Universal germline genetic testing in patients with hematologic malignancies using DNA isolated from nail clippings.

Not available.

Sox17 Deficiency Promotes Pulmonary Arterial Hypertension via HGF/c-Met Signaling.

BACKGROUND: In large-scale genomic studies, Sox17, an endothelial-specific transcription factor, has been suggested as a putative causal gene of pulmonary arterial hypertension (PAH); however, its role and molecular mechanisms remain to be elucidated. We investigated the functional impacts and acting mechanisms of impaired Sox17 (SRY-related HMG-box17) pathway in PAH and explored its potential as a therapeutic target. METHODS: In adult mice, Sox17 deletion in pulmonary endothelial cells (ECs) induced PAH under hypoxia with high penetrance and severity, but not under normoxia. RESULTS: Key features of PAH, such as hypermuscularization, EC hyperplasia, and inflammation in lung arterioles, right ventricular hypertrophy, and elevated pulmonary arterial pressure, persisted even after long rest in normoxia. Mechanistically, transcriptomic profiling predicted that the combination of Sox17 deficiency and hypoxia activated c-Met signaling in lung ECs. HGF (hepatocyte grow factor), a ligand of c-Met, was upregulated in Sox17-deficient lung ECs. Pharmacologic inhibition of HGF/c-Met signaling attenuated and reversed the features of PAH in both preventive and therapeutic settings. Similar to findings in animal models, Sox17 levels in lung ECs were repressed in 26.7% of PAH patients (4 of 15), while those were robust in all 14 non-PAH controls. HGF levels in pulmonary arterioles were increased in 86.7% of patients with PAH (13 of 15), but none of the controls showed that pattern. CONCLUSIONS: The downregulation of Sox17 levels in pulmonary arterioles increases the susceptibility to PAH, particularly when exposed to hypoxia. Our findings suggest the reactive upregulation of HGF/c-Met signaling as a novel druggable target for PAH treatment.

pH-Modulated Nanoarchitectonics for Enhancement of Multivalency-Induced Vesicle Shape Deformation at Receptor-Presenting Lipid Membrane Interfaces.

Multivalent ligand-receptor interactions between receptor-presenting lipid membranes and ligand-modified biological and biomimetic nanoparticles influence cellular entry and fusion processes. Environmental pH changes can drive these membrane-related interactions by affecting membrane nanomechanical properties. Quantitatively, however, the corresponding effects on high-curvature, sub-100 nm lipid vesicles are scarcely understood, especially in the multivalent binding context. Herein, we employed the label-free localized surface plasmon resonance (LSPR) sensing technique to track the multivalent attachment kinetics, shape deformation, and surface coverage of biotin ligand-functionalized, zwitterionic lipid vesicles with different ligand densities on a streptavidin receptor-coated supported lipid bilayer under varying pH conditions (4.5, 6, 7.5). Our results demonstrate that more extensive multivalent interactions caused greater vesicle shape deformation across the tested pH conditions, which affected vesicle surface packing as well. Notably, there were also pH-specific differences, i.e., a higher degree of vesicle shape deformation was triggered at a lower multivalent binding energy in pH 4.5 than in pH 6 and 7.5 conditions. These findings support that the nanomechanical properties of high-curvature lipid membranes, especially the membrane bending energy and the corresponding responsiveness to multivalent binding interactions, are sensitive to solution pH, and indicate that multivalency-induced vesicle shape deformation occurs slightly more readily in acidic pH conditions relevant to biological environments.

Ultrawide meta-film replication process for the mass production of a flexible microwave absorbing meta-surface.

The manufacturing process for an ultrawide flexible microwave absorbing meta-surface was developed and optimized experimentally. The developed replication process consists of four main steps to demonstrate double-square loop array meta-structures: (1) mechanical machining of a master mold, (2) soft mold replication and patterned film imprinting, (3) conductive ink blade filling, (4) lamination of a base flexible film to meta sheet. Based on experimental optimization of the individual steps, the manufacturing process for a large-area flexible meta-film was established successfully. The feasibility of a developed process has been demonstrated with a 200 mm × 500 mm fabricated meta-film with a focus on microwave absorbing uniformity in the X-band region.

Unraveling How Cholesterol Affects Multivalency-Induced Membrane Deformation of Sub-100 nm Lipid Vesicles.

Cholesterol plays a critical role in modulating the lipid membrane properties of biological and biomimetic systems and recent attention has focused on its role in the functions of sub-100 nm lipid vesicles and lipid nanoparticles. These functions often rely on multivalent ligand-receptor interactions involving membrane attachment and dynamic shape transformations while the extent to which cholesterol can influence such interaction processes is largely unknown. To address this question, herein, we investigated the attachment of sub-100 nm lipid vesicles containing varying cholesterol fractions (0-45 mol %) to membrane-mimicking supported lipid bilayer (SLB) platforms. Biotinylated lipids and streptavidin proteins were used as model ligands and receptors, respectively, while the localized surface plasmon resonance sensing technique was employed to track vesicle attachment kinetics in combination with analytical modeling of vesicle shape changes. Across various conditions mimicking low and high multivalency, our findings revealed that cholesterol-containing vesicles could bind to receptor-functionalized membranes but underwent appreciably less multivalency-induced shape deformation than vesicles without cholesterol, which can be explained by a cholesterol-mediated increase in membrane bending rigidity. Interestingly, the extent of vesicle deformation that occurred in response to increasingly strong multivalent interactions was less pronounced for vesicles with greater cholesterol fraction. The latter trend was rationalized by taking into account the strong dependence of the membrane bending energy on the area of the vesicle-SLB contact region and such insights can aid the engineering of membrane-enveloped nanoparticles with tailored biophysical properties.

Distinct Binding Properties of Neutravidin and Streptavidin Proteins to Biotinylated Supported Lipid Bilayers: Implications for Sensor Functionalization.

The exceptional strength and stability of noncovalent avidin-biotin binding is widely utilized as an effective bioconjugation strategy in various biosensing applications, and neutravidin and streptavidin proteins are two commonly used avidin analogues. It is often regarded that the biotin-binding abilities of neutravidin and streptavidin are similar, and hence their use is interchangeable; however, a deeper examination of how these two proteins attach to sensor surfaces is needed to develop reliable surface functionalization options. Herein, we conducted quartz crystal microbalance-dissipation (QCM-D) biosensing experiments to investigate neutravidin and streptavidin binding to biotinylated supported lipid bilayers (SLBs) in different pH conditions. While streptavidin binding to biotinylated lipid receptors was stable and robust across the tested pH conditions, neutravidin binding strongly depended on the solution pH and was greater with increasingly acidic pH conditions. These findings led us to propose a two-step mechanistic model, whereby streptavidin and neutravidin binding to biotinylated sensing interfaces first involves nonspecific protein adsorption that is mainly influenced by electrostatic interactions, followed by structural rearrangement of adsorbed proteins to specifically bind to biotin functional groups. Practically, our findings demonstrate that streptavidin is preferable to neutravidin for constructing SLB-based sensing platforms and can improve sensing performance for detecting antibody-antigen interactions.

Comparing Protein Adsorption onto Alumina and Silica Nanomaterial Surfaces: Clues for Vaccine Adjuvant Development.

Protein adsorption onto nanomaterial surfaces is important for various nanobiotechnology applications such as biosensors and drug delivery. Within this scope, there is growing interest to develop alumina- and silica-based nanomaterial vaccine adjuvants and an outstanding need to compare protein adsorption onto alumina- and silica-based nanomaterial surfaces. Herein, using alumina- and silica-coated arrays of silver nanodisks with plasmonic properties, we conducted localized surface plasmon resonance (LSPR) experiments to evaluate real-time adsorption of bovine serum albumin (BSA) protein onto alumina and silica surfaces. BSA monomers and oligomers were prepared in different water-ethanol mixtures and both adsorbing species consistently showed quicker adsorption kinetics and more extensive adsorption-related spreading on alumina surfaces as compared to on silica surfaces. We rationalized these experimental observations in terms of the electrostatic forces governing protein-surface interactions on the two nanomaterial surfaces and the results support that more rigidly attached BSA protein-based coatings can be formed on alumina-based nanomaterial surfaces. Collectively, the findings in this study provide fundamental insight into protein-surface interactions at nanomaterial interfaces and can help to guide the development of protein-based coatings for medical and biotechnology applications such as vaccines.

Artificial Rainfall on Grain Quality and Baking Characteristics of Winter Wheat Cultivars in Korea.

Wheat (Triticum aestivum L.) stands as a significant cereal crop globally, including in Korea, where its consumption reached 35.7 kg per capita in 2023. In the southern regions of Korea, wheat cultivation follows paddy rice, with harvesting typically occurring during the rainy season in mid-June. This timing, coupled with the high humidity and unpredictable rainfall, often leads to pre-harvest sprouting and subsequent deterioration in flour quality. To assess the impact of rain on flour quality, an artificial rain treatment was administered 45 days after heading in an open field greenhouse, followed by flour quality analysis. The color measurement revealed an increase in the L* parameter, indicative of enhanced kernel vitreousness, attributed to endosperm starch degradation via alpha-amylase activation induced by water absorption. Moreover, significant changes were observed in ash content and the gluten index within the wetted group, resulting in decreased dough strength and stability, ultimately leading to a reduction in loaf volume. Consequently, it is recommended that wheat be harvested 4-7 days after reaching the physiological maturity stage to avoid the rainy season and ensure the production of high-quality wheat.

Synergizing breeding strategies via combining speed breeding, phenotypic selection, and marker-assisted backcrossing for the introgression of Glu-B1i in wheat.

Wheat is a major food crop that plays a crucial role in the human diet. Various breeding technologies have been developed and refined to meet the increasing global wheat demand. Several studies have suggested breeding strategies that combine generation acceleration systems and molecular breeding methods to maximize breeding efficiency. However, real-world examples demonstrating the effective utilization of these strategies in breeding programs are lacking. In this study, we designed and demonstrated a synergized breeding strategy (SBS) that combines rapid and efficient breeding techniques, including speed breeding, speed vernalization, phenotypic selection, backcrossing, and marker-assisted selection. These breeding techniques were tailored to the specific characteristics of the breeding materials and objectives. Using the SBS approach, from artificial crossing to the initial observed yield trial under field conditions only took 3.5 years, resulting in a 53% reduction in the time required to develop a BC2 near-isogenic line (NIL) and achieving a higher recurrent genome recovery of 91.5% compared to traditional field conditions. We developed a new wheat NIL derived from cv. Jokyoung, a leading cultivar in Korea. Milyang56 exhibited improved protein content, sodium dodecyl sulfate-sedimentation value, and loaf volume compared to Jokyoung, which were attributed to introgression of the Glu-B1i allele from the donor parent, cv. Garnet. SBS represents a flexible breeding model that can be applied by breeders for developing breeding materials and mapping populations, as well as analyzing the environmental effects of specific genes or loci and for trait stacking.

Physicochemical and chemosensory properties of pomegranate (Punica granatum L.) seeds under various oven-roasting conditions.

This study investigated the effects of oven-roasting temperature (160, 180, and 200 â„ƒ) and time (5, 10, 15, and 20 min) on pomegranate seeds. Physicochemical properties, such as color (L*, a*, and b* values), browning index (BI), total phenolic and flavonoid contents, 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity, and chemosensory properties, including taste and volatile compounds, were analyzed. The L* and a* values, and level of sourness, umami, sweetness, and terpenes decreased, whereas the b* value, BI, and level of saltiness, bitterness, furan derivatives, pyrazines, and sulfur-containing compounds, increased with roasting time. The findings of this study showed that the positive roasting conditions for pomegranate seeds were 10-20 min at 160 â„ƒ and, 5-10 min at 180 â„ƒ. This study is expected to be used as a primary reference for selecting the optimal oven-roasting conditions in which positive effects appear and for developing products utilizing pomegranate seeds.

Chemosensory of hemp seed oil extracted with hemp seed(Cannabis sativa L.) roasted under various conditions using electronic sensors and GC-MS/Olfactometry.

This study analyzed the flavor of six types of hemp seed oil (HSO) extracted with roasted hemp seed (RHS) under various conditions (Raw, 140 °C_9 min, 140 °C_12 min, 160 °C_12 min, 180 °C_6 min). Electronic tongue (E-tongue), electronic nose (E-nose), GC-MS (gas chromatography-mass spectrometry), and GC-O (gas chromatography-olfactometry) were used for HSO flavor analysis. As a result of the E-tongue analysis, the sweetness tends to increase in most samples as roasting. A total of 89 and 77 volatile compounds were detected through E-nose and GC-MS, and the main volatile compounds were identified as Maillard reaction products. A total of 16 odor active compounds were detected in the GC-O analysis, and in the case of 160 ℃_12 min and 180 ℃_6 min, the scent of Roasted hemp seed oil was more dominant than other aroma profiles. The results of this study are basic data on the flavor characteristics of HSO.

The inhalation effect of Osmanthus fragrans var. Aurantiacus on physiological parameters in chronically stressed rats.

This study evaluated the effects of inhaling Osmanthus fragrans var. aurantiacus (OFA) extracts in Sprague-Dawley (SD) rats experiencing chronic stress. Rats were exposed to restraint stress or circadian disruption and were inhaled either distilled water or OFA extracts. Electronic nose (E-nose) analysis identified 35 volatile aromatic compounds (VACs) in OFA extracts. Chronic stress led to a decrease in body weight initially, serotonin concentration, and the weights of the liver, kidneys, and fat pads. Additionally, circadian disruption increased melatonin levels and decreased cholesterol concentrations. Inhalation of OFA increased dietary intake during the early phase and restored the tissue weights that have changed by chronic stress. Furthermore, it led to an increase in melatonin levels and changes in cholesterol levels. Taken together, our results indicate that OFA inhalation improves physiological changes caused by chronic stress through regulating dietary intake, restoring tissue weights, and modulating hormone and cholesterol levels.

Influence of torrefaction pretreatment for ethanol fermentation from waste money bills.

Waste money bills (WMB) that are no longer legal tender are nonrecyclable and are generally useless. In this work, we used this cellulose-rich material for ethanol fermentation for the first time. Torrefaction of this nonlignocellulosic waste material was attempted to examine whether such material could benefit from this process as a conventional lignocellulosic material does. Effects of two important parameters, that is, residence times (20, 40, and 60 Min) and temperatures (140, 160, 180, 200, and 220°C), on the torrefaction yield were studied under an inert atmosphere. Glucose and ethanol yields were compared using a factorial experimental design. The highest glucose yield (81.59 mg/mL) was obtained with a torrefaction treatment consisting of 40 min at 180 °C, and it was increased 44.89% compared to untreated WMB. Based on ethanol feasibility studies conducted on WMB, this estimated quantity of glucose could be produced for subsequent fermentation to ethanol (38.92 mg/mL) and it was increased 47.92% compared to the untreated sample. The fermentation rate was also enhanced by adding 0.4 mM benzoic acid under anaerobic conditions. It is concluded that production of ethanol from WMB would reduce waste management costs and thus would be profitable.

Alkaline pretreatment improves saccharification and ethanol yield from waste money bills.

Waste money bills (WMB) is a by-product of the money making process that consists of rich-cellulosic material for many biotechnological applications. This waste money bills is unusable and usually exhausted. Saccharification was improved using various concentrations of sodium hydroxide, NaOH (0.0, 0.5, 1.0, 2.0, 2.5, and 3.0% v/v) and various reaction times (20, 30, and 40 min) during pretreatment at 121 °C. Prior to ethanol fermentation, the highest glucose yield (62.2 mg/mL) was found by pretreatment consisting of 30 min at 2.0% NaOH, and it increased 33.8% as compared to an untreated sample. The highest amount of ethanol was obtained (26.1 mg/mL) during fermentation, and this was increased 95.3 and 22.5% as compared to aerobic and anaerobic conditions respectively during pretreatment with 2.0% NaOH for 30 min. Under anaerobic conditions, ethanol fermentation was enhanced by adding 0.4 mmol benzoic acid. Production of ethanol from waste money bills would cut waste management costs and make profitable.

Effect of torrefaction for the pretreatment of rice straw for ethanol production.

BACKGROUND: Rice straw is an attractive lignocellulosic material for ethanol production, since it is one of the most abundant renewable resources. It generally has high cellulose and hemicellulose contents that can be readily hydrolysed into sugars for subsequent ethanol fermentation. The pretreatment method plays an important role in increasing the efficiency of enzymatic saccharification, thereby making the whole process economically viable. Torrefaction is an appropriate pretreatment technique for enhancing the enzymatic reaction and subsequent ethanol production. RESULTS: The effects of two important parameters, i.e. residence time (20, 40 and 60 min) and temperature (160, 180, 200, 220, 240 and 260 °C), were studied under an inert atmosphere. The highest yield of 351 ± 5.49 mg g(-1) total sugars was obtained after torrefaction treatment at 220 °C for 40 min, representing a 60.68% increase compared with the untreated sample. Based on ethanol studies conducted on rice straw, this estimated quantity of sugars could produce 150 ± 2.40 mg g(-1) ethanol, a 50.67% increase compared with the untreated sample under anaerobic conditions. The fermentation rate was enhanced by adding 0.4 mmol L(-1) benzoic acid. CONCLUSION: The use of this waste material could reduce competition with food materials for ethanol production. It can be considered as an alternative sustainable waste management option.

Enhanced Emulsifying Ability of Deoxycholate through Dynamic Interaction with Layered Double Hydroxide.

The emulsifying ability of the naturally occurring surfactant deoxycholic acid (DCA) was improved by dynamic interaction with nanometric layered particles, layered double hydroxide (LDH). As DCA molecules are rigid due to the facial configuration of hydrophobic-hydrophilic groups, they tend to form molecular aggregation in an acidic condition or imbalanced water-lipid ratios. In this study, the homogeneous hybrids of DCA and LDH were obtained by the in situ growth of LDH at a DCA molecule. The DCA-LDH hybrid successfully prevented the molecular aggregation of DCA at an acidic pH and imbalanced water-to-oil ratio. The dynamic light scattering showed that the hydrodynamic radius of micelle in the emulsion made with DCA-LDH maintained its small size (<500 nm), while upon pH change and dilution with water, that made with DCA only uncontrollably increased up to ~3000 nm. The polydispersity index value of the DCA-LDH emulsion remained constant (<0.3) after the pH change and dilution with water, indicating the high stability of the formulation. Furthermore, time-dependent turbidity monitoring revealed that the DCA-only formulation suffered from serious coalescence and creaming compared with the DCA-LDH formulation. It is suggested that the dynamic interaction between LDH layers and DCA prevented molecular aggregation under unfavorable conditions for the oil-in-water emulsion.

Controlled molecular arrangement of easily aggregated deoxycholate with layered double hydroxide.

Deoxycholate (DA) is a natural emulsifying agent involved in the absorption of dietary lipids. Due to the facial distribution of hydrophobic-hydrophilic region, DA easily aggregates under ambient conditions, and this property hinders the practical application of DA in clinical applications. In this study, we found that the molecular arrangement of DA molecules could be controlled by using layered double hydroxide (LDH) under a specific reaction condition. The effect of reaction methods such as co-precipitation, ion exchange and reconstruction on the molecular arrangement of DA was investigated by X-ray diffraction, Fourier-transform infrared spectroscopy, high-resolution transmission electron microscopy and differential scanning calorimetry. It was demonstrated that the self-aggregation of DA molecules could be suppressed by the oriented arrangement of DA between the gallery space of LDH. The DA moiety was well stabilized in the LDH layers due to the electrostatic interaction between DA molecules and LDH layers. The most ordered arrangement of DA molecules was observed when DA was incorporated into LDH via a reconstruction method. The DA molecules arranged in LDH via reconstruction did not show significant exothermic or endothermic behaviour up to 400°C, showing that the DA moiety lost its intermolecular attraction in between LDH layers.

Acceleration of wheat breeding: enhancing efficiency and practical application of the speed breeding system.

BACKGROUND: Crop breeding should be accelerated to address global warming and climate change. Wheat (Triticum aestivum L.) is a major food crop. Speed breeding (SB) and speed vernalization (SV) techniques for spring and winter wheat have recently been established. However, there are few practical examples of these strategies being used economically and efficiently in breeding programs. We aimed to establish and evaluate the performance of a breeder-friendly and energy-saving generation acceleration system by modifying the SV + SB system. RESULTS: In this study, a four-generation advancement system for wheat (regardless of its growth habits) was established and evaluated using an energy-efficient extended photoperiod treatment. A glasshouse with a 22-hour photoperiod that used 10 h of natural sunlight and 12 h of LED lights, and minimized temperature control during the winter season, was successful in accelerating generation. Even with one or two field tests, modified speed breeding (mSB) combined with a speed vernalization system (SV + mSB) reduced breeding time by more than half compared to traditional field-based methods. When compared to the existing SV + SB system, the SV + mSB system reduced energy use by 80% to maintain a 22-hour photoperiod. Significant correlations were found between the SV + mSB and field conditions in the number of days to heading (DTH) and culm length (CL). Genetic resources, recombinant inbred lines, and breeding materials that exhibited shorter DTH and CL values under SV + mSB conditions showed the same pattern in the field. CONCLUSIONS: The results of our SV + mSB model, as well as its practical application in wheat breeding programs, are expected to help breeders worldwide incorporate generation acceleration systems into their conventional breeding programs.

k-SALSA: k-anonymous synthetic averaging of retinal images via local style alignment.

The application of modern machine learning to retinal image analyses offers valuable insights into a broad range of human health conditions beyond ophthalmic diseases. Additionally, data sharing is key to fully realizing the potential of machine learning models by providing a rich and diverse collection of training data. However, the personallyidentifying nature of retinal images, encompassing the unique vascular structure of each individual, often prevents this data from being shared openly. While prior works have explored image de-identification strategies based on synthetic averaging of images in other domains (e.g. facial images), existing techniques face difficulty in preserving both privacy and clinical utility in retinal images, as we demonstrate in our work. We therefore introduce k-SALSA, a generative adversarial network (GAN)-based framework for synthesizing retinal fundus images that summarize a given private dataset while satisfying the privacy notion of k-anonymity. k-SALSA brings together state-of-the-art techniques for training and inverting GANs to achieve practical performance on retinal images. Furthermore, k-SALSA leverages a new technique, called local style alignment, to generate a synthetic average that maximizes the retention of fine-grain visual patterns in the source images, thus improving the clinical utility of the generated images. On two benchmark datasets of diabetic retinopathy (EyePACS and APTOS), we demonstrate our improvement upon existing methods with respect to image fidelity, classification performance, and mitigation of membership inference attacks. Our work represents a step toward broader sharing of retinal images for scientific collaboration. Code is available at https://github.com/hcholab/k-salsa.

Multivalency-Induced Shape Deformation of Nanoscale Lipid Vesicles: Size-Dependent Membrane Bending Effects.

The size of membrane-enveloped virus particles, exosomes, and lipid vesicles strongly impacts functional properties in biological and applied contexts. Multivalent ligand-receptor interactions involving nanoparticle shape deformation are critical to such functions, yet the corresponding effect of nanoparticle size remains largely elusive. Herein, using an indirect nanoplasmonic sensing approach, we investigated how the nanoscale size properties of ligand-modified lipid vesicles affect real-time binding interactions, especially vesicle deformation processes, with a receptor-modified, cell membrane-mimicking platform. Together with theoretical analyses, our findings reveal a pronounced, size-dependent transition in the membrane bending properties of nanoscale lipid vesicles between 60 and 180 nm in diameter. For smaller vesicles, a large membrane bending energy enhanced vesicle stiffness while the osmotic pressure energy was the dominant modulating factor for larger, less stiff vesicles. These findings advance our fundamental understanding of how nanoparticle size affects multivalency-induced nanoparticle shape deformation and can provide guidance for the design of biomimetic nanoparticles with tailored nanomechanical properties.