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[Display omitted] The key elements that influence the properties and capabilities of particulate photocatalysts are their crystallinity, size, and surface active sites. However, simultaneously controlling these three variables remains a challenge. In this study, we present the first exploration into the use of a simple ethylenediaminetetraacetate (EDTA) etching technique to decrease the particle size and increase the surface active sites of photocatalysts while preserving their high crystallinity. By employing SrTiO 3 as a model photocatalyst, we were able to create an ordered step nanostructure on the surface of sintered SrTiO 3. As a result of the EDTA treatment, the particle size was reduced while the crystallinity was maintained. The separation of photogenerated electrons and holes is enhanced by the combination of reduced particle size and high crystallinity. To enhance chemical reaction activities, the organized surface nano-step structures serve as high-activity sites. As a result, when subjected to simulated light irradiation, the EDTA-treated SrTiO 3 samples demonstrate improved photocatalytic performance for water splitting into H 2 and O 2 in a stoichiometric amount that is 3.8 times greater than that of untreated SrTiO 3. Since EDTA interacts with most metals, this simple EDTA etching technique has the potential to be further developed to modify additional photocatalysts with exceptional performance for a variety of applications. [ABSTRACT FROM AUTHOR]

Accurate processing and analysis of non-human primate (NHP) brain magnetic resonance imaging (MRI) serves an indispensable role in understanding brain evolution, development, aging, and diseases. Despite the accumulation of diverse NHP brain MRI datasets at various developmental stages and from various imaging sites/scanners, existing computational tools designed for human MRI typically perform poor on NHP data, due to huge differences in brain sizes, morphologies, and imaging appearances across species, sites, and ages, highlighting the imperative for NHP-specialized MRI processing tools. To address this issue, in this paper, we present a robust, generic, and fully automated computational pipeline, called non-human primates Brain Extraction and Segmentation Toolbox (nBEST), whose main functionality includes brain extraction, non-cerebrum removal, and tissue segmentation. Building on cutting-edge deep learning techniques by employing lifelong learning to flexibly integrate data from diverse NHP populations and innovatively constructing 3D U-NeXt architecture, nBEST can well handle structural NHP brain MR images from multi-species, multi-site, and multi-developmental-stage (from neonates to the elderly). We extensively validated nBEST based on, to our knowledge, the largest assemblage dataset in NHP brain studies, encompassing 1,469 scans with 11 species (e.g., rhesus macaques, cynomolgus macaques, chimpanzees, marmosets, squirrel monkeys, etc.) from 23 independent datasets. Compared to alternative tools, nBEST outperforms in precision, applicability, robustness, comprehensiveness, and generalizability, greatly benefiting downstream longitudinal, cross-sectional, and cross-species quantitative analyses. We have made nBEST an open-source toolbox (https://github.com/TaoZhong11/nBEST) and we are committed to its continual refinement through lifelong learning with incoming data to greatly contribute to the research field. • We proposed nBEST, a deep-learning toolbox for processing MR images of non-human primate brains. • nBEST leverages lifelong learning and 3D U-NeXt models, performing brain extraction, non-cerebrum removal, and tissue segmentation. • Validated with 1,400+ scans from 11 species, nBEST shows extensive applicabilit. • nBEST is available online with a user manual. [ABSTRACT FROM AUTHOR]

Duck egg quality improvement is an essential target for Asian poultry breeding. In total, 15 RNA-Seq libraries (magnum, isthmus, and uterus at two different physiological states) were sequenced from 48 weeks old Pekin ducks. De novo assembly and annotation methods were utilized to generate new reference transcripts. Our results revealed that 1264 and 2517 genes were differentially expressed in magnum and uterus in the presence versus absence of an egg, respectively. We identified 1089 genes that were differentially expressed in isthmus compared to uterus (in both presence and absence of a calcifying egg). We observed that 11 common DEGs were detected in the egg white proteomes of 6 different bird species including domestic Chicken, Duck, Goose, Turkey, Quail, and Pigeon. On the other hand, only one of the top five most highly expressed genes in duck isthmus was in this category for the chicken isthmus (SPINK7). Among the large number of DEGs during eggshell formation in ducks, only 41 genes showed a similar differential expression pattern in both duck and chicken. By combining chicken QTL database, chicken oviduct transcriptome and egg proteome data for five bird species, we have obtained high-quality gene lists for egg formation. This is the first study to elucidate the transcriptomic changes in different duck oviduct segments during egg formation, and to integrate QTL, proteome and transcriptome data to probe the functional genes associated with albumen secretion and eggshell mineralization. • De novo assembly yielded 97,264 unigenes • We observed species-specific/common egg white related genes of 6 bird species • SPINK7 is potentially a new gene that is involved in some initial phase of biomineralization in avian eggshell formation • There are significant differences in eggshell phenotypes between chicken and duck eggs [ABSTRACT FROM AUTHOR]

This study describes the first report of application of Metschnikowia pulcherrima combined with Saccharomyces cerevisiae to ferment plum wine. Variable factors studied include inoculum ratio (M. pulcherrima: S. cerevisiae = 10:1, 1:1, and 1:10), as well as simultaneous versus sequential inoculation, with tested trials spanning 10:1sim, 1:1sim, 1:10sim, 10:1seq, 1:1seq, and 1:10seq, respectively. The yeast growth kinetics, physicochemical characteristics, organic acids, aroma profiles, and sensory evaluation were investigated. During fermentation, M. pulcherrima growth was inhibited by S. cerevisiae. Compared to each simultaneous analog, sequential fermentation which was inoculated with the same yeast ratio consumed less sugar and produced lower ethanol content. Organic acids in each sample varied with the use of different inoculation strategies. A total of 48 aroma compounds were quantified, and 1:1seq sample was observed to be abundant in esters and terpenes but relatively low in higher alcohols, fatty acids, and phenols. Sensory evaluation of the variously-prepared samples revealed that 1:1seq sample featured a highly intense 'global aroma', 'fruity', and 'alcohol' notes. PCA illustrated that different inoculation protocols of mixed culture fermentation influenced plum wine aroma except 1:10sim. Ultimately, 1:1seq was identified as a promising candidate for production of high-quality plum wine. • Metschnikowia pulcherrima was reported in plum wine at first time. • Plum wines produced with varied protocols were evaluated. • Sequential fermentation was more conducive to improve plum wine aroma and quality. • 1:1seq is a good way for the improvement of fruity aroma in plum wine. [ABSTRACT FROM AUTHOR]

Longitudinal brain imaging atlases with densely sampled time-points and ancillary anatomical information are of fundamental importance in studying early developmental characteristics of human and non-human primate brains during infancy, which feature extremely dynamic imaging appearance, brain shape and size. However, for non-human primates, which are highly valuable animal models for understanding human brains, the existing brain atlases are mainly developed based on adults or adolescents, denoting a notable lack of temporally densely-sampled atlases covering the dynamic early brain development. To fill this critical gap, in this paper, we construct a comprehensive set of longitudinal brain atlases and associated tissue probability maps (gray matter, white matter, and cerebrospinal fluid) with totally 12 time-points from birth to 4 years of age (i.e., 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, and 48 months of age) based on 175 longitudinal structural MRI scans from 39 typically-developing cynomolgus macaques, by leveraging state-of-the-art computational techniques tailored for early developing brains. Furthermore, to facilitate region-based analysis using our atlases, we also provide two popular hierarchy parcellations, i.e., cortical hierarchy maps (6 levels) and subcortical hierarchy maps (6 levels), on our longitudinal macaque brain atlases. These early developing atlases, which have the densest time-points during infancy (to the best of our knowledge), will greatly facilitate the studies of macaque brain development. [ABSTRACT FROM AUTHOR]

The pre-harvest applications of antagonists are promising strategies to minimize various postharvest diseases. Given this, we sought to evaluate the capability of Pseudomonas fluorescens ZX in inducing resistance of postharvest citrus fruit against blue and green molds, caused by Penicillium italicum and Penicillium digitatum , respectively. Results showed that pre-treatment with P. fluorescens ZX significantly inhibited blue and green molds, generally providing stronger protection with increasing number of sprays. More specifically, three applications of the antagonist reduced disease incidence by about 47% and 41%, reduced lesion diameter by around 40% and 28%, and reduced disease index by approximately 69% and 57%, when exposed to blue and green molds, respectively. Mechanistically, these protective effects might be linked to the increased activities of superoxide dismutase, ascorbate peroxidase, peroxidase, and polyphenoloxidase, along with substantial response of phenolic acids (syringic, p -coumaric, ferulic, and sinapinic acids) and flavonoids (rutin, neohesperidin, hesperetin, sinensetin and tangeretin). P. fluorescens ZX survived well on fruit surface, and more importantly, pre-treatments exhibited no negative effects on fruit quality; on the contrary, it partly improved fruit quality during postharvest storage. Collectively, these results indicated that multiple pre-harvest applications of P. fluorescens ZX are useful for control of postharvest diseases. [Display omitted] • Pre-treatment with P. fluorescens ZX markedly reduced postharvest citrus diseases. • Generally, increasing spray numbers evoked higher levels of defensive responses. • Pre-treatments did not impair and partly improved the fruit quality during storage. • Pre-treatment effectively stimulated the accumulation of several special phenols. [ABSTRACT FROM AUTHOR]

[Display omitted] • Biofumigation by VOCs from P. fluorescens ZX managed gray mold on postharvest grapes. • Biofumigation by VOCs resulted in damage on the morphology of hyphae. • VOCs and sulphur containing compounds showed inhibitory effect. • VOCs from P. fluorescens ZX colonized on healthy grapes could inhibit gray mold on grapes. • Pre-fumigation by VOCs could control the development of gray mold. Volatile organic compounds (VOCs) produced by antagonistic microorganisms have the potential for controlling postharvest diseases on fruit and vegetables. In this study, the biocontrol efficacy of VOCs emitted by Pseudomonas fluorescens ZX was determined in vitro and in vivo against gray mold, caused by Botrytis cinerea , on grapes. In vitro , application of VOCs produced by bacterial suspension of P. fluorescens ZX at initial inoculum concentration of 1 × 109 colony-forming units (CFU)/mL inhibited B. cinerea mycelial growth from 52 to 23 mm and spore germination from 88.56 to 39.67%. In vivo tests indicated that, for grapes, disease incidence and disease index were markedly reduced by VOCs from P. fluorescens ZX incubated on NA plates, in NB, and on healthy grapes. Pre-fumigation with VOCs could inhibit development of gray mold on grapes. Furthermore, P. fluorescens ZX-producing VOCs exhibited favorable effects on postharvest natural decay of grapes. In vitro testing of selected pure chemicals demonstrated that dimethyl trisulfide (20 μL/L), dimethyl disulfide (40 μL/L), geranyl formate (640 μL/L), acetic acid (160 μL/L), butyric acid (320 μL/L), 2-methylbutyric acid (160 μL/L), isobutyric acid (160 μL/L) and isovaleric acid (320 μL/L) could completely inhibit mycelial growth of B. cinerea on PDA plates. These eight substances also exerted a strong inhibitory effect on gray mold on grapes. Additionally, SEM analysis showed that VOCs could affect the morphological and structural characteristics of B. cinerea both in vitro and in vivo. Collectively, VOCs produced by P. fluorescens ZX are promising for biocontrol of gray mold on grapes through fumigant action. [ABSTRACT FROM AUTHOR]

Abstract: Cardia bifida is an anomaly of the embryonic heart in which the bilateral myocardial rudiments fail to travel to the midline, resulting in the formation of two separate hearts in lateral positions. In zebrafish, eight loci responsible for the cardia bifida phenotype were identified in the large-scale genetic screen. Wortmannin has been reported to be a highly selective inhibitor of phosphoinositide 3-kinase and myosin light chain kinase activity. We provide the first evidence that wortmannin treatment of zebrafish embryos can induce cardia bifida in a dose-dependent manner and that wortmannin alters cardiac development between 6 and 16h post-fertilization. In addition, we demonstrate that wortmannin induces zebrafish cardia bifida through a mechanism independent of phosphoinositide 3-kinase and myosin light chain kinase. Our findings may provide new insights into the cardiomyocyte function and disfunction. [Copyright &y& Elsevier]

As non-human primates, macaques have a close phylogenetic relationship to human beings and have been proven to be a valuable and widely used animal model in human neuroscience research. Accurate skull stripping (aka. brain extraction) of brain magnetic resonance imaging (MRI) is a crucial prerequisite in neuroimaging analysis of macaques. Most of the current skull stripping methods can achieve satisfactory results for human brains, but when applied to macaque brains, especially during early brain development, the results are often unsatisfactory. In fact, the early dynamic, regionally-heterogeneous development of macaque brains, accompanied by poor and age-related contrast between different anatomical structures, poses significant challenges for accurate skull stripping. To overcome these challenges, we propose a fully-automated framework to effectively fuse the age-specific intensity information and domain-invariant prior knowledge as important guiding information for robust skull stripping of developing macaques from 0 to 36 months of age. Specifically, we generate Signed Distance Map (SDM) and Center of Gravity Distance Map (CGDM) based on the intermediate segmentation results as guidance. Instead of using local convolution, we fuse all information using the Dual Self-Attention Module (DSAM), which can capture global spatial and channel-dependent information of feature maps. To extensively evaluate the performance, we adopt two relatively-large challenging MRI datasets from rhesus macaques and cynomolgus macaques, respectively, with a total of 361 scans from two different scanners with different imaging protocols. We perform cross-validation by using one dataset for training and the other one for testing. Our method outperforms five popular brain extraction tools and three deep-learning-based methods on cross-source MRI datasets without any transfer learning. [ABSTRACT FROM AUTHOR]

Cells have evolved molecular chaperones that modulate phase separation and misfolding of amyloidogenic proteins to prevent neurodegenerative diseases. Protein disulfide isomerase (PDI), mainly located at the endoplasmic reticulum and also present in the cytosol, acts as both an enzyme and a molecular chaperone. PDI is observed to be S-nitrosylated in the brain of Alzheimer's disease patients, but the mechanism has remained elusive. We herein report that both wild-type PDI and its quadruple cysteine mutant only having chaperone activity, significantly inhibit pathological phosphorylation and abnormal aggregation of Tau in cells, and significantly decrease the mitochondrial damage and Tau cytotoxicity resulting from Tau aberrant aggregation, highlighting the chaperone property of PDI. More importantly, we show that wild-type PDI is selectively recruited by liquid droplets of Tau, which significantly inhibits phase separation and stress granule formation of Tau, whereas S-nitrosylation of PDI abrogates the recruitment and inhibition. These findings demonstrate how phase separation of Tau is physiologically regulated by PDI and how S-nitrosylation of PDI, a perturbation in this regulation, leads to disease. Image 1 • Chaperones are recruited to Tau droplets to inhibit Tau accumulation in the droplets. • Recruitment of chaperones alters the dynamic properties of Tau phase-separated droplets. • S-nitrosylation of PDI abrogates its ability to recognize targeted proteins physically. • S-nitrosylation of PDI abrogates its ability to inhibit the phase separation of Tau. [ABSTRACT FROM AUTHOR]

Abstract Photoreceptor cells are highly specialized sensory neurons capable of visual phototransduction. The connecting cilia in the retinal photoreceptors link the inner segment to the outer segment and mediate the transport of opsins in vision. Although our previous study demonstrates that Prostaglandin E2 (PGE 2) signaling is required for ciliogenesis in zebrafish, its roles in retinal ciliogenesis and photoreceptor cell development remain unknown. Here, we investigated the function of prostaglandin signaling in retina and photoreceptor cell development. We generated zebrafish mutations in prostaglandin endoperoxide synthase 1 (PTGS1) and prostaglandin endoperoxide synthase 2 (PTGS2), two rate-limiting enzymes responsible for prostaglandin production. We found that ptgs2b knockdown in ptgs1 -/- ptgs2a -/- double mutants significantly reduced the length of connecting cilia and resulted in severe defects in photoreceptor cell differentiation. Furthermore, mutation in PGE 2 transporter Leakytail (Lkt)/ATP-binding cassette transporter 4 (ABCC4) exhibited loss of connecting cilia and outer segment in photoreceptor cells, leading to mislocalization of opsins in the cell bodies of photoreceptors. Together, our findings suggest that PGE 2 production and transport are crucial for connecting cilia formation and photoreceptor cell development. Highlights • The first study to construct the ptgs1 -/- ptgs2a -/- double mutants in zebrafish. • Deficiency in prostaglandin synthesis affects photoreceptor cell development. • Mutation in PGE 2 export exhibits loss of connecting cilia and mislocalization of opsins. [ABSTRACT FROM AUTHOR]

[Display omitted] • The photocatalyst with ternary hollow core-shell structure, which can effectively separate electrons from holes and store electrons in an electron library, was synthesized by template method and self-assembly method. • The storage capacity of electronic library with adjustable microelectronic structure is affected by surface polarization, which could support the requirement call from the CoP QDs as active-sites • The smooth electron transfer channels from electron libraries to quantum dots as active sites can improve the separation and efficient utilization of photoexcited electrons. Photocatalysis is facing huge challenges especially the separation and efficient utilization of photocarriers. Herein, we report that a ternary hollow core–shell photocatalyst is synthesized by template and self-assembled method. The experimental results show that the electron separation efficiency and utilization efficiency are significantly improved, not only because the ternary hollow core–shell structure spatially separates the oxidation area MnOx from the reduction area Co-MOF, but also because lots of emergent electrons are stored in Co-MOF as an electronic library, contributing to the formation of surface polarization to support the requirement call from the CoP quantum dots (QDs) as active-sites. It's the first report that the effectively separated electron-rich and electron-poor microelectronic states of the tunable Co-MOF promotes electron utilization by affecting the storage capacity of the electron library promoting photocatalytic hydrogen production. The tests show that Mn@Cd-CoP QDs/MCN (35.31 mmol/h/g), Mn@Cd-CoP QDs/BCN (23.69 mmol/h/g) and Mn@Cd-CoP QDs (11.08 mmol/h/g) have the better hydrogen production performances, which is about 38 times, 26 times and 12 times higher than CdS (0.9244 mmol/h/g), respectively. The pioneering exploration about the ternary hollow core–shell structure bonded with MOFs materials with abundant CoP QDs will open up a new perspective to design high-performance for solar-chemical energy conversion. [ABSTRACT FROM AUTHOR]

Brain extraction and image quality assessment are two fundamental steps in fetal brain magnetic resonance imaging (MRI) 3D reconstruction and quantification. However, the randomness of fetal position and orientation, the variability of fetal brain morphology, maternal organs around the fetus, and the scarcity of data samples, all add excessive noise and impose a great challenge to automated brain extraction and quality assessment of fetal MRI slices. Conventionally, brain extraction and quality assessment are typically performed independently. However, both of them focus on the brain image representation, so they can be jointly optimized to ensure the network learns more effective features and avoid overfitting. To this end, we propose a novel two-stage dual-task deep learning framework with a brain localization stage and a dual-task stage for joint brain extraction and quality assessment of fetal MRI slices. Specifically, the dual-task module compactly contains a feature extraction module, a quality assessment head and a segmentation head with feature fusion for simultaneous brain extraction and quality assessment. Besides, a transformer architecture is introduced into the feature extraction module and the segmentation head. We utilize a multi-step training strategy to guarantee a stable and successful training of all modules. Finally, we validate our method by a 5-fold cross-validation and ablation study on a dataset with fetal brain MRI slices in different qualities, and perform a cross-dataset validation in addition. Experiments show that the proposed framework achieves very promising performance. • A novel two-stage dual-task deep learning framework for fetal MRI slices. • A compact dual-task module for joint brain extraction and quality assessment. • The introduction of a novel transformer architecture for fetal brain MRI processing. • Promising performance on 5-fold cross-validation and cross-dataset validation. [ABSTRACT FROM AUTHOR]

P-21 activated kinases, or PAKs, are serine–threonine kinases that play important roles in diverse heart functions include heart development, cardiovascular development and function in a range of models; however, the mechanisms by which PAKs mediate heart regeneration are unknown. Here, we demonstrate that PAK2 and PAK4 expression is induced in cardiomyocytes and vessels, respectively, following zebrafish heart injury. Inhibition of PAK2 and PAK4 using a specific small molecule inhibitor impedes cardiomyocyte proliferation/dedifferentiation and cardiovascular regeneration, respectively. Cdc42 is specifically expressed in the ventricle and may function upstream of PAK2 but not PAK4 under normal conditions and that cardiomyocyte proliferentation during heart regeneration relies on Rac1-mediated activation of Pak2. Our results indicate that PAKs play a key role in heart regeneration. [ABSTRACT FROM AUTHOR]

• Creation of spatio-temporal volumetric atlas of the infant brain (0–24 months) using 542 longitudinal T1w and T2w scans from 240 developing infants. • Includes components: group-representative T1w and T2w images, tissue probability maps, tissue segmentation maps, cortical parcellation map, and subcortical labels. • Atlas is high spatial resolution, extensive age-range coverage, and densely sampled time points. • Atlas has increased structural details and sharper tissue contrast by introducing brain tissue probability maps to improve registration accuracy. Spatiotemporal (four-dimensional) infant-dedicated brain atlases are essential for neuroimaging analysis of early dynamic brain development. However, due to the substantial technical challenges in the acquisition and processing of infant brain MR images, 4D atlases densely covering the dynamic brain development during infancy are still scarce. Few existing ones generally have fuzzy tissue contrast and low spatiotemporal resolution, leading to degraded accuracy of atlas-based normalization and subsequent analyses. To address this issue, in this paper, we construct a 4D structural MRI atlas for infant brains based on the UNC/UMN Baby Connectome Project (BCP) dataset, which features a high spatial resolution, extensive age-range coverage, and densely sampled time points. Specifically, 542 longitudinal T1w and T2w scans from 240 typically developing infants up to 26-month of age were utilized for our atlas construction. To improve the co-registration accuracy of the infant brain images, which typically exhibit dynamic appearance with low tissue contrast, we employed the state-of-the-art registration method and leveraged our generated reliable brain tissue probability maps in addition to the intensity images to improve the alignment of individual images. To achieve consistent region labeling on both infant and adult brain images for facilitating region-based analysis across ages, we mapped the widely used Desikan cortical parcellation onto our atlas by following an age-decreasing mapping manner. Meanwhile, the typical subcortical structures were manually delineated to facilitate the studies related to the subcortex. Compared with the existing infant brain atlases, our 4D atlas has much higher spatiotemporal resolution and preserves more structural details, and thus can boost accuracy in neurodevelopmental analysis during infancy. [ABSTRACT FROM AUTHOR]

Non-coding RNAs have been shown to play vital roles in muscle development. However, the biological roles of long non-coding natural antisense transcripts, antisense lncRNAs (ASlncRNAs), are largely unknown in embryonic muscle development. Here, we identified a total of 466 ASlncRNAs in the longissimus dorsi muscle. And 48 differentially expressed ASlncRNAs were identified based on pairwise comparisons (P < 0.05), sixteen of which were validated by qPCR. Additionally, 466 ASlncRNAs were predicted to target 335 protein coding genes based on complementary base-pairing. Enrichment analysis suggests that ASlncRNAs may be involved in muscle development by negatively regulating the expression of target genes. Furthermore, 170 ASlncRNAs were identified as potential miRNA precursors, suggesting that these ASlncRNAs may be involved in the regulation of muscle development by producing miRNA precursors. Our results provide a catalog of goat muscle-related ASlncRNAs, and will contribute to a fuller understanding of the roles of ASlncRNAs in muscle development. • RNA-seq reveals natural antisense lncRNAs involved in embryonic muscle development of goat, and 48 differentially expressed ASlncRNAs were identified. • Functional analysis suggests that ASlncRNAs may be involved in skeletal muscle development by negatively regulating the expression of target genes and producing miRNA precursors. [ABSTRACT FROM AUTHOR]

Abstract: In vertebrate embryos, the dorsal aorta and the posterior cardinal vein form in the trunk to comprise the original circulatory loop. Previous studies implicate Hedgehog (Hh) signaling in the development of the dorsal aorta. However, the mechanism controlling specification of artery versus vein remains unclear. Here, we investigated the cell-autonomous mechanism of Hh signaling in angioblasts (endothelial progenitor cells) during arterial–venous specification utilizing zebrafish mutations in Smoothened (Smo), a G protein-coupled receptor essential for Hh signaling. smo mutants exhibit an absence of the dorsal aorta accompanied by a reciprocal expansion of the posterior cardinal vein. The increased number of venous cells is equivalent to the loss of arterial cells in embryos with loss of Smo function. Activation of Hh signaling expands the arterial cell population at the expense of venous cell fate. Time-lapse imaging reveals two sequential waves of migrating progenitor cells that contribute to the dorsal aorta and the posterior cardinal vein, respectively. Angioblasts deficient in Hh signaling fail to contribute to the arterial wave; instead, they all migrate medially as a single population to form the venous wave. Cell transplantation analyses demonstrate that Smo plays a cell-autonomous role in specifying angioblasts to become arterial cells, and Hh signaling-depleted angioblasts differentiate into venous cells instead. Collectively, these studies suggest that arterial endothelial cells are specified and formed via repressing venous cell fate at the lateral plate mesoderm by Hh signaling during vasculogenesis. [Copyright &y& Elsevier]

Abstract: Phospholipase D (PLD) hydrolyzes phosphatidylcholine to generate phosphatidic acid and choline. Studies in cultured cells and Drosophila melanogaster have implicated PLD in the regulation of many cellular functions, including intracellular vesicle trafficking, cell proliferation and differentiation. However, the function of PLD in vertebrate development has not been explored. Here we report cloning and characterization of a zebrafish PLD1 (pld1) homolog. Like mammalian PLDs, zebrafish Pld1 contains two conservative HKD motifs. Maternally contributed pld1 transcripts are uniformly distributed in early embryo. Localized expression of pld1 is observed in the notochord during early segmentation, in the somites during later segmentation and in the liver at the larval stages. Studies in intact and cell-free preparations demonstrate evolutionary conservation of regulation. Inhibition of Pld1 expression using antisense morpholino oligonucleotides (MO) interfering with the translation or splicing of pld1 impaired intersegmental vessel (ISV) development. Incubating embryos with 1-butanol, which diverts production of phosphatidic acid to a phosphatidylalcohol, caused similar ISV defects. To determine where Pld1 is required for ISV development we performed transplantation experiments. Analyses of the mosaic Pld1 deficient embryos showed partial suppression of ISV defects in the segments containing transplanted wild-type notochord cells but not in the ones containing wild-type somitic cells. These results provide the first evidence that function of Pld1 in the developing notochord is essential for vascular development in vertebrates. [Copyright &y& Elsevier]

Abstract: NDRG4 is a novel member of the NDRG family (N-myc downstream-regulated gene). The roles of NDRG4 in development have not previously been evaluated. We show that, during zebrafish embryonic development, ndrg4 is expressed exclusively in the embryonic heart, the central nervous system (CNS) and the sensory system. Ndrg4 knockdown in zebrafish embryos causes a marked reduction in proliferative myocytes and results in hypoplastic hearts. This growth defect is associated with cardiac phenotypes in morphogenesis and function, including abnormal heart looping, inefficient circulation and weak contractility. We reveal that ndrg4 is required for restricting the expression of versican and bmp4 to the developing atrioventricular canal. This constellation of ndrg4 cardiac defects phenocopies those seen in mutant hearts of heartstrings (hst), the tbx5 loss-of-function mutants in zebrafish. We further show that ndrg4 expression is significantly decreased in hearts with reduced tbx5 activities. Conversely, increased expression of tbx5 that is due to tbx20 knockdown leads to an increase in ndrg4 expression. Together, our studies reveal an essential role of ndrg4 in regulating proliferation and growth of cardiomyocytes, suggesting that ndrg4 may function downstream of tbx5 during heart development and growth. [Copyright &y& Elsevier]

Phage displayed peptide library was used to select tumor necrosis factor α (TNFα) binding peptides. After three sequential rounds of biopanning, some linear TNFα-binding peptides were identified from a 12-mer peptide library. A consensus sequence (L/M)HEL(Y/F)(L/M)X(W/Y/F), where X might be variable residue, was deduced from sequences of these peptides. The phages bearing these peptides showed specific binding to immobilized TNFα, with over 80% of phages bound being competitively eluted by free TNFα. To confirm the binding activity and to explore further functional properties, three peptides with typical structure were selected and expressed as GST-fused protein. These recombinant peptides effectively competed for [125I]TNFα binding to TNFR1 in a dose-dependent manner, with IC50 from 10 to 160 μM. Furthermore, the GST-fused derivatives showed inhibitory effects on TNFα-induced cytotoxicity. Taken together, these data demonstrate that the TNFα-binding peptides are effective antagonists of TNFα and the deduced motif might be useful in development of novel low molecular weight anti-TNFα drugs. [Copyright &y& Elsevier]

Background. Obstructive jaundice damages critical functions in the liver. However, the mechanisms involved in hepatic dysfunction are obscure. Nitric oxide is implicated in liver injury under various pathological conditions. We previously reported that proinflammatory cytokine interleukin-1β (IL-1β) stimulated the production of nitric oxide in hepatocytes, which was associated with mitochondrial dysfunction. Studies were performed to examine whether obstructive jaundice influences the production of nitric oxide in hepatocytes and alters hepatic energy metabolism.Material and methods. Hepatocytes were isolated and cultured from a rat model of obstructive jaundice or sham control. Nitric oxide production, ATP content, and ketone body ratio (acetoacetate/β-hydroxybutyrate; KBR) were compared between the two groups in the presence of IL-1β.Results. Hepatocytes obtained from obstructive jaundice rats markedly increased the levels of nitric oxide production stimulated by IL-1β compared with those from sham control. Western blot analysis revealed that the enhancement of nitric oxide production was a posttranslational event, since protein levels of inducible nitric oxide synthase (NOS) were unchanged between the two groups. IL-1β decreased cellular ATP content in obstructive jaundice but not in sham control. Further, the KBR, which is a marker of mitochondrial redox state, was lower in obstructive jaundice than in sham control. Addition of NG-monomethyl-l-arginine, an inhibitor of NOS, abolished the decreases in ATP content and KBR as well as the nitric oxide production.Conclusions. These results indicate that a priming of nitric oxide production following obstructive jaundice is associated with the alteration of hepatic energy metabolism in part through mitochondrial dysfunction. Regulation of nitric oxide production may be a useful therapy for preventing liver dysfunction in obstructive jaundice. [Copyright &y& Elsevier]

[Display omitted] • Eight new compounds were found from T. harzianum by the one strain many compounds. • Trichoharin A had potential of chemical entrapment and killing of insects. • Most compounds indicated obvious feeding attractant, and antifungal activities. • The biocontrol induced by the host-fungus interaction was the antifungal metabolites. Eight new compounds (1 – 8) were discovered from Trichoderma harzianum associated with edible mushroom by the one strain many compounds (OSMAC) strategy. Triharzianin A (1) is the first naturally scaffold characterized by a C 13 -prostaglandin skeleton. The configurations of 1 – 3 , and 5 were determined by the Mosher's method, experimental and calculated ECD spectra, and plausible biosynthesis of stereospecific epoxidation. Most compounds indicated obvious feeding attractant activities to silkworm with attraction rates at 30–90%. Compound 7 showed anti-acetylcholinesterase (anti-AChE) activity with a ratio of 29% at a concentration of 50 μM for insecticidal potential. So 2,​3-​dialkylchromone (7) had potential of chemical entrapment and killing of insects. Compounds 2 , 3 and 7 – 11 showed antifungal activities against Aspergillus fumigates , and Trichoderma sp. from mushroom with MICs ≤ 300 μM. The four fermentation extracts also indicated obvious feeding attractant activities to silkworm for the activities brought by active metabolites from T. harzianum. The material base of biocontrol induced by the interaction of host-fungal symbiont can be investigated by the antifungal metabolites against pathogen fungi. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nine new pyrrole-alkaloid derivatives were isolated from Lepidium meyenii. • Lepipyrrolins A-B (1 and 2) represents the first examples of dimeric pyrrole 2‑carbaldehyde alkaloids. • Compound 1 showed selective cytotoxicity against SMMC-7721. Nine new pyrrole alkaloids, including two undescribed dimeric pyrrole 2‑carbaldehyde alkaloids, lepipyrrolins A-B (1 – 2), seven pyrrole-alkaloid derivatives, macapyrrolins D–J (3 – 9), along with three known ones (10 – 12) were isolated from the rhizomes of Lepidium meyenii. Their structures and absolute configurations were demonstrated by extensive spectroscopic data (1D, 2D NMR, HRESIMS), and calculated electronic circular dichroism (ECD) experiment. Compounds 1 , 3 – 12 were tested for their nitric oxide inhibitory effects. Furthermore, compound 1 was evaluated for its cytotoxic activity against five human tumor cell lines (HL-60, SMMC-7221, A549, MCF-7, and SW480) in vitro, and displayed selective cytotoxicity against SMMC-7721 with IC 50 value of 16.78 ± 0.49 μM. [ABSTRACT FROM AUTHOR]

Abnormal activities in reward-related regions are associated with overeating or obesity. Preliminary studies have shown that changes in neural activity in obesity include not only regional reward regions abnormalities but also impairments in the communication between reward-related regions and multiple functional areas. A recent study has shown that the transitions between different neural networks are nonrandom and hierarchical, and that activation of particular brain networks is more likely to occur after other brain networks. The aims of this study were to investigate the key nodes of reward-related regions in obese males and explore the hierarchical integrated processing of key nodes. Twenty-four obese males and 24 normal-weight male controls of similar ages were recruited. The fMRI data were acquired using 3.0 T MRI. The fMRI data preprocessing was performed in DPABI and SPM 12. Degree centrality analyses were conducted using GRETNA toolkit, and Granger causality analyses were calculated using DynamicBC toolbox. Decreased degree centrality was observed in left ventral medial prefrontal cortex (vmPFC) and right parahippocampal/hippocampal gyrus in group with obesity. The group with obesity demonstrated increased effective connectivity between left vmPFC and several regions (left inferior temporal gyrus, left supplementary motor area, right insular cortex, right postcentral gyrus, right paracentral lobule and bilateral fusiform gyrus). Increased effective connectivity was observed between right parahippocampal/hippocampal gyrus and left precentral/postcentral gyrus. Decreased effective connectivity was found between right parahippocampal/hippocampal gyrus and left inferior parietal lobule. This study identified the features of hierarchical interactions between the key reward nodes and multiple function networks. These findings may provide more evidence for the existing view of hierarchical organization in reward processing. [ABSTRACT FROM AUTHOR]

The prevalence of autism spectrum disorders (ASD) is increasing, but its etiology remains elusive and hence an effective treatment is not available. Previous research conducted on animal models suggests that microbiota-gut-brain axis may contribute to ASD pathology and more human research is needed. This study was divided into two stages,.At the discovery stage, we compared the differences in gut microbiota profiles (using 16S rRNA sequencing), fecal SCFAs (using GC-MS) and plasma neurotransmitters (using UHPLC-MS/MS) of 26 children with ASD and 24 normal children. All 26 children with ASD participated in the intervention stage, and we measured the gut microbiota profiles, SCFAs and neurotransmitters before and after probiotics + FOS (n = 16) or placebo supplementation (n = 10). We found that gut microbiota was in a state of dysbiosis and significantly lower levels of Bifidobacteriales and Bifidobacterium longum were observed at the discovery stage in children with ASD. An increase in beneficial bacteria (Bifidobacteriales and B. longum) and suppression of suspected pathogenic bacteria (Clostridium) emerged after probiotics + FOS intervention, with significant reduction in the severity of autism and gastrointestinal symptoms. Compared to children in the control group, significantly lower levels of acetic acid, propionic acid and butyric acid were found, and a hyperserotonergic state (increased serotonin) and dopamine metabolism disorder (decreased homovanillic acid) were observed in children with ASD. Interestingly, the above SCFAs in children with autism significantly elevated after probiotics + FOS intervention and approached those in the control group. In addition, our data demonstrated that decreased serotonin and increased homovanillic acid emerged after probiotics + FOS intervention. However, the above-mentioned changes did not appear in the placebo group for ASD children. Probiotics + FOS intervention can modulate gut microbiota, SCFAs and serotonin in association with improved ASD symptoms, including a hyper-serotonergic state and dopamine metabolism disorder. [ABSTRACT FROM AUTHOR]

Microtubule-binding proteins provide an alternative and vital pathway to the functional diversity of microtubules. Considerable work is still required to understand the complexities of microtubule-associated cellular processes and to identify novel microtubule-binding proteins. In this study, we identify Bcl2-associated athanogene cochaperone 6 (BAG6) as a novel microtubule-binding protein and reveal that it is crucial for primary ciliogenesis. By immunofluorescence we show that BAG6 largely colocalizes with intracellular microtubules and by co-immunoprecipitation we demonstated that it can interact with α-tubulin. Additionally, both the UBL and BAG domains of BAG6 are indispensable for its interaction with α-tubulin. Moreover, the assembly of primary cilia in RPE-1 cells is significantly inhibited upon the depletion of BAG6. Notably, BAG6 inhibition leads to an abnormal G0/G1 transition during the cell cycle. In addition, BAG6 colocalizes and interactes with the centrosomal protein γ-tubulin, suggesting that BAG6 might regulate primary ciliogenesis through its action in centrosomal function. Collectively, our findings suggest that BAG6 is a novel microtubule-bindng protein crucial for primary ciliogenesis. [ABSTRACT FROM AUTHOR]

• Eight new compounds were isolated from a co-culture of Armillaria sp. and Epicoccum sp. • These new compounds were only detected in the co-cultures. • Absolute configurations were determined via ECD methods. • Compound 6 showed in vitro cytotoxicity to five human cancer cell lines. An investigation of a co-culture of the Armillaria sp. and endophytic fungus Epicoccum sp. YUD17002 associated with Gastrodia elata led to the isolation of eight new compounds, including five protoilludane-type sesquiterpenes (1 – 5) and three aryl esters (6 – 8), together with six known analogues (9 – 14). The assignments of their structures were conducted via extensive analyses of the spectroscopic data and comparison of experimental and calculated electronic circular dichroism (ECD) data. Notably, these new compounds were not present in the pure culture controls and were only detected in the co-cultures. Compound 4 is the first example of an ent -protoilludane sesquiterpenoid scaffold bearing a five-membered lactone. Compound 6 exhibited moderate in vitro cytotoxic activities against five human cancer cell lines (HL-60, A549, MCF-7, SMMC-7721, and SW480) with IC 50 values ranging from 15.80 to 23.03 μM. Moreover, 6 showed weak acetylcholinesterase inhibitory activity (IC 50 value of 23.85 μM). [ABSTRACT FROM AUTHOR]