Summary Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.

The successful transmission of chromosomes during mitosis and meiosis relies on the establishment and subsequent release of cohesion between replicated chromatids. Cohesion is mediated by a four-subunit structural maintenance of chromosome complex, called cohesins. REC8 is a key component of this meiotic cohesion complex in most model organisms studied to date. Here, we isolated and dissected the functions of OsREC8, a rice (Oryza sativa) REC8 homolog, using two null Osrec8 mutants. We showed that OsREC8 encodes a protein that localized to meiotic chromosomes from approximately meiotic interphase to metaphase I. Homologous pairing and telomere bouquet formation were abnormal in Osrec8 meiocytes. Furthermore, fluorescent in situ hybridization experiments on Osrec8 meiocytes demonstrated that the mutation eliminated meiotic centromeric cohesion completely during prophase I and also led to the bipolar orientation of the kinetochores during the first meiotic division and accordingly resulted in premature separation of sister chromatid during meiosis I. Immunolocalization analyses revealed that the loading of PAIR2, PAIR3, OsMER3, and ZEP1 all depended on OsREC8. By contrast, the presence of the OsREC8 signal in pair2, pair3, Osmer3, and zep1 mutants indicated that the loading of OsREC8 did not rely on these four proteins. These results suggest that OsREC8 has several essential roles in the meiotic processes.

Novel iodine-induced sulfonylation and sulfenylation of imidazopyridines have been described using sodium sulfinates as the sulfur source. This strategy enables highly selective difunctionalization of imidazo[1,2-a]pyridine to access sulfones and sulfides in good yields. A wide range of substrates and functional groups were well-tolerated under optimized conditions. Moreover, control experiments have been conducted, indicating a radical pathway involved in the reaction mechanisms.

A series of novel ruthenium(II) complexes supported by a symmetrical NNN ligand were prepared and fully characterized. These complexes exhibited good performance in transfer hydrogenation to form new C-C bonds using alcohols as the alkylating agents, generating water as the only byproduct. A broad range of substrates, including (hetero)aryl- or alkyl-ketones and alcohols, were well tolerated under the optimized conditions. Notably, α-substituted methylene ketones were also investigated, which afforded α-branched steric hindrance products. A potential application of α-alkylation of methylene acetone to synthesize donepezil was demonstrated, which provided the desired product in 83% yield. Finally, this catalytic system could be applied to a one-pot double alkylation procedure with sequential addition of two different alcohols. The current protocol is featured with several characteristics, including a broad substrate scope, low catalyst (0.50 mol %) loadings, and environmental benignity.

The role of flavonoids as the major red, blue, purple and brown pigments in plants has gained these secondary products a great deal of attention over the years. In this study, we characterized a rice inhibitor for brown furrows1 (ibf1) mutant. In the ibf1 mutant, brown pigments specifically accumulate in hull furrows during seed maturation and reach a maximum level in dry seeds. Higher amounts of total flavonoids and anthocyanin in hull may be responsible for the brown pigmentation of ibf1. The IBF1 gene, which encodes a similar kelch repeat-containing F-box protein, was isolated by map-based cloning approach. Real-time RT-PCR and GUS activity assays revealed that IBF1 specifically expressed in reproductive tissues. GFP-IBF1 fusion protein mainly localized in cytoplasm. The expression of some major structural enzymatic genes involved in flavonoids biosynthesis could be up- or down-regulated to some different extent in ibf1 mutant. Our data suggested that IBF1 as a suppressor could inhibit the brown pigmentation of rice hull furrows.

BackgroundSubterranean rodents have evolved many features to adapt to their hypoxic environment. The brain is an organ that is particularly vulnerable to damage caused by exposure to hypoxic conditions. To investigate the mechanisms of adaption to a hypoxic underground environment, we carried out a cross-species brain transcriptome analysis by RNA sequencing and identified genes that are differentially expressed between the subterranean vole Lasiopodomys mandarinus and the closely related above-ground species Lasiopodomys brandtii under chronic hypoxia [10.0% oxygen (O2)] and normoxia (20.9% O2).ResultsA total of 355 million clean reads were obtained, including 69,611 unigenes in L. mandarinus and 69,360 in L. brandtii. A total of 235 and 92 differentially expressed genes (DEGs) were identified by comparing the hypoxic and control groups of L. mandarinus and L. brandtii, respectively. A Gene Ontology (GO) analysis showed that upregulated DEGs in both species had similar functions in response to hypoxia, whereas downregulated DEGs in L. mandarinus were enriched GO terms related to enzymes involved in aerobic reactions. In the Kyoto Encyclopedia of Genes and Genomes pathway analysis, upregulated DEGs in L. mandarinus were associated with angiogenesis and the increased O2 transport capacity of red blood cells, whereas downregulated DEGs were associated with immune responses. On the other hand, upregulated DEGs in L. brandtii were associated with cell survival, vascular endothelial cell proliferation, and neuroprotection, while downregulated genes were related to the synaptic transmission by neurons.ConclusionsL. mandarinus actively adapts its physiological functions to hypoxic conditions, for instance by increasing O2 transport capacity and modulating O2 consumption. In contrast, L. brandtii reacts passively to hypoxia by decreasing overall activity in order to reduce O2 consumption. These results provide insight into hypoxia adaptation mechanisms in subterranean rodents that may be applicable to humans living at high altitudes or operating in other O2-poor environments.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5318-1) contains supplementary material, which is available to authorized users.

As important post-translational modifications, protein cysteine modifications (PCMs) occurring at cysteine thiol group play critical roles in the regulation of various biological processes in eukaryotes. Due to the rapid advancement of high-throughput proteomics technologies, a large number of PCM events have been identified but remain to be curated. Thus, an integrated resource of eukaryotic PCMs will be useful for the research community. In this work, we developed an integrative database for protein cysteine modifications in eukaryotes (iCysMod), which curated and hosted 108 030 PCM events for 85 747 experimentally identified sites on 31 483 proteins from 48 eukaryotes for 8 types of PCMs, including oxidation, S-nitrosylation (-SNO), S-glutathionylation (-SSG), disulfide formation (-SSR), S-sulfhydration (-SSH), S-sulfenylation (-SOH), S-sulfinylation (-SO2H) and S-palmitoylation (-S-palm). Then, browse and search options were provided for accessing the dataset, while various detailed information about the PCM events was well organized for visualization. With human dataset in iCysMod, the sequence features around the cysteine modification sites for each PCM type were analyzed, and the results indicated that various types of PCMs presented distinct sequence recognition preferences. Moreover, different PCMs can crosstalk with each other to synergistically orchestrate specific biological processes, and 37 841 PCM events involved in 119 types of PCM co-occurrences at the same cysteine residues were finally obtained. Taken together, we anticipate that the database of iCysMod would provide a useful resource for eukaryotic PCMs to facilitate related researches, while the online service is freely available at http://icysmod.omicsbio.info.

In particular, the quantum path difference between the long and short trajectories of electron excursion causes the HHG yield to experience interference-based temporal and spectral modulations (He, L.; et al.