Structure of the Major G-Quadruplex in the Human EGFR Oncogene Promoter Adopts a Unique Folding Topology with a Distinctive Snap-Back Loop.

EGFR tyrosine kinase inhibitors have made remarkable success in targeted cancer therapy. However, therapeutic resistance inevitably occurred and EGFR-targeting therapy has been demonstrated to have limited efficacy or utility in glioblastoma, colorectal cancer, and hepatocellular carcinoma. Therefore, there is a high demand for the development of new targets to inhibit EGFR signaling. Herein, we found that the EGFR oncogene proximal promoter sequence forms a unique type of snap-back loop containing G-quadruplex (G4), which can be targeted by small molecules. For the first time, we determined the NMR solution structure of this snap-back EGFR-G4, a three-tetrad-core, parallel-stranded G4 with naturally occurring flanking residues at both the 5'-end and 3'-end. The snap-back loop located at the 3'-end region forms a stable capping structure through two stacked G-triads connected by multiple potential hydrogen bonds. Notably, the flanking residues are consistently absent in reported snap-back G4s, raising the question of whether such structures truly exist under in vivo conditions. The resolved EGFR-G4 structure has eliminated the doubt and showed distinct structural features that distinguish it from the previously reported snap-back G4s, which lack the flanking residues. Furthermore, we found that the snap-back EGFR-G4 structure is highly stable and can form on an elongated DNA template to inhibit DNA polymerase. The unprecedented high-resolution EGFR-G4 structure has thus contributed a promising molecular target for developing alternative EGFR signaling inhibitors in cancer therapeutics. Meanwhile, the two stacked triads may provide an attractive site for specific small-molecule targeting.

Type I IFNs repolarized a CD169+ macrophage population with anti-tumor potentials in hepatocellular carcinoma.

Macrophages constitute a major component in human hepatocellular carcinoma (HCC) and perform various functions to facilitate disease progression. Reprogramming or reconstituting the tumor surveillance phenotypes of macrophages represents an attractive immunotherapeutic strategy in cancer treatments. The current study identified CD169 as a potential target for macrophage repolarization since it signified a population of macrophages positively correlated with an activated immune signature and better prognosis of patients with HCC. In vitro experiments revealed that a low dose of type I interferon (IFN) could effectively reprogram human monocyte-derived macrophages to upregulate CD169 expression, and such induced CD169+ macrophages exhibited significantly enhanced phagocytotic and CD8+ T cell-activating capacities compared to controls. A low dose of IFNα also inhibited hepatoma growth in mice in vivo, presumably through polarizing the CD169+ macrophage population and enhancing CD8+ T cell activities. Notably, IFNα also induced substantial PD-L1 expression on macrophages in vivo, and thus blockade of PD-L1 could further increase the anti-tumor efficacy of IFNα in the treatment of HCC. We propose a low dose of IFNα in combination with a PD-L1 blocking agent as a potential anti-tumor therapeutic strategy via its effects on macrophage polarization.

Oxidative Damage Induces a Vacancy G-Quadruplex That Binds Guanine Metabolites: Solution Structure of a cGMP Fill-in Vacancy G-Quadruplex in the Oxidized BLM Gene Promoter.

Guanine (G)-oxidation to 8-oxo-7,8-dihydroguanine (OG) by reactive oxygen species in genomic DNA has been implicated with various human diseases. G-quadruplex (G4)-forming sequences in gene promoters are highly susceptible to G-oxidation, which can subsequently cause gene activation. However, the underlying G4 structural changes that result from OG modifications remain poorly understood. Herein, we investigate the effect of G-oxidation on the BLM gene promoter G4. For the first time, we show that OG can induce a G-vacancy-containing G4 (vG4), which can be filled in and stabilized by guanine metabolites and derivatives. We determined the NMR solution structure of the cGMP-fill-in oxidized BLM promoter vG4. This is the first complex structure of an OG-induced vG4 from a human gene promoter sequence with a filled-in guanine metabolite. The high-resolution structure elucidates the structural features of the specific 5'-end cGMP-fill-in for the OG-induced vG4. Interestingly, the OG is removed from the G-core and becomes part of the 3'-end capping structure. A series of guanine metabolites and derivatives are evaluated for fill-in activity to the oxidation-induced vG4. Significantly, cellular guanine metabolites, such as cGMP and GTP, can bind and stabilize the OG-induced vG4, suggesting their potential regulatory role in response to oxidative damage in physiological and pathological processes. Our work thus provides exciting insights into how oxidative damage and cellular metabolites may work together through a G4-based epigenetic feature for gene regulation. Furthermore, the NMR structure can guide the rational design of small-molecule inhibitors that specifically target the oxidation-induced vG4s.

Melatonin promotes Arabidopsis primary root growth in an IAA-dependent manner.

Melatonin has been characterized as a growth regulator in plants. Melatonin shares tryptophan as the precursor with the auxin indole-3-acetic acid (IAA), but the interplay between melatonin and IAA remains controversial. In this study, we aimed to dissect the relationship between melatonin and IAA in regulating Arabidopsis primary root growth. We observed that melatonin concentrations ranging from 10-9 to 10-6 M functioned as IAA mimics to promote primary root growth in Arabidopsis wild type, as well as in pin-formed (pin) single and double mutants. Transcriptome analysis showed that changes in gene expression after melatonin and IAA treatment were moderately correlated. Most of the IAA-regulated genes were co-regulated by melatonin, indicating that melatonin and IAA regulated a similar subset of genes. Melatonin partially rescued primary root growth defects in pin single and double mutant plants. However, melatonin treatment had little effect on primary root growth in the presence of high concentrations of auxin biosynthesis inhibitors, or polar transport inhibitor, and could not rescue the root length defect of the IAA biosynthesis quintuple mutant yucQ. Therefore, we propose that melatonin promotes primary root growth in an IAA-dependent manner.

Abnormal Newborn Screening Follow-up for Severe Combined Immunodeficiency in an Amish Cohort with Cartilage-Hair Hypoplasia.

Cartilage-hair hypoplasia (CHH) is an autosomal recessive, short limb skeletal dysplasia with a variable immunologic phenotype. The spectrum of immune function ranges from clinically normal to severe combined immunodeficiency (SCID). Multiple studies have shown that abnormal immune parameters may not predict severe outcomes. Newborn screening (NBS) using T cell receptor excision circle (TREC) assay can now effectively identify infants with severe T cell deficiency who are at risk for SCID. NBS has allowed for cost-effective identification of patients with SCID and improved outcomes with hematopoietic stem cell transplant (HSCT). Ohio reports two abnormal TREC results: decreased and absent TREC. This study evaluated the laboratory and clinical differences in eight Amish patients with CHH with an abnormal TREC result on the NBS. There were four patients with absent TREC and four patients with decreased TREC. The absent TREC patients had lower CD3, CD4, naïve CD4, CD8 cells, and phytohemagglutinin (PHA)-induced lymphocyte proliferation. Three patients with absent TREC were diagnosed with SCID and two underwent successful HSCT. Patients with absent TREC experienced more CHH-related morbidity including anemia requiring transfusion, Hirschsprung's disease, and failure to thrive. No patients with decreased TREC required HSCT. Our study indicates that CHH patients with absent TREC tend to have more severe immunological and clinical phenotype than patients with decreased TREC. Confirmation of these trends in a larger group would guide providers and parents in a timely referral for HSCT, or cost-effective surveillance monitoring of children with a life-threatening illness.

Live cell evaluation of granzyme delivery and death receptor signaling in tumor cells targeted by human natural killer cells.

Growing interest in natural killer (NK) cell-based therapy for treating human cancer has made it imperative to develop new tools to measure early events in cell death. We recently demonstrated that protease-cleavable luciferase biosensors detect granzyme B and pro-apoptotic caspase activation within minutes of target cell recognition by murine cytotoxic lymphocytes. Here we report successful adaptation of the biosensor technology to assess perforin-dependent and -independent induction of death pathways in tumor cells recognized by human NK cell lines and primary cells. Cell-cell signaling via both Fc receptors and NK-activating receptors led to measurable luciferase signal within 15 minutes. In addition to the previously described aspartase-cleavable biosensors, we report development of granzyme A and granzyme K biosensors, for which no other functional reporters are available. The strength of signaling for granzyme biosensors was dependent on perforin expression in IL-2-activated NK effectors. Perforin-independent induction of apoptotic caspases was mediated by death receptor ligation and was detectable after 45 minutes of conjugation. Evidence of both FasL and TRAIL-mediated signaling was seen after engagement of Jurkat cells by perforin-deficient human cytotoxic lymphocytes. Although K562 cells have been reported to be insensitive to TRAIL, robust activation of pro-apoptotic caspases by NK cell-derived TRAIL was detectable in K562 cells. These studies highlight the sensitivity of protease-cleaved luciferase biosensors to measure previously undetectable events in live cells in real time. Further development of caspase and granzyme biosensors will allow interrogation of additional features of granzyme activity in live cells including localization, timing, and specificity.

The Arabidopsis Cys2/His2 zinc finger transcription factor ZAT18 is a positive regulator of plant tolerance to drought stress.

Environmental stress poses a global threat to plant growth and reproduction, especially drought stress. Zinc finger proteins comprise a family of transcription factors that play essential roles in response to various abiotic stresses. Here, we found that ZAT18 (At3g53600), a nuclear C2H2 zinc finger protein, was transcriptionally induced by dehydration stress. Overexpression (OE) of ZAT18 in Arabidopsis improved drought tolerance while mutation of ZAT18 resulted in decreased plant tolerance to drought stress. ZAT18 was preferentially expressed in stems, siliques, and vegetative rosette leaves. Subcellular location results revealed that ZAT18 protein was predominantly localized in the nucleus. ZAT18 OE plants exhibited less leaf water loss, lower content of reactive oxygen species (ROS), higher leaf water content, and higher antioxidant enzyme activities after drought treatment when compared with the wild type (WT). RNA sequencing analysis showed that 423 and 561 genes were transcriptionally modulated by the ZAT18 transgene before and after drought treatment, respectively. Pathway enrichment analysis indicated that hormone metabolism, stress, and signaling were over-represented in ZAT18 OE lines. Several stress-responsive genes including COR47, ERD7, LEA6, and RAS1, and hormone signaling transduction-related genes including JAZ7 and PYL5 were identified as putative target genes of ZAT18. Taken together, ZAT18 functions as a positive regulator and plays a crucial role in the plant response to drought stress.

Real-time detection of CTL function reveals distinct patterns of caspase activation mediated by Fas versus granzyme B.

Activation of caspase-mediated apoptosis is reported to be a hallmark of both granzyme B- and Fas-mediated pathways of killing by CTLs; however, the kinetics of caspase activation remain undefined owing to an inability to monitor target cell-specific apoptosis in real time. We have overcome this limitation by developing a novel biosensor assay that detects continuous, protease-specific activity in target cells. Biosensors were engineered from a circularly permuted luciferase, linked internally by either caspase 3/7 or granzyme B/caspase 8 cleavage sites, thus allowing activation upon proteolytic cleavage by the respective proteases. Coincubation of murine CTLs with target cells expressing either type of biosensor led to a robust luminescent signal within minutes of cell contact. The signal was modulated by the strength of TCR signaling, the ratio of CTL/target cells, and the type of biosensor used. Additionally, the luciferase signal at 30 min correlated with target cell death, as measured by a (51)Cr-release assay. The rate of caspase 3/7 biosensor activation was unexpectedly rapid following granzyme B- compared with Fas-mediated signal induction in murine CTLs; the latter appeared gradually after a 90-min delay in perforin- or granzyme B-deficient CTLs. Remarkably, the Fas-dependent, caspase 3/7 biosensor signal induced by perforin-deficient human CTLs was also detectable after a 90-min delay when measured by redirected killing. Thus, we have used a novel, real-time assay to demonstrate the distinct pattern of caspase activation induced by granzyme B versus Fas in human and murine CTLs.

[Right ventricular systolic function of patients with pneumoconiosis based on the evaluation of systolic displacement of tricuspid annulus].

OBJECTIVE: To determine the tricuspid annular plane systolic excursion (TAPSE) using M-mode echocardiography, and to evaluate the right ventricular systolic function in patients with pneumoconiosis. METHODS: One hundred and eighty-three patients with pneumoconiosis were enrolled as subjects, and one hundred and ninety-nine healthy volunteers were used as controls. According to the types of ventilation dysfunction, patients were divided into four groups: normal type, obstructive type, restrictive type, and mixed type. In the apex four-chamber sections, the displacement of tricuspid annular plane on the right ventricular free wall side was measured from end-diastole to end-systole using M-mode echocardiography. RESULTS: The average TAPSE in the pneumoconiosis group was significantly lower than that in the control group (18.61 ± 3.08 vs 22.38 ± 3.03 mm, P < 0.01). Along with the progression of pneumoconiosis, the TAPSE values in patients with stage I, II, and III pneumoconiosis were significantly decreased compared with those in the control group (P < 0.01). The TAPSE values in patients diagnosed with normal, obstructive, restrictive, and mixed types of pneumoconiosis in pulmonary function tests were all significantly lower than those in the control group (P < 0.01). Among all patients, patients with mixed type of pneumoconiosis had the most significant reduction in the TAPSE. CONCLUSION: The TAPSE is substantially decreased in patients with pneumoconiosis and further decreased along with the progression of pneumoconiosis. Measurement of the TAPSE is an easy way to evaluate the right ventricular systolic function in patients with pneumoconiosis.

Accuracy of radiomics in the diagnosis and preoperative high-risk assessment of endometrial cancer: a systematic review and meta-analysis.

Background: With the increasing use of radiomics in cancer diagnosis and treatment, it has been applied by some researchers to the preoperative risk assessment of endometrial cancer (EC) patients. However, comprehensive and systematic evidence is needed to assess its clinical value. Therefore, this study aims to investigate the application value of radiomics in the diagnosis and treatment of EC. Methods: Pubmed, Cochrane, Embase, and Web of Science databases were retrieved up to March 2023. Preoperative risk assessment of EC included high-grade EC, lymph node metastasis, deep myometrial invasion status, and lymphovascular space invasion status. The quality of the included studies was appraised utilizing the RQS scale. Results: A total of 33 primary studies were included in our systematic review, with an average RQS score of 7 (range: 5-12). ML models based on radiomics for the diagnosis of malignant lesions predominantly employed logistic regression. In the validation set, the pooled c-index of the ML models based on radiomics and clinical features for the preoperative diagnosis of endometrial malignancy, high-grade tumors, lymph node metastasis, lymphovascular space invasion, and deep myometrial invasion was 0.900 (95%CI: 0.871-0.929), 0.901 (95%CI: 0.877-0.926), 0.906 (95%CI: 0.882-0.929), 0.795 (95%CI: 0.693-0.897), and 0.819 (95%CI: 0.705-0.933), respectively. Conclusions: Radiomics shows excellent accuracy in detecting endometrial malignancies and in identifying preoperative risk. However, the methodological diversity of radiomics results in significant heterogeneity among studies. Therefore, future research should establish guidelines for radiomics studies based on different imaging sources. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=364320 identifier CRD42022364320.

A repeated halving approach to fabricate ultrathin single-walled carbon nanotube films for transparent supercapacitors.

Ultrathin SWCNT transparent and conductive films on flexible and transparent substrates are prepared via repeatedly halving the directly grown SWCNT films and flexible and transparent supercapacitors with excellent performance were fabricated.

Indium tin oxide nanowires grown by one-step thermal evaporation-deposition process at low temperature.

Indium tin oxide (ITO), as one of the most important transparent conducting oxide, is widely used in electro-optical field. We have developed a simple one-step method to synthesize ITO nanowires at low temperature of 600 degrees C. In detail, mixtures of InN nanowires and SnO powder, with the molar ratio of 10:1, have been used as precursors for the thermal evaporation-deposition of ITO nanowires on silicon/quartz slices. During the growth process, the evaporation temperature is maintained at 600 degrees C, which favors the decomposition of InN and oxidation of In, with a limited incorporation of Sn in the resulting compound (In:Sn approximately 11:1 in atomic ratio). As far as we know, this is the lowest growth temperature reported on the thermal deposition of ITO nanowires. The diameters of the nanowires are about 120 nm and the lengths are up to tens of micrometers. XRD characterization indicates the high crystallization of the nanowires. HRTEM results show the nanowires grow along the [200] direction. The transmittance of the nanowire film on quartz slice is more than 75% in the visible region. Based on photolithography and lift-off techniques, four-terminal measurement was utilized to test the resistivity of individual nanowire (6.11 x 10(-4) omega x cm). The high crystallization quality, good transmittance and low resistivity make as-grown ITO nanowires a promising candidate as transparent electrodes of nanoscale devices.

Temperature dependent resistance of as-grown and chemical treated single walled carbon nanotubes films.

Single Walled Carbon Nanotube (SWCNT) films were directly synthesized via Floating Catalyst Chemical Vapor Deposition (FCCVD) method. Temperature dependent resistance measurements were carried out on the as-grown and chemical treated SWCNTs films. A "U" shaped curve was obtained for each sample, with a significant variation in the crossover temperatures between the as-grown and treated samples. A heterogeneous model was adopted to interpret the experimental data, revealing the coexistence of anisotropic 1D metallic conduction, conventional metallic conduction and fluctuation assisted tunneling. Our results implied very low barriers, verifying the good intertube and interbundle contacts in the directly synthesized SWCNTs films. We speculated that oxidization and acid treatments would affect the overall configuration of the films, leading to the changes in the temperature dependence of resistance. In addition, Raman and absorption spectra indicated that oxidization and acid process would cause moderate changes in the hole carrier concentration of the films.

Optical and electrical performance of HfO2 coated ZnO nanorod arrays.

In this paper, we demonstrate the optical and electrical performance of ZnO nanorod arrays after surface passivation. The material of larger band gaps (HfO2) was chosen for the surface passivation layer through atom layer deposition (ALD), in order to confine the carriers within the core material efficiently. In the case of nanorods with high defects, HfO2 coating treatment not only improved near band edge (NBE) but also greatly enhanced the defect luminescence, while in the case of nanorods with low defects, surface coating suppressed defect luminescence and promoted the NBE emission as well as electrical performance therein. PL investigation at 10 K displayed that after surface coating phonon related emission was confined along c-axis and the exciton emission related to surface states was largely restrained. Therefore, it's suggested that surface passivation of ZnO nanorod arrays decreases the surface defect, enhances the side confinement of nanorod, and thus improves the optical and electrical performance efficiently.

In-situ Raman spectra of single-walled carbon nanotube/epoxy nanocomposite film under strain.

In-situ Raman spectra under continuous strain have been carried out to follow the load transfer efficiency in a single-walled carbon nanotube/epoxy nanocomposite film, which was fabricated by a facile and filter-free infiltration method using directly synthesized SWNT film as skeleton. It was found that in the low elastic range of 1%, with the increase of applied strain, the G- and G+ Raman bands downshift nearly lineally with corresponding ultrahigh rates up to -12 and -17 cm(-1)/% strain, respectively. As the applied strain decrease, these Raman bands upshift to their original frequencies with almost the same rates. These precise relationships between the Raman band shift and the applied strain enable this nanocomposite film promising stress or stain sensors. Furthermore, some Raman radial breathing modes (RBMs) disappear (appear) under larger strain (1.6%) and recover (vanish) when the strain is released, also verify the effective deformation of micro SWNTs induced by extra macro strain applied on the nanocomposite film. More interestingly, these frequency shifts and intensity vibrations are recoverable and repeatable, indicating the high elasticity of deformation in this strain region of 2%.

A facile method to fabricate ultrathin vertical ZnO nanowall arrays.

We demonstrate a facile method to synthesize ultrathin vertical ZnO nanowall arrays only through a one-step catalyst fabrication procedure. After being coated with uniformly dispersed gold particles, the substrates were polished gently to create discrete gold nanoparticle alignment as catalyst. The commercial ZnO powder and activated carbon powder with an atom ratio of 1:1 were utilized as source materials, and the whole growth process occurred in a conventional tube furnace chemical vapor deposition (CVD) system. The SEM images confirm that the ZnO nanowall arrays grow vertically along certain tracks made by polishing. The walls are about 17 nm wide, 90 nm high and 1 microm long after 90 min growth. After second growth, the nanowalls become 20 nm wide, 205 nm high, and 2 microm long. AFM images indicate that the alignment of discrete Au particles with certain separations due to polishing plays the key role in realizing vertical ZnO nanowall arrays.

Influence of subway train fire locations on the characteristics of smoke movement in a curved tunnel.

Scenario models of a moving subway train can help investigate the influence of different fire locations on smoke propagation characteristics in curved tunnels. To this end, this study adopts the three-dimensional Unsteady Reynolds Average Navier-Stokes equations method and the renormalization group k-ε two-equation turbulence model with buoyancy correction for numerical analysis. The motion of the train is replicated using the slip grid technique. The results indicate that when a fire breaks out on a moving train in tunnels, the piston wind leads the longitudinal movement of the smoke. If a fire erupts in the head or middle car of a moving train, the time of smoke backflow is delayed by 30 s or 17 s, respectively, compared to that for the tail car. The obtained results provide a theoretical basis for reasonably controlling the smoke flow in subway tunnels and reducing casualties in fire accidents.

circDENND4C, a novel serum marker for epithelial ovarian cancer, acts as a tumor suppressor by downregulating miR-200b/c.

RESEARCH OBJECTIVE: To explore the diagnostic value of circ-DENN domain containing 4 C (circDENND4C) in epithelial ovarian cancer (EOC) and the corresponding mechanism. METHODS: We determined the expression of circDENND4C and miR-200b/c in tissues and serum specimens as well as EOC cell lines using qRT-PCR. Basic clinical data, and serum HE4 and CAl25 levels were acquired from patients' clinical records. Expression-related correlations and the diagnostic value of serum circDENND4C in EOC were also estimated. CCK-8 and flow cytometry were performed to detect the effect of circDENND4C on cell proliferation and apoptosis. RESULTS: circDENND4C level was lowest while miR-200b/c was highest in EOC tissues, followed by benign and normal tissues. Similarly, serum circDENND4C was lowest while miR-200b/c was highest in EOC patients. Moreover, serum circDENND4C was lower in patients with benign ovarian tumors than in healthy women, while miR-200b/c expression was higher. circDENND4C was negatively associated with miR-200b/c in EOC tissues and serum specimens, and serum circDENND4C was also negatively correlated with serum HE4 and CAl25 in EOC patients. circDENND4C expression in both tissue and serum was negatively related to FIGO and TNM stage, and tumor size in EOC. Serum circDENND4C could distinguish healthy persons from patients with benign ovarian tumors and EOC, and they showed a higher specificity and accuracy than serum CA125 or HE4 in EOC diagnosis. circDENND4C upregulation significantly suppressed EOC cell proliferation and facilitated apoptosis by downregulating miR-200b/c in vitro. CONCLUSIONS: Summarily, circDENND4C acts as a tumor inhibitor by downregulating miR-200b/c in EOC and could be a possible tumor marker for EOC diagnosis.KEY MESSAGEScircDENND4C expression was lowest while miR-200b/c was highest in EOC tissues or serums, followed by benign and normal tissues or serums.circDENND4C was involved in malignant progression of EOC, concretely, overexpression of circDENND4C suppressed EOC cell proliferation and stimulated apoptosis via downregulating miR-200b/c, and circDENND4C expression in both tissue and serum was closely related to FIGO and TNM stages and tumor size in EOC.Serum circDENND4C showed a higher specificity and accuracy than serum CA125 or HE4 in EOC diagnosis.HIGHLIGHTScircDENND4C expression was lowest while miR-200b/c was highest in EOC tissues, followed by benign and normal tissues.Serum circDENND4C was lowest while miR-200b/c was highest in EOC patients, followed by benign patients and healthy women.Overexpression of circDENND4C suppresses EOC cell proliferation and stimulates apoptosis via downregulating miR-200b/c.circDENND4C expression in both tissue and serum was closely related to FIGO and TNM stage and tumor size in EOC.Serum circDENND4C showed a higher specificity and accuracy than serum CA125 or HE4 in EOC diagnosis.

Diagnostic accuracy of superb microvascular imaging for detecting intraplaque neovascularization: a systematic review and meta-analysis.

Background: Atherosclerotic plaques can cause carotid artery stenosis, and "vulnerable plaques" can even lead to ischemic stroke. The objective of this study was to assess the accuracy of superb microvascular imaging (SMI) for the detection of carotid intraplaque neovascularization (IPN) in patients with atherosclerotic plaques. Methods: We searched the Cochrane Library, Embase, Medline, and Wanfang databases until January 17, 2023. We included original studies with information on diagnostic accuracy of SMI for the evaluation of carotid IPN. The primary outcome was the accuracy of SMI for detecting carotid IPN. A meta-analysis was performed to estimate the accuracy of each parameter. We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) to assess the risk of bias for each included article. Meta-regression was performed to determine items that may have contributed to heterogeneity in the sensitivity or specificity of the test. Results: This meta-analysis included 20 studies with 1,589 carotid plaques in 1,225 patients. The analysis showed a sensitivity and specificity of SMI for detecting IPN of 93% [95% confidence interval (CI): 87-96%] and 80% (95% CI: 71-87%), respectively. The risk of bias across the QUADAS-2 domains was low. Only the proportion of dyslipidemia influenced the estimates of sensitivity and specificity. Conclusions: This review suggests that SMI has a good diagnostic performance for detecting carotid IPN. The very high sensitivity with excellent post-test probability indicated that SMI can be recommended to screen for carotid IPN among patients with carotid plaques.

Superfast-response and ultrahigh-power-density electromechanical actuators based on hierarchal carbon nanotube electrodes and chitosan.

Here we report a novel single-walled carbon nanotube (SWNT) based bimorph electromechanical actuator, which consists of unique as-grown SWNT films as double electrode layers separated by a chitosan electrolyte layer consisting of an ionic liquid. By taking advantage of the special hierarchical structure and the outstanding electrical and mechanical properties of the SWNT film electrodes, our actuators show orders-of-magnitude improvements in many aspects compared to previous ionic electroactive polymer (i-EAP) actuators, including superfast response (19 ms), quite wide available frequency range (dozens to hundreds of Hz), incredible large stress generating rate (1080 MPa/s), and ultrahigh mechanical output power density (244 W/kg). These remarkable achievements together with their facile fabrication, low driving voltage, flexibility, and long durability enable the SWNT-based actuators many applications such as artificial muscles for biomimetic flying insects or robots and flexible deployable reflectors.