SUMMARY Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole exome sequencing and DNA copy number analyses, and 196 HCC also by DNA methylation, RNA, miRNA, and proteomic expression. DNA sequencing and mutation analysis identified significantly mutated genes including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or down-regulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed. Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts. Integrated analyses enabled development of a p53 target gene expression signature correlating with poor survival. Potential therapeutic targets for which inhibitors exist include WNT signaling, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.

Selective catalytic reduction with NH 3 (NH 3 −SCR) is the most efficient technology to reduce the emission of nitrogen oxides (NO x ) from coal-fired industries, diesel engines, etc. Although V 2 O 5 −WO 3 (MoO 3 )/TiO 2 and CHA structured zeolite catalysts have been utilized in commercial applications, the increasing requirements for broad working temperature window, strong SO 2 /alkali/heavy metal-resistance, and high hydrothermal stability have stimulated the development of new-type NH 3 −SCR catalysts. This review summarizes the latest SCR reaction mechanisms and emerging poisonresistant mechanisms in the beginning and subsequently gives a comprehensive overview of newly developed SCR catalysts, including metal oxide catalysts ranging from VO x , MnO x , CeO 2 , and Fe 2 O 3 to CuO based catalysts; acidic compound catalysts containing vanadate, phosphate and sulfate catalysts; ion exchanged zeolite catalysts such as Fe, Cu, Mn, etc. exchanged zeolite catalysts; monolith catalysts including extruded, washcoated, and metal-mesh/foam-based monolith catalysts. The challenges and opportunities for each type of catalysts are proposed while the effective strategies are summarized for enhancing the acidity/redox circle and poison-resistance through modification, creating novel nanostructures, exposing specific crystalline planes, constructing protective/sacrificial sites, etc. Some suggestions are given about future research directions that efforts should be made in. Hopefully, this review can bridge the gap between newly developed catalysts and practical requirements to realize their commercial applications in the near future.

SUMMARY Mucus production by goblet cells of the large intestine serves as a crucial anti microbial protective mechanism at the interface between the eukaryotic and prokaryotic cells of the mammalian intestinal ecosystem. However, the regulatory pathways involved in goblet cell-induced mucus secretion remain largely unknown. Here we demonstrate that the NLRP6 inflammasome, a recently described regulator of colonic microbiota composition and bio-geographical distribution, is a critical orchestrator of goblet cell mucin granule exocytosis. NLRP6 deficiency leads to defective autophagy in goblet cells and abrogated mucin secretion into the large intestinal lumen. Consequently, NLRP6 inflammasome-deficient mice are unable to clear enteric pathogens from the mucosal surface, rendering them highly susceptible to persistent infection. This study identifies the first innate immune regulatory pathway governing goblet cell mucus secretion, linking non-hematopoietic inflammasome signaling to autophagy and highlighting the goblet cell as a critical innate immune player in the control of intestinal host-microbial mutualism.

Significance Analysis of INTeractome (SAINT) is a statistical method for probabilistically scoring protein-protein interaction data from affinity purification-mass spectrometry (AP-MS) experiments. The utility of the software has been demonstrated in many protein-protein interaction mapping studies, yet the extensive testing also revealed some practical drawbacks. In this paper, we present a new implementation, SAINTexpress, with a simpler statistical model and a quicker scoring algorithm, leading to significant improvements in computational speed and sensitivity of scoring. SAINTexpress also incorporates external interaction data to compute a supplemental topology-based score to improve the likelihood of identifying co-purifying protein complexes in a probabilistically objective manner. Overall, these changes are expected to improve the performance and user experience of SAINT across various types of high quality datasets.

We presented a case of a 30-week pregnant woman with COVID-19 delivering a healthy baby with no evidence of COVID-19.

Over-expression of B7-H1 (PD-L1) molecule in the tumor microenvironment (TME) is a major immune evasion mechanism in some cancer patients and antibody blockade of the B7-H1/PD-1 interaction can normalize compromised immunity without excessive side-effects. Using a genomescale T-cell activity array, we identified Siglec-15 as a critical immune suppressor. While only expressed on some myeloid cells normally, Siglec-15 is broadly upregulated on human cancer cells and tumor-infiltrating myeloid cells, and its expression is mutually exclusive to B7-H1, partially due to its induction by M-CSF and downregulation by IFN-γ. We demonstrate that Siglec-15 suppresses antigen-specific T-cell responses in vitro and in vivo. Genetic ablation or antibody blockade of Siglec-15 amplifies anti-tumor immunity in the TME and inhibits tumor Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

The origin of millet from Neolithic China has generally been accepted, but it remains unknown whether common millet (Panicum miliaceum) or foxtail millet (Setaria italica) was the first species domesticated. Nor do we know the timing of their domestication and their routes of dispersal. Here, we report the discovery of husk phytoliths and biomolecular components identifiable solely as common millet from newly excavated storage pits at the Neolithic Cishan site, China, dated to between ca. 10,300 and ca. 8,700 calibrated years before present (cal yr BP). After ca. 8,700 cal yr BP, the grain crops began to contain a small quantity of foxtail millet. Our research reveals that the common millet was the earliest dry farming crop in East Asia, which is probably attributed to its excellent resistance to drought.Holocene ͉ origins of agriculture ͉ phytoliths ͉ Neolithic ͉ Cishan F oxtail millet (Setaria italica) and common millet (or broomcorn millet; Panicum miliaceum) were among the world's most important and ancient domesticated crops. They were staple foods in the semiarid regions of East

BackgroundPrecise genome editing via homology-directed repair (HDR) after double-stranded DNA (dsDNA) cleavage facilitates functional genomic research and holds promise for gene therapy. However, HDR efficiency remains low in some cell types, including some of great research and clinical interest, such as human induced pluripotent stem cells (iPSCs).ResultsHere, we show that a double cut HDR donor, which is flanked by single guide RNA (sgRNA)-PAM sequences and is released after CRISPR/Cas9 cleavage, increases HDR efficiency by twofold to fivefold relative to circular plasmid donors at one genomic locus in 293 T cells and two distinct genomic loci in iPSCs. We find that a 600 bp homology in both arms leads to high-level genome knockin, with 97–100% of the donor insertion events being mediated by HDR. The combined use of CCND1, a cyclin that functions in G1/S transition, and nocodazole, a G2/M phase synchronizer, doubles HDR efficiency to up to 30% in iPSCs.ConclusionsTaken together, these findings provide guidance for the design of HDR donor vectors and the selection of HDR-enhancing factors for applications in genome research and precision medicine.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1164-8) contains supplementary material, which is available to authorized users.