Effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery.

OBJECTIVE: This research aimed to ascertain the effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery. METHODS: Obese patients undergoing laparoscopic surgery under general anesthesia were separated into the control group (group C) and the dexmedetomidine group (group D) (n = 30). Patients in group D were infused with dexmedetomidine (1 µg/kg) intravenously for 10 min and then at a rate of 0.5 mg/kg h until 30 min before the end of the surgery, and those in group C were infused with an equal volume of saline. The surgery time points were divided into: before anesthesia induction (T0), 5 min after intubation (T1), 30 min after pneumoperitoneum (T2), 10 min after pneumoperitoneum release (T3), at the time of extubation (T4), 3 min after extubation (T5), and 24 h after surgery (T6). Arterial blood was collected for blood gas analysis to record arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2). Dynamic lung compliance (Cdyn), oxygenation index (OI), alveolar-arterial oxygen partial pressure difference (A-aDO2), and respiratory index (RI) were calculated. The time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation were recorded. Plasma IL-8 and IL-10 levels were measured from T0 to T6. RESULTS: The time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation in group D were not statistically significant when compared with those in group C. Versus at the T1 time point, A-aDO2 and RI were higher and Cdyn and OI were lower in both groups at T2 and T3 time points. Versus group C, group D had higher Cdyn and OI and lower A-aDO2 and RI at T2 and T3 time points. Versus at the T0 time point, at each time point from T1 to T6, IL-8 and IL-10 levels were higher in both groups. Versus group C, group D had lower IL-8 and higher IL-10 levels at each time point from T1 to T6. CONCLUSION: In obese patients undergoing laparoscopic surgery under general anesthesia, the use of dexmedetomidine can improve the lung compliance and OI of the patients, inhibit the inflammatory response of the lungs of the patients and thus have a certain protective effect on the lung function.

Loss of anthocyanidin synthase gene is associated with white flowers of Salvia miltiorrhiza Bge. f. alba, a natural variant of S. miltiorrhiza.

MAIN CONCLUSION: 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.

SmGDB: genome database of Salvia miltiorrhiza, an important TCM Plant.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Inflammation-Related Gene Signature: An Individualized Risk Prediction Model for Kidney Renal Clear Cell Carcinoma.

BACKGROUND: There is much evidence that confirms the inextricable link between inflammation and malignancy. Inflammation-related regulators were involved in the progression of kidney renal clear cell carcinoma (KIRC). However, the predictive role of single gene biomarkers is inadequate, and more accurate prognostic models are necessary. We undertook the current research to construct a robust inflammation-related gene signature that could stratify patients with KIRC. METHODS: The transcriptome sequencing data along with clinicopathologic information of KIRC were obtained from TCGA. A list of inflammation-related genes was acquired from the Molecular Signatures Database. Using the RNA-seq and survival time data from the TCGA training cohort, an inflammation-related gene signature was built using bioinformatic methods, and its performance in predicting patient prognosis was assessed by Kaplan-Meier and ROC curve analyses. Furthermore, we explored the association of risk score with immune score, stromal score, tumor immune-infiltrating cells (TIICs), immunosuppressive molecules, m6A regulators, and autophagy-related biomarkers. RESULTS: Herein, nine inflammation-related hub genes (ROS1, PLAUR, ACVR2A, KLF6, GABBR1, APLNR, SPHK1, PDPN, and ADORA2B) were determined and used to build a predictive model. All sets, including training set, four testing sets, and the entire TCGA group, were divided into two groups (low and high risk), and Kaplan-Meier curves all showed an adverse prognosis for patients in the high-risk group. ESTIMATE algorithm revealed a higher immune score in the high-risk subgroup. CIBERSORT algorithm illustrated that the high-risk group showed higher-level immune infiltrates. Furthermore, LAG3, TIGIT, and CTLA4 were overexpressed in the high-risk subgroup and positively associated with risk scores. Moreover, except for METTL3 and ALKBH5, the other m6A regulators decreased in the high-risk subgroup. CONCLUSIONS: In conclusion, a novel inflammation-related gene signature comprehensively constructed in the current study may help stratify patients with KIRC.

A new mechanism of POCD caused by sevoflurane in mice: cognitive impairment induced by cross-dysfunction of iron and glucose metabolism.

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.

Effect of sevoflurane on iron homeostasis and toxicity in the brain of mice.

Sevoflurane (Sev), a commonly used volatile anesthetic, could induce nerve damage and cognitive deficiency. Oxidative stress induced by iron overload promotes nerve damage and cell apoptosis in the brain. This study revealed a new toxic mechanism of Sev to the brain occurred through the dysfunction of iron metabolism. Twelve-month-old C57BL/6 mice were randomly assigned to the following three groups: control group; 2% Sev (6 h) group; and Sev plus iron deficiency group. Iron levels and iron metabolism-related proteins and apoptosis-related factors in hippocampus and cortex tissues were detected by using synchrotron radiation micro-X-ray fluorescence (µ-XRF) and western blotting. Our results showed that a decline in cognitive function was observed in mice treated with Sev. Sev significantly induced iron accumulation through upregulating ferritin and downregulating transferrin receptor 1 which involved in ferroportin1 (Fpn1)/hepcidin pathway and increasing reactive oxygen species (ROS) and malondialdehyde (MDA) content of hippocampus and cortex. Sev aggravated BACE1 expression and Aß accumulation. Changes in the ratio of Bcl2/Bax and Tau/p-Tau intensified the cell apoptosis in hippocampus and cortex tissues. Interestingly, the cognitive deficiency and neurotoxicity induced by Sev could be ameliorated significantly by feeding a low-iron diet to mice prior to anesthesia. The data uncovered a new lesion mechanism of Sev from the role of iron metabolism. This study also suggested that the reduction in iron levels could protect the brain against neurological damage induced by Sev.

Prenatal sevoflurane exposure: Effects of iron metabolic dysfunction on offspring cognition and potential mechanism.

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.

A high-quality reference genome sequence of Salvia miltiorrhiza provides insights into tanshinone synthesis in its red rhizomes.

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.

Sevoflurane anesthesia during pregnancy in mice induces cognitive impairment in the offspring by causing iron deficiency and inhibiting myelinogenesis.

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.

Propofol prevents oxidative stress and apoptosis by regulating iron homeostasis and targeting JAK/STAT3 signaling in SH-SY5Y cells.

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.

Dynamics of alkaline phosphatase activity in relation to phytoplankton and bacteria in a coastal embayment Daya Bay, South China.

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.

The porewater nutrient and heavy metal characteristics in sediment cores and their benthic fluxes in Daya Bay, South China.

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.