YAP1 regulates esophageal stem cells' self-renewal and differentiation.

Esophageal epithelium is one of the most proliferative and regenerative epithelia in our body, indicating robust stem cell activity. However, the underlying mechanisms regulating the self-renewal and differentiation of esophageal stem cells need to be more elucidated. Here, we identify the role of YAP1 in esophageal stem cells. YAP1 is differentially expressed in the nuclei of esophageal basal cells. Furthermore, the treatment of verteporfin, a YAP1 inhibitor, interfered with esophageal organoid formation. Consistently, YAP1 deletion decreased esophageal organoid formation and the expression of basal genes while increasing the expression of suprabasal genes. Finally, global transcriptomic analysis revealed that YAP1 inhibition induced a significant enrichment of gene sets related to keratinization and cornification, while depleting gene sets related to DNA repair and chromosome maintenance. Our data uncover a novel regulatory mechanism for esophageal stem cells, which could provide a potential strategy for esophageal regenerative medicine.

Work hardening in colloidal crystals.

Colloidal crystals exhibit interesting properties1-4 that are in many ways analogous to their atomic counterparts. They have the same crystal structures2,5-7, undergo the same phase transitions8-10, and possess the same crystallographic defects11-14. In contrast to these structural properties, the mechanical properties of colloidal crystals are quite different from those of atomic systems. For example, unlike in atomic systems, the elasticity of hard-sphere colloidal crystals is purely entropic15; as a result, they are so soft that they can be melted just by stirring16,17. Moreover, crystalline materials deform plastically when subjected to increasing shear and become stronger because of the ubiquitous process of work hardening18; but this has so far never been observed in colloidal crystals, to our knowledge. Here we show that hard-sphere colloidal crystals exhibit work hardening. Moreover, despite their softness, the shear strength of colloidal crystals can increase and approach the theoretical limit for crystals, a value reached in very few other materials so far. We use confocal microscopy to show that the strength of colloidal crystals increases with dislocation density, and ultimately reaches the classic Taylor scaling behaviour for atomic materials19-21, although hard-sphere interactions lack the complexity of atomic interactions. We demonstrate that Taylor hardening arises through the formation of dislocation junctions22. The Taylor hardening regime, however, is established only after a transient phase, and it ceases when the colloidal crystals become so hard that the strain is localized within a thin boundary layer in which slip results from an unconventional motion of dislocations. The striking resemblance between colloidal and atomic crystals, despite the many orders of magnitude difference in particle size and shear modulus, demonstrates the universality of work hardening.

Integrated proteogenomic characterization of glioblastoma evolution.

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention.

Effect of activated carbon electrode material characteristics on hardness control performance of membrane capacitive deionization.

Capacitive deionization (CDI) is an electrochemical-based water treatment technology that has attracted attention as an effective hardness-control process. However, few systematic studies have reported the criteria for the selection of suitable electrode materials for membrane capacitive deionization (MCDI) to control hardness. In this study, the effect of electrode material characteristics on the MCDI performance for hardness control was quantitatively analyzed. The results showed that the deionization capacity and the deionization rate were affected by the specific capacitance and BET-specific surface area of the activated carbon electrode. In addition, the deionization rate also showed significant relationship with the BET specific surface area. Furthermore, it was observed that the deionization capacity and the deionization rate have a highly significant relationship with the BET specific surface area divided by the wettability performance expressed as the minimum wetting rate (MWR). These findings highlighted that the electrode material should have a large surface area and good wettability to increase the deionization capacity and the deionization rate of MCDI for hardness control. The results of this study are expected to provide effective criteria for selecting MCDI electrode materials aiming hardness control.

Dislocation interactions during plastic relaxation of epitaxial colloidal crystals.

The severe difficulty to resolve simultaneously both the macroscopic deformation process and the dislocation dynamics on the atomic scale limits our understanding of crystal plasticity. Here we use colloidal crystals, imaged on the single particle level by high-speed three-dimensional (3D) confocal microscopy, and resolve in real-time both the relaxation of the epitaxial misfit strain and the accompanying evolution of dislocations. We show how dislocation interactions give rise to the formation of complex dislocation networks in 3D and to unexpectedly sharp plastic relaxation. The sharp relaxation is facilitated by attractive interactions that promote the formation of new dislocations that are more efficient in mediating strain. Dislocation networks form fragmented structures, as dislocation growth is blocked by either attractive interactions, which result in the formation of sessile dislocation junctions, or by repulsion from perpendicular segments. The strength of these blocking mechanisms decreases with the thickness of the crystal film. These results reveal the critical role of dislocation interactions in plastic deformation of thin films and can be readily generalized from the colloidal to the atomic scale.

Establishment of a chemical tongue injury-recovery mouse model.

Tongue epithelium is one of the most proliferative and regenerative epithelia in our body. However, tongue stem cell research is hampered partly by the lack of optimal animal models to study tongue injury, repair, and regeneration. Here, we establish a novel chemically induced tongue injury-recovery mouse model. Focal application of sodium hydroxide for a limited time led to the denudation of suprabasal layers, leaving the basal layer. Time course study revealed that tongue epithelial cells robustly proliferate over one week after the tongue injury. Importantly, we demonstrated that our novel mouse model could be employed in the lineage tracing of the tongue stem cells under the injury and repair process and further showed that tongue stem cells proliferate faster and generate larger clones in the injury condition than in the steady state condition. Our data indicate the development of a novel chemically induced tongue injury-recovery mouse model for tongue stem cell research, which will significantly facilitate the preclinical study for the pathogenesis and treatment of caustic ingestion.

Analysis of the accuracy of automatic electrocardiogram interpretation in ST-segment elevation myocardial infarction.

OBJECTIVE: This study aimed to analyze the association between the culprit artery and the diagnostic accuracy of automatic electrocardiogram (ECG) interpretation in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: This single-centered, retrospective cohort study included adult patients with STEMI who visited the emergency department between January 2017 and December 2020. The primary endpoint was the association between the culprit artery occlusion and the misinterpretation of ECG, evaluated by the chi-square test or Fisher exact test. RESULTS: The rate of misinterpretation of the automated ECG for patients with STEMI was 26.5% (31/117 patients). There was no significant correlation between the ST segment change in the four involved leads (anteroseptal, lateral, inferior, and aVR) and the misinterpretation of ECG (all P > 0.05). Single culprit artery occlusion significantly affected the misinterpretation of ECG compared with multiple culprit artery occlusion (single vs. multiple, 27/86 [31.3%] vs. 4/31 [12.9%], P = 0.045). There was no association between culprit artery and the misinterpretation of ECG (P = 0.132). CONCLUSION: Single culprit artery occlusion might increase misinterpretation of ECG compared with multiple culprit artery occlusions in the automatic interpretation of STEMI.

Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous Capsules.

Breast augmentations with silicone implants can have adverse effects on tissues that, in turn, lead to capsular contracture (CC). One of the potential ways of overcoming CC is to control the implant/host interaction using immunomodulatory agents. Recently, a high ratio of anti-inflammatory (M2) macrophages to pro-inflammatory (M1) macrophages has been reported to be an effective tissue regeneration approach at the implant site. In this study, a biofunctionalized implant was coated with interleukin (IL)-4 to inhibit an adverse immune reaction and promoted tissue regeneration by promoting polarization of macrophages into the M2 pro-healing phenotype in the long term. Surface wettability, nitrogen content, and atomic force microscopy data clearly showed the successful immobilization of IL-4 on the silicone implant. Furthermore, in vitro results revealed that IL-4-coated implants were able to decrease the secretion of inflammatory cytokines (IL-6 and tumor necrosis factor-α) and induced the production of IL-10 and the upregulation of arginase-1 (mannose receptor expressed by M2 macrophage). The efficacy of this immunomodulatory implant was further demonstrated in an in vivo rat model. The animal study showed that the presence of IL-4 diminished the capsule thickness, the amount of collagen, tissue inflammation, and the infiltration of fibroblasts and myofibroblasts. These results suggest that macrophage phenotype modulation can effectively reduce inflammation and fibrous CC on a silicone implant conjugated with IL-4.

Effects of Thermal Conductive Materials on the Freeze-Thaw Resistance of Concrete.

To solve the problem of black ice, many studies are being carried out. The key in recent days is enhancing the thermal conductivity of concrete. In this study, to improve the thermal conductivity, silicon carbide was used to substitute 50% and 100% of the fine aggregate. In addition, steel fiber is not only for enhancing the mechanical properties but could enhance thermal conductive material. Hence, the arched-type steel fiber was used up to a 1% volume fraction in this study. Furthermore, graphite was used for 5% of the volume fraction for enhancing the thermal conductivity. However, thermal damage would occur due to the difference in thermal conductivity between materials. Therefore, the thermal durability must be verified first. The target application of the concrete in this study was its use as road paving material. To evaluate the thermal durability, freeze-thaw and rapid cyclic thermal attacks were performed. The thermal conductivity of the specimens was increased with the increase in thermal conductive materials. Graphite has already been reported to have a negative effect on mechanical properties, and the results showed that this was the case. However, the steel fiber compensated for the negative effect of graphite, and the silicon carbide provided a filler effect. Graphite also had a negative effect on the freeze-thaw and rapid cyclic thermal attack, but the steel fiber compensated for the reduction in thermal durability. The silicon carbide also helped to improve the thermal durability in the same way as steel fiber. Comprehensively, the steel fiber enhanced all of the properties of the tests. Using 100% silicon carbide was considered the acceptable range, but 50% of silicon carbide was the best. Graphite decreased all the properties except for the thermal conductivity. Therefore, the content of graphite or using other conductive materials used should be carefully considered in further studies.

The characterization of exosomes from fibrosarcoma cell and the useful usage of Dynamic Light Scattering (DLS) for their evaluation.

Exosomes are a type of extracellular vesicles containing mRNA, miRNA, and proteins of origin cells, which can control the characteristics of other cells or surroundings. Despite increasing evidence on oncogenic properties of tumor-derived exosomes, fibrosarcoma-derived exosomes remain largely unrevealed. While the proper extraction and characterization of exosomes is critical in exosomes research, there are various limitations in techniques to measure the size and homogeneity of exosomes. Here, we analyzed exosomes from a fibrosarcoma cell line WEHI-164 compared with a breast cancer cell line MDA-MD-231 as a control. Results from dot blot and western blot analysis demonstrated that GM1 ganglioside, and TSG101, HSC70 and GAPDH proteins were contained in exosomes from the WEHI-164 fibrosarcoma cell line. The existence of tetraspanins such as CD81, CD63 and CD9 was confirmed in the exosomes by ExoView analysis. The results obtained from TEM showed their sphere-like shapes of around 50 to 70 nm in radius. Through DLS, we found out that the mean radius of the exosomes derived from WEHI-164 and MDA-MB-231 cell lines was 94.4 nm and 107.8 nm, respectively, with high homogeneity. When comparing the radius measured by TEM with the radius measured by DLS, it was revealed that the difference between the two methods was about 40 nm. This study has significance in characterizing the molecular properties of exosomes from a fibrosarcoma, which has not been researched much before, and in providing clear evidence that DLS can be used as an efficient, convenient and noninvasive technique to simply check the homogeneity and size of exosomes.

High chlorine evolution performance of electrochemically reduced TiO2 nanotube array coated with a thin RuO2 layer by the self-synthetic method.

Recently, reduced TiO2 nanotube arrays via electrochemical self-doping (r-TiO2) are emerging as a good alternative to conventional dimensionally stable anodes (DSAs) due to their comparable performance and low-cost. However, compared with conventional DSAs, they suffer from poor stability, low current efficiency, and high energy consumption. Therefore, this study aims to advance the electrochemical performances in the chlorine evolution of r-TiO2 with a thin RuO2 layer coating on the nanotube structure (RuO2@r-TiO2). The RuO2 thin layer was successfully coated on the surface of r-TiO2. This was accomplished with a self-synthesized layer of ruthenium precursor originating from a spontaneous redox reaction between Ti3+ and metal ions on the r-TiO2 surface and thermal treatment. The thickness of the thin RuO2 layer was approximately 30 nm on the nanotube surface of RuO2@r-TiO2 without severe pore blocking. In chlorine production, RuO2@r-TiO2 exhibited higher current efficiency (∼81.0%) and lower energy consumption (∼3.0 W h g-1) than the r-TiO2 (current efficiency of ∼64.7% of and energy consumption of ∼5.2 W h g-1). In addition, the stability (ca. 22 h) was around 20-fold enhancement in RuO2@r-TiO2 compared with r-TiO2 (ca. 1.2 h). The results suggest a new route to provide a thin layer coating on r-TiO2 and to synthesize a high performance oxidant-generating anode.

Robust Magnetized Graphene Oxide Platform for In Situ Peptide Synthesis and FRET-Based Protease Detection.

Graphene oxide (GO)/peptide complexes as a promising disease biomarker analysis platform have been used to detect proteolytic activity by observing the turn-on signal of the quenched fluorescence upon the release of peptide fragments. However, the purification steps are often cumbersome during surface modification of nano-/micro-sized GO. In addition, it is still challenging to incorporate the specific peptides into GO with proper orientation using conventional immobilization methods based on pre-synthesized peptides. Here, we demonstrate a robust magnetic GO (MGO) fluorescence resonance energy transfer (FRET) platform based on in situ sequence-specific peptide synthesis of MGO. The magnetization of GO was achieved by co-precipitation of an iron precursor solution. Magnetic purification/isolation enabled efficient incorporation of amino-polyethylene glycol spacers and subsequent solid-phase peptide synthesis of MGO to ensure the oriented immobilization of the peptide, which was evaluated by mass spectrometry after photocleavage. The FRET peptide MGO responded to proteases such as trypsin, thrombin, and ß-secretase in a concentration-dependent manner. Particularly, ß-secretase, as an important Alzheimer's disease marker, was assayed down to 0.125 ng/mL. Overall, the MGO platform is applicable to the detection of other proteases by using various peptide substrates, with a potential to be used in an automated synthesis system operating in a high throughput configuration.

Microfluidic Generation of Amino-Functionalized Hydrogel Microbeads Capable of On-Bead Bioassay.

Microfluidic generation of hydrogel microbeads is a highly efficient and reproducible approach to create various functional hydrogel beads. Here, we report a method to prepare crosslinked amino-functionalized polyethylene glycol (PEG) microbeads using a microfluidic channel. The microbeads generated from a microfluidic device were evaluated by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and confocal laser scanning microscopy, respectively. We found that the microbeads were monodisperse and the amino groups were localized on the shell region of the microbeads. A swelling test exhibited compatibility with various solvents. A cell binding assay was successfully performed with RGD peptide-coupled amino-functionalized hydrogel microbeads. This strategy will enable the large production of the various functional microbeads, which can be used for solid phase peptide synthesis and on-bead bioassays.

A highly sensitive plasma-based amyloid-ß detection system through medium-changing and noise cancellation system for early diagnosis of the Alzheimer's disease.

We developed an interdigitated microelectrode (IME) sensor system for blood-based Alzheimer's disease (AD) diagnosis based on impedimetric detection of amyloid-ß (Aß) protein, which is a representative candidate biomarker for AD. The IME sensing device was fabricated using a surface micromachining process. For highly sensitive detection of several tens to hundreds of picogram/mL of Aß in blood, medium change from plasma to PBS buffer was utilized with signal cancellation and amplification processing (SCAP) system. The system demonstrated approximately 100-folds higher sensitivity according to the concentrations. A robust antibody-immobilization process was used for stability during medium change. Selectivity of the reaction due to the affinity of Aß to the antibody and the sensitivity according to the concentration of Aß were also demonstrated. Considering these basic characteristics of the IME sensor system, the medium change was optimized in relation to the absolute value of impedance change and differentiated impedance changes for real plasma based Aß detection. Finally, the detection of Aß levels in transgenic and wild-type mouse plasma samples was accomplished with the designed sensor system and the medium-changing method. The results confirmed the potential of this system to discriminate between patients and healthy controls, which would enable blood-based AD diagnosis.

Intra-abdominal necrotic lipoma diagnosed by computed tomography as a paraprostatic cyst.

A dog with a history of diarrhea and dyschezia exhibited an oval-shaped, soft-tissue opacity mass in the abdomen on radiographs. CT examination revealed a large fluid-filled structure displacing the urinary bladder, prostate, and colon. The mass had continuity with the prostate; therefore, it was tentatively diagnosed as a paraprostatic cyst. Cytologic examination was performed and the mass was considered a non-inflammatory cyst. However, after surgery, histopathologic examination revealed a necrotic, inflamed cystic lipoma. This case shows that unusual intra-abdominal lipomas may have a cystic appearance.

Evaluation of the ureteral jet in dogs by using color Doppler ultrasonography.

Ureteral jets are the result of a forceful ejection of urine from the vesicoureteral junction into the urinary bladder. By using color Doppler ultrasonography (US), we aimed to identify distinct ureteral jets in dogs, provide insight into ureteral obstruction, and facilitate study of urodynamics and vesicoureteric sphincter function via pulsed Doppler US. Color Doppler US was applied to detect urinary flow from the right ureteral orifices in eight healthy beagles. Under anesthesia, 0.9% saline (2.5 mL/kg/h) and furosemide (0.5 mg/kg) were administered intravenously to assist in detection of distinct ureteral jets and examine their frequency, velocity, duration, and waveform. In all dogs, ureteral jets were visualized under diuresis and anesthesia within 2 to 5 min (mean 3.57 ± 0.90 min) of the furosemide injection. Mean frequency, peak velocity, and duration of right ureteral jets in seven dogs in whom six ureteral jet waveform patterns were identified were 9.86 ± 3.09 jets/min, 34.07 ± 10.02 cm/sec, and 2.82 ± 1.08 sec, respectively. During the 10 min period starting 10 min after the initial jet appeared, only three waveforms were identified. Color Doppler US of ureteral jets may aid in assessing vesicoureteric sphincter function and ureteral abnormalities, such as ureteral obstruction, in dogs.

Monitoring of trace metals in coastal sediments around Korean Peninsula.

Spatial distributions and temporal variations of trace metals in Korean coastal sediments were investigated by determining seven metals (As, Cd, Cr, Cu, Hg, Pb, and Zn) in sediment collected from 71 stations between 2004 and 2010 (n=491). High metal concentrations were found in the southeastern coast, where there are many cities and industrial complexes, indicating that metal concentrations in Korean coastal sediment are significantly influenced by human activities associated with urbanization and industrialization. However, metal concentrations in sediment did not markedly vary temporally, which was because the coast is managed sustainably and because of the characteristics of the sediment environments. Based on the sediment quality guidelines and geoaccumulation index, Korean coastal sediments are practically unpolluted with Cd, Cr, Cu, Hg, Pb and Zn but moderately polluted with As. More intensive monitoring is required to determine the potential As sources and to understand the As geochemical cycles in Korean coastal sediments.

Chirality extension of an oxazine building block en route to total syntheses of (+)-hyacinthacine A2 and sphingofungin B.

Concise and stereocontrolled syntheses of (+)-hyacinthacine A2 and sphingofungin B were achieved via a diastereomerically enriched oxazine intermediate. The key strategies include palladium(0)-catalyzed intramolecular oxazine formation and diastereoselective nucleophilic addition to an aldehyde. (+)-Hyacinthacine A2 was synthesized in 13 steps and 10.2% overall yield and the synthesis of sphingofungin B proceeded in a linear sequence over 15 steps and 6.9% overall yield from (R)-methyl 2-benzamido-3-((tert-butyldimethylsilyl)oxy)propanoate.

Catalytic upgrading of xylan over mesoporous Y catalyst.

In-situ catalytic cracking of xylan, a model compound of hemicellulose, was carried out using pyrolysis-gas chromatography/mass spectrometry over mesoporous Y for the first time. Experiments were conducted at three different temperatures, 400 degrees C, 450 degrees C, and 500 degrees C, to investigate the effect of reaction temperature. Three different biomass-to-catalyst ratios, 1:1, 1:2, and 1:3, were tested at 500 degrees C to examine the effect of catalyst dose. In addition, the catalytic activity of mesoporous Y was compared with that of Al-MCM-41. The catalysts used were characterized by N2 adsorption-desorption, temperature programmed desorption of NH3, and X-ray diffraction. The main pyrolysis products of xylan were acids, hydrocarbons, phenolics, oxygenates, aromatics, and polycyclic aromatic hydrocarbons. Mesoporous Y, which has acid sites with larger quantity and stronger acidity than those of Al-MCM-41, was shown to enhance the quality of bio-oil to a larger extent, producing a larger quantity of high-value-added products, such as aromatics and furans.

Conversion of kraft lignin over hierarchical MFI zeolite.

Catalytic pyrolysis of kraft lignin was carried out using pyrolysis gas chromatography/mass spectrometry. Hierarchical mesoporous MFI was used as the catalyst and another mesoporous material Al-SBA-15 was also used for comparison. The characteristics of mesoporous MFI were analyzed by X-ray diffraction patterns, N2 adsorption-desorption isotherms, and temperature programmed desorption of NH3. Two catalyst/lignin mass ratios were tested: 5/1 and 10/1. Aromatics and alkyl phenolics were the main products of the catalytic pyrolysis of lignin over mesoporous MFI. In particular, the yields of mono-aromatics such as benzene, toluene, ethylbenzene, and xylene were increased substantially by catalytic upgrading. Increase in the catalyst dose enhanced the production of aromatics further, which is attributed to decarboxylation, decarbonlyation, and aromatization reactions occurring over the acid sites of mesoporous MFI.