Selective Labeling and Identification of the Tumor Cell Proteome of Pancreatic Cancer In Vivo

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers. Dissecting the tumor cell proteome from that of the non-tumor cells in the PDAC tumor bulk is critical for tumorigenesis studies, biomarker discovery, and development of therapeutics. However, investigating the tumor cell proteome has proven evasive due to the tumor’s extremely complex cellular composition. To circumvent this technical barrier, we have combined bioorthogonal noncanonical amino acid tagging (BONCAT) and data-independent acquisition mass spectrometry (DIA-MS) in an orthotopic PDAC model to specifically identify the tumor cell proteome in vivo. Utilizing the tumor cell-specific expression of a mutant tRNA synthetase transgene, this approach provides tumor cells with the exclusive ability to incorporate an azide-bearing methionine analogue into newly synthesized proteins. The azide-tagged tumor cell proteome is subsequently enriched and purified via a bioorthogonal reaction and then identified and quantified using DIA-MS. Applying this workflow to the orthotopic PDAC model, we have identified thousands of proteins expressed by the tumor cells. Furthermore, by comparing the tumor cell and tumor bulk proteomes, we showed that the approach can distinctly differentiate proteins produced by tumor cells from those of non-tumor cells within the tumor microenvironment. Our study, for the first time, reveals the tumor cell proteome of PDAC under physiological conditions, providing broad applications for tumorigenesis, therapeutics, and biomarker studies in various human cancers

Use of a leaf chlorophyll content index to improve the prediction of above-ground biomass and productivity

Improving the accuracy of predicting plant productivity is a key element in planning nutrient management strategies to ensure a balance between nutrient supply and demand under climate change. A calculation based on intercepted photosynthetically active radiation is an effective and relatively reliable way to determine the climate impact on a crop above-ground biomass (AGB). This research shows that using variations in a chlorophyll content index (CCI) in a mathematical function could effectively obtain good statistical diagnostic results between simulated and observed crop biomass. In this study, the leaf CCI, which is used as a biochemical photosynthetic component and calibration parameter, increased simulation accuracy across the growing stages during 2016–2017. This calculation improves the accuracy of prediction and modelling of crops under specific agroecosystems, and it may also improve projections of AGB for a variety of other crops

Metabolites changes of a low-temperature and low-salt fermented Chinese kohlrabi during fermentation based on non-targeted metabolomic analysis

A low-temperature and low-salt industrially fermented Chinese kohlrabi (LSCK) was developed in this study, with the salt usage decreased by approximately 70% compared to the traditional high-salt fermented Chinese kohlrabi (HSCK). The differences in physicochemical properties, metabolites and overall flavors during LSCK fermented for 0, 45 and 90 days (d) were analyzed by gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS), electronic nose (E-nose) and other techniques. The results showed that the total acid content increased significantly from 3.68 to 8.59 g/kg. However, the protein content significantly decreased from 2.52/100 to 0.66 g/100 g. The number of lactic acid bacteria cells increased significantly from 3.69 to 4.46 log10CFU/g. Based on multivariate statistical analysis, 21, 14, and 15 differential metabolites were identified in the three treatment groups A1 (0 and 45 days), A2 (45 and 90 days), and A3 (0 and 90 days) respectively (VIP > 1, p < 0.05, |log2FC| ≥ 1.1). Carbohydrates, sugar alcohols, amino acids and their derivatives were the main differential metabolites in the LSCKs fermented for different periods. Aminoacyl−tRNA biosynthesis and glycine, serine and threonine metabolism pathways significantly correlated with the differential metabolites based on Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis (p < 0.05). Furthermore, the overall odors were significantly different among the LSCKs with different fermentation periods, as detected by E-nose. The present study describes the change trend of metabolites during LSCK fermentation and elucidates important metabolic pathways in LSCK, providing a theoretical basis for the target regulation of functional metabolites in kohlrabi and the optimization of LSCK processing

Observation of topological electronic structure in quasi-1D superconductor TaSe3

Topological superconductors (TSCs), with the capability to host Majorana bound states that can lead to non-Abelian statistics and application in quantum computation, have been one of the most intensively studied topics in condensed matter physics recently. Up to date, only a few compounds have been proposed as candidates of intrinsic TSCs, such as doped topological insulator CuxBi2Se3 and iron-based superconductor FeTe0.55Se0.45. Here, by carrying out synchrotron and laser based angle-resolved photoemission spectroscopy (ARPES), we systematically investigated the electronic structure of a quasi-1D superconductor TaSe3, and identified the nontrivial topological surface states. In addition, our scanning tunneling microscopy (STM) study revealed a clean cleaved surface with a persistent superconducting gap, proving it suitable for further investigation of potential Majorana modes. These results prove TaSe3 as a stoichiometric TSC candidate that is stable and exfoliable, therefore a great platform for the study of rich novel phenomena and application potentials.Comment: to appear in Matte

Associations between plasma metal mixture exposure and risk of hypertension: A cross-sectional study among adults in Shenzhen, China

BackgroundMetal exposure affects human health. Current studies mainly focus on the individual health effect of metal exposure on hypertension (HTN), and the results remain controversial. Moreover, the studies assessing overall effect of metal mixtures on hypertension risk are limited.MethodsA cross-sectional study was conducted by recruiting 1,546 Chinese adults who attended routine medical check-ups at the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen. The plasma levels of 13 metals were measured using inductively coupled plasma mass spectrometry. Multivariate logistic regression model, restricted cubic spline (RCS) model and the Bayesian Kernel Machine Regression (BKMR) model were applied to explore the single and combined effect of metals on the risk of HTN.ResultsA total of 642 (41.5%) participants were diagnosed with HTN. In the logistic regression model, the adjusted odds ratios (ORs) were 0.71 (0.52, 0.97) for cobalt, 1.40 (1.04, 1.89) for calcium, 0.66 (0.48, 0.90), and 0.60 (0.43, 0.83) for aluminum in the second and third quartile, respectively. The RCS analysis showed a V-shaped or an inverse V-shaped dose-response relationship between metals (aluminum or calcium, respectively) and the risk of HTN (P for non-linearity was 0.017 or 0.009, respectively). However, no combined effect was found between metal mixture and the risk of hypertension.ConclusionsPlasma levels of cobalt, aluminum and calcium were found to be associated with the risk of HTN. Further studies are needed to confirm our findings and their potential mechanisms with prospective studies and experimental study designs

The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Qualitative and quantitative changes in human mitochondrial DNA (mtDNA) have been implicated in various cancer types. A 4,977 bp deletion in the major arch of the mitochondrial genome is one of the most common mutations associated with a variety of human diseases and aging.</p> <p>Methods</p> <p>We conducted a comprehensive study on clinical features and mtDNA of 104 colorectal cancer patients in the Wenzhou area of China. In particular, using a quantitative real time PCR method, we analyzed the 4,977 bp deletion and mtDNA content in tumor tissues and paired non-tumor areas from these patients.</p> <p>Results</p> <p>We found that the 4,977 bp deletion was more likely to be present in patients of younger age (≤65 years, p = 0.027). In patients with the 4,977 bp deletion, the deletion level decreased as the cancer stage advanced (p = 0.031). Moreover, mtDNA copy number in tumor tissues of patients with this deletion increased, both compared with that in adjacent non-tumor tissues and with in tumors of patients without the deletion. Such mtDNA content increase correlated with the levels of the 4,977 bp deletion and with cancer stage (p < 0.001).</p> <p>Conclusions</p> <p>Our study indicates that the mtDNA 4,977 bp deletion may play a role in the early stage of colorectal cancer, and it is also implicated in alteration of mtDNA content in cancer cells.</p

The Local Origin of the Tibetan Pig and Additional Insights into the Origin of Asian Pigs

BACKGROUND: The domestic pig currently indigenous to the Tibetan highlands is supposed to have been introduced during a continuous period of colonization by the ancestors of modern Tibetans. However, there is no direct genetic evidence of either the local origin or exotic migration of the Tibetan pig. METHODS AND FINDINGS: We analyzed mtDNA hypervariable segment I (HVI) variation of 218 individuals from seven Tibetan pig populations and 1,737 reported mtDNA sequences from domestic pigs and wild boars across Asia. The Bayesian consensus tree revealed a main haplogroup M and twelve minor haplogroups, which suggested a large number of small scale in situ domestication episodes. In particular, haplogroups D1 and D6 represented two highly divergent lineages in the Tibetan highlands and Island Southeastern Asia, respectively. Network analysis of haplogroup M further revealed one main subhaplogroup M1 and two minor subhaplogroups M2 and M3. Intriguingly, M2 was mainly distributed in Southeastern Asia, suggesting for a local origin. Similar with haplogroup D6, M3 was mainly restricted in Island Southeastern Asia. This pattern suggested that Island Southeastern Asia, but not Southeastern Asia, might be the center of domestication of the so-called Pacific clade (M3 and D6 here) described in previous studies. Diversity gradient analysis of major subhaplogroup M1 suggested three local origins in Southeastern Asia, the middle and downstream regions of the Yangtze River, and the Tibetan highlands, respectively. CONCLUSIONS: We identified two new origin centers for domestic pigs in the Tibetan highlands and in the Island Southeastern Asian region

GC-TOF-MS-Based Non-Targeted Metabolomic Analysis of Differential Metabolites in Chinese Ultra-Long-Term Industrially Fermented Kohlrabi and Their Associated Metabolic Pathways

Fermented kohlrabi is a very popular side dish in China. Chinese kohlrabies industrially fermented for 0 years (0Y), 5 years (5Y), and 10 years (10Y) were employed and analyzed by non-targeted metabolomics based on GC-TOF-MS, and the differential metabolites were screened using multivariate statistical analysis techniques, including principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA). The results showed that 47, 38, and 33 differential metabolites were identified in the three treatment groups of 0Y and 5Y (A1), 0Y and 10Y (A2), and 5Y and 10Y (A3), respectively (VIP > 1, p γ-aminobutyric acid, and other compounds. Four metabolic pathways termed alanine, aspartate, and glutamate metabolism, arginine biosynthesis, arginine and proline metabolism, and glycolysis/gluconeogenesis were the most significant pathways correlated with the differential metabolites, as analyzed according to the Kyoto Encyclopedia of Genes and Genomes (KEGG). The odors for the three ultra-long-term industrially fermented kohlrabies were significantly different, as detected by E-nose. The present work describes the changes in metabolites between different ultra-long-term industrially fermented kohlrabies and the associated metabolic pathways, providing a theoretical basis for the targeted regulation of characteristic metabolite biosynthesis in Chinese fermented kohlrabi

A new lightweight design method integrating shape optimization with life cycle assessment for extrusion dies

Extrusion dies, in which melted raw materials are forced continuously into a profile to produce various plastic products, are often empirically designed leading to overweight and waste in materials, energy and emissions. Lightweight design method has been applied to reduce weight and increase material efficiency of extrusion dies at design stage. However, the research work was often focused on weight reduction with function requirements as the design constricts. Environmental impacts (EIs) over the entire life cycle of dies are not considered, as a result, it may result in environmental burdens being shifted from design stage to other stages of life cycle of products. Aiming at it, a new lightweight design method is proposed to integrate life cycle assessment (LCA) with shape optimization. The optimization mathematic models for the proposed method are developed, in which the EIs of extrusion dies are modeled as a function of shape variables and processing parameters. An example of extrusion dies for plastic pipe was presented to illustrate the effectiveness of the proposed method. The results showed that 13% weight reduction whist achieving reduction in EIs over the life cycle of dies in comparison with 18% weight reduction yet 29% increase in EIs at manufacturing stage and resultant increase in EIs over the life cycle using conventional lightweight design method in which EIs are not taken into account. It indicated that the proposed lightweight method could have great potentials to reduce weight and prevent environmental burdens shift problem