Speed behaviour and mental workload of small-spacing expressway interchanges based on field driving test.

Many small-spacing interchanges (SSI) appear with the improvement of the expressway network. To investigate the speed and mental workload characteristics in the SSI and acquire the mechanism of the influence of speed on the drivers' workload, 37 participants were recruited to perform a field driving test. Each driver performed four driving conditions (i.e. ramp-mainline, mainline-ramp, mainline driving, and auxiliary lane driving). The speed and drivers' electrocardiogram (ECG) data were collected using SpeedBox speed acquisition equipment and PhysioLAB physiological instrument. The heart rate increase (HRI) index was used to analyse the drivers' mental workload regularity. The relationship model between speed and HRI was developed to examine the impact of speed on HRI. The results show that the speed variation in the SSI displayed two patterns: 'decrease - increase and continuous decrease.' The drivers' HRI variation presented four patterns: 'convex curve, continuously increasing, continuously decreasing and concave curve'. SSI's influenced area length is given based on the speed and HRI variation regularity. HRI is significantly higher when driving in the ramp-mainline condition in the SSI than when driving in other conditions, indicating that drivers are more nervous when merging with the mainline traffic. HRI increases significantly in the first 50% of the weaving area in four driving conditions, indicating that vehicle weaving greatly influences the drivers' mental workload. A positive correlation exists between vehicle speed and drivers' HRI without interference from other vehicles and road alignment.

The shorter spacing of the interchange will result in a more difficult driving task for the drivers. This study shows that drivers have the highest mental workload in ramp-mainline driving condition at small-spacing interchanges. The first half of the weaving area is the area where drivers' mental workload increases significantly, and is a high-risk section for small-spacing interchanges. This study can provide a reference for the revision of the allowable minimum interchange spacing in the corresponding specification, and the calibration of the simulation test parameters for similar scenarios.

[Study on Impedance of Implantable Cardiac Pacemaker in Unipolar/Bipolar Pacing Mode by in Vitro Experiment].

The unipolar/bipolar pacing mode of pacemaker is related to its circuit impedance, which affects the battery life. In this study, the in vitro experiment scheme of pacemaker circuit impedance test was constructed. The human blood environment was simulated by NaCl solution, and the experimental environment temperature was controlled by water bath. The results of in vitro experiments showed that under the experimental conditions similar to clinical human parameters, the difference between the circuit impedance of bipolar mode and unipolar mode is 120~200 Ω. The results of the in vitro experiment confirmed that the circuit impedance of bipolar circuit was larger than that of unipolar mode, which was found in clinical practice. The results of this study have reference value to the optimization of pacing mode and the reduction of pacemaker power consumption.

N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide promotes bone formation via the canonical Wnt/ß-catenin signaling pathway.

Osteoporosis is characterized by low bone mineral density and microarchitectural deterioration of bone tissue. N-(3-methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide (MBOC) is one of the macamides isolated from Maca (Lepidium meyenii Walp.), a cruciferous plant from the Andes of Peru. In this study, C3H/10T1/2 mesenchymal stem cells were treated with MBOC in osteogenic induction medium. An ovariectomized (OVX) mouse model was used to investigate the effect of 1-month MBOC treatment on the prevention of postmenopausal osteoporosis. Remarkably, trabecular thickness, trabecular number, and bone volume/tissue volume of the distal femoral metaphysis were significantly increased in OVX + MBOC mice compared with OVX mice, as revealed by microcomputed tomography analysis. Trabecular separation was decreased in OVX + MBOC mice compared with OVX mice. Consistently, MBOC increased the levels of osteocalcin and runt-related transcription factor 2 in OVX mice, as well as the expression of runt-related transcription factor 2, osterix, and alkaline phosphatase in C3H/10T1/2 cells. Mechanistically, MBOC activates the canonical Wnt/ß-catenin signaling pathway via inhibiting phosphorylation of GSK-3ß at Tyr216 and maintaining ß-catenin expression. Collectively, the current study demonstrates the robustness of MBOC in the induction of mesenchymal stem cells osteogenic differentiation and consequent bone formation, suggesting that MBOC may be a potentially effective drug to treat postmenopausal osteoporosis.

[Research advances in the role of aptamers in the diagnosis and targeted therapy of pediatric cancer].

Aptamers are single-stranded DNA or RNA which are isolated from synthesized random oligonucleotide library in vitro via systematic evolution of ligands by exponential enrichment (SELEX) and can bind to metal ions, small molecules, carbohydrates, lipids, proteins, and others targets with high affinity and specificity. Aptamers have the advantages of simple preparation, good thermal stability, and low immunogenicity and have great potential in the medical fields such as molecular imaging, biosensing, early diagnosis of diseases, and targeted therapy. Aptamer technology may be useful for early diagnosis and targeted therapy of pediatric cancer, and may avoid the side effects of conventional chemotherapy, such as growth and development disorders and long-term organ dysfunction. This article reviews the latest research advances in the selection and application of aptamers for pediatric cancer.

Roles of ST2, IL-33 and BNP in predicting major adverse cardiovascular events in acute myocardial infarction after percutaneous coronary intervention.

This study investigated roles of serum ST2, IL-33 and BNP in predicting major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Blood samples were collected from the included AMI patients (n = 180) who underwent PCI. All patients were divided into the MACEs and MACEs-free groups. Enzyme-linked immunosorbent assay was performed to measure serum levels of ST2, IL-33 and BNP. Severity of coronary artery lesion was evaluated by Gensini score. Pearson correlation analysis was used. A receiver operating characteristics curve was drawn to evaluate the potential roles of ST2, IL-33 and BNP in predicting MACEs, and Kaplan-Meier curve to analyse the 1-year overall survival rate. Logistic regression analysis was conducted to analyse the independent risk factors for MACEs. Compared with the MACEs-free group, the serum levels of ST2, IL-33 and BNP were significantly higher in the MACEs group. Serum levels of ST2, IL-33 and BNP were positively correlated with each other and positively correlated with Gensini score. The area under curves of ST2, IL-33 and BNP, respectively, were 0.872, 0.675 and 0.902. The relative sensitivity and specificity were, respectively, 76.27% and 85.92%, 69.49% and 58.68%, as well as, 96.61% and 77.69%. Serum levels of ST2, IL-33 and BNP were independent risk factors for MACEs. The 1-year overall survival rate was higher in AMI patients with lower serum levels of ST2, IL-33 and BNP. In conclusion, serum levels of ST2, IL-33 and BNP have potential value in predicting MACEs in AMI patients undergoing PCI.

[CRISPR/Cas: a novel way of RNA-guided genome editing].

Bacteria and archaea have evolved an adaptive immune system, known as type II prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system, which uses short RNA to direct the degradation of target sequences present in invading viral and plasmid DNAs. Recent advances in CRISPR/Cas system provide an improved method for genome editing, showing robust and specific RNA-guided endonuclease activity at targeted endogenous genomic loci. It is the latest technology to modify genome DNA specifically and effectively following zinc finger nucleases (ZFNs) and TALE nucleases (TALENs). Compared with ZFNs and TALENs, CRISPR/Cas is much simpler and easier to engineer. This review summarizes recent progress, and discusses the prospects of CRISPR/Cas system, with an emphasis on its structure, principle, applications and potential challenges.

[Research on partial least squares for determination of impurities in the presence of high concentration of matrix by ICP-AES].

A method for detecting trace impurities in high concentration matrix by ICP-AES based on partial least squares (PLS) was established. The research showed that PLS could effectively correct the interference caused by high level of matrix concentration error and could withstand higher concentrations of matrix than multicomponent spectral fitting (MSF). When the mass ratios of matrix to impurities were from 1 000 : 1 to 20 000 : 1, the recoveries of standard addition were between 95% and 105% by PLS. For the system in which interference effect has nonlinear correlation with the matrix concentrations, the prediction accuracy of normal PLS method was poor, but it can be improved greatly by using LIN-PPLS, which was based on matrix transformation of sample concentration. The contents of Co, Pb and Ga in stream sediment (GBW07312) were detected by MSF, PLS and LIN-PPLS respectively. The results showed that the prediction accuracy of LIN-PPLS was better than PLS, and the prediction accuracy of PLS was better than MSF.

Comparison of posterior decompression techniques and conventional laminectomy for lumbar spinal stenosis.

Objectives: To compare the efficacy of posterior decompression techniques with conventional laminectomy for lumbar spinal stenosis. Methods: The Embase, PubMed, and Cochrane Library databases were searched with no language limitations from inception to January 13, 2022. The main outcomes were functional disability, perceived recovery, leg and back pain, complications. A random effects model was used to pooled data. Risk ratio (RR), mean difference (MD) and 95% confidence interval (CI) were used to report results. The study protocol was published in PROSPERO (CRD42022302218). Results: 14 trials including 1,106 participants were included in the final analysis. Bilateral laminotomy was significantly more efficacious in improve functionality than laminectomy [MD: -2.94; (95% CI, -4.12 to -1.76)]. Low incidence of iatrogenic instability due to bilateral laminectomy compared with laminectomy [RR: 0.11; (95% CI, 0.02 to 0.59)]. In addition, between those who received bilateral laminotomy and those undergoing laminectomy, the result showed significant difference regarding recovery [RR: 1.31; (95% CI, 1.03 to 1.67)]. Conclusions: This study provides evidence that bilateral laminotomy has advantages in functional recovery, postoperative stability, and postoperative rehabilitation outcomes. Further research is needed to determine whether posterior techniques provide a safe and effective option for conventional laminectomy.

Systemic immune inflammation index and system inflammation response index are potential biomarkers of atrial fibrillation among the patients presenting with ischemic stroke.

BACKGROUND: Chronic inflammatory disorders in atrial fibrillation (AF) contribute to the onset of ischemic stroke. Systemic immune inflammation index (SIII) and system inflammation response index (SIRI) are the two novel and convenient measurements that are positively associated with body inflammation. However, little is known regarding the association between SIII/SIRI with the presence of AF among the patients with ischemic stroke. METHODS: A total of 526 ischemic stroke patients (173 with AF and 353 without AF) were consecutively enrolled in our study from January 2017 to June 2019. SIII and SIRI were measured in both groups. Logistic regression analysis was used to analyse the potential association between SIII/SIRI and the presence of AF. Finally, the correlation between hospitalization expenses, changes in the National Institutes of Health Stroke Scale (NIHSS) scores and SIII/SIRI values were measured. RESULTS: In patients with ischemic stroke, SIII and SIRI values were significantly higher in AF patients than in non-AF patients (all p < 0.001). Moreover, with increasing quartiles of SIII and SIRI in all patients, the proportion of patients with AF was higher than that of non-AF patients gradually. Logistic regression analyses demonstrated that log-transformed SIII and log-transformed SIRI were independently associated with the presence of AF in patients with ischemic stroke (log-transformed SIII: odds ratio [OR]: 1.047, 95% confidence interval CI = 0.322-1.105, p = 0.047; log-transformed SIRI: OR: 6.197, 95% CI = 2.196-17.484, p = 0.001). Finally, a positive correlation between hospitalization expenses, changes in the NIHSS scores and SIII/SIRI were found, which were more significant in patients with AF (all p < 0.05). CONCLUSIONS: Our study suggests SIII and SIRI are convenient and effective measurements for predicting the presence of AF in patients with ischemic stroke. Moreover, they were correlated with increased financial burden and poor short-term prognosis in AF patients presenting with ischemic stroke.

Impaired Left Atrial Performance Resulting From Age-Related Arial Fibrillation Is Associated With Increased Fibrosis Burden: Insights From a Clinical Study Combining With an in vivo Experiment.

Background: Atrial fibrillation (AF) is increasingly considered an age-related degenerative disease, whose process is associated with the development of impaired left atrial (LA) performance. However, the subtle dynamic changes of LA performance in AF during aging have yet to be fully elucidated. Atrial fibrosis is a key substrate for the development of AF, but the progression of fibrosis during aging and its relationship with LA dysfunction need to be further explored. Methods: A total of 132 control individuals and 117 persistent AF patients were prospectively studied. Subjects were further stratified into three age groups (age group 1: younger than 65 years, age group 2: between 65 and 79 years old, and age group 3: older than 80 years). The two-dimensional speckle tracking imaging was carried out for analyzing the alterations in LA function underlying LA remodeling, whereas electroanatomic mapping was performed to investigate LA fibrosis burden. In animal study, aged mice and young mice served as research subjects. Echocardiography and histological staining were used to assess LA performance and fibrosis burden, respectively. Results: Echocardiography showed progressive increases in LA dimension and LA stiffness index, and progressive decreases in LA global longitudinal strain and LA strain rates with advancing age in both AF and control cohorts, which was more prominent in AF cohort. Electroanatomic mapping showed progressive decrease in mean LA voltage and progressive increases in LA surface area, low-voltage area %, and LA volume with advancing age, whereas more significant alterations were observed in AF patients. Moreover, left atrial global longitudinal strain was positively correlated with mean LA voltage, whereas LA stiffness index was negatively related to mean LA voltage. In animal experiment, increased LA size and pulmonary artery dimension as well as longer P-wave duration and more prominent LA fibrosis were found in aged mice. Conclusions: This study provides new evidence of subtle changes in structure and performance of left atrium and their association with atrial fibrosis in both AF and non-AF subjects during physiological aging. In addition, our study also provides normal values for LA structure and performance in both AF and non-AF conditions during aging. These measurements may provide an early marker for onset of AF and LA adverse remodeling.

Promoter methylation induced epigenetic silencing of DAZAP2, a downstream effector of p38/MAPK pathway, in multiple myeloma cells.

Multiple myeloma (MM) is hematological malignancy characterized by clonal proliferation of malignant plasma cells in the bone marrow environment. Previously, we identified DAZAP2 as a candidate cancer suppressor gene, the downregulation of which is regulated by its own promoter methylation status. In the current study, we analyzed the DAZAP2 promoter in MM cell lines KM3, MM.1S, OPM-2, and ARH77 by bisulfite genomic sequencing assay. We identified the binding site for transcription factor cyclic adenosine monophosphate response element binding (CREB) in the DAZAP2 promoter CpG2, and we found that hypermethylation of the CREB binding motif in the DAZAP2 promoter is responsible for the reduced DAZAP2 expression in MM cells. Later we checked the p38/MAPK signaling cascade, which is reported to regulate expression and function of CREB. Our results showed that the p38/MAPK signaling pathway drives the expression of DAZAP2 by phosphorylation of CREB, and hypermethylation of CREB binding motif in DAZAP2 promoter can inhibit binding of CREB to the latter, thus downregulating DAZAP2 expression. Moreover, treating the MM cells with 5-aza-2' deoxycytidine to demethylate DAZAP2 promoter restored the binding of CREB to its binding motif, and thus upregulated DAZAP2 expression. Our results not only identified DAZAP2 as a new downstream target of p38/MAPK/CREB signaling cascade, but we also clarified that the downregulation of DAZAP2 in MM cells is caused by hypermethylation of CREB binding motif in its own promoter region, which implies that demethylation of DAZAP2 promoter can be a novel therapeutic strategy for MM treatment.

Evaluation of x-inactivation status and cytogenetic stability of human dermal fibroblasts after long-term culture.

Human primary fibroblasts are a popular type of somatic cells for the production of induced pluripotent stem (iPS) cells. Here we characterized biological properties of primary fibroblasts in terms of cell-growth rate, cytogenetic stability, and the number of inactive X chromosomes during long-term passaging. We produced eight lines of female human dermal fibroblasts (HDFs) and found normal karyotype and expected pattern of X chromosome inactivation (XCI) at low passages (Passage P1-5). However, four out of the eight HDF lines at high passage numbers (≥ P10) exhibited duplicated hallmarks of inactive X chromosome including two punctuate signals of histone H3 lysine 27 trimethylation (H3K27me3) and X inactive-specific transcript (XIST) RNA signals in approximately 8.5-18.5% of the cells. Our data suggest that the copy number of inactive X chromosomes in a subset of female HDF is increased by a two-fold. Consistently, DNA fluorescent in situ hybridization (FISH) identified 3-4 copies of X chromosomes in one nucleus in this subset of cells with two inactive Xs. We conclude that female HDF cultures exhibit a higher risk of genetic anomalies such as carrying an increased number of X chromosomes including both active and inactive X chromosomes at a high passage (≥ P10).

Protective effect of adenosine A2A receptor activation in small-for-size liver transplantation.

The aim of the present study was to investigate the potential role of adenosine A(2A) receptor (A(2A)R) activation in small-for-size liver transplantation. A rat orthotopic liver transplantation model was performed by using 40% (range: 36-46%) liver grafts. Recipients were given either saline (control group) or CGS 21680 (2-p-(2-Carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride, a selective A(2A)R agonist), or CGS 21680+ ZM 241385 (a selective A(2A)R antagonist) immediately after reperfusion for 3 h. Compared with control group, CGS 21680 used at both low dose (0.05 microg/kg/min) and high dose (0.5 microg/kg/min) increased the survival rate from 16.7% (2/12) to 83.3% (10/12) and 66.7% (8/12), respectively. These effects correlated with improved liver function and preserved hepatic architecture. CGS 21680 effectively decreased neutrophil infiltration, suppressed pro-inflammatory (TNF-alpha, IL-1beta and IL-6) expression, promoted expression of antiapoptotic molecules, and inhibited apoptosis. The effects of CGS 21680 were prevented when ZM 241385 was co-administrated. In conclusion, the present study showed that A(2A)R activation alleviated portal hypertension, suppressed inflammatory response, reduced apoptosis, and potentiated the survival of small-for-size liver grafts. Our findings provide the rationale for a novel therapeutic approach using A(2A)R activation to maximize the availability of small-for-size liver grafts.