Evaluation of a Vaccine Candidate Designed for Broad-Spectrum Protection against Type A Foot-and-Mouth Disease in Asia.

Foot-and-mouth disease (FMD) vaccines are currently the most powerful protective and preventive measures used to control FMD. In this study, the chimeric vaccine strain containing antigenic epitopes from the FMD virus serotype A, which belongs to the ASIA topotype, was produced and evaluated. The chimeric vaccine strains contain sea-97/G1 (VP4, VP2, VP3) and A22 Iraq (VP1) or G-VII (VP1) for use in FMD vaccines in Asia. The 50% protective dose was determined in mice. Vaccinated mice were challenged with three different type A viruses (Sea-97/G1, Sea-97/G2, G-VII clade) seven days post-vaccination (dpv), and mice that received the vaccine candidates were protected against the three viruses. The protective capability of one of the vaccine candidates was evaluated in pigs. Vaccinated pigs were challenged with three different type A viruses (Sea-97/G1, Sea-97/G2, G-VII clade) at 28 dpv, and pigs that received the vaccine candidate were protected against the three viruses. The results showed that this vaccine candidate, which was designed to provide protection against FMD in Asia, efficiently protected pigs against virus challenge and thus has potential as a broad-spectrum vaccine for various epidemic FMD viruses.

Cellular heterogeneity and plasticity during NAFLD progression.

Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease that can progress to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis, and hepatocellular carcinoma (HCC). NAFLD ranges from simple steatosis (or nonalcoholic fatty liver [NAFL]) to NASH as a progressive form of NAFL, which is characterized by steatosis, lobular inflammation, and hepatocellular ballooning with or without fibrosis. Because of the complex pathophysiological mechanism and the heterogeneity of NAFLD, including its wide spectrum of clinical and histological characteristics, no specific therapeutic drugs have been approved for NAFLD. The heterogeneity of NAFLD is closely associated with cellular plasticity, which describes the ability of cells to acquire new identities or change their phenotypes in response to environmental stimuli. The liver consists of parenchymal cells including hepatocytes and cholangiocytes and nonparenchymal cells including Kupffer cells, hepatic stellate cells, and endothelial cells, all of which have specialized functions. This heterogeneous cell population has cellular plasticity to adapt to environmental changes. During NAFLD progression, these cells can exert diverse and complex responses at multiple levels following exposure to a variety of stimuli, including fatty acids, inflammation, and oxidative stress. Therefore, this review provides insights into NAFLD heterogeneity by addressing the cellular plasticity and metabolic adaptation of hepatocytes, cholangiocytes, hepatic stellate cells, and Kupffer cells during NAFLD progression.

Operando electron microscopy investigation of polar domain dynamics in twisted van der Waals homobilayers.

Conventional antiferroelectric materials with atomic-scale anti-aligned dipoles undergo a transition to a ferroelectric (FE) phase under strong electric fields. The moiré superlattice formed in the twisted stacks of van der Waals crystals exhibits polar domains alternating in moiré length with anti-aligned dipoles. In this moiré domain antiferroelectic (MDAF) arrangement, the distribution of electric dipoles is distinguished from that of two-dimensional FEs, suggesting dissimilar domain dynamics. Here we performed an operando transmission electron microscopy investigation on twisted bilayer WSe2 to observe the polar domain dynamics in real time. We find that the topological protection, provided by the domain wall network, prevents the MDAF-to-FE transition. As one decreases the twist angle, however, this transition occurs as the domain wall network disappears. Exploiting stroboscopic operando transmission electron microscopy on the FE phase, we measure a maximum domain wall velocity of 300 µm s-1. Domain wall pinnings by various disorders limit the domain wall velocity and cause Barkhausen noises in the polarization hysteresis loop. Atomic-scale analysis of the pinning disorders provides structural insight on how to improve the switching speed of van der Waals FEs.

Alterations of Epidermal Lipid Profiles and Skin Microbiome in Children With Atopic Dermatitis.

PURPOSE: We aimed to investigate epidermal lipid profiles and their association with skin microbiome compositions in children with atopic dermatitis (AD). METHODS: Specimens were obtained by skin tape stripping from 27 children with AD and 18 healthy subjects matched for age and sex. Proteins and lipids of stratum corneum samples from nonlesional and lesional skin of AD patients and normal subjects were quantified by liquid chromatography tandem mass spectrometry. Skin microbiome profiles were analyzed using bacterial 16S rRNA sequencing. RESULTS: Ceramides with nonhydroxy fatty acids (FAs) and C18 sphingosine as their sphingoid base (C18-NS-CERs) N-acylated with C16, C18 and C22 FAs, sphingomyelin (SM) N-acylated with C18 FAs, and lysophosphatidylcholine (LPC) with C16 FAs were increased in AD lesional skin compared to those in AD nonlesional skin and that of control subjects (all P < 0.01). SMs N-acylated with C16 FAs were increased in AD lesional skin compared to control subjects (P < 0.05). The ratio of NS-CERs with long-chain fatty acids (LCFAs) to short-chain fatty acids (SCFAs) (C24-32:C14-22), the ratio of LPC with LCFAs to SCFAs (C24-30:C16-22) as well as the ratio of total esterified omega-hydroxy ceramides to total NS-CERs were negatively correlated with transepidermal water loss (rho coefficients = -0.738, -0.528, and -0.489, respectively; all P < 0.001). The proportions of Firmicutes and Staphylococcus were positively correlated to SCFAs including NS ceramides (C14-22), SMs (C17-18), and LPCs (C16), while the proportions of Actinobacteria, Proteobacteria, Bacteroidetes, Corynebacterium, Enhydrobacteria, and Micrococcus were negatively correlated to these SCFAs. CONCLUSIONS: Our results suggest that pediatric AD skin shows aberrant lipid profiles, and these alterations are associated with skin microbial dysbiosis and cutaneous barrier dysfunction.

Continuous Electroencephalogram Use and Hospital Outcomes in Critically Ill Children.

PURPOSE: To examine the association between CEEG use and discharge status, length of hospitalization, and health care cost in a critically ill pediatric population. METHODS: Four thousand three hundred forty-eight critically ill children were identified from a US nationwide administrative health claims database; 212 (4.9%) of whom underwent CEEG during admissions (January 1, 2015-june 30, 2020). Discharge status, length of hospitalization, and health care cost were compared between patients with and without CEEG use. Multiple logistic regression analyzed the association between CEEG use and these outcomes, controlling for age and underlying neurologic diagnosis. Prespecified subgroups analysis was performed for children with seizures/status epilepticus, with altered mental status and with cardiac arrest. RESULTS: Compared with critically ill children without CEEG, those who underwent CEEG were likely to have shorter hospital stays than the median (OR = 0.66; 95% CI = 0.49-0.88; P = 0.004), and also total hospitalization costs were less likely to exceed the median (OR = 0.59; 95% CI = 0.45-0.79; P < 0.001). There was no difference in odds of favorable discharge status between those with and without CEEG (OR = 0.69; 95% CI = 0.41-1.08; P = 0.125). In the subgroup of children with seizures/status epilepticus, those with CEEG were less likely to have unfavorable discharge status, compared with those without CEEG (OR = 0.51; 95% CI = 0.27-0.89; P = 0.026). CONCLUSIONS: Among critically ill children, CEEG was associated with shorter stay and lower costs of hospitalization but was not associated with change of favorable discharge status except the subgroup with seizures/status epilepticus.

Tcf7l2 in hepatocytes regulates de novo lipogenesis in diet-induced non-alcoholic fatty liver disease in mice.

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes may more easily progress towards severe forms of non-alcoholic steatohepatitis (NASH) and cirrhosis. Although the Wnt effector transcription factor 7-like 2 (TCF7L2) is closely associated with type 2 diabetes risk, the role of TCF7L2 in NAFLD development remains unclear. Here, we investigated how changes in TCF7L2 expression in the liver affects hepatic lipid metabolism based on the major risk factors of NAFLD development. METHODS: Tcf7l2 was selectively ablated in the liver of C57BL/6N mice by inducing the albumin (Alb) promoter to recombine Tcf7l2 alleles floxed at exon 5 (liver-specific Tcf7l2-knockout [KO] mice: Alb-Cre;Tcf7l2f/f). Alb-Cre;Tcf7l2f/f and their wild-type (Tcf7l2f/f) littermates were fed a high-fat diet (HFD) or a high-carbohydrate diet (HCD) for 22 weeks to reproduce NAFLD/NASH. Mice were refed a standard chow diet or an HCD to stimulate de novo lipogenesis (DNL) or fed an HFD to provide exogenous fatty acids. We analysed glucose and insulin sensitivity, metabolic respiration, mRNA expression profiles, hepatic triglyceride (TG), hepatic DNL, selected hepatic metabolites, selected plasma metabolites and liver histology. RESULTS: Alb-Cre;Tcf7l2f/f essentially exhibited increased lipogenic genes, but there were no changes in hepatic lipid content in mice fed a normal chow diet. However, following 22 weeks of diet-induced NAFLD/NASH conditions, liver steatosis was exacerbated owing to preferential metabolism of carbohydrate over fat. Indeed, hepatic Tcf7l2 deficiency enhanced liver lipid content in a manner that was dependent on the duration and amount of exposure to carbohydrates, owing to cell-autonomous increases in hepatic DNL. Mechanistically, TCF7L2 regulated the transcriptional activity of Mlxipl (also known as ChREBP) by modulating O-GlcNAcylation and protein content of carbohydrate response element binding protein (ChREBP), and targeted Srebf1 (also called SREBP1) via miRNA (miR)-33-5p in hepatocytes. Eventually, restoring TCF7L2 expression at the physiological level in the liver of Alb-Cre;Tcf7l2f/f mice alleviated liver steatosis without altering body composition under both acute and chronic HCD conditions. CONCLUSIONS/INTERPRETATION: In mice, loss of hepatic Tcf7l2 contributes to liver steatosis by inducing preferential metabolism of carbohydrates via DNL activation. Therefore, TCF7L2 could be a promising regulator of the NAFLD associated with high-carbohydrate diets and diabetes since TCF7L2 deficiency may lead to development of NAFLD by promoting utilisation of excess glucose pools through activating DNL. DATA AVAILABILITY: RNA-sequencing data have been deposited into the NCBI GEO under the accession number GSE162449 ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE162449 ).

Staphylococcus aureus causes aberrant epidermal lipid composition and skin barrier dysfunction.

BACKGROUND: Staphylococcus (S) aureus colonization is known to cause skin barrier disruption in atopic dermatitis (AD) patients. However, it has not been studied how S. aureus induces aberrant epidermal lipid composition and skin barrier dysfunction. METHODS: Skin tape strips (STS) and swabs were obtained from 24 children with AD (6.0 ± 4.4 years) and 16 healthy children (7.0 ± 4.5 years). Lipidomic analysis of STS samples was performed by mass spectrometry. Skin levels of methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA) were evaluated. The effects of MSSA and MRSA were evaluated in primary human keratinocytes (HEKs) and organotypic skin cultures. RESULTS: AD and organotypic skin colonized with MRSA significantly increased the proportion of lipid species with nonhydroxy fatty acid sphingosine ceramide with palmitic acid ([N-16:0 NS-CER], sphingomyelins [16:0-18:0 SM]), and lysophosphatidylcholines [16:0-18:0 LPC], but significantly reduced the proportion of corresponding very long-chain fatty acids (VLCFAs) species (C22-28) compared to the skin without S. aureus colonization. Significantly increased transepidermal water loss (TEWL) was found in MRSA-colonized AD skin. S. aureus indirectly through interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, and IL-33 inhibited expression of fatty acid elongase enzymes (ELOVL3 and ELOVL4) in HEKs. ELOVL inhibition was more pronounced by MRSA and resulted in TEWL increase in organotypic skin. CONCLUSION: Aberrant skin lipid profiles and barrier dysfunction are associated with S. aureus colonization in AD patients. These effects are attributed to the inhibition of ELOVLs by S. aureus-induced IL-1ß, TNF-α, IL-6, and IL-33 seen in keratinocyte models and are more prominent in MRSA than MSSA.

Bifidobacterium longum and Galactooligosaccharide Improve Skin Barrier Dysfunction and Atopic Dermatitis-like Skin.

PURPOSE: The beneficial effects of a combination therapy using Bifidobacterium longum and galactooligosaccharide (GOS) for the treatment of atopic dermatitis (AD) have not been elucidated. METHODS: Gene expressions of interleukin (IL)-4 and IL-13 from peripheral blood mononuclear cells and fecal abundance of B. longum from 12-month-old infants were evaluated. Human primary epidermal keratinocytes (HEKs) and hairless mice were treated with B. longum, GOS, B. longum-derived extracellular vesicles (BLEVs), dinitrochlorobenzene (DNCB), or a synbiotic mixture of B. longum and GOS. Expression of epidermal barrier proteins and cytokines as well as serum immunoglobulin E (IgE) levels were analyzed in HEKs and mice. Dermatitis scores, transepidermal water loss (TEWL), epidermal thickness, and fecal B. longum abundance were evaluated in mice. RESULTS: Fecal abundance of B. longum was negatively correlated with blood IL-13 expression in infants. B. longum or BLEVs increased expression of filaggrin (FLG) and loricrin (LOR) in HEKs. B. longum increased the efficacy of GOS to upregulate FLG and LOR expressions in HEKs. Oral administration of GOS increased fecal abundance of B. longum in mice. Oral administration of B. longum attenuated DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, and deficiency of epidermal barrier proteins. Moreover, the combination of B. longum and GOS showed greater effects to improve DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, serum IgE levels, IL-4 over-expression, and the deficiency of epidermal barrier proteins than the administration of B. longum alone. CONCLUSIONS: B. longum and GOS improve DNCB-induced skin barrier dysfunction and AD-like skin.

STAT6 in mitochondrial outer membrane impairs mitochondrial fusion by inhibiting MFN2 dimerization.

Although it is reported that mitochondria-localized nuclear transcription factors (TFs) regulate mitochondrial processes such as apoptosis and mitochondrial transcription/respiration, the functions and mechanisms of mitochondrial dynamics regulated by mitochondria-localized nuclear TFs are yet to be fully characterized. Here, we identify STAT6 as a mitochondrial protein that is localized in the outer membrane of mitochondria (OMM). STAT6 in OMM inhibits mitochondrial fusion by blocking MFN2 dimerization. This implies that STAT6 has a critical role in mitochondrial dynamics. Moreover, mitochondrial accumulation of STAT6 in response to hypoxic conditions reveals that STAT6 is a regulator of mitochondrial processes including fusion/fission mechanisms.

Electroforming-free threshold switching of NbO x -based selector devices by controlling conducting phases in the NbO x layer for the application to crossbar array architectures.

Bipolar threshold switching characteristics, featuring volatile transition between the high-resistance state (HRS) at lower voltage than threshold voltage (V th) and the low-resistance state (LRS) at higher voltage irrespective of the voltage polarity, are investigated in the Nb(O)/NbO x /Nb(O) devices with respect to deposition and post-annealing conditions of NbO x layers. The device with NbO x deposited by reactive sputtering with 12% of O2 gas mixed in Ar shows threshold switching behaviors after electroforming operation at around +4 V of forming voltage (V f). On the other hand, electroforming-free threshold switching is achieved from the device with NbO x deposited in the reduced fraction of 7% of O2 gas and subsequently annealed at 250 °C in vacuum, thanks to the increase of the amount of conducting phases within the NbO x layer. Threshold switching is thought to be driven by the formation of a temporally percolated filament composed of conducting NbO and NbO2 phases in the NbO x layer, which were formed as a result of the interaction with Nb electrodes such as oxygen ion migration either by annealing or electrical biasing. The presence of a substantial amount of oxygen in the Nb electrodes up to ∼40 at%, named Nb(O) herein, would alleviate excessive migration of oxygen and consequent overgrowth of the filament during operation, thus enabling reliable threshold switching. These results demonstrate a viable route to realize electroforming-free threshold switching in the Nb(O)/NbO x /Nb(O) devices by controlling the contents of conducting phases in the NbO x layer for the application to selector devices in high-density crossbar memory and synapse array architectures.

Al2O3-Coated Si-Alloy Prepared by Atomic Layer Deposition as Anodes for Lithium-Ion Batteries.

Silicon-based anodes can increase the energy density of Li-ion batteries (LIBs) owing to their large weights and volumetric capacities. However, repeated charging and discharging can rapidly deteriorate the electrochemical properties because of a large volume change in the electrode. In this study, a commercial Fe-Si powder was coated with Al2O3 layers of different thicknesses via atomic layer deposition (ALD) to prevent the volume expansion of Si and suppress the formation of crack-induced solid electrolyte interfaces. The Al2O3 content was controlled by adjusting the trimethyl aluminum exposure time, and higher Al2O3 contents significantly improved the electrochemical properties. In 300 cycles, the capacity retention rate of a pouch full-cell containing the fabricated anodes increased from 69.8% to 72.3% and 79.1% depending on the Al2O3 content. The powder characterization and coin and pouch cell cycle evaluation results confirmed the formation of an Al2O3 layer on the powder surface. Furthermore, the expansion rate observed during the charging/discharging of the pouch cell indicated that the deposited layer suppressed the powder expansion and improved the cell stability. Thus, the performance of an LIB containing Si-alloy anodes can be improved by coating an ALD-synthesized protective Al2O3 layer.

Dietary Diversity during Early Infancy Increases Microbial Diversity and Prevents Egg Allergy in High-Risk Infants.

We aimed to investigate associations of dietary diversity (DD) with gut microbial diversity and the development of hen's egg allergy (HEA) in infants. We enrolled 68 infants in a high-risk group and 32 infants in a control group based on a family history of allergic diseases. All infants were followed from birth until 12 months of age. We collected infant feeding data, and DD was defined using 3 measures: the World Health Organization definition of minimum DD, food group diversity, and food allergen diversity. Gut microbiome profiles and expression of cytokines were evaluated by bacterial 16S rRNA sequencing and real-time reverse transcriptase-polymerase chain reaction. High DD scores at 3 and 4 months were associated with a lower risk of developing HEA in the high-risk group, but not in the control group. In the high-risk group, high DD scores at 3, 4, and 5 months of age were associated with an increase in Chao1 index at 6 months. We found that the gene expression of IL-4, IL-5, IL-6, and IL-8 were higher among infants who had lower DD scores compared to those who had higher DD scores in high-risk infants. Additionally, high-risk infants with a higher FAD score at 5 months of age showed a reduced gene expression of IL-13. Increasing DD within 6 months of life may increase gut microbial diversity, and thus reduce the development of HEA in infants with a family history of allergic diseases.

Large-Area Uniform 1-nm-Level Amorphous Carbon Layers from 3D Conformal Polymer Brushes. A "Next-Generation" Cu Diffusion Barrier?

A reliable method for preparing a conformal amorphous carbon (a-C) layer with a thickness of 1-nm-level, is tested as a possible Cu diffusion barrier layer for next-generation ultrahigh-density semiconductor device miniaturization. A polystyrene brush of uniform thickness is grafted onto 4-inch SiO2 /Si wafer substrates with "self-limiting" chemistry favoring such a uniform layer. UV crosslinking and subsequent carbonization transforms this polymer film into an ultrathin a-C layer without pinholes or hillocks. The uniform coating of nonplanar regions or surfaces is also possible. The Cu diffusion "blocking ability" is evaluated by time-dependent dielectric breakdown (TDDB) tests using a metal-oxide-semiconductor (MOS) capacitor structure. A 0.82 nm-thick a-C barrier gives TDDB lifetimes 3.3× longer than that obtained using the conventional 1.0 nm-thick TaNx diffusion barrier. In addition, this exceptionally uniform ultrathin polymer and a-C film layers hold promise for selective ion permeable membranes, electrically and thermally insulating films in electronics, slits of angstrom-scale thickness, and, when appropriately functionalized, as a robust ultrathin coating with many other potential applications.

Tuning Hot Carrier Dynamics of InP/ZnSe/ZnS Quantum Dots by Shell Morphology Control.

Isotropic InP/ZnSe/ZnS quantum dots (QDs) are prepared at a high reaction temperature, which facilitates ZnSe shell growth on random facets of the InP core. Fast crystal growth enables stacking faults elimination, which induces anisotropic growth, and as a result, improves the photoluminescence (PL) quantum yield by nearly 20%. Herein, the effect of the QD morphology on photophysical properties is investigated by observing the PL blinking and ultrafast charge carrier dynamics. It is found that hot hole trapping is considerably suppressed in isotropic InP QDs, indicating that the stacking faults in the anisotropic InP/ZnSe structures act as defects for luminescence. These results highlight the importance of understanding the correlation between QD shapes and hot carrier dynamics, and present a way to design highly luminescent QDs for further promising display applications.

Questionnaire Survey on Current Red Blood Cell Transport and Storage in Korea for Reducing Wastage.

BACKGROUND: To ensure safe red blood cell (RBC) transfusion practice, it is important to comply with storage and transport requirements of RBC units. We conducted a comprehensive survey on the practice of RBC transport and storage to explore the awareness of and compliance with the 30-minute rule, the current status of RBC unit transport, and possible utility of temperature indicators (TIs) to reduce RBC wastage. METHODS: From June to August of 2019, 64 blood bank physicians (14 questions) in 64 secondary- and tertiary-care hospitals and 673 nurses (13 questions) in 42 tertiary-care hospitals replied to a questionnaire survey. The results of the survey were analyzed with descriptive statistics. RESULTS: Among the physicians surveyed, 97.0% (N=62) of hospitals had transfusion guidelines in place. The RBC wastage in 2018 ranged from less than five units to more than 200 units. Among the nurses surveyed, 99.4% (N=669) were aware of and complied with the 30-minute rule; 13.5% (N=91) of the nurses had experience of RBC wastage due to violation of the 30-minute rule. Both physicians (67%, N=43) and nurses (83.1%, N=559) responded that TIs would help reduce RBC wastage. CONCLUSIONS: This is the first survey on the practices related to RBC transport and storage in Korea. This study provides fundamental data on current practice for the blood cold chain, insights into RBC wastage, and highlights the utility of TIs.

Wide range modulation of synaptic weight in thin-film transistors with hafnium oxide gate insulator and indium-zinc oxide channel layer for artificial synapse application.

Wide range synaptic weight modulation with a tunable drain current was demonstrated in thin-film transistors (TFTs) with a hafnium oxide (HfO2-x) gate insulator and an indium-zinc oxide (IZO) channel layer for application to artificial synapses in neuromorphic systems. The drain current in these TFTs was reduced significantly by four orders of magnitude on application of a negative gate bias, then could be restored to its original value by applying a positive bias. The reduced drain current under negative biasing is interpreted as being caused by voltage-driven oxygen ion migration from the HfO2-x gate insulator to the IZO channel, which reduces the oxygen vacancy concentration in the IZO channel. In addition to emulating the analog-type potentiation and depression motions in artificial synapses, the tunable drain current presents paired-pulse facilitation and short-term and long-term plasticity behaviors. These wide-ranging and nonvolatile synaptic behaviors with tunable drain currents are indicative of the potential of the proposed TFTs for artificial synapse applications.

Seasonal and monthly variation in peak expiratory flow rate in children with asthma.

BACKGROUND: Although understanding the seasonal patterns of asthma deterioration is important to prevent asthma exacerbation, previous approaches have limitations in evaluating the actual trend of asthma exacerbation. OBJECTIVE: This study aimed to evaluate the seasonal and monthly variations in the peak expiratory flow rate (PEFR) among children with asthma. METHODS: A total of 89 patients with asthma were enrolled between December 2012 and March 2015. The PEFR in the morning and evening was recorded daily, and the percentage change in PEFR from baseline was calculated. Generalized estimating equation models were constructed after adjusting for age, sex, body mass index, and sensitization to house dust mites or pollen. RESULTS: The PEFR records of 11,222 person-days showed a significant decrease in the morning and evening in autumn than in winter by -1.9% (95% confidence interval [CI], -3.73 to -0.15) and -2.1% (95% CI, -3.80 to -0.37), respectively. The morning PEFR was significantly lower in April, August, October, and December than in January with changes of -4.2% (95% CI, -7.08 to -1.23) in April, -3.1% (95% CI, -5.79 to -0.47) in August, -3.7% (95% CI, -6.09 to -1.21) in October, and -1.9% (95% CI, -3.62 to -0.12) in December. The percentage change of evening PEFR significantly decreased by -3.3% (95% CI, -6.38 to -0.25) in April and by -3.3% (95% CI, -5.56 to -1.07) in October. CONCLUSION: The PEFR in children with asthma was lower in autumn than in winter. In terms of monthly patterns, the PEFR was significantly reduced in April and October than in January. These results can serve as a basis for preventing asthma exacerbations by developing seasonal or monthly management strategies for children with asthma.

Metabolic Spectrum of Liver Failure in Type 2 Diabetes and Obesity: From NAFLD to NASH to HCC.

Liver disease is the spectrum of liver damage ranging from simple steatosis called as nonalcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC). Clinically, NAFLD and type 2 diabetes coexist. Type 2 diabetes contributes to biological processes driving the severity of NAFLD, the primary cause for development of chronic liver diseases. In the last 20 years, the rate of non-viral NAFLD/NASH-derived HCC has been increasing rapidly. As there are currently no suitable drugs for treatment of NAFLD and NASH, a class of thiazolidinediones (TZDs) drugs for the treatment of type 2 diabetes is sometimes used to improve liver failure despite the risk of side effects. Therefore, diagnosis, prevention, and treatment of the development and progression of NAFLD and NASH are important issues. In this review, we will discuss the pathogenesis of NAFLD/NASH and NAFLD/NASH-derived HCC and the current promising pharmacological therapies of NAFLD/NASH. Further, we will provide insights into "adipose-derived adipokines" and "liver-derived hepatokines" as diagnostic and therapeutic targets from NAFLD to HCC.

GADD45ß Regulates Hepatic Gluconeogenesis via Modulating the Protein Stability of FoxO1.

Increased hepatic gluconeogenesis is one of the main contributors to the development of type 2 diabetes. Recently, it has been reported that growth arrest and DNA damage-inducible 45 beta (GADD45ß) is induced under both fasting and high-fat diet (HFD) conditions that stimulate hepatic gluconeogenesis. Here, this study aimed to establish the molecular mechanisms underlying the novel role of GADD45ß in hepatic gluconeogenesis. Both whole-body knockout (KO) mice and adenovirus-mediated knockdown (KD) mice of GADD45ß exhibited decreased hepatic gluconeogenic gene expression concomitant with reduced blood glucose levels under fasting and HFD conditions, but showed a more pronounced effect in GADD45ß KD mice. Further, in primary hepatocytes, GADD45ß KD reduced glucose output, whereas GADD45ß overexpression increased it. Mechanistically, GADD45ß did not affect Akt-mediated forkhead box protein O1 (FoxO1) phosphorylation and forskolin-induced cAMP response element-binding protein (CREB) phosphorylation. Rather it increased FoxO1 transcriptional activity via enhanced protein stability of FoxO1. Further, GADD45ß colocalized and physically interacted with FoxO1. Additionally, GADD45ß deficiency potentiated insulin-mediated suppression of hepatic gluconeogenic genes, and it were impeded by the restoration of GADD45ß expression. Our finding demonstrates GADD45ß as a novel and essential regulator of hepatic gluconeogenesis. It will provide a deeper understanding of the FoxO1-mediated gluconeogenesis.

Effect of the Bilayer Period of Atomic Layer Deposition on the Growth Behavior and Electrical Properties of the Amorphous In-Zn-O Film.

This study reports on the effect of a bilayer period on the growth behavior, microstructure evolution, and electrical properties of atomic layer deposition (ALD) deposited In-Zn-O (IZO) films, fixing the ALD cycle ratio of In-O/Zn-O as 9:1. Here, the bilayer period is defined as the total number of ALD cycles in one supercycle of In-O and Zn-O by alternately stacking Zn-O and In-O layers at a temperature of 220 °C. IZO films with a bilayer period from 10 to 40 cycles, namely, IZO[In-O/Zn-O = 9:1] to IZO[36:4], result to form an amorphous phase with a resistivity of 4.94 × 10-4 Ω·cm. However, by increasing the bilayer period above 100 cycles, the IZO films begin to form a mixed amorphous-nanocrystalline microstructure, resulting from the limited intermixing at the interfaces. Concomitantly, the overall film resistivity is considerably increased with a simultaneous decrease in both the carrier mobility and the concentration. These results not only reveal the importance of the bilayer period in designing the ALD stacking sequence in the ALD-IZO, but also provide the possibility of forming various multilayered materials with different electrical properties.