Untargeted LC–MS/MS-Based Metabolomic Profiling for the Edible and Medicinal Plant Salvia miltiorrhiza Under Different Levels of Cadmium Stress

Salvia miltiorrhiza, a medicinal and edible plant, has been extensively applied to treat cardiovascular diseases and chronic hepatitis. Cadmium (Cd) affects the quality of S. miltiorrhiza, posing serious threats to human health. To reveal the metabolic mechanisms of S. miltiorrhiza's resistance to Cd stress, metabolite changes in S. miltiorrhiza roots treated with 0 (CK), 25 (T1), 50 (T2) and 100 (T3) mg kg−1 Cd by liquid chromatography coupled to mass spectrometry (LC–MS/MS) were investigated. A total of 305 metabolites were identified, and most of them were amino acids, organic acids and fatty acids, which contributed to the discrimination of CK from the Cd-treated groups. Among them, S. miltiorrhiza mainly upregulated o-tyrosine, chorismate and eudesmic acid in resistance to 25 mg kg−1 Cd; DL-tryptophan, L-aspartic acid, L-proline and chorismite in resistance to 50 mg kg−1 Cd; and L-proline, L-serine, L-histidine, eudesmic acid, and rosmarinic acid in resistance to 100 mg kg−1 Cd. It mainly downregulated unsaturated fatty acids (e.g., oleic acid, linoleic acid) in resistance to 25, 50, and 100 mg kg−1 Cd and upregulated saturated fatty acids (especially stearic acid) in resistance to 100 mg kg−1 Cd. Biosynthesis of unsaturated fatty acids, isoquinoline alkaloid, betalain, aminoacyl-tRNA, and tyrosine metabolism were the significantly enriched metabolic pathways and the most important pathways involved in the Cd resistance of S. miltiorrhiza. These data elucidated the crucial metabolic mechanisms involved in S. miltiorrhiza Cd resistance and the crucial metabolites that could be used to improve resistance to Cd stress in medicinal plant breeding

Silencing SOCS3 Markedly Deteriorates Spondyloarthritis in Mice Induced by Minicircle DNA Expressing IL23

Objective: Despite extensive studies, the precise mechanism underlying spondyloarthritis, especially ankylosing spondylitis, remains elusive. This study aimed to develop an ideal animal model for an insight into mechanism of spondyloarthritis and functional relevance of SOCS3 in spondyloarthritis.Methods: Since SOCS3 is a major regulator of IL23-STAT3 signaling, we generated SOCS3 knockdown transgenic (TG) mice for development of an animal model of spondyloarthritis. A hydrodynamic delivery method was employed to deliver minicircle DNA expressing IL23 (mc-IL23) into wild-type (WT) and the TG mice. Knockdown/overexpression systems mediated by lentivirus and retrovirus were used to determine whether SOCS3 regulated osteoblast differentiation.Results: Forced expression of IL23 induced severe joint destruction and extensive bone loss in SOCS3 knockdown TG mice, while this treatment only caused moderate symptoms in WT mice. Furthermore, severe spondyloarthritis was found in IL23-injected TG mice as compared to mild disease observed in WT controls under same condition. Moreover, our studies showed that IL23 promoted osteoblast differentiation via activation of STAT3 pathway and disruption of SOCS3 expression greatly increased phosphorylation of STAT3. In addition, silencing SOCS3 resulted in enhanced osteoblast differentiation through activation of Smad1/5/9 signaling, as evidenced by elevated phosphorylation level of Smad1/5/9. Experiments further demonstrated that SOCS3 interacted with Smad1 and thus suppressed the BMP2-Smad signaling.Conclusions: The results reveal that SOCS3 is involved in IL23-induced spondyloarthritis and acts as a key regulator of osteoblast differentiation, and suggest that SOCS3 knockdown TG mice may be an ideal animal model for further studies of spondyloarthritis

Mesoscale phenomena and their contribution to the global response: a focus on the magnetotail transition region and magnetosphere-ionosphere coupling

An important question that is being increasingly studied across subdisciplines of Heliophysics is “how do mesoscale phenomena contribute to the global response of the system?” This review paper focuses on this question within two specific but interlinked regions in Near-Earth space: the magnetotail’s transition region to the inner magnetosphere and the ionosphere. There is a concerted effort within the Geospace Environment Modeling (GEM) community to understand the degree to which mesoscale transport in the magnetotail contributes to the global dynamics of magnetic flux transport and dipolarization, particle transport and injections contributing to the storm-time ring current development, and the substorm current wedge. Because the magnetosphere-ionosphere is a tightly coupled system, it is also important to understand how mesoscale transport in the magnetotail impacts auroral precipitation and the global ionospheric system response. Groups within the Coupling, Energetics and Dynamics of Atmospheric Regions Program (CEDAR) community have also been studying how the ionosphere-thermosphere responds to these mesoscale drivers. These specific open questions are part of a larger need to better characterize and quantify mesoscale “messengers” or “conduits” of information—magnetic flux, particle flux, current, and energy—which are key to understanding the global system. After reviewing recent progress and open questions, we suggest datasets that, if developed in the future, will help answer these questions

Research on Quality Detection Methods for Automotive Transmission

Given the problems in intelligent diagnosis methods for automotive transmission, it is difficult to obtain the fault signal features and a large enough sample size to study. To solve these problems, a method integrating order tracking, cepstrum, support vector machine (SVM) and extremal curve is proposed in this paper. Order tracking and cepstrum are combined for processing the non- stationary vibration signal emitted by automotive transmission. As conventional intelligent methods cannot produce true results for insufficient samples, a method that combines SVM and extremal curve is presented. Input the vector acquired from the feature signals into the SVM model for the first detection, and then do the second detection by means of extremal curve which in turn can enrich the training samples in SVM model thus making the SVM model be more perfect. Analytical description and experimental studies are presented for the methods of signal processing and quality detection. The experimental results demonstrate the effectiveness and practicability of the proposed method

The complete chloroplast genome of Mitreola yangchunensis (Loganiaceae)

The complete chloroplast (cp) genome of Mitreola yangchunensis was sequenced and assembled for the first time. The genome is 154,665 bp in length, containing a large single-copy (LSC) region of 85,351 bp, a small single-copy region (SSC) of 18,218 bp and a pair of inverted repeats (IRs) of 25,548 bp. It contains 113 unique genes, including 79 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. The overall GC content is 37.9%, while the corresponding values of LSC, SSC, and IR regions are 35.9, 32.0, and 43.4%, respectively. Phylogenetic analyses using complete cp genomes showed that M. yangchunensis is most closely related to Mitrasacme pygmaea in Loganiaceae, and Gelsemiaceae and Loganiaceae form a single cluster with high support value

The complete chloroplast genome of Stephania tetrandra (Menispermaceae)

The complete chloroplast genome of Stephania tetrandra was sequenced and assembled for the first time. The chloroplast genome is 159,974 bp in length, containing a large single-copy (LSC) region of 90,539 bp and a small single-copy region (SSC) of 20,735 bp, separated by a pair of inverted repeats (IRs) of 24,350 bp. The genome contains 113 unique genes, including 79 protein-coding genes (PCGs), 30 tRNA genes, and four rRNA genes. Among them, 15 genes have one intron each and three genes contain two introns. The overall GC content is 37.8%, while the corresponding values of LSC, SSC, and IR regions are 35.8, 32.4, and 43.7%, respectively. Phylogenetic analysis showed that S. tetrandra is more closely related to the clade of two species within Stephania, providing new insight into the evolution of Menispermaceae

Regional intra-arterial vs. systemic chemotherapy for advanced pancreatic cancer: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the efficacy and safety of regional intra-arterial chemotherapy (RIAC) versus systemic chemotherapy for stage III/IV pancreatic cancer. METHODS: Randomized controlled trials of patients with advanced pancreatic cancer treated by regional intra-arterial or systemic chemotherapy were identified using PubMed, ISI, EMBASE, Cochrane Library, Google, Chinese Scientific Journals Database (VIP), and China National Knowledge Infrastructure (CNKI) electronic databases, for all publications dated between 1960 and December 31, 2010. Data was independently extracted by two reviewers. Odds ratios and relative risks were pooled using either fixed- or random-effects models, depending on I(2) statistic and Q test assessments of heterogeneity. Statistical analysis was performed using RevMan 5.0. RESULTS: Six randomized controlled trials comprised of 298 patients met the standards for inclusion in the meta-analysis, among 492 articles that were identified. Eight patients achieved complete remission (CR) with regional intra-arterial chemotherapy (RIAC), whereas no patients achieved CR with systemic chemotherapy. Compared with systemic chemotherapy, patients receiving RIAC had superior partial remissions (RR = 1.99, 95% CI: 1.50, 2.65; 58.06% with RIAC and 29.37% with systemic treatment), clinical benefits (RR = 2.34, 95% CI: 1.84, 2.97; 78.06% with RAIC and 29.37% with systemic treatment), total complication rates (RR = 0.72, 95% CI: 0.60, 0.87; 49.03% with RIAC and 71.33% with systemic treatment), and hematological side effects (RR = 0.76, 95% CI: 0.63, 0.91; 60.87% with RIAC and 85.71% with systemic treatment). The median survival time with RIAC (5-21 months) was longer than for systemic chemotherapy (2.7-14 months). Similarly, one year survival rates with RIAC (28.6%-41.2%) were higher than with systemic chemotherapy (0%-12.9%.). CONCLUSION: Regional intra-arterial chemotherapy is more effective and has fewer complications than systemic chemotherapy for treating advanced pancreatic cancer