Indirubin-3'-monoxime exhibits potent antiviral and anti-inflammatory effects against human adenoviruses in vitro and in vivo.

Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3'-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent.

A penicillinase-modified poly(N-isopropylacrylamide-co-acrylamide) smart hydrogel biosensor with superior recyclability for sensitive and colorimetric detection of penicillin G.

Antibiotics are widely used for treating bacterial infections. However, excessive or improper use of antibiotics can pose a serious threat to human health and water environments, and thus, developing cost-effective, portable and effective strategies to analyze and detect antibiotics is highly desired. Herein, we reported a responsive photonic hydrogel (RPH)-based optical biosensor (PPNAH) with superior recyclability for sensitive and colorimetric determination of a typical ß-lactam antibiotic penicillin G (PG) in water. This sensor was composed of poly(N-isopropylacrylamide-co-acrylamide) smart hydrogel with incorporated penicillinase and Fe3O4@SiO2 colloidal photonic crystals (CPCs). The sensor could translate PG concentration signals into changes in the diffraction wavelength and structural color of the hydrogel. It possessed high sensitivity and selectivity to PG and excellent detection performances for other two typical ß-lactam antibiotics. Most importantly, due to the unique thermosensitivity of the poly(N-isopropylacrylamide) moieties in the hydrogel, the PG-responded PPNAH sensor could be facilely regenerated via a simple physical method at least fifty times while without compromising its response performance. Besides, our sensor was suitable for monitoring the PG-contaminated environmental water and displayed satisfactory detection performances. Such a sensor possessed obvious advantages of superior recyclability, highly chemical stability, low production cost, easy fabrication, wide range of visual detection, simple and intuitive operation for PG detection, and environmental-friendliness, which holds great potential in sensitive and colorimetric detection of the PG residues in polluted water.

Photo-responsive nanoporous liquid crystal polymer films for selective dye adsorption.

Photo-responsive nanoporous polymer films (AZOF-R(NC6)) have been developed by a template method based on a hydrogen-bonding supramolecular liquid crystal (LC) and a light-sensitive azobenzene LC crosslinker in this work. Anionic nanopores were obtained after the removal of template NC6 using KOH solution. The AZOF-R(NC6) demonstrates charge-selective dye adsorption and the maximum adsorption capacity for Rh6G is 504.6 mg g-1. The AZOF-R(NC6) film without UV light treatment shows a 32% higher adsorption capacity for Rh6G than the AZOF-R(NC6) film treated with UV light within the initial 10 min. In addition, UV light can trigger the release of the adsorbed dye from the polymer film due to the pore size change arising from the trans-cis isomerization. Besides, the used polymer film can be effectively regenerated using a HCl solution. Such functional polymer films with highly ordered nanopores and photo-responsive properties hold great promise in selective adsorption and mass separations.

Reduced radiation dose and volume of contrast medium in heart rate-based, one-stop computed tomography angiography of coronary, carotid and cerebrovascular arteries.

BACKGROUND: Computed tomography angiography (CTA) is a reliable, non-invasive screening method for diagnosing panvascular disease. By using low contrast agent volume, CTA imaging enables one-stop multi-organ scanning, thereby minimizing the potential risk of contrast-induced nephropathy in patients with impaired renal function. PURPOSE: To evaluate the feasibility of one-stop CTA following a heart rate (HR)-based protocol using a low volume of contrast medium (CM) for examination of the coronary, carotid and cerebrovascular arteries. MATERIAL AND METHODS: Sixty patients undergoing coronary carotid, and cerebrovascular CTA after a single injection of CM were recruited and randomly divided into two groups. Group A (n = 30) underwent CTA following a traditional protocol. The timing of the scans in Group B (n = 30) was determined according to the patient's HR. RESULTS: The CT values for the thoracic aorta (432.2 ± 104.28 HU), anterior cerebral artery (303.96 ± 99.29 HU), and right coronary artery (366.70 ± 85.10 HU) in Group A did not differ significantly from those in Group B (445.80 ± 106.13, 293.73 ± 75.25 and 344.13 ± 111.04 HU, respectively). The qualities of most of the scanned images for both groups were scored as 3 or 4 (on a five-point scale). The radiation dose and the volume of CM were significantly higher in Group A (303.05 ± 110.95 mGy) (100 mL) than in Group B (239.46 ± 101.12 mGy) (50 mL). CONCLUSION: The radiation dose and volume of CM were significantly reduced in CTA following the HR-based protocol. The personalized administration of CM also simplified the scanning process.

Evaluation of Clinical Efficacy of Contrast-Enhanced Ultrasound in the Diagnosis of Ectopic Tubal Pregnancy.

Objective: To explore whether contrast-enhanced ultrasound (CEUS) can improve tubal ectopic pregnancy detection rate, tubal dilation, tubal hematoma, and gestational sac. Methods: This retrospective study included 34 patients with suspected ectopic pregnancy who underwent contrast-enhanced ultrasound at Dongzhimen Hospital of Beijing University of Chinese Medicine between March 2021 and September 2016. Of these, 27 patients were confirmed to have tubal pregnancy by laparoscopic surgery and histopathology. Four ultrasound physicians (2 experts and 2 non-experts) conducted a retrospective analysis of conventional color Doppler ultrasound and the combination of conventional color Doppler ultrasound with contrast-enhanced ultrasound (color Doppler ultrasound + CEUS). They analyzed the differences in confidence levels and reproducibility in identifying tubal dilation, tubal hematoma, and gestational sac implantation sites. Additionally, the characteristic features of ectopic pregnancy on contrast-enhanced ultrasound were summarized, including gestational sac morphology, triple ring sign, enhancement patterns (branching or punctate), tubal dilation (with or without hematoma), contrast enhancement of tubal walls, and presence of free fluid. Results: In the expert group, the correct identification rate of the gestational sac implantation site on ultrasound images increased from 13/34 (38.2%) with conventional color Doppler ultrasound to 20/34 (58.8%) with color Doppler ultrasound + CEUS, the differences were statistically significant (38.2% vs. 58.8%, P = .039). The correct identification rate of tubal dilation increased from 6/34 (17.7%) to 25/34 (73.5%) (P = .001), and the correct identification rate of tubal hematoma increased from 3/34 (8.8%) to 17/34 (50.0%) with color Doppler ultrasound + CEUS (P < .001). In the non-expert group, the correct identification rate of the gestational sac implantation site increased from 8/24 (23.5%) with conventional ultrasound to 19/34 (55.9%) with ultrasound + CEUS (P = .003). The correct identification rate of tubal dilation increased from 6/34 (17.7%) to 23/34 (67.7%) (P < .001), and the correct identification rate of tubal hematoma increased from 3/34 (8.82%) to 12/34 (35.3%) with color Doppler ultrasound + CEUS (P = .012). Conclusion: The analysis of contrast-enhanced ultrasound images provides characteristic features and diagnostic points for tubal ectopic pregnancy, including gestational sac, thick ring sign, tubal dilation, and tubal dilation with hematoma. This approach improves the accuracy of partial pregnancy of unknown location (PUL) diagnosis and reduces the technical dependence on ultrasound personnel.

Pressure-sensitive multivesicular liposomes as a smart drug-delivery system for high-altitude pulmonary edema.

Changes in bodily fluid pressures, such as pulmonary artery pressure, play key roles in high-altitude pulmonary edema (HAPE) and other disorders. Smart delivery systems releasing a drug in response to these pressures might facilitate early medical interventions. However, pressure-responsive delivery systems are unavailable. We here constructed hydrostatic pressure-sensitive multivesicular liposomes (PSMVLs) based on the incomplete filling of the internal vesicle space with neutral lipids. These liposomes were loaded with amlodipine besylate (AB), a next-generation calcium channel inhibitor, to treat HAPE on time. AB-loaded PSMVLs (AB-PSMVLs) were destroyed, and AB was released through treatment under hydrostatic pressure of at least 25 mmHg. At 25 mmHg, which is the minimum pulmonary artery pressure value in HAPE, 38.8% of AB was released within 1 h. In a mouse HAPE model, AB-PSMVLs concentrated in the lung and released AB to diffuse into the vascular wall. Intravenously injected AB-PSMVLs before HAPE modeling resulted in a stronger protection of lung tissues and respiratory function and lower occurrence of pulmonary edema than treatment with free drug or non-pressure-sensitive AB-loaded liposomes. This study offers a new strategy for developing smart drug delivery systems that respond to changes in bodily fluid pressures.

Diagnostic performance of contrast-enhanced ultrasound combined with shear wave elastography in differentiating benign from malignant breast lesions: a systematic review and meta-analysis.

Background: The value of contrast-enhanced ultrasound (CEUS), shear wave elastography (SWE) and their combination in the diagnosis of benign and malignant breast lesions have not been systematically evaluated. This study aimed to evaluate the diagnostic value of CEUS combined with SWE in benign and malignant breast lesions. Methods: We searched six electronic databases for literature to evaluate the value of CEUS combined with SWE in the diagnosis of benign and malignant breast lesions from inception to May 2023. Review Manager 5.4 (Cochrane), Meta-DiSc 1.4, and Stata 14.0 (StataCorp) were used for meta-analysis. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC) were calculated to evaluate the diagnostic performance. Results: Ultimately, 17 studies were analyzed including 1,962 lesions in total. The overall quality of the included literature was acceptable, and no significant publication bias was found among the included studies. The pooled diagnostic performance measures for CEUS were as follows: SEN: 0.86 [95% confidence interval (CI): 0.84-0.88], SPE: 0.78 (95% CI: 0.75-0.80), PLR: 4.10 (95% CI: 2.86-5.90), NLR: 0.20 (95% CI: 0.15-0.25), DOR: 23.68 (95% CI: 16.77-33.44), and AUC: 0.90 (95% CI: 0.87-0.93); while, for SWE, SEN: 0.83 (95% CI: 0.81-0.86), SPE: 0.81 (95% CI: 0.78-0.83), PLR: 4.36 (95% CI: 3.18-5.97), NLR: 0.22 (95% CI: 0.17-0.29), DOR: 23.13 (95% CI: 14.70-36.40), and AUC: 0.90 (95% CI: 0.87-0.92). The measures for the pooled diagnostic performance of CEUS combined with SWE were as follows: SEN: 0.92 (95% CI: 0.90-0.94), SPE: 0.87 (95% CI: 0.85-0.89), PLR: 7.10 (95% CI: 5.24-9.61), NLR: 0.11 (95% CI: 0.07-0.16), DOR: 83.51 (95% CI: 49.67-140.39), and AUC: 0.96 (95% CI: 0.94-0.98). There was no statistically significant difference in SEN, SPE, and accuracy (ACC) between CEUS and SWE (P>0.05), but they were significantly lower than those of CEUS combined with SWE (P<0.001). Conclusions: The diagnostic performance of CEUS combined with SWE is higher than that of using CEUS or SWE alone and can further improve the diagnosis of breast lesions.

Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus.

A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic cause. Here, we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesity or diabetes. We performed this panel in 481 patients to detect causative variants and compared these results with whole-exome sequencing (WES) data available for 146 of these patients. The coverage of targeted gene panel sequencing was significantly higher than that of WES. The diagnostic yield in patients sequenced by the panel was 32.9% with subsequent WES leading to three additional diagnoses with two novel genes. In total, 178 variants in 83 genes were detected in 146 patients by targeted sequencing. Three of the 178 variants were missed by WES, although the WES-only approach had a similar diagnostic yield. For the 335 samples only receiving targeted sequencing, the diagnostic yield was 32.2%. In conclusion, taking into account the lower costs, shorter turnaround time, and higher quality of data, targeted sequencing is a more effective screening method for monogenic obesity and diabetes compared to WES. Therefore, this approach could be routinely established and used as a first-tier test in clinical practice for specific patients.

A K+-sensitive photonic crystal hydrogel sensor for efficient visual monitoring of hyperkalemia/hypokalemia.

Potassium ions (K+) play crucial roles in many biological processes. Abnormal K+ levels in the body are usually associated with physiological disorders or diseases, and thus, developing K+-sensitive sensors/devices is of great importance for disease diagnosis and health monitoring. Herein, we report a K+-sensitive photonic crystal hydrogel (PCH) sensor with bright structural colors for efficient monitoring of serum potassium. This PCH sensor consists of a poly(acrylamide-co-N-isopropylacrylamide-co-benzo-15-crown-5-acrylamide) (PANBC) smart hydrogel with embedded Fe3O4 colloidal photonic crystals (CPCs), which could strongly diffract visible light and endow the hydrogel with brilliant structural colors. The rich 15-crown-5 (15C5) units appended on the polymer backbone could selectively bind K+ ions to form stable 2 : 1 [15C5]2/K+ supramolecular complexes. These bis-bidentate complexes served as physical crosslinkers to crosslink the hydrogel and contracted its volume, and thus reduced the lattice spacing of Fe3O4 CPCs and blue-shifted the light diffraction, and finally reported on the K+ concentrations by a color change of the PCH. Our fabricated PCH sensor possessed high K+ selectivity and pH- and thermo-sensitive response performances to K+. Most interestingly, the K+-responding PANBC PCH sensor could be conveniently regenerated via simple alternate flushing with hot/cold water due to the excellent thermosensitivity of the introduced PNIPAM moieties into the hydrogel. Such a PCH sensor provides a simple, low-cost and efficient strategy for visualized monitoring of hyperkalemia/hypokalemia, which will significantly promote the development of biosensors.

Up-regulation of PUM1 by miR-218-5p promotes colorectal tumor-initiating cell properties and tumorigenesis by regulating the PI3K/AKT axis.

Background: Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Advanced stage CRC, during the recent past, had a dismal prognosis and only a few available treatments. Pumilio homologous protein 1 (PUM1) is reportedly aberrant in human malignancies, including CRC. However, the role of PUM1 in the regulation of tumor-initiating cells (T-ICs) remains unknown. Methods: The levels of messenger RNAs (mRNAs) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunoblot analyses. Statistical analyses were performed to determine the associations between the levels of PUM1 and tumor features and patient outcomes. Whether PUM1 is a downstream target of miR-218-5p was verified by bioinformatics target gene prediction and qRT-PCR. Results: Herein, it was found that T-ICs, chemoresistance, and recurrent CRC samples all manifest increased PUM1 expression. Functional investigations have shown that PUM1 increased the self-renewal, tumorigenicity, malignant proliferation, and chemoresistance of colorectal cells. PUM1 activates the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway biochemically. Furthermore, it was discovered that miR-218-5p specifically targets T-ICs' PUM1 3'-untranslated region (3'-UTR). More importantly, the PUM1/PI3K/AKT axis regulates CRC cells' responses to treatment with cetuximab, and PUM1 overexpression increased cetuximab resistance. More evidence points to the possibility that low PUM1 may predict cetuximab benefits in CRC patients after analysis of the patient cohort, patient-derived tumor organoids, and patient-derived xenografts (PDXs). Conclusions: Taken together, the result of this work points to the critical function of the miR-218-5p/PUM1/PI3K/AKT regulatory circuit in regulating T-ICs characteristics and thus suggests possible therapeutic targets for CRC.

A chiral magnetic molybdenum disulfide nanocomposite for direct enantioseparation of RS-propranolol.

We herein report a novel chiral magnetic molybdenum disulfide nanocomposite (MMoS2/PNG-CD) with a high enantioselectivity and excellent thermosensitivity and magnetism. The prepared MMoS2/PNG-CD shows temperature-dependent chiral discrimination and enantioselectivity toward a chiral drug RS-propranolol (RS-PPL), which is based on the molecular recognition ability of beta-cyclodextrin (ß-CD) and the thermosensitivity of poly(N-isopropylacrylamide) (PNIPAM). The synthesized MMoS2/PNG2-CD by using a monomer molar ratio of GMA to NIPAM of 2 : 1 demonstrates a high selectivity toward R-PPL over S-PPL due to the synergistic effect of the PNIPAM moieties and ß-CD hosts. The thermo-induced volume phase transition (VPT) of the introduced PNIPAM moieties significantly affects the inclusion constants of the ß-CD/R-PPL complex, and thus the loading and desorption of R-PPL on the MMoS2/PNG2-CD. The enantioselectivity at temperatures below the lower critical solution temperature (LCST) of the PNG-ß-CD grafting chains is much higher than that at temperatures above the LCST. As a result, the regeneration of the MMoS2/PNG2-CD is easily achieved via simply changing the operating temperature. Moreover, the regenerated MMoS2/PNG2-CD can be readily recovered from the RS-PPL solution under an external magnetic field for reuse. Such a multifunctional molybdenum disulfide nanocomposite with a high enantioselectivity and excellent thermosensitivity and regenerability is promising to serve as a high-performance nanoselector for direct resolution of various ß-blocker drugs.

Development and validation of a model for predicting the risk of suicide in patients with cancer.

OBJECTIVE: The objective of this study was to establish a nomogram model to predict SI in patients with cancer and further evaluate its performance. METHOD: This study was performed among 390 patients in oncology departments of Affiliated Hospital of Nantong University from April 2020 to January 2021. Of these, eligible patients who were diagnosed with cancer were split into training and validation cohorts according the ratio of 2:1 randomly. In the training cohort, multivariate regression was performed to determine the independent variables related to SI. A nomogram was built incorporating these variables. The model performance was evaluated by an independent validation cohort. RESULTS: The prevalence of SI in patients with cancer was 22.31% and 19.23% in training and validation cohorts, respectively. The nomogram model suggested independent variables for SI, including depression, emotional function, time after diagnosis, family function and educational status. The area under the curve (AUC) was 0.93 (95%CI, 0.90-0.97) and 0.82 (95%CI, 0.74-0.90) in training and validation cohorts respectively, which indicated good discrimination of the nomogram in predicting SI in cancer patients. The p-value of the goodness of fit (GOF) test was 0.197 and 0.974 in training and validation cohorts respectively, suggesting our nomogram model has acceptable calibration power, and the calibration curves further indicated good calibration power. CONCLUSION: In conclusion, the nomogram model for predicting individualized probability of SI could help clinical caregivers estimate the risk of SI in patients with cancer and provide appropriate management.

Suicide rates among people with serious mental illness: a systematic review and meta-analysis.

BACKGROUND: People with serious mental illness are at great risk of suicide, but little is known about the suicide rates among this population. We aimed to quantify the suicide rates among people with serious mental illness (bipolar disorder, major depression, or schizophrenia). METHODS: PubMed and Web of Science were searched to identify studies published from 1 January 1975 to 10 December 2020. We assessed English-language studies for the suicide rates among people with serious mental illness. Random-effects meta-analysis was used. Changes in follow-up time and the suicide rates were presented by a locally weighted scatter-plot smoothing (LOESS) curve. Suicide rate ratio was estimated for assessments of difference in suicide rate by sex. RESULTS: Of 5014 identified studies, 41 were included in this analysis. The pooled suicide rate was 312.8 per 100 000 person-years (95% CI 230.3-406.8). Europe was reported to have the highest pooled suicide rate of 335.2 per 100 000 person-years (95% CI 261.5-417.6). Major depression had the highest suicide rate of 534.3 per 100 000 person-years (95% CI 30.4-1448.7). There is a downward trend in suicide rate estimates over follow-up time. Excess risk of suicide in males was found [1.90 (95% CI 1.60-2.25)]. The most common suicide method was poisoning [21.9 per 100 000 person-years (95% CI 3.7-50.4)]. CONCLUSIONS: The suicide rates among people with serious mental illness were high, highlighting the requirements for increasing psychological assessment and monitoring. Further study should focus on region and age differences in suicide among this population.

GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages.

G-protein-signaling modulator 1 (GPSM1) exhibits strong genetic association with Type 2 diabetes (T2D) and Body Mass Index in population studies. However, how GPSM1 carries out such control and in which types of cells are poorly understood. Here, we demonstrate that myeloid GPSM1 promotes metabolic inflammation to accelerate T2D and obesity development. Mice with myeloid-specific GPSM1 ablation are protected against high fat diet-induced insulin resistance, glucose dysregulation, and liver steatosis via repression of adipose tissue pro-inflammatory states. Mechanistically, GPSM1 deficiency mainly promotes TNFAIP3 transcription via the Gαi3/cAMP/PKA/CREB axis, thus inhibiting TLR4-induced NF-κB signaling in macrophages. In addition, we identify a small-molecule compound, AN-465/42243987, which suppresses the pro-inflammatory phenotype by inhibiting GPSM1 function, which could make it a candidate for metabolic therapy. Furthermore, GPSM1 expression is upregulated in visceral fat of individuals with obesity and is correlated with clinical metabolic traits. Overall, our findings identify macrophage GPSM1 as a link between metabolic inflammation and systemic homeostasis.

The significance of cognitive-behavioral therapy on suicide: An umbrella review.

BACKGROUND: Suicide becomes a widespread public health concern. Cognitive-behavioral therapy (CBT) is used to correct negative thoughts and behaviors of patients at risk of suicide. The aim of this research is to summarize and evaluate the existing evidence to explore the impact of CBT on suicide. METHOD: We conducted a systematic searched in PubMed, Web of Science, Cochrane database from the first available year to March 2021. The methodological quality was evaluated by AMSTAR-2 tool, and the evidence quality was evaluated by GRADE classification. We summarized all the comparative effects of CBT on suicide, and used forest plots to describe the impact of CBT on suicide related outcomes included suicidal ideation, suicide attempts. The random effects model was used to summarize data. RESULTS: Nine systematic reviews and meta-analysis were included. Most of the systematic reviews and meta-analysis were of medium methodological and evidence quality. The impact of CBT on suicide outcomes could be divided into the following two categories: CBT reduced levels of suicidal ideation (SMD -0.28, 95 % CI -0.36 to -0.21), CBT relieved suicide attempts (RR 0.77, 95 % CI 0.69 to 0.87). CONCLUSION: Based on the current evidence, CBT could relieve suicide, including suicide ideation, suicide attempts. CBT is scalable and cost-effective. It is helpful for health professionals to formulate personalized CBT programs, promote clinical and community applications and integrate them into comprehensive suicide interventions and prevention strategies.

Characterizing stroke-induced changes in the variability of lower limb kinematics using multifractal detrended fluctuation analysis.

Movement variability reflects the adaptation of the neuromuscular control system to internal or external perturbations, but its relationship to stroke-induced injury is still unclear. In this study, the multifractal detrended fluctuation analysis was used to explore the stroke-induced changes in movement variability by analyzing the joint angles in a treadmill-walking task. Eight healthy subjects and ten patients after stroke participated in the experiment, performing a treadmill-walking task at a comfortable speed. The kinematics data of the lower limbs were collected by the motion-capture system, and two indicators, the degree of multifractality (α) and degree of correlation [h(2)], were used to investigate the mechanisms underlying neuromuscular control. The results showed that the knee and ankle joint angles were multifractal and persistent at various scales, and there was a significant difference in the degree of multifractality and the degree of correlation at the knee and ankle joint angles among the three groups, with the values being ranked in the following order: healthy subjects < non-paretic limb < paretic limb. These observations highlighted increased movement variability and multifractal strength in patients after stroke due to neuromotor defects. This study provided evidence that multifractal detrended analysis of the angles of the knee and ankle joints is useful to investigate the changes in movement variability and multifractal after stroke. Further research is needed to verify and promote the clinical applications.

A Heart Rate-Dependent Protocol of "One-Stop" Computed Tomography Angiography of Coronary Combined with Pulmonary Arteries Reduces the Dosages of Contrast Agent.

Background: The personalized, heart rate-dependent computed tomography angiography (CTA) protocol can reduce the use of contrast medium (CM) and the radiation dose. This is especially beneficial for patients with CTA of coronary combined with pulmonary arteries. Purpose: To evaluate the feasibility of low CM in one-stop coronary and pulmonary arterial CTA tailored by patients' heart rate. Material and Methods: 94 patients set to undergo CTA of coronary combined with pulmonary arteries with one-stop scans. Patients were prospectively randomized into two groups: For group A (n = 47), the timing of the scans was determined according to the patient's HR using 30 mL CM; For group B (n = 47), in which the routine bolus tracking was applied by setting the ascending aortic threshold of 80 HU with 70 mL CM, scans were performed simultaneously. Results: Compared with group B, group A had slightly higher computed tomography (CT) value and image quality of pulmonary artery (CT value: group A 484.7HU; group B 457.9HU; t = 2.446, P = .016; image quality: χ2 = 8.292, P = .016), but in coronary artery wasn't statistically different between two groups(image quality: χ2 = 2.516, P = .642). Conclusion: The heart rate-dependent CM injection protocol can greatly reduce the use of CM, simplify the work-flow, and may obtain comparable or even better image quality compared with the routine bolus tracking.

Mediating effect of self-esteem on the relationship between leisure experience and aggression.

Previous research has shown that both the daily experiences and personal traits of adolescents are linked to aggression. Our aim was to further investigate the relationship between leisure experience, self-esteem, and aggression according to the general aggression model. In addition, within frustration-aggression theory, we proposed that leisure experience and aggression have a negative correlation. Furthermore, based on broaden-and-build theory, we explored the mediating role of self-esteem between leisure experience and aggression. The participants included 660 Chinese teenagers with an average age of 14.3. Among them, male students accounted for 310 (49.4%) and female students accounted for 318 (50.6%). The results showed that leisure experience was positively correlated with self-esteem and negatively correlated with aggression, while self-esteem was also negatively correlated with aggression. Additionally, self-esteem fully mediated the relationship between leisure experience and aggression. Our study could enrich research on leisure and provide a basis for protective factors of aggression in adolescents.

Tanshinone IIA-Loaded Micelles Functionalized with Rosmarinic Acid: A Novel Synergistic Anti-Inflammatory Strategy for Treatment of Atherosclerosis.

Rosmarinic acid (RA) and tanshinone IIA (TA) which are effective components in Salvia miltiorrhiza show anti-inflammatory potential against atherosclerosis. Based on polysulfated propylene-polyethylene glycol (PPS-PEG), RA was grafted onto this polymer via amide bonds to form a micelle carrier for TA encapsulation: PPS-PEG-RA@TA. A potent inhibitory effect on lipopolysaccharide (LPS) -induced proliferation of endothelial cells with significant intracellular uptake was observed with this system. This could have been the result of release of TA in a reactive oxygen species (ROS) environment and stronger antioxidant effect of RA. The synergistic effect was optimized when the combination was used in a molar ratio of 1:1. Mechanistic studies showed that, compared with PPS-PEG-RA and TA+RA, PPS-PEG-RA@TA micelles could more effectively regulate the nuclear factor-kappa B (NF-κB) pathway to reduce expression of vascular cell adhesion molecule-1 (VCAM-1), inhibit the inflammatory cascade and reduce endothelial-cell injury. One month after intravenous injection of PPS-PEG-RA@TA micelles, the plaque area in murine aortic vessels was reduced significantly, and serious toxic side-effects were not observed in vivo, along with excellent biocompatibility. In summary, PPS-PEG-RA@TA micelles could achieve synergistic treatment of atherosclerosis.