Search

Background: Hypoglycemia is a significant problem for all neonates and requires minimally invasive and reliable monitoring. The primary objective of this study was to verify the safety and accuracy of the continuous glucose monitoring (CGM) of full‐term neonates using Freestyle Libre, a flash glucose monitoring (FGM) device. Methods: The study was conducted on 20 neonates. Shortly after birth, we placed the FGM sensor on the outside of the neonates' thighs. We scanned the CGM values at 60, 120, 180, and 360 min after birth and simultaneously obtained blood glucose values with plantar capillaries by heel puncture. The neonates wore the sensors for up to 6 h and then they were removed. Results: Of the 75 data points to be measured, 65 points (86.7%) were obtained by scan. There was no change in the sensor attachment site in 12 of 18 completed cases in this study but we observed slight induration in four cases (22.2%) and slight redness in one case (5.5%) at the sensor puncture site. A moderate correlation was observed between the CGM and blood glucose values. The CGM values tended to be low at 120, 180, and 360 min after birth, and tended to be high only at 60 min after birth. Conclusions: The CGM device was safe to wear on the neonate and the CGM data correlated well with blood glucose levels. There was dissociation between CGM data and blood glucose levels in the acute period soon after birth when the blood glucose levels changed rapidly. [ABSTRACT FROM AUTHOR]

In our previous study, a novel method combining underwater high-voltage plasma discharge with acoustic cavitation (ACAP) was developed and implemented using rhodamine B (RhB) as a model organic pollutant. Results revealed that injecting argon gas into the ACAP reactor positively influences RhB decomposition efficiency, but there is still further potential for improvement. The aim of this study was therefore to further improve the efficiency of the ACAP process through Fenton reactions. Two options for ferrous ion supply were considered: the addition of FeCl2 or the dissolution of iron from ACAP reactor steel parts into the RhB-containing solution. The results revealed that the degradation efficiency is increased by 20% due to the Fenton reactions when the concentration of ferrous ions reaches an optimal value. Lower pH was found to be desirable for the effect of Fenton reactions. Based on measurements using high performance liquid chromatography, a plausible mechanism of RhB degradation by the ACAP process assisted by Fenton reactions is additionally proposed and discussed. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) are used in a wide range of applications, and the size control and stability of the nanoparticles are crucial aspects in their applications. In the present study, cyclized poly(ethylene glycol) (c-PEG) with various molecular weights, along with linear PEG with hydroxy chain ends (HO–PEG–OH) and methoxy chain ends (MeO–PEG–OMe) were applied for the Tollens' synthesis of AgNPs. The particle size was significantly affected by the topology and end groups of PEG. For example, the size determined by TEM was 40 ± 7 nm for HO–PEG5k–OH, 21 ± 4 nm for c-PEG5k, and 48 ± 9 nm for MeO–PEG5k–OMe when the molar ratio of PEG to AgNO3 (ω) was 44. The stability of AgNPs was also drastically improved by cyclization; the relative UV–Vis absorption intensity (A/A0 × 100%) at λmax to determine the proportion of persisting AgNPs in an aqueous NaCl solution (37.5 mM) was 58% for HO–PEG5k–OH, 80% for c-PEG5k, and 40% for MeO–PEG5k–OMe, despite the fact that AgNPs with c-PEG5k were much smaller than those with HO–PEG5k–OH and MeO–PEG5k–OMe. [ABSTRACT FROM AUTHOR]

Aluminum contaminations, particularly iron, present a serious challenge to aluminum recycling technology. This is why many studies have focused on the reduction of detrimental effects of iron-containing contaminations through addition of elements such as manganese and chromium. However, the desirable modifying effect is often difficult to achieve because it would require concentrations of added elements greater than the allowable limits for many aluminum alloys. Thus, an alternative way to obtain the modifying effect, by using a much smaller amount of the modifying elements which are added to the aluminum melt as solid particles, was proposed in this study. The main goal of the present study was to investigate the possibilities of fabricating an aluminum master alloy by adding CrSi2 particles onto the surface of the vortex formed during mechanical agitation of molten aluminum. Two kinds of CrSi2 powder were used: one was commercial powder, and the other was self-synthesized CrSi2 via mechanical alloying by planetary ball milling. The results revealed that CrSi2 particles with a larger size penetrate the melt better. Particles of three kinds were found to exist in the Al melt after the addition of CrSi2 powder: (1) inclusions of eutectic origin formed at the last stage of crystallization, (2) mixtures of Al-Cr compounds and original CrSi2 particles and (3) original CrSi2 particles. Low melt temperatures and short treatment times were found to favor the fabrication of master alloys because they impeded the dissolution of CrSi2 particles into the Al melt and, thus, allowed one to fabricate the master alloy containing the particles of the second and third types. [ABSTRACT FROM AUTHOR]

The quality and size of liver grafts are critical factors that influence living‐donor liver transplantation (LDLT) function and safety. However, the biomarkers used for predicting graft quality are lacking. In this study, we sought to identify unique graft quality markers, aside from donor age, by using the livers of non‐human primates. Hepatic gene microarray expression data from young and elderly cynomolgus macaques revealed a total of 271 genes with significantly increased expression in the elderly. These candidate genes were then narrowed down to six through bioinformatics analyses. The expression patterns of these candidate genes in human donor liver tissues were subsequently examined. Importantly, we found that grafts exhibiting up‐regulated expression of these six candidate genes were associated with an increased incidence of liver graft failure. Multivariable analysis further revealed that up‐regulated expression of LRRN2 (encoding leucine‐rich repeat protein, neuronal 2) in donor liver tissue served as an independent risk factor for graft failure (odds ratio 4.50, confidence interval 2.08–9.72). Stratification based on graft expression of LRRN2 and donor age was also significantly associated with 6‐month graft survival rates. Conclusion: Up‐regulated LRRN2 expression of liver graft is significantly correlated with graft failure in LDLT. In addition, combination of graft LRRN2 expression and donor age may represent a promising marker for predicting LDLT graft quality. [ABSTRACT FROM AUTHOR]

Simple Summary: Pituitary adenoma pathophysiology has been studied mainly using murine cell lines, animal models, and pituitary tumor samples. However, the lack of human pituitary cell line is a significant limiting factor in studying the molecular mechanisms of human pituitary tumors. Recently, pituitary induction methods from human-induced pluripotent stem cells (hiPSCs) have been established. These methods can induce human pituitary hormone-producing cells that retain physiological properties. hiPSCs in which tumor-causing gene mutations are introduced using genome-editing techniques, such as CRISPR/Cas9 systems, provide great opportunities to establish in vitro human pituitary adenoma disease models. The models will be a novel platform to discover novel drugs and investigate tumorigenesis and pathophysiology. The purpose of this review is to provide an overview of the applications of iPSCs for pituitary and neoplastic disorder research and genome-editing technologies to create strategies for developing pituitary adenoma models using iPSCs. Pituitary adenomas are characterized by abnormal growth in the pituitary gland. Surgical excision is the first-line treatment for functional (hormone-producing) pituitary adenomas, except for prolactin-producing adenomas; however, complete excision is technically challenging, and many patients require long-term medication after the treatment. In addition, the pathophysiology of pituitary adenomas, such as tumorigenesis, has not been fully understood. Pituitary adenoma pathophysiology has mainly been studied using animal models and animal tumor-derived cell lines. Nevertheless, experimental studies on human pituitary adenomas are difficult because of the significant differences among species and the lack of reliable cell lines. Recently, several methods have been established to differentiate pituitary cells from human pluripotent stem cells (hPSCs). The induced pituitary hormone-producing cells retain the physiological properties already lost in tumor-derived cell lines. Moreover, CRISPR/Cas9 systems have expedited the introduction of causative gene mutations in various malignant tumors into hPSCs. Therefore, hPSC-derived pituitary cells have great potential as a novel platform for studying the pathophysiology of human-specific pituitary adenomas and developing novel drugs. This review presents an overview of the recent progresses in hPSC applications for pituitary research, functional pituitary adenoma pathogenesis, and genome-editing techniques for introducing causative mutations. We also discuss future applications of hPSCs for studying pituitary adenomas. [ABSTRACT FROM AUTHOR]

Author(s): Masaki Yagi [1]; Satoshi Kishigami [2]; Akito Tanaka [1]; Katsunori Semi [1]; Eiji Mizutani [2, 3]; Sayaka Wakayama [2, 3]; Teruhiko Wakayama [2, 3]; Takuya Yamamoto (corresponding author) [1, [...]

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is essential for improving prognosis; however, diagnosing PDAC at an early stage is challenging. In patients with localized high‐grade pancreatic intraepithelial neoplasia (HG‐PanIN), whose tumorous lesion is undetectable on cross‐sectional images such as computed tomography or magnetic resonance image, long‐term survival is expected. Pancreatic cystic lesions or main pancreatic duct (MPD) dilatation are important indirect findings for the initial diagnosis of HG‐PanIN. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) should play important roles in detecting abnormal image findings, such as local irregular MPD stenosis, caliber MPD changes, small cystic lesions, or branch duct dilatation. Additionally, EUS could detect hypoechoic areas around the MPD stenosis in some patients with HG‐PanIN. Subsequently, endoscopic retrograde cholangiopancreatography (ERCP) and its associated pancreatic juice cytology, including serial pancreatic juice aspiration cytologic examination (SPACE) after placement of an endoscopic nasopancreatic drainage (ENPD) tube, may have high diagnostic accuracy for confirming the malignancy in HG‐PanIN. Although ERCP and its associated pancreatic cytology, including SPACE, may be associated with post‐ERCP pancreatitis (PEP), a recent randomized trial suggested that a 4‐Fr ENPD tube may reduce the incidence of PEP. In the future, further prospective multicenter studies are required to establish a standard method of SPACE. Additionally, further studies for novel biomarkers could help to establish evolutionary methods with duodenal fluid and pancreatic juice for the early and accurate diagnosis of early‐stage PDAC. [ABSTRACT FROM AUTHOR]

Block copolymers (BCPs) have garnered considerable interest due to their ability to form microphase-separated structures suitable for nanofabrication. For these applications, it is critical to achieve both sufficient etch selectivity and a small domain size. To meet both requirements concurrently, we propose the use of oligosaccharide and oligodimethylsiloxane as hydrophilic and etch-resistant hydrophobic inorganic blocks, respectively, to build up a novel BCP system, i.e., carbohydrate-inorganic hybrid BCP. The carbohydrate-inorganic hybrid BCPs were synthesized via a click reaction between oligodimethylsiloxane with an azido group at each chain end and propargyl-functionalized maltooligosaccharide (consisting of one, two, and three glucose units). In the bulk state, small-angle X-ray scattering revealed that these BCPs microphase separated into gyroid, asymmetric lamellar, and symmetric lamellar structures with domain-spacing ranging from 5.0 to 5.9 nm depending on the volume fraction. Additionally, we investigated microphase-separated structures in the thin film state and discovered that the BCP with the most asymmetric composition formed an ultrafine and highly oriented gyroid structure as well as in the bulk state. After reactive ion etching, the gyroid thin film was transformed into a nanoporous-structured gyroid SiO2 material, demonstrating the material's promising potential as nanotemplates. [ABSTRACT FROM AUTHOR]

The topology effects of cyclization on thermal phase transition behaviors were investigated for a series of amphiphilic Pluronic copolymers of both hydrophilic–hydrophobic–hydrophilic and hydrophobic–hydrophilic–hydrophobic block sequences. The dye solubilization measurements revealed the lowered critical micelle temperatures (TCMT) along with the decreased micellization enthalpy (ΔHmic) and entropy (ΔSmic) for the cyclized species. Furthermore, the transmittance and dynamic light scattering (DLS) measurements indicated a block sequence-dependent effect on the clouding phenomena, where a profound decrease in cloud point (Tc) was only found for the copolymers with a hydrophilic–hydrophobic–hydrophilic block sequence. Thus, the effect of cyclization on these critical temperatures was manifested differently depending on its block sequence. Finally, a comparison of the linear hydroxy-terminated, methoxy-terminated, and cyclized species indicated the effect of cyclization to be unique from a simple elimination of the terminal hydrophilic moieties. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus-1 (HIV-1) has infected more than 60 million people and caused nearly 30 million deaths worldwide (1), ultimately the consequence of cytolytic infection of [CD4.sup.+] T cells. In humans and in macaque models, most of these cells contain viral DNA and are rapidly eliminated at the peak of viraemia (2-4), yet the mechanism by which HIV-1 induces helper T-cell death has not been defined. Here we show that virus-induced cell killing is triggered by viral integration. Infection by wild-type HIV-1, but not an integrase-deficient mutant, induced the death of activated primary CD4 lymphocytes. Similarly, raltegravir, a pharmacologic integrase inhibitor, abolished HIV-1-induced cell killing both in cell culture and in [CD4.sup.+] T cells from acutely infected subjects. The mechanism of killing during viral integration involved the activation of DNA-dependent protein kinase (DNA-PK), a central integrator of the DNA damage response, which caused phosphorylation of p53 and histone H2AX. Pharmacological inhibition of DNA-PK abolished cell death during HIV-1 infection in vitro, suggesting that processes which reduce DNA-PK activation in CD4 cells could facilitate the formation of latently infected cells that give rise to reservoirs in vivo. We propose that activation of DNA-PK during viral integration has a central role in [CD4.sup.+] T-cell depletion, raising the possibility that integrase inhibitors and interventions directed towards DNA-PK may improve T-cell survival and immune function in infected individuals., To investigate the molecular mechanism underlying HIV-1-induced cell death during acute infection, we first infected CEMX174 T leukaemia cells with HIV-[1.sub.NL4-3] and monitored viral replication and cell death (Fig. 1a). [...]

CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction with B cells correlates with production of SIV-specific immunoglobulins. However, the fate of TFH cells and their participation in SIV-induced antibody production is not well understood. We investigated the phenotype, function, location, and molecular signature of TFH cells in rhesus macaques. Similar to their human counterparts, TFH cells in rhesus macaques represented a heterogeneous population with respect to cytokine function. In a highly differentiated subpopulation of TFH cells, characterized by [CD150.sup.lo] expression, production of Th1 cytokines was compromised while IL-4 production was augmented, and cells exhibited decreased survival, cycling, and trafficking capacity. TFH cells exhibited a distinct gene profile that was markedly altered by SIV infection. TFH cells were infected by SIV; yet, in some animals, these cells actually accumulated during chronic SIV infection. Generalized immune activation and increased IL-6 production helped drive TFH differentiation during SIV infection. Accumulation of TFH cells was associated with increased frequency of activated germinal center B cells and SIV-specific antibodies. Therefore, chronic SIV does not disturb the ability of TFH cells to help B cell maturation and production of SIV-specific immunoglobulins., Introduction The generation of antigen-specific B cells is dependent upon their interaction with T follicular helper (TFH) cells in the B cell follicles of the LN and spleen (SP) (1), [...]

Dietary restriction is the most effective and reproducible intervention to extend lifespan in divergent species (1). In mammals, two regimens of dietary restriction, intermittent fasting (IF) and chronic caloric restriction, have proven to extend lifespan and reduce the incidence of age-related disorders (2). An important characteristic of IF is that it can increase lifespan even when there is little or no overall decrease in calorie intake (2). The molecular mechanisms underlying IF-induced longevity, however, remain largely unknown. Here we establish an IF regimen that effectively extends the lifespan of Caenorhabditis elegans and show that the low molecular weight GTPase RHEB-1 has a dual role in lifespan regulation; RHEB-1 is required for the IF-induced longevity, whereas inhibition of RHEB-1 mimics the caloric-restriction effects. RHEB-1 exerts its effects in part by the insulin/insulin growth factor (IGF)-like signalling effect or DAF-16 in IF. Our analyses demonstrate that most fasting-induced upregulated genes require RHEB-1 function for their induction, and that RHEB-1 and TOR signalling are required for the fasting-induced downregulation of an insulin-like peptide, INS-7. These findings identify the essential role of signalling by RHEB-1 in IF-induced longevity and gene expression changes, and suggest a molecular link between the IF-induced longevity and the insulin/IGF-like signalling pathway., In an IF regimen, which has not been established in invertebrate model organisms, food is provided ad libitum to both control and experimental groups, but the experimental group is subjected [...]

In pregnant mice, the maternal liver expands drastically during gestation, which is believed to be essential to accommodate various metabolic demands caused by physiological changes and fetal growth. Although hepatocyte proliferation and hypertrophy have been reported, little is known about the dynamics of biliary epithelial cells (BECs), which comprise the bile duct epithelium in the liver. Here, we show that BECs transiently proliferate during the early stage of gestation. Lineage tracing revealed that BEC progeny were retained in the bile duct epithelium and did not differentiate into hepatocytes, indicating BEC self‐replication during pregnancy. RNA‐sequencing analysis of BECs identified their early pregnancy‐signature transcriptomes, which highlighted Yes‐associated protein (YAP) signaling‐related genes. Nuclear accumulation of YAP was enhanced in BECs during pregnancy but was barely detectable in hepatocytes. In addition, the pharmacological inhibition of YAP attenuated BEC proliferation and liver weight gain during pregnancy. Our results delineate the proliferation and transcriptomic dynamics of BECs during pregnancy and suggest the relevance of YAP‐mediated signals. [ABSTRACT FROM AUTHOR]