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Gynaephora qinghaiensis (Lepidoptera: Lymantriidae: Gynaephora), a serious economic pest in alpine meadows, is mainly distributed in Yushu prefecture, Qinghai province, China. In this study, we aimed to investigate the genetic diversity and population structure of G. qinghaiensis through analyzing the sequence of 194 mitochondrial cytochrome oxidase subunit (COI) genes (658 bp in length) identified from 10 geographic populations located in three different countries, including Zhiduo, Zaduo, and Chengduo, of Yushu prefecture. Eleven haplotypes were identified from all populations of G. qinghaiensis with high levels of haplotype diversity (0.78500) and low levels of nucleotide diversity (0.00511). High levels of genetic differentiation and low levels of gene flow were also detected among the populations of G. qinghaiensis. Analysis of molecular variance (AMOVA) showed that 90.13% of the variation was attributed to distribution among groups (Chengduo, Zhiduo, and Zaduo), and 5.22% and 4.65% were, respectively, attributed to distribution among populations, within group, and within populations. The result of mantel test showed a highly significant positive correlation (P

Psoriasis is an immune-mediated chronic inflammatory skin disease. Keratinocyte hyperproliferation has been regarded as a significant event in psoriasis pathogenesis. Considering the vital role of miRNA-mediated mRNA repression in psoriasis pathogenesis, in the present study, we attempted to investigate the mechanism of keratinocyte overproliferation from the point of miRNA-mRNA regulation. Both online microarray expression profiles and experimental results indicated that the expression of LXR-α and PPAR-γ was downregulated in psoriasis lesion skin. LXR-α or PPAR-γ overexpression alone was sufficient to inhibit keratinocyte proliferation, decrease KRT5 and KRT14 protein levels and increase KRT1 and KRT10 protein levels. miR-203 negatively regulated LXR-α and PPAR-γ expression through direct targeting. miR-203 inhibition exerted the opposite effects to LXR-α or PPAR-γ overexpression on HaCaT cells. More importantly, LXR-α or PPAR-γ overexpression could markedly remarkably attenuate the effects of miR-203 overexpression in keratinocytes, indicating that miR-203 promotes keratinocyte proliferation by targeting LXR-α and PPAR-γ. In conclusion, the miR-203-LXR-α/PPAR-γ axis modulates the proliferation of keratinocytes and might be a novel target for psoriasis treatment, which needs further in vivo investigation.

Gynaephora qinghaiensis is a pest on the Qinghai-Tibet Plateau (QTP) that has led to substantial destruction of grassland vegetation. Its pupae are also natural hosts of parasitic wasp. Sexual dimorphism in immune responses is prevalent in vertebrates and invertebrates. However, sexual dimorphism in immune responses of insects, particularly G. qinghaiensis, is poorly understood at the transcriptional level. Here, we performed transcriptome sequencing in male and female pupae of G. qinghaiensis. A total of 118,357,040 clean reads were obtained and assembled into 114,944 unigenes. To explore the difference of immune responses in pupae of both sexes (male and female) of G. qinghaiensis. based on transcriptional level, we characterized the expression profiles of candidate transcripts in the two sexes of G. qinghaiensis. A total of 3,469 unigenes (1,888 up-regulated and 1,581 down-regulated genes) were differentially expressed in pupae of both sexes. Among the differentially expressed genes (DEGs), 263 unigenes related to immune responses were found in the two sexes in G. qinghaiensis; of these, 202 were up-regulated and 61 were down-regulated in the female pupae compared to male pupae. This indicates there were some differences in the expression of immune-related genes between male and female G. qinghaiensis pupae. Therefore, we speculated that the differences in immune responses also likely exsited in pupae of both sexes. Our report provides a valuable genomic resource for further studies of Gynaephora and improves our understanding of the molecular mechanisms underlying immunological differences between male and female insects.

Agrobacterium sp. LAD9 capable of heterotrophic-aerobic nitrogen removal was applied into a single biological aerated filter (BAF) for bioaugmented treatment of municipal wastewater. The achievemen...

The whole genome projects open the prelude to the diversity and complexity of biological genome by generating immense data. For the sake of exploring the riddle of the genome, scientists around the world have dedicated themselves in annotating for these massive data. However, searching for the exact and valuable information is like looking for a needle in a haystack. Advances in gene editing technology have allowed researchers to precisely manipulate the targeted functional genes in the genome by the state-of-the-art gene-editing tools, so as to facilitate the studies involving the fields of biology, agriculture, food industry, medicine, environment and healthcare in a more convenient way. As a sort of pioneer editing devices, the CRISPR/Cas systems having various versatile homologs and variants, now are rapidly giving impetus to the development of synthetic genomics and synthetic biology. Firstly, in the chapter, we will present the classification, structural and functional diversity of CRISPR/Cas systems. Then we will emphasize the applications in synthetic genome of yeast (Saccharomyces cerevisiae) using CRISPR/Cas technology based on year order. Finally, the summary and prospection of synthetic genomics as well as synthetic biotechnology based on CRISPR/Cas systems and their further utilizations in yeast are narrated.

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an Hlf-tdTomato reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45– and CD45+ pre-HSCs in the embryonic day (E) 10.5 AGM region. By in vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, we further revealed that unlike the CD45– counterpart in which both Hlf-tdTomato-positive and negative sub-populations harbored HSC competence, the CD45+ E10.5 pre-HSCs existed exclusively in Hlf-tdTomato-positive cells. The result indicates that the cells should gain the expression of Hlf prior to or together with CD45 to give rise to functional HSCs. Furthermore, we constructed a novel Hlf-CreER mouse model and performed time-restricted genetic lineage tracing by a single dose induction at E9.5. We observed the labeling in E11.5 AGM precursors and their contribution to the immunophenotypic HSCs in fetal liver (FL). Importantly, these Hlf-labeled early cells contributed to and retained the size of the HSC pool in the bone marrow (BM), which continuously differentiated to maintain a balanced and long-term multi-lineage hematopoiesis in the adult. Therefore, we provided another valuable mouse model to specifically trace the fate of emerging HSCs during development.

Hematopoietic stem cells (HSCs) are derived from hemogenic endothelial cells (HECs) during embryogenesis. The HSC-primed HECs increased to the peak at embryonic day (E) 10 and have been efficiently captured by the marker combination CD41–CD43–CD45–CD31+CD201+Kit+CD44+ (PK44) in the aorta-gonad-mesonephros (AGM) region of mouse embryos most recently. In the present study, we investigated the spatiotemporal and functional heterogeneity of PK44 cells around the time of emergence of HSCs. First, PK44 cells in the E10.0 AGM region could be further divided into three molecularly different populations showing endothelial- or hematopoietic-biased characteristics. Specifically, with the combination of Kit, the expression of CD93 or CD146 could divide PK44 cells into endothelial- and hematopoietic-feature biased populations, which was further functionally validated at the single-cell level. Next, the PK44 population could also be detected in the yolk sac, showing similar developmental dynamics and functional diversification with those in the AGM region. Importantly, PK44 cells in the yolk sac demonstrated an unambiguous multilineage reconstitution capacity after in vitro incubation. Regardless of the functional similarity, PK44 cells in the yolk sac displayed transcriptional features different from those in the AGM region. Taken together, our work delineates the spatiotemporal characteristics of HECs represented by PK44 and reveals a previously unknown HSC competence of HECs in the yolk sac. These findings provide a fundamental basis for in-depth study of the different origins and molecular programs of HSC generation in the future.

Gastrointestinal (GI) microbiota play an important role in promoting growth in piglets. However, studies on microbiota composition at various growth stages are lacking. We measured body weights of Jinfen White and Mashen piglets every 7 days and collected their fecal samples by rectal swabbing at nine time points during suckling (1–28 days) and nursery (35–70 days) stages to gain insight into microbiota variability during piglet growth. The fecal microbiota were characterized via 16S rRNA gene sequencing to analyze the effects of microbial diversity on piglet growth and development preliminarily. The results showed that although the two breeds of piglets have similar body weights at birth, weaned Jinfen White piglets demonstrated a significantly greater body weight and daily weight gain than weaned Mashen piglets (P < 0.01). A total of 1,976 operational taxonomic units (OTUs) belonging to 27 phyla and 489 genera were uncovered, in which the highest numbers of OTUs belong to the phyla Firmicutes and Bacteroidetes. Lactobacillus, Bacteroides, and Prevotellaceae NK3B31 groups accounting for 12.4, 8.8, and 5.8% of OTUs, respectively, showed relatively high abundance at the genus level. Nine sampling time points were divided into three growth stages, namely, immediate postfarrowing (1 day old), suckling (7, 14, and 21 days old), and nursery (28, 35, 49, 63, and 70 days old), on the basis of the results of microbial diversity, principal coordinate, and co-occurrence network analyses. In addition, it identified 54 discriminative features in the microbiota between two breeds of piglets by LEfSe analysis, in which 17 genera enriched the microbiota community of Jinfen White piglets. Finally, abundances of 29 genera showed significant positive correlations with body weights and daily weight gain of piglets. Conversely, abundances of 12 genera demonstrated significant negative correlations with body weights of piglets. The results of our study will provide a theoretical basis for succession patterns in fecal microbiota of piglets and suggest the need for meticulous management of piglets in pig production.

Leptin is a well-known adipokine that plays critical role in adiposity. To further investigate the role of leptin in adiposity, we utilized leptin overexpressing transgenic pigs and evaluated the effect of leptin on growth and development, fat deposition, and lipid metabolism at tissue and cell level. Leptin transgenic pigs were produced and divided into two groups: elevated leptin expression (leptin ( +)) and normal leptin expression group (control). Results indicated that leptin ( +) pigs had elevated leptin protein and mRNA expression levels and exhibited sluggish growth and development followed by decreased subcutaneous fat thickness, low serum triglycerides, saturated, unsaturated fatty acids and high cholesterol esters (p

The aim of this research was to screen candidate genes affecting growth traits in pigs by studying the difference expression genes (DEGs) between the longissimus dorsi of Large White (LW) and Mashen (MS) pigs. RNA-sequencing (RNA-seq) technology was applied to analyse the transcriptomes from six longissimus dorsi in two pig breeds (LW and MS). Based on sequencing, the DEGs were screened, and functional annotation and enrichment analysis were performed. The results showed that 697 different significant genes were obtained (p

Biodegradation is a promising way to reduce phenanthrene (PHE) in environment. PHE biodegradation by bioaugmentation of axenic and mixed cultures of Massilia sp. WF1 (a highly efficient PHE-degrading bacteria) and Phanerochaete chrysosporium (P. chrysosporium, an extensively researched model fungus in organic pollutant bioremediation) was investigated in aqueous and autoclaved/un-autoclaved soil cultures. In the liquid cultures, the strain WF1 could use PHE (ca. 10 mg L-1) as the sole carbon source, and the presence of d-fructose (500 mg L-1) had no obvious effect on its PHE degradation; while the opposite was observed for P. chrysosporium. The bioaugmentation of strain WF1 and P. chrysosporium co-culture showed the highest PHE-degradation efficiency, especially in the aqueous and the autoclaved soil (PHE, ca. 50 mg kg-1) cultures, indicating a synergistic interaction of the co-culture during PHE dissipation. It was further observed that the indigenous microorganisms (mainly the Gram-positive bacteria) played a dominant role during PHE biodegradation and showed an antagonistic action against the strain WF1-P. chrysosporium co-culture, which weakened the synergistic action of the co-culture in the un-autoclaved soil. Besides, the abundances of PAH-RHDα GP and nidA genes were negatively correlated with residual PHE in the soil. Our findings provide the scientific support for bioremediation of PAHs in environment.

microRNA-128 (miR-128), a brain-enriched microRNA, has been reported to play a crucial role in the treatment of diseases. The c-Jun N-terminal kinase (JNK) signaling pathway exerts various biological functions such as regulation of cell proliferation, differentiation and apoptosis. In this study, we investigated the role of the miRNA-128-JNK signaling pathway in proliferation, apoptosis and autophagy of porcine adipose-derived stem cells (ASCs).After over-expressing miR-128 in porcine ASCs, cell proliferation was determined by 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide (XTT) method, cell apoptosis was observed by Flow cytometry (FCM), the expression of miR-128, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) was measured by RNA preparation and reverse transcription polymerase chain reaction (RT-PCR), and protein expression of JNK, phosphorylated JNK (p-JNK) and LC3B was analyzed by Western Blot analysis.The over-expression of miR-128 potently promoted cell proliferation and autophagy while suppressed the apoptosis of porcine ASCs. In addition, the down-regulated expression level of p-JNK was detected in miR-128-over-expressed porcine ASCs. However, followed by the block of the JNK signaling pathway using SP600125 inhibitor, the effects of miR-128 on the proliferation, apoptosis and autophagy of porcine ASCs were significantly suppressed.It is demonstrated that the miR-128-JNK signaling pathway is a potential therapeutic target for the treatment of obesity.

Nutritional interventions play a critical role in modifying the intestinal microbiome of host animals. This study was conducted to interrogate the physiological effects on fecal microflora of weaned piglets via the dietary supplemented with two types of products of Citrus reticulata "Chachi", respectively. For this purpose, A total of 72 piglets with uniform sizes were randomly assigned to four dietary treatment groups consisted of a negative control group (NCG), a fermented citrus reticulata "Chachi" pulp group (FCRPG), a Citri Reticulatae Pericarpium group (CRPG) and a positive control group (PCG) in a 21-day feeding trial. After the raising experiment, fresh feces of piglets were analyzed systematically using multi-omics technologies. Metagenomics method with high-throughput compositional characterization indicated that the architecture and diversity of fecal microbiome were both influenced by these two additives and compound antibiotics. Metabolite analysis showed that FCRPG have an significant effects on fecal short-chain fatty acids (SCFAs) among four treatment groups. Results of functional proteomics approaches found that FCRPG presented the highest butyrate metabolic level, and CRPG showed the highest flavone and flavonol biosynthesis level in feces. In addition, NCP produced an effective effect on adjusting fecal microbiome proflie. Consequently, our findings demonstrate that dietary supplementation with FCRP or CRP modulates the microbial taxa, metabolic and proteomic alterations in fecal microbiota of weaned piglets for health maintaining.

The mammalian cell cycle is driven by a complex of cyclins and their associated cyclin-dependent kinases (CDKs). Abnormal dysregulation of cyclin-CDK is a hallmark of cancer. D-type cyclins and their associated CDKs (CDK4 and CDK6) are key components of cell cycle machinery in driving G1 to S phase transition via phosphorylating and inactivating the retinoblastoma protein (RB). A body of evidence shows that the cyclin Ds-CDKs axis plays a critical role in cancer through various aspects, such as control of proliferation, senescence, migration, apoptosis, and angiogenesis. CDK4/6 dual-inhibitors show significant efficacy in pre-clinical or clinical cancer therapies either as single agents or in combination with hormone, chemotherapy, irradiation or immune treatments. Of note, as the associated partner of D-type cyclins, CDK6 shows multiple distinct functions from CDK4 in cancer. Depletion of the individual CDK may provide a therapeutic strategy for patients with cancer.

Ophiocordyceps sinensis, a Chinese complementary and alternative medicine (CAM), is an entomopathogenic, fungus, parasitizing larvae of the moth genus Thitarodes. It has three stages of the life cycle, i.e., the anamorph mycelia prior to infection (Cm_Os), the mycelia sclerotium forming in the caterpillar (Te_Ca), and the fruiting bodies or stromata (Te_St). Characterization of the O. sinensis transcriptome among these stages could provide a better understanding of the underlying biology processes. Transcriptomics of the O. sinensis asexual mycelia and hyphae in deceased caterpillars and perithecial stroma was assessed by using Illumina HiSeq™ 2000 technology. A total of 14,922 unigenes were identified and categorized into 46 sub-categories under three gene ontology categories ("biological process", "cellular component", and "molecular function"). Of these genes, 5520 were differentially expressed among the libraries of these three groups of samples (P 0.05), and 391 genes occurred in all three groups. Compared to the anamorph stage, there were 3049 differentially expressed genes (DEGs) in the teleomorph stage, but only 1023 DEGs occurred within the teleomorph groups (Te_St vs. Te_Ca). Collectively, this study provides a novel resource to further investigate O. sinensis and their three different development stages.

Rationale: Genome-wide association studies identified single-nucleotide polymorphisms near the SORT1 locus strongly associated with decreased plasma LDL-C (low-density lipoprotein cholesterol) levels and protection from atherosclerotic cardiovascular disease and myocardial infarction. The minor allele of the causal SORT1 single-nucleotide polymorphism locus creates a putative C/EBPα (CCAAT/enhancer-binding protein α)-binding site in the SORT1 promoter, thereby increasing in homozygotes sortilin expression by 12-fold in liver, which is rich in this transcription factor. Our previous studies in mice have showed reductions in plasma LDL-C and its principal protein component, apoB (apolipoprotein B) with increased SORT1 expression, and in vitro studies suggested that sortilin promoted the presecretory lysosomal degradation of apoB associated with the LDL precursor, VLDL (very-low-density lipoprotein). Objective: To determine directly that SORT1 overexpression results in apoB degradation and to identify the mechanisms by which this reduces apoB and VLDL secretion by the liver, thereby contributing to understanding the clinical phenotype of lower LDL-C levels. Methods and Results: Pulse-chase studies directly established that SORT1 overexpression results in apoB degradation. As noted above, previous work implicated a role for lysosomes in this degradation. Through in vitro and in vivo studies, we now demonstrate that the sortilin-mediated route of apoB to lysosomes is unconventional and intersects with autophagy. Increased expression of sortilin diverts more apoB away from secretion, with both proteins trafficking to the endosomal compartment in vesicles that fuse with autophagosomes to form amphisomes. The amphisomes then merge with lysosomes. Furthermore, we show that sortilin itself is a regulator of autophagy and that its activity is scaled to the level of apoB synthesis. Conclusions: These results strongly suggest that an unconventional lysosomal targeting process dependent on autophagy degrades apoB that was diverted from the secretory pathway by sortilin and provides a mechanism contributing to the reduced LDL-C found in individuals with SORT1 overexpression.

Ganoderic triterpenoid (GT) is a promising anti-tumour constituent in Ganoderma lucidum. The aim of this study was to investigate induction by and a possible signalling mechanism of nitric oxide (NO) for GT synthesis. Compared to the control, the biomass decreased by 43.5% at 120 h and the GT yield increased by 40.94% at 72 h in the presence of a 5 mM NO donor sodium nitroprusside supplement. The gene expression profiles of G. lucidum in response to NO were investigated by RNA-sequencing. Functional annotation and an enrichment analysis of the differentially expressed genes indicated that NO inhibited mycelial growth probably via the suppression of the glycolysis genes involved in carbohydrate metabolism. NO may function directly as a regulator of gene expression in the mevalonate pathway to induce GT biosynthesis, and the hyper-production of GT in response to NO could also be accomplished by a signalling function involving Ca2+ and a reactive oxygen species (ROS) pathway. The results of this study are useful for large-scale GT production and can facilitate further studies on the endogenous signalling pathways involved in the GT biosynthetic pathway.

Chronic skin inflammation in atopic eczema is associated with elevated expression of proinflammatory genes and activation of innate immune responses in keratinocytes. MicroRNAs (miRNAs) are short, single-stranded RNA molecules that silence genes via the degradation of target mRNAs or inhibition of translation. Recent studies have demonstrated that miR-124 is associated with regulation of inflammation factors in several diseases. The aim of this study was to investigate the role of miR-124 in skin inflammation of atopic eczema. We showed that miR-124 expression is decreased in chronic lesional skin of patients with atopic eczema, and could be strongly inhibited by IFN-γ and TNF-α. Through Western blot, real-time PCR and luciferase assays, we revealed that miR-124 inhibited the expression of p65, a member of NF-κB family which can regulate many factors involved in the immune response and inflammatory reactions, through direct targeting. Further, upon IFN-γ or TNF-α stimulation, IL8, CCL5 and CCL8 showed to be significantly upregulated by IFN-γ or TNF-α, downregulated by miR-124; the promotive effect of IFN-γ and TNF-α could be partially reversed by miR-124. The levels of IL8, CCL5 and CCL8 could be significantly downregulated by p65 knockdown, upregulated by miR-124 inhibition; the suppressive effect of p65 knockdown could be partially reversed by miR-124. Moreover, contrary to miR-124, p65, IL8, CCL5 and CCL8 mRNA expression was upregulated in chronic lesional skin of patients with atopic eczema, and all inversely correlated with miR-124. Taken together, our data demonstrate that miR-124 controls NF-κB-dependent inflammatory responses in keratinocytes and chronic skin inflammation in atopic eczema; rescuing miR-124 expression presents a promising strategy for atopic eczema treatment.

D-type cyclins (D1, D2 and D3) and their associated cyclin-dependent kinases (CDK4 and CDK6) are components of the core cell cycle machinery that drives cell proliferation. Inhibitors of CDK4 and CDK6 are currently being tested in clinical trials for patients with several cancer types, with promising results. Here, using human cancer cells and patient-derived xenografts in mice, we show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2. This re-directs the glycolytic intermediates into the pentose phosphate (PPP) and serine pathways. Inhibition of cyclin D3-CDK6 in tumour cells reduces flow through the PPP and serine pathways, thereby depleting the antioxidants NADPH and glutathione. This, in turn, increases the levels of reactive oxygen species and causes apoptosis of tumour cells. The pro-survival function of cyclin D-associated kinase operates in tumours expressing high levels of cyclin D3-CDK6 complexes. We propose that measuring the levels of cyclin D3-CDK6 in human cancers might help to identify tumour subsets that undergo cell death and tumour regression upon inhibition of CDK4 and CDK6. Cyclin D3-CDK6, through its ability to link cell cycle and cell metabolism, represents a particularly powerful oncoprotein that affects cancer cells at several levels, and this property can be exploited for anti-cancer therapy.

As a pest on the Qinghai-Tibet Plateau, Gynaephora qinghaiensis causes severe damage to grassland vegetation and its pupae are also natural hosts of Thektogaster sp. To successfully parasitize, endoparasitoids generally introduce or secrete multiple parasitic factors into the host body during the spawning stage to suppress the host immune response. To study the parasitic effects of Thektogaster sp. on G. qinghaiensis, a transcriptome analysis of immune-related genes in parasitized and nonparasitized G. qinghaiensis pupae was performed. A total of 371,260,704 clean reads were assembled into 118,144 unigenes with an average length of 884.33 base pairs. Of these, 23,660 unigenes were annotated in at least one database and 94,484 unigenes were not annotated in any databases. These findings indicated that the majority of the genetic resources (79.97% of all unigenes) in Gynaephora should be further explored. Parasitization significantly affected the transcriptional profile of G. qinghaiensis pupae. The present study identified 12,322 differentially expressed genes and 57 immune-related genes were identified in parasitized G. qinghaiensis pupae. Most immune-related genes were downregulated, potentially resulting from the inhibitory effect of Thektogaster sp. on G. qinghaiensis pupae after parasitization. Overall, the transcriptome analysis sheds valuable light on the molecular mechanisms of G. qinghaiensis parasitization by Thektogaster sp. and promotes the development of novel biocontrol strategies for Gynaephora based on immune defense.

The presence of Eschericia coli (E. coli) leads to potential outbreaks of disease, demonstrating the importance of understanding how such organisms survive in secondary environments such as soil. Biotic and abiotic soil characteristics play a role in E. coil survival, but it remains unclear how these two aspects interact with survival and whether it is linked to toxin genes. Here we evaluated the survival of three E. coli O157:H7strains: Shiga toxin-producing E. coli, its mutant without stx genes and strain without virulence genes in 4 distinct Chinese soils. To further disentangle the effects of microbial diversity, soils were manipulated to generate a gradient of microbial diversity (10(-1), 10(-6), and a sterile soil [gamma-irradiated control]). Overall, our results showed the E. coli O157:H7 survival time decreased in all treatments, ranging from 8.23 +/- 5.42 to 62.33 +/- 35.80 days. The fastest decline was with the Shiga toxin-producing strain at 10(-1) dilution, whereas the strain without virulence genes, persisted the longest 178 days in the gamma sterilized control. These results confirmed the importance of biodiversity upon E. coli invasion and revealed virulence genes negatively influenced survival. The negative correlation between community niche or niche breadth of soil communities and survival, indicated that resource competition also was the major driver of E. coli O157:H7 survival. Moreover, path analyses revealed that soil pH exerted a critical role on the persistence of E. coli O157:H7, higher pH values produced longer survival time in each strain. These conclusions are of relevance for agricultural situations, where anthropogenic influences lead to decreased soil diversity, increased soil pH and resource input through manure application, which can potentially increase the survival time of E. coil O157:H7, the expanding the window of opportunity for food contamination.

The objectives of this study were to investigate (i) how the changes in cultivation pattern of vegetable affect soil microbial communities and (ii) the relationships between soil physico-chemical properties and microbial community structure. Soil samples were collected from fields growing vegetable crops with various times of plastic-greenhouse cultivation (0, 1, 4, 7 and 15 years, respectively). Phospholipid fatty acid (PLFA) analysis was conducted to reveal the soil microbial community of the test soils. The open-field soil had the highest total PLFAs amount. Although the Shannon-Weaver index was also highest in the open-field soil, the difference was not significant. Plastic-greenhouse cultivation decreased PLFAs species diversity and richness. Cluster analysis and principal component analysis (PCA) of the PLFA profiles revealed distinct groupings at different times during plastic-greenhouse cultivation. Ultimately, PLFA analyses showed that long-term plastic-greenhouse cultivation make the physiological status of soil microbial community worse and increased stress level of microorganisms. And soil microbial community was significantly affected by field water capacity and water-soluble organic carbon. The study highlights the potential risk of long-term plastic-greenhouse cultivation to soil microbial community.

Ophiocordyceps sinensis, one of the well-known traditional Chinese medicine, has multiple health-promoting effects. It is used as herbal remedy and health food in Asian countries, together with its cultured mycelia used as a substitute of natural O. sinensis. In the present study, natural O. sinensis collected from three geographical regions and its cultured mycelia derived from three strains were analyzed by gas chromatography-mass spectrometry (GC-MS) combined with chemometrics. A total of 72 metabolites were identified from all samples with different metabolic profiles observed between natural O. sinensis and cultured mycelia. Among them, 50 metabolites showed significant differences between natural O. sinensis and cultured mycelia. Higher levels of trehalose, glycerol and citric acid in natural O. sinensis were found compared to those in cultured mycelia, while myo-inositol and some amino acids were more abundant in cultured mycelia. In addition, chemical compositions of natural O. sinensis varied depending on the geographical regions. Natural O. sinensis from three locations were clearly differentiated by the concentrations of meso-erythritol, D-mannitol, glucose and organic acids. The current study provides a comprehensive metabolic profiles of natural O. sinensis and its cultured mycelia, which is potentially important for understanding the metabolism of O. sinensis and facilitating the application of cultured mycelia as a supplement of natural O. sinensis.

The presence of Eschericia coli O157:H7 in the natural environment is a serious threat to human health. The native microbial community in soil plays an important role in resisting E. coli O157:H7 invasion. This study examined the responses of soil microbial community to E. coli O157:H7 invasion during a 32-day incubation. The E. coli O157:H7 persisted longer in γ-irradiated soil than non-irradiated soil while glucose addition decreased its persistence in the irradiated soil which was associated with an increasing recovery of the native community. The invasion of E. coli O157:H7 increased soil organic carbon mineralization, an indicator of microbial activity, in both non-irradiated and irradiated soils, while glucose addition significantly promoted the carbon mineralization process. The 16S rRNA sequencing data showed the gradual recovery of the native bacterial population including specific taxa such as proteobacteria and actinobacteria following irradiation. It is concluded that soil microbial function and structure can affect persistence of E. coli O157:H7 and that lower biodiversity of the native community favors its persistence.

Rhodococcus sp. WB9, a strain isolated from polycyclic aromatic hydrocarbons contaminated soil, degraded phenanthrene (PHE, 100 mg L−1) completely within 4 days. 18 metabolites were identified during PHE degradation, including 5 different hydroxyphenanthrene compounds resulted from multiple routes of initial monooxygenase attack. Initial dioxygenation dominantly occurred on 3,4-C positions, followed by meta-cleavage to form 1-hydroxy-2-naphthoic acid (1H2N). More than 95.2% of 1H2N was transported to and kept in extracellular solution without further degradation. However, intracellular 1H2N was converted to 1,2-naphthalenediol that was branched to produce salicylate and phthalate. Furthermore, 131 genes in strain WB9 genome were related to aromatic hydrocarbons catabolism, including the gene coding for salicylate 1-monooxygenase that catalyzed the oxidation of 1H2N to 1,2-naphthalenediol, and complete gene sets for the transformation of salicylate and phthalate toward tricarboxylic acid (TCA) cycle. Metabolic and genomic analyses reveal that strain WB9 has the ability to metabolize intracellular 1H2N to TCA cycle intermediates, but the extracellular 1H2N can’t enter the cells, restricting 1H2N bioavailability and PHE mineralization.

Ophiocordyceps sinensis, a well-known Chinese complementary herb, is a rare and valuable therapeutic resource. Cordyceps militaris (C. militaris) is a commonly used substitute for O. sinensis. A metabolomic-based approach for exploring the similarities and differences in the metabolites of O. sinensis and C. militaris in water-boiled and 50% ethanol-soaked extracts is of great significance. To distinguish between the global metabolite profiles of O. sinensis and C. militaris extracts obtained from either the water-boiled or 50% ethanol-soaked methods, we investigated the herb samples using 1HNMR-based metabolic fingerprints combined with multivariate statistical analysis. This study revealed that a total of 52 primary metabolites were identified and quantified from O. sinensis and C. militaris samples. Forty-three (83% of 52) metabolites were detectable in both O. sinensis and C. militaris. According to the variable importance in projection (VIP) value and p-value from the Mann-Whitney test, 7 metabolites (alanine, aspartate, glutamate, mannitol, ornithine, serine, and trehalose) differed between O. sinensis and C. militaris. Arginine, glucose, putrescine, pyroglutamate, betaine, O-phosphocholine, and xylose differed significantly between the water-boiled and 50% ethanol-soaked methods used to prepare the herb extracts. This study demonstrated that water-boiled extraction was a much faster method (30 min. vs 360 days) that resulted in a 30% higher number of extracted metabolites (compared to 50% for the ethanol-soaked method) for both O. sinensis and C. militaris.

Organochlorines are critical soil contaminants and the use of biochar has recently shown potential to improve soil remediation. However, little is known about biochar-microbe interactions nor the impact on environmental processes such as the immobilization and biodegradation of organochlorine compounds. In this study, we performed microcosm experiments to elucidate how biochar affected the biodegradation and sequestration of pentachlorophenol (PCP). Our results showed that the amendment of biochar markedly inhibited PCP biodegradation due to a strong sorption affinity for PCP under both aerobic and anaerobic conditions. Notably, the inhibitory effect was relatively weaker under anaerobic conditions than under aerobic conditions. The addition of biochar can dramatically shift the bacterial community diversity in the PCP-spiked soils. Under aerobic conditions, biochar significantly stimulated the growth of PCP-degrading bacteria Bacillus and Sphingomonas, but reduced the opportunities for microbes to contact with PCP directly. Under anaerobic conditions, the non-strict organohalide-respiring bacteria Desulfovibrio, Anaeromyxobacter, Geobacter and Desulfomonile were the main drivers of PCP transformation. Our results imply that the use of biochar as a soil remediation strategy for organochlorine compounds should be cautious.

Mycobacterium sp. WY10 was a highly effective PAHs-degrading bacterium that can degrade phenanthrene (PHE, 100 mg L−1) completely within 60 h and 83% of pyrene (PYR, 50 mg L-1) in 72 h. In this study, ten and eleven metabolites, respectively, were identified in PHE and PYR degradation cultures, and a detailed PHE and PYR metabolism maps were constructed based on the metabolic results. The strain WY10 degraded PHE and PYR with initial dioxygenation mainly on 3,4- and 4,5-carbon positions, respectively. Thereafter, PYR degradation entered the PHE degradation pathway via the ortho-cleavage. It was observed that the “lower pathway” of PHE and PYR degradations were different. Based on the kinetics of residual metabolites, PHE was degraded in a dominant phthalate pathway and a minor salicylate pathway. However, both phthalate and salicylate pathways played important roles on PYR degradation. The WY10 genome revealed there were fifty-three genes related to PAHs degradations, including a complete gene set for PHE and PYR degradation via the phthalate pathway. The candidate gene/ORF, BOH72_19755, encoding salicylate synthase might contribute in the salicylate pathway.

Background. The intestinal microbiota plays essential functions that affect piglet health at the weaning stage. However, our understanding of the succession of bacterial intestinal communities during weaning and Nursery Periods of pig is limited. Methods. To better understand this, we performed 16S rDNA gene sequencing of the contents of four distinct intestinal segments [duodenum (D), jejunum (J), ileum (I), and cecum (C)] in six Chinese Shanxi Black pigs at day 25 (B25 group; i.e., weaning) and day 70 (B70 group; i.e., nursery). Results. We found that the dominant phyla are Proteobacteria, Bacteroidetes, and Firmicutes. In addition, the dominant genera were Acinetobacter, Prevotella, Streptococcus, and SMB53 (Clostridiaceae). The microbiota in the B25 group across segments were significantly different from that in the corresponding segments in the B70 group. In addition, the distinct segments in the B70 group presented a continuum consisting of compartmentalized architecture whereas the distinct segments in B25 group were relatively similar. The predicted molecular function analysis revealed higher enrichments in associated metabolisms as well as stress-induced functions in the B25 group. Conclusions. This study provides insights into the succession of intestinal microbiota in Chinese Shanxi Black pigs before and after weaning, and provides reference for improving the intestinal development of piglets.

Microbial ecological studies have been remarkably promoted by the high-throughput sequencing approach with explosive information of taxonomy and relative abundance. However, relative abundance does not reflect the quantity of the microbial community and the inter-sample differences among taxa. In this study, we refined and applied an integrated high-throughput absolute abundance quantification (iHAAQ) method to better characterize soil quantitative bacterial community through combining the relative abundance (by high-throughput sequencing) and total bacterial quantities (by quantitative PCR). The proposed iHAAQ method was validated by an internal reference strain EDL933 and a laboratory strain WG5. Application of the iHAAQ method to a soil phenanthrene biodegradation study showed that for some bacterial taxa, the changes of relative and absolute abundances were coincident, while for others the changes were opposite. With the addition of a microbial activity inhibitor (NaN3), the absolute abundances of soil bacterial taxa, including several dominant genera of Bacillus, Flavobacterium, and Paenibacillus, decreased significantly, but their relative abundances increased after 28 days of incubation. We conclude that the iHAAQ method can offer more comprehensive information to reflect the dynamics of soil bacterial community with both relative and absolute abundances than the relative abundance from high-throughput sequencing alone.

Circulating tumor cells (CTCs) are in limited numbers and heterogeneous, making their detection, isolation, and enumeration a major challenge. To overcome these difficulties, we developed a novel method to detect and enumerate CTCs with invasive property. Our assay consists of three simple steps: enrichment, Matrigel invasion assay, and immunostaining. We have validated this method using mouse xenograft tumor models and confirmed its utility in human cancer patients. Our method does not require special equipment and antigen expression for CTC selection, is less likely to be affected by the heterogeneity of the CTCs, and could be applicable to virtually all cancers. Most important, our method enumerates invasive CTCs, which may allow more accurate correlations with clinical outcome and treatment response compared with other CTC detection methods.

Mutations in the KRAS gene are very common in non-small cell lung cancer (NSCLC), but effective therapies targeting KRAS have yet to be developed. Interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a potent inducer of cell death, has increased following the observation that TRAIL can selectively kill a wide variety of human cancer cells without killing normal cells both in vitro and in xenograft models. However, results from clinical trials of TRAIL-based therapy are disappointingly modest at best and many have demonstrated a lack of therapeutic benefit. Current research has focused on selecting a subpopulation of cancer patients who may benefit from TRAIL-based therapy and identifying best drugs to work with TRAIL. In the current study, we found that NSCLC cells with a KRAS mutation were highly sensitive to treatment with TRAIL and 5-fluorouracil (5FU). Compared with other chemotherapeutic agents, 5FU displayed the highest synergy with TRAIL in inducing apoptosis in mutant KRAS NSCLC cells. We also found that, on a mechanistic level, 5FU preferentially repressed survivin expression and induced expression of TRAIL death receptor 5 to sensitize NSCLC cells to TRAIL. The combination of low-dose 5FU and TRAIL strongly inhibited xenograft tumor growth in mice. Our results suggest that the combination of TRAIL and 5FU may be beneficial for patients with mutant KRAS NSCLC.

The natural (S0) and chemically modified Phanerochaete chrysosporium including the methylation of amino groups (S1), acetylation of hydroxyl groups (S2), lipid removal (S3), esterification of carboxyl groups (S4), and base hydrolysis (S5) were characterized, and their sorption for phenanthrene (PHE) was investigated. The sorption isotherm of PHE on natural biomasses was apparently linear, while it was nonlinear for the modified ones. The partition coefficient (K d ) describing the sorption affinity of PHE by biomasses followed the order of S0 (9.24 L g−1) > S5 (8.94 L g−1) > S1 (7.13 L g−1) > S2 (6.97 L g−1) > S3 (6.38 L g−1) > S4 (3.51 L g−1) and decreased as temperature increased. The PHE adsorption fitted well to the pseudo-second-order kinetic model, and the sorption capacity was in the order of S5 (2041.5 μg g−1) > S0 (1768.8 μg g−1) > S2 (1570.9 μg g−1) > S1 (1552.9 μg g−1) > S3 (1346.4 μg g−1) > S4 (991.0 μg g−1). Moreover, the π–π and electron donor–acceptor interactions may govern PHE sorption which processed spontaneously and exothermally. The natural and modified biomasses, especially the base hydrolysis treated ones, were economical and effective biosorbents for PHE removal.

Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical benefit. However, many patients with cancer fail to respond to compounds that target the PD-1 and PD-L1 interaction, and the underlying mechanism(s) is not well understood. Recent studies revealed that response to PD-1-PD-L1 blockade might correlate with PD-L1 expression levels in tumour cells. Hence, it is important to understand the mechanistic pathways that control PD-L1 protein expression and stability, which can offer a molecular basis to improve the clinical response rate and efficacy of PD-1-PD-L1 blockade in patients with cancer. Here we show that PD-L1 protein abundance is regulated by cyclin D-CDK4 and the cullin 3-SPOP E3 ligase via proteasome-mediated degradation. Inhibition of CDK4 and CDK6 (hereafter CDK4/6) in vivo increases PD-L1 protein levels by impeding cyclin D-CDK4-mediated phosphorylation of speckle-type POZ protein (SPOP) and thereby promoting SPOP degradation by the anaphase-promoting complex activator FZR1. Loss-of-function mutations in SPOP compromise ubiquitination-mediated PD-L1 degradation, leading to increased PD-L1 levels and reduced numbers of tumour-infiltrating lymphocytes in mouse tumours and in primary human prostate cancer specimens. Notably, combining CDK4/6 inhibitor treatment with anti-PD-1 immunotherapy enhances tumour regression and markedly improves overall survival rates in mouse tumour models. Our study uncovers a novel molecular mechanism for regulating PD-L1 protein stability by a cell cycle kinase and reveals the potential for using combination treatment with CDK4/6 inhibitors and PD-1-PD-L1 immune checkpoint blockade to enhance therapeutic efficacy for human cancers.

Psoriasis is a common chronic inflammatory skin disease which is characterized by hyperproliferation and aberrant differentiation of keratinocytes; however the exact pathogenesis is largely unknown. Interleukin-22 (IL-22) has demonstrated its vital role in T cell-mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. The microRNAs (miRNAs) are a class of small non-coding RNA molecules that play important roles in cellular processes by regulating gene expression at the post-transcriptional level. MiR-330 has been reported to inhibit the proliferation and migration of mouse keratinocytes. In the present study, we indicated that miR-330 expression in lesion tissue of psoriasis patients was specifically down-regulated, and could inhibit IL-22-induced proliferation of HaCaT and HKC cell. Wnt/β-catenin pathway plays an essential role in the pathogenesis of psoriasis. By direct targeting CTNNB1, miR-330 could significantly downregulate IL-22-induced CTNNB1 expression. In addition, we found that the downstream targets of β-catenin, CyclinD1 and Axin2, could be affected by miR-330; miR-330 could suppress CyclinD1 protein expression and rescue Axin2 protein expression. Taken together, we indicated miR-330 inhibits IL-22-induced proliferation of HaCaT and HKC cell by targeting CTNNB1 and subsequently affect the downstream factors, CyclinD1 and Axin2 for the first time, and provide diagnostic markers and a novel target for psoriasis treatment.

Pollutant-degrading bacteria migrated by fungi may enhance the contacts between microorganisms and pollutants and improve the bioremediation efficiency of persistent organic pollutants in soil. Here, the migration of phenanthrene (PHE)-degrading bacteria Massilia sp. WF1 and Mycobacterium sp. WY10 by the hydrophobic fungi Phanerochaete chrysosporium (P. chrysosporium) and its effects on the PHE biodegradation in soil were investigated. Migration of the hydrophilic bacterium WF1 was better than that of the hydrophobic bacterium WY10 by P. chrysosporium mycelia since strain WF1 possesses flagellum and the type III secretion system. The interaction energy change of P. chrysosporium-WF1 was lower, but the interaction forces (van der Waals attractions, capillary forces, and cross-linking effects) were stronger than those of P. chrysosporium-WY10. Thus, the adhesive attraction between strain WF1 and P. chrysosporium was stronger, and consequently, strain WF1 was migrated by P. chrysosporium to a greater extent than WY10. The corresponding migration mechanism was inferred to be a bacterial ‘passive’ method: bacteria adhered to mycelia before they migrated with the growing mycelia. Moreover, migrated strain WF1 via P. chrysosporium showed effective PHE biodegradation in soil. Fungus-mediated migration of pollutant-degrading bacteria may play an important role in the bioremediation of pollutants in soil.

More than ten percent of people suffer from at least one episode of depression and related mental disorders in a lifetime, and depression and related mental disorders are one of the world’s greatest public health problems. A multiple system theory holds that dysregulation of the multiple systems underlies the pathogenesis of depression and related mental disorders, and new therapies based on the multiple system dysregulation theory are urgently needed. In this study, the antidepressant effect of decoction from herbCistanche deserticolaY.C.Ma andCistanche tubulosawas examined. HerbCistanchedecoction reduced the immobility period significantly in the mouse tail suspension test. Mice treated with herb decoction showed an improved ability of spatial learning and memory in the Morris water maze test. Groups treated herb decoction displayed a downregulated monoamine oxidase (MAO) activity; the dopamine (DA) concentration in the brain was upregulated, indicating herbCistanchedecoction improved the nerve excitability; the serum concentration of corticosterone (CORT) was downregulated, showing that mice benefited from a reduced stress level. Hence, the antidepressant efficacy and mechanism of traditional Chinese herbCistanchewere explored in this study. HerbCistancheshowed a potential to be developed as a complementary and alternative therapy for depression.

Cyclin C was cloned as a growth-promoting G1 cyclin, and was also shown to regulate gene transcription. Here we report that in vivo cyclin C acts as a haploinsufficient tumour suppressor, by controlling Notch1 oncogene levels. Cyclin C activates an 'orphan' CDK19 kinase, as well as CDK8 and CDK3. These cyclin-C-CDK complexes phosphorylate the Notch1 intracellular domain (ICN1) and promote ICN1 degradation. Genetic ablation of cyclin C blocks ICN1 phosphorylation in vivo, thereby elevating ICN1 levels in cyclin-C-knockout mice. Cyclin C ablation or heterozygosity collaborates with other oncogenic lesions and accelerates development of T-cell acute lymphoblastic leukaemia (T-ALL). Furthermore, the cyclin C encoding gene CCNC is heterozygously deleted in a significant fraction of human T-ALLs, and these tumours express reduced cyclin C levels. We also describe point mutations in human T-ALL that render cyclin-C-CDK unable to phosphorylate ICN1. Hence, tumour cells may develop different strategies to evade inhibition by cyclin C.

The survival of Escherichia coli O157:H7 in soils can contaminate vegetables, fruits, drinking water, etc. However, data on the impact of E. coli O157:H7 on soil microbial communities are limited. In this study, we monitored the changes in the indigenous microbial community by using the phospholipid fatty acid (PLFA) method to investigate the interaction of the soil microbial community with E. coli O157:H7 in soils. Simple correlation analysis showed that the survival of E. coli O157:H7 in the test soils was negatively correlated with the ratio of Gram-negative (G − ) to Gram-positive (G + ) bacterial PLFAs (G − /G + ratio). In particular, levels of 14 PLFAs were negatively correlated with the survival time of E. coli O157:H7. The contents of actinomycetous and fungal PLFAs in the test soils declined significantly ( P , E. coli O157:H7. The G − /G + ratio declined slightly, while the ratio of bacterial to fungal PLFAs (B/F ratio) and the ratio of normal saturated PLFAs to monounsaturated PLFAs (S/M ratio) increased, after E. coli O157:H7 inoculation. Principal component analysis results further indicated that invasion by E. coli O157:H7 had some effects on the soil microbial community. Our data revealed that the toxicity of E. coli O157:H7 presents not only in its pathogenicity but also in its effect on soil microecology. Hence, close attention should be paid to the survival of E. coli O157:H7 and its potential for contaminating soils.

Pyruvate kinase isoform M2 (PKM2) is an enzyme-catalyzing conversion of phosphoenolpyruvate to pyruvate in the glycolysis pathway. It was demonstrated that PKM2 interacts with tyrosine phosphopeptide, and the interaction with the tyrosine phosphopeptide affects the pyruvate kinase activity of PKM2. Our experiments suggest that PKM2 is also an active protein kinase (Gao, X., Wang, H., Yang, J. J., Liu, X., and Liu, Z. R. (2012) Mol. Cell 45, 598–609). We report here that growth signals reciprocally regulate the pyruvate kinase and protein kinase activities of PKM2 by different mechanisms. On the one hand, growth signals induce protein tyrosine phosphorylations. The tyrosine-phosphorylated protein(s) regulates the conversion of pyruvate kinase and protein kinase of PKM2 by directly interacting with PKM2. Binding of the tyrosyl-phosphorylated proteins at the fructose 1,6-bisphosphate-binding site converts the tetrameric PKM2 to a dimer. On the other hand, growth stimulations also lead to PKM2 phosphorylation, which consequently regulates the conversion of protein kinase and pyruvate kinase activities. Growth factor stimulations significantly increase the dimer/tetramer PKM2 ratio in cells and consequently activate the protein kinase activity of PKM2. Our study suggests that the conversion between the pyruvate kinase and protein kinase activities of PKM2 may be an important mechanism mediating the effects of growth signals in promoting cell proliferation. Background: Pyruvate kinase M2 is also a protein kinase. It is not known how the pyruvate kinase and protein kinase are controlled. Results: Growth stimulations increase the dimer/tetramer PKM2 ratio and activate the protein kinase activity of PKM2. Conclusion: The growth signals reciprocally regulate the pyruvate kinase and protein kinase activities of PKM2. Significance: Studies reveal an important example regarding how cancer cells cope with bioenergetic stress during growth.

Soil microbiota play a critical role in soil biogeochemical processes and have a profound effect on soil functions. Recent studies have revealed microbial co-occurrence patterns in soil microbial communities, yet the geographic pattern of topological features in soil microbial co-occurrence networks at the continental scale are largely unknown. Here, we investigated the shifts of topological features in co-occurrence networks inferred from soil microbiota along a continental scale in eastern China. Integrating archaeal, bacterial and fungal community datasets, we inferred a meta-community co-occurrence network and analyzed node-level and network-level topological shifts associated with five climatic regions. Both node-level and network-level topological features revealed geographic patterns wherein microorganisms in the northern regions had closer relationships but had a lower interaction influence than those in the southern regions. We further identified topological differences associated with taxonomic groups and demonstrated that co-occurrence patterns were random for archaea and non-random for bacteria and fungi. Given that microbial interactions may contribute to soil functions more than species diversity, this geographic shift of topological features provides new insight into studying microbial biogeographic patterns, their organization and impacts on soil-associated function.

The trace element iron is crucial for living organisms, since it plays essential roles in numerous cellular functions. Systemic iron overload and the elevated level of ferritin, a ubiquitous intracellular protein that stores and releases iron to maintain the iron homeostasis in cells, has long been epidemiologically associated with obesity and obesity-related diseases. However, the underlying mechanisms of this association remain unclear. Here, using Caenorhabditis elegans, we show that iron overload induces the expression of sgk-1, encoding the serum and glucocorticoid-inducible kinase, to promote the level of ferritin and fat accumulation. Mutation of cyp-23A1, encoding a homolog of human cytochrome P450 CYP7B1 that is related to neonatal hemochromatosis, further enhances the elevated expression of ftn-1, sgk-1, and fat accumulation. sgk-1 positively regulates the expression of acs-20 and vit-2, genes encoding homologs of the mammalian FATP1/4 fatty acid transport proteins and yolk lipoproteins, respectively, to facilitate lipid uptake and translocation for storage under iron overload. This study reveals a completely novel pathway in which sgk-1 plays a central role to synergistically regulate iron and lipid homeostasis, offering not only experimental evidence supporting a previously unverified link between iron and obesity, but also novel insights into the pathogenesis of iron and obesity-related human metabolic diseases.

The cell wall-cosolvent partition coefficients (Km) of polycyclic aromatic hydrocarbons (PAHs) were determined for Rhizopus oryzae cell walls by controlling the volume fraction of methanol (f) ranging from 0.1 to 0.5. Five cosolvent models were employed for extrapolating the cell wall-water partition coefficients (Kw) in pure water. The extrapolated Kw values of four PAHs on R. oryzae cell walls were ranged from 2.9 to 5.1. Comparison of various Kw values of pyrene generated from extrapolation and the QSPR model, together with predicted different (PD), mean percentage deviations (MPD), and root mean square errors (RSE), revealed that the performance of the LL and Bayesian models were the best among all five tested cosolvent models. This study suggests that R. oryzae cell walls play an important role in the partitioning of PAHs during bioremediation because of the high Kw of fungal cell walls.

P68 RNA helicase is a prototypical DEAD box RNA helicase. The protein plays a very important role in early organ development and maturation. In consistence with the function of the protein in transcriptional regulation and pre-mRNA splicing, p68 was found to predominately localize in the cell nucleus. However, recent experiments demonstrate a transient cytoplasmic localization of the protein. We report here that p68 shuttles between the nucleus and the cytoplasm. The nucleocytoplasmic shuttling of p68 is mediated by two nuclear localization signal (NLS) and two nuclear exporting signal (NES) sequence elements. Our experiments reveal that p68 shuttles via a classical RanGTPase dependent pathway.

One 50 m × 50 m standard plot was sampled in a natural forest of Populus euphratica in Awati County, situated at the edge of the Tarim Basin, Xinjiang Uygur Autonomous Region, China. The field investigation was conducted with a contiguous grid quadrate method. By means of a test of variance/mean value ratio, aggregation intensity index and theoretical distribution models, the spatial distribution pattern and the dynamics of primary populations in P. euphratica forest were studied. The results showed that the spatial distribution pattern of two dominant arbor populations conformed to clumped distribution. The aggregation intensity of the P. euphratica population was higher than that of P. pruinosa population. The spatial distribution pattern of two companion plant populations in the shrub layer also conformed to clump type, though the aggregation intensity of Tamarix chinensis was higher. In the herb layer, the distribution patterns of Glycyrrhiza uralensis and Asparagus persicus conformed respectively to a clumped pattern and a random pattern. The results of a Taylor power method test and Iwao’s \( m* - \bar x \) regression model also verified that both P. euphratica and P. pruinosa populations belong to a clumped pattern. Although the distribution pattern of P. pruinosa population at different development stages all belonged to a clumped distribution pattern, the aggregation intensity dropped gradually along with age development. The distribution patterns of the P. euphratica population at different development stages changed from random type to clumped type, and further to random type. The differences in spatial distribution patterns of different populations at different development stages were related not only to ecological and biological characteristics of each species in the communities in the light of competitive exclusion principle among the populations, but were also closely related to the habitats in which the species lived in.