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We stratified pancreatic ductal adenocarcinoma (PDAC) based on the tumorigenic properties of cancer cells, and aimed to identify clinically useful immunohistochemical (IHC) markers with mechanistic insights. The tumorigenic properties of PDACs were determined using patient-derived xenograft in NOD/SCID/IL2Rγnull mice. The success of tumor engraftment was significantly correlated to poor survival, and its predictive values were superior to clinicopathological parameters. To search IHC-based biomarkers as surrogate for high tumorigenicity with prognostic values, 11 candidates of potentially clinical useful prognostic markers were selected. Among them, 5hmC content of the cancer cells was validated. Elevated 5hmC content positively correlated with in vivo tumorigenicity and poor prognosis in both primary and validation cohorts. Enrichment of cancer-associated 5hmC in CDX2 and FOXA1 lineage-specific transcriptional factor genes further pointed out the potential role of 5hmC in modulating cellular differentiation to enhance tumor malignancy during PDAC progression. Tumor-associated 5hmC content defined a subpopulation of PDAC with high lineage plasticity and tumorigenic potential, and was a prognostic IHC marker that provided a clinical basis for future management of PDAC.

Glow discharge ionization source can be used to analyze solid sample, liquid sample and gas sample. At present, glow discharge optical emission spectrometer (GD-OES) and glow discharge mass spectrometer (GD-MS) are mainly used to the elemental analysis of inorganic solid samples and quantitative depth profile analysis, including direct current (DC) power supply and radio frequency (RF) power supply. In this paper, the ionization of liquid sample and gas sample by low frequency radio frequency glow discharge (Lf-RFGD) was researched, and the glow discharge structure constructed was connected to timeof flight mass spectrometer(TOF MS). The influences of the vacuum degree of ionization chamber, the size of sample inlet capillary, the auxiliary gas pressure, the discharge radio frequency and the voltage difference between electrode plates on the ionization efficiency were studied. The optimal analysis conditions are the vacuum degree of ionization chamber is about 30 Pa, the length of sample inlet capillary is 150 mm and the inner diameter is 0.25 mm, the auxiliary gas pressure is about1.0 MPa, the low discharge frequency is 2 MHz, the voltage difference between electrode plates is about 100 V. Under these conditions, the discharge power is about 20 W,the detection limit of liquid sample is 0.1 pg and volatile sample is 20 mg/m3, and the detection resolution (full width at half maximum, FWHM) is about 3 000. Combined with samples testing, the Lf-RFGD TOF MS was preliminarily applied to the drug solution and volatile organic compounds (VOCs). However, the sensitivity of this instrument for detecting non volatile liquid sample was not good compared with the conventional detection instrument. The reason is that high proton affinity and low ionization potential are needed to obtain good detection sensitivity in the positive ion mode of mass spectrometer, and non volatile liquid sample without pretreatment is not easy to meet the condition of high proton affinity under low power glow discharge condition. Successfully, a lowcost, portable approach based on the application of atmospheric sampling Lf-RFGD TOF MS has been developed for near real time measurement of trace VOCs. In this context, the glow discharge excitation source offers attractive alternative for development of low cost VOCs and elemental analysis instrument. Lf-RFGD as an excitation source has unique advantages with respect to development of hand held instrument such as low cost, low power consumption, and analytical versatility.

Lymph node (LN) metastasis is commonly associated with systemic distant organ metastasis in human breast cancer and is an important prognostic predictor for survival of breast cancer patients. However, whether tumor-draining LNs (TDLNs) play a significant role in modulating the malignancy of cancer cells for distant metastasis remains controversial. Using a syngeneic mouse mammary tumor model, we found that breast tumor cells derived from TDLN have higher malignancy and removal of TDLNs significantly reduced distant metastasis. Up-regulation of oncogenic Il-17rb in cancer cells derived from TDLNs contributes to their malignancy. TGF-β1 secreted from regulatory T cells (Tregs) in the TDLNs mediated the up-regulation of Il-17rb through downstream Smad2/3/4 signaling. These phenotypes can be abolished by TGF-β1 neutralization or depletion of Tregs. Consistently, clinical data showed that the up-regulation of IL-17RB in cancer cells from LN metastases correlated with the increased prevalence of Tregs as well as the aggressive growth of tumors in mouse xenograft assay. Together, these results indicate that Tregs in TDLNs play an important role in modulating the malignancy of breast cancer cells for distant metastasis. Blocking IL-17RB expression could therefore be a potential approach to curb the process.

Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated fibroblasts. Here we find, through systematic screening, that primary mammary gland-derived adipocytes (MGDAs) promote growth of breast cancer cells that express monocarboxylate transporter 2 (MCT2) both in vitro and in vivo. We show that β-hydroxybutyrate is secreted by MGDAs and is required to enhance breast cancer cells malignancy in vitro. Consistently, β-hydroxybutyrate is sufficient to promote tumorigenesis of a mouse xenograft model of MCT2-expressing breast cancer cells. Mechanistically we observe that upon co-culturing with MGDAs or treatment with β-hydroxybutyrate, breast cancer cells expressing MCT2 increase the global histone H3K9 acetylation and upregulate several tumour-promoting genes. These results suggest that adipocytes promote malignancy of MCT2-expressing breast cancer via β-hydroxybutyrate potentially by inducing the epigenetic upregulation of tumour-promoting genes.

Objective: In order to resolve a lot of redundant information and low precision of apple internal quality evaluation existed in apple near infrared spectroscopy, improving the precision of apple internal quality evaluation. Methods: A new apple inner quality evaluation model based on deep belief network （DBN） and grey wolf optimization algorithm was proposed. According to the characteristic of high dimension and complexity of apple spectral data, the method of selecting characteristic wavelengths of apple spectral data was determined by comparing the results of selecting characteristic wavelengths of full-band, principal component analysis and continuous projection. The parameters of DBN model were optimized by GWO Algorithm, and a continuous projection method for feature wavelength selection and GWO-DBN model for apple inner quality evaluation were proposed. Results: Compared with PSO-DBN, GA-DBN and DBN, the accuracy of apple inner quality evaluation based on GWO-DBN was the highest. Conclusion: This algorithm can effectively improve the accuracy of apple inner quality evaluation and provide a new method for apple inner quality evaluation.