Force-Encoding DNA Nanomachines for Simultaneous and Direct Detection of Multiple Pathogenic Bacteria in Blood.

Pathogen detection is growing in importance in the early stages of bacterial infection and treatment due to the significant morbidity and mortality associated with bloodstream infections. Although various diagnostic approaches for pathogen detection have been proposed, most of them are time-consuming, with insufficient sensitivity and limited specificity and multiplexing capability for clinical use. Here, we report a force-encoding DNA nanomachine for simultaneous and high-throughput detection of multiple pathogens in blood through force-induced remnant magnetization spectroscopy (FIRMS). The force-encoding DNA nanomachines coupled with DNA walkers enable analytical sensitivity down to a single bacterium via a cascade signal amplification strategy. More importantly, it allows for rapid and specific profiling of various pathogens directly in blood samples, without being affected by factors such as light color and solution properties. We expect that this magnetic sensing platform holds great promise for various applications in biomedical research and clinical diagnostics.

The amino acid sensor MetRS is required for methionine-induced milk protein synthesis in a domestic pigeon model.

This study was conducted to investigate whether methionyl-tRNA synthetase (MetRS) is a mediator of Met-induced crop milk protein synthesis via the janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) signalling pathway in breeding pigeons. In Experiment 1, a total of 216 pairs of breeding pigeons were divided into 3 groups (control, Met-deficient, and Met-rescue groups). In Experiments 2 and 3, forty pairs of breeding pigeons from each experiment were allocated into 4 groups. The 2nd experiment included a control group and 3 MetRS inhibitor (REP8839) groups. The 3rd experiment included a Met-deficient group, Met-sufficient group, REP8839 + Met-deficient group, and REP8839 + Met-sufficient group. Experiment 1 showed that Met supplementation increased crop development, crop milk protein synthesis, the protein expression of MetRS and JAK2/STAT5 signalling pathway, and improved squab growth. Experiment 2 showed that crop development, crop milk protein synthesis, and the protein expression of MetRS and the JAK2/STAT5 signalling pathway were decreased, and squab growth was inhibited by the injection of 1.0 mg/kg BW REP8839, which was the selected dose for the 3rd experiment. These results showed that Met supplementation increased crop development, crop milk protein synthesis, and the expression of MetRS and JAK2/STAT5 signalling pathway and rescued squab growth after the injection of REP8839. Moreover, the Co-IP results showed that there was an interaction between MetRS and JAK2. Taken together, these findings indicate that MetRS mediates Met-induced crop milk protein synthesis via the JAK2/STAT5 signalling pathway, resulting in improved squab growth in breeding pigeons.

Molecular mapping and candidate gene identification of two major quantitative trait loci associated with silique length in oilseed rape (Brassica napus L.).

Rapeseed is a significant global source of plant oil. Silique size, particularly silique length (SL), impacts rapeseed yield. SL is a typical quantitative trait controlled by multiple genes. In our previous study, we constructed a DH population of 178 families known as the 158A-SGDH population. In this study, through SL QTL mapping, we identified twenty-six QTL for SL across five replicates in two environments. A QTL meta-analysis revealed eight consensus QTL, including two major QTL: cqSL.A02-1 (11.32-16.44% of PVE for SL), and cqSL.C06-1 (10.90-11.95% of PVE for SL). Based on biparental resequencing data and microcollinearity analysis of target regions in Brassica napus and Arabidopsis, we identified 11 candidate genes at cqSL.A02-1 and 6 candidate genes at cqSL.C06-1, which are potentially associated with silique development. Furthermore, transcriptome analysis of silique valves from both parents on the 14th, 21st, and 28th days after pollination (DAP) combined with gene function annotation revealed three significantly differentially expressed genes at cqSL.A02-1, BnaA02G0058500ZS, BnaA02G0060100ZS, and BnaA02G0060900ZS. Only the gene BnaC06G0283800ZS showed significant differences in parental transcription at cqSL.C06-1. Two tightly linked insertion-deletion markers for the cqSL.A02-1 and cqSL.C06-1 loci were developed. Using these two QTL, we generated four combinations: A02SGDH284C06158A, A02SGDH284C06SGDH284, A02158AC06158A, and A02158AC06SGDH284. Subsequent analysis identified an ideal QTL combination, A02158AC06SGDH284, which exhibited the longest SL of this type, reaching 6.06 ± 0.10 cm, significantly surpassing the other three combinations. The results will provide the basis for the cloning of SL-related genes of rapeseed, along with the development of functional markers of target genes and the breeding of rapeseed varieties. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01464-x.

The regulative effect and repercussion of probiotics and prebiotics on osteoporosis: involvement of brain-gut-bone axis.

Osteoporosis (OP) is a systemic disease characterized by decreased bone mass and degeneration of bone microstructure. In recent years, more and more researches have focused on the close relationship between gut microbiota (GM) and the occurrence and progression of OP, and the regulation of probiotics and prebiotics on bone metabolism has gradually become a research hotspot. Based on the influence of brain-gut-bone axis on bone metabolism, this review expounds the potential mechanisms of probiotics and prebiotics on OP from next perspectives: regulation of intestinal metabolites, regulation of intestinal epithelial barrier function, involvement of neuromodulation, involvement of immune regulation and involvement of endocrine regulation, so as to provide a novel and promising idea for the prevention and treatment of OP in the future.

Effect of goal-directed fluid therapy based on plasma colloid osmotic pressure on the postoperative pulmonary complications of older patients undergoing major abdominal surgery.

BACKGROUND: As an important component of accelerated rehabilitation surgery, goal-directed fluid therapy (GDT) is one of the optimized fluid therapy strategies and is closely related to perioperative complications and mortality. This article aimed to study the effect of combining plasma colloid osmotic pressure (COP) with stroke volume variation (SVV) as a target for intraoperative GDT for postoperative pulmonary complications in older patients undergoing major abdominal surgery. METHODS: In this study, older patients (n = 100) undergoing radical resection of gastroenteric tumors were randomized to three groups: Group C (n1 = 31) received a conventional infusion regimen, Group S1 (n2 = 34) received GDT based on SVV, and Group S2 (n3 = 35) received GDT based on SVV and COP. The results were recorded, including the lung injury score (LIS); PaO2/FiO2 ratio; lactic acid value at the times of beginning (T0) and 1 h (T1), 2 h (T2), and 3 h (T3) after liquid infusion in the operation room; the total liquid infusion volume; infusion volumes of crystalline and colloidal liquids; urine production rate; pulmonary complications 7 days after surgery; and the severity grading of postoperative pulmonary complications. RESULTS: The patients in the S2 group had fewer postoperative pulmonary complications than those in the C group (P < 0.05) and the proportion of pulmonary complications of grade 1 and higher than grade 2 in S2 group was significantly lower than that in C group (P <0.05); the patients in the S2 group had a higher PaO2/FiO2 ratio than those in the C group (P < 0.05), lower LIS than those in the S1 and C groups (P < 0.05), less total liquid infusion than those in the C group (P < 0.05), and more colloidal fluid infusion than those in the S1 and C groups (P < 0.05). CONCLUSION: The findings of our study show that intraoperative GDT based on COP and SVV can reduce the incidence of pulmonary complications and conducive to shortening the hospital stay in older patients after gastrointestinal surgery. TRIAL REGISTRATION: Chinese Clinical Trial. no. ChiCTR2100045671. Registry at www.chictr.org.cn on April 20, 2021.

Assessing Vehicle Wandering Effects on the Accuracy of Weigh-in-Motion Measurement Based on In-Pavement Fiber Bragg Sensors through a Hybrid Sensor-Camera System.

Weigh-in-motion (WIM) systems are essential for efficient transportation and monitoring parameters such as vehicle number, speed, and weight to ensure regulatory compliance and enhance road safety. Recently, WIM measurements using the Glass Fiber Reinforced Polymer Fiber Bragg Grating (GFRP-FBG) sensors have shown robustness and effectiveness. However, the accuracy of weight evaluation using the WIM systems based on GFRP-FBG sensors can be significantly influenced by the vehicle-wandering effect, which introduces uncertainties in wheel position determination and weight calculations. This paper assessed the impact of vehicle wandering on the accuracy of a WIM measurement system based on GFRP-FBG sensors by utilizing a new hybrid sensor-camera system that integrates roadside cameras and in-pavement GFRP-FBG sensors. The detailed methodology and framework of the developed hybrid system are introduced, followed by field testing on Highway I-94 in the United States. The field testing results indicate that by using the hybrid system, the wheel load detection accuracy of the WIM system based on GFRP-FBG sensors can be controlled to be a Type I or Type III WIM according to the ASTM 1318E-09 standard, with an average accuracy ranging from 87.83% to 94.65%. At the same time, when the wander distance is less than or equal to 9 cm, the developed WIM system proves to be very cost-effective as it only comprises two GFRP-FBG sensors, one temperature FBG sensor, and one camera. These findings indicate the practical potential to enhance the accuracy of WIM systems based on GFRP-FBG sensors designed for highways for low-coast, reliable, and accurate measurements by addressing vehicle wandering effects.

Short report: relationship between self-reported sleep characteristics and falls-associated fractures in elderly individuals: a population-based study.

Currently, the data for effect of sleep on falls-associated fractures in elderly individuals are still limited. This current study was aimed to assess the link between self-reported sleep characteristics and falls-associated fractures in elderly individuals. This study included a total of 20,497 participants from National Health and Nutritional Examination Survey (NHANES) 2005-2008, and 6,174 participants aged 45 years and older were identified. Self-reported sleep characteristics and conditions of falls-associated fractures of individuals were obtained via the method of personal questionnaires. In a total of 610 participants with exact history of fractures, 168 individuals with falls-associated fractures were identified, and the prevalence was 27.5%. The mean age of falls-associated fractures group was (72.1 ± 8.8) years, and the female (P < 0.001) occupied a higher proportion. Factors of living alone (P = 0.003), combined with hypertension (P = 0.003) and osteoporosis (P < 0.001), sleeping less or more (P = 0.009), and frequent snoring (P = 0.007) were linked to falls-associated fractures. Compared with sleep duration of 6 to 8 h/night, sleep duration of ≤4 h/night (odds ratio [OR] 1.858, 95% confidence interval [CI] 1.115-3.094) and of ≥9 h/night (OR 1.932, 95% CI 1.195-3.123) were related to an increased risk of falls-associated fractures. Collectively, our nationwide data noted that sleep characteristics were closely related to falls-associated fractures in elderly individuals, and a longer sleep duration may exhibit a protective effect against the falls-associated fractures, but it should be limited within 9 h/night.

Sevoflurane Induces a Cyclophilin D-Dependent Decrease of Neural Progenitor Cells Migration.

Clinical studies have suggested that repeated exposure to anesthesia and surgery at a young age may increase the risk of cognitive impairment. Our previous research has shown that sevoflurane can affect neurogenesis and cognitive function in young animals by altering cyclophilin D (CypD) levels and mitochondrial function. Neural progenitor cells (NPCs) migration is associated with cognitive function in developing brains. However, it is unclear whether sevoflurane can regulate NPCs migration via changes in CypD. To address this question, we treated NPCs harvested from wild-type (WT) and CypD knockout (KO) mice and young WT and CypD KO mice with sevoflurane. We used immunofluorescence staining, wound healing assay, transwell assay, mass spectrometry, and Western blot to assess the effects of sevoflurane on CypD, reactive oxygen species (ROS), doublecortin levels, and NPCs migration. We showed that sevoflurane increased levels of CypD and ROS, decreased levels of doublecortin, and reduced migration of NPCs harvested from WT mice in vitro and in WT young mice. KO of CypD attenuated these effects, suggesting that a sevoflurane-induced decrease in NPCs migration is dependent on CypD. Our findings have established a system for future studies aimed at exploring the impacts of sevoflurane anesthesia on the impairment of NPCs migration.

Efficient, Selective CO2 Photoreduction Enabled by Facet-Resolved Redox-Active Sites on Colloidal CdS Nanosheets.

Advances in nanotechnology have enabled precise design of catalytic sites for CO2 photoreduction, pushing product selectivity to near unity. However, activity of most nanostructured photocatalysts remains underwhelming due to fast recombination of photogenerated electron-hole pairs and sluggish hole transfer. To address these issues, we construct colloidal CdS nanosheets (NSs) with the large basal planes terminated by S2- atomic layers as intrinsic photocatalysts (CdS-S2- NSs). Experimental investigation reveals that the S2- termination endows ultrathin CdS-S2- NSs with facet-resolved redox-catalytic sites: oxidation occurs on S2--terminated large basal facets and reduction happens on side facets. Such an allocation of redox sites not only promotes spatial separation of photoinduced electrons and holes but also facilitates balanced extraction of holes and electrons by shortening the hole diffusion distance along the (001) direction of the ultrathin NSs. Consequently, the CdS-S2- NSs exhibit superb performance for photocatalytic CO2-to-CO conversion, which was verified by the isotope-labeled experiments to be a record-breaking performance: a CO selectivity of 99%, a CO formation rate of 2.13 mol g-1 h-1, and an effective apparent quantum efficiency of 42.1% under the irradiation (340 to 450 nm) of a solar simulator (AM 1.5G). The breakthrough performance achieved in this work provides novel insights into the precise design of nanostructures for selective and efficient CO2 photoreduction.

Force-Coded Strategy for the Simultaneous Detection of Multiple Tumor-Related Proteins.

Multiplexed simultaneous detection of various cancer markers is required for accurate diagnosis and treatment of early cancer. In this work, we present a force-coded strategy for the simultaneous detection of tumor-related proteins with tunable dynamic range via magnetic sensing. The multiplexing capability of this method is achieved by designing DNA devices that can recognize different biomarkers and code them with different binding forces measured by the force-induced remnant magnetization spectroscopy, which is not influenced by the color of the light and the solution. Moreover, the force-coded assay with high sensitivity and adjustable detection range is robust, which could be used for practical biological applications such as magnetic sensing, handheld miniaturized systems, and potential in vivo diagnosis.

Evaluation of the knowledge, awareness, and attitudes toward epilepsy among nurses.

BACKGROUND: The standard of care provided to patients with chronic epilepsy might be affected by clinical nurses' understanding, awareness, and attitudes toward the condition. The objective of this study was to assess the knowledge, awareness, and attitudes toward chronic epilepsy among clinical nurses in the Second Affiliated Hospital of Zhejiang University School of Medicine, China. METHODS: Two hundred and thirty-eight nurses from the neurosurgery, neurology, epilepsy center, other internal medicine and other surgery department working at our hospital participated in this descriptive and cross-sectional study in 2022. The data were collected through an electronic questionnaire, which comprised four domains including demographic and clinical epilepsy-related questions, awareness of epilepsy section, 18 items for knowledge and a 15-item scale for attitudes. Mann-Whitney U tests, Kruskal-Wallis H tests, post hoc analysis, Pearson correlation analysis, and descriptive statistics were used to analyze the non-normal distribution of the dataset. RESULTS: The clinical nurses' average score on the awareness of epilepsy section was 14.93 ± 2.69 (maximum score: 20), the knowledge of epilepsy section scored 15.41 ± 2.30 (maximum score: 18), and the epilepsy attitude section scored 30.65 ± 7.40. The knowledge and awareness accuracy of the responses to the epilepsy-related questions were positively and significantly correlated (r = 0.251, p < 0.001). The multiple linear regression model found that the department (p < 0.001) and rank (p = 0.015) of nurses were independently associated with awareness toward epilepsy. Meanwhile, there was a statistically significant difference between the departments of nurses and accuracy on the Epilepsy Knowledge Scale (H = 18.340, p < 0.001). In addition, 92.77% of nurses agreed that people with chronic epilepsy have the same rights as all people. Unfortunately, over 30% of nurses maintained an uncertain attitude toward the employment, marriage, and emotion related to epilepsy. CONCLUSION: Our findings revealed that nurses had a general awareness and understanding of epilepsy, attitudes toward epilepsy. Specifically, nurses working in the Neurology Department and the Epilepsy Center were predisposed to have a considerably better level of awareness and knowledge of epilepsy. Additionally, as their understanding of epilepsy grew, so did their sensitivity to those who suffer from the condition. The study also recommends that epilepsy experts deliver additional lectures and training sessions to enhance nurses' knowledge of first-aid for seizures.

Tetramethylpyrazine protects neural stem cells against sevoflurane-induced toxicity through Akt/GSK-3ß pathway.

Sevoflurane, a commonly used anesthetic, has been found to cause neural stem cell (NSC) injury, thereby contributing to neurocognitive impairment following general anesthesia. Tetramethylpyrazine (TMP), one of the most widely used medicinal compounds isolated from a traditional Chinese herb, possess neuroprotective activity. However, its effect on sevoflurane-induced NSC injury remains unclear. NSCs were pretreated with indicated concentrations of TMP for 2 h and then exposed to sevoflurane for 6 h. Cell injury was measured using lactate dehydrogenase (LDH) release assay. Cell viability and proliferation were detected by cell counting kit-8 (CCK-8) assay and 5-bromo-2'-deoxyuridine (BrdU) labeling, respectively. Apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The levels of cleaved caspase-3, phosphorylated protein kinase B (Akt) and phosphorylated glycogen synthase kinase-3ß (GSK-3ß) were detected by western blotting. Our results showed exposure to sevoflurane decreased the viability and proliferation of NSCs, while TMP preserved NSC viability and proliferation after sevoflurane exposure. In addition, the expression of cleaved caspase-3 and TUNEL positive cells were markedly decreased in TMP-treated NSCs compared with the control. Furthermore, pretreatment with TMP significantly increased the levels of phosphorylated Akt and GSK-3ß in sevoflurane-injured NSCs. However, an upstream inhibitor of Akt, LY294002 abolished the protective of TMP on the cell viability of NSCs. In conclusion, these findings indicate that TMP protects NSCs from sevoflurane-induced toxicity through Akt/GSK-3ß pathway.

Multisignal optical temperature-sensing properties of Eu3+ -doped NaYF4 nanoparticles.

In this paper, the multisignal (different emissions/colours) temperature sensing of NaYF4 :Eu3+ nanoparticles is investigated, which is based on fluorescence intensity ratios (FIRs) between 5 D0 →7 FJ (J=1-4) and 5 D1 →7 FJ' emissions. The 5 D1 →7 FJ' (J'=0-2) emissions can be clearly observed due to the low photon energy of NaYF4 . Based on the FIRs between different 5 D0 →7 FJ and 5 D1 →7 FJ' emissions, higher absolute/relative temperature sensitivities are obtained. Compared with the FIR between whole 5 D0 →7 FJ and 5 D1 →7 FJ' emissions, the maximum value of Sa was improved from 0.27 K-1 to 5.02 K-1 and that of Sr was improved from 0.89%·K-1 to 1.27%·K-1 . Furthermore, the FIRs between different colours of emissions were investigated for the application of wide-range multicolour temperature sensing.

Three-Dimensional Microwave Head Imaging with GPU-Based FDTD and the DBIM Method.

We present a preliminary study of microwave head imaging using a three-dimensional (3-D) implementation of the distorted Born iterative method (DBIM). Our aim is to examine the benefits of using the more computationally intensive 3-D implementation in scenarios where limited prior information is available, or when the target occupies an area that is not covered by the imaging array's transverse planes. We show that, in some cases, the 3-D implementation outperforms its two-dimensional (2-D) counterpart despite the increased number of unknowns for the linear problem at each DBIM iteration. We also discuss how the 3-D algorithm can be implemented efficiently using graphic processing units (GPUs) and validate this implementation with experimental data from a simplified brain phantom. In this work, we have implemented a non-linear microwave imaging approach using DBIM with GPU-accelerated FDTD. Moreover, the paper offers a direct comparison of 2-D and 3-D microwave tomography implementations for head imaging and stroke detection in inhomogenous anatomically complex numerical head phantoms.

3D Mapping of the Lateral Malleolus Fractures for Predicting Syndesmotic Injuries in Supination External Rotation Type Ankle Fractures.

Supination external rotation (SER) type ankle fracture is the most common ankle fracture in the Lauge-Hansen classification and is often accompanied with syndesmotic injury. However, the mechanism of this injury is indistinct and a suggestive role can be given by preoperative imaging. This study was to preoperatively predict whether SER type ankle fractures are accompanied with syndesmotic injuries by the means of lateral malleolus fracture mapping. One hundred and forty-eight patients diagnosed with SER type ankle fractures were retrospectively enrolled in this study. The baseline data were collected and computed tomography data were reconstructed in 3-dimensional (3D) model. Patients were divided into stable and unstable groups according to intraoperative Cotton test and whether the inferior tibiofibular screw was placed. All fracture lines were superimposed on the ankle template to create a fracture map, and the data on the fracture map were further measured. Logistic regression was conducted to identify relevant factors and the cutoff values were given using receiver operating characteristic curves. Forty-one patients were enrolled in the unstable group and 107 patients were enrolled in the stable group. The lateral malleolus fracture lines of the unstable group were higher and steeper than that in the stable group on lateral and posterior views. The fracture height of the posterior cortex and peak height were the significant contributing factors, and the cut-off values of posterior cortex, peak height and inclination angle were 40.35 mm (sensitivity: 78%, specificity: 82%), 55.34 mm (sensitivity: 85%, specificity: 70%) and 55.6° (sensitivity: 66%, specificity: 86%), respectively. In general, when the fracture lines of the lateral malleolus were high and steep, it was usually indicative of a syndesmotic injury and can be predicted by the preoperative 3D reconstruction of fracture height of posterior cortex, peak height and inclination angle. If the cut-off values of these indicators are exceeded, the syndesmotic injuries may be presented and need to be verified in the intraoperative Cotton test to decide whether to insert an inferior tibiofibular screw.

6-Gingerol relieves myocardial ischaemia/reperfusion injury by regulating lncRNA H19/miR-143/ATG7 signaling axis-mediated autophagy.

Myocardial ischemia/reperfusion injury (MIRI) causes severe damage in cardiac tissue, thereby resulting in a high rate of mortality. 6-Gingerol (6-G) is reported to play an essential role in alleviating MIRI. However, the underlying mechanism remains obscure. This study was intended to explore the potential mechanism by which 6-G functions. Q-PCR was employed to quantify the relative RNA levels of long noncoding RNA (lncRNA) H19 (H19), miR-143, and ATG7, an enzyme essential for autophagy, in HL-1 cells. Western blotting, immunofluorescence, and immunohistochemistry were employed for protein evaluation in cultured cells or mouse tissues. Cell viability, cytotoxicity, and apoptosis were analysed by CCK-8, LDH, and flow cytometry assays, respectively. The binding sites for miR-143 were predicted using starBase software and experimentally validated through a dual-luciferase reporter system. Here, we found that 6-G elevated cellular H19 expression in hypoxia/reoxygenation (H/R)-treated HL-1 cells. Moreover, 6-G increased Bcl-2 expression but reduced cleaved caspase 3 and caspase 9 protein levels. Mechanistically, H19 directly interacted with miR-143 and lowered its cellular abundance by acting as a molecular sponge. Importantly, ATG7 was validated as a regulated gene of miR-143, and the depletion of miR-143 by H19 caused an increased in ATG7 expression, which in turn promoted the autophagy process. Last, mouse experiments highly supported our in vitro findings that 6-G relieves MIRI by enhancing autophagy. The H19/miR-143/ATG7 axis was shown to be critical for the function of 6-G in relieving MIRI.

Self-Catalyzed Growth of Co-N-C Nanobrushes for Efficient Rechargeable Zn-Air Batteries.

Highly efficient and stable bifunctional electrocatalysts for oxygen reduction and evolution are essential for aqueous rechargeable Zn-air batteries, which require highly active sites as well as delicate structural design for increasing effective active sites and facilitating mass/electron transfer. Herein, a scalable and facile self-catalyzed growth strategy is developed to integrate highly active Co-N-C sites with 3D brush-like nanostructure, achieving Co-N-C nanobrushes with Co,N-codoped carbon nanotube branches grown on Co,N-codoped nanoparticle assembled nanowire backbones. Systematic investigations suggest that nanobrushes deliver significantly improved electrocatalytic activity compared with nanowire or nanotube counterparts and the longer nanotube branches give the better performance. Benefiting from the increase of accessible highly active sites and enhanced mass transfer and electron transportation, the present Co-N-C nanobrush exhibits superior electrocatalytic activity and durability when used as a bifunctional oxygen catalyst. It enables a rechargeable Zn-air battery with a high peak power density of 246 mW cm-2 and excellent cycling stability. These results suggest that the reported synthetic strategy may open up possibilities for exploring efficient electrocatalysts for diverse applications.

Daphnetin ameliorates glucocorticoid-induced osteoporosis via activation of Wnt/GSK-3ß/ß-catenin signaling.

Glucocorticoids have been widely used in multiple inflammatory and autoimmune diseases. However, long-term glucocorticoid therapy may result in osteoporosis. The present study aimed to evaluate the potential therapeutic effects and investigate the underlying mechanisms of Daphnetin (Daph) on glucocorticoid-induced osteoporosis (GIOP). In vivo, male Sprague Dawley rats were intramuscularly injected with dexamethasone (DEX) to induce GIOP and Daph was given intraperitoneally. Bone histological changes, mineral content, microstructure parameters and bone turnover markers were detected. Gut microbiota composition and intestinal barrier function were further assessed. In vitro, MC3T3-E1 pre-osteoblasts were treated with DEX and the abilities of Daph on osteoblast proliferation, differentiation and mineralization were assessed. A Wnt signaling inhibitor, XAV939, was added additionally to evaluate the effect of Daph on Wnt signaling. The results showed that in vivo, Daph increased the DEX-induced reduction in body weight gain, bone mineral content and microstructure parameters and restored the levels of bone turnover markers in GIOP rats. In vitro, Daph promoted osteoblast proliferation, differentiation and mineralization in DEX-treated MC3T3-E1 pre-osteoblasts. Moreover, Daph activated the Wnt/GSK-3ß/ß-catenin signaling pathway. XAV939 successfully abolished the beneficial effects of Daph on GIOP in vitro. Besides, Daph showed improvement on gut microbiota disorder and intestinal barrier dysfunction post GIOP. Collectively, these data demonstrated that Daph effectively ameliorates GIOP and the possible mechanism may be that Daph activated Wnt/GSK-3ß/ß-catenin signaling.

Dexmedetomidine Inhibits Neuroinflammation by Altering Microglial M1/M2 Polarization Through MAPK/ERK Pathway.

Neuroinflammation is critical in the pathogenesis of neurological diseases. Microglial pro-inflammatory (M1) and anti-inflammatory (M2) status determines the outcome of neuroinflammation. Dexmedetomidine exerts anti-inflammatory effects in many neurological conditions. Whether dexmedetomidine functions via modulation of microglia M1/M2 polarization remains to be fully elucidated. In the present study, we investigated the anti-inflammatory effects of dexmedetomidine on the neuroinflammatory cell model and explored the potential mechanism. BV2 cells were stimulated with LPS to establish a neuroinflammatory model. The cell viability was determined with MTT assay. NO levels were assessed using a NO detection kit. The protein levels of IL-10, TNF-α, iNOS, CD206, ERK1/2, and pERK1/2 were quantified using Western blotting. LPS significantly increased pro-inflammatory factors TNF-α and NO, and M1 phenotypic marker iNOS, and decreased anti-inflammatory factor IL-10 and M2 phenotypic marker CD206 in BV2 cells. Furthermore, exposure of BV2 cells to LPS significantly raised pERK1/2 expression. Pretreatment with dexmedetomidine attenuated LPS-elicited changes in p-ERK, iNOS, TNF-α, NO, CD206 and IL-10 levels in BV2 cells. However, co-treatment with dexmedetomidine and LM22B-10, an agonist of ERK, reversed dexmedetomidine-elicited changes in p-ERK, iNOS, TNF-α, NO, CD206 and IL-10 levels in LPS-exposed BV2 cells. We, for the first time, showed that dexmedetomidine increases microglial M2 polarization by inhibiting phosphorylation of ERK1/2, by which it exerts anti-inflammatory effects in BV2 cells.

Edaravone protects primary-cultured rat cortical neurons from ketamine-induced apoptosis via reducing oxidative stress and activating PI3K/Akt signal pathway.

Ketamine caused neuroapoptosis in the development of rat brain, in which oxidative stress play an important role. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, exerts neuroprotective effects in many neurological disease models. Here we investigated whether edaravone protects primary-cultured neurons against ketamine-induced apoptosis and its potential mechanism. Edaravone increased neuronal viability, decreased neuronal apoptosis, increased the ratio of Bcl-2/Bax after ketamine exposure. Edaravone also increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) level in ketamine-exposed neurons. In addition, edaravone increased protein levels of phosphorylated-protein kinase B (p-Akt), phosphorylated-glycogen synthase kinase-3ß (p-GSK-3ß) and phosphorylated-forkhead box protein O1 (p-FoxO1) in ketamine-exposed neurons. The neuroprotective effects of edaravone were reversed by LY294002, a specific phosphatidylinositol 3-kinase (PI3K) inhibitor. These findings demonstrated that edaravone protected neurons against ketamine-induced apoptosis by diminishing oxidative stress and activating PI3K/Akt signal pathway.