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Sevoflurane (Sev) is a commonly used anesthetic in hospitals that can cause neurotoxicity. Postoperative cognitive dysfunction (POCD) is a common clinical problem induced by some anesthetics. However, the exact mechanism of neurotoxicity induced by Sev is unclear. Here we studied a new mechanism of POCD induced by Sev. We treated 15-month-old mice with 2% Sev for 6 hours, and we had found that Sev causes POCD. Using isobaric tags for relative and absolute quantitation (iTRAQ), we found that the transporter and the metabolism of carbohydrates and inorganic ions were involved in the cognitive impairment induced by Sev. Using synchrotron radiation micro-X-ray fluorescence (μ-XRF), we showed that Sev caused the iron overload in the brain of 15-month-old mice. Subsequently, excessive iron led to oxidative stress and impaired mitochondrial function that further led to glucose metabolism disorder and reduced ATP production by regulating the expression of key enzyme genes or proteins including G6Pase, Pck1, and Cs. Meanwhile, Sev also inhibited the oxygen consumption rate and glucose absorption by downregulating the expression of glucose transporter 1 in cerebral vascular endothelial cells. The cross-dysfunction of iron and glucose metabolism caused the apoptosis in the cortex and hippocampus through Bcl2/Bax pathway. In conclusion, the data here showed a new mechanism that Sev caused apoptosis by cross-dysregulation of iron and glucose metabolism and induced energy stress in mice. Maintaining iron and glucose metabolism homeostasis may play an important role in cognitive impairment induced by Sev.

SmANS deletion leads to white flower mutation in Salvia miltiorrhiza. SmANS deletion leads to white flower mutation in Salvia miltiorrhiza. Abstract Salvia miltiorrhiza is an essential traditional Chinese medicine (TCM) with purple flowers, and S. miltiorrhiza Bge. f. alba is a unique intraspecific variation with white flowers. The molecular mechanism of flower color formation in S. miltiorrhiza will provide vital information for the variation and evolution. Here, we performed HPLC, transcriptomic, and re-sequencing analyses of purple-flowered S. miltiorrhiza line 'Zihua105' (ZH105) and white-flowered S. miltiorrhiza Bge. f. alba line 'Baihua18' (BH18). Delphinidin was the most anthocyanidin in ZH105, which become the main different between ZH105 vs. BH18 flowers. Transcriptome analysis revealed 299 differentially expressed genes (DEGs). SmANS, the anthocyanidin synthase gene in the down-stream anthocyanin biosynthesis pathway, was significantly expressed in ZH105 corollas, suggesting it might play a key role in white petal formation. Whole-genome re-sequencing revealed that a 6.75 kb segment located on chromosome 5, which contains the complete sequence of the SmANS genes, was lost in BH18 and another S. miltiorrhiza Bge. f. alba line. In contrast, the other five purple-flowered S. miltiorrhiza lines both possessed this segment. Further molecular marker identification also confirmed that wild S. miltiorrhiza Bge. f. alba lines lost regions that contained a complete or important part of SmANS sequences. Subsequently, the research showed that the deletion mutant of SmANS genes resulted in the natural white flower color variant of S. miltiorrhiza.

For decades, the neurotoxicity caused by anesthetics in mammalian brain development has gained increasing attention. Exposure to anesthetics leads to neurotoxicity and apoptosis of nerve cells, which in turn induces cognitive dysfunction. Although most of the data came from animal studies, general anesthetics have been shown to have adverse effects on cognitive function in infants and young children in recent years. This concern has led to a number of retrospective studies that observed an association between general anesthesia in pregnant women and neurobehavioral problems in fetuses or offspring. Every year, many pregnant women undergo non-obstetric anesthesia due to various reasons such as traffic accidents, fetal interventions, acute appendicitis, symptomatic cholelithiasis, and trauma. A matter of concern for these pregnant women is whether anesthesia has a detrimental effect on fetal brain development in the womb and whether the fetus has cognitive impairment after birth. In humans, the association of anesthetic exposure in infants with the long-term impairment of neurologic functions has been reported in several retrospective clinical studies. Recently, we have found that sevoflurane anesthesia during pregnancy in mice-induced cognitive impairment in the offspring by causing iron deficiency and inhibiting myelinogenesis. Sevoflurane is a commonly used general anesthetic in the hospitals, which can induce neurotoxicity and cause cognitive impairment in fetuses, infants, children, and adults. However, the exact mechanism of sevoflurane-induced damage to the central nervous system (CNS) is not fully understood. Based on our recent results, this paper reviewed the effects of sevoflurane on cognitive impairment and pathological changes such as neurogenesis, neuronal apoptosis, and iron metabolism dysfunction in the offspring.

Salvia miltiorrhiza is an important traditional Chinese medicinal (TCM) plant and a model plant in the genetic study of TCM. A series of omics related to Danshen have been published. Integrating, managing, storing, and sharing data has become an urgent problem to be solved in S. miltiorrhiza genetic studies.The genome database is the link for the exchange, acquisition, and use of different omics data between data producers and users, maximizing value and utilization of data.The genome database included DSS3 genome and five RNA-Seq data. The back-end performs data search and retrieval through the LAMP (Linux, Apache, MySQL, PHP) framework.Here, we present SmGDB (S. miltiorrhiza genome database; http://8.140.162.85/ ), which houses the latest version of genome sequence and annotation data for S. miltiorrhiza, combining three unpublished RNA-Seq data from our group and two released RNA-Seq data. We also identified a novel gene cluster including seven CYP71D genes involved in the tanshinone synthesis pathway based on genome sequences and expression data. Besides, SmGDB provides user-friendly web interfaces for querying and browsing gene annotation, structure, location, and expression profiles for concerned genes. Popular bioinformatics tools such as 'BLAST', 'Search', 'Heatmap', 'JBrowse', etc., were also provided in SmGDB.SmGDB will provide utility for characterizing the structure of the S. miltiorrhiza genome and better understanding gene functions and biological processes underlying complex secondary metabolism in Danshen.

Background: Long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) have been shown to play fundamental roles in plant development. However, the information of these noncoding RNAs (ncRNAs) in Salvia miltiorrhiza remains largely unexplored. In this study, the expression pattern of ncRNAs in six tissues from the same strain of S. miltiorrhiza was analyzed to study the biological function of ncRNAs on active ingredients synthesis.Methods: Analysis of tanshinone content differences of two root simples was carried out on high-performance liquid chromatography (HPLC). RNA sequencing, GO and KEGG enrichment analysis were applied to analyzing the targets of diferentially expressed ncRNAs in different organs.Results: A total of 6,929 lncRNAs, 6,239 circRNAs, and 360 miRNAs were identified. Forty-eight lncRNAs, 70 miRNAs, and 26 circRNAs expressed differentially between red and white root tissues with significantly different tanshinone content. GO and KEGG pathway analysis of target genes of differently expressed ncRNAs indicated that some target genes are involved in the synthesis pathway of terpene, including diterpene and sesquiterpene. We also found many target genes related to secondary metabolites, including 2-C-Methyl-d-erythritol 2,4-cyclodiphosphate Synthase (SmMCS) and several CYP450s. Furthermore, most target genes may be related to the resistance of pathogens, such as receptor kinases, disease-resistant proteins, and pentatricopeptide repeat-containing proteins. Conclusions: The present study exhibited the tissue-specific expression patterns of ncRNAs preliminarily in S. miltiorrhiza, which may reflect that the formation of white root or red root is related to regulation by ncRNAs. It would provide a basis for further research about the regulation mechanism in the tanshinone synthesis process.

Phenolic acids are one of the main active components in Salvia miltiorrhiza root, which have been proved to have extensive pharmacological activities. In this study, quantitative trait loci (QTL) for phenolic acids contents were identified by a new genetic map constructed based on genomic simple sequence repeat (SSR) markers. The results demonstrated that the map comprised eight linkage groups which were in accord with the haploid chromosome number of S. miltiorrhiza (2n = 2x = 16). The map spanned 397.5 cM with average inter-marker distance as 3.6 cM. A total of six QTL were identified through interval mapping, including three salvianolic acid B (SAB) content-related QTL on linkage group (LG) 7, two lithospermic acid (LA) content markers on LG2 and LG4, as well as one rosmarinic acid (RA) content-linked QTL on LG7. These QTL could be used in marker-assisted breeding for the phenolic acids contents of S. miltiorrhiza.

Background: Cassia tora L. is an annual leguminous plant. Its seeds had wide utility in herbal medicine in Asian, but is usually regard as a potent, invasive weed which even helps farmers eliminate other parasitic weed species. However, compared with other important legume crops, C. tora is far from fully developed and the genetic basis is greatly lacking. A reference genome sequence will be great valuable resource for its genome evolution, genetic breeding and development.Results: Here, we de novo assembled a chromosome-scale genome for C. tora by combining PacBio sequencing technology with chromatin interaction mapping, resulting in 621-Mb genome with a contig N50 of 2.5 Mb, of which 77.44% was ordered and oriented on 13 pseudochromosomes. The genome contained 32,361 protein-coding genes with a repetitive DNA content of approximately 58.15%. Gypsy-type LTRs constituted the largest subfamily. LTR insertion events seldom occurred in this genome over the past 10 million years. Comparative genomic analyses showed that C. tora diverged ~95 million years ago (MYA), which revealed it has the most distant genetic relationship with 11 other legumes. Compared with other legume crops, Cassia tora is maybe an ancient species in Leguminosae.Conclusions: The high-quality reference genome sequence reported here furnishes unprecedented insights into genome dynamics and provides an important basis for future research on legume genome evolution.

Salvia miltiorrhiza Bunge, also known as red sage or Danshen, is an important traditional Chinese medicine (TCM) that has been used for thousands of years to treat cardiovascular and other diseases. It is also considered an important model TCM plant. Here, a high‐quality reference genome of S. miltiorrhiza was generated by combining PacBio long‐read sequencing and chromatin interaction mapping (Hi‐C) technologies, resulting in the chromosome‐scale assembly of a 594.75‐Mb genome sequence with a contig N50 of 2.70 Mb. This assembly shows the highest level of continuity for a Danshen genome generated thus far. The S. miltiorrhiza genome contained 32,483 protein‐coding genes, with a repetitive DNA content of approximately 64.84%. The high percentage of young LTRs suggests that multiple TE transposition bursts occurred recently in S. miltiorrhiza. Genes unique to secondary metabolism pathways were expanded in the S. miltiorrhiza genome. A new CYP450 gene cluster was identified in the phloem of red roots where active components were synthesized. This reference genome sequence will facilitate future studies aimed at the elucidation of the secondary metabolism synthesis pathway and the genetic improvement of S. miltiorrhiza.

Aiming to the human-machine environment adaptability evaluation indicators are qualitative indicators in the process of equipment operational tests, which is difficult to evaluate effectively. This paper applies satisfaction calculation model and gives assessment flow of human-machine environment adaptability. Finally, the application process of this method is explained through an example, the research result provides a practical and effective assessment method for the equipment human-machine environment adaptability during operational tests.

Alkaline phosphatase activity (APA) is always used to evaluate the phosphorus (P) status of phytoplankton community and considered as a proxy for phosphate (DIP) stress or deficiency. In this study, we presented seasonal distributions of APA [including free APA (F-APA) and particulate APA (P-APA)] and enzyme kinetics and compared to the distribution of phosphorus concentrations, planktonic biomass and other environmental variables reflecting community P status in moderate DIP-deficient Jiaozhou Bay, North China. Low potential APA (Vmax) were detected in winter (mean 51.3 nM h-1), which was probably due to low water temperature, while higher APA corresponded well to high phosphate requirement and high biological productivity in other three seasons. Normalized total APA (specified by chlorophyll a and bacteria biomass) showed an inverse hyperbolic relationship with DIP and the threshold phosphate concentration for the transition from high to low APA was around 0.2 μM in Jiaozhou Bay. Combined with results of APA, P concentrations (including DIP and DOP) and half saturation constant (Km), our findings suggested that phytoplankton and bacteria in Jiaozhou Bay may be experiencing a relief from P-limitation in winter; while in other three seasons, these organisms were mainly under persistent P stress. Moreover, in order to compensate for phosphate deficiency, we hypothesize that plankton not only by means of promoting enzyme production as indicated by increase of Vmax, but also by an improved enzyme affinity as represented by a decrease of the Michaelis constant (Km). Consequently, higher APA and lower DOP stocks in summer were probably a result of greater utilization of the DOP pool to maintain high primary production.

Cardiac Computed Tomography (CT) images provide detailed anatomic information about internal organs, while the segmentation of these images is essential for accurate medical diagnoses. Nowadays, deep learning techniques are widely used in the image segmentation, which requires a large number of annotated training datasets. However, there are lack of CT cardiac images with labeled ground truth. In this paper, an STU segmentation method is proposed, which concludes the style transfer method and the U-net convolutional network. The style transfer is used for generating the ground truth dataset by transferring the style of CT cardiac images to the content of electron microscopic (EM) images which have public annotated datasets. Moreover, the style of the specific region of the heart, whose edges are blurrier than other regions, is used for improving the segmentation results. Then, the ground truth EM images with transferred style are used for training the U-net which enables precise localization and can be trained from very few images. The final segmentation results were evaluated by the cardiologist. The cardiologist is satisfied with the segmentation results achieved by the ST-U method.

The present study aimed to test the hypothesis that propofol (PRO) could exert a neuroprotective effect via inhibiting oxidative stress induced by iron accumulation. Human SH-SY5Y cells were pretreated with ferric citrate (FAC), and then were protected by PRO. Cell viability was measured by MTT method. Iron levels were assayed by ICP-MS. Cell apoptosis was examined by TUNEL and digital holographic technique. Malondialdehyde (MDA), reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) depolarization were measured by MDA, DCFH-DA and JC-1 kits, respectively. The expression of proteins or genes involved in iron metabolism such as ferritin, TfR1, DMT1, Fpn1 and hepcidin, and other apoptosis-related proteins including Bcl2, Bax, Bid, Cox2, IL-6, JAK1 and STAT3 were detected by western blot. Our results showed low concentration of PRO (5 μM) could significantly prevent FAC induced apoptosis via inhibiting oxidative stress and iron accumulation. PRO suppressed the increase of ROS and MDA and decrease of MMP induced by FAC. PRO significantly down-regulated the expression of ferritin and up-regulated the expression of TfR1and Fpn1, but had no effect of DMT1. Furthermore, this effect was not done by PRO chelating iron. Meanwhile, PRO suppressed the inflammatory response through inhibiting IL-6 and Cox2 expression and activating JAK/STAT3 signaling induced by iron overload. In conclusion, here we demonstrated a new antioxidation mechanism of PRO. PRO could protect against nerve cell injury induced by overload of iron through regulating iron metabolism and inhibiting stress oxidative and inflammation reaction pathways by targeting JAK/STAT3 signaling.

Maternal anesthetic exposure during pregnancy is associated with an increased risk of cognitive impairment in offspring. The balance of cerebral iron metabolism is essential for the development of brain tissue. Iron deficiency affects the myelinogenesis and nerve tissue development, especially in fetus or infant, which has a key role in cognitive function. We aimed to investigate whether maternal sevoflurane (Sev) exposure caused cognitive impairment in offspring through inducing iron deficiency and inhibiting myelinogenesis. Pregnant mice (gestation stage day 14) were treated with 2% Sev for 6 h. Cognitive function of offspring mice was determined by the Morris water maze and Context fear conditioning test. Iron levels were assayed by Perl's iron staining and synchrotron imaging. Hippocampus and cortex tissues or cerebral microvascular endothelial cells of offspring mice (postnatal day 35) were harvested and subjected to Western blot and/or immunhistochemistry to assess ferritin, transferrin receptor 1(TfR1), Ferroportin-1 (FpN1), myelin basic protein (MBP), tight junction protein ZO-1, occludin, and claudin-5 levels. Beginning with postnatal day 30, the offspring were treated with iron therapy for 30 days, and the indicators above were tested. Our results showed Sev dramatically decreased the iron levels of brain and impaired cognitive function in offspring mice. Sev decreased the expression of heavy chain ferritin (FtH), light chain ferritin (FtL), MBP, ZO-1, occludin, claudin-5, and FpN1, and increased TfR1 in hippocampus and cortex or cerebral microvascular endothelial cells of offspring mice, indicating that Sev caused the iron deficiency and impaired the myelinogenesis in the brain of offspring. Interestingly, iron therapy prompted the myelinogenesis and improved impaired cognitive function at postnatal day 60. Our research uncovered a new mechanism which showed that iron deficiency induced by Sev and myelin formation disorder due to decreased iron of brain may be an important risk factor for cognitive impairment in offspring. It was necessary for offspring to be supplied iron supplement whose mother suffered exposure to sevoflurane during pregnancy.

Previous studies conducted on Daya Bay implied that the bay had been undergoing potential phosphorus limitation. In this context, alkaline phosphatase activity (APA) and the associated microbes were investigated in three different seasons in Daya Bay, South China Sea. Both bulk-community (fractioned into dissolved and particulate) and single-cell assays of APA were used to estimate the P status of phytoplankton at the community and species level. Unexpected high potential APA (Vmax) was observed in Daya Bay. Bulk APA showed that the maximum value in the spring (mean 583.26 nM h−1) corresponded well to low phosphate concentration. Furthermore, particulate APA (P-APA) showed an inverse hyperbolic relationship with phosphate, implying the coexistence of both constitutive and inducible AP; meanwhile, a threshold phosphate concentration for the transition from high to low APA was found around 0.2 μM in our study. P-APA and dissolved APA (D-APA) exhibited a tight link with phytoplankton and bacteria, which indicated that both of them were two main carriers of the enzyme. During the spring cruise, we encountered a small-scaled bloom of Gymnodinium that was probably at a declining phase. Extreme high levels of bulk and D-APA were characterized at this spring bloom event, and we suspected that bacteria especially active bacteria played an important role in APA production and partitioning at the post-bloom phase. In Daya Bay, diatoms were the dominant phytoplankton groups and percentages of ELF (Enzyme Labelled Fluorescence) labelled diatoms followed the same seasonal fluctuation as bulk APA, which suggested that diatoms were responsible for major variations of the bulk AP activity except for the spring bloom. Taken together, we considered that phytoplankton may be experiencing more P stress in spring and that the mineralization of organic P via alkaline phosphatase may help phytoplankton overcome P deficiency.

Nutrient and heavy metal (Fe, Mn, Ni, Cu, Pb, Zn, Cr, Cd and As) concentrations in porewater in sediment cores and their diffusive benthic fluxes were investigated in Daya Bay, South China, to study the accumulation and transfer of nutrients/metals at the sediment-water interface, and to discuss the impact of human activities on nutrients/metals. Nutrients and heavy metals displayed different profiles in porewater, which was mainly attributed to the distinct biogeochemical conditions in sediments. Total mean fluxes of nutrients (except NO3 and NO2) and metals in study area were positive, indicating nutrients and metals diffused from the sediment to overlying water, and sediment was generally the source of nutrients/metals. Human activities and the weak hydrodynamic force made nutrients/metals accumulate in sediment, so the sediment should be paid more attention to as the endogenesis of contamination in Daya Bay waters.