Efficacy and Safety of WCFA19 (Weissella confusa WIKIM51) in Reducing Body Fat in Overweight and Obese Adults.

Background: WCFA19 (Weissella confusa WIKIM51), found during the fermentation of kimchi, is known for its inhibitory effects on body weight and body fat. This study looked at the impact of WCFA19 isolated from dandelion kimchi on weight loss in overweight and obese adults that are otherwise healthy. Methods: This study was conducted as a multicenter, double-blind, randomized, placebo-controlled study with 104 overweight and obese subjects. Subjects were randomized evenly into the test group (WCFA19, 500 mg, n = 40) or control group (n = 34) for 12 weeks from 14 June 2021 to 24 December 2021. Effects were based on DEXA to measure changes in body fat mass and percentage. Results: Among the 74 subjects analyzed, WCFA19 oral supplementation for 12 weeks resulted in a significant decrease in body fat mass of 633.38 ± 1396.17 g (p = 0.0066) in overweight and obese individuals in the experimental group. The control group showed an increase of 59.10 ± 1120.57 g (p = 0.7604), indicating a statistically significant difference between the two groups. There was also a statistically significant difference (p = 0.0448) in the change in body fat percentage, with a decrease of 0.41 ± 1.22% (p = 0.0424) in the experimental group and an increase of 0.17 ± 1.21% (p = 0.4078) in the control group. No significant adverse events were reported. Conclusions: Oral supplementation of 500 mg of WCFA19 for 12 weeks is associated with a decrease in body weight, particularly in body fat mass and percentage.

Baf155 regulates skeletal muscle metabolism via HIF-1a signaling.

During exercise, skeletal muscle is exposed to a low oxygen condition, hypoxia. Under hypoxia, the transcription factor hypoxia-inducible factor-1α (HIF-1α) is stabilized and induces expressions of its target genes regulating glycolytic metabolism. Here, using a skeletal muscle-specific gene ablation mouse model, we show that Brg1/Brm-associated factor 155 (Baf155), a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, is essential for HIF-1α signaling in skeletal muscle. Muscle-specific ablation of Baf155 increases oxidative metabolism by reducing HIF-1α function, which accompanies the decreased lactate production during exercise. Furthermore, the augmented oxidation leads to high intramuscular adenosine triphosphate (ATP) level and results in the enhancement of endurance exercise capacity. Mechanistically, our chromatin immunoprecipitation (ChIP) analysis reveals that Baf155 modulates DNA-binding activity of HIF-1α to the promoters of its target genes. In addition, for this regulatory function, Baf155 requires a phospho-signal transducer and activator of transcription 3 (pSTAT3), which forms a coactivator complex with HIF-1α, to activate HIF-1α signaling. Our findings reveal the crucial role of Baf155 in energy metabolism of skeletal muscle and the interaction between Baf155 and hypoxia signaling.

Cerenkov luminescence imaging of interscapular brown adipose tissue using a TSPO-targeting PET probe in the UCP1 ThermoMouse.

Rationale: [18F]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) has been widely used as an imaging technique to measure interscapular brown adipose tissue (iBAT) activity. However, it is challenging to obtain iBAT-specific images using [18F]FDG-PET because increased uptake of [18F]FDG is observed in tumors, muscle, and inflamed tissues. Uncoupling protein 1 (UCP1) in the mitochondrial membrane, a well-known molecular marker of BAT, has been proposed as a useful BAT imaging marker. Recently, the UCP1 ThermoMouse was developed as a reporter mouse for monitoring UCP1 expression and investigating BAT activation. In addition, Translocator protein-18 kDa (TSPO) located in the outer mitochondrial membrane is also overexpressed in BAT, suggesting that TSPO-targeting PET has potential for iBAT imaging. However, there are no studies monitoring BAT using TSPO-targeting PET probes in the UCP1 ThermoMouse. Moreover, the non-invasive Cerenkov luminescence imaging (CLI) using Cerenkov radiation from the PET probe has been proposed as an alternative option for PET as it is less expensive and user-friendly. Therefore, we selected [18F]fm-PBR28-d 2 as a TSPO-targeting PET probe for iBAT imaging to evaluate the usefulness of CLI in the UCP1 ThermoMouse. Methods: UCP1 ThermoMouse was used to monitor UCP1 expression. Western blotting and immunohistochemistry were performed to measure the level of protein expression. [18F]fm-PBR28-d 2 and [18F]FDG were used as radioactive probes for iBAT imaging. PET images were acquired with SimPET, and optical images were acquired with IVIS 100. Results: UCP1 ThermoMouse showed that UCP1 and TSPO expressions were correlated in iBAT. In both PET and CLI, the TSPO-targeting probe [18F]fm-PBR28-d 2 was superior to [18F]FDG for acquiring iBAT images. The high molar activity of the probe was essential for CLI and PET imaging. We tested the feasibility of TSPO-targeting probe under cold exposure by imaging with TSPO-PET/CLI. Both signals of iBAT were clearly increased after cold stimulation. Under prolonged isoflurane anesthesia, TSPO-targeting images showed higher signals from iBAT in the short-term than in long-term groups. Conclusion: We demonstrated that TSPO-PET/CLI reflected UCP1 expression in iBAT imaging better than [18F]FDG-PET/CLI under the various conditions. Considering convenience and cost, TSPO-CLI could be used as an alternative TSPO-PET technique for iBAT imaging.

Supraparticle Engineering for Highly Dense Microspheres: Yttria-Stabilized Zirconia with Adjustable Micromechanical Properties.

Various supraparticles have been extensively studied owing to their excellent catalytic properties that are attributed to their inherent porous structure; however, their mechanical properties have not garnered attention owing to their less dense structure. We demonstrate a rational approach for fabricating assembled supraparticles and, subsequently, highly dense microspheres. In addition, 3 mol % yttria-stabilized zirconia (3YSZ) and alumina particles were selected as building blocks and assembled into higher-order architectures using a droplet-based template method (spray drying) for validation with proof-of-concept. Moreover, structural features such as density, size, sphericity, and morphology of supraparticles were controlled by adjusting the competing kinetics occurring between the assembly of building blocks and evaporation of the solvent in the droplets. The preparatory aqueous suspension and process parameters were optimized as well. A detailed understanding of the formation mechanism facilitated the yield of tailor-made supraparticles and, thereafter, highly dense microspheres (approximate relative density = 99%) with excellent sphericity (>98%) via heat treatment. The microspheres displayed highest hardness (26.77 GPa) and superior elastic modulus (210.19 GPa) compared with the mechanical properties of the 3YSZ samples reported to date. Ultimately, the proposed supraparticle engineering provided insight for controlling the structural features and resultant micromechanical properties, which widely extends the applicability of supraparticle-based functional materials for practical purposes that require materials with high density and excellent mechanical properties.

[18F]CB251 PET/MR imaging probe targeting translocator protein (TSPO) independent of its Polymorphism in a Neuroinflammation Model.

The 18 kDa translocator protein (TSPO) has been proposed as a biomarker for the detection of neuroinflammation. Although various PET probes targeting TSPO have been developed, a highly selective probe for detecting TSPO is still needed because single nucleotide polymorphisms in the human TSPO gene greatly affect the binding affinity of TSPO ligands. Here, we describe the visualization of neuroinflammation with a multimodality imaging system using our recently developed TSPO-targeting radionuclide PET probe [18F]CB251, which is less affected by TSPO polymorphisms. Methods: To test the selectivity of [18F]CB251 for TSPO polymorphisms, 293FT cells expressing polymorphic TSPO were generated by introducing the coding sequences of wild-type (WT) and mutant (Alanine → Threonine at 147th Amino Acid; A147T) forms. Competitive inhibition assay was conducted with [3H]PK11195 and various TSPO ligands using membrane proteins isolated from 293FT cells expressing TSPO WT or mutant-A147T, representing high-affinity binder (HAB) or low-affinity binder (LAB), respectively. IC50 values of each ligand to [3H]PK11195 in HAB or LAB were measured and the ratio of IC50 values of each ligand to [3H]PK11195 in HAB to LAB was calculated, indicating the sensitivity of TSPO polymorphism. Cellular uptake of [18F]CB251 was measured with different TSPO polymorphisms, and phantom studies of [18F]CB251-PET using 293FT cells were performed. To test TSPO-specific cellular uptake of [18F]CB251, TSPO expression was regulated with pCMV-TSPO (or shTSPO)/eGFP vector. Intracranial lipopolysaccharide (LPS) treatment was used to induce regional inflammation in the mouse brain. Gadolinium (Gd)-DOTA MRI was used to monitor the disruption of the blood-brain barrier (BBB) and infiltration by immune cells. Infiltration of peripheral immune cells across the BBB, which exacerbates neuroinflammation to produce higher levels of neurotoxicity, was also monitored with bioluminescence imaging (BLI). Peripheral immune cells isolated from luciferase-expressing transgenic mice were transferred to syngeneic inflamed mice. Neuroinflammation was monitored with [18F]CB251-PET/MR and BLI. To evaluate the effects of anti-inflammatory agents on intracranial inflammation, an inflammatory cytokine inhibitor, 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid methyl ester (CDDO-Me) was administered in intracranial LPS challenged mice. Results: The ratio of IC50 values of [18F]CB251 in HAB to LAB indicated similar binding affinity to WT and mutant TSPO and was less affected by TSPO polymorphisms. [18F]CB251 was specific for TSPO, and its cellular uptake reflected the amount of TSPO. Higher [18F]CB251 uptake was also observed in activated immune cells. Simultaneous [18F]CB251-PET/MRI showed that [18F]CB251 radioactivity was co-registered with the MR signals in the same region of the brain of LPS-injected mice. Luciferase-expressing peripheral immune cells were located at the site of LPS-injected right striatum. Quantitative evaluation of the anti-inflammatory effect of CDDO-Me on neuroinflammation was successfully monitored with TSPO-targeting [18F]CB251-PET/MR and BLI. Conclusion: Our results indicate that [18F]CB251-PET has great potential for detecting neuroinflammation with higher TSPO selectivity regardless of polymorphisms. Our multimodal imaging system, [18F]CB251-PET/MRI, tested for evaluating the efficacy of anti-inflammatory agents in preclinical studies, might be an effective method to assess the severity and therapeutic response of neuroinflammation.

Side branching and luminal lineage commitment by ID2 in developing mammary glands.

Mammary glands develop through primary ductal elongation and side branching to maximize the spatial area. Although primary ducts are generated by bifurcation of terminal end buds, the mechanism through which side branching occurs is still largely unclear. Here, we show that inhibitor of DNA-binding 2 (ID2) drives side branch formation through the differentiation of K6+ bipotent progenitor cells (BPs) into CD61+ luminal progenitor cells (LPs). Id2-null mice had side-branching defects, along with developmental blockage of the differentiation of K6+ BPs into CD61+ LPs. Notably, CD61+ LPs were found in budding and side branches, but not in terminal end buds. Hormone reconstitution studies using ovariectomized MMTV-hemagglutinin-nuclear localized sequence-tagged Id2 transgenic mice revealed that ID2 is a key mediator of progesterone, which drives luminal lineage differentiation and side branching. Our results suggest that CD61 is a marker of side branches and that ID2 regulates side branch formation by inducing luminal lineage commitment from K6+ BPs to CD61+ LPs.

Towards Harmonious Coexistence in the Unlicensed Spectrum: Rational Cooperation of Operators.

5G New Radio (NR) operating in the unlicensed spectrum is accelerating the Fourth Industrial Revolution by supporting Internet of Things (IoT) networks or Industrial IoT deployments. Specifically, LTE-Advanced (LTE-A) is looking to achieve spectrum integration through coexistence with multi-radio access technology (RAT) systems in the same unlicensed bands with both licensed-assisted and stand-alone access. The listen-before-talk (LBT) mechanism is mainly considered to enable an LTE operator to protect other incumbent unlicensed systems. In this article, we investigate the behaviors of multiple LTE operators along with the deployment of WiFi networks in the unlicensed spectrum from both short- and long-term points of view. In countries without mandatory LBT requirements, we show that an LTE operator is susceptible to collusion with another LTE operator, thus exploiting scarce spectrum resources by deceiving other wireless networks into thinking that channels are always busy; hence, mandatory usage of LTE with LBT is highly recommended at national level to achieve harmonious coexistence in the unlicensed spectrum. We discuss several possible coexistence scenarios to resolve the operator's dilemmaas well as to improve unlicensed spectrum efficiency among multi-RAT systems, which is viable in the near future.

On Optimal Cooperative Sensing with Energy Detection in Cognitive Radio.

In this paper, we propose an optimal cooperative sensing technique for cognitive radio to maximize sensing performance based on energy detection. In most spectrum sensing research, many cooperation methods have been proposed to overcome the sensitivity of energy detection so that both primary and secondary users are better off in terms of spectral efficiency. However, without assigning a proper sensing threshold to each sensing node, cooperation may not be effective unless the received average primary user signal-to-noise ratio (SNR) is identical. We show that equal threshold energy detection severely degrades sensing performance when cooperative sensing nodes experience diverse average SNRs, and it is not unusual for even single-node sensing to be better than cooperative sensing. To this end, based on the Neyman-Pearson criterion we formulate an optimization problem to maximize sensing performance by using optimized thresholds. Since this is a non-convex optimization problem, we provide a condition that convexifies the problem and thus serves as a sufficient optimality condition. We find that, perhaps surprisingly, in all practical cases one may consider this condition satisfied, and thus optimal sensing performance can be obtained. Through extensive simulations, we demonstrate that the proposed technique achieves a globally optimal solution, i.e., it maximizes the probability of detection under practical operating parameters such as the target probability of false alarm, different SNRs, and the number of cooperative sensing nodes.

Sex hormones establish a reserve pool of adult muscle stem cells.

Quiescent satellite cells, known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle following injury throughout life. Although they mainly originate from multipotent stem/progenitor cells of the somite, the mechanism underlying the establishment of quiescent satellite cell populations is unknown. Here, we show that sex hormones induce Mind bomb 1 (Mib1) expression in myofibres at puberty, which activates Notch signalling in cycling juvenile satellite cells and causes them to be converted into adult quiescent satellite cells. Myofibres lacking Mib1 fail to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Our findings reveal that the hypothalamic-pituitary-gonadal axis drives Mib1 expression in the myofibre niche. Moreover, the same axis regulates the re-establishment of quiescent satellite cell populations following injury. Our data show that sex hormones establish adult quiescent satellite cell populations by regulating the myofibre niche at puberty and re-establish them during regeneration.

Risk Prediction Using Genome-Wide Association Studies on Type 2 Diabetes.

The success of genome-wide association studies (GWASs) has enabled us to improve risk assessment and provide novel genetic variants for diagnosis, prevention, and treatment. However, most variants discovered by GWASs have been reported to have very small effect sizes on complex human diseases, which has been a big hurdle in building risk prediction models. Recently, many statistical approaches based on penalized regression have been developed to solve the "large p and small n" problem. In this report, we evaluated the performance of several statistical methods for predicting a binary trait: stepwise logistic regression (SLR), least absolute shrinkage and selection operator (LASSO), and Elastic-Net (EN). We first built a prediction model by combining variable selection and prediction methods for type 2 diabetes using Affymetrix Genome-Wide Human SNP Array 5.0 from the Korean Association Resource project. We assessed the risk prediction performance using area under the receiver operating characteristic curve (AUC) for the internal and external validation datasets. In the internal validation, SLR-LASSO and SLR-EN tended to yield more accurate predictions than other combinations. During the external validation, the SLR-SLR and SLR-EN combinations achieved the highest AUC of 0.726. We propose these combinations as a potentially powerful risk prediction model for type 2 diabetes.

Prediction of Quantitative Traits Using Common Genetic Variants: Application to Body Mass Index.

With the success of the genome-wide association studies (GWASs), many candidate loci for complex human diseases have been reported in the GWAS catalog. Recently, many disease prediction models based on penalized regression or statistical learning methods were proposed using candidate causal variants from significant single-nucleotide polymorphisms of GWASs. However, there have been only a few systematic studies comparing existing methods. In this study, we first constructed risk prediction models, such as stepwise linear regression (SLR), least absolute shrinkage and selection operator (LASSO), and Elastic-Net (EN), using a GWAS chip and GWAS catalog. We then compared the prediction accuracy by calculating the mean square error (MSE) value on data from the Korea Association Resource (KARE) with body mass index. Our results show that SLR provides a smaller MSE value than the other methods, while the numbers of selected variables in each model were similar.

The grain growth behavior of NiO in thermally-stable mesoporous gadolinium-doped ceria network for intermediate-temperature solid oxide fuel cell anode materials.

The grain growth behavior of NiO nano grains in mesoporous gadolinium-doped ceria (GDC) network was investigated for anode materials of intermediate-temperature solid oxide fuel cell (SOFC). Both mesoporous GDC and NiO-GDC powders were synthesized using tri-block copolymer, Pluronic F127 as a structure-directing agent, and then X-ray diffraction, N2 adsorption/desorption isotherms, thermo gravimetric analysis, field-emission scanning electron microscopy and transmission electron microscopy were used for characterization of the mesoporous structure. Mesoporous GDC synthesized using pluronic F127 triblock copolymer had ordered double mesoporous structure with an average pore size of 9.68 nm and was thermally stable up to 700 degrees C. NiO grains in the mesoporous GDC network grew to have an octahedral shape with truncated-edges, but massive NiO agglomeration occurred as the calcination temperature increases up to 850 degrees C.

The memristive properties of a single VO2 nanowire with switching controlled by self-heating.

A two-terminal memristor memory based on a single VO2 nanowire is reported that can not only provide switchable resistances in a large range of about four orders of magnitude but can also maintain the resistances by a low bias voltage. The phase transition of the single VO2 nanowire was driven by the bias voltage of 0.34 V without using any heat source. The memristive behavior of the single VO2 nanowire was confirmed by observing the switching and non-volatile properties of resistances when voltage pulses and low bias voltage were applied, respectively. Furthermore, multiple retainable resistances in a large range of about four orders of magnitude can be utilized by controlling the number and the amount of voltage pulses under the low bias voltage. This is a key step towards the development of new low-power and two-terminal memory devices for next-generation non-volatile memories.

Effect of the initial structure on the electrical property of crystalline silicon films deposited on glass by hot-wire chemical vapor deposition.

Crystalline silicon films on an inexpensive glass substrate are currently prepared by depositing an amorphous silicon film and then crystallizing it by excimer laser annealing, rapid thermal annealing, or metal-induced crystallization because crystalline silicon films cannot be directly deposited on glass at a low temperature. It was recently shown that by adding HCI gas in the hot-wire chemical vapor deposition (HWCVD) process, the crystalline silicon film can be directly deposited on a glass substrate without additional annealing. The electrical properties of silicon films prepared using a gas mixture of SiH4 and HCl in the HWCVD process could be further improved by controlling the initial structure, which was achieved by adjusting the delay time in deposition. The size of the silicon particles in the initial structure increased with increasing delay time, which increased the mobility and decreased the resistivity of the deposited films. The 0 and 5 min delay times produced the silicon particle sizes of approximately 10 and approximately 28 nm, respectively, in the initial microstructure, which produced the final films, after deposition for 300 sec, of resistivities of 0.32 and 0.13 Omega-cm, mobilities of 1.06 and 1.48 cm2 V(-1) S(-1), and relative densities of 0.87 and 0.92, respectively.

Electrical and optical properties of amorphous (In, Sn)-Ga-Zn-O thin film.

Films of amorphous In(1-x)Sn(x)GaZnO(delta) (a-ISGZO) (x = 0.0-1.0) were pulsed laser deposited at a temperature range of room temperature to 300 degrees C, and in order to systematically investigate the effect of replacing In with Sn on the properties of amorphous In-Ga-Zn-O (a-IGZO), the electrical and optical properties were measured. The amount of Sn in the deposited film, which was determined by X-ray photoelectron spectroscopy, was very close to the composition of the targets used. Hall mobility and carrier concentration decreased, and resistivity increased as the amount of Sn in the film increased. It was observed that the increase of Sn concentration in films was accompanied by the decrease of oxygen vacancy concentration, which led to the decrease of carrier concentration. The electrical mobility was decreased as the amount of Sn increased, which can be attributed to the increased number of subgap states, which was determined by the UV/VNIS spectrophotometer. Optical transparencies of all samples were larger than 80% in the visible light range. Band gap values were also found to increase as the amount of Sn increased.