Time-Dependent Effects of Anesthetic Isoflurane on Reactive Oxygen Species Levels in HEK-293 Cells

The inhalation anesthetic isoflurane has been reported to induce caspase activation and apoptosis, which may lead to learning and memory impairment. However, the underlying mechanisms of these effects are largely unknown. Isoflurane has been shown to induce elevation of cytosol calcium levels, accumulation of reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore, reduction in mitochondria membrane potential, and release of cytochrome c. The time course of these effects, however, remains to be determined. Therefore, we performed a pilot study to determine the effects of treatment with isoflurane for various times on ROS levels in HEK-293 cells. The cells were treated with 2% isoflurane plus 21% O2 and 5% CO2 for 15, 30, 60, or 90 min. We then used fluorescence imaging and microplate fluorometer to detect ROS levels. We show that 2% isoflurane for 60 or 90 min, but not 15 or 30 min, induced ROS accumulation in the cells. These data illustrated that isoflurane could cause time-dependent effects on ROS levels. These findings have established a system to further determine the time course effects of isoflurane on cellular and mitochondria function. Ultimately, the studies would elucidate, at least partially, the underlying mechanisms of isoflurane-induced cellular toxicity

A bibliometric analysis of the neurotoxicity of anesthesia in the developing brain from 2002 to 2021

BackgroundThe neurotoxicity effects of anesthetic exposure on the developing brain have been one of the current research hotspots and numerous articles were published in the past decades. However, the quality and comparative information of these articles have not been reported. This research aimed to provide a comprehensive overview of the current state of the field by investigating research hotspots and publication trends concerning the neurotoxicity of anesthesia in the developing brain.Materials and methodsOn 15 June 2022, we searched articles on the neurotoxicity of anesthesia in the developing brain through the Science Citation Index databases from 2002 to 2021. Data of the author, title, publication, funding agency, date of publication, abstract, type of literature, country, journal, keywords, number of citations, and research direction were collected for further analysis.ResultsWe searched and analyzed 414 articles in English on the field of neurotoxicity of anesthesia in the developing brain from 2002 to 2021. The country with the largest number of publications was The United States (US) (n = 226), which also had the largest total number of citations (10,419). Research in this field reached a small peak in 2017. Furthermore, the largest number of articles were published in three journals, Anesthesiology, Anesthesia and Analgesia, and Pediatric Anesthesia. The top 20 articles that were cited most often were studied. In addition, the top hotspots of this area in clinical investigations and basic research were analyzed separately.ConclusionThis study provided an overview of the development in the neurotoxicity of anesthesia in the developing brain using bibliometric analysis. Current clinical studies in this area were mainly retrospective; in the future, we should place more emphasis on prospective, multicenter, long-term monitoring clinical studies. More basic research was also needed on the mechanisms of neurotoxicity of anesthesia in the developing brain

Identification of drought-responsive microRNAs in Medicago truncatula by genome-wide high-throughput sequencing

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are small, endogenous RNAs that play important regulatory roles in development and stress response in plants by negatively affecting gene expression post-transcriptionally. Identification of miRNAs at the global genome-level by high-throughout sequencing is essential to functionally characterize miRNAs in plants. Drought is one of the common environmental stresses limiting plant growth and development. To understand the role of miRNAs in response of plants to drought stress, drought-responsive miRNAs were identified by high-throughput sequencing in a legume model plant, <it>Medicago truncatula</it>.</p> <p>Results</p> <p>Two hundreds eighty three and 293 known miRNAs were identified from the control and drought stress libraries, respectively. In addition, 238 potential candidate miRNAs were identified, and among them 14 new miRNAs and 15 new members of known miRNA families whose complementary miRNA*s were also detected. Both high-throughput sequencing and RT-qPCR confirmed that 22 members of 4 miRNA families were up-regulated and 10 members of 6 miRNA families were down-regulated in response to drought stress. Among the 29 new miRNAs/new members of known miRNA families, 8 miRNAs were responsive to drought stress with both 4 miRNAs being up- and down-regulated, respectively. The known and predicted targets of the drought-responsive miRNAs were found to be involved in diverse cellular processes in plants, including development, transcription, protein degradation, detoxification, nutrient status and cross adaptation.</p> <p>Conclusions</p> <p>We identified 32 known members of 10 miRNA families and 8 new miRNAs/new members of known miRNA families that were responsive to drought stress by high-throughput sequencing of small RNAs from <it>M. truncatula</it>. These findings are of importance for our understanding of the roles played by miRNAs in response of plants to abiotic stress in general and drought stress in particular.</p

Elevated ozone decreases the multifunctionality of belowground ecosystems

Elevated tropospheric ozone (O-3) affects the allocation of biomass aboveground and belowground and influences terrestrial ecosystem functions. However, how belowground functions respond to elevated O-3 concentrations ([O-3]) remains unclear at the global scale. Here, we conducted a detailed synthesis of belowground functioning responses to elevated [O-3] by performing a meta-analysis of 2395 paired observations from 222 publications. We found that elevated [O-3] significantly reduced the primary productivity of roots by 19.8%, 16.3%, and 26.9% for crops, trees and grasses, respectively. Elevated [O-3] strongly decreased the root/shoot ratio by 11.3% for crops and by 4.9% for trees, which indicated that roots were highly sensitive to O-3. Elevated [O-3] impacted carbon and nitrogen cycling in croplands, as evidenced by decreased dissolved organic carbon, microbial biomass carbon, total soil nitrogen, ammonium nitrogen, microbial biomass nitrogen, and nitrification rates in association with increased nitrate nitrogen and denitrification rates. Elevated [O-3] significantly decreased fungal phospholipid fatty acids in croplands, which suggested that O-3 altered the microbial community and composition. The responses of belowground functions to elevated [O-3] were modified by experimental methods, root environments, and additional global change factors. Therefore, these factors should be considered to avoid the underestimation or overestimation of the impacts of elevated [O-3] on belowground functioning. The significant negative relationships between O-3-treated intensity and the multifunctionality index for croplands, forests, and grasslands implied that elevated [O-3] decreases belowground ecosystem multifunctionality

Epigenetic mechanism of miR-26b-5p-enriched MSCs-EVs attenuates spinal cord injury

Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) are promising therapies for the treatment of spinal cord injury (SCI). This study sought to explore the epigenetic mechanism of miR-26b-5p-enriched MSCs-EVs in SCI. MSCs and MSCs-EVs were isolated and characterized. The SCI rat model was established, followed by Basso-Beattie-Bresnahan scoring and H&E staining. In vitro cell models were established in PC12 cells with lipopolysaccharide (LPS) treatment, followed by cell viability evaluation using CCK-8 assay. The levels of miR-26b-5p, lysine demethylase 6A (KDM6A), NADPH oxidase 4 (NOX4), reactive oxygen species (ROS), and inflammatory factors (TNF-α/IL-1β/IL-6) in tissues and cells were detected. The levels of cy3-lablled miR-26b-5p in tissues and cells were observed by confocal microscopy. The binding of miR-26b-5p to KDM6A 3′UTR and the enrichments of KDM6A and H3K27me3 at the NOX4 promoter were analyzed. MSCs-EVs attenuated motor dysfunction, inflammation, and oxidative stress in SCI rats. MSCs-EVs delivered miR-26b-5p into PC12 cells to reduce LPS-induced inflammation and ROS production and enhance cell viability. miR-26b-5p inhibited KDM6A, and KDM6A reduced H3K27me3 at the NOX4 promoter to promote NOX4. Overexpression of KDM6A or NOX4 reversed the alleviative role of MSCs-EVs in SCI or LPS-induced cell injury. Overall, MSCs-EVs delivered miR-26b-5p into cells to target the KDM6A/NOX4 axis and facilitate the recovery from SCI

Metabolic response of soybean leaves induced by short-term exposure of ozone

The ever-increasing ozone (O-3) concentration has led to reduced production and altered quality of soybean. Abundant reports have explored the damage mechanisms of O-3 on soybean. However, how the elevated O-3 affects metabolite profiling of soybean remains to be poorly understood. Here, we compare the metabolic profile of soybean leaves under charcoal filtered air (CF, <20 ppb) and short-term elevated O-3 concentration (EO, 100 ppb). High level of O-3 affects metabolites for the tricarbonic acid (TCA) cycle, reactive oxygen species, cell wall composition and amino acids. Significantly, jasmonic acid-related metabolite promoting stomata closure is highly induced with 125-fold change. Furthermore, O-3 fumigation alters the expression of genes contributing to the biosynthesis of certain metabolites in TCA cycle. Together, these findings identify a wide range of changed metabolites in response to O-3 pollution. Our results pave the way for the genetic improvement of soybean to adapt to O-3 pollution to maintain stable yields

Cause Analysis and Solution of Boron Concentration Reduction in Three Generation Nuclear Power Passive Core Makeup Tank (CMT)

During the normal operation of the third-generation nuclear power plant, according to the requirements of the technical specification (TS), the CMT should be sampled every seven days, which should be controlled between 3400ppm and 4500ppm. However, due to various reasons, the boron concentration of CMT will drop abnormally. In order to meet the requirements of the technical specification, it is necessary to supplement boron to CMT frequently, which will cause a series of serious problems. Therefore, it is necessary and urgent to solve the problem of abnormal reduction of boron concentration in CMT

Analysis and treatment of large-scale nuclear heating commissioning problems

Through the modification of a nuclear power plant, the extraction steam on the exhaust pipe of the high-pressure cylinder of the steam turbine is used to heat the circulating water of the heat network, and the pressurized anf heated circulating water of the heat network is supplied to the secondary thermal power station, and then supplied to various users after heat exchange, realizing the first large-scale nuclear heating in China. This paper introduces the function and process of nuclear heating system, and focuses on the analysis of the problems in the commissioning process, which provides a reference for the commissioning of other domestic nuclear power plants after nuclear heating modification

Mechanism of Fat Mass and Obesity‐Related Gene‐Mediated Heme Oxygenase‐1 m6A Modification in the Recovery of Neurological Function in Mice with Spinal Cord Injury

Objectives This study examined the mechanism of fat mass and obesity‐related gene (FTO)‐mediated heme oxygenase‐1 (HO‐1) m6A modification facilitating neurological recovery in spinal cord injury (SCI) mice. FTO/HO‐1 was identified as a key regulator of SCI as well as a potential target for treatment of SCI. Methods An SCI mouse was treated with pcDNA3.1‐FTO/pcDNA3.1‐NC/Dac51. An oxygen/glucose deprivation (OGD) cell model simulated SCI, with cells treated with pcDNA3.1‐FTO/si‐HO‐1/Dac51. Motor function and neurobehavioral evaluation were assessed using the Basso, Beattie, and Bresnahan (BBB) scale and modified neurological severity score (mNSS). Spinal cord pathology and neuronal apoptosis were assessed. Further, FTO/HO‐1 mRNA and protein levels, HO‐1 mRNA stability, the interaction of YTHDF2 with HO‐1 mRNA, neuronal viability/apoptosis, and HO‐1 m6A modification were evaluated. Results Spinal cord injury mice exhibited reduced BBB, elevated mNSS scores, disorganized spinal cord cells, scattered nuclei, and severe nucleus pyknosis. pcDNA3.1‐FTO elevated FTO mRNA, protein expression, and BBB score; reduced the mNSS score of SCI mice; decreased neuronal apoptosis; improved the cell arrangement; and improved nucleus pyknosis in spinal cord tissues. OGD decreased FTO expression. FTO upregulation ameliorated OGD‐induced neuronal apoptosis. pcDNA3.1‐FTO reduced HO‐1 mRNA and protein and HO‐1 m6A modification, while increasing HO‐1 mRNA stability and FTO in OGD‐treated cells. FTO upregulated HO‐1 by modulating m6A modification. HO‐1 downregulation attenuated the effect of FTO. pcDNA3.1‐FTO/Dac51 increased the HO‐1 m6A level in mouse spinal cord tissue homogenate, reduced BBB, boosted mNSS scores of SCI mice, aggravated nucleus pyknosis, and increased neuronal apoptosis in spinal cord tissues, confirming that FTO mediated HO‐1 m6A modification facilitated neurological recovery in SCI mice. Conclusion The fat mass and obesity‐related gene modulates HO‐1 mRNA stability by regulating m6A modification levels, thereby influencing HO‐1 expression and promoting neurological recovery in SCI mice