The Enhancement of the Thermal Conductivity of Epoxy Resin Reinforced by Bromo-Oxybismuth.

With the gradual miniaturization of electronic devices, the thermal conductivity of electronic components is increasingly required. Epoxy (EP) resins are easy to process, exhibit excellent electrical insulation properties, and are light in weight and low in cost, making them the preferred material for thermal management applications. In order to endow EPs with better dielectric and thermal conductivity properties, bromo-oxygen-bismuth (BiOBr) prepared using the hydrothermal method was used as a filler to obtain BiOBr/EP composites, and the effect of BiOBr addition on the properties of the BiOBr/EP composites was also studied. The results showed that the addition of a small amount of BiOBr could greatly optimize the dielectric properties and thermal conductivity of EP resin, and when the content of BiOBr was 0.75 wt% and 1.00 wt%, the dielectric properties and thermal conductivity of the composite could reach the optimum, respectively. The high dielectric constant and excellent thermal conductivity of BiOBr/EP composites are mainly due to the good layered structure of BiOBr, which can provide good interfacial polarization and thermal conductivity.

Integrated metabolite profiling and transcriptome analysis reveal candidate genes involved in the formation of yellow Nelumbo nucifera.

As a worldwide major ornamental flower and a edible plant, lotus (Nelumbo nucifera) is also used as medicine and tea beverage. Here, transcriptome and metabolites of yellow (MLQS) and white (YGB) lotus cultivars during five key flower coloration stages were profiled. 2014 differentially expressed genes were detected with 11 carotenoids in lotus were identified for the first time. Then, regulatory networks between and within functional modules was reconstructed, and the correlation between module-metabolites and gene-metabolites was conducted within 3 core modules. 18 candidate genes related to the formation of yellow flower were screened out and a gene regulatory model for the flower color difference between MLQS and YGB were speculated as follows: The substrate competition between F3'H and F3'5'H and substrate specificity of FLS, together with differential expression of CCD4a and CCD4b were contribute to the differences in flavonoids and carotenoids. Besides, UGT73C2, UGT91C1-2 and SGTase, and regulation of UGTs by transcription factors PLATZ, MADS, NAC031, and MYB308 may also play a role in the upstream regulation. The following verification results indicated that functional differences existed in the coding sequences of NnCCD4b and promoters of NnCCD4a of MLQS and YGB. In all, this study preliminarily reveals the mechanism of yellow flower coloration in lotus and provides new ideas for the study of complex ornamental characters of other plants.

A PDX1 cistrome and single-cell transcriptome resource of the developing pancreas.

Pancreatic and duodenal homeobox 1 (PDX1) is crucial for pancreas organogenesis, yet the dynamic changes in PDX1 binding in human or mouse developing pancreas have not been examined. To address this knowledge gap, we performed PDX1 ChIP-seq and single-cell RNA-seq using fetal human pancreata. We integrated our datasets with published datasets and revealed the dynamics of PDX1 binding and potential cell lineage-specific PDX1-bound genes in the pancreas from fetal to adult stages. We identified a core set of developmentally conserved PDX1-bound genes that reveal the broad multifaceted role of PDX1 in pancreas development. Despite the well-known dramatic changes in PDX1 function and expression, we found that PDX1-bound genes are largely conserved from embryonic to adult stages. This points towards a dual role of PDX1 in regulating the expression of its targets at different ages, dependent on other functionally congruent or directly interacting partners. We also showed that PDX1 binding is largely conserved in mouse pancreas. Together, our study reveals PDX1 targets in the developing pancreas in vivo and provides an essential resource for future studies on pancreas development.

Facile and simple fabrication of superhydrophobic and superoleophilic MS/PDA/DT sponge for efficient oil/water separation.

To overcome the problems of frequent leakage accidents during oil exploitation, a superhydrophobic and superoleophilic porous MS/PDA/DT sponge was successfully prepared via mild solvent evaporation method, and a polydopamine assisted surface coating of 1-dodecanethiol (DT) on a melamine sponge (MS) substrate. Surface structure and performance of the MS/PDA/DT sponge were characterized by Scanning Electron Microscope (SEM), Fourier transform infrared spectrometer (FTIR), and Video Optical Contact Angle (CA) metre. The results showed that the as-prepared MS/PDA/DT sponge has a high-water contact angle (WCA) of 147.2°, which is probably attributed to both the rough surface derived from in situ growth and the low surface energy due to grafting of hydrophobic 1-dodecanethiol. The durability of the as-constructed MS/PDA/DT sponge was studied by repeated abrasion tests. After 50 abrasion cycles, the superhydrophobicity of the MS/PDA/DT sponge good mechanical durability. The MS/PDA/DT sponge can effectively absorb oil with an absorption capacity of up to 24 times its weight. The superhydrophobic and superoleophilic MS/PDA/DT sponge has the potential as a promising adsorbent for oil/water separation.Highlights The MS/PDA/DT sponge was prepared via the mild solvent evaporation method.The contact angle of the MS/PDA/DT sponge was 147.2o.The adsorption capacity of the MS/PDA/DT sponge was 24 times their weight.The cost-efficient, environmentally friendly porous materials show high oil/water separation efficiency.

Facile synthesis of superhydrophobic MS/TiO2/PDMS sponge for efficient oil-water separation.

To obtain a kind of superhydrophobic sponge with high oil and water selectivity, the MS/TiO2/PDMS sponge was prepared via a two-step hydrophobic fabrication based on the melamine sponge (MS), tetrabutyl titanate (TBOT), and polydimethylsiloxane (PDMS). The effects of modification time, the concentrations of TBOT and PDMS on the properties of the MS/TiO2/PDMS sponge were studied, and the separation mechanism was also discussed based on the interaction between the oil and the surface of the MS/TiO2/PDMS sponge. The results suggest that under optimal conditions, the MS/TiO2/PDMS sponge show superhydrophobicity. The contact angle and adsorption capacity for oil of the MS/TiO2/PDMS sponge are 149.2° and 98.5 g·g-1, respectively, and they can be recycled for about 25 cycles after oil-water separation test. This study prepares a new composite material with high oil-water selectivity, which is a good foundation for the development and research of new oil adsorbents.

Tetrahydroxy stilbene glycoside regulates TGF-ß/fractalkine/CX3CR1 based on network pharmacology in APP/PS1 mouse model.

Alzheimer's disease (AD) is a serious, progressive neurodegenerative disease that involves irreversible neuronal death. Tetrahydroxy stilbene glycoside (TSG) is an active compound extracted from P. multiflorum, a traditional Chinese herbal medicine, but its role in neuroprotection is unclear. Herein, we aimed to validate the effects of TSG on APP/PS1 model mice and the underlying mechanism. RNA-seq was performed to identify differentially expressed genes in APP/PS1 mouse, with PCR and immunohistochemistry used for validation. Experiments were performed after bioinformatic analysis for verification. Neuronal damage was observed by H&E staining. Key proteins involved in the pathway such as CX3CR1, Iba1 and TGF-ß were examined by immunohistochemical analysis. The KEGG analysis suggested that these genes might act by multiple pathways to build the pharmacological network of TSG in AD progression. These data provide the credible evidence that TSG improved neuronal damage and regulated neuroprotective mechanisms. Together, our work has detailed the whole and major genes in APP/PS1 model mouse regulated by TSG, and highlighted the anti-inflammatory function of TSG in mediating CX3CR1 and TGF-ß as the TGF-ß/fractalkine/CX3XR1 signaling pathway, especially in microglia. Moreover, TSG has potential value in synaptic transmission and neurotrophic action on neurodegenerative diseases. In summary, TSG is a promising candidate for preventing and treating the progression of AD.

Decreased KATP Channel Activity Contributes to the Low Glucose Threshold for Insulin Secretion of Rat Neonatal Islets.

Transitional hypoglycemia in normal newborns occurs in the first 3 days of life and has clinical features consistent with hyperinsulinism. We found a lower threshold for glucose-stimulated insulin secretion from freshly isolated embryonic day (E) 22 rat islets, which persisted into the first postnatal days. The threshold reached the adult level by postnatal day (P) 14. Culturing P14 islets also decreased the glucose threshold. Freshly isolated P1 rat islets had a lower threshold for insulin secretion in response to 2-aminobicyclo-(2, 2, 1)-heptane-2-carboxylic acid, a nonmetabolizable leucine analog, and diminished insulin release in response to tolbutamide, an inhibitor of ß-cell KATP channels. These findings suggested that decreased KATP channel function could be responsible for the lower glucose threshold for insulin secretion. Single-cell transcriptomic analysis did not reveal a lower expression of KATP subunit genes in E22 compared with P14 ß cells. The investigation of electrophysiological characteristics of dispersed ß cells showed that early neonatal and cultured cells had fewer functional KATP channels per unit membrane area. Our findings suggest that decreased surface density of KATP channels may contribute to the observed differences in glucose threshold for insulin release.

FBXW7 mediates high glucose­induced SREBP­1 expression in renal tubular cells of diabetic nephropathy under PI3K/Akt pathway regulation.

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and lipid metabolism abnormality serves a key role in the pathogenesis of DN. Sterol regulatory element­binding protein 1 (SREBP­1) overexpression mediates aberrant lipid accumulation in renal tubular cells of DN. However, the exact mechanism involved in increased SREBP­1 has not been fully elucidated. The aim of the present study was to explore the mechanism involved in SREBP­1 upregulation. Diabetic mice and high glucose­cultured HKC cells were chosen to detect the expression of FBXW7 and SREBP­1 using immunohistochemistry, western blotting and PCR. The present study demonstrated that F­box and WD repeat domain containing 7 (FBXW7) expression was decreased in renal tubular cells of diabetic mice. Moreover, the co­expression of FBXW7 and SREBP­1 was observed in renal tubular cells, but not in the glomeruli. High glucose­induced the downregulation of FBXW7 expression in in vitro cultured HKC cells, which was accompanied by SREBP­1 upregulation. In addition, overexpression of FBXW7 in HKC cells led to SREBP­1 downregulation. By contrast, knockdown of FBXW7 caused SREBP­1 upregulation in HKC cells. It was found that the PI3K/Akt signaling pathway was activated in high glucose­stimulated HKC cells, and inhibition of PI3K/Akt pathway using LY294002 increased FBXW7 expression and decreased SREBP­1 expression. Taken together, the present results suggested that FBXW7 mediated high glucose­induced SREBP­1 expression in renal tubular cells of DN, under the regulation of the PI3K/Akt signaling pathway.

Formation mechanism of zigzag patterned P(NIPAM-co-AA)/CuS composite microspheres by in situ biomimetic mineralization for morphology modulation.

Poly(N-isopropylacrylamide-co-acrylic acid)/copper sulfide (P(NIPAM-co-AA)/CuS) composite microspheres with variable zigzag patterned surfaces have been synthesized by employing an in situ biomimetic mineralization reaction between H2S and Cu2+ immersed in P(NIPAM-co-AA) microspheres for morphology modulation. The morphology and composition of the P(NIPAM-co-AA)/CuS composite microspheres with zigzag patterned surfaces prepared in different conditions were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectrometry (FT-IR). The polymeric microgels swelled by Cu(Ac)2 solution after freeze-drying treatment were of porous structure, indicating that there were polymeric frameworks and rich-water domains in the microgels before the deposition. Furthermore, due to the limited uneven deposition of metal sulfide on the polymeric skeleton of the hydrogel surface, the surface polymeric skeleton will be anisotropically shrunk when the composite microspheres lose water and shrink, thus forming a wrinkle pattern on the surface of the composite microspheres. The factors affecting the deposition amount and distribution of metal sulfide will affect the zigzag patterned morphology. Based on the experimental results, a formation mechanism of the P(NIPAM-co-AA)/CuS composite microspheres with zigzag patterned surface, "the deformed shrinkage of the surface texture", has been proposed. The formation mechanism of the surface morphology in the composite microspheres is helpful for understanding and controlling the process of mineralization, for preparing materials expected by controlling the experiment conditions, and for expanding the application of the composites.

Brazilin Treatment Produces Antidepressant- and Anxiolytic-Like Effects in Mice.

Increasing evidence shows depression relevant to oxidative stress and inflammation. Anti-inflammatory strategies or antioxidants have led to the development of new antidepressants. Brazilin is a natural product from the Chinese traditional medicine Caesalpinia sappan L., exerting anti-inflammatory, antioxidant, anti-platelet concentration, and anti-cancer effects. While the antidepressant effect of brazilin is largely unknown. In present study, we investigated the effects of brazilin on H2O2-induced oxidative injury in PC12 cells and on depression- and anxiety-like behaviors of chronically mild stressed (CMS)-induced depression mice. It was found that brazilin pre-treatment (both 10 and 20 µM) significantly increased cell viability and decreased cell apoptosis in H2O2-treated PC12 cells. Furthermore, repetitive administration of brazilin to CMS-induced depression mice by intraperitoneal injection (10 mg/kg) made the mice significantly lose their latency of feeding in novelty-suppressed feeding test (NSF), have more the sucrose preference in sucrose preference test (SPT), and more time spent in the central zone without affecting their crossing activity in open field test (OFT). These results suggested that brazilin can play a role in antidepressant and anxiolytic-like behaviors for CMS-induced depression mice probably through inhibiting the oxidative stress. Therefore, brazilin is worth to be further explored for treating depressive and anxiety disorders.

Genome-wide analyses of the bHLH gene family reveals structural and functional characteristics in the aquatic plant Nelumbo nucifera.

Lotus (Nelumbo nucifera Gaertn.) is an economically important aquatic plant with multiple applications, but water salinity and cold stress seriously affect lotus yield and distribution. The basic helix-loop-helix (bHLH) transcription factors (TFs) play a vital role in plant growth and development, metabolic regulation processes and responses to environmental changes. However, systematic analyses of the bHLH TF family in lotus has not yet been reported. Here, we report the identification and description of bHLH genes in lotus (NnbHLHs) with a focus on functional prediction, particularly for those involved in stress resistance. In all, 115 NnbHLHs were identified in the lotus genome and classified into 19 subfamilies. The chromosomal distribution, physicochemical properties, bHLH domain, conserved motif compositions and evolution of these 115 NnbHLHs were further analyzed. To better understand the functions of the lotus bHLH family, gene ontology, cis-element, and phylogenetic analyses were conducted. NnbHLHs were predicted to be involved in plant development, metabolic regulation and responses to stress, in accordance with previous findings. Overall, 15 NnbHLHs were further investigated with functional prediction via quantitative real-time PCR analyses. Meanwhile, expression profiles of NnbHLHs in four tissues indicated that many NnbHLHs showed tissue preference in their expression. This study is supposed to provide a good foundation for further research into the functions and evolution of NnbHLHs, and identifies candidate genes for stress resistance in lotus.

Differences in flavonoid pathway metabolites and transcripts affect yellow petal colouration in the aquatic plant Nelumbo nucifera.

BACKGROUND: The Asia lotus (Nelumbo nucifera Gaertn.) is an ornamental aquatic plant with high economic value. Flower colour is an important ornamental trait, with much of N. nucifera breeding focusing on its yellow flowers. To explore the yellow flower colouration mechanism in N. nucifera, we analysed its pigment constituents and content, as well as gene expression in the flavonoid pathway, in two N. nucifera cultivars. RESULTS: We performed metabolomic and gene expression analyses in two N. nucifera cultivars with yellow and white flowers, Molinqiuse (MLQS) and Yeguangbei (YGB), respectively, at five stages of flower colouration. Based on phenotypic observation and metabolite analyses, the later stages of flower colouration (S3-S5) were determined to be key periods for differences between MLQS and YGB, with dihydroflavonols and flavonols differing significantly between cultivars. Dihydroquercetin, dihydrokaempferol, and isorhamnetin were significantly higher in MLQS than in YGB, whereas kaempferol was significantly higher in YGB. Most of the key homologous structural genes in the flavonoid pathway were significantly more active in MLQS than in YGB at stages S1-S4. CONCLUSION: In this study, we performed the first analyses of primary and secondary N. nucifera metabolites during flower colouration, and found that isorhamnetin and kaempferol shunting resulted in petal colour differences between MLQS and YGB. Based on our data integration analyses of key enzyme expression in the putative flavonoid pathways of the two N. nucifera cultivars, NnFLS gene substrate specificity and differential expression of NnOMTs may be related to petal colour differences between MLQS and YGB. These results will contribute to determining the mechanism of yellow flower colouration in N. nucifera, and will improve yellow petal colour breeding in lotus species.

JUND regulates pancreatic ß cell survival during metabolic stress.

OBJECTIVE: In type 2 diabetes (T2D), oxidative stress contributes to the dysfunction and loss of pancreatic ß cells. A highly conserved feature of the cellular response to stress is the regulation of mRNA translation; however, the genes regulated at the level of translation are often overlooked due to the convenience of RNA sequencing technologies. Our goal is to investigate translational regulation in ß cells as a means to uncover novel factors and pathways pertinent to cellular adaptation and survival during T2D-associated conditions. METHODS: Translating ribosome affinity purification (TRAP) followed by RNA-seq or RT-qPCR was used to identify changes in the ribosome occupancy of mRNAs in Min6 cells. Gene depletion studies used lentiviral delivery of shRNAs to primary mouse islets or CRISPR-Cas9 to Min6 cells. Oxidative stress and apoptosis were measured in primary islets using cell-permeable dyes with fluorescence readouts of oxidation and activated cleaved caspase-3 and-7, respectively. Gene expression was assessed by RNA-seq, RT-qPCR, and western blot. ChIP-qPCR was used to determine chromatin enrichment. RESULTS: TRAP-seq in a PDX1-deficiency model of ß cell dysfunction uncovered a cohort of genes regulated at the level of mRNA translation, including the transcription factor JUND. Using a panel of diabetes-associated stressors, JUND was found to be upregulated in mouse islets cultured with high concentrations of glucose and free fatty acid, but not after treatment with hydrogen peroxide or thapsigargin. This induction of JUND could be attributed to increased mRNA translation. JUND was also upregulated in islets from diabetic db/db mice and in human islets treated with high glucose and free fatty acid. Depletion of JUND in primary islets reduced oxidative stress and apoptosis in ß cells during metabolic stress. Transcriptome assessment identified a cohort of genes, including pro-oxidant and pro-inflammatory genes, regulated by JUND that are commonly dysregulated in models of ß cell dysfunction, consistent with a maladaptive role for JUND in islets. CONCLUSIONS: A translation-centric approach uncovered JUND as a stress-responsive factor in ß cells that contributes to redox imbalance and apoptosis during pathophysiologically relevant stress.

Repeated arctigenin treatment produces antidepressant- and anxiolytic-like effects in mice.

Depression is the root of various diseases. It is one of the most debilitating conditions globally. Antidepressant drugs are usually the first-line of depression treatment. Arctigenin (ARC), one of active ingredient of Arctium lappa L, has been found to exert neuroprotective, anti-decrepitude, and anti-inflammatory activities. Thus, the aim of this study was to investigate the potential antidepressant- and anxiolytic-like effects of ARC using acute and chronic mild stress (CMS) mice model. ICR mice model received acute stress or chronic mild stress assessed by open field test (OFT), novelty suppressed feeding (NSF), sucrose preference test (SPT), forced-swimming test (FST), and tail suspension test (TST). After the final test, blood was collected to detect the serum levels of angiogenin (ANG), thrombopoietin (TPO), and vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay (ELISA). The behavioral results showed that repeated ARC (10, 30 mg/kg) administration significantly relieved the antidepressant- and anxiolytic-like effects. And repeated ARC administration at the dose of 10 and 30 mg/kg could significantly block depressive- and anxiety-like behaviors caused by CMS. Finally, ELISA results showed that ARC administration increased the serum levels of angiogenin (ANG), thrombopoietin (TPO), and vascular endothelial growth factor (VEGF). Results showed that chronic ARC administration produces antidepressant- and anxiolytic-like effects, which provides direct evidence for the first time that ARC may be a novel strategy for the treatment of depression and even stress-related disorders. The present data supports further exploration for developing ARC administration as a novel therapeutic strategy for depression and even stress-related disorders.

Solvation effect and binding of rhaponticin with iron: a spectroscopic and DFT/TDDFT study.

In this article, both experimental and computational methods are employed to investigate the photophysics of rhaponticin (RH). The bathochromic shift was observed in absorption and fluorescence spectra with increasing solvent polarity, which implied that the charge transition of RH involved was π → π*. The results showed that RH possess strong intramolecular charge transfer (ICT), and the most important parameter to characterize the photophysical behavior of RH is the intermolecular hydrogen bonding ability of the solvent. The hydrogen bonding effect occurred at the localized electron-acceptor oxygen at the glycoside bond. Density functional theory (DFT) and time dependent density functional theory (TDDFT) were used to obtain the most stable structure, electronic excitation energy, dipole moments and charge distribution. The result was found to be 2.23 and 3.67 D in ground state and excited state respectively. Fluorescence quenching of RH owing to the photoinduced electron transfer (PET) is facilitated in alkaline media. The pK a value of RH was 6.39, which defined RH as a highly efficient "off-on" switcher. The effect of different metal ions on the fluorescence spectra of RH was also investigated, and the fluorescence quenching of RH depended on the nature of ions. The best performance was accomplished for binding with the Fe3+ ion. The interactions of RH with the Fe3+ ion were studied by FT-IR and HPLC, and the binding parameter was calculated by the Stern-Volmer equation. The results obtained reveal the binding activity of RH can make this a candidate as a good source of new agents for thalassemic patients.

Detection of Highly Differentiated Genomic Regions Between Lotus (Nelumbo nucifera Gaertn.) With Contrasting Plant Architecture and Their Functional Relevance to Plant Architecture.

The lotus (Nelumbo nucifera Gaertn.) is one of the most economically and ornamentally important perennial aquatic plants. Plant architecture is an important trait for lotus classification, cultivation, breeding, and applications. In this study, traits representing plant architecture were measured in 390 lotus germplasms for 3 years. According to the phenotypic distribution, 21 large architecture (LA) and 22 small architecture (SA) germplasms exhibiting extreme phenotypes were selected as representatives of plant architecture. Microscopy analyses revealed that LA lotuses possessed far more vertical cells and longer cell lengths than SA lotuses, and there was a closer linear relationship between vertical cell number and plant architecture than cell length and plant architecture. Furthermore, based on whole genome re-sequencing data from 10 LA and 10 SA lotus germplasms, fixation index (FST) genome scan identified 11.02 Mb of genomic regions that were highly differentiated between the LA and SA lotus groups. Chi-square test revealed that 17,154 single nucleotide polymorphisms (SNPs) and 1,554 insertions and deletions (InDels) showed distinct allelic distribution between the LA and SA lotus groups within these regions. A total of 126 variants with distinct allelic distribution in the highly differentiated region were predicted to cause amino acid changes in 60 genes. Among the 41 genes with functional annotation, the expression patterns of six genes involved in cell division and cell wall construction were confirmed using quantitative reverse-transcription PCR (qRT-PCR). In addition, 34 plant architecture-associated InDel markers were developed and verified in the remaining 11 LA and 12 SA lotus plant architecture representatives. This study identified promising functional markers and candidates for molecular breeding and will facilitate further elucidation of the genetic mechanisms underlying plant architecture in the lotus.

A PDX1-ATF transcriptional complex governs ß cell survival during stress.

OBJECTIVE: Loss of insulin secretion due to failure or death of the insulin secreting ß cells is the central cause of diabetes. The cellular response to stress (endoplasmic reticulum (ER), oxidative, inflammatory) is essential to sustain normal ß cell function and survival. Pancreatic and duodenal homeobox 1 (PDX1), Activating transcription factor 4 (ATF4), and Activating transcription factor 5 (ATF5) are transcription factors implicated in ß cell survival and susceptibility to stress. Our goal was to determine if a PDX1-ATF transcriptional complex or complexes regulate ß cell survival in response to stress and to identify direct transcriptional targets. METHODS: Pdx1, Atf4 and Atf5 were silenced by viral delivery of gRNAs or shRNAs to Min6 insulinoma cells or primary murine islets. Gene expression was assessed by qPCR, RNAseq analysis, and Western blot analysis. Chromatin enrichment was measured in the Min6 ß cell line and primary isolated mouse islets by ChIPseq and ChIP PCR. Immunoprecipitation was used to assess interactions among transcription factors in Min6 cells and isolated mouse islets. Activation of caspase 3 by immunoblotting or by irreversible binding to a fluorescent inhibitor was taken as an indication of commitment to an apoptotic fate. RESULTS: RNASeq identified a set of PDX1, ATF4 and ATF5 co-regulated genes enriched in stress and apoptosis functions. We further identified stress induced interactions among PDX1, ATF4, and ATF5. PDX1 chromatin occupancy peaks were identified over composite C/EBP-ATF (CARE) motifs of 26 genes; assessment of a subset of these genes revealed co-enrichment for ATF4 and ATF5. PDX1 occupancy over CARE motifs was conserved in the human orthologs of 9 of these genes. Of these, Glutamate Pyruvate Transaminase 2 (Gpt2), Cation transport regulator 1 (Chac1), and Solute Carrier Family 7 Member 1 (Slc7a1) induction by stress was conserved in human islets and abrogated by deficiency of Pdx1, Atf4, and Atf5 in Min6 cells. Deficiency of Gpt2 reduced ß cell susceptibility to stress induced apoptosis in both Min6 cells and primary islets. CONCLUSIONS: Our results identify a novel PDX1 stress inducible complex (es) that regulates expression of stress and apoptosis genes to govern ß cell survival.

Narirutin produces antidepressant-like effects in a chronic unpredictable mild stress mouse model.

Depression is a highly debilitating and life-threatening mental disorder, which is accompanied by dysregulation of the peripheral and central immune system. Narirutin (NR), which has antioxidant and anti-inflammatory activities, is one of the active constituents isolated from Citrus unshiu. However, its potential antidepressant-like and anxiolytic-like effects are poorly understood. The present study was aimed to investigate whether NR confers an antidepressant-like effect in mice exposed to a chronic mild stress (CMS) model of depression. The results showed that NR treatment for 1 week significantly alleviated the depressive-like behaviours of CMS-exposed mice, as indicated by restored decreased sucrose preference and shortened floating time in the forced swimming test. Moreover, NR treatment significantly blocked the CMS-induced anxiety-like behaviors, including increased time spent in the central zone in the open field test, and shortened the latency to feeding in the novelty suppressed feeding test. Taken together, our findings suggested that NR exerted potential antidepressant-like and anxiolytic-like effects in CMS mice model of depression, which support further exploration into developing NR as a novel agent to treat depression and even other stress-related disorders.

Effect of Alkali Metal Atoms Doping on Structural and Nonlinear Optical Properties of the Gold-Germanium Bimetallic Clusters.

A new series of alkali-based complexes, AM@GenAu (AM = Li, Na, and K), have been theoretically designed and investigated by means of the density functional theory calculations. The geometric structures and electronic properties of the species are systematically analyzed. The adsorption of alkali metals maintains the structural framework of the gold-germanium bimetallic clusters, and the alkali metals prefer energetically to be attached on clusters' surfaces or edges. The high chemical stability of Li@Ge12Au is revealed by the spherical aromaticity, the hybridization between the Ge atoms and Au-4d states, and delocalized multi-center bonds, as well as large binding energies. The static first hyperpolarizability (ßtot) is related to the cluster size and geometric structure, and the AM@GenAu (AM = Na and K) clusters exhibit the much larger ßtot values up to 13050 a.u., which are considerable to establish their strong nonlinear optical (NLO) behaviors. We hope that this study will promote further application of alkali metals-adsorbed germanium-based semiconductor materials, serving for the design of remarkable and tunable NLO materials.

ATF5 regulates ß-cell survival during stress.

The stress response and cell survival are necessary for normal pancreatic ß-cell function, glucose homeostasis, and prevention of diabetes. The homeodomain transcription factor and human diabetes gene pancreas/duodenum homeobox protein 1 (Pdx1) regulates ß-cell survival and endoplasmic reticulum stress susceptibility, in part through direct regulation of activating transcription factor 4 (Atf4). Here we show that Atf5, a close but less-studied relative of Atf4, is also a target of Pdx1 and is critical for ß-cell survival under stress conditions. Pdx1 deficiency led to decreased Atf5 transcript, and primary islet ChIP-sequencing localized PDX1 to the Atf5 promoter, implicating Atf5 as a PDX1 target. Atf5 expression was stress inducible and enriched in ß cells. Importantly, Atf5 deficiency decreased survival under stress conditions. Loss-of-function and chromatin occupancy experiments positioned Atf5 downstream of and parallel to Atf4 in the regulation of eIF4E-binding protein 1 (4ebp1), a mammalian target of rapamycin (mTOR) pathway component that inhibits protein translation. Accordingly, Atf5 deficiency attenuated stress suppression of global translation, likely enhancing the susceptibility of ß cells to stress-induced apoptosis. Thus, we identify ATF5 as a member of the transcriptional network governing pancreatic ß-cell survival during stress.