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Background: Human milk is unquestionably beneficial for preterm infants. We investigated how the transition from tube to oral/breastfeeding impacts the preterm infants' oral and gut microbiome and metabolome., Methods: We analyzed stool, saliva, and milk samples collected from a cohort of preterm infants enrolled in the MAP Study, a prospective observational trial. The microbiome and metabolome of the samples were analyzed from 4 longitudinal sample time points, 2 during tube feeds only and 2 after the initiation of oral/breastfeeding., Results: We enrolled 11 mother-infant dyads (gestational age = 27.9 (23.4-32.2)) and analyzed a total of 39 stool, 44 saliva, and 43 milk samples over 4 timepoints. In saliva samples, there was a shift towards increased Streptococcus and decreased Staphylococcus after oral feeding/breastfeeding initiation (p < 0.05). Milk sample metabolites were strongly influenced by the route of feeding and milk type (p < 0.05) and represented the pathways of Vitamin E metabolism, Vitamin B12 metabolism, and Tryptophan metabolism., Conclusion: Our analysis demonstrated that the milk and preterm infant's saliva microbiome and metabolome changed over the course of the first four to 5 months of life, coinciding with the initiation of oral/breastfeeds., Impact: The microbiome and metabolome is altered in the infant's saliva but not their stool, and in mother's milk when feeds are transitioned from tube to oral/breastfeeding. We assessed the relationship between the gut and oral microbiome/metabolome with the milk microbiome/metabolome over a longitudinal period of time in preterm babies. Metabolites that changed in the infants saliva after the initiation of oral feeds have the potential to be used as biomarkers for disease risk., (© 2024. The Author(s).)

In 2020, we identified cancer-specific microbial signals in The Cancer Genome Atlas (TCGA) [1]. Multiple peer-reviewed papers independently verified or extended our findings [2-12]. Given this impact, we carefully considered concerns by Gihawi et al. [13] that batch correction and database contamination with host sequences artificially created the appearance of cancer type-specific microbiomes. (1) We tested batch correction by comparing raw and Voom-SNM-corrected data per-batch, finding predictive equivalence and significantly similar features. We found consistent results with a modern microbiome-specific method (ConQuR [14]), and when restricting to taxa found in an independent, highly-decontaminated cohort. (2) Using Conterminator [15], we found low levels of human contamination in our original databases (~1% of genomes). We demonstrated that the increased detection of human reads in Gihawi et al. [13] was due to using a newer human genome reference. (3) We developed Exhaustive, a method twice as sensitive as Conterminator, to clean RefSeq. We comprehensively host-deplete TCGA with many human (pan)genome references. We repeated all analyses with this and the Gihawi et al. [13] pipeline, and found cancer type-specific microbiomes. These extensive re-analyses and updated methods validate our original conclusion that cancer type-specific microbial signatures exist in TCGA, and show they are robust to methodology., (© 2024. The Author(s).)

Objective: To investigate the association between phototherapy (PT) and the development of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants., Study Design: A retrospective case-control study was conducted on VLBW infants with or without NEC (stage IIA or greater) born at ≤35 weeks' gestation in a tertiary hospital over 7 years. Sample size calculation, trend test, as well as univariate and multiple logistic regression analyses were employed., Results: A total of 824 VLBW infants were reviewed, with 74 cases and 122 controls finally enrolled. The odds of NEC increased with the duration and number of PT sessions. Exposure to >120 h and >4 instances of PT were significantly associated with NEC in multivariate analysis., Conclusion: This is the first study suggesting a potential association between PT and development of NEC in VLBW infants. This association needs further exploration., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

We investigated the associations between retinal vascular geometric measurements and idiopathic epiretinal membrane (ERM). Whether changes in retinal vascular geometry are independent of systemic cardiovascular risk factors was also evaluated. This retrospective, cross sectional study included 98 patients with idiopathic ERM, and 99 healthy age-matched controls. Quantitative retinal vascular parameters were measured from digital retinal fundus photographs using a semi-automated computer-assisted program. Multivariate logistic regression analyses were performed to evaluate associations between retinal vascular geometric parameters and the presence of idiopathic ERM after adjusting for systemic cardiovascular risk factors. There was no significant difference in the baseline characteristics of the two groups, except that the ERM group had a higher proportion of females than the control group. In multivariate regression analyses, female sex (odds ratio [OR] 0.402; 95% CI 0.196-0.802; P = 0.011), wider retinal venular caliber (OR 16.852; 95% CI 5.384-58.997; P < 0.001) and decreased total fractal dimension (OR 0.156; 95% CI 0.052-0.440; P = 0.001) were associated with idiopathic ERM. Idiopathic ERM was associated with alterations in global retinal microvascular geometric parameters, wider retinal venules, and less complex vascular branching patterns, independent of cardiovascular risk factors., (© 2023. The Author(s).)

Despite advances in sequencing, lack of standardization makes comparisons across studies challenging and hampers insights into the structure and function of microbial communities across multiple habitats on a planetary scale. Here we present a multi-omics analysis of a diverse set of 880 microbial community samples collected for the Earth Microbiome Project. We include amplicon (16S, 18S, ITS) and shotgun metagenomic sequence data, and untargeted metabolomics data (liquid chromatography-tandem mass spectrometry and gas chromatography mass spectrometry). We used standardized protocols and analytical methods to characterize microbial communities, focusing on relationships and co-occurrences of microbially related metabolites and microbial taxa across environments, thus allowing us to explore diversity at extraordinary scale. In addition to a reference database for metagenomic and metabolomic data, we provide a framework for incorporating additional studies, enabling the expansion of existing knowledge in the form of an evolving community resource. We demonstrate the utility of this database by testing the hypothesis that every microbe and metabolite is everywhere but the environment selects. Our results show that metabolite diversity exhibits turnover and nestedness related to both microbial communities and the environment, whereas the relative abundances of microbially related metabolites vary and co-occur with specific microbial consortia in a habitat-specific manner. We additionally show the power of certain chemistry, in particular terpenoids, in distinguishing Earth's environments (for example, terrestrial plant surfaces and soils, freshwater and marine animal stool), as well as that of certain microbes including Conexibacter woesei (terrestrial soils), Haloquadratum walsbyi (marine deposits) and Pantoea dispersa (terrestrial plant detritus). This Resource provides insight into the taxa and metabolites within microbial communities from diverse habitats across Earth, informing both microbial and chemical ecology, and provides a foundation and methods for multi-omics microbiome studies of hosts and the environment., (© 2022. The Author(s).)

PTEN is among the most commonly lost or mutated tumor suppressor genes in human cancer. PTEN, a bona fide lipid phosphatase that antagonizes the highly oncogenic PI3K-AKT-mTOR pathway, is considered a major dose-dependent tumor suppressor. Although PTEN function can be compromised by genetic mutations in inherited syndromes and cancers, posttranslational modifications of PTEN may also play key roles in the dynamic regulation of its function. Notably, deregulated ubiquitination and deubiquitination lead to detrimental impacts on PTEN levels and subcellular partitioning, promoting tumorigenesis. While PTEN can be targeted by HECT-type E3 ubiquitin ligases for nuclear import and proteasomal degradation, studies have shown that several deubiquitinating enzymes, including HAUSP/USP7, USP10, USP11, USP13, OTUD3 and Ataxin-3, can remove ubiquitin from ubiquitinated PTEN in cancer-specific contexts and thus reverse ubiquitination-mediated PTEN regulation. Researchers continue to reveal the precise molecular mechanisms by which cancer-specific deubiquitinases of PTEN regulate its roles in the pathobiology of cancer, and new methods of pharmacologically for modulating PTEN deubiquitinases are critical areas of investigation for cancer treatment and prevention. Here, we assess the mechanisms and functions of deubiquitination as a recently appreciated mode of PTEN regulation and review the link between deubiquitinases and PTEN reactivation and its implications for therapeutic strategies., (© 2022. The Author(s).)

Preterm infants are at a greater risk for the development of asthma and atopic disease, which can lead to lifelong negative health consequences. This may be due, in part, to alterations that occur in the gut microbiome and metabolome during their stay in the Neonatal Intensive Care Unit (NICU). To explore the differential roles of family history (i.e., predisposition due to maternal asthma diagnosis) and hospital-related environmental and clinical factors that alter microbial exposures early in life, we considered a unique cohort of preterm infants born ≤ 34 weeks gestational age from two local level III NICUs, as part of the MAP (Microbiome, Atopic disease, and Prematurity) Study. From MAP participants, we chose a sub-cohort of infants whose mothers had a history of asthma and matched gestational age and sex to infants of mothers without a history of asthma diagnosis (control). We performed a prospective, paired metagenomic and metabolomic analysis of stool and milk feed samples collected at birth, 2 weeks, and 6 weeks postnatal age. Although there were clinical factors associated with shifts in the diversity and composition of stool-associated bacterial communities, maternal asthma diagnosis did not play an observable role in shaping the infant gut microbiome during the study period. There were significant differences, however, in the metabolite profile between the maternal asthma and control groups at 6 weeks postnatal age. The most notable changes occurred in the linoleic acid spectral network, which plays a role in inflammatory and immune pathways, suggesting early metabolomic changes in the gut of preterm infants born to mothers with a history of asthma. Our pilot study suggests that a history of maternal asthma alters a preterm infants' metabolomic pathways in the gut, as early as the first 6 weeks of life., (© 2022. The Author(s).)

Previous studies indicated that miRNA plays an important role in human biological processes especially in the field of diseases. However, constrained by biotechnology, only a small part of the miRNA-disease associations has been verified by biological experiment. This impel that more and more researchers pay attention to develop efficient and high-precision computational methods for predicting the potential miRNA-disease associations. Based on the assumption that molecules are related to each other in human physiological processes, we developed a novel structural deep network embedding model (SDNE-MDA) for predicting miRNA-disease association using molecular associations network. Specifically, the SDNE-MDA model first integrating miRNA attribute information by Chao Game Representation (CGR) algorithm and disease attribute information by disease semantic similarity. Secondly, we extract feature by structural deep network embedding from the heterogeneous molecular associations network. Then, a comprehensive feature descriptor is constructed by combining attribute information and behavior information. Finally, Convolutional Neural Network (CNN) is adopted to train and classify these feature descriptors. In the five-fold cross validation experiment, SDNE-MDA achieved AUC of 0.9447 with the prediction accuracy of 87.38% on the HMDD v3.0 dataset. To further verify the performance of SDNE-MDA, we contrasted it with different feature extraction models and classifier models. Moreover, the case studies with three important human diseases, including Breast Neoplasms, Kidney Neoplasms, Lymphoma were implemented by the proposed model. As a result, 47, 46 and 46 out of top-50 predicted disease-related miRNAs have been confirmed by independent databases. These results anticipate that SDNE-MDA would be a reliable computational tool for predicting potential miRNA-disease associations.

Glacier retreat is a major long-standing global issue; however, the ecological impacts of such retreats on marine organisms remain unanswered. Here, we examined changes to the polar benthic community structure of "diatoms" under current global warming in a recently retreated glacial area of Marian Cove, Antarctica. The environments and spatiotemporal assemblages of benthic diatoms surveyed in 2018-2019 significantly varied between the intertidal (tidal height of 2.5 m) and subtidal zone (10 and 30 m). A distinct floral distribution along the cove (~ 4.5 km) was characterized by the adaptive strategy of species present, with chain-forming species predominating near the glacier. The predominant chain-forming diatoms, such as Fragilaria striatula and Paralia sp., are widely distributed in the innermost cove over years, indicating sensitive responses of benthic species to the fast-evolving polar environment. The site-specific and substrate-dependent distributions of certain indicator species (e.g., F. striatula, Navicula glaciei, Cocconeis cf. pinnata) generally reflected such shifts in the benthic community. Our review revealed that the inner glacier region reflected trophic association, featured with higher diversity, abundance, and biomass of benthic diatoms and macrofauna. Overall, the polar benthic community shift observed along the cove generally represented changing environmental conditions, (in)directly linked to ice-melting due to the recent glacier retreat.

Colorectal cancer is a devastating disease with a low 5-year survival rate. Recently, many researchers have studied the mechanisms of tumor progression related to the tumor microenvironment. Here, we addressed the prognostic value of tumor-associated macrophages (TAMs) using a total of 232 CRC patient tissue samples and investigated the mechanisms underlying TAM-related colon cancer progression with respect to PI3Kγ regulation using in vitro, in vivo, and ex vivo approaches. Patients with M2/M1 < 3 had significantly improved progression-free survival and overall survival compared with patients with M2/M1 > 3. M1 and M2 macrophages elicited opposite effects on colon cancer progression via the FBW7-MCL-1 axis. Blocking macrophage PI3Kγ had cytotoxic effects on colon cancer cells and inhibited epithelial-mesenchymal transition features by regulating the FBW7-MCL-1 axis. The results of this study suggest that macrophage PI3Kγ may be a promising target for immunotherapy in colon cancer.

Systematic characterization of the cancer microbiome provides the opportunity to develop techniques that exploit non-human, microorganism-derived molecules in the diagnosis of a major human disease. Following recent demonstrations that some types of cancer show substantial microbial contributions 1-10 , we re-examined whole-genome and whole-transcriptome sequencing studies in The Cancer Genome Atlas 11 (TCGA) of 33 types of cancer from treatment-naive patients (a total of 18,116 samples) for microbial reads, and found unique microbial signatures in tissue and blood within and between most major types of cancer. These TCGA blood signatures remained predictive when applied to patients with stage Ia-IIc cancer and cancers lacking any genomic alterations currently measured on two commercial-grade cell-free tumour DNA platforms, despite the use of very stringent decontamination analyses that discarded up to 92.3% of total sequence data. In addition, we could discriminate among samples from healthy, cancer-free individuals (n = 69) and those from patients with multiple types of cancer (prostate, lung, and melanoma; 100 samples in total) solely using plasma-derived, cell-free microbial nucleic acids. This potential microbiome-based oncology diagnostic tool warrants further exploration.

Urbanization represents a profound shift in human behaviour, and has considerable cultural and health-associated consequences 1,2 . Here, we investigate chemical and microbial characteristics of houses and their human occupants across an urbanization gradient in the Amazon rainforest, from a remote Peruvian Amerindian village to the Brazilian city of Manaus. Urbanization was found to be associated with reduced microbial outdoor exposure, increased contact with housing materials, antimicrobials and cleaning products, and increased exposure to chemical diversity. The degree of urbanization correlated with changes in the composition of house bacterial and microeukaryotic communities, increased house and skin fungal diversity, and an increase in the relative abundance of human skin-associated fungi and bacteria in houses. Overall, our results indicate that urbanization has large-scale effects on chemical and microbial exposures and on the human microbiota.

Toll-like receptors (TLRs) recognize pathogen/damage-associated molecular patterns and initiate inflammatory signaling cascades. Occasionally, overexpression of TLRs leads to the onset of numerous inflammatory diseases, necessitating the development of selective inhibitors to allow a protective yet balanced immune response. Here, we demonstrate that a novel peptide (TIP1) derived from Toll/interleukin-1 receptor (TIR) domain-containing adapter protein inhibited multiple TLR signaling pathways (MyD88-dependent and MyD88-independent) in murine and human cell lines. TIP1 also inhibited NLRP3-mediated IL-1β secretion, as we validated at both the protein and mRNA levels. Biophysical experiments confirmed that TIP1 specifically binds to the BB loop of the TLR4-TIR domain. Animal studies revealed that TIP1 inhibited the secretion of lipopolysaccharide (LPS)-induced proinflammatory cytokines in collagen-induced arthritis (CIA) and kaolin/carrageenan-induced arthritis (K/C) rodent models. TIP1 also rescued animals from sepsis and from LPS-induced kidney/liver damage. Importantly, TIP1 ameliorated the symptoms of rheumatoid arthritis in CIA and K/C rodent models, suggesting that TIP1 has therapeutic potential for the treatment of TLR-mediated autoimmune/inflammatory diseases.

Neural tissue regeneration is a significant challenge, because severe nerve injury is quite difficult to regenerate spontaneously. Although, many studies have been devoted to promote nerve regeneration, there are still many technical challenges to achieve satisfactory results. In this study, we designed biomimetic matrices composed of aligned laminin core-polydioxanone/collagen shell (Lam-PDO/Col) fibers, which can provide both topographical and biochemical cues for promoting neuritogenesis. The aligned Lam-PDO/Col core-shell fiber matrices were fabricated by magnetic field-assisted electrospinning with the coaxial system, and their potential as biofunctional scaffolds for promoting neuritogenesis was explored. It was demonstrated that the aligned Lam-PDO/Col core-shell fibers were successfully fabricated, and the laminin in the core of fibers was steadily and continuously released from fibers. In addition, the cellular behaviors of hippocampal neuronal cells on the matrices were significantly enhanced. Moreover, the aligned Lam-PDO/Col fiber matrices effectively improved and guided neurite outgrowth as well as the neurogenic differentiation by providing both topographical and biochemical cues through aligned fiber structure and sustained release of laminin. Collectively, it is suggested that the aligned Lam-PDO/Col core-shell fiber matrices are one of the most promising approaches for promoting neuritogenesis and neural tissue regeneration.

Diabetes is a risk factor for acute kidney injury (AKI) and chronic kidney disease (CKD). Diabetic patients are easy to progress to CKD after AKI. Currently, activation of fibrotic signalling including transforming growth factor-β 1 (TGF-β 1 ) is recognized as a key mechanism in CKD. Here, we investigated the influence of diabetes on CKD progression after AKI by using a unilateral renal ischaemia-reperfusion injury (IRI) model in diabetic mice. IRI induced extensive tubular injury, fibrosis and lymphocyte recruitment at 3 weeks after IRI, irrespective of diabetes. However, diabetes showed sustained tubular injury and markedly increased fibrosis and lymphocyte recruitment compared with non-diabetes at 5 week after IRI. The mRNAs and proteins related to TGF-β 1 and sonic hedgehog (Shh) signalling were significantly higher in diabetic versus non-diabetic IRI kidneys. During the in vitro study, the hyperglycaemia induced the activation of TGF-β 1 and Shh signalling and also increased profibrogenic phenotype change. However, hyperglycaemic control with insulin did not improve the progression of renal fibrosis and the activation of TGF-β 1 and Shh signalling. In conclusion, diabetes promotes CKD progression of AKI via activation of the TGF-β 1 and Shh signalling pathways, but insulin treatment was not enough for preventing the progression of renal fibrosis.

The mammal gut microbiome, which includes host microbes and their respective genes, is now recognized as an essential second genome that provides critical functions to the host. In humans, studies have revealed that lifestyle strongly influences the composition and diversity of the gastrointestinal microbiome. We hypothesized that these trends in humans may be paralleled in mammals subjected to anthropogenic forces such as domestication and captivity, in which diets and natural life histories are often greatly modified. We investigated fecal microbiomes of Przewalski's horse (PH; Equus ferus przewalskii), the only horses alive today not successfully domesticated by humans, and herded, domestic horse (E. f. caballus) living in adjacent natural grasslands. We discovered PH fecal microbiomes hosted a distinct and more diverse community of bacteria compared to domestic horses, which is likely partly explained by different plant diets as revealed by trnL maker data. Within the PH population, four individuals were born in captivity in European zoos and hosted a strikingly low diversity of fecal microbiota compared to individuals born in natural reserves in France and Mongolia. These results suggest that anthropogenic forces can dramatically reshape equid gastrointestinal microbiomes, which has broader implications for the conservation management of endangered mammals.

Pseudolaric acid B (PAB), a diterpene acid isolated from the root bark of Pseudolarix kaempferi Gordon, exerts anti-tumor effects in several cancer cell lines. Our previous study showed that PAB mainly induced senescence via p53-p21 activation rather than apoptosis in suppression of the growth of human lung cancer A549 cells (p53 wild-type). In p53-null human lung cancer H1299 cells, however, PAB caused apoptosis without senescence. In this study we investigated what mechanism was responsible for the switch from senescence to apoptosis in PAB-treated human lung cancer cell lines. Senescent cells were examined by SA-β-gal staining. Glucose uptake and the apoptosis ratio were assessed using a FACScan flow cytometer. Commercial assay kits were used to measure the levels of ATP and lactate. Transfection of siRNA was used to knockdown the expression of p53 or p21. Western blot analysis was applied to measure the protein expression levels. In p53 wild-type A549 cells, PAB (20 μmol/L) caused senescence, and time-dependently increased glucose utilization; knockdown of p53 or p21 significantly decreased the uptake and metabolism of glucose but elevated PAB-induced apoptosis. Inhibition of glucose utilization using a glycolytic inhibitor 2-DG (1 mmol/L) significantly enhanced apoptosis induction. Similar results were observed in another p53 wild-type H460 cells treated with PAB. Opposite results were found in p53-null H1299 cells, where PAB time-dependently decreased glucose utilization, and induced only apoptosis. Our results demonstrate that PAB-induced senescence is associated with enhanced glucose utilization, and lower glucose utilization might contribute to apoptosis induction. Thus, blocking glucose utilization contributes to the switch from senescence to apoptosis, and p53 plays an important role in this process.

We report on infrared spectroscopy experiments on the electronic response in (Sr 1-x La x ) 2 IrO 4 (x = 0, 0.021, and 0.067). Our data show that electron doping induced by La substitution leads to an insulator-to-metal transition. The evolution of the electronic structure across the transition reveals the robustness of the strong electronic correlations against the electron doping. The conductivity data of the metallic compound show the signature of the pseudogap that bears close similarity to the analogous studies of the pseudogap in the underdoped cuprates. While the low energy conductivity of the metallic compound is barely frequency dependent, the formation of the pseudogap is revealed by the gradual suppression of the featureless conductivity below a threshold frequency of about 17 meV. The threshold structure develops below about 100 K which is in the vicinity of the onset of the short-range antiferromagnetic order. Our results demonstrate that the electronic correlations play a crucial role in the anomalous charge dynamics in the (Sr 1-x La x ) 2 IrO 4 system.

Mass relaxation profile of a perovskite-type oxide, BaCe 0.9 Y 0.1 O 3-δ , was studied to understand decoupled diffusion of oxygen and hydrogen species during hydration/dehydration. The mass relaxation measurements are performed by thermogravimetric analysis (TGA) under various humidity conditions (Dry, -3.0 ≤ log(pH 2 O/atm) ≤ -1.6) at a constant oxygen partial pressure (log(pO 2 /atm) = -1.00 ± 0.01). The decoupled ions participated in hydration/dehydration reactions were proven to be at different ratios from the result introduced by the 8R m function. The enthalpy and entropy of non-stoichiometric hydration reaction, which considers each ratio of charge-carrier species, were -144.7 ± 3.7 kJ/mol and -147.8 ± 3.2 J/mol · K, respectively.

Hipposponlachnins A (1) and B (2), possessing an unprecedented tetracyclo [9.3.0.0 2,8 .0 3,7 ] tetradecane ring system, and the probable biogenetic precursor [3, (1R*,2E,4R*,7E,10S*,11S*,12R*)-10, 18-diacetoxydolabella-2,7-dien-6-one] of 1‒2 were isolated from the South China Sea marine sponge Hippospongia lachne. The structures of the novel compounds were determined using integrated spectroscopic methods in combination with single-crystal X-ray diffraction analysis. Compounds 1‒2 showed potent inhibitory activity on the release of β-hexosaminidase, a biomarker for degranulation, as well as the production of pro-inflammatory cytokine IL-4 and lipid mediator LTB 4 in DNP-IgE-stimulated RBL-2H3 cells.

Mammalian oocyte asymmetric division relies on the eccentric positioning of the spindle, resulting in the polar body formation. Small signaling G protein Rac1 is a member of GTPases, which regulates a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. However, effects of Rac1 on the porcine oocyte maturation and early embryo development are not fully understood. In present study we investigated the role of Rac1 in oocyte maturation and embryo cleavage. We first found that Rac1 localized at the cortex of the porcine oocytes, and disrupting the Rac1 activities by treating with NSC 23766 led to the failure of polar body emission. In addition, a majority of treated oocytes exhibited abnormal spindle morphology, indicating that Rac1 may involve into porcine oocyte spindle formation. This might be due to the regulation of Rac1 on MAPK, since p-MAPK expression decreased after NSC 23766 treatments. Moreover, we found that the position of most meiotic spindles in treated oocytes were away from the cortex, indicating the roles of Rac1 on meiotic spindle positioning. Our results also showed that inhibition of Rac1 activity caused the failure of early embryo development. Therefore, our study showed the critical roles of Rac1 GTPase on porcine oocyte maturation and early embryo cleavage.

We report on infrared spectroscopic studies of the electronic response of the (Sr1-xLax)3Ir2O7 system. Our experiments revealed hallmarks of strong electronic correlations in the evolution of the electronic response across the filling-controlled insulator-metal transition. We observed a collapse of the Jeff = 1/2 Mott gap accompanying the transfer of the spectral weight from the high-energy region to the gap region with electron doping. The intraband conductivity at the metallic side of the transition was found to consist of coherent Drude-like and incoherent responses. The sum rule and the extended Drude model analyses further indicated a large mass enhancement. Our results demonstrate a critical role of the electronic correlations in the charge dynamics of the (Sr1-xLax)3Ir2O7 system.

Alcohol consumption is one of the major causes of hepatic steatosis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Ethanol metabolism alters the NAD(+)/NADH ratio, thereby suppressing the activity of sirtuin family proteins, which may affect lipid metabolism in liver cells. However, it is not clear how long-term ingestion of ethanol eventually causes lipid accumulation in liver. Here, we demonstrate that chronic ethanol ingestion activates peroxisome proliferator-activated receptor γ (PPARγ) and its target gene, monoacylglycerol O-acyltransferase 1 (MGAT1). During ethanol metabolism, a low NAD(+)/NADH ratio repressed NAD-dependent deacetylase sirtuin 1 (SIRT1) activity, concomitantly resulting in increased acetylated PPARγ with high transcriptional activity. Accordingly, SIRT1 transgenic mice exhibited a low level of acetylated PPARγ and were protected from hepatic steatosis driven by alcohol or PPARγ2 overexpression, suggesting that ethanol metabolism causes lipid accumulation through activation of PPARγ through acetylation. Among the genes induced by PPARγ upon alcohol consumption, MGAT1 has been shown to be involved in triglyceride synthesis. Thus, we tested the effect of MGAT1 knockdown in mice following ethanol consumption, and found a significant reduction in alcohol-induced hepatic lipid accumulation. These results suggest that MGAT1 may afford a promising approach to the treatment of fatty liver disease.

Glucocorticoids are associated with obesity, but the underlying mechanism by which they function remains poorly understood. Previously, we showed that small G protein Dexras1 is expressed by glucocorticoids and leads to adipocyte differentiation. In this study, we explored the mechanism by which Dexras1 mediates adipogenesis and show a link to the insulin-like growth factor-1 (IGF-1) signaling pathway. Without Dexras1, the activation of MAPK and subsequent phosphorylation of CCAAT/enhancer binding protein β (C/EBPβ) is abolished, thereby inhibiting mitotic clonal expansion and further adipocyte differentiation. Dexras1 translocates to the plasma membrane upon insulin or IGF-1 treatment, for which the unique C-terminal domain (amino acids 223-276) is essential. Dexras1-dependent MAPK activation is selectively involved in the IGF-1 signaling, because another Ras protein, H-ras localized to the plasma membrane independently of insulin treatment. Moreover, neither epidermal growth factor nor other cell types shows Dexras1-dependent MAPK activation, indicating the importance of Dexras1 in IGF-1 signaling in adipogenesis. Dexras1 interacts with Shc and Raf, indicating that Dexras1-induced activation of MAPK is largely dependent on the Shc-Grb2-Raf complex. These results suggest that Dexras1 is a critical mediator of the IGF-1 signal to activate MAPK, linking glucocorticoid signaling to IGF-1 signaling in adipogenesis.

The real time detection of quantitative oxygen release from the cathode is performed by in-situ Gas Chromatography as a tool to not only determine the amount of oxygen release from a lithium-ion cell but also to address the safety concerns. This in-situ gas chromatography technique monitoring the gas evolution during electrochemical reaction presents opportunities to clearly understand the effect of surface modification and predict on the cathode stability. The oxide cathode, 0.5Li2MnO3∙0.5LiNi0.4Co0.2Mn0.4O2, surface modified by amorphous cobalt-phosphate nanoparticles (a-CoPO4) is prepared by a simple co-precipitation reaction followed by a mild heat treatment. The presence of a 40 nm thick a-CoPO4 coating layer wrapping the oxide powders is confirmed by electron microscopy. The electrochemical measurements reveal that the a-CoPO4 coated overlithiated layered oxide cathode shows better performances than the pristine counterpart. The enhanced performance of the surface modified oxide is attributed to the uniformly coated Co-P-O layer facilitating the suppression of O2 evolution and offering potential lithium host sites. Further, the formation of a stable SEI layer protecting electrolyte decomposition also contributes to enhanced stabilities with lesser voltage decay. The in-situ gas chromatography technique to study electrode safety offers opportunities to investigate the safety issues of a variety of nanostructured electrodes.

Recent claim on the direct observation of a negative capacitance (NC) effect from a single layer epitaxial Pb(Zr0.2,Ti0.8)O3 (PZT) thin film was carefully reexamined, and alternative interpretations that can explain the experimental results without invoking the NC effect are provided. Any actual ferroelectric capacitor has an interfacial layer, and experiment always measures the sum of voltages across the interface layer and the ferroelectric layer. The main observation of decreasing ferroelectric capacitor voltage (VF) for increasing ferroelectric capacitor charge (QF), claimed to be the direct evidence for the NC effect, could be alternatively interpreted by either the sudden increase in the positive capacitance of a ferroelectric capacitor or decrease in the voltage across the interfacial layer due to resistance degradation. The experimental time-transient VF and QF could be precisely simulated by these alternative models that fundamentally assumes the reverse domain nucleation and growth. Supplementary experiments using an epitaxial BaTiO3 film supported this claim. This, however, does not necessarily mean that the realization of the NC effect within the ferroelectric layer is impractical under appropriate conditions. Rather, the circuit suggested by Khan et al. may not be useful to observe the NC effect directly.

We report here that Arabidopsis PROTEIN S-ACYL TRANSFERASE14 (PAT14), through its palmitate transferase activity, acts at the vacuolar trafficking route to repress salicylic acid (SA) signaling, thus mediating age-dependent but not carbon starvation-induced leaf senescence. Functional loss of PAT14 resulted in precocious leaf senescence and its transcriptomic analysis revealed that senescence was dependent on salicylic acid. Overexpressing PAT14 suppressed the expression of SA responsive genes. Introducing the SA deficient mutants, npr1-5 and NahG, but not other hormonal mutants, completely suppressed the precocious leaf senescence of PAT14 loss-of-function, further supporting the epistatic relation between PAT14 and the SA pathway. By confocal fluorescence microscopy, we showed that PAT14 is localized at the Golgi, the trans-Golg network/early endosome, and prevacuolar compartments, indicating its roles through vacuolar trafficking. By reporter analysis and real time PCRs, we showed that the expression PAT14, unlike most of the senescence associated genes, is not developmentally regulated, suggesting post-transcriptional regulatory mechanisms on its functionality. We further showed that the maize and wheat homologs of PAT14 fully rescued the precocious leaf senescence of pat14-2, demonstrating that the role of PAT14 in suppressing SA signaling during age-dependent leaf senescence is evolutionarily conserved between dicots and monocots.

The maximum power density of SOFC with 8YSZ electrolyte as the function of thickness was calculated by integrating partial conductivities of charge carriers under various DC bias conditions at a fixed oxygen chemical potential gradient at both sides of the electrolyte. The partial conductivities were successfully taken using the Hebb-Wagner polarization method as a function of temperature and oxygen partial pressure, and the spatial distribution of oxygen partial pressure across the electrolyte was calculated based on Choudhury and Patterson's model by considering zero electrode polarization. At positive voltage conditions corresponding to SOFC and SOEC, the high conductivity region was expanded, but at negative cell voltage condition, the low conductivity region near n-type to p-type transition was expanded. In addition, the maximum power density calculated from the current-voltage characteristic showed approximately 5.76 W/cm(2) at 700 (o)C with 10 μm thick-8YSZ, while the oxygen partial pressure of the cathode and anode sides maintained ≈0.21 and 10(-22) atm.

Resistance switching (RS) devices with ultra-thin Ta2O5 switching layer (0.5-2.0 nm) with a cell diameter of 28 nm were fabricated. The performance of the devices was tested by voltage-driven current-voltage (I-V) sweep and closed-loop pulse switching (CLPS) tests. A Ta layer was placed beneath the Ta2O5 switching layer to act as an oxygen vacancy reservoir. The device with the smallest Ta2O5 thickness (0.5 nm) showed normal switching properties with gradual change in resistance in I-V sweep or CLPS and high reliability. By contrast, other devices with higher Ta2O5 thickness (1.0-2.0 nm) showed abrupt switching with several abnormal behaviours, degraded resistance distribution, especially in high resistance state, and much lower reliability performance. A single conical or hour-glass shaped double conical conducting filament shape was conceived to explain these behavioural differences that depended on the Ta2O5 switching layer thickness. Loss of oxygen via lateral diffusion to the encapsulating Si3N4/SiO2 layer was suggested as the main degradation mechanism for reliability, and a method to improve reliability was also proposed.

Unipolar resistance switching (RS) in TiO2 thin films originates from the repeated formation and rupture of the Magnéli phase conducting filaments through repeated nano-scale phase transitions. By applying the Johnson-Mehl-Avrami (JMA) type kinetic model to the careful analysis on the evolution of transient current in a pulse-switching, it was possible to elucidate the material specific evolution of the Magnéli phase filament. This methodology was applied to the two types of TiO2 films grown by plasma-enhanced atomic layer deposition (PEALD) and sputtering. These two samples have structurally and electrically distinctive properties: PEALD film exhibited high variability in switching parameters and required an electroforming while sputtered film showed higher uniformity without distinct electroforming process. The JMA-type kinetic analysis of the RS behaviors revealed that the rejuvenation of the filament is accomplished by repeated one-dimensional nucleation followed by a two-dimensional growth in PEALD samples, whereas one-dimensional nucleation-free mechanism dominates in sputtered films.

Despite nanomaterials with unique properties playing a vital role in scientific and technological advancements of various fields including chemical and electrochemical applications, the scope for exploration of nano-scale applications is still wide open. The intimate correlation between material properties and synthesis in combination with the urgency to enhance the empirical understanding of nanomaterials demand the evolution of new strategies to promising materials. Herein we introduce a rapid pyro-synthesis that produces highly crystalline functional nanomaterials under reaction times of a few seconds in open-air conditions. The versatile technique may facilitate the development of a variety of nanomaterials and, in particular, carbon-coated metal phosphates with appreciable physico-chemical properties benefiting energy storage applications. The present strategy may present opportunities to develop "design rules" not only to produce nanomaterials for various applications but also to realize cost-effective and simple nanomaterial production beyond lab-scale limitations.

The tumor suppressor RASSF1A is inactivated in many human cancers and is implicated in regulation of microtubule stability, cell cycle progression and apoptosis. However, the precise mechanisms of RASSF1A action and their regulation remain unclear. Here we show that Skp2, an oncogenic subunit of the Skp1-Cul1-F-box ubiquitin ligase complex, interacts with, ubiquitinates, and promotes the degradation of RASSF1A at the G1-S transition of the cell cycle. This Skp2-dependent destruction of RASSF1A requires phosphorylation of the latter on serine-203 by cyclin D-cyclin-dependent kinase 4. Interestingly, mutation of RASSF1A-phosphorylation site Ser(203) to alanine results in a delay in cell cycle progression from G1 to S phase. Moreover, enforced expression of Skp2 abolishes the inhibitory effect of RASSF1A on cell proliferation. Finally, the delay in G1-S progression after Skp2 removal is normalized by depletion of RASSF1A. These findings suggest that the Skp2-mediated degradation of RASSF1A plays an important role in cell proliferation and survival.