Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.

Patchy profile sign in RAPID software: a specific marker for intracranial atherosclerotic stenosis in acute ischemic stroke.

Purpose: Identifying the etiology of acute ischemic stroke (AIS) before endovascular treatment (EVT) is important but challenging. In CT perfusion imaging processed by perfusion software, we observed a phenomenon called patchy profile sign (PPS), that is, the hypoperfusion morphology in RAPID software is a discontinuous sheet pattern. This phenomenon is predominantly observed in patients diagnosed with intracranial atherosclerotic stenosis (ICAS). The study intends to assess whether the PPS can be used to differentiate ICAS from intracranial embolism. Method: Patients with AIS due to M1 segment occlusion of the MCA who underwent mechanical thrombectomy were retrospectively enrolled. The receiver operating characteristic (ROC) curve analysis was performed to assess the value of PPS in predicting ICAS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the PPS for prediction of ICAS were calculated. Results: A total of 51 patients were included in the study. The PPS was observed in 10 of 19 (52.6%) patients with ICAS, and in 2 of 32 (6.3%) patients with intracranial embolism (p < 0.001). Interobserver agreement for identifying PPS was excellent (κ = 0.944). The sensitivity, specificity, PPV, NPV, and accuracy of the PPS for predicting ICAS were 52.6, 93.8, 83.3, 76.9, and 78.4%, respectively. Conclusion: The PPS on RAPID software is an imaging marker with high specificity for ICAS. Larger sample sizes are imperative to validate the findings.

Ligand Exchange of Quantum Dots: A Thermodynamic Perspective.

Colloidal quantum dots (QDs) consist of an inorganic core and organic surface ligands. Surface ligands play a dominant role in maintaining the colloidal stability of QDs and passivating the surface defects of QDs. However, the original ligands introduced in the synthetic process of QDs cannot meet the requirements for diverse applications; therefore, ligand exchanges with functional ligands are mandatory. Understanding the ligand exchange process requires a comprehensive combination of the concepts and techniques of surface chemistry. In this Perspective, the ligand exchange process is discussed in detail. Specifically, we elaborate on the thermodynamics that can reveal the feasibility and mechanism of ligand exchange. It depicts a critical physical picture of the surface of QDs along with the following ligand exchange.

Myocardial work is independent risk factor for coronary artery lesions in children with Kawasaki disease.

BACKGROUND: The recognition ability of noninvasive echocardiographic myocardial work for coronary artery lesions (CAL) in children with Kawasaki disease (KD) has not been well characterized. This study aimed to determine whether impaired myocardial work is an independent risk factor for CAL in children with KD. METHODS: Between December 2021 and April 2023, left ventricular (LV) myocardial work of 59 KD children was evaluated by myocardial work echocardiography, and their demographic, clinical and laboratory data were collected simultaneously. Multivariable logistic regression analysis was used to identify the independent risk factors for CAL. RESULTS: Twenty-seven of 59 KD children had CAL according to the diagnostic criteria of echocardiography. There were significantly different heart rates, white blood cell count, LV ejection fraction, global work index (GWI), global work efficiency and global wasted work (GWW) between KD children with and without CAL ( P < 0.05). Multivariate logistic regression analysis identified that GWI [odds ratio (OR) = 0.985; P = 0.001], GWW (OR = 1.039; P = 0.019), erythrocyte sedimentation rate (ESR, OR = 1.051; P = 0.049) and C-reactive protein (CRP) (OR = 1.017; P = 0.044) were independent risk factors for CAL in children with KD. The area under receiver operating characteristic curve (AUC) of 0.847 for GWI was superior to that for GWW (AUC = 0.708), ESR (AUC = 0.645) and CRP (AUC = 0.626) to predict CAL in KD children ( P < 0.05). The optimal cutoff value of GWI was 1089 mmHg, with a sensitivity of 59.26% and a specificity of 96.87%. CONCLUSION: GWI and GWW were independent risk factors for CAL in KD children with high discrimination ability.

Prediction of an impaired myocardial work using infarct size in acute myocardial infarction.

BACKGROUND: The relationship between myocardial infarct size (MIS) on late gadolinium-enhanced cardiac MRI (LGE MRI) and myocardial work (MW) indices assessed with MW echocardiography (MWE) has not been well characterized. This study aimed to determine an impaired MW using MIS in patients with acute myocardial infarction. METHODS: Left ventricular (LV) two-dimensional speckle-tracking echocardiography, MWE, and LGE MRI were performed in 33 patients with ST-segment elevation myocardial infarction and in 30 age- and sex-comparable controls. LV global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) and MIS were acquired, respectively. RESULTS: MIS was negatively correlated with GWI (r = -0.60, P  = 0.005), GCW (r =- 0.66, P  = 0.002) and GWE (r = -0.71, P  = 0.0004), but positively correlated with GLS (r = 0.68, P  = 0.001). With the receiver operating characteristic curve, the cutoff value of MIS for the prediction of an impaired GLS was 16.5% [area under the curve (AUC) = 0.867)], an impaired GWI was 19.2% (AUC = 0.727), an impaired GCW was 19.2% (AUC = 0.725), an increased GWW was 15.8% (AUC = 0.656), an impaired GWE was 15.8% (AUC = 0.880). CONCLUSION: MIS is a strong predictor of impaired MW. Timely reduction of infarct size is essential to improve myocardial function.

Number of segments with motion abnormalities is better correlated with infarct size in acute myocardial infarction.

BACKGROUND: The relationship between the number of segments with motion abnormalities (SMA) on the bull's-eye plots of speckle-tracking echocardiography (STE) and myocardial infarct size (MIS) on late gadolinium-enhanced cardiac MRI (LGE-cMRI) has not been well characterized. This study aimed to determine MIS using the number of SMA in patients with acute myocardial infarction (MI). METHODS: Left ventricular two-dimensional STE and LGE-cMRI were performed in 380 patients with ST-segment elevation MI within 48 h and 5-6 days after primary percutaneous intervention, respectively. RESULTS: Patients with impaired global and regional myocardial strain, work and greater number of SMA had significantly larger infarcts ( P  < 0.05). Multivariate logistic regression analysis that included myocardial strain, work, and number of SMA showed that total number of SMA [odds ratio (OR) = 1.976; 95% confidence interval (CI): 1.539-2.538, P  < 0.0001], the number of segments with paradoxalic systolic movements (SPSM, OR = 3.703; 95% CI: 2.112-6.493, P  < 0.0001) were independent risk factors of large MIS (>19%). The area under receiver operating characteristic curve (AUC) of 0.904 (0.866~0.942) for total number of SMA was superior to that for global longitudinal strain (GLS, AUC = 0.813, 0.761~0.865), global work efficiency (GWE, AUC = 0.794, 0.730~0.857) and number of SPSM (AUC = 0.851, 0.804-0.899) to predict a large MIS ( P  < 0.05). The optimal cutoff value of total number of SMA was 7, with a sensitivity of 85.31%, a specificity of 81.48%, and an accuracy of 83.27%. CONCLUSION: Total number of SMA is better associated with infarct size, which provided an incremental prognostic value above established prognostic parameters such as GLS and GWE.

A Non-Immunized and BSA-Template Aggregation-Induced Emission Sensor for Noninvasive Detection of Cystatin C in the Clinical Diagnosis of Diabetes Nephropathy.

Diabetes nephropathy (DN) is one of the main causes of death in patients with diabetes. Cystatin C (Cys C) is a reliable indicator of glomerular filtration function. Therefore, it is urgent and meaningful to obtain early warning of DN by noninvasive measurement of Cys C. In this investigation, a novel fluorescence sensor (BSA-AIEgen sensor) was synthesized by cross-linking the aggregation-induced emission (AIE) characteristics of 2-(4-bromophenyl)-3-(4-(4-(diphenylamino) styryl) phenyl) fumaronitrile (TPABDFN) and bovine serum albumin (BSA), which exhibited the "On" state owing to the restriction of the intramolecular motions (RIM) phenomenon of TPABDFN. Intriguingly, a decrease in fluorescence of BSA-AIEgen sensors could be found owing to BSA on the surface of BSA-AIEgen sensor hydrolyzed by papain, but a reverse phenomenon emerged with the increase of Cys C content as the inhibitor of papain. Hence, Cys C was successfully detected by employing the fluorescent differential display and the linear range was from 12.5 ng/mL to 800 ng/mL (R2 = 0.994) with the limit of detection (LOD) of 7.10 ng/mL (S/N = 3). Further, the developed BSA-AIEgen sensor successfully differentiates patients with diabetes nephropathy from volunteers with the advantages of high specificity, low cost, and simple operation. Accordingly, it is expected to become a non-immunized method to monitor Cys C for the early warning, noninvasive diagnosis, and drug efficacy evaluation of diabetes nephropathy.

Mediator Complex Subunit 8:Expression in Gastric Cancer, Prognostic Significance,and Impact on Cell Cycle / 中国医学科学院学报

Objective To investigate the expression and prognostic significance of mediator complex subunit 8 (MED8) in gastric cancer and its impact on the cell cycle.Methods The expression of MED8 in gastric cancer and adjacent tissues and its correlation with patients' prognosis were analyzed using public databases.A validation cohort of 104 patients who underwent radical resection for gastric cancer in the First Affiliated Hospital of Bengbu Medical College from June 2012 to July 2017 was included.The receiver operating characteristic curve was established to evaluate the predictive value of MED8 for postoperative 5-year survival.Bioinformatics tools were used to predict the biological roles of MED8 in gastric cancer.The effect of the MED8 level on the G1/S phase transition of gastric cancer cells (MGC-803) was analyzed via lentivirus transduction and flow cytometry.Western blotting was carried out to assess the impact of MED8 expression on the protein levels of cyclin-dependent kinase 4(Cdk4) and G1/S-specific cyclin-D1(CyclinD1) in MGC-803 cells.Results The high expression of MED8 in the gastric cancer tissue was associated with poor prognosis (P<0.001) and had prognostic significance (area under curve=0.733,P<0.001).Gene enrichment analysis suggested that MED8 may participate in the cell cycle process.Flow cytometry results revealed that the upregulation of MED8 expression promoted the transition of MGC-803 cells from the G1 phase to the S phase (P<0.001),while the downregulation of MED8 had the opposite effect (P<0.001).Western blotting showed increases in the protein levels of Cdk4 and CyclinD1 in MGC-803 cells with upregulated MED8 expression (all P<0.001),and decreases in the cells with downregulated MED8 expression (all P<0.001).Conclusion MED8 is highly expressed in gastric cancer and may affect its progression and prognosis by regulating the G1/S phase transition of gastric cancer cells.

Assessment of Myocardial Work of the Left Ventricle before and after PCI in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome by Pressure-Strain Loop Technology.

Objectives: Noninvasive left ventricular pressure-strain loop (PSL) is a new method for quantitative evaluation of myocardial work, which is developed on the basis of speckle tracking echocardiography. It is necessary to fit the noninvasive left ventricular pressure and the strain by speckle tracking echocardiography to construct a pressure-strain loop. Compared with traditional left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), it has potential application value and is a useful supplement for clinical evaluation of left ventricular systolic function. We perform this study to evaluate the changes of myocardial function in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) before and after percutaneous coronary intervention (PCI) with noninvasive left ventricular pressure-strain loop (PSL). Methods: 33 NSTE-ACS patients admitted to the Department of Cardiovascular Medicine of the Affiliated Lianyungang Hospital of Xuzhou Medical University who successfully underwent early PCI were included as the PCI group. At the same time, 30 healthy patients matched in age and sex were selected as the control group. All patients received routine echocardiography. The parameters such as GWI, GCW, GWW, and GWE were obtained by EchoPAC 203 software. The differences in the general clinical data and echocardiographic parameters between the two groups, including controls and patients 1 day before surgery and 1 month after surgery, were compared. Results: Compared with the control group, GWI, GCW, and GWI in the PCI group were decreased 1 day before surgery and 1 month after surgery, while GWW was increased, with statistical significance (P < 0.05). In the PCI group, compared with 1 day before surgery, GWI and GCW were all increased 1 month after surgery (P < 0.05), and GWW and GWE were not significantly different between the two groups (P > 0.05). Conclusion: The noninvasive left ventricular PSL technology can early and accurately evaluate the myocardial function impairment in NSTE-ACS patients and the recovery of myocardial function after PCI, providing a new noninvasive method for clinical postoperative myocardial function evaluation.

ALDH3B1 expression is correlated with histopathology and long-term prognosis of gastric cancer / 南方医科大学学报

OBJECTIVE@#To investigate the expression of aldehyde dehydrogenase 3B1 (ALDH3B1) in gastric cancer and explore its correlation with the pathological parameters and long-term prognosis of the patients.@*METHODS@#We analyzed the clinical data of 101 patients who underwent radical gastrectomy for gastric cancer in our hospital between January, 2013 and November, 2016, and examined the expression of ALDH3B1 in paraffin-embedded samples of gastric cancer tissues and adjacent tissues from these cases by immunohistochemical staining. We evaluated the correlation between ALDH3B1 expressions and histopathological parameters and assessed the predictive value of ALDH3B1 expression for long-term survival of the patients. We also examined the effect of lentivirus-mediated interference and overexpression of ALDH3B1 on the malignant behaviors of MGC-803 gastric cancer cells.@*RESULTS@#The expressions of ALDH3B1 and Ki67 were significantly higher in gastric cancer tissues than in adjacent tissues (P < 0.05). In gastric cancer patients, ALDH3B1 expression was positively correlated with peripheral blood CEA and CA19-9 levels (P < 0.01). The proportion of patients with CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T stage of 3- 4, and N stage of 2-3 was significantly greater in high ALDH3B1 expression group than in low expression group. Kaplan-Meier survival analysis showed that the 5-year survival rate was significantly lower in gastric cancer patients with high ALDH3B1 expressions (P < 0.01). Univariate and Cox multiple regression analyses identified a high expression of ALDH3B1 (P < 0.05, HR= 0.231, 95% CI: 0.064-0.826), CEA≥5 μg/L (P < 0.01, HR=4.478, 95% CI: 1.530-13.110), CA19-9≥37 kU/L (P < 0.01, HR=3.877, 95% CI: 1.625-9.247), T stage of 3-4 (P < 0.01, HR=4.953, 95% CI: 1.768-13.880), and N stage of 2-3 (P < 0.05, HR=2.152, 95% CI: 1.152-4.022) as independent risk factors affecting 5-year survival after radical gastrectomy. The relative ALDH3B1 expression level, at the cut-off point of 4.66, showed a sensitivity of 76.47% and a specificity of 76% for predicting 5-year postoperative death (P < 0.01). In the cell experiment, overexpression of ALDH3B1 obviously promoted the proliferation, migration and invasion of MGC-803 cells.@*CONCLUSION@#As an independent risk factor affecting 5-year survival after radical gastrectomy, ALDH3B1 is highly expressed in gastric cancer and correlated with pathological parameters of the tumor, and a high ALDH3B1 expression may promote proliferation, invasion and metastasis of gastric cancer cells.

MiR-17-5p Inhibits TXNIP/NLRP3 Inflammasome Pathway and Suppresses Pancreatic ß-Cell Pyroptosis in Diabetic Mice.

Objective: Diabetes mellitus is a chronic progressive inflammatory metabolic disease with pancreatic ß-cells dysfunction. The present study aimed to investigate whether miR-17-5p plays a protective effect on pancreatic ß-cells function in diabetes mellitus (DM) mice and dissect the underlying mechanism. Methods: C57BL/6J mice were randomly divided into control, DM, DM + Lentivirus negative control (LV-NC), and DM + Lenti-OE™ miR-17-5p (LV-miR-17-5) groups. DM was established by feeding a high-fat diet and intraperitoneal injection with streptozotocin (STZ) in mice. Blood glucose and glucose tolerance in circulation were measured. Meanwhile, the activation of nod-like receptor protein 3 (NLRP3) inflammasome, pancreas pyroptosis, and the expression of miR-17-5p and thioredoxin-interacting protein (TXNIP) were detected in the pancreas of DM mice. Pancreatic ß-cell line INS-1 subjected to different concentrations of glucose was used in in vitro experiments. Results: Compared with control mice, glucose tolerance deficit, elevated blood glucose level, and decreased pancreatic islet size, were presented in DM mice, which was associated with a downregulation of miR-17-5p. Importantly, exogenous miR-17-5p alleviated pancreas injury, and consequently improved glucose tolerance and decreased blood glucose in DM mice. In vitro experiments showed that high glucose decreased miR-17-5p expression and impaired insulin secretion in INS-1 cells. Mechanistically, miR-17-5p inhibited the expression of TXNIP and NLRP3 inflammasome activation, and thus decreased pancreatic ß-cell pyroptosis. Conclusion: Our results demonstrated that miR-17-5p improves glucose tolerance, and pancreatic ß-cell function and inhibits TXNIP/NLRP3 inflammasome pathway-related pyroptosis in DM mice.

The relation between aortic arch branching types and the location of large vessel occlusion in cardioembolic stroke.

Cardiac embolism is the leading etiology of ischemic strokes. There are arguments about the left-right propensity of cardioembolic strokes.This study aimed to reveal the relationship between the different aortic arch types and the location of large vessel occlusion (LVO) in cardioembolic stroke.We retrospectively identified all patients with acute ischemic stroke admitted to our comprehensive stroke center who had medium- to high-risk cardioembolicsources according to the TOAST classification.Only those with LVO and available images of the aortic arch were included. Patients were classified into 3 groups according to the aortic arch types: Type I (n = 44), Type II (n = 105), Type III (n = 36).The thrombus was divided into large thrombus or small thrombus based on the location of LVO.Overall, left-sided strokes (50.8%) were almost equal to right-sided (49.2%). There was a growing tendency for the percentage of left-sided infarcts with advancement of the aortic arch types either in the total cases or in the atrial fibrillation cases, with no statistical difference between the 3 aortic arch types.In type III aortic arch, left-sided strokes (69.0%) were twice than right-sided (31%) in large thrombus (P < 0.05), while right-sided strokes (85.7%) were more common than left-sided (14.3%) in small thrombus (P < 0.05).Conversely, in type Ⅰ and II aortic arches, left-sided strokes were more common than right-sided in small thrombus, while right-sided strokes were more common than left-sided in large thrombus (P < 0.05). The left-right propensity of cardioembolic stroke is related to the proximity of clot lodging in different aortic arch types.

The Natural History and Reperfusion Therapy Outcomes of Acute Ischemic Stroke due to Isolated M2 Occlusions.

OBJECTIVE: Currently, the standard treatment modality for patients with acute ischemic stroke (AIS) presenting with isolated M2 occlusions is not specific. We therefore assessed the difference in treatment outcomes for patients with isolated M2 occlusions. METHODS: We retrospectively analyzed consecutive patients with AIS presenting with isolated M2 occlusions from October 1, 2018, to June 30, 2020. Patients were divided into 3 groups based on the treatments they received: no reperfusion therapy (NRT), intravenous thrombolysis treatment (IVT), and endovascular intervention (EVT), which comprised IVT in conjunction with EVT or EVT alone. The primary outcomes were improvements in modified Rankin Scale (mRS) scores at 90 days and National Institutes of Health Stroke Scale (NIHSS) scores at 24 hours after treatment compared with the baseline. The secondary efficacy outcome comprised a good outcome rate defined as a 90 - day mRS score ≤ 2, final infarct volume (FIV), 90-day mortality rate, and successful recanalization rate, which was defined as a modified thrombolysis in cerebral infarction score ≥ 2b. Safety outcomes included symptomatic intracerebral hemorrhage and procedure-related complications. RESULTS: Seventy patients were enrolled and divided into 3 groups: the NRT group (n = 25), IVT group (n = 27), and EVT group (n = 18). Twenty-four-hour posttreatment NIHSS scores were substantially decreased by EVT compared with NRT (adjusted ß -4.01, 95% confidence interval [CI] -6.60 to -1.43; P = 0.003) or IVT (adjusted ß, -3.61 [95% CI, -6.45 to -0.77]; P = 0.013). Compared with the outcomes observed after NRT, patients who received EVT were more likely to achieve lower 90-day mRS scores (adjusted ß, -1.42 [95% CI, -2.66 to -0.63]; P = 0.007), higher good outcome rates (adjusted odds ratio, 8.73 [95% CI, 1.43-53.24]; P = 0.019), and smaller FIVs (adjusted ß, -29.66 [95% CI, -59.73 to 0.42]; P = 0.048). The recanalization rate of EVT was high (88.89%), and procedure-related complications were rare (5.56%). CONCLUSIONS: For acute, isolated M2 occlusions, EVT could dramatically and rapidly improve neurological deficits with high safety and effectiveness. These changes were observed at 24 hours after treatment and were maintained over the long term.

Dendritic cells transduced with TIPE-2 recombinant adenovirus induces T cells suppression.

INTRODUCTION: TIPE-2 has been identified as a negative regulator of both innate and adaptive immunity and is involved in several inflammatory diseases. However, the role of immune suppression of dendritic cells (DCs) transduced with TIPE-2 has not been well studied. METHODS: In this study, DCs were transduced with TIPE-2 recombinant adenovirus, and then were cocultured with allogeneic CD4+ or CD8 + T cells. The proliferation, cytokine production and activation marker levels of CD4+ or CD8 + T cell were detected. RESULTS: The data demonstrated that T cell proliferation, cytokine production and activation marker levels were attenuated after treated with TIPE-2 transduced DCs. CONCLUSIONS: These results suggested that TIPE-2 transduced DCs are capable of inducing allogeneic CD4+ or CD8 + T cell immune suppression, which provide a promising way for the therapeutical strategies of transplantation or autoimmune diseases.

Astroglial Connexins in Neurological and Neuropsychological Disorders and Radiation Exposure.

Radiotherapy is a common treatment for brain and spinal cord tumors and also a risk factor for neuropathological changes in the brain leading to different neurological and neuropsychological disorders. Astroglial connexins are involved in brain inflammation, development of Alzheimer's Disease (AD), depressive, epilepsy, and amyotrophic lateral sclerosis, and are affected by radiation exposure. Therefore, it is speculated that radiation-induced changes of astroglial connexins may be related to the brain neuropathology and development of neurological and neuropsychological disorders. In this paper, we review the functional expression and regulation of astroglial connexins expressed between astrocytes and different types of brain cells (including oligodendrocytes, microglia, neurons and endothelial cells). The roles of these connexins in the development of AD, depressive, epilepsy, amyotrophic lateral sclerosis and brain inflammation have also been summarized. The radiation-induced astroglial connexins changes and development of different neurological and neuropsychological disorders are then discussed. Based on currently available data, we propose that radiation-induced astroglial connexins changes may be involved in the genesis of different neurological and neuropsychological disorders which depends on the age, brain regions, and radiation doses/dose rates. The abnormal astroglial connexins may be novel therapeutic targets for the prevention of radiation-induced cognitive impairment, neurological and neuropsychological disorders.

Simultaneous Determination of Phenolic Acids, Anthraquinones, Flavonoids, and Triterpenes of Cynomorii Herba in Different Harvest Times by LC-MS/MS.

A sensitive and accurate method was developed for the simultaneous determination of twelve components including phenolic acids (gallic acid, protocatechuic aldehyde, protocatechuic acid, and ferulic acid), flavonoids (catechin, epicatechin, rutin, luteolin, luteolin-7-glucoside, and epicatechin gallate), anthraquinones (emodin), and triterpenes (ursolic acid) in Cynomorii herba in different harvest times by liquid chromatography tandem mass spectrometry (LC-MS/MS). The chromatographic separation was achieved on an Eclipse plus C18 (3.0 mm × 50 mm, 1.8 µm) column at 40°C. The mobile phase consisted of acetonitrile and 0.05% formic acid with a gradient elution at a flow rate of 0.4 mL·min -1. Under the optimized conditions, there was good linear relation (r ≥ 0.9944) and satisfactory precision (RSD values less than 5.65%). The recoveries of the twelve components were in the range of 93.5-105%. Moreover, the limits of detection (LOD) ranged from 0.003 to 21 ng mL-1 for the twelve analytes. In conclusion, the validated method was successfully applied to analyze the change regularity of the twelve components of Cynomorii herba in different harvest times. It provides a theoretical basis for choosing the suitable harvesting time of Cynomorii herba.

The Chromosome-Based Rubber Tree Genome Provides New Insights into Spurge Genome Evolution and Rubber Biosynthesis.

The rubber tree, Hevea brasiliensis, produces natural rubber that serves as an essential industrial raw material. Here, we present a high-quality reference genome for a rubber tree cultivar GT1 using single-molecule real-time sequencing (SMRT) and Hi-C technologies to anchor the ∼1.47-Gb genome assembly into 18 pseudochromosomes. The chromosome-based genome analysis enabled us to establish a model of spurge chromosome evolution, since the common paleopolyploid event occurred before the split of Hevea and Manihot. We show recent and rapid bursts of the three Hevea-specific LTR-retrotransposon families during the last 10 million years, leading to the massive expansion by ∼65.88% (∼970 Mbp) of the whole rubber tree genome since the divergence from Manihot. We identify large-scale expansion of genes associated with whole rubber biosynthesis processes, such as basal metabolic processes, ethylene biosynthesis, and the activation of polysaccharide and glycoprotein lectin, which are important properties for latex production. A map of genomic variation between the cultivated and wild rubber trees was obtained, which contains ∼15.7 million high-quality single-nucleotide polymorphisms. We identified hundreds of candidate domestication genes with drastically lowered genomic diversity in the cultivated but not wild rubber trees despite a relatively short domestication history of rubber tree, some of which are involved in rubber biosynthesis. This genome assembly represents key resources for future rubber tree research and breeding, providing novel targets for improving plant biotic and abiotic tolerance and rubber production.

Metformin inhibited Nod-like receptor protein 3 inflammasomes activation and suppressed diabetes-accelerated atherosclerosis in apoE-/- mice.

AIMS: The present study aimed to investigate the effect of metformin on diabetes-accelerated atherosclerosis and whether Nod-like receptor protein 3 (NLRP3) inflammasome is a target for metformin. MATERIALS AND METHODS: ApoE-/- male mice were divided randomly into control, streptozocin-induced diabetes mellitus and metformin groups. Metabolic parameters, atherosclerotic lesion, activation of NLRP3 inflammasomes and related signaling pathways were detected. THP-1-differentiated macrophages were used in in vitro experiments. RESULTS: Compared with control mice, increased plasma lipids and proinflammatory interleukin-1ß, aggravated macrophage infiltration into the atherosclerotic lesion, and accelerated development of atherosclerosis were observed in diabetic mice, which were associated with the activation of NLRP3 inflammasomes and dysregulation of thioredoxin-1 and thioredoxin-interacting protein. Treatment with metformin alleviated diabetes-induced metabolic disorders and atherosclerosis, as well as NLRP3 inflammasomes activation and dysregulation of thioredoxin-1/thioredoxin-interacting protein. In vitro experiments showed that high glucose induced the accumulation of reactive oxygen species and activated NLRP3 inflammasomes, which was significantly suppressed by treatment with metformin or antioxidant N-acetyl-L-cysteine. Moreover, Compound C, an inhibitor of adenosine 5'-monophosphate-activated protein kinase (AMPK), blocked the anti-inflammatory effect of metformin, indicating that metformin inhibited high glucose-induced NLRP3 inflammasomes activation through AMPK activation. Moreover, high glucose decreased thioredoxin-1 expression and increased thioredoxin-interacting protein expression, which was also reversed by metformin. CONCLUSIONS: Metformin inhibited NLRP3 inflammasomes activation and suppressed diabetes-accelerated atherosclerosis in apoE-/- mice, which at least partially through activation of AMPK and regulation of thioredoxin-1/thioredoxin-interacting protein.

Effect of fixed orthodontic treatment on oral microbiota and salivary proteins.

The aim of the present prospective comparative cohort study was to analyze changes in Streptococcus (S.) mutans and Lactobacillus in the saliva of patients with fixed orthodontics. Salivary parameters, including secretory immunoglobulin A (sIgA), myeloperoxidase (MPO) and lactate dehydrogenase (LDH), were investigated during orthodontic treatment, as well as immune response and inflammatory processes. A total of 15 patients were included and treated with fixed appliances. Whole saliva was obtained at four time-points: Prior to bonding (T1), 3 months after bonding (T2), 6 months after bonding (T3) and 18 months after bonding (T4). Quantitative polymerase chain reaction was performed to evaluate changes in total bacteria, S. mutans and Lactobacillus DNA in saliva. ELISA was applied to measure sIgA, MPO and LDH levels. The level of total bacteria remained stable during the 18-month treatment period, and the quantity of Lactobacillus exhibited a slight but non-significant increase. S. mutans remained stable over the first 6 months and significantly increased at T4 (P<0.05), and there was a significant difference in S. mutans levels between two types of braces. A higher level of S. mutans was found in patients with conventional braces, as compared to those with self-ligating braces (P<0.05) who exhibited an unchanged level of S. mutans during this period. The amount of sIgA, MPO and LDH remained constant during the orthodontic treatment period. No correlation was detected between sIgA and bacterial quantity. In conclusion, S. mutans in patients with conventional braces increased significantly in the late period of treatment, which indicated that white spot lesions may occur after long-term orthodontic treatment. As the type of braces may be considered a latent influencing factor, self-ligating braces should be preferred. However, the effect of fixed orthodontic treatment on Lactobacillus and sIgA, MPO and LDH in the oral microenvironment was insignificant (Chinese Clinical Trial Registry no. ChiCTR-RCH-13003295).

Quantification of eight active ingredients in crude and processed radix polygoni multiflori applying miniaturized matrix solid-phase dispersion microextraction followed by UHPLC.

A rapid, efficient, and green sample preparation method has been developed to extract eight active ingredients (gallic acid, catechins, epicatechin, polydatin, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside, resveratrol, emodin, and physcion) in radix polygoni multiflori by miniaturized matrix solid-phase dispersion microextraction. Simple and sensitive ultra high performance liquid chromatography combined with ultraviolet detection has been applied to analyze the multiple compounds. The best results were obtained by adding 25 mg sample into 25 mg adsorbent and grinding for 2 min with disorganized silica as adsorbent and 1 mL 150 mM 1-dodecyl-3-methylimidazolium bromide as a green eluting solvent. Good linearity (r2  > 0.998) for each analyte was obtained by this method. The intra-day and inter-day precision (RSD) were both below 5.31%, and the recoveries of the analytes ranged from 93.3 to 100.0%. This simple miniaturized matrix solid-phase dispersion microextraction method for analyzing the compounds in radix polygoni multiflori needs a short time and requires little sample and reagent. Thus, this method is far more eco-friendly and efficient than traditional extraction methods (reflux and ultrasound-assisted extraction). The present investigation provided a promising method for the fast preparation and discrimination of chemical differences in crude and processed radix polygoni multiflori.