Sevoflurane causes cognitive impairment by inducing iron deficiency and inhibiting the proliferation of neural precursor cells in infant mice.

AIMS: Numerous studies on animals have shown that exposure to general anesthetics in infant stage may cause neurocognitive impairment. However, the exact mechanism is not clear. The dysfunction of iron metabolism can cause neurodevelopmental disorders. Therefore, we investigated the effect of iron metabolism disorder induced by sevoflurane (Sev) on cognitive function and the proliferation of neural precursor cells (NPCs) and neural stem cells (NSCs) in infant mice. METHODS: C57BL/6 mice of postnatal day 14 and neural stem cells NE4C were treated with 2% Sev for 6 h. We used the Morris water maze (MWM) to test the cognitive function of infant mice. The proliferation of NPCs was measured using bromodeoxyuridine (BrdU) label and their markers Ki67 and Pax6 in infant brain tissues 12 h after anesthesia. Meanwhile, we used immunohistochemical stain, immunofluorescence assay, western blot, and flow cytometer to evaluate the myelinogenesis, iron levels, and cell proliferation in cortex and hippocampus or in NE4C cells. RESULTS: The results showed that Sev significantly caused cognitive deficiency in infant mice. Further, we found that Sev inhibited oligodendrocytes proliferation and myelinogenesis by decreasing MBP and CC-1 expression and iron levels. Meanwhile, Sev also induced the iron deficiency in neurons and NSCs by downregulating FtH and FtL expression and upregulating the TfR1 expression in the cortex and hippocampus, which dramatically suppressed the proliferation of NSCs and NPCs as indicated by decreasing the colocalization of Pax6+ and BrdU+ cells, and caused the decrease in the number of neurons. Interestingly, iron supplementation before anesthesia significantly improved iron deficiency in cortex and hippocampus and cognitive deficiency induced by Sev in infant mice. Iron therapy inhibited the decrease of MBP expression, iron levels in neurons and oligodendrocytes, and DNA synthesis of Pax6+ cells in hippocampus induced by Sev. Meanwhile, the number of neurons was partially recovered in hippocampus. CONCLUSION: The results from the present study demonstrated that Sev-induced iron deficiency might be a new mechanism of cognitive impairment caused by inhaled anesthetics in infant mice. Iron supplementation before anesthesia is an effective strategy to prevent cognitive impairment caused by Sev in infants.

Amelioration of nitroglycerin-induced migraine in mice via Wuzhuyu decoction: Inhibition of the MZF1/PGK1 pathway and activation of NRF2 antioxidant response.

ETHNOPHARMACOLOGICAL RELEVANCE: Migraine, a chronic and intricate disorder, manifests as recurrent episodic headaches accompanied by various neurological symptoms. Wuzhuyu Decoction (WZYD) is a traditional Chinese medical formula with promising effects in treating migraines; however, its underlying mechanisms have not yet been clarified. AIM OF STUDY: The study aimed to evaluate WZYD's effectiveness in migraine treatment and investigate the potential mechanism of WZYD's effects on migraine and oxidative stress. MATERIALS AND METHODS: Behavior tests and immunofluorescence assay for the intensity of migraine markers to assess the migraine-relieving effect of WZYD after chronic migraine model induced by nitroglycerin in mice. The impacts of WZYD on oxidative stress-related markers, including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO1), and NAD (P)H quinone oxidoreductase 1 (NQO1) in brain tissue were examined. In addition, protein expression or mRNA levels of the MZF1/PGK1 were detected using Western blot or PCR, respectively. Finally, the MZF1 overexpression vector was constructed to the higher level of MZF1. The MZF1/PGK1 signaling pathway expression was evaluated by markers of oxidative stress including NRF2 and others in this series of experiments. RESULTS: Through murine model experimentation, we observed that WZYD effectively alleviates migraine symptoms, signifying its therapeutic efficacy. Mechanistically, WZYD emerges as a potent activator of the NRF2, acting as a robust defense against oxidative stress. In vitro investigations demonstrated that WZYD combats oxidative stress and curbs cell apoptosis induced by these detrimental conditions. Furthermore, by suppressing the transcriptional expression of PGK1, an influential player in the NRF2 pathway, WZYD effectively activates NRF2 signaling. Intriguingly, we have identified MZF1 as the mediator orchestrating the regulation of the PGK1/NRF2 pathway by WZYD. CONCLUSION: The study confirms the effectiveness of WZYD in alleviating migraine symptoms. Mechanistically, WZYD activated the NRF2 signaling pathway; moreover, the action of WZYD involved the down-regulation of PGK1 mediated by MZF1, which promoted the activation of the NRF2 pathway. This study advances our understanding of the intricate mechanisms driving WZYD's efficacy, paving the way for novel treatments in migraine management.

Transmembrane serine protease 6, a novel target for inhibition of neuronal tumor growth.

Transmembrane serine protease 6 (Tmprss6) has been correlated with the occurrence and progression of tumors, but any specific molecular mechanism linking the enzyme to oncogenesis has remained elusive thus far. In the present study, we found that Tmprss6 markedly inhibited mouse neuroblastoma N2a (neuro-2a) cell proliferation and tumor growth in nude mice. Tmprss6 inhibits Smad1/5/8 phosphorylation by cleaving the bone morphogenetic protein (BMP) co-receptor, hemojuvelin (HJV). Ordinarily, phosphorylated Smad1/5/8 binds to Smad4 for nuclear translocation, which stimulates the expression of hepcidin, ultimately decreasing the export of iron through ferroportin 1 (FPN1). The decrease in cellular iron levels in neuro-2a cells with elevated Tmprss6 expression limited the availability of the metal forribo nucleotide reductase activity, thereby arresting the cell cycle prior to S phase. Interestingly, Smad4 promoted nuclear translocation of activating transcription factor 3 (ATF3) to activate the p38 mitogen-activated protein kinases signaling pathway by binding to ATF3, inducing apoptosis of neuro-2a cells and inhibiting tumor growth. Disruption of ATF3 expression significantly decreased apoptosis in Tmprss6 overexpressed neuro-2a cells. Our study describes a mechanism whereby Tmprss6 regulates the cell cycle and apoptosis. Thus, we propose Tmprss6 as a candidate target for inhibiting neuronal tumor growth.

Effect of Bi Content on the Microstructure, Mechanical and Tribological Properties of Cu-Sn Alloy.

To reduce the use of the toxic Pb element in the Cu-Sn alloy with high friction performance, Cu-xBi-10Sn alloys with different Bi contents were prepared by gravity casting, and the effect of Bi content on the microstructure, mechanical properties and wear property of Cu-Sn alloys were studied. The results showed that the Bi element was distributed in bands or long strips on the dendritic arms and did not form compounds with other elements. With the increase in Bi content, the hardness and tensile strength of Cu-xBi-10Sn alloys present a trend of increasing first and then decreasing. When the Bi content was 7 wt.%, the maximum hardness value was obtained, and the ultimate tensile strength was close to that of Cu-10Pb-10Sn alloy. Compared with Cu-10Pb-10Sn alloy, Cu-7Bi-10Sn alloy also possessed better friction reduction and wear resistance under the oil lubrication condition.

Clinical and Epidemiological Characteristics of Rhabdomyolysis: A Retrospective Study.

Background: Rhabdomyolysis (RM) refers to a clinical syndrome in which muscle cells are damaged by various causes and the clinical manifestations are mainly muscle pain, weakness, and dark urine. Acute kidney injury (AKI) is a serious complication of RM with complex mechanisms and high mortality. Therefore, understanding the pathogenesis and clinical manifestations, early diagnosis and treatment of RM are crucial to improve its prognosis. Method: Analysis of medical records of RM patients admitted to Tianjin Medical University General Hospital from October 2019 to October 2022. Statistical software SPSS 25.0 was used to analyze the data. The risk factors of RM-complicated AKI were analyzed by logistic regression. The receiver operating characteristic (ROC) curve was plotted, the area under the curve (AUC) was calculated, and the optimal cutoff value was determined by the Youden index. P < 0.05 indicates a statistically significant difference between the groups. Result: Among the 71 patients, the median age of the patients was 53.0 (30.0, 71.0) years and was 2.5 times higher in men than in women. Infection was the most common etiology. History of alcohol consumption, CK, and creatinine were independent influencing factors for AKI due to RM. Logistic regression analysis showed that CK combined with creatinine had a better predictive value than the single index. Conclusion: Our study revealed the clinical and laboratory characteristics of RM in the population attending the Tianjin Medical University General Hospital in the last three years, which is a reference for future multicenter, prospective studies.

Rutaecarpine alleviates migraine in nitroglycerin-induced mice by regulating PTEN/PGK1 signaling pathway to activate NRF2 antioxidant system.

BACKGROUND: Due to its widespread prevalence, migraine is a common neurovascular condition that has a major impact on people's health and quality of life. Rutaecarpine (RUT) is one of the main effective components of Evodia rutaecarpa, which has a wide range of biological activities. However, the exact mechanism by which RUT improves migraine remain unknown. PURPOSE: The purpose of this study was to investigate whether RUT improves migraine by inhibiting oxidative stress via activating the Nrf2 antioxidant system through the PTEN/PGK1 signaling pathway. METHODS: In vivo, a mouse model of chronic migraine (CM) was established by repeated intraperitoneal injection of nitroglycerin (NTG). After treatment with RUT and Sumatriptan, behavioral tests were performed, followed by measurements of oxidative stress-related indicators in the trigeminal nucleus caudalis, expression of proteins associated with the Nrf2 antioxidant system, and the PTEN/PGK1 pathway. In vitro, PC12 cells were stimulated by 100 µM H2O2 for 24 h to induce oxidative stress, which was then treated with RUT. Furthermore, the role of PTEN in antioxidant stress of RUT was elucidated by knockout of the PTEN gene. RESULTS: The results showed that RUT treatment improved NTG-induced migraine in mice by inhibiting oxidative stress. Importantly, RUT inhibited oxidative stress in NTG-induced mice or H2O2-induced PC12 cells via activating the Nrf2 antioxidant system by inhibiting PGK1 activity through PTEN. These results provide evidence that RUT improves migraine by activation of the Nrf2 antioxidant system through the PTEN/PGK1 pathway and provide new insights into the potential use of RUT as an effective drug development candidate for migraine.

Sevoflurane inhibited reproductive function in male mice by reducing oxidative phosphorylation through inducing iron deficiency.

Sevoflurane (Sev) is one of the commonly used inhalation anesthetic chemicals in clinics. It has great impact on spermatogenesis and fertilization in male animals. The underlying mechanism remains largely unexplored. Based on our previous research, we hypothesized that Sev induced iron metabolism disturbance in the testis and epididymis and inhibited the spermatogenesis. In this study, two-month-old C57BL/6 male mice were treated with 3% Sev for 6 h, and their fertility (including sperm concentration, sperm mobility, and the number of offspring) was evaluated. Mice testis, epididymis, and sperm were harvested and subjected to Western blot analysis and immunofluorescence analysis. Iron levels were reflected by the gene expression of iron metabolism-related proteins (including ferritin, TfR1, and FpN1) and ICP-MS and Perl's iron staining. Electron transport and oxidative phosphorylation levels were measured by Oxygraph-2k and ATP contents. The activity of ribonucleotide reductase was evaluated by assay kit. DNA synthesis status in testis and/or epididymis was marked with BrdU. Cell proliferation was evaluated by double immunofluorescence staining of specific protein marker expression. Our results revealed that the mice exposed to Sev showed damaged testicular and epididymis structure and significantly reduced the sperm concentration, sperm motility, and fertility. Sev decreases the iron levels through down-regulating the expression of H-ferritin, L-ferritin, and FpN1, and up-regulating the expression of TfR1 in the testis and epididymis. Iron levels also significantly reduced in germ cells which decrease the number of germ cells, including sperm, Sertoli cells, and primary spermatocyte. Iron deficiency not only decreases electron transport, oxidative phosphorylation level, and ATP production but also suppresses the activity of ribonucleotide reductase and the expression of Ki67, DDX4, GATA1, and SCP3, indicating that Sev affects the spermatogenesis and development. Meanwhile, Sev impaired the blood-testis barrier by decreasing the ZO1 expression in the testis and epididymis. The damage effect induced by Sev can be significantly ameliorated by iron supplementation. In conclusion, our study illustrates a new mechanism by which Sev inhibits spermatogenesis and fertility through an oxidative phosphorylation pathway due to iron deficiency of epididymis and testis or sperm. Furthermore, the damaging effects could be ameliorated by iron supplementation.

BoostTree and BoostForest for Ensemble Learning.

Bootstrap aggregating (Bagging) and boosting are two popular ensemble learning approaches, which combine multiple base learners to generate a composite model for more accurate and more reliable performance. They have been widely used in biology, engineering, healthcare, etc. This article proposes BoostForest, which is an ensemble learning approach using BoostTree as base learners and can be used for both classification and regression. BoostTree constructs a tree model by gradient boosting. It increases the randomness (diversity) by drawing the cut-points randomly at node splitting. BoostForest further increases the randomness by bootstrapping the training data in constructing different BoostTrees. BoostForest generally outperformed four classical ensemble learning approaches (Random Forest, Extra-Trees, XGBoost and LightGBM) on 35 classification and regression datasets. Remarkably, BoostForest tunes its parameters by simply sampling them randomly from a parameter pool, which can be easily specified, and its ensemble learning framework can also be used to combine many other base learners.

Effect of extremely low frequency electromagnetic field on the pathogenicity of Magnaporthe oryzae.

Numerous works have reported that extremely low frequency electromagnetic fields (ELF-EMFs) were associated with human health; however, little is known about their effects on the occurrence of agricultural diseases. In this study, Magnaporthe oryzae was used as a model organism, and its pathogenicity under 50 Hz, 3 mT ELF-EMF was studied. Our results showed that the pathogenicity, growth rate, and conidia generation of M. oryzae were enhanced under ELF-EMF exposure. In addition, M. oryzae exposed to ELF-EMF showed enhanced tolerance to cell wall-perturbing agents sodium lauryl sulphate, and increased expression of cell wall integrity-related genes, including RAC1, CDC42, RHO2, and NOX2. In addition, the level of reactive oxygen species (ROS) and the expression level of ROS scavenger system-related gene MoAP1 increased in ELF-EMF-exposed samples, whereas the total antioxidant capacity and the activities of superoxide dismutase and catalase did not change. Results of our study demonstrated that exposure to 50 Hz, 3 mT ELF-EMF enhanced the infection ability of M. oryzae, which present new important challenges for understanding the effect of ELF-EMF exposure on farmland ecology, especially on agricultural diseases.

Extracorporeal Carbon Dioxide Removal in Patients with Acute Respiratory Distress Syndrome or Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2R) was used to prevent invasive mechanical ventilation and associated mechanical damage in patients with acute respiratory distress syndrome (ARDS). OBJECTIVES: This study aimed to investigate the efficacy and safety of ECCO2R treatment in patients with ARDS or chronic obstructive pulmonary disease (COPD). METHODS: MEDLINE, EMBASE, and the Cochrane Library were systematically searched for relevant studies that reported patient prognosis, blood gas parameters, and ECCO2R-related adverse events (AEs) published as of September 2020. Odds ratios (ORs), weighted mean differences (WMDs), and their corresponding 95% confidence intervals (CIs) were used to compare the outcomes. RESULTS: Fifteen studies involving 532 ARDS or COPD patients were included. Compared with controls, ECCO2R did not influence the 28-day mortality (OR = 0.73, 95% CI: 0.28-1.87, p = 0.51), the length of hospital stay (WMD = 3.34, 95% CI: -5.22 to 11.90, p = 0.444), and the length of intensive care unit stay (WMD = -0.39, 95% CI: -8.76 to 7.99, p = 0.928). Compared with baseline values, partial pressure of carbon dioxide (PaCO2) in the ECCO2R group was significantly reduced, while the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) and pH increased. The overall rate of ECCO2R-related AEs was 35% (95% CI: 17-53%, p < 0.001), and bleeding was the most common AE with a rate of 22% (95% CI: 13-31%, p = 0.002). The rate of ECCO2R-related deaths was low. CONCLUSIONS: In conclusion, there was no statistically significant difference in the prognosis of patients with and without ECCO2R treatment. ECCO2R significantly reduced PaCO2 and improved PaO2/FiO2 and pH values in patients with ARDS or COPD. Bleeding was the most common ECCO2R-related AE.

Correction: Giant magnetoelectric coupling observed at high frequency in NiFe2O4-BaTiO3 particulate composite.

[This corrects the article DOI: 10.1039/D0RA05782G.].

Performance of resistive index and semi-quantitative power doppler ultrasound score in predicting acute kidney injury: A meta-analysis of prospective studies.

This study aimed to assess the predictive value of the renal resistive index (RRI) and power Doppler ultrasound (PDU) on subsequent acute kidney injury (AKI) risk using a meta-analytic approach. We searched eligible studies in PubMed, EmBase, and the Cochrane library from inception until August 2021. The parameters included the sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curves (AUC). Twenty-three prospective studies involving 2,400 patients were selected. The pooled sensitivity and specificity of the RRI and PDU were 0.76 and 0.79, and 0.64 and 0.90, respectively. The pooled PLR and NLR were 3.64 and 0.31, and 6.58 and 0.40 for the RRI and PDU, respectively. The DORs of the RRI and PDU for predicting AKI were 11.76, and 16.32, respectively. The AUCs of the RRI and PDU for predicting AKI were 0.83, and 0.86, respectively. There were no significant differences between the RRI and PDU for predicting AKI in terms of sensitivity, PLR, NLR, DOR, and AUC. The specificity of the RRI was lower than that of the PDU for predicting AKI. This study found that the predictive performance of the RRI and PDU from the Doppler ultrasound for AKI was similar, which need to be further verified based on the direct comparison results.

[Research progress of combined anaerobic ammonium oxidation (ANAMMOX) process for nitrogen removal].

Anaerobic ammonia oxidation (ANAMMOX) process is an efficient and low-cost biological nitrogen removal process. However, it still faces some challenges in mainstream applications due to the limitation of substrate types and nitrate accumulation. In recent years, the combined process of anammox has been widely studied to solve the above problems. In this paper, the combined processes of anammox developed in recent years are reviewed, and discussed from the process principle, advantages and disadvantages, influencing factors, process extensibility and the key bottlenecks existing in the promotion and application, as well as the relevant work of the subject group. Finally, we take an outlook on the development of the combined anaerobic ammonia oxidation process in municipal domestic wastewater treatment.

circFAT1(e2) Inhibits Cell Apoptosis and Facilitates Progression in Vascular Smooth Muscle Cells through miR-298/MYB Axis.

Presently, as one of the three types of muscles in the human body, smooth muscle carries out many biological activities. Meanwhile, its abnormal development also leads to many diseases. Circular RNA, belonging to the noncoding RNA family, is demonstrated to function importantly in various diseases including smooth muscle. Here, we assumed circFAT1(e2) probably exhibited a primary role in vascular smooth muscle. Therefore, we conducted cell viability and cell apoptosis assay to validate the effects of circFAT1(e2) on vascular smooth muscle progression. Then, we supposed miR-298 was one target of circFAT1(e2) and executed corresponding experiments to test this hypothesis. Dual-luciferase reporter assay indicated miR-298 could bind to circFAT1(e2) and then modulated MYB level, thus regulating smooth muscle progression. Subsequently, based on the GSE41177 dataset, we identified 1982 differentially expressed genes (DEGs) in atrial fibrillation, and all DEGs were upregulated, including MYB. Finally, enrichment analysis of upregulated genes indicated that they were related to endodermal cell differentiation. The protein-protein interaction network revealed that EGFR, GNG2, and FPR2 were related to atrial fibrillation. In conclusion, our data find that circFAT1(e2) sponges miR-298 and then regulates MYB expression, thus affecting atrial fibrillation progression. Our findings provide a newly produced indicator and target for vascular smooth muscle diagnosis and treatment.

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.

Ferritinophagy-Mediated Ferroptosis Involved in Paraquat-Induced Neurotoxicity of Dopaminergic Neurons: Implication for Neurotoxicity in PD.

Parkinson's disease (PD) is a progressive nervous system disorder. Until now, the molecular mechanism of its occurrence is not fully understood. Paraquat (PQ) was identified as a neurotoxicant and is linked to increased PD risk and PD-like neuropathology. Ferroptosis is recognized as a new form of regulated cell death. Here, we revealed a new underlying mechanism by which ferritinophagy-mediated ferroptosis is involved in PD induced by PQ. The effect of PQ on movement injury in mice was investigated by the bar fatigue and pole-climbing test. SH-SY5Y human neuroblastoma cells were used to evaluate the mechanism of ferroptosis. Our results showed that PQ induced movement injury by causing the decrease in tyrosine hydroxylase in mice. In vitro, PQ significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression significantly, which were important markers in ferroptosis. Fer-1, an inhibitor of ferroptosis, could significantly ameliorate the ferroptosis induced by PQ. Meanwhile, Bcl2, Bax, and p-38 were involved in apoptosis induced by PQ. In conclusion, ferritinophagy-mediated ferroptosis pathway played an important role in PD occurrence. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of PD occurrence. The inhibition of the ferroptosis and apoptosis together may be a new strategy for the prevention of neurotoxicity or PD in the future.

Application of intraoperative ultrasound in neurosurgery for hypertensive intracerebral hemorrhage.

OBJECTIVE: To explore the clinical significance of intraoperative ultrasound in neurosurgery for hypertensive intracerebral hemorrhage (ICH). METHODS: Patients with hypertensive ICH who required to undergo surgical treatment were assigned into treatment group (126 cases), who were assisted by intraoperative ultrasound, and control group (122 cases), who were not assisted by intraoperative ultrasound. In the treatment group, intraoperative ultrasound was used for real-time positioning after opening the bone flap, so as to guide the surgery. After surgery, conventional treatment and follow-up were conducted, and the statistical analysis was eventually performed to compare the therapeutic efficacy of the two groups. RESULTS: The mean rate of hematoma clearance was (95.20 ± 5.18)% in the treatment group and (86.20 ± 4.85)% in the control group (P<0.05); the average time required for intraoperative hematoma clearance was 44.5±3.2 min in the treatment group and 66.3±5.1 min in the control group (P < 0.05). Finally, the treatment group was superior to the control group in terms of therapeutic efficacy and overall prognosis (P = 0.03 and 0.025, respectively). CONCLUSIONS: Intraoperative ultrasound possessed the features of precise positioning, real-time guidance, and being user-friendly, which can shorten the operation time, increase the efficacy of surgery, and improve patients' overall prognosis, highlighting high clinical significance of intraoperative ultrasound in neurosurgery.

4-Methylcytosine distribution follows the power function in Geobacter sulfurreducens genome.

Single-molecule real-time DNA sequencing revealed that 4-methylcytosine (m4C) commonly exists in bacterial genomes. In this work, samples with different m4C methylation patterns were studied. Results reveal that m4C modification is a biochemical reaction with distance effect, and its distribution follows the power function in the positive, negative, and double strands of genomic DNA sequences of Geobacter sulfurreducens. Furthermore, the value of regression coefficient in the fitting formula for double strands was the sum of those in the fitting formulae for positive and negative strands. Meanwhile, the value of exponent coefficient was the average, implicating an interesting mathematical phenomenon about power function. Considering the potent role of m4C in gene expression and the present results being obtained from the same genomic DNA sequence, this work suggests that the patterns of m4C distribution may be served as a signal for G. sulfurreducens to rapidly identify the genes to respond to environmental stresses or signals. This study opens a new avenue to extend our knowledge about the modification mechanisms and the epigenetic information of m4C modification in prokaryotes.

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.