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BackgroundPancreatic cancer (PC) is one of the most lethal human cancers, and radiation therapy (RT) is an important treating option. Many patients diagnosed with PC do not achieve objective responses because of the existence of intrinsic and acquired radioresistance. Therefore, biomarkers, which predict radiotherapy benefit in PC, are eagerly needed to be identified.MethodsWhole-exome sequencing of six pancreatic ductal adenocarcinoma patients (PDAC) (three with a good response and three with a poor response) who had received radical surgery and then radiotherapy has been performed as standard of care treatment. Somatic and germline variants and the mutational signatures were analyzed with bioinformatics tools and public databases. Functional enrichment and pathway-based protein-protein interaction analyses were utilized to address the possibly mechanism in radioresistance. MTT, LDH, and colony formation assay were applied to evaluate cell growth and colony formation ability.ResultsIn the present study, somatic mutations located in 441 genes were detected to be radiosensitivity-related loci. Seventeen genes, including the Smad protein family members (SMAD3 and SMAD4), were identified to influence the radiosensitivity in PDAC. The SMAD3 and SMAD4 genes mutate differently between radiosensitive and radioresistant PDAC patients. Mutation of SMAD3 potentiates the effects of ionizing radiation (IR) on cell growth and colony formation in PDAC cells, whereas mutation of SMAD4 had the opposite effects. SMAD3 and SMAD4 regulate the radiosensitivity of PDAC, at least in part, by P21 and FOXO3a, respectively.ConclusionsThese results indicate that mutations of SMAD3 and SMAD4 likely cause the difference of response to radiotherapy in PDAC, which might be considered as the biomarkers and potential targets for the radiotherapy of pancreatic cancer.

Ginger (Zingiber officinale), the type species of Zingiberaceae, is one of the most widespread medicinal plants and spices. Here, we report a high-quality, chromosome-scale reference genome of ginger ‘Zhugen’, a traditionally cultivated ginger in Southwest China used as a fresh vegetable, assembled from PacBio long reads, Illumina short reads, and high-throughput chromosome conformation capture (Hi-C) reads. The ginger genome was phased into two haplotypes, haplotype 1 (1.53 Gb with a contig N50 of 4.68 M) and haplotype 0 (1.51 Gb with a contig N50 of 5.28 M). Homologous ginger chromosomes maintained excellent gene pair collinearity. In 17,226 pairs of allelic genes, 11.9% exhibited differential expression between alleles. Based on the results of ginger genome sequencing, transcriptome analysis, and metabolomic analysis, we proposed a backbone biosynthetic pathway of gingerol analogs, which consists of 12 enzymatic gene families, PAL, C4H, 4CL, CST, C3’H, C3OMT, CCOMT, CSE, PKS, AOR, DHN, and DHT. These analyses also identified the likely transcription factor networks that regulate the synthesis of gingerol analogs. Overall, this study serves as an excellent resource for further research on ginger biology and breeding, lays a foundation for a better understanding of ginger evolution, and presents an intact biosynthetic pathway for species-specific gingerol biosynthesis.

Diabetic cardiomyopathy can cause cardiac dysfunction and eventually lead to heart failure and sudden death. Long noncoding RNA (lncRNA) Gas5 has been reported to play a function in cardiomyocyte. Here we studied the function of Gas5 on newborn mouse cardiomyocyte (NMC) apoptosis to detect its molecular mechanism. High-glucose treatment was implemented to induce the apoptosis of NMC in this study. And terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, JC-1 assay, and flow cytometry analysis were conducted to know about the apoptosis of NMC when Gas5 and Tcf3 were silenced. Meanwhile, RNA pull-down assay and luciferase reporter assay were conducted to verify the binding of RNAs. Finally, rescue assay was implemented to evaluate the influence on apoptosis situation affected by competing endogenous RNA pathways. Tcf3 was found to bind to the Gas5 promoter to activate the expression of Gas5. Meanwhile, Gas5 and Tcf3 were both found to promote the apoptosis of NMC. Also, mmu-miR-320-3p could bind to Gas5 and Tcf3. Moreover, the Gas5/miR-320-3p/Tcf3 pathway was found to modulate the apoptosis of NMC. In conclusion, Tcf3-activated lncRNA Gas5 regulates NMC apoptosis in diabetic cardiomyopathy.

Background Aroma is one of the most important aspects of fruit quality and can reflect the characteristics of different fruits. Aroma-active compounds can usefully be employed to trace the production areas of two citrus cultivars ('Eureka' lemon and 'Huapi' kumquat) and to evaluate their aroma quality. Results 'Huapi' kumquat peel displayed higher monoterpene and sesquiterpene compound content, whereas 'Eureka' lemon peel exhibited higher monoterpene and monoterpene aldehyde compound content. 'Eureka' lemon peel ('Wanzhou' cultivar) had higher nerol acetate and geraniol acetate compound content. Kumquat peel ('Suichuan' and 'Rongan' cultivars) had higher sesquiterpene content. In addition, 30 and 31 aroma-active compounds were observed in kumquat and lemon, respectively, based on their odor activity values. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) results indicated that classification for production areas based on aroma-active compounds was useful. The selected aroma-active compounds have been checked as aroma quality parameters that could be used with multivariate analysis to establish a model of aroma quality evaluation. Higher aroma quality values from kumquat and lemon were collected from Rongan and Wanzhou cultivars, respectively. Conclusion Aroma-active compounds can be used to discriminate production areas using multivariate statistics. An objective method was established to evaluate the aroma quality of citrus fruits. 'Huapi' kumquat and 'Eureka' lemon, which had the highest aroma quality, was harvested from the Rongan and Wanzhou production areas. This was the first time that the aroma quality of citrus fruits was evaluated using multivariate analysis. © 2019 Society of Chemical Industry.

Background and Aims Transport of membranes and proteins in eukaryotic cells is mediated by vesicular carriers. Coatomer complex I (COPI)-coated vesicles are involved in the transport between endoplasmic reticulum (ER) and Golgi complex. Several studies indicated that some subunits of COPI were correlated with the cell proliferation of malignant tumors. The present study focused on the function of coatomer protein complex subunit β 2 (COPB2), one of seven proteins in COPI, in prostate cancer (PCa). Methods COPB2 gene expression was first analyzed by immunohistochemistry (IHC) in 15 paired PCa and carcinoma adjacent normal tissue from patients. To investigate the role of COPB2 in PCa, we used lentivirus-mediated small interfering RNA (siRNA) to knockdown COPB2 expression in human PCa cell line PC-3 and assessed it by RT-qPCR. Cellomics ArrayScan VTI imaging and colony formation were conducted to evaluate cell proliferation. Cell cycle phase arrest and apoptosis were assayed by flow cytometry. Results COPB2 gene was upregulated in the PCa tissue. Cell proliferation was significantly inhibited in COPB2-silenced PC-3 cells using both Cellomics ArrayScan VTI imaging and colony formation assays. S-phase cell counts were significantly decreased; G1- and G2-phase cell counts were significantly increased in COPB2-siRNA group than the control group. Apoptosis was significantly increased in COPB2-siRNA cells. Conclusions COPB2 significantly promoted PC-3 cell proliferation and colony formation through the cell cycle and apoptosis pathway. Moreover, COPB2 showed a clinical correlation and may serve as a biomarker for the detection for PCa.

Integrated management, utilizing different non-chemical methods, is an approach to controlling postharvest losses that is being actively investigated. In the present study, the use of an antagonistic yeast, Candida diversa, combined with harpin (a hypersensitive response elicitor) treatment was evaluated for their ability to prevent infection of kiwifruit after they were artificially inoculated with Botrytis cinerea or Penicillium expansum. Natural infection of treated fruit was also assessed. As a standalone treatment, C. diversa or harpin significantly reduced gray (B. cinerea) and blue mold (P. expansum) infections on kiwifruit, relative to the untreated control fruit, and also reduced the level of natural infection. The combination of C. diversa and harpin treatment, however, provided a superior level of control on fruit, relative to either treatment alone. Harpin did not negatively impact C. diversa growth in kiwifruit wounds. Treatment of kiwifruit with C. diversa and harpin alone or in combination also induced the activity of enzymes involved in defense response, such as polyphenol oxidase, peroxidase and superoxide dismutase. Harpin alone or in combination with C. diversa enhanced accumulation of lignin content in kiwifruit as well. The mode of action by which harpin enhanced biocontrol efficacy of C. diversa may be partially attributed to the elicitation of defense response in kiwifruit. Integrating the use of antagonistic yeast with harpin treatment has potential as an effective method for the control of postharvest decay in kiwifruit.

The aim of the present study was to investigate the therapeutic effects of water-soluble extracts of Banxiaxiexin decoction, a classical traditional Chinese medicine formulation, on BALB/c mice with experimentally induced ulcerative colitis (UC). Water-soluble extracts of Banxiaxiexin decoction were intragastrically administered to BALB/c mice with oxazolone (OXA)-induced colitis. Sulfasalazine (SASP) was administered intragastrically to OXA-treated mice to establish the SASP group (positive control). Following drug administration, the disease activity index (DAI) and the histopathological inflammation score were recorded. In addition, the expression levels of interleukin (IL)-5 and IL-13 mRNA in the colonic tissue were determined by fluorescent quantitative polymerase chain reaction. The DAI and histopathological inflammation score of the model group were significantly greater compared with those of the control group, and the mRNA expression levels of IL-5 and IL-13 in the colonic tissue were also significantly higher in the model group compared with those in the control group. The intragastric administration of water-soluble extracts of Banxiaxiexin decoction significantly lowered the DAI and histopathological inflammation score. The mRNA expression levels of IL-5 and IL-13 in the colonic tissue were also significantly lowered. The therapeutic effect of Banxiaxiexin decoction was found to be comparable to that of SASP. In conclusion, the results from the present study demonstrate that water-soluble extracts of the traditional Chinese medicine formulation Banxiaxiexin decoction have a therapeutic effect on BALB/c mice with OXA-induced colitis.

The ability of chitosan and oligochitosan to enhance ginger (Zingiber officinale) resistance to rhizome rot caused by Fusarium oxysporum in storage was investigated. Both chitosan and oligochitosan at 1 and 5g/L significantly inhibited rhizome rot, with the best control at 5g/L. Chitosan and oligochitosan applied at 5g/L also reduced weight loss, measured as a decrease in fresh weight, but did not affect soluble solids content or titratable acidity of rhizomes. The two compounds applied at 5g/L induced β-1,3-glucanase and phenylalanine ammonia-lyase enzyme activity and the transcript levels of their coding genes, as well as the total phenolic compounds in rhizome tissues. Therefore, the ability of chitosan and oligochitosan to reduce rot in stored rhizomes may be associated with their ability to induce defense responses in ginger. These results have practical implications for the application of chitosan and oligochitosan to harvested ginger rhizomes to reduce postharvest losses.

Chlorogenic acid (CGA), abundant in coffee and particular fruits, can modulate hypertension and vascular dysfunction. Hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) proliferation has been tightly linked to vascular remodeling in pulmonary arterial hypertension (PAH). Thus, the present study was designed to investigate the effect of CGA on hypoxia-induced proliferation in cultured rat PASMCs. The data showed that CGA potently inhibited PASMCs proliferation and DNA synthesis induced by hypoxia. These inhibitory effects were associated with G1 cell cycle arrest and down-regulation of cell cycle proteins. Treatment with CGA reduced hypoxia-induced hypoxia inducible factor 1α (HIF-1α) expression and trans-activation. Furthermore, hypoxia-evoked c-Src phosphorylation was inhibited by CGA. In vitro ELISA-based tyrosine kinase assay indicated that CGA was a direct inhibitor of c-Src. Moreover, CGA attenuated physical co-association of c-Src/Shc/Grb2 and ERK2 phosphorylation in PASMCs. These results suggest that CGA inhibits hypoxia-induced proliferation in PASMCs via regulating c-Src-mediated signaling pathway. In vivo investigation showed that chronic CGA treatment inhibits monocrotaline-induced PAH in rats. These findings presented here highlight the possible therapeutic use of CGA in hypoxia-related PAH.

We studied the effects of high concentration of chromium (Cr) stress on physiological and biochemical characters and accumulation of Cr in Pingyang Tezao tea [Camellia sinensis (L) O. Kutze 'Pingyangtezao'] through a pot experiment. The results show that the indicators of photosynthesis were all suppressed with increasing Cr stress, and antioxidation and protection systems were destroyed. We also discovered that the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) decreased, while the content of proline (Pro) and malondialdehyde (MDA) and relative conductivities increased. The accumulating Cr in all organs had a positive correlation with Cr concentration. Deposition of Cr in organs was in the following order: stubble > root > leave > stem > branch ≈ new stem (a bud and two leaves). We conclude that high concentration of Cr stress had strong inhibition and damage to the normal metabolism and cell implement structure, as well as on the function of tea plant.

CLPTM1L is believed to be associated with lung cancer. However, there is little information regarding its expression and function. Here using immunohistochemistry, we found that CLPTM1L expression was markedly increased in lung cancer tissues relative to normal tissues, especially in lung adenocarcinoma. CLPTM1L expression was not found to be associated with stages, smoking status, lymph node metastasis, or T lymphocyte infiltration but with differentiation stage. We found CLPTM1L to be enriched in the mitochondrial compared with plasma membrane protein extracts. CLPTM1L-EGFP transfection showed that the molecule product was expressed in cytoplasm and indicated the mitochondrial localization stained with mitochondrial marker MitoTracker. CLPTM1L transferred lung cancer cell line 95-D showed no growth inhibition or cell apoptosis, but it did show inhibited sensitivity to cis-diamminedichloroplatinum(II) (cisplatin, CDDP). Knockdown of CLPTM1L by RNAi did not interfere with cell proliferation but it did increase cell sensitivity to CDDP and activation of caspase-9 and caspase-3/7. These data indicate CLPTM1L is a mitochondria protein and that it may be associated with anti-apoptotic mechanism which affects drug-resistance in turn.