we present SPICE compatible compact modeling of IGZO transistors and inverters having an atomic layer deposition (ALD) Al2O3 gate insulator on a polyethylene terephthalate (PET) substrate. Specifically, the modeling was performed to predict the behavior of the circuit using stretched exponential function (SEF) in a bending radius of 10 mm and operating voltages ranging between 4 and 8 V. The simulation results of the IGZO circuits matched well with the measured values in various operating conditions. It is expected that the proposed method can be applied to process improvement or circuit design by predicting the direct current (DC) and alternating current (AC) responses of flexible IGZO circuits. [ABSTRACT FROM AUTHOR]

The primary purposes of this study are to investigate the feasibility of electrochemical deposition treatment (EDT) as a comprehensive rehabilitation method for corrosion-induced deterioration in reinforced concrete with various severity levels, and to propose a guideline for the determination of critical factors to advance EDT. This study includes three experimental phases, each of which simulates the initiation (de-passivation), propagation (high corrosion activity), and acceleration (formation of a surface-breaking crack) periods of corrosion-induced deterioration. After completion of a series of accelerated corrosion tests, damaged concrete samples with different severity levels are rehabilitated by a series of EDT processes using a MgCl2 solution in an electrolyte. The main variables for this experiment are the concentration levels (0, 0.3, 1.0 and 3.0 M) of a MgCl2 solution for test phase 1, charging time (0, 2, and 7 days) in EDT for test phase 2, and configuration of pre- and post-treatment processes in EDT for test phase 3. The rehabilitation performance of EDT is evaluated by analyzing the AC impedance properties of the steel-and-concrete interface using electrochemical impedance spectroscopy (EIS) for the test phases 1 and 2, and microscopic alternation in concrete cracks using optical microscopic image and SEM/EDX. It is demonstrated that EDT is an effective method for preventing and mitigating corrosion-induced deterioration in the initiation and rust propagation periods of corrosion and for repairing (closing and filling) a corrosion-induced surface-breaking crack in the acceleration phase of corrosion. Corrosion-resistant performance of concrete increases as the concentration levels of a MgCl2 solution in an electrolyte increases and as the charging time in EDT increases. In addition, a post-treatment process (applying a NaOH solution) after the electrochemical deposition process significantly improves crack-repairing performance of EDT. [ABSTRACT FROM AUTHOR]

High-flow nasal cannula (HFNC) therapy is commonly used to prevent reintubation after planned extubation. In clinical practice, there are no appropriate tools to evaluate whether HFNC therapy was successful or failed after planned extubation. In this retrospective observational study, we investigated whether the use of the ROX index was appropriate to differentiate between HFNC success and failure within 72 h after extubation and to develop an integrated model including the ROX index to improve the prediction of HFNC success in patients receiving HFNC therapy after planned extubation. Of 276 patients, 50 patients (18.1%) were reintubated within 72 h of extubation. ROX index values of >8.7 at 2 h, >8.7 at 6 h, and >10.4 at 12 h after HFNC therapy were all meaningful predictors of HFNC success in extubated patients. In addition, the integrated model including the ROX index had a better predictive capability for HFNC success than the ROX index alone. In conclusion, the ROX index at 2, 6, and 12 h could be applied to extubated patients to predict HFNC success after planned extubation. To improve its predictive power, we should also consider an integrated model consisting of the ROX index, sex, body mass index, and the total duration of ventilator care. [ABSTRACT FROM AUTHOR]

Cross-eye gain in cross-eye jamming systems is highly dependent on amplitude ratio and the phase difference between jammer antennas. It is well known that cross-eye jamming is most effective for the amplitude ratio of unity and phase difference of 180 degrees. It is assumed that the instabilities in the amplitude ratio and phase difference can be modeled as zero-mean Gaussian random variables. In this paper, we not only quantitatively analyze the effect of amplitude ratio instability and phase difference instability on performance degradation in terms of reduction in cross-eye gain but also proceed with analytical performance analysis based on the first order and second-order Taylor expansion. [ABSTRACT FROM AUTHOR]

Porous IrO2/Ti/IrO2 catalyst electrodes were obtained by coating IrO2 on both sides of three types of porous Ti powder sheets (sample 1, sample 2, and sample 3) using different surface treatment methods, and a hydrogen evolution catalyst electrode was obtained by coating Pt/C on carbon gas diffusion layers. A Nafion115 membrane was used as an electrolyte for the membrane electrode assemblies (MEA). Water electrolysis was investigated at cell temperatures up to 150 °C, and the electrical characteristics of the three types of porous IrO2/Ti/IrO2 catalyst electrodes were investigated. The sheet resistance of sample 1 was higher than those of samples 2 and 3, although during water electrolysis, a high current density was observed due to the nanostructure of the IrO2 catalyst. In addition, the structural stabilities of Nafion and Aquivion membranes up to 150 °C were investigated by using small angle X-ray scattering (SAXS). The polymer structures of Nafion and Aquivion membranes were stable up to 80 °C, whereas the crystalline domains grew significantly above 120 °C. In other words, the initial polymer structure did not recover after the sample was heated above the glass transition temperature. [ABSTRACT FROM AUTHOR]

The electrochemical performance of modified natural graphite (MNG) and artificial graphite (AG) was investigated as a function of electrode density ranging from 1.55 to 1.7 g∙cm−3. The best performance was obtained at 1.55 g∙cm−3 and 1.60 g∙cm−3 for the AG and MNG electrodes, respectively. Both AG, at a density of 1.55 g∙cm−3, and MNG, at a density of 1.60 g∙cm−3, showed quite similar performance with regard to cycling stability and coulombic efficiency during cycling at 30 and 45 °C, while the MNG electrodes at a density of 1.60 g∙cm−3 and 1.7 g∙cm−3 showed better rate performance than the AG electrodes at a density of 1.55 g∙cm−3. The superior rate capability of MNG electrodes can be explained by the following effects: first, their spherical morphology and higher electrode density led to enhanced electrical conductivity. Second, for the MNG sample, favorable electrode tortuosity was retained and thus Li+ transport in the electrode pore was not significantly affected, even at high electrode densities of 1.60 g∙cm−3 and 1.7 g∙cm−3. MNG electrodes also exhibited a similar electrochemical swelling behavior to the AG electrodes. [ABSTRACT FROM AUTHOR]

In this study, we analyzed the threshold voltage shift characteristics of bottom-gate amorphous indium-gallium-zinc-oxide (IGZO) thin-film transistors (TFTs) under a wide range of positive stress voltages. We investigated four mechanisms: electron trapping at the gate insulator layer by a vertical electric field, electron trapping at the drain-side GI layer by hot-carrier injection, hole trapping at the source-side etch-stop layer by impact ionization, and donor-like state creation in the drain-side IGZO layer by a lateral electric field. To accurately analyze each mechanism, the local threshold voltages of the source and drain sides were measured by forward and reverse read-out. By using contour maps of the threshold voltage shift, we investigated which mechanism was dominant in various gate and drain stress voltage pairs. In addition, we investigated the effect of the oxygen content of the IGZO layer on the positive stress-induced threshold voltage shift. For oxygen-rich devices and oxygen-poor devices, the threshold voltage shift as well as the change in the density of states were analyzed. [ABSTRACT FROM AUTHOR]

Home and ambulatory blood pressure (BP) measurements are recommended for the diagnosis of hypertension. However, the clinical characteristics of individuals showing a diagnostic disagreement between their home and ambulatory BP measurements are unclear. Of the 470 individuals who were not on antihypertensive drug treatment with a BP ≥140/90 mmHg at an outpatient clinic, 399 who had valid office, home, and ambulatory BP results were included. Hypertension was diagnosed based on an average home BP ≥135/85 mmHg and/or an average daytime ambulatory BP ≥135/85 mmHg. The participants were divided into three groups: Agree-NT (home and ambulatory BP normotension), Disagree (home BP normotension and ambulatory BP hypertension, or home BP normotension and ambulatory BP hypertension), and Agree-HT (home and ambulatory BP hypertension). Eighty-four individuals (21.1%) were classified as the Disagree group. The mean serum creatinine, triglycerides, and electrocardiogram voltage in the Disagree group were intermediate between those observed in the Agree-NT and the Agree-HT group. In the Disagree group, the mean levels of office and home diastolic BP, all of the components of ambulatory BP, the aortic systolic BP, and the BP variabilities were found to be intermediate between those of the Agree-NT and the Agree-HT groups. These results indicate that individuals showing a diagnostic disagreement between their home and ambulatory BP may have cardiovascular risks that are intermediate between those with sustained home and ambulatory normotension and hypertension. [ABSTRACT FROM AUTHOR]

A crosslinked sulfonated polyphenylsulfone (CSPPSU) polymer and polyvinyl alcohol (PVA) were thermally crosslinked; then, a CSPPSU-vinylon membrane was synthesized using a formalization reaction. Its use as an electrolyte membrane for fuel cells was investigated. PVA was synthesized from polyvinyl acetate (PVAc), using a saponification reaction. The CSPPSU-vinylon membrane was synthesized by the addition of PVA (5 wt%, 10 wt%, 20 wt%), and its chemical, mechanical, conductivity, and fuel cell properties were studied. The conductivity of the CSPPSU-10vinylon membrane is higher than that of the CSPPSU membrane, and a conductivity of 66 mS/cm was obtained at 120 °C and 90% RH (relative humidity). From a fuel cell evaluation at 80 °C, the CSPPSU-10vinylon membrane has a higher current density than CSPPSU and Nafion212 membranes, in both high (100% RH) and low humidification (60% RH). By using a CSPPSU-vinylon membrane instead of a CSPPSU membrane, the conductivity and fuel cell performance improved. [ABSTRACT FROM AUTHOR]

Sulfonated polyphenylsulfone (SPPSU) with a high ion exchange capacity (IEC) was synthesized using commercially available polyphenylsulfone (PPSU), and a large-area (16 × 18 cm2) crosslinked sulfonated polyphenylsulfone (CSPPSU) membrane was prepared. In addition, we developed an activation process in which the membrane was treated with alkaline and acidic solutions to remove sulfur dioxide (SO2), which forms as a byproduct during heat treatment. CSPPSU membranes obtained using this activation method had high thermal, mechanical and chemical stabilities. In I-ViR free studies for fuel cell evaluation, high performances similar to those using Nafion were obtained. In addition, from the hydrogen (H2) gas crossover characteristics, the durability is much better than that of a Nafion212 membrane. In the studies evaluating the long-term stabilities by using a constant current method, a stability of 4000 h was obtained for the first time. These results indicate that the CSPPSU membrane obtained by using our activation method is promising as a polymer electrolyte membrane. [ABSTRACT FROM AUTHOR]

The primary objective of the present work is to measure the corrosion rate of reinforcing steel embedded in concrete structures in a simulated marine environment of high chloride concentration. The selection of a single frequency that corresponds to the solution resistance and single frequency that corresponds to the charge transfer resistance were performed and measurements were carried out in a relatively faster time. A total of seven cement mortar specimens were prepared. The effect of varying cover thickness (5–50 mm) and rebar distance (10–80 mm) on the electrical resistance of the concrete and corrosion rate of the steel was examined. To simulate the corrosion of reinforced concrete in a marine environment, cement mortars were exposed to 25 wet–dry cycles that involve an immersion for 8 h in 3 wt.% NaCl solution and drying time of 16 h under room temperature. Alternative current (AC) impedance measurements were carried out within a frequency range from 100 kHz to 1 mHz. Results show that the formation of rust layers on rebars has caused a significant decrease in the maximum phase shift to θ = −30°. An accelerated corrosion rate of the rebars was observed during drying stage. [ABSTRACT FROM AUTHOR]

Recently, video frame interpolation research developed with a convolutional neural network has shown remarkable results. However, these methods demand huge amounts of memory and run time for high-resolution videos, and are unable to process a 4K frame in a single pass. In this paper, we propose a fast 4K video frame interpolation method, based upon a multi-scale optical flow reconstruction scheme. The proposed method predicts low resolution bi-directional optical flow, and reconstructs it into high resolution. We also proposed consistency and multi-scale smoothness loss to enhance the quality of the predicted optical flow. Furthermore, we use adversarial loss to make the interpolated frame more seamless and natural. We demonstrated that the proposed method outperforms the existing state-of-the-art methods in quantitative evaluation, while it runs up to 4.39× faster than those methods for 4K videos. [ABSTRACT FROM AUTHOR]

The high abundance of mitochondria and the expression of mitochondrial uncoupling protein 1 (UCP1) confer upon brown adipose tissue (BAT) the unique capacity to convert chemical energy into heat at the expense of ATP synthesis. It was long believed that BAT is present only in infants, and so, it was not considered as a potential therapeutic target for metabolic syndrome; however, the discovery of metabolically active BAT in adult humans has re-stimulated interest in the contributions of BAT metabolic regulation and dysfunction to health and disease. Here we demonstrate that brown adipocyte autophagy plays a critical role in the regulation BAT activity and systemic energy metabolism. Mice deficient in brown adipocyte autophagy due to BAT-specific deletion of Atg7—a gene essential for autophagosome generation—maintained higher mitochondrial content due to suppression of mitochondrial clearance and exhibited improved insulin sensitivity and energy metabolism. Autophagy was upregulated in BAT of older mice compared to younger mice, suggesting its involvement in the age-dependent decline of BAT activity and metabolic rate. These findings suggest that brown adipocyte autophagy plays a crucial role in metabolism and that targeting this pathway may be a potential therapeutic strategy for metabolic syndrome. [ABSTRACT FROM AUTHOR]

Visual quality and algorithm efficiency are two main interests in video frame interpolation. We propose a hybrid task-based convolutional neural network for fast and accurate frame interpolation of 4K videos. The proposed method synthesizes low-resolution frames, then reconstructs high-resolution frames in a coarse-to-fine fashion. We also propose edge loss, to preserve high-frequency information and make the synthesized frames look sharper. Experimental results show that the proposed method achieves state-of-the-art performance and performs 2.69x faster than the existing methods that are operable for 4K videos, while maintaining comparable visual and quantitative quality. [ABSTRACT FROM AUTHOR]

The current study was designed to compare in vivo efficacy between beeswax alcohol (BWA) and coenzyme Q 10 (CoQ 10 ) to treat fatty liver changes, oxidative stress, and damages in major organs of zebrafish by 12 weeks with high-cholesterol (HC) and galactose (Gal) supplementation. At week 12, the HC control and HC+Gal control groups showed 96% and 92% survivability, respectively, while co-supplementation of the 0.5% BWA and 1.0% BWA groups exhibited 96% and 100% survivability. However, co-supplementation of the 0.5% CoQ 10 and 1.0% CoQ 10 groups revealed the lowest survivability, around 92% and 89%, respectively. The 0.5% BWA and 1.0% BWA groups showed 21% ( p < 0.001) and 41% ( p < 0.001), respectively, lower total cholesterol (TC) than the HC+Gal control, while the 1.0% CoQ 10 group showed only 15% lower TC than the control. Interestingly, the 0.5% BWA and 1.0% BWA groups showed 22% ( p < 0.001) and 38% ( p < 0.001), respectively, lower triglyceride (TG) than the HC+Gal control. However, both the 0.5% CoQ 10 and 1.0% CoQ 10 groups showed similar TG levels as the control, suggesting that CoQ 10 supplementation had no effect on lowering serum TG. The 1.0% BWA group showed the highest plasma HDL-C and HDL-C/TC (%) up to 3.2-fold and 5.5-fold, respectively, higher than those of the HC+Gal control, while the 1.0% CoQ 10 group showed 2.4-fold and 2.8-fold higher plasma HDL-C and HDL-C/TC (%), respectively, than the control. The plasma aspartate transaminase (AST) and alanine transaminase (ALT) levels were lowest in the 1.0% BWA group, 51% and 72%, respectively, lower than HC+Gal control, suggesting the lowest extent of hepatic damage. In hepatic tissue, neutrophil infiltration and interleukin (IL)-6 production were the lowest in the 1.0% BWA group, around 67% and 85%, respectively, lower than the HC+Gal control. Fatty liver change, cellular apoptosis, and cell senescence in hepatic tissue were remarkably lowered in the 1.0% BWA group, while the CoQ 10 group showed much less effect than the BWA group. In kidney, ovary, and testis tissue, the 1.0% BWA group showed the lowest production of reactive oxygen species, the extent of cellular senescence, and cellular apoptosis with the healthiest cell morphology. In conclusion, supplementation of BWA remarkably protected the liver, kidney, ovary, and testis from oxidative damage by cholesterol and galactose consumption, with the least serum AST and ALT levels, inflammatory parameters, and senescence markers.

Natural products with high antioxidant activity are considered as innovative prevention strategies to effectively prevent age-related macular degeneration (AMD) in the early stage because the generation of reactive oxygen species (ROS) leading to the development of drusen is reported as an important cause of this disease. To investigate the prevention effects of the methanol extracts of Euphorbia heterophylla L. (MEE) on AMD, its effects on the antioxidant activity, inflammatory response, apoptosis pathway, neovascularization, and retinal tissue degeneration were analyzed in N-retinylidene-N-retinylethanolamine (A2E)-landed spontaneously arising retinal pigment epithelia (ARPE)-19 cells and BALB/c mice after exposure to blue light (BL). The MEE contained 10 active components and showed high free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and nitric oxide (NO) radicals. The pretreatments of high-dose MEE remarkably suppressed the production of intracellular ROS (88.2%) and NO (25.2%) and enhanced (SOD) activity (84%) and the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) in A2E + BL-treated ARPE-19 cells compared to Vehicle-treated group. The activation of the inducible nitric oxide synthase (iNOS)-induced cyclooxygenase-2 (COX-2) mediated pathway, inflammasome activation, and expression of inflammatory cytokines was significantly inhibited in A2E + BL-treated ARPE-19 cells after the MEE pretreatment. The activation of the apoptosis pathway and increased expression of neovascular proteins (36% for matrix metalloproteinase (MMP)-9) were inhibited in the MEE pretreated groups compared to the Vehicle-treated group. Furthermore, the thickness of the whole retina (31%), outer nuclear layer (ONL), inner nuclear layer (INL), and photoreceptor layer (PL) were significantly increased by the MEE pretreatment of BALB/c mice with BL-induced retinal degeneration. Therefore, these results suggest that the MEE, with its high antioxidative activity, protects against BL-induced retinal degeneration through the regulation of the antioxidative system, inflammatory response, apoptosis, and neovascularization in the AMD mouse model.

Complement component 3 (C3) deficiency has recently been reported as one of the novel causes of constipation. To identify a unique gene specific to constipation caused by C3 deficiency, the total RNA extracted from the mid colon of C3 knockout (C3 KO) mice was hybridized to oligonucleotide microarrays, and the function of the candidate gene was verified in in vitro and in vivo models. C3 KO mice used for microarrays showed definite phenotypes of constipation. Overall, compared to the wild type (WT), 1237 genes were upregulated, and 1292 genes were downregulated in the C3 KO mice. Of these, the major genes included were lysine (K)-specific demethylase 5D ( KDM5D ), olfactory receptor 870 ( Olfr870 ), pancreatic lipase ( PNLIP ), and alkaline phosphatase intestinal ( ALPI ). Specifically, the ALPI gene was selected as a novel gene candidate based on alterations during loperamide (Lop)-induced constipation and intestinal bowel disease (IBD). The upregulation of ALPI expression treated with acetate recovered the expression level of mucin-related genes in primary epithelial cells of C3 KO mice as well as most phenotypes of constipation in C3 KO mice. These results indicate that ALPI plays an important role as the novel gene associated with C3 deficiency-induced constipation.

Recent studies have highlighted the potential of Mesenchymal Stem Cells (MSCs) as an alternative treatment for Alopecia Areata (AA) due to their immunosuppressive properties. While MSCs have shown promise in cell experiments, their effectiveness in vivo remains uncertain. This study aims to validate local administration of MSC therapy's efficacy in AA treatment through animal experiments. AA was induced through Interferon-gamma (IFN-γ) administration in mice, and MSC treatment (MSCT)'s effects were assessed visually and through tissue analysis. The MSC-treated group showed more hair regrowth compared to the control (CTL) group. MSCT notably reduced local inflammatory cytokines (JAK1, JAK2, STAT1, STAT3, IFN-γR, IL-1β, IL-16, IL-17α, and IL-18) in AA-induced mice's skin, but systemic cytokine levels remained unchanged. Furthermore, MSC treatment normalized the expression of Wnt/β-catenin signaling pathway genes (LEF1 and β-catenin) and growth factors (FGF7 and FGF2), which are crucial for hair cycle regulation. This study lays the groundwork for further exploring MSCs as a potential treatment for AA, but more research is needed to fully understand their therapeutic potential.

Policosanol is a blend of long-chain aliphatic alcohols (LCAAs) and is well-known for several health-beneficial activities; however, the functionality of policosanol varied substantially based on the composition of LCAAs. In this study, two distinct policosanols, Raydel ® (extracted from Cuban sugarcane wax) and BOC Sciences (extracted from Chinese sugarcane wax), were dietarily supplemented (0.1% w / w ) for 12 weeks in hyperlipidemic zebrafish to examine their influence on the blood lipid profile and functionality of the liver, kidney, and reproductive organs. The results demonstrated a noteworthy impact of both policosanols on preventing high-cholesterol diet (HCD, 4% w / w )-induced dyslipidemia by decreasing total cholesterol (TC) and triglyceride (TG) levels in the plasma. However, compared to BOC Sciences, the Raydel ® policosanol exhibited a significantly ( p < 0.05) higher efficacy in reducing HCD-induced TC and TG levels. A substantial effect was observed exclusively with the Raydel ® policosanol in mitigating HCD-impaired low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) levels. Hepatic histology and immunohistochemistry (IHC) analysis revealed the higher efficacy of Raydel ® policosanol over BOC Sciences policosanol to prevent HCD-provoked fatty liver changes, cellular senescence, oxidative stress, and interleukin (IL)-6 production. Consistently, a significantly higher effect of Raydel ® over BOC Sciences policosanol was observed on the protection of kidney, testis, and ovary morphology hampered by HCD consumption. In addition, Raydel ® policosanol exhibited a notably stronger effect (~2-fold, p < 0.05) on the egg-laying ability of the zebrafish compared to policosanol from BOC Sciences. Furthermore, Raydel ® policosanol plays a crucial role in improving embryo viability and mitigating developmental defects caused by the intake of an HCD. Conclusively, Raydel ® policosanol displayed a substantially higher efficacy over BOC Sciences policosanol to revert HCD-induced dyslipidemia, the functionality of vital organs, and the reproductive health of zebrafish.

Older Korean immigrants are one of the most understudied and marginalized Asian ethnic groups in the United States, despite their rapid population growth. Many older Korean immigrants encounter distinct challenges in assimilating into their new country as first-generation immigrants, including cultural conflict, language barriers, low economic status, and a lack of social support. These issues may be compounded for those who live alone, which is considered a negative factor in their mental and physical health. However, little is known about the correlates and health issues of older Korean immigrants living alone. This study's objective was to explore correlates and health issues among older Korean immigrants living alone. Based on established scoping review methodology five databases, CINAHL, PubMed, MEDLINE, SocINDEX, and Health Source Nursing/Academic Edition, were used to find relevant studies. Twelve articles were reviewed, and four major themes were identified as correlates and health issues among older Korean immigrants living alone in the United States: depression, changed family relationships, social interactions, and factors on general health and well-being. The findings have significant implications for healthcare professionals for understanding the unique culture, situation, and physical and psychosocial vulnerability of older Korean immigrants living alone.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder. While metformin has demonstrated the ability to inhibit cyst growth in animal models of ADPKD via activation of adenosine monophosphate-activated protein kinase (AMPK), its effectiveness in humans is limited due to its low potency. This study explored the impact of HL156A, a new and more potent AMPK activator, in a mouse model of ADPKD., Methods: To investigate whether HL156A inhibits the proliferation of renal cyst cells in ADPKD in vitro, exogenous human telomerase reverse transcriptase (hTERT)-immortalized renal cyst cells from ADPKD patients were treated with HL156A, and an MTT (dimethylthiazol-diphenyltetrazolium bromide) assay was performed. To assess the cyst-inhibitory effect of HL156A in vivo, we generated Pkd1 conditional knockout (KO) mice with aquaporin 2 (AQP2)-Cre, which selectively expresses Cre recombinase in the collecting duct. The effectiveness of HL156A in inhibiting cyst growth and improving renal function was confirmed by measuring the number of cysts and blood urea nitrogen (BUN) levels in the collecting duct-specific Pkd1 KO mice., Results: When cyst cells were treated with up to 20 µM of metformin or HL156A, HL156A reduced cell viability by 25% starting at a concentration of 5 µM, whereas metformin showed no effect. When AQP2-Cre male mice were crossed with Pkd1 flox/flox female mice, and when AQP2-Cre female mice were crossed with Pkd1 flox/flox male mice, the number of litters produced by both groups was comparable. In collecting duct-specific Pkd1 KO mice, HL156A was found to inhibit cyst growth, reducing both the number and size of cysts. Furthermore, it was confirmed that kidney function improved as HL156A treatment led to a reduction in elevated BUN levels. Lastly, it was observed that the increase in AMPK phosphorylation induced by HL156A decreased ERK phosphorylation and α-SMA expression., Conclusion: HL156A has potential as a drug that can restore kidney function in ADPKD patients by inhibiting cyst growth.

Recently, the need to develop a robust three-dimensional (3D) cell culture system that serves as a valuable in vitro tumor model has been emphasized. This system should closely mimic the tumor growth behaviors observed in vivo and replicate the key elements and characteristics of human tumors for the effective discovery and development of anti-tumor therapeutics. Therefore, in this study, we developed an effective 3D in vitro model of human prostate cancer (PC) using a marine collagen-based biomimetic 3D scaffold. The model displayed distinctive molecular profiles and cellular properties compared with those of the 2D PC cell culture. This was evidenced by (1) increased cell proliferation, migration, invasion, colony formation, and chemoresistance; (2) upregulated expression of crucial multidrug-resistance- and cancer-stemness-related genes; (3) heightened expression of key molecules associated with malignant progressions, such as epithelial-mesenchymal transition transcription factors, Notch, matrix metalloproteinases, and pluripotency biomarkers; (4) robust enrichment of prostate cancer stem cells (CSCs); and (5) enhanced expression of integrins. These results suggest that our 3D in vitro PC model has the potential to serve as a research platform for studying PC and prostate CSC biology, as well as for screening novel therapies targeting PC and prostate CSCs.

The chloroplast genome plays a crucial role in elucidating genetic diversity and phylogenetic relationships. Vitis vinifera L. (grapevine) is an economically important species, prompting exploration of wild genetic resources to enhance stress resilience. We meticulously assembled the chloroplast genomes of two Korean Vitis L. species, V. flexuosa Thunb. and V. amurensis Rupr., contributing valuable data to the Korea Crop Wild Relatives inventory. Through exhaustive specimen collection spanning diverse ecological niches across South Korea, we ensured comprehensive representation of genetic diversity. Our analysis, which included rigorous codon usage bias assessment and repeat analysis, provides valuable insights into amino acid preferences and facilitates the identification of potential molecular markers. The assembled chloroplast genomes were subjected to meticulous annotation, revealing divergence hotspots enriched with nucleotide diversity, thereby presenting promising candidates for DNA barcodes. Additionally, phylogenetic analysis reaffirmed intra-genus relationships and identified related crops, shedding light on evolutionary patterns within the genus. Comparative examination with chloroplast genomes of other crops uncovered conserved sequences and variable regions, offering critical insights into genetic evolution and adaptation. Our study advances the understanding of chloroplast genomes, genetic diversity, and phylogenetic relationships within Vitis species, thereby laying a foundation for enhancing grapevine genetic diversity and resilience to environmental challenges.

Policosanol is a mixture of long-chain aliphatic alcohols (LCAAs) derived from various plant and insect origins that are marketed by various companies with distinct formulations and brand names. Policosanols offer several beneficial effects to treat dyslipidemia and hypertension; however, a comprehensive functionality comparison of various policosanol brands has yet to be thoroughly explored. In the present study five distinct policosanol brands from different origins and countries, Raydel-policosanol, Australia (PCO1), Solgar-policosanol, USA (PCO2), NutrioneLife-monacosanol, South Korea (PCO3), Mothernest-policosanol, Australia (PCO4), and Peter & John-policosanol, New Zealand (PCO5) were compared via dietary supplementation (1% in diet, final wt / wt ) to zebrafish for six weeks to investigate their impact on survivability, blood lipid profile, and functionality of vital organs under the influence of a high-cholesterol diet (HCD, final 4%, wt / wt ). The results revealed that policosanol brands (PCO1-PCO5) had a substantial preventive effect against HCD-induced zebrafish body weight elevation and hyperlipidemia by alleviating total cholesterol (TC) and triglycerides (TG) in blood. Other than PCO3, all the brands significantly reduced the HCD's elevated low-density lipoprotein cholesterol (LDL-C). On the contrary, only PCO1 displayed a significant elevation in high-density lipoprotein cholesterol (HDL-C) level against the consumption of HCD. The divergent effect of PCO1-PCO5 against HCD-induced hepatic damage biomarkers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), was observed. PCO1, PCO2, and PCO4 efficiently curtailed the AST and ALT levels; however, PCO3 and PCO5 potentially aggravated the HCD's elevated plasma AST and ALT levels. Consistently, the hepatic histology outcome revealed the least effectiveness of PCO3 and PCO5 against HCD-induced liver damage. On the contrary, PCO1 exhibited a substantial hepatoprotective role by curtailing HCD-induced fatty liver changes, cellular senescent, reactive oxygen species (ROS), and interleukin-6 (IL-6) production. Likewise, the histological outcome from the kidney, testis, and ovary revealed the significant curative effect of PCO1 against the HCD-induced adverse effects. PCO2-PCO5 showed diverse and unequal results, with the least effective being PCO3, followed by PCO5 towards HCD-induced kidney, testis, and ovary damage. The multivariate interpretation based on principal component analysis (PCA) and hierarchical cluster analysis (HCA) validated the superiority of PCO1 over other policosanol brands against the clinical manifestation associated with HCD. Conclusively, different brands displayed distinct impacts against HCD-induced adverse effects, signifying the importance of policosanol formulation and the presence of aliphatic alcohols on the functionality of policosanol products.

Background and Objectives: Hip fracture surgery, which affects quality of life, can be a major challenge in geriatric populations. Although sarcopenia is known to be associated with postoperative outcomes, there are few studies on the association between sarcopenia and postoperative acute kidney injury (AKI) in this population. We investigated the association between sarcopenia and postoperative AKI in elderly patients following hip fracture surgery. Materials and Methods: We retrospectively reviewed the records of patients who underwent hip fracture surgery at our institution from March 2019 to December 2021. Patients under the age of 65, patients with no preoperative computed tomography (CT) scans and patients with inappropriate cross-sectional images for measurement were excluded. The psoas-lumbar vertebral index (PLVI), which is the ratio of the average area of both psoas muscles to the area of the fourth lumbar vertebral body, was measured from preoperative CT scans. Sarcopenia was defined as a PLVI within the lowest 25% for each sex, and patients were categorized into sarcopenic and nonsarcopenic groups. The occurrence of AKI was determined based on the serum creatinine level within postoperative day 7 using the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Univariate and multivariate logistic regression analyses were performed to evaluate the associations between clinical variables and the occurrence of AKI. Results: Among the 348 enrolled patients, 92 patients were excluded, and 256 patients were analyzed. The PLVI cutoff values for defining sarcopenia lower than 25% for male and female patients were 0.57 and 0.43, respectively. The overall incidence of AKI was 18.4% (47 patients), and AKI occurred more frequently in sarcopenic patients than in nonsarcopenic patients (29.7% vs. 14.6%, p = 0.007). According to the multivariate logistic regression, which included all variables with a p value < 0.05 in the univariate analysis and adjusted for age, body mass index (BMI) and American Society of Anesthesiologists (ASA) physical status, sarcopenia was revealed to be an independent predictor of postoperative AKI (odds ratio = 5.10, 95% confidence interval = 1.77-14.77; p = 0.003). Conclusions: Preoperative sarcopenia, which corresponds to the lowest quartile of PLVI values, is associated with postoperative AKI among elderly patients who underwent hip fracture surgery.

The present study compares sugarcane-wax purified policosanols sourced from Cuba (Raydel ® ) and China (BOC Sciences) and utilized following the synthesis of reconstituted high-density lipoproteins (rHDL). The two policosanols exhibited distinctly different ingredient ratios of long-chain aliphatic alcohols, particularly 1-octacosanol (C28) and 1-tetratriacotanol (C34). After synthesizing rHDL with apolipoprotein A-I (apoA-I), the two policosanols bound well with phospholipid and apoA-I to form the discoidal rHDL. Notably, rHDL-1, containing Cuban policosanol, displayed the largest particle diameter at approximately 78 ± 3 nm. In contrast, both control rHDL (rHDL-0) and rHDL containing Chinese policosanol (rHDL-2) exhibited smaller particles, with diameters of approximately 58 ± 3 nm and 61 ± 2 nm, respectively. Furthermore, rHDL-1 demonstrated enhanced anti-glycation activity, safeguarding apoA-I from degradation within HDL, and displayed the antioxidant ability to inhibit LDL oxidation. A microinjection of each rHDL into zebrafish embryos in the presence of carboxymethyllysine (CML) revealed rHDL-1 to have the strongest antioxidant activity with the highest embryo survivability and normal developmental morphology. Dermal application to recover the wound revealed rHDL-1 to have the highest wound-healing activity (75%) and survivability (92%) in the cutaneous wound area in the presence of CML. In adult zebrafish, injecting CML (250 μg) caused acute death and hyperinflammation, marked by heightened neutrophil infiltration and interleukin (IL)-6 production in liver. However, co-administering rHDL-1 notably increased survival (85%) and exhibited strong anti-inflammatory properties, reducing IL-6 production while improving the blood lipid profile. However, a co-injection of rHDL-2 resulted in the lowest survivability (47%) with more hepatic inflammation. In conclusion, Cuban policosanol (Raydel ® ) has more desirable properties for the in vitro synthesis of rHDL with stronger anti-glycation and antioxidant activities than those of Chinese policosanol (BOC Sciences). Moreover, Raydel-policosanol-integrated rHDL demonstrates a noteworthy effect on accelerated wound healing and robust anti-inflammatory properties, leading to increased survivability in zebrafish embryos and adults by effectively suppressing CML-induced hyperinflammation.

Royal jelly is a honeybee product with substantial pharmacological and health promotional activities. Nevertheless, the health implications associated with the prolonged dietary supplementation of royal jelly have yet to be elucidated extensively. Herein, 72 weeks of dietary supplementation of royal jelly at 5% and 10% ( w / w ) were investigated to assess the impact on zebrafish survivability, body weight, liver, testis, ovary functionality, and blood lipid profile. The results revealed no adverse effect of 72 weeks of royal jelly supplementation on zebrafish survivability. Conversely, a noteworthy enhancement in the zebrafish body weight was observed in royal-jelly-supplemented zebrafish in a concentration-dependent manner [5% and 10% ( w / w )]. Interestingly, female zebrafish were found to be more biased, with a significant 17% ( p < 0.001) and 23% ( p < 0.001) higher body weight enhancement after 72 weeks of consumption of 5% and 10% ( w / w ) royal jelly, compared to the male zebrafish. The histological outcome revealed no sign of hepatotoxicity; moreover, diminished reactive oxygen species (ROS) and apoptosis were observed in the hepatic tissue of the royal-jelly-supplemented group. Consistent with the histological outcomes, the liver function biomarkers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), exhibited a significant decrease of 1.9-fold ( p = 0.006) and 1.4-fold ( p = 0.003) in zebrafish supplemented with royal jelly compared to those on a normal diet (ND) and zebrafish given supplements. Also, no sign of ovary and testis-related toxicity was observed in the royal-jelly-supplemented group during the 72-week period. Furthermore, the 10% ( w / w ) royal-jelly-consuming zebrafish exhibited a notable 2.1-fold increase ( p = 0.018) in egg-laying ability compared to the ND-supplemented zebrafish. The 10% ( w / w ) royal jelly supplementation also effectively maintained the blood lipid profile by curtailing serum triglycerides (TG) and elevating high-density lipoprotein cholesterol (HDL-C). Conclusively, royal jelly dietary supplementation for a prolonged time found royal jelly to be safe to consume, to efficiently improve hepatic function, reproduction, and sexual health, and to augment the serum HDL-C level.

CIGB-258 is a 3 kDa altered peptide ligand from heat shock protein (HSP) 60 that exhibits anti-inflammatory activity against the acute toxicity of carboxymethyllysine (CML) with antioxidant and anti-glycation activities via protection of high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I). It is necessary to test a synergistic interaction between apoA-I and CIGB-258 in reconstituted high-density lipoproteins (rHDL). Several rHDLs were synthesized containing palmitoyloleoyl phosphatidylcholine (POPC), cholesterol, apoA-I, and CIGB-258 at molar ratios of 95:5:1:0, 95:5:1:0.1, 95:5:1:0.5, and 95:5:1:1 for rHDL-(1:0), rHDL-(1:0.1), rHDL-(1:0.5), and rHDL-(1:1), respectively. As the CIGB-258 content in rHDL was increased, the particle size of rHDL was 1.4-times higher than rHDL-(1:0) to rHDL-(1:1), from 60 nm to 83 nm, respectively. As the CIGB-258 content was increased, the rHDL showed the most resistance to isothermal denaturation by a urea treatment, and rHDL-(1:1) exhibited the highest structural stability and the strongest antioxidant ability against LDL oxidation. Co-treatment of rHDL-(1:0), rHDL-(1:0.5), and rHDL-(1:1) resulted in up to 10%, 24%, and 34% inhibition of HDL glycation, inhibition of HDL glycation, which was caused by the CML, with protection of apoA-I. Microinjection of each rHDL into zebrafish embryos in the presence of CML showed that a higher CIGB-258 content in rHDL was associated with higher survivability with the least inflammation and apoptosis. Furthermore, an intraperitoneal injection of rHDL and CML showed that a higher CIGB-258 content in rHDL was also associated with higher survivability of zebrafish and faster recovery of swimming ability. The rHDL-(1:1) group showed the lowest triglyceride, AST, and ALT serum levels with the least production of interleukin-6, oxidized product, and neutrophil infiltration in hepatic tissue. In conclusion, CIGB-258 could bind well to phospholipids and cholesterol to stabilize apoA-I in the rHDL structure against denaturation stress and larger particle sizes. The rHDL containing CIGB-258 enhanced the in vitro antioxidant ability against LDL oxidation, the anti-glycation activity to protect HDL, and the in vivo anti-inflammatory activity against CML toxicity in zebrafish adults and embryos. Overall, incorporating apoA-I and CIGB-258 in rHDL resulted in a synergistic interaction to enhance the structural and functional correlations in a dose-dependent manner of CIGB-258.

The current study compared three policosanols from Cuba (sugarcane, Raydel ® , policosanol (1), China (rice bran, Shaanxi, policosanol (2), and the USA (sugarcane, Lesstanol ® , policosanol (3) in the treatment of dyslipidemia and protection of the liver, ovary, and testis in hypercholesterolemic zebrafish. After twelve weeks of supplementation of each policosanol (PCO, final 0.1% in diet, w / w ) with a high cholesterol diet (HCD, final 4%, w / w ), the Raydel policosanol (PCO1) group showed the highest survivability, approximately 89%. In contrast, Shaanxi policosanol (PCO2) and Lesstanol policosanol (PCO3) produced 73% and 87% survivability, respectively, while the HCD alone group showed 75% survivability. In the 12th week, the PCO1 group demonstrated the most modest increase in body weight along with significantly lower levels of total cholesterol (TC) and triglycerides (TG) in comparison to the HCD control group. Additionally, the PCO1 group exhibited the highest proportion of high-density lipoprotein (HDL)-cholesterol within TC. Notably, the PCO1 group displayed the lowest level of aspartate aminotransferase and alanine aminotransferase, minimal infiltration of inflammatory cells, reduced interleukin (IL)-6 production in the liver, a notable decline in reactive oxygen species (ROS) generation and mitigated fatty liver changes. HCD supplementation induced impairment of kidney morphology with the greatest extent of ROS production and apoptosis. On the other hand, the PCO 1 group showed a remarkably improved morphology with the least ROS generation and apoptosis. Within the ovarian context, the PCO1 group exhibited the most substantial presence of mature vitellogenic oocytes, accompanied by minimal levels of ROS and apoptosis. Similarly, in the testicular domain, the PCO1 group showcased optimal morphology for spermatogenesis, characterized by the least interstitial area and diminished production of ROS in testicular cells. At week 8, the PCO1 group showed the highest egg-laying ability, with around 244 eggs produced per mating. In contrast, the HCD alone, PCO2, and PCO3 groups showed significantly lower egg-laying ability (49, 59, and 86 eggs, respectively). The embryos from the PCO1 group exhibited the highest survivability with the fastest swimming ability and developmental speed. These results suggest that PCO1 consumption significantly enhanced the reproduction system, egg-laying ability, and embryo survivability. In conclusion, among the three policosanols, Cuban (Raydel ® ) policosanol had the strongest effect on survivability, improving dyslipidemia, liver protection, kidney, ovary, and testis with a restoration of the cell morphology, and the least ROS production and apoptosis-induced by HCD supplementation.

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model. Immortalized human epidermal keratinocytes were transduced with a recombinant adenovirus expressing microRNA specific for WWOX to downregulate its expression. Inflammatory responses were detected using Western blotting, real-time quantitative reverse transcription polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay. In human epidermal keratinocytes, WWOX knockdown reduced nuclear factor-kappa B signaling and levels of proinflammatory cytokines induced by polyinosinic: polycytidylic acid [(poly(I:C)] in vitro. Furthermore, calcium chelator and protein kinase C (PKC) inhibitors significantly reduced poly(I:C)-induced inflammatory reactions. WWOX plays a role in the inflammatory reaction of epidermal keratinocytes by regulating calcium and PKC signaling. Targeting WWOX could be a novel therapeutic approach for psoriasis in the future.

The rapid growth of the elderly population is making the need for extensive and advanced information about age-related organ dysfunction a crucial research area. The kidney is one of the organs most affected by aging. Aged kidneys undergo functional decline, characterized by a reduction in kidney size, decreased glomerular filtration rate, alterations in renal blood flow, and increased inflammation and fibrosis. This review offers a foundation for understanding the functional and molecular mechanisms of aging kidneys and for selecting identifying appropriate targets for future treatments of age-related kidney issues.

Complement component 3 (C3) deficiency has recently been known as a cause of constipation, without studies on the therapeutic efficacy. To evaluate the therapeutic agents against C3-deficiency-induced constipation, improvements in the constipation-related parameters and the associated molecular mechanisms were examined in FVB/N-C3 em1Hlee /Korl knockout (C3 KO) mice treated with uridine (Urd) and the aqueous extract of Liriope platyphylla L. (AEtLP) with laxative activity. The stool parameters and gastrointestinal (GI) transit were increased in Urd- and AEtLP-treated C3 KO mice compared with the vehicle (Veh)-treated C3 KO mice. Urd and AEtLP treatment improved the histological structure, junctional complexes of the intestinal epithelial barrier (IEB), mucin secretion ability, and water retention capacity. Also, an improvement in the composition of neuronal cells, the regulation of excitatory function mediated via the 5-hydroxytryptamine (5-HT) receptors and muscarinic acetylcholine receptors (mAChRs), and the regulation of the inhibitory function mediated via the neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) were detected in the enteric nervous system (ENS) of Urd- and AEtLP-treated C3 KO mice. Therefore, the results of the present study suggest that C3-deficiency-induced constipation can improve with treatment with Urd and AEtLP via the regulation of the mucin secretion ability, water retention capacity, and ENS function.

Reconstituted high-density lipoproteins (rHDL) containing each policosanol from Cuba (Raydel ® ), China (Shaanxi Pioneer), and the United States (Lesstanol ® ) were synthesized to compare the physiological properties of policosanol depending on sources and origin countries. After synthesis with apolipoproteinA-I (apoA-I) into rHDL, all policosanols bound well with phospholipid and apoA-I to form discoidal rHDL. An rHDL containing Cuban policosanol (rHDL-1) showed the largest rHDL particle size of around 83 ± 3 nm, while rHDL containing Chinese policosanol (rHDL-2) or American policosanol (rHDL-3) showed smaller particles around 63 ± 3 nm and 60 ± 2 nm in diameter, respectively. The rHDL-1 showed the strongest anti-glycation activity to protect the apoA-I degradation of HDL from fructose-mediated glycation: approximately 2.7-times higher ability to suppress glycation and 1.4-times higher protection ability of apoA-I than that of rHDL-2 and rHDL-3. The rHDL-1 showed the highest antioxidant ability to inhibit cupric ion-mediated LDL oxidation in electromobility and the quantification of oxidized species. A microinjection of each rHDL into a zebrafish embryo in the presence of carboxymethyllysine (CML) showed that rHDL-1 displayed the strongest anti-oxidant activity with the highest embryo survivability, whereas rHDL-2 and rHDL-3 showed much weaker protection ability, similar to rHDL alone (rHDL-0). An intraperitoneal injection of CML (250 μg) into adult zebrafish caused acute death and hyperinflammation with an elevation of infiltration of neutrophils and IL-6 production in the liver. On the other hand, a co-injection of rHDL-1 resulted in the highest survivability and the strongest anti-inflammatory ability to suppress IL-6 production with an improvement of the blood lipid profile, such as elevation of HDL-C and lowering of the total cholesterol, LDL-cholesterol, and triglyceride. In conclusion, Cuban policosanol exhibited the most desirable properties for the in vitro synthesis of rHDL with the stabilization of apoA-I, the largest particle size, anti-glycation against fructation, and antioxidant activities to prevent LDL oxidation. Cuban policosanol in rHDL also exhibited the strongest in vivo antioxidant and anti-inflammatory activities with the highest survivability in zebrafish embryos and adults via the prevention of hyperinflammation in the presence of CML.

Many policosanols from different sources, such as sugar cane and rice bran, have been marketed worldwide to improve blood lipid profiles. But so far, no comparative study has commenced elucidating the effect of different policosanols to improve the blood lipid profile and other beneficial effects. This study compared the efficacy of four different policosanols, including one sugar cane wax alcohol from Cuba (Raydel ® ) and three policosanols from China (Xi'an Natural sugar cane, Xi'an Realin sugar cane, and Shaanxi rice bran), to treat dyslipidemia in hyperlipidemic zebrafish. After 12 weeks of consumption of each policosanol (final 0.1% in diet, wt/wt) and a high-cholesterol diet (HCD, final 4%, wt/wt), the Raydel policosanol group and the Xi'an Natural policosanol group showed the highest survivability, of approximately 81%. In contrast, the Xi'an Realin policosanol and the Shaanxi policosanol groups showed 57% and 67% survivability, respectively. Among the five HCD groups, the Raydel policosanol group showed the lowest serum total cholesterol (TC, p < 0.001 versus HCD control) and triglyceride ( p < 0.001 versus HCD control), with the highest percentage of high-density lipoproteins-cholesterol in TC. The Raydel policosanol group also showed the lowest serum aspartate aminotransferase and alanine aminotransferase levels, with the least infiltration of inflammatory cells and interleukin-6 production in hepatocytes with a marked reduction in reactive oxygen species (ROS) production and fatty liver changes. In the ovary, the Raydel policosanol group also showed the highest content of mature vitellogenic oocytes with the lowest production of reactive oxygen species and cellular apoptosis in ovarian cells. In the testes, the Raydel policosanol group also showed the healthiest morphology for spermatogenesis, with the lowest interstitial area and reactive oxygen species production in testicular cells. Conclusively, among the tested policosanols, Cuba (Raydel ® ) policosanol exhibited a comparatively better effect in maintaining zebrafish body weight, survivability, blood lipid profile, hepatic function biomarkers, fatty liver changes, ROS generation, inflammation, and restoration of the cell morphology in ovaries and testes affected by the HCD consumption.

Three-dimensional (3D) printed calcium phosphate cement (CPC) scaffolds are increasingly being used for bone tissue repair. Traditional materials used for CPC scaffolds, such as bovine and porcine bone, generally contain low amounts of calcium phosphate compounds, resulting in reduced production rates of CPC scaffolds. On the other hand, cockle shells contain more than 99% CaCO 3 in the form of amorphous aragonite with excellent biocompatibility, which is expected to increase the CPC production rate. In this study, 3D-printed cockle shell powder-based CPC (CSP-CPC) scaffolds were developed by the material extrusion method. Lactic acid and hyaluronic acid were used to promote the printability. The characterization of CSP-CPC scaffolds was performed using Fourier transform infrared spectra, X-ray diffraction patterns, and scanning electron microscopy. The biocompatibility of CSP-CPC scaffolds was evaluated using cell viability, Live/Dead, and alkaline phosphatase assays. In addition, CSP-CPC scaffolds were implanted into the mouse calvarial defect model to confirm bone regeneration. This study provides an opportunity to create high value added in fishing villages by recycling natural products from marine waste.

Background: Although knowledge of the genetic factors influencing kidney disease is increasing, epigenetic profiles, which are associated with chronic kidney disease (CKD), have not been fully elucidated. We sought to identify the DNA methylation status of CpG sites associated with reduced kidney function and examine whether the identified CpG sites are associated with CKD development., Method: We analyzed DNA methylation patterns of 440 participants in the Korean Genome and Epidemiology Study (KoGES) with estimated glomerular filtration rates (eGFRs) ≥ 60 mL/min/1.73 m 2 at baseline. CKD development was defined as a decrease in the eGFR of <60 at any time during an 8-year follow-up period ("CKD prediction" analysis). In addition, among the 440 participants, 49 participants who underwent a second methylation profiling were assessed for an association between a decline in kidney function and changes in the degree of methylation of CpG sites during the 8 years ("kidney function slope" analysis)., Results: In the CKD prediction analysis, methylation profiles of a total of 403,129 CpG sites were evaluated at baseline in 440 participants, and increased and decreased methylation of 268 and 189 CpG sites, respectively, were significantly correlated with the development of CKD in multivariable logistic regression. During kidney function slope analysis using follow-up methylation profiles of 49 participants, the percent methylation changes in 913 CpG sites showed a linear relationship with the percent change in eGFR during 8 years. During functional enrichment analyses for significant CpG sites found in the CKD prediction and kidney function slope analyses, we found that those CpG sites represented MAPK, PI3K/Akt, and Rap1 pathways. In addition, three CpG sites from three genes, NPHS2 , CHCHD4 , and AHR , were found to be significant in the CKD prediction analysis and related to a decline in kidney function., Conclusion: It is suggested that DNA methylation on specific genes is associated with the development of CKD and the deterioration of kidney function., Competing Interests: The authors declare no conflict of interest.

Acne vulgaris is a common skin disease characterized by increased sebum production, inflammation, and Cutibacterium acnes (CA: formerly Propionibacterium acnes ) hyperproliferation in pilosebaceous follicles. This study evaluated the efficacy of FRO, a formula composed of fermented Rhus verniciflua Stokes and Orostachys japonicus , against acne pathogenesis via antimicrobial assessment and an in vitro analysis. Stimulated model cells treated with hormones, CA, or lipopolysaccharide (LPS) were designed based on the characteristics of acne pathogenesis, including inflammation and sebum hypersecretion. High-performance liquid chromatography, disc diffusion, MTS, and western blotting assays were used to examine potential anti-acne effects. FRO was determined to contain phenolics such as gallic acid, fisetin, quercetin, and kaempferol. FRO exerted antimicrobial activity against CA and inhibited reactive oxygen species production that was otherwise increased by LPS or CA in HaCaT cells. Additionally, FRO exerted anti-inflammatory effects by inhibiting iNOS, TNF-α, IL-6, p-STAT-3, and p-NF-κB, which were previously upregulated by LPS or CA in THP-1 and HaCaT cells. FRO inhibited lipogenesis induced by steroid hormones and CA by decreasing FAS and SREBP-1 levels in sebocytes. Additionally, FRO down-regulated the androgen receptor, 5α-reductase, SREBP-1, and FAS levels, which were upregulated by steroid hormone in LNCaP cells. Taken together, our findings suggest that FRO alleviates acne by inhibiting the growth of CA, inflammation, and excess sebum and could be used for functional cosmetics or acne treatments.

Patients with diabetes must have self-efficacy to perform necessary self-care tasks. Self-efficacy has been considered as one of the primary motivators on diabetes self-care; therefore, it is essential for health care professionals to assess the self-efficacy of patients with diabetes to provide optimal care. Despite older Korean immigrants having greater difficulty in diabetes management, research on self-efficacy for them is lacking. This study aims to examine the psychometric property of the General Self-Efficacy scale Korean version for older Korean immigrants with diabetes in the United States. In this cross-sectional, methodological study, data were collected using convenience sampling. Cronbach's alpha, exploratory factor analysis, and confirmatory factor analysis were employed to examine the psychometric properties. Cronbach's alpha for the entire GSE scale Korean version is 0.81. The initial Eigenvalues show two factors, coping and confidence; however, the confirmatory factor analysis showed reasonable goodness of fit to the data ( χ 2 (35) = 86.24, p < 0.01), χ 2 / df ratio = 2.46, AGFI = 0.87, GFI = 0.91, IFI = 0.90, ECVI = 0.74, CFI = 0.89, and RMSEA = 0.093 in the one-factor model. The General Self-Efficacy scale Korean version demonstrated acceptable reliability and validity. It can be used to investigate self-efficacy and to devise culturally tailored diabetes interventions.

The purpose of this study is to derive an optimal drug release formulation with human clinical bioequivalence in developing a sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate fixed-dose combination (FDC) tablet as a treatment for type 2 diabetes mellitus. As a treatment for type 2 diabetes mellitus, the combined prescription of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is common. Therefore, this study simplified the number of individual drugs taken and improved drug compliance by developing FDC tablets containing sitagliptin phosphate monohydrate as a DPP-4 inhibitor and dapagliflozin propanediol hydrate as an SGLT-2 inhibitor. To derive the optimal dosage form, we prepared single-layer tablets, double-layer tablets, and dry-coated tablets and evaluated the drug control release ability, tableting manufacturability, quality, and stability. Single-layer tablets caused problems with stability and drug dissolution patterns. When the dissolution test was performed on the dry-coated tablets, a corning effect occurred, and the core tablet did not completely disintegrate. However, in the quality evaluation of the double-layer tablets, the hardness was 12-14 kilopond, the friability was 0.2%, and the disintegration was within 3 min. In addition, the stability test revealed that the double-layer tablet was stable for 9 months under room temperature storage conditions and 6 months under accelerated storage conditions. In the drug release test, only the FDC double-layer tablet showed the optimal drug release pattern that satisfied each drug release rate. In addition, the FDC double-layer tablet showed a high dissolution rate of over 80% in the form of immediate-release tablets within 30 min in a pH 6.8 dissolution solution. In the human clinical trial, we co-administered a single dose of a sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate FDC double-layered tablet and the reference drug (Forxiga ® , Januvia ® ) in healthy adult volunteers. This study showed clinically equivalent results in the stability and pharmacodynamic characteristics between the two groups.

Inflammation and atherosclerosis are intimately associated via the production of dysfunctional high-density lipoproteins (HDL) and modification of apolipoprotein (apo) A-I. A putative interaction between CIGB-258 and apoA-I was investigated to provide mechanistic insight into the protection of HDL. The protective activity of CIGB-258 was tested in the CML-mediated glycation of apoA-I. The in vivo anti-inflammatory efficacy was compared in paralyzed hyperlipidemic zebrafish and its embryo in the presence of CML. Treatment of CML induced greater glycation extent of HDL/apoA-I and proteolytic degradation of apoA-I. In the presence of CML, however, co-treatment of CIGB-258 inhibited the glycation of apoA-I and protected the degradation of apoA-I, exerting enhanced ferric ion reduction ability. Microinjection of CML (500 ng) into zebrafish embryos resulted in acute death with the lowest survivability with severe developmental defects with interleukin (IL)-6 production. Conversely, a co-injection of CIGB-258 or Tocilizumab produced the highest survivability with a normal development speed and morphology. In hyperlipidemic zebrafish, intraperitoneal injection of CML (500 μg) caused the complete loss of swimming ability and severe acute death with only 13% survivability 3 h post-injection. A co-injection of the CIGB-258 resulted in a 2.2-fold faster recovery of swimming ability than CML alone, with higher survivability of approximately 57%. These results suggest that CIGB-258 protected hyperlipidemic zebrafish from the acute neurotoxicity of CML. Histological analysis showed that the CIGB-258 group had 37% lower infiltration of neutrophils in hepatic tissue and 70% lower fatty liver changes than those of the CML-alone group. The CIGB-258 group exhibited the smallest IL-6 expression in the liver and the lowest blood triglyceride level. CIGB-258 displayed potent anti-inflammatory activity in hyperlipidemic zebrafish by inhibiting apoA-I glycation, promoting rapid recovery from the paralysis of CML toxicity and suppression of IL-6, and lowering fatty liver changes.