The intratumor mycobiome promotes lung cancer progression via myeloid-derived suppressor cells.

Although polymorphic microbiomes have emerged as hallmarks of cancer, far less is known about the role of the intratumor mycobiome as living microorganisms in cancer progression. Here, using fungi-enriched DNA extraction and deep shotgun metagenomic sequencing, we have identified enriched tumor-resident Aspergillus sydowii in patients with lung adenocarcinoma (LUAD). By three different syngeneic lung cancer mice models, we find that A. sydowii promotes lung tumor progression via IL-1ß-mediated expansion and activation of MDSCs, resulting in suppressed activity of cytotoxic T lymphocyte cells and accumulation of PD-1+ CD8+ T cells. This is mediated by IL-1ß secretion via ß-glucan/Dectin-1/CARD9 pathway. Analysis of human samples confirms that enriched A. sydowii is associated with immunosuppression and poor patient outcome. Our findings suggest that intratumor mycobiome, albeit at low biomass, promotes lung cancer progression and could be targeted at the strain level to improve patients with LUAD outcome.

[Characterization of Tailpipe Emissions from in-use Excavators].

In this paper, the objective is to characterize real-world tailpipe emissions for excavators. Eight excavators in several construction sites in Chengdu were selected in this study. A portable emission measurement system (PEMS) was used for real-world emissions measurements (i. e., CO, HC, NO, and PM2.5) for three predefined operation modes:idling, moving, and working. The results showed that the tailpipe emissions of excavators vary depending on the operation mode as well as the equipment. NO emissions were relatively stable when the engine was idling compared to when the excavator was moving or doing actual work. In addition, excavators that complied to different emissions standards also exhibited different emissions, with those that met higher emission standards producing fewer emissions. For example, when comparing excavators complying with Stage Ⅱ emission standards to those complying with Stage Ⅰ emission standards, the NO and PM2.5 emissions appeared to decrease. On average, the NO emissions decreased by 8%, 35%, and 5%, and the PM2.5 emissions decreased by 88%, 87%, and 80% for the idling, moving, and working modes, respectively. Furthermore, the studies showed significant differences existed between the emissions factors in the real-world measurements and those recommended by national guidance. This indicated that real-world emission measurements of non-road equipment will play a key role in emissions inventory development. This study demonstrated that PEMS can be used to characterize real-world emissions from non-road equipment.

[The design of muti-target antitumor drugs affecting on FTase and Raf-1 kinase].

Ras/Raf/MEK/ERK singal transduction plays an important role in cell proliferation, differentiation, apoptosis, metastasis and metabolism. This investigation focused on this signal pathway and chose farnesyl transferase (FTase) as the main target and Raf-1 kinase as the second target. A lot of compounds were selected to construct the pharmacophore models of farnesyl transferase inhibitors (FTIs) and Raf-1 kinase inhibitors by using computer-aided drug design (CADD). The pharmacophore of FTIs is constituted by a hydrogen bonding acceptor, an aromatic ring, a positive ionizable and two hydrophobic regions; the pharmacophore of Raf-1 kinase is constituted by a hydrogen donor, a hydrogen acceptor, a hydrophobic regions and an aromatic ring. There are some similarities between the two pharmacophores. After analysis of the constructions of these two pharmacophores, some new aminomethylbenzoic acid derivatives with good forecasting activity against both of FTase and Raf-1 kinase were designed with these new pharmacophore models.

[Progress in the study of antitumor drug targeting on the Ras signaling pathway].

Ras signaling pathway is closely related to the formation and growth of tumor. Currently, targeting on this signaling pathway is a hot research point for the design and development of anticancer drugs. In this paper, Ras protein as well as its related targets and inhibitors in signaling pathway were reviewed. It is expected to give research-related reference materials for the design of new anticancer drugs.

Design, synthesis, and cytoprotective effect of 2-aminothiazole analogues as potent poly(ADP-ribose) polymerase-1 inhibitors.

A series of novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors were designed within 2-aminothiazole analogues (4-10) based on a constructed three-dimensional pharmacophore model. After synthesis, the inhibitory effect on PARP-1 activity and the cytoprotective action of these compounds were tested and evaluated. Among them, compounds 4-6 and 10 appeared to be potent PARP-1 inhibitors with IC(50) values less than 1 microM, which had been perfectly predicted by pharmacophore model. These compounds proved to be highly potent against cell injury induced by H(2)O(2) and oxygen-glucose deprivation (OGD) in PC12 cells. These novel 2-aminothiazole analogues are potentially applicable as neuroprotective agents for the treatment of neurological diseases.