mTOR and MDM2 signaling pathways are frequently deregulated in cancer development, and inhibition of mTOR or MDM2 independently enhances carcinoma-cell apoptosis. However, responses to mTOR and MDM2 antagonists in renal cell carcinoma (RCC) remain unknown.

Multifunctional nanocarriers for targeted bioimaging and drug delivery have attracted much attention in early diagnosis and therapy of cancer. In this work, we develop a novel aptamer-guided nanocarrier based on the mesoporous metal-organic framework (MOF) shell and up-conversion luminescent NaYF4:Yb(3+)/Er(3+) nanoparticles (UCNPs) core for the first time to achieve these goals. These UCNPs, chosen as optical labels in biological assays and medical imaging, could emit strong green emission under 980 nm laser. The MOF structure based on iron (III) carboxylate materials [MIL-100 (Fe)] possesses high porosity and non-toxicity, which is of great value as nanocarriers for drug storage/delivery. As a unique nanoplatform, the hybrid inorganic-organic drug delivery vehicles show great promising for simultaneous targeted labeling and therapy of cancer cells.

Increasing evidence indicates that brown adipose tissue (BAT) transplantation enhances whole-body energy metabolism in a mouse model of diet-induced obesity. However, it remains unclear whether BAT also has such beneficial effects on genetically obese mice. To address this issue, we transplanted BAT from C57/BL6 mice into the dorsal subcutaneous region of age- and sex-matched leptin deficient Ob/Ob mice. Interestingly, BAT transplantation led to a significant reduction of body weight gain with increased oxygen consumption and decreased total body fat mass, resulting in improvement of insulin resistance and liver steatosis. In addition, BAT transplantation increased the level of circulating adiponectin, whereas it reduced the levels of circulating free T3 and T4, which regulate thyroid hormone sensitivity in peripheral tissues. BAT transplantation also increased β3-adrenergic receptor and fatty acid oxidation related gene expression in subcutaneous and epididymal (EP) white adipose tissue. Accordingly, BAT transplantation increased whole-body thermogenesis. Taken together our results demonstrate that BAT transplantation may reduce obesity and its related diseases by activating endogenous BAT.

Natural products containing phosphonic or phosphinic acid functionalities often display potent biological activities with applications in medicine and agriculture. The herbicide phosphinothricin-tripeptide (PTT) was the first phosphinate natural product discovered, yet despite numerous studies, questions remain surrounding key transformations required for its biosynthesis. In particular, the enzymology required to convert phosphonoformate to carboxyphosphonoenolpyruvate and the mechanisms underlying phosphorus methylation remain poorly understood. In addition, the model for non-ribosomal peptide synthetase assembly of the intact tripeptide product has undergone numerous revisions that have yet to be experimentally tested. To further investigate the biosynthesis of this unusual natural product, we completely sequenced the PTT biosynthetic locus from Streptomyces hygroscopicus and compared it with the orthologous cluster from Streptomyces viridochromogenes. We also sequenced and analyzed the closely related phosalacine (PAL) biosynthetic locus from Kitasatospora phosalacinea. Using data drawn from the comparative analysis of the PTT and PAL pathways, we also evaluate three related recently discovered phosphonate biosynthetic loci from Streptomyces sviceus, Streptomyces sp. WM6386 and Frankia alni. Our observations address long-standing biosynthetic questions related to PTT and PAL production and suggest that additional members of this pharmacologically important class await discovery.

Endometriosis is a common gynecological condition with unclear pathogenesis. Although a dysregulated lncRNA expression profile has been speculated, very few studies have addressed this hypothesis. We determined the differential lncRNA and mRNA expression patterns between endometriosis and control tissues, and between eutopic and normal endometrium in the proliferative phase, using RNA sequencing. The potential targets of lncRNA were predicted on the basis of cis and trans action, and lncRNAs were functionally annotated in relation to their co-expressed mRNAs. Dysregulated lncRNAs and mRNAs were screened relative to the biological features of endometriosis, and the five filtered lncRNAs were validated using qRT-PCR. A total of 9924 novel lncRNA transcripts were identified, and 86 lncRNAs and 1228 mRNAs were differentially expressed between the endometriosis and control groups. GO and KEGG pathway analysis showed that the differentially expressed lncRNAs were enriched in the biological processes and signaling pathways involved in endometriosis. A coding-noncoding gene (CNC) co-expression network was constructed using the dysregulated lncRNAs and their co-expressed mRNAs to simulate the complex intergenic interactions. This study is the first to use sequencing technology to elucidate the differentially lncRNA expression profiles of eutopic and normal endometrium in the proliferative phase of endometriosis. The dysregulated lncRNAs can potentially be novel diagnostic biomarkers and therapeutic targets of endometriosis.

Glioblastoma (GBM) is a common malignant tumour in the human brain, but its molecular mechanisms have not been systematically evaluated. The aim of this study was to identify potential key oncogenes associated with the progression of GBM and to elucidate their mechanisms. The gene expression profile of GSE50161, selected from the Gene Expression Omnibus database, was analysed to find cancer‑associated genes and gene functions in GBM. In total, 486 differentially expressed genes, including 128 upregulated genes, were identified. The function and pathway enrichment of these genes were analysed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Survival analysis for three selected partially upregulated genes, CDK1, CCNB1 and CDC20, showed that their high expression was significantly associated with poor survival in GBM. CDK1 was selected for validation of its function and molecular mechanism in GBM. This gene was significantly overexpressed in GBM cancer tissues and cells compared with normal control cells. In addition, knockdown of CDK1 clearly inhibited GBM cell proliferation. Notably, we demonstrated that CDK1 was involved in the Akt signalling pathway, where it promotes the process involved in GBM malignancy.

Today, most endeavours require teamwork by people with diverse skills and characteristics. In managing teamwork, decisions are often made under uncertainty and resource constraints. The strategies and the effectiveness of the strategies different people adopt to manage teamwork under different situations have not yet been fully explored, partially due to a lack of detailed large-scale data. In this paper, we describe a multi-faceted large-scale dataset to bridge this gap. It is derived from a game simulating complex project management processes. It presents the participants with different conditions in terms of team members' capabilities and task characteristics for them to exhibit their decision-making strategies. The dataset contains detailed data reflecting the decision situations, decision strategies, decision outcomes, and the emotional responses of 1,144 participants from diverse backgrounds. To our knowledge, this is the first dataset simultaneously covering these four facets of decision-making. With repeated measurements, the dataset may help establish baseline variability of decision-making in teamwork management, leading to more realistic decision theoretic models and more effective decision support approaches.

Tea plants produce extremely diverse and abundant specialized metabolites, the types and levels of which are developmentally and environmentally regulated. However, little is known about how developmental cues affect the synthesis of many of these molecules. In this study, we conducted a comparative profiling of specialized metabolites from six different tissues in a premium oolong tea cultivar, Tieguanyin, which is gaining worldwide popularity due to its uniquely rich flavors and health benefits. UPLC-QTOF MS combined with multivariate analyses tentatively identified 68 metabolites belonging to 11 metabolite classes, which exhibited sharp variations among tissues. Several metabolite classes, such as flavonoids, alkaloids, and hydroxycinnamic acid amides were detected predominantly in certain plant tissues. In particular, tricoumaroyl spermidine and dicoumaroyl putrescine were discovered as unique tea flower metabolites. This study offers novel insights into tissue-specific specialized metabolism in Tieguanyin, which provides a good reference point to explore gene-metabolite relationships in this cultivar.

To investigate the effects of tumor protein p53 (p53 or TP53) α gene on the chemosensitivity of the H1299 human lung adenocarcinoma cell line, the recombinant vector pEGFP-p53α was constructed. The vector pEGFP-p53α was transfected into the cultured p53-null H1299 cells using Lipofectamine 2000. The G418-resistant cells were then selected. The expression of the p53α gene in these cells was examined using reverse transcription-polymerase chain reaction, and TP53 protein expression was examined using western blot analysis and immunocytochemistry. An MTT assay and colony formation assay were used to analyze the response of the transfected cells to cisplatin (CDDP). DAPI staining was used to determine the level of apoptosis of the transfected cells. The transfected H1299 human lung adenocarcinoma cells stably expressed TP53 protein. The MTT assay demonstrated that the 50% inhibitory concentrations for the H1299, H1299/pEGFP-N1 and H1299/pEGFP-p53α cells were 28, 24 and 18 µmol/l, respectively. The survival rate of H1299/pEGFP-p53α cells was significantly reduced compared with that of H1299 and H1299/pEGFP-N1 cells (P<0.05). The colony formation assay and DAPI staining identified that the colony formation rate and the number of apoptotic cells of H1299/pEGFP-p53α were significantly reduced, compared with those of the H1299 and H1299/pEGFP-N1 cells (P<0.05). Therefor, the present study demonstrated that the transfection of H1299 cells with the p53α gene resulted in an increase in sensitivity to CDDP chemotherapy. The combination of CDDP and gene therapy for H1299 lung adenocarcinoma cell line provides an experimental basis for clinical research.

Filamentous fungi have been of great interest because of their excellent ability as cell factories to manufacture useful products for human beings. The development of genetic transformation techniques is a precondition that enables scientists to target and modify genes efficiently and may reveal the function of target genes. The method to deliver foreign nucleic acid into cells is the sticking point for fungal genome modification. Up to date, there are some general methods of genetic transformation for fungi, including protoplast-mediated transformation, Agrobacterium-mediated transformation, electroporation, biolistic method and shock-wave-mediated transformation. This article reviews basic protocols and principles of these transformation methods, as well as their advantages and disadvantages.

Small RNAs are a group of regulatory RNA molecules that control gene expression at transcriptional or post-transcriptional levels among eukaryotes. The silkworm, Bombyx mori L., genome harbors abundant repetitive sequences derived from families of retrotransposons and transposons, which together constitute almost half of the genome space and provide ample resource for biogenesis of the three major small RNA families. We systematically discovered transposable-element (TE)-associated small RNAs in B. mori genome based on a deep RNA-sequencing strategy and the effort yielded 182, 788 and 4,990 TE-associated small RNAs in the miRNA, siRNA and piRNA species, respectively. Our analysis suggested that the three small RNA species preferentially associate with different TEs to create sequence and functional diversity, and we also show evidence that a Bombyx non-LTR retrotransposon, bm1645, alone contributes to the generation of TE-associated small RNAs in a very significant way. The fact that bm1645-associated small RNAs partially overlap with each other implies a possibility that this element may be modulated by different mechanisms to generate different products with diverse functions. Taken together, these discoveries expand the small RNA pool in B. mori genome and lead to new knowledge on the diversity and functional significance of TE-associated small RNAs.

The host response to a virus is determined by intracellular signaling pathways that are modified during infection. These pathways converge as networks and produce interdependent phenotypes, making it difficult to link virus-induced signals and responses at a systems level. Coxsackievirus B3 (CVB3) infection induces death of cardiomyocytes, causing tissue damage and virus dissemination, through incompletely characterized host cell signaling networks. We built a statistical model that quantitatively predicts cardiomyocyte responses from time-dependent measurements of phosphorylation events modified by CVB3. Model analysis revealed that CVB3-stimulated cytotoxicity involves tight coupling between the host ERK and p38 MAPK pathways, which are generally thought to control distinct cellular responses. The kinase ERK5 requires p38 kinase activity and inhibits apoptosis caused by CVB3 infection. By contrast, p38 indirectly promotes apoptosis via ERK1/2 inhibition but directly causes CVB3-induced necrosis. Thus, the cellular events governing pathogenesis are revealed when virus-host programs are monitored systematically and deconvolved mathematically.

To compare the two RNA-sequencing protocols, ribo-minus RNA-sequencing (rmRNA-seq) and polyA-selected RNA-sequencing (mRNA-seq), we acquired transcriptomic data-52 and 32 million alignable reads of 35 bases in length-from the mouse cerebrum, respectively. We found that a higher proportion, 44% and 25%, of the uniquely alignable rmRNA-seq reads, is in intergenic and intronic regions, respectively, as compared to 23% and 15% from the mRNA-seq dataset. Further analysis made an additional discovery of transcripts of protein-coding genes (such as Histone, Heg1, and Dux), ncRNAs, snoRNAs, snRNAs, and novel ncRNAs as well as repeat elements in rmRNA-seq dataset. This result suggests that rmRNA-seq method should detect more polyA- or bimorphic transcripts. Finally, through comparative analyses of gene expression profiles among multiple datasets, we demonstrated that different RNA sample preparations may result in significant variations in gene expression profiles.

MicroRNAs (miRNAs) are small endogenous, non-coding RNAs that specifically bind to the 3' untranslated region (3'UTR) of target genes in animals. However, some recent studies have demonstrated that miRNAs also target the coding regions of mammalian genes. Here, we show that miRNA-181a downregulates the expression of a large number of zinc finger genes (ZNFs). Bioinformatics analysis revealed that these ZNFs contain many miR-181a seed-matched sites within their coding sequences (CDS). In particular, miR-181a 8-mer-matched sequences were mostly localized to the regions coding for the ZNF C2H2 domain. A series of reporter assays confirmed that miR-181a inhibits the expression of ZNFs by directly targeting their CDS. These inhibitory effects might be due to the multiple target sites located within the ZNF genes. In conclusion, our findings indicate that some miRNA species may regulate gene family by targeting their coding regions, thus providing an important and novel perspective for decoding the complex mechanism of miRNA/mRNA interplay.

Magnesium (Mg) deficiency, a widespread yet overlooked problem in agriculture, has been reported to retard plant growth and development, through affecting key metabolic pathways. However, the metabolic responses of plant to Mg deficiency is still not fully understood. Here we report a metabolomic study to evaluate the metabolic responses to Mg deficiency in soybean leaves and roots. Hydroponic grown soybean were exposed to Mg starvation for 4 and 8 days, respectively. Metabolic changes in the first mature trifoliolate leaves and roots were quantified by conducting GC-TOF-MS based metabolomic analysis. Principal component analysis (PCA) showed that Mg deficient plants became distinguishable from controls at 4 days after stress (DAS) at metabolic level, and were clearly discriminated at 8 DAS. Mg deficiency could cause large metabolite alterations on carbon and nitrogen metabolism. At 8 DAS, carbon allocation from shoot to root is decreased by Mg deficiency. Remarkably, most amino acids (such as phenylalanine, asparagine, leucine, isoleucine, glycine, glutamine, and serine) showed pronounced accumulation in the leaves, while most organic acids (including pyruvic acid, citric acid, 2-keto-glutaric acid, succinic acid, fumaric acid, and malic acid) were significantly decreased in the roots. Our study shows that the carbon and nitrogen metabolic responses are distinct in leaves and roots under Mg deficiency.

Immunosuppressive treatment regimens are complex and require ongoing self-management. Medication adherence can be difficult to achieve for several reasons. The current meta-analysis and systematic review investigated whether adherence interventions improved immunosuppressive treatment adherence in kidney transplant recipients. Medline, Cochrane, EMBASE, and Google Scholar were searched until October 17, 2016 using the following search terms: kidney transplantation, compliance, adherence, and immunosuppressive therapy. Randomized controlled trials and two-arm prospective, retrospective, and cohort studies were included. The primary outcomes were adherence rate and adherence score. Eight studies were included with a total for 546 patients. Among participants receiving intervention, the adherence rate was significantly higher than the control group (pooled OR=2.366, 95% CI 1.222 to 4.578, p=0.011). Participants in the intervention group had greater adherence scores than those in the control group (pooled standardized difference in means =1.706, 95% CI 0.346 to 3.065, p=0.014). Sensitivity analysis indicated that findings for adherence rate were robust. However, for adherence score, the significance of the association disappeared after removing one of the studies indicating the findings may have been overly influenced by this one study. Intervention programs designed to increase immunosuppressive adherence in patients with kidney transplant improve treatment adherence.

Thiol capped gold nanoparticles with small size, high dispersity, and broad light absorption covering ultraviolet (UV) to near infrared (NIR) region have been developed for catalysis, fluorescence imaging and photodynamic therapy (PDT). The constitution of the metal core in such nanoparticles can strongly influence the luminescence, catalysis, and stability properties. However, to date, a corresponding investigation of the influence of the metallic core on the generation of reaction oxygen species (ROS) and its therapeutic efficiency towards tumor cells remains to be lacking. Herein, we fabricated bimetallic nanoparticles by introducing bismuth into captopril capped gold nanoparticles. Surprisingly, the introduction of the Bi was found enhance the photothermal effect of the nanoparticles to a great extent, and the variation trends for the thermal effect, ROS generation rate, and tumor cell inhibition effect were found to disparate with the changes in the Au and Bi composition. The origin of the photothermal effect was deduced through density functional theory calculations based on microscopic construction. Combined with the intrinsic photodynamic effect, the bimetallic nanoparticles showed an outstanding tumor cell inhibition effect. Furthermore, due to the excellent CT imaging property, our designed nanoparticles provide the exciting possibility to realize CT imaging guided and light-mediated tumor therapy.

B7-H4 is among the B7 family members which may serve as a new targetable immune checkpoint molecule. It was reported that high level of serum B7-H4 level may be correlated with lymphoma. Nevertheless, the role of B7-H4 in Epstein-Barr Virus-Positive diffuse large B cell lymphoma (EBV+DLBCL) has not been addressed although it has been suggested that B7-H4 could promote tumor growth and metastatic progression in certain cancers.

Endometriosis is a benign gynaecological disease with malignant characteristics that severely affects women's quality of life. Long noncoding RNA maternally expressed gene 3 (LncRNA MEG3) is a tumour suppressor that is downregulated in various cancer cells and tissues, and regulates multiple biological processes. Emerging studies have revealed that the interactions between MEG3 and proteins are involved in disease progression. Galectin-1 affects cell motility, signal transduction and vascularization, and is overexpressed in endometriosis. Our study is the first to explore the role of MEG3-210 transcript in endometriosis and to reveal the regulatory mechanism mediated by the interaction between MEG3-210 and Galectin-1.

Maintaining homeostasis of the decidual immune microenvironment at the maternal-fetal interface is essential for placentation and reproductive success. Although distinct decidual immune cell subpopulations have been identified under normal conditions, systematic understanding of the spectrum and heterogeneity of leukocytes under recurrent miscarriage in human deciduas remains unclear. To address this, we profiled the respective transcriptomes of 18,646 primary human decidual immune cells isolated from patients with recurrent pregnancy loss (RPL) and healthy controls at single-cell resolution. We discovered dramatic differential distributions of immune cell subsets in RPL patients compared with the normal decidual immune microenvironment. Furthermore, we found a subset of decidual natural killer (NK) cells that support embryo growth were diminished in proportion due to abnormal NK cell development in RPL patients. We also elucidated the altered cellular interactions between the decidual immune cell subsets in the microenvironment and those of the immune cells with stromal cells and extravillous trophoblast under disease state. These results provided deeper insights into the RPL decidual immune microenvironment disorder that are potentially applicable to improve the diagnosis and therapeutics of this disease.