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Background Genomic instability is a hallmark of various cancers, and DNA repair is an essential process for maintaining genomic integrity. Mammalian cells have developed various DNA repair mechanisms in response to DNA damage. Compared to the cellular response to DNA damage, the in vivo DNA damage response (DDR) of specific tissues has not been studied extensively. Objective In this study, mice were exposed to whole-body gamma (γ)-irradiation to evaluate the specific DDR of various tissues. We treated male C57BL6/J mice with γ-irradiation at different doses, and the DDR protein levels in different tissues were analyzed. Results The level of gamma-H2A histone family member X (γH2AX) increased in most organs after exposure to γ-irradiation. In particular, the liver, lung, and kidney tissues showed higher γH2AX induction upon DNA damage, compared to that in the brain, muscle, and testis tissues. RAD51 was highly expressed in the testis, irrespective of irradiation. The levels of proliferating cell nuclear antigen (PCNA) and ubiquitinated PCNA increased in lung tissues upon irradiation, suggesting that the post-replication repair may mainly operate in the lungs in response to γ-irradiation. Conclusion These results suggest that each tissue has a preferable repair mechanism in response to γ-irradiation. Therefore, the understanding and application of tissue-specific DNA damage responses could improve the clinical approach of radiotherapy for treating specific cancers.

Myelosuppression is a major adverse effect of chemotherapy. With the increasing number of cancer patients worldwide, there is a growing interest in therapeutic approaches that reduce the adverse effects of chemotherapy.

The present study investigated the potential subchronic toxicity of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG) in mice. The test reagent was administered once-daily by intravenous injection for 4 weeks at 0, 100, 200, or 300 mg/kg/day doses. Additional recovery groups (vehicle control and high dose groups) were observed for a 2-week recovery period. During the test period, mortality, clinical signs, body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. An increase in the percentages of basophil and large unstained cells was observed in the 200 and 300 mg/kg/day groups of both sexes. In addition, the absolute and relative weights of the spleen were higher in males given 300 mg/kg/day relative to the concurrent controls. However, these findings were considered of no toxicological significance because the changes were minimal, were not accompanied by other relevant results (eg, correlating microscopic changes), and were not observed at the end of the 2-week recovery period indicating recovery of the findings. Based on the results, SAMiRNA-AREG did not cause treatment-related adverse effects at dose levels of up to 300 mg/kg/day in mice after 4-week repeated intravenous doses. Under these conditions, the no-observed-adverse-effect level of the SAMiRNA-AREG was ≥300 mg/kg/day in both sexes and no target organs were identified.

Sustainable and green energy techniques are in high demand as new energy sources. Over the decades, streaming potential/current has attracted attention as a hydrovoltaic energy technology. However,...

Celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, was approved as a non-steroidal anti-inflammatory drug (NSAID), and this therapeutic application has been expanded to several other diseases, including colon cancer. Notably, a treatment strategy combining the use of celecoxib and radiation therapy has been employed for improving the control of local cancers. In this study, we examined the effect of celecoxib on irradiation-induced intestinal damage. The twenty four mice (BALB/c) were divided into four groups; 1) sham-irradiated control group, 2) celecoxib-treated group, 3) irradiated group, and 4) celecoxib-treated irradiation group. Mice were orally administered celecoxib at a dose of 25 mg/kg in a 0.1 mL volume, daily for 4 days after irradiation exposure (10 Gy). Then, histological examinations of the jejunal villous height, crypt survival, and crypt size were performed. The expression of COX-2 after administration of celecoxib in irradiated mice was examined by employing immunohistochemistry, Western blotting, and qPCR analysis. The jejunal villi height and the crypt survival were reduced in the irradiation group compared with the sham-irradiated group. Celecoxib treatment in irradiation mice even more decreased those indicators. Crypt size was increased in the radiation group compared to the sham-irradiated control group, whereas the size was decreased in the celecoxibtreated irradiation group compared with the group exposed to the radiation injury. COX-2 expression was detected in the crypt of the small intestine, and COX-2 expression was increased in the crypt lesion following radiation exposure. However, COX-2 expression was reduced in the celecoxib-treated irradiation group. Therefore, in the present study, we confirmed that celecoxib treatment after irradiation aggravated the irradiation-induced intestinal damage. These results suggest that a caution need to be administered when celecoxib treatment is performed in combination with radiation therapy for cancer treatment.

Graphical abstract, Highlights • SAMiRNA-AREG is a modified siRNA nanoparticle for treatment of pulmonary fibrosis. • Safety pharmacology of SAMiRNA-AREG was evaluated using core battery studies. • No adverse effects on the neurobehavior, respiratory, and cardiovascular systems. • These data provide important safety data for clinical trials in humans., The present safety pharmacology core battery studies (neurobehavior, respiratory, cardiovascular system, and human ether a-go-go (hERG) channel current) investigated the potential harmful effects of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG). The SAMiRNA-AREG was administered by single intravenous injection at up to 300 mg/kg and 100 mg/kg in mice and monkeys, respectively. The hERG assay was performed in Chinese hamster ovary (CHO) cells at SAMiRNA-AREG concentrations of up to 200 μg/mL. In the evaluation on neurobehavior, a transient decrease in body temperature was found at 0.5 h (30 min) post-dose at both sexes in mice, with a single 300 mg/kg dose of SAMiRNA-AREG. However, these effects had returned to normal at 1 h post-dose. In the evaluation on hERG channel current, there were statistically significant differences in the inhibition of peak hERG potassium channel current between the 20, 100, and 200 μg/mL SAMiRNA-AREG treatment groups and the vehicle control group. However, these effects were less potent than that of E-4031, a positive control article. For the respiratory and cardiovascular systems, no treatment-related changes were observed in mice or monkeys. Thus, under these experimental conditions, these studies suggest that SAMiRNA-AREG showed no adverse effects on the neurobehavior, respiratory, and cardiovascular function.

Development of efficient surface passivation methods for semiconductor devices is crucial to counter the degradation in their electrical performance owing to scattering or trapping of carriers in the channels induced by molecular adsorption from the ambient environment. However, conventional dielectric deposition involves the formation of additional interfacial defects associated with broken covalent bonds, resulting in accidental electrostatic doping or enhanced hysteretic behavior. In this study, centimeter-scaled van der Waals passivation of transition metal dichalcogenides (TMDCs) is demonstrated by stacking hydrocarbon (HC) dielectrics onto MoSe

The non-POU domain-containing octamer-binding protein (NONO, also referred to as p54nrb) is a multifunctional nuclear protein engaging in transcriptional regulation, mRNA splicing, nuclear retention of defective RNA, and DNA repair. Emerging evidence has demonstrated that p54nrb is subjected to various posttranslational modifications, including phosphorylation and methylation, which may be important regulators of its multifunction. However, among these modifications, direct evidence of p54nrb acetylation and its underlying mechanism remains unclear. In this study, we reported that lysine 371 of p54nrb was reversibly acetylated by the acetyltransferase general control non-depressible 5 (GCN5) and deacetylase sirtuin 1 (SIRT1), which was crucial for activity of p54nrb to inhibit interleukin-8 (IL-8) expression. Mechanistically, GCN5-mediated acetylation attenuates the recruitment of p54nrb on its core binding motif within the IL-8 gene promoter, preferentially increasing the expression of the IL-8 gene. In contrast, deacetylation by SIRT1 reverses this process. Altogether, our data suggest that reversible acetylation is an important switch for the multiple nuclear functions of p54nrb/NONO.

A clothing-type wearable display can be utilized in fashion, bio-healthcare, and safety industries as well as smart textiles for the internet of things (IoTs) and wearable devices. In response to this trend, we demonstrate a textile display that can endure the active movements of a human body. It can be applied to any kind of textile, and is durable against conditions such as rain, sweat, and washing. As a key technology for realizing the multi-directional wrinkle-able textile display, we fabricated a stress-lowering textile platform with an ultrathin planarization layer replicated from the flat surface of glass. An elastomeric strain buffer for reducing mechanical stress is also inserted into the textile platform. Here, organic light-emitting diodes (OLEDs) with red, green and blue color, thin film transistors (TFTs) fabricated at a low temperature below 150 °C, and a washable encapsulation layer blocking both gas and liquid were demonstrated on the textile platform.

Purpose This study aims to investigate the effect of gonadotropin-releasing hormone agonist (GnRHa) on growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis and to evaluate whether -202 A/C IGF binding protein-3 (IGFBP-3) promoter polymorphism affects the growth velocity in girls with central precocious puberty (CPP) during treatment. Methods Data was collected from 97 girls, aged below 9 years, diagnosed with precocious puberty and treated with GnRHa for at least 1 year in Kangdong Sacred Heart Hospital from 2014 to 2015. Their body height, weight, change in height standard deviation scores (∆SDSs), serum IGF-1, serum IGFBP-3, bone age (BA), and -202 A/C IGFBP-3 promoter polymorphism were measured before and after GnRHa treatment. Interrelationship between the variables was further calculated. Results During treatment, height SDS, IGF-1 SDS, IGFBP-3 SDS, and IGF-1/IGFBP-3 ratio significantly decreased. Significant correlations were observed between the ∆IGF-1 SDS and ∆height SDS (r = 0.405, p < 0.001). The presence of C allele was significantly correlated with IGF-1 SDS after the treatment (p = 0.049) and IGFBP-3 SDS before and after the treatment respectively, (p = 0.012 and p = 0.001) but not with ∆IGF-1 SDS, ∆IGFBP-3 SDS, ∆IGF-1/IGFBP-3 ratio, or ∆height SDS. Conclusion Growth velocity during GnRHa treatment is related to ∆IGF-1 SDS, concluding the apparent impact of GnRHa on the GH-IGF-1 axis. -202 A/C IGFBP-3 promoter polymorphism does not affect the growth velocity of GnRHa in CPP girls.

Centrosomes are the primary microtubule-organizing centers that are important for mitotic spindle assembly. Centrosome amplification is commonly observed in human cancer cells and contributes to genomic instability. However, it is not clear how centrosome duplication is dysregulated in cancer cells. Here, we report that ATAD5, a replisome protein that unloads PCNA from chromatin as a replication factor C-like complex (RLC), plays an important role in regulating centrosome duplication. ATAD5 is present at the centrosome, specifically at the base of the mother and daughter centrioles that undergo duplication. UAF1, which interacts with ATAD5 and regulates PCNA deubiquitination as a complex with ubiquitin-specific protease 1, is also localized at the centrosome. Depletion of ATAD5 or UAF1 increases cells with over-duplicated centrosome whereas ATAD5 overexpression reduces such cells. Consistently, the proportion of cells showing the multipolar mode of chromosome segregation is increased among ATAD5-depleted cells. The localization and function of ATAD5 at the centrosomes do not require other RLC subunits. UAF1 interacts and co-localizes with ID1, a protein that increases centrosome amplification upon overexpression. ATAD5 depletion reduces interactions between UAF1 and ID1 and increases ID1 signal at the centrosome, providing a mechanistic framework for understanding the role of ATAD5 in centrosome duplication.

Deep ultrasound localization microscopy (deep-ULM) allows sub-wavelength resolution imaging with deep learning. However, the injection of contrast agents (CAs) in deep-ULM is debatable because of their potential risk. In this study, we propose a deep learning-based super-resolution ultrasound (DL-SRU), which employs the concept of deep-ULM and a convolutional neural network. The network is trained with synthetic tracer images to localize positions of red blood cells (RBCs) and reconstruct vessel geometry at high resolution, even for CA-free ultrasound (US) images. The proposed algorithm is validated by comparing the full width at half-maximum values of the vascular profiles reconstructed by other techniques, such as the standard ULM and the US average intensity under in silico and in vitro conditions. RBC localization by DL-SRU is also compared with that by other localization approaches to validate its performance under in vivo condition, especially for veins in the human lower extremity. Furthermore, a two-frame particle tracking velocimetry (PTV) algorithm is applied to DL-SRU localization for accurate flow velocity measurement. The velocity profile obtained by applying the PTV is compared with a theoretical value under in vitro condition to verify its compatibility with the flow measurement modality. The velocity vectors of individual RBCs are obtained to determine the applicability to in vivo conditions. DL-SRU can achieve high-resolution vessel morphology and flow dynamics in vasculature, mapping 110 super-resolved images per second on a standard PC, regardless of various imaging conditions. As a result, the DL-SRU technique is much more robust in localization compared with previous deep-ULM. In addition, the performance of DL-SRU is nearly the same as that of deep-ULM in rapid computational processing and high measurement accuracy. Thus, DL-SRU might become an effective and useful instrument in clinical practice.

Fibrosis is a serious unintended side effect of radiation therapy. In this study, we aimed to investigate whether amphiregulin (AREG) plays a critical role in fibrosis development after total-body irradiation (TBI). We found that the expression of AREG and fibrotic markers, such as α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1α1), was elevated in the kidneys of 6 Gy TBI mice. Expression of AREG and α-SMA was mainly elevated in the proximal and distal tubules of the kidney in response to TBI, which was confirmed by immunofluorescence staining. Knockdown of Areg mRNA using self-assembled-micelle inhibitory RNA (SAMiRNA) significantly reduced the expression of fibrotic markers, including α-SMA and COL1α1, and inflammatory regulators. Finally, intravenous injections of SAMiRNA targeting mouse Areg mRNA (SAMiRNA-mAREG) diminished radiation-induced collagen accumulation in the renal cortex and medulla. Taken together, the results of the present study suggest that blocking of AREG signaling via SAMiRNA-mAREG treatment could be a promising therapeutic approach to alleviate radiation-induced kidney fibrosis.

An ideal cancer therapeutic strategy involves the selective killing of cancer cells without affecting the surrounding normal cells. However, researchers have failed to develop such methods for achieving selective cancer cell death because of shared features between cancerous and normal cells. In this study, we have developed a therapeutic strategy called the cancer-specific insertions-deletions (InDels) attacker (CINDELA) to selectively induce cancer cell death using the CRISPR-Cas system. CINDELA utilizes a previously unexplored idea of introducing CRISPR-mediated DNA double-strand breaks (DSBs) in a cancer-specific fashion to facilitate specific cell death. In particular, CINDELA targets multiple InDels with CRISPR-Cas9 to produce many DNA DSBs that result in cancer-specific cell death. As a proof of concept, we demonstrate here that CINDELA selectively kills human cancer cell lines, xenograft human tumors in mice, patient-derived glioblastoma, and lung patient-driven xenograft tumors without affecting healthy human cells or altering mouse growth.

Titanium nitride (TiN) is a material of interest for electrodes owing to its high-temperature stability, robustness, low-cost, and suitable electrical properties. Herein, we studied the surface morphology and electrical properties of TiN thin film deposited onto an Si/SiO2 substrate through direct current (DC) sputtering with a high-purity TiN target in an argon-gas environment. The electrical properties and surface morphology of TiN thin film significantly improved with increased source power and decreased working pressure. The improved electrical properties could be attributed to the suppressed secondary phase (Ti2N) formation and the reduced electron scattering on smoother surface. Consequently, high-quality TiN thin film with the lowest resistivity (ρ = 0.1 mΩ·cm) and the smallest surface roughness (RMS roughness, Rq = 0.3 nm) was obtained under the optimized condition. The TiN film was further used as the bottom electrode for a metal–insulator–metal (MIM) capacitor. Results demonstrated that the electrical properties of TiN film were comparable to those of noble-metal thin films. Therefore, the TiN thin film fabricated by DC sputtering method had excellent electrical properties and good Rq, indicating its potential applications in MIM capacitors and Si technology.

The genome sequence of Tomato spotted wilt orthotospovirus (TSWV) isolated from gerbera was determined. The genome consists of L, M, and S segments containing 8,920, 4,775, and 2,970 nucleotides, respectively. BLASTn analysis showed respective identities of 99.84%, 99.71%, and 99.50% with another Korean isolate, GS, from pepper.

The genome sequence of Tomato spotted wilt orthotospovirus (TSWV) isolated from gerbera was determined. The genome consists of L, M, and S segments containing 8,920, 4,775, and 2,970 nucleotides, respectively. BLASTn analysis showed respective identities of 99.84%, 99.71%, and 99.50% with another Korean isolate, GS, from pepper.

Chemical functionalization is demonstrated to enhance the p-type electrical performance of two-dimensional (2D) layered tungsten diselenide (WSe2) field-effect transistors (FETs) using a one-step dipping process in an aqueous solution of ammonium sulfide [(NH4)2S(aq)]. Molecularly resolved scanning tunneling microscopy and spectroscopy reveal that molecular adsorption on a monolayer WSe2 surface induces a reduction of the electronic band gap from 2.1 to 1.1 eV and a Fermi level shift toward the WSe2 valence band edge (VBE), consistent with an increase in the density of positive charge carriers. The mechanism of electronic transformation of WSe2 by (NH4)2S(aq) chemical treatment is elucidated using density functional theory calculations which reveal that molecular "SH" adsorption on the WSe2 surface introduces additional in-gap states near the VBE, thereby, inducing a Fermi level shift toward the VBE along with a reduction in the electronic band gap. As a result of the (NH4)2S(aq) chemical treatment, the p-branch ON-currents (ION) of back-gated few-layer ambipolar WSe2 FETs are enhanced by about 2 orders of magnitude, and a ∼6× increase in the hole field-effect mobility is observed, the latter primarily resulting from the p-doping-induced narrowing of the Schottky barrier width leading to an enhanced hole injection at the WSe2/contact metal interface. This (NH4)2S(aq) chemical functionalization technique can serve as a model method to control the electronic band structure and enhance the performance of devices based on 2D layered transition-metal dichalcogenides.

Al2O3 and Al2O3/HfO2 bilayer gate stacks were directly deposited on the surface of 2D materials via low temperature ALD/CVD of Al2O3 and high temperature ALD of HfO2 without any surface functionalization. The process is self-nucleating even on inert surfaces because a chemical vapor deposition (CVD) component was intentionally produced in the Al2O3 deposition by controlling the purge time between TMA and H2O precursor pulses at 50 °C. The CVD growth component induces formation of sub-1 nm AlOx particles (nanofog) on the surface, providing uniform nucleation centers. The ALD process is consistent with the generation of sub-1 nm gas phase particles which stick to all surfaces and is thus denoted as nanofog ALD. To prove the ALD/CVD Al2O3 nucleation layer has the conformality of a self-limiting process, the nanofog was deposited on a high aspect ratio Si3N4/SiO2/Si pattern surface; conformality of >90% was observed for a sub 2 nm film consistent with a self-limiting process. MoS2 and HOPG (highly oriented pyrolytic graphite) metal oxide semiconductor capacitors (MOSCAPs) were fabricated with single layer Al2O3 ALD at 50 °C and with the bilayer Al2O3/HfO2 stacks having Cmax of ∼1.1 µF/cm2 and 2.2 µF/cm2 respectively. In addition, Pd/Ti/TiN gates were used to increase Cmax by scavenging oxygen from the oxide layer which demonstrated Cmax of ∼2.7 µF/cm2. This is the highest reported Cmax and Cmax/Leakage of any top gated 2D semiconductor MOSCAP or MOSFET. The gate oxide prepared on a MoS2 substrate results in more than an 80% reduction in Dit compared to a Si0.7Ge0.3(0 0 1) substrate. This is attributed to a Van der Waals interaction between the oxide layer and MoS2 surface instead of a covalent bonding allowing gate oxide deposition without the generation of dangling bonds.

Poly ADP-ribosylation (PARylation) is a post-translational modification process. Following the discovery of PARP-1, numerous studies have demonstrated the role of PARylation in the DNA damage and repair responses for cellular stress and DNA damage. Originally, studies on PARylation were confined to PARP-1 activation in the DNA repair pathway. However, the interplay between PARylation and DNA repair suggests that PARylation is important for the efficiency and accuracy of DNA repair. PARylation has contradicting roles; however, recent evidence implicates its importance in inflammation, metabolism, and cell death. These differences might be dependent on specific cellular conditions or experimental models used, and suggest that PARylation may play two opposing roles in cellular homeostasis. Understanding the role of PARylation in cellular function is not only important for identifying novel therapeutic approaches; it is also essential for gaining insight into the mechanisms of unexplored diseases. In this review, we discuss recent reports on the role of PARylation in mediating diverse cellular functions and homeostasis, such as DNA repair, inflammation, metabolism, and cell death.

Background This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). Methods We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000–September 2017) at our center. Results Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34+ cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. Conclusion Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis., Graphical Abstract

Core-binding factor (CBF)-acute myeloid leukemia (AML) generally have a favorable prognosis. However, approximately 50% of patients experience disease relapse during or after post-remission therapy. Retrospective studies on autologous hematopoietic cell transplantation (AHCT) have shown improved survival with decreased relapse rate in CBF-AML. In this prospective study, we evaluate the outcomes of AHCT following high-dose cytarabine (HiDAC) consolidation in patients with CBF-AML in first complete remission (CR). Adult patients with CBF-AML achieving first CR after induction chemotherapy were eligible for the study. High-dose chemotherapy before AHCT included intravenous busulfan (3.2 mg/kg/day, days − 7 to − 5) and etoposide (400 mg/m2/day, days − 3 to − 2). Twenty-nine patients, 17 with t(8;21) and 12 with inv(16), underwent AHCT following 2 or 3 courses of HiDAC consolidation. The estimated 5-year overall and disease-free survival rates were between 89.0% and 82.5%, respectively. The cumulative incidences of relapse and non-relapse mortality were between 17.5% and 0%, respectively. Presence of measurable residual disease (MRD) before AHCT and KIT mutation were significantly associated with relapse after transplantation. In conclusion, the post-remission strategy of AHCT following HiDAC consolidation in CBF-AML was feasible and efficacious. Assays for MRD and KIT mutation may guide selection of patients who will benefit from AHCT in CBF-AML in first CR.

The modern semiconductor industry is going through rapid changes as new markets and technologies appear. In this paper, such technology-intensive firms&rsquo, relationship between technological capability and financial performance is analyzed with regression analysis. Revenue and market capitalization are used as dependent variables. For the independent variables, the technological intensity, technological diversity, technological asset, and technological efficiency are used. The analysis results revealed different effects of technological capability on financial performance. Also, regression analysis is conducted by dividing firms into high and low groups based on technological asset and technological efficiency, and the analysis result revealed different effects of technological intensity and technological diversity on financial performance. For technological asset, the financial performance in the high group is affected more by technological intensity, and the financial performance in the low group is affected more by technological diversity. For technological efficiency, only the financial performance in the high group is affected by technological intensity. Although both groups&rsquo, financial performance is somewhat affected by technological diversity, there was no statistically significant differences between the groups. By separating the effect of technological capability on financial performance, this research can provide more detailed analysis results compared to previous literature and the methods of managing technological capability for semiconductor firms.

For more than three decades, numerous studies have demonstrated the function of p53 in cell cycle, cellular senescence, autophagy, apoptosis, and metabolism. Among diverse functions, the essential role of p53 is to maintain cellular homeostatic response to stress by regulating proliferation and apoptosis. Recently, adipocytes have been studied with increasing intensity owing to the increased prevalence of metabolic diseases posing a serious public health concern and because metabolic dysfunction can directly induce tumorigenesis. The prevalence of metabolic diseases has steadily increased worldwide, and a growing interest in these diseases has led to the focus on the role of p53 in metabolism and adipocyte differentiation with or without metabolic stress. However, our collective understanding of the direct role of p53 in adipocyte differentiation and function remains insufficient. Therefore, this review focuses on the newly discovered roles of p53 in adipocyte differentiation and function.

Studies of medical flow imaging have technical limitations for accurate analysis of blood flow dynamics and vessel wall interaction at arteries. We propose a new deep learning-based boundary detection and compensation (DL-BDC) technique in ultrasound (US) imaging. It can segment vessel boundaries by harnessing the convolutional neural network and wall motion compensation in the analysis of near-wall flow dynamics. The network enables training from real and synthetic US images together. The performance of the technique is validated through synthetic US images and tissue-mimicking phantom experiments. The neural network performs well with high Dice coefficients of over 0.94 and 0.9 for lumens and walls, outperforming previous segmentation techniques. Then, the performance of the wall motion compensation is examined for compliant phantoms. When DL-BDC is applied to flow influenced by wall motion, root-mean-square errors are less than 0.07%. The technique is utilized to analyze flow dynamics and wall interaction with varying elastic moduli of the phantoms. The results show that the flow dynamics and wall shear stress values are consistent with the expected values of the compliant phantoms, and their wall motion behavior is observed with pulse wave propagation. This strategy makes US imaging capable of simultaneous measurement of blood flow and vessel dynamics in human arteries for their accurate interaction analysis. DL-BDC can segment vessel walls fast, accurately, and robustly. It enables to measure the near-wall flow precisely by determining the vessel boundary dynamics. This approach can be beneficial in flow dynamics and wall interaction analyses in various biomedical applications.

Amphiregulin (AREG) is a transmembrane glycoprotein recently implicated in kidney fibrosis. Previously, we reported that the AREG-targeting Self-Assembled-Micelle inhibitory RNA (SAMiRNA-AREG) alleviated fibrosis by stably silencing the AREG gene, and reduced the side effects of conventional siRNA treatment of pulmonary fibrosis. However, the therapeutic effect of SAMiRNA-AREG in renal fibrosis has not been studied until now. We used two animal models of renal fibrosis generated by a unilateral ureteral obstruction (UUO) and an adenine diet (AD) to investigate whether SAMiRNA-AREG inhibited renal fibrosis. To investigate the delivery of SAMiRNA-AREG to the kidney, Cy5-labeled SAMiRNA-AREG was injected into UUO- and AD-induced renal fibrosis models. In both kidney disease models, SAMiRNA-AREG was delivered primarily to the damaged kidney. We also confirmed the protective effect of SAMiRNA-AREG in renal fibrosis models. SAMiRNA-AREG markedly decreased the UUO- and AD-induced AREG mRNA expression. Furthermore, the mRNA expression of fibrosis markers, including α-smooth muscle actin, fibronectin, α1(I) collagen, and α1(III) collagen in the UUO and AD-induced kidneys, was diminished in the SAMiRNA-AREG-treated mice. The transcription of inflammatory markers (tumor necrosis factor-α and monocyte chemoattractant protein-1) and adhesion markers (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1) was attenuated. The hematoxylin and eosin, Masson’s trichrome, and immunohistochemical staining results showed that SAMiRNA-AREG decreased renal fibrosis, AREG expression, and epidermal growth factor receptor (EGFR) phosphorylation in the UUO- and AD-induced models. Moreover, we studied the effects of SAMiRNA-AREG in response to TGF-β1 in mouse and human proximal tubule cells, and mouse fibroblasts. TGF-β1-induced extracellular matrix production and myofibroblast differentiation were attenuated by SAMiRNA-AREG. Finally, we confirmed that upregulated AREG in the UUO or AD models was mainly localized in the distal tubules. In conclusion, SAMiRNA-AREG represents a novel siRNA therapeutic for renal fibrosis by suppressing EGFR signals.

Diabetes mellitus is a chronic metabolic disease, and its progression leads to serious complications. Although various novel therapeutic approaches for diabetes mellitus have developed in the last three decades, its prevalence has been rising more rapidly worldwide. Silk-related materials have been used as anti-diabetic remedies in Oriental medicine and many studies have shown the effects of silk fibroin (SF) in both in vitro and in vivo models. In our previous works, we reported that hydrolyzed SF improved the survival of HIT-T15 cells under high glucose conditions and ameliorated diabetic dyslipidemia in a mouse model. However, we could not provide a precise molecular mechanism. To further evaluate the functions of hydrolyzed SF on the pancreatic &beta, cell, we investigated the effects of hydrolyzed SF on the pancreatic &beta, cell proliferation and regeneration in the mouse model. Hydrolyzed SF induced the expression of the proliferating cell nuclear antigen (PCNA) and reduced the apoptotic cell population in the pancreatic islets. Hydrolyzed SF treatment not only induced the expression of transcription factors involved in the pancreatic &beta, cell regeneration in RT-PCR results but also increased neurogenin3 and Neuro D protein levels in the pancreas of those in the group treated with hydrolyzed SF. In line with this, hydrolyzed SF treatment generated insulin mRNA expressing small cell colonies in the pancreas. Therefore, our results suggest that the administration of hydrolyzed SF increases the pancreatic &beta, cell proliferation and regeneration in C57BL/KsJ-Leprdb/db mice.

Deformation of vulnerable stenosis under pulsatile flow conditions and flow-induced stress acting on a fibrous cap are revealed to be proportional to the square of flow rate divided by fibrous cap thickness. Angle variation of jet flow at the throat of vulnerable stenosis is recommended as a diagnostic index for predicting the stress on the cap.

Several arterial diseases are closely related with mechanical properties of the blood vessel and interactions of flow-vessel dynamics such as mean flow velocity, wall shear stress (WSS) and vascular strain. However, there is an opportunity to improve the measurement accuracy of vascular properties and hemodynamics by adopting deep learning-based ultrasound imaging for flow-vessel dynamics (DL-UFV). In this study, the DL-UFV is proposed by devising an integrated neural network for super-resolved localization and vessel wall segmentation, and it is also combined with tissue motion estimation and flow measurement techniques such as speckle image velocimetry and speckle tracking velocimetry for measuring velocity field information of blood flow. Performance of the DL-UFV is verified by comparing with other conventional techniques in tissue-mimicking phantoms. After the performance verification, in vivo feasibility is demonstrated in the murine carotid artery with different pathologies: aging and diabetes mellitus (DM). The mutual comparison of flow-vessel dynamics and histological analyses shows correlations between the immunoreactive region and abnormal flow-vessel dynamics interactions. The DL-UFV improves biases in measurements of velocity, WSS, and strain with up to 4.6-fold, 15.1-fold, and 22.2-fold in the tissue-mimicking phantom, respectively. Mean flow velocities and WSS values of the DM group decrease by 30% and 20% of those of the control group, respectively. Mean flow velocities and WSS values of the aging group (34.11 cm/s and 13.17 dyne/cm2) are slightly smaller than those of the control group (36.22 cm/s and 14.25 dyne/cm2). However, the strain values of the aging and DM groups are much smaller than those of the control group (p < 0.05). This study shows that the DL-UFV performs better than the conventional ultrasound-based flow and strain measurement techniques for measuring vascular stiffness and complicated flow-vessel dynamics. Furthermore, the DL-UFV demonstrates its excellent performance in the analysis of the hemodynamic and hemorheological effects of DM and aging on the flow and vascular characteristics. This work provides useful hemodynamic information, including mean flow velocity, WSS and strain with high-resolution for diagnosing the pathogenesis of arterial diseases. This information can be used for monitoring progression and regression of atherosclerotic diseases in clinical practice.

Thermal ALD of TaNx and TiNx films was performed using hydrazine (N2H4) as a reactive N-containing source. Ultralow temperature (100 °C and 300 °C) growth of TaNx was observed using N2H4 and tris(diethylamido)(tert-butylimido) tantalum (TBTDET); XPS showed nearly stoichiometric Ta3N5 films were deposited with below 10% O and 5% C incorporation. Stoichiometric TiNx films grown at 300 °C with tetrakis(dimethylamido) titanium (TDMAT) showed an RMS roughness below 2 nm consistent with good nucleation density. High conductivity nitride films were grown by a thermal low-temperature TiNx ALD process using anhydrous N2H4 and titanium tetrachloride (TiCl4) from 300 to 400 °C; uniform, nearly stoichiometric films of 0.44 nm RMS roughness were deposited. Compared to NH3 grown films, XPS confirmed N2H4 grown films contained fewer O, C, and Cl impurities consistent with lower resistivities being observed with N2H4. The data is consistent with N2H4 serving as a reducing agent and a good proton donor to Ta and Ti ligands.