Association between Troponin Elevation and Decreased Myocardial Blood Flow Reserve in Patients without Obstructive Coronary Artery Disease.

INTRODUCTION: To study the prognostic factors of patients with chest pain and without obstructive coronary artery disease is of great significance for the management of such patients. We assessed whether a high-sensitivity troponin I (hs-TnI) is associated with prognosis in patients with chest pain and without obstructive coronary artery disease. METHODS: From 2011 to 2017, 489 consecutively hospitalized patients with chest pain and without significant coronary artery stenosis (<50%) were tested for hs-TnI and underwent stress myocardial contrast echocardiography (MCE). Myocardial blood flow reserve (MBFR) was measured by stress MCE. Patients were followed (median, 41 months) for composite endpoints, including cardiovascular death and non-fatal myocardial infarction. Cox proportional hazards models were performed to determine associations between hs-TnI and the composite endpoints. RESULTS: Among 489 patients with chest pain and without significant coronary artery stenosis, 257 patients (52.6%) had elevated hs-TnI. Compared to patients with normal hs-TnI, patients with elevated hs-TnI were older (p = 0.013) and had a higher prevalence of atrial fibrillation (p = 0.003), higher left ventricular mass index (p = 0.002) and E/e' septal (p < 0.001), and a lower MBFR (p < 0.001). After adjustment, there was still a significant association between hs-TnI and MBFR (odds ratio = 1.145; 95% confidence interval [CI], 1.079-1.214; p < 0.001). Compared with patients with normal hs-TnI, patients with elevated hs-TnI had a greater cumulative event rate (log-rank p = 0.002). Males (hazard ratio [HR], 4.770; 95% CI, 1.175-19.363; p = 0.029) and reduced MBFR (HR, 2.496; 95% CI, 1.446-4.311; p = 0.001) were risk factors associated with composite endpoints in patients with elevated hs-TnI. CONCLUSIONS: In patients with chest pain and without obstructive coronary artery disease, elevated hs-TnI is associated with decreased myocardial perfusion by contrast echocardiography as well as a higher incidence of cardiovascular events.

Engineering a Red Fluorescent Protein Chromophore for Visualization of RNA G-Quadruplexes.

Synthetic red fluorescent protein (RFP) chromophores have emerged as valuable tools for biological imaging and therapeutic applications, but their application in the visualization of endogenous RNA G-quadruplexes (G4s) in living cells has been rarely reported so far. Here, by integrating the group of the excellent G4 dye ThT, we modulate RFP chromophores to create a novel fluorescent probe DEBIT with red emission. DEBIT selectively recognizes the G4 structure with the advantage of strong binding affinity, high selectivity, and excellent photostability. Using DEBIT as a fluorescent indicator, the real-time monitoring of RNA G4 in biological systems can be achieved. In summary, our work expands the application of synthetic RFP chromophores and provides an essential dye category to the classical G4 probes.

Height-Switching Dynamics of Mixed Polymer Brushes with Polymers of Different Stiffnesses.

Mixed brushes consisting of flexible and semiflexible polymers of the same chain length exhibit a height-switching phenomenon because of rigidity-dependent critical adsorption [Yang et al. Macromolecules 2020, 53, 7369]. Semiflexible polymers stand higher at weak surface attraction (high temperature), but they close to the attractive surface at strong attraction (low temperature). In this work, the height-switching dynamics of the mixed polymer brushes is studied by Metropolis Monte Carlo simulation. The height-switching time is calculated by a sudden change in the surface attraction. Two surface attraction change modes, i.e., the weak-to-strong mode where the attraction is changed from weak to strong and the strong-to-weak mode where it is changed from strong to weak, are investigated. Simulation results show that the height-switching time is related to the grafting density, the polymer stiffness, and surface attraction change mode. We find that the height-switching time is significantly decreased for the strong-to-weak mode. And our results also show that the height switching in the mixed polymer brushes is reversible.

Nanozyme-based dual-signal sensing system for colorimetric and photothermal detection of AChE activity in the blood of liver-injured mice.

Acetylcholinesterase (AChE), a crucial enzyme related to liver function, is involved in numerous physiological processes such as neurotransmission and muscular contraction. The currently reported techniques for detecting AChE mainly rely on a single signal output, limiting their high-accuracy quantification. The few reported dual-signal assays are challenging to implement in dual-signal point-of-care testing (POCT) because of the need for large instruments, costly modifications, and trained operators. Herein, we report a colorimetric and photothermal dual-signal POCT sensing platform based on CeO2-TMB (3,3',5,5'-tetramethylbenzidine) for the visualization of AChE activity in liver-injured mice. The method compensates for the false positives of a single signal and realizes the rapid, low-cost portable detection of AChE. More importantly, the CeO2-TMB sensing platform enables the diagnosis of liver injury and provides an effective tool for studying liver disease in basic medicine and clinical applications. Rapid colorimetric and photothermal biosensor for sensitive detection of acetylcholinesterase (I) and acetylcholinesterase levels in mouse serum (II).

Transcriptome Analyses Show Changes in Gene Expression Triggered by a 31-bp InDel within OsSUT3 5'UTR in Rice Panicle.

Pollen development and its fertility are obligatory conditions for the reproductive success of flowing plants. Sucrose transporter 3 (OsSUT3) is known to be preferentially expressed and may play critical role in developing pollen. A 31-bp InDel was identified as a unique variation and was shown to be responsible for the expression of downstream gene in our previous study. In this study, to analyze the changes of gene expression triggered by 31-bp InDel during pollen development, two vectors (p385-In/Del::OsSUT3-GUS) were constructed and then stably introduced into rice. Histochemical and quantitative real-time PCR (qRT-PCR) analysis of transgenic plants showed that 31-bp deletion drastically reduced the expressions of downstream genes, including both OsSUT3 and GUS in rice panicle at booting stage, especially that of OsSUT3. The transcriptome profile of two types of panicles at booting stage revealed a total of 1028 differentially expressed genes (DEGs) between 31-bp In and 31-bp Del transgenic plants. Further analyses showed that 397 of these genes were significantly enriched for the 'metabolic process' and 'binding'. Among them, nineteen genes had a strong relationship with starch and sucrose metabolism and were identified as candidate genes potentially associated with the starch accumulation in rice pollen, which that was also verified via qRT-PCR. In summary, 31-bp InDel plays a crucial role not only in the regulation of downstream genes but in the expression of sucrose-starch metabolizing genes in multiple biological pathways, and provides a different regulation mechanism for sucrose metabolism in pollen.

Chromosome-specific painting unveils chromosomal fusions and distinct allopolyploid species in the Saccharum complex.

Karyotypes provide key cytogenetic information on the phylogenetic relationships and evolutionary origins in related eukaryotic species. Despite our knowledge of the chromosome numbers of sugarcane and its wild relatives, the chromosome composition and evolution among the species in the Saccharum complex have been elusive owing to the complex polyploidy and the large numbers of chromosomes of these species. Oligonucleotide-based chromosome painting has become a powerful tool of cytogenetic studies especially for plant species with large numbers of chromosomes. We developed oligo-based chromosome painting probes for all 10 chromosomes in Saccharum officinarum (2n = 8x = 80). The 10 painting probes generated robust fluorescence in situ hybridization signals in all plant species within the Saccharum complex, including species in the genera Saccharum, Miscanthus, Narenga and Erianthus. We conducted comparative chromosome analysis using the same set of probes among species from four different genera within the Saccharum complex. Excitingly, we discovered several novel cytotypes and chromosome rearrangements in these species. We discovered that fusion from two different chromosomes is a common type of chromosome rearrangement associated with the species in the Saccharum complex. Such fusion events changed the basic chromosome number and resulted in distinct allopolyploids in the Saccharum complex.

Study on laser-induced damage of TbBiIG crystal at 1064†nm.

With the development of miniaturization of high-energy laser systems, a new Faraday rotator material must be studied to realize the miniaturization and integration of optical isolators. In this paper, high-quality (TbBi)3Fe5O12 (TbBiIG) and Ca-doped (TbBi)3Fe5O12 (Ca: TbBiIG) single crystal films with hundreds of microns thickness were grown by liquid phase epitaxy method on (111) oriented garnet substrate. The crystal structure, magneto-optical (MO), optical and laser induced damage properties were investigated in detail. We found that the (TbBi)3Fe5O12 film has outstanding magneto-optical and laser-induced damage properties. Optical and MO properties indicate that TbBiIG films have a high specific faraday rotation angle of 1452 deg/cm at 1310 nm, and 2812 deg/cm at 1064 nm, absorption coefficient (α) is 5.63 cm-1 and 15.7 cm-1 at 1310 nm and 1064 nm, respectively. The laser-induced damage threshold (LIDT) of TbBiIG irradiated by a multi-frequency laser is 8.91 J/cm2. The light absorption has a significant impact on LIDT value. Rare-earth ion doped iron garnet (RIG) material is a very potential MO material, which can greatly reduce the size and weight of optical isolators in the 1064 nm band.

Langevin dynamics simulation on optimal conditions for large and stable loops of adsorbed homopolymers on substrates.

Adsorption of polymer chains on a solid surface is a universal interfacial behavior. Loops in the adsorbed chains are considered to exert a significant effect on the overall properties of a substrate-supported polymer film via entanglement with non-adsorbed chains in the film. In this work, the size and stability of loops formed by adsorbed homopolymer chains on an attractive substrate were studied by Langevin dynamics simulations. The size of loops decreases while the stability increases with increasing attraction strength of the substrate. In contrast, with an increase in the polymer concentration, the size of loops increases but the stability decreases. However, both the size and stability of loops increase with increasing chain length. Simulation results show that the optimal conditions for forming large and stable loops are long homopolymer chains, substrates with moderate attraction strength, and moderate polymer concentration.

All-optical spatial terahertz modulator with surface-textured and passivated silicon.

For a Si-based all-optical spatial terahertz modulator (STM), an enhanced modulation efficiency under low illumination density would be of great significance to exploit the competence of THz technology in real-world applications. We presented here an implementation of such a device by microtexturing and passivating the Si surface, forming a truncated pyramidal array (TPA). This TPA structure with SiO2 passivating coatings not only decreases light reflectance and expands the active area for THz modulation but also remarkably increases the photogenerated carrier lifetime. These 3-fold benefits render Si-TPA superior to bare-Si with respect to the achievable modulation efficiency, especially at low irradiation power. Furthermore such a Si-TPA device is also more applicable than its counterpart that is only passivated by SiO2 nanocoatings, even though the Si-SiO2 has a slightly increased modulation efficiency. These periodically aligned pyramids resembled as a mesa array significantly suppress the lateral diffusion induced by longer diffusion, resulting in an equivalent resolution of bare-Si. This novel Si-TPA based STM is highly desired for realizing a high-performance THz imager and provides a feasible approach to breaking the trade-off between resolution and modulation efficiency.

Terahertz magneto-optical response of bismuth-gadolinium-substituted rare-earth garnet film.

We report the magneto-optical Faraday response of bismuth-gadolinium-substituted rare-earth iron garnet at terahertz frequencies ranging from 100 GHz to 1.2 THz. The maximum transmittance of ±45° component is about 60% near the frequency point of 0.63 THz. When the external magnetic field change from -100 mT to +100 mT, the Faraday rotation angle is between -6° and +7.5°. The overall change of ellipticity is relatively small. The maximum value of the Verdet constant is about 260 °/mm/T at 0.1 THz and then gradually decreases to 80 °/mm/T at 1.2 THz. Within the considered frequency range, the thick film exhibits magnetically tunable, non-reciprocal characters and a strong magneto-optical effect within a small external magnetic field at room temperature, which will be widely used for the terahertz isolators, circulators, nonreciprocal phase shifters, and magneto-optical modulators.

Simulation study on the critical adsorption and diffusion of polymer chains on heterogeneous surfaces with random adsorption sites.

The critical adsorption and diffusion of a linear polymer chain on a heterogeneous surface with randomly distributed adsorption sites are studied using dynamic Monte Carlo simulations. Results show that the critical fraction of the adsorption sites at which critical adsorption takes place decreases exponentially with the increasing polymer-surface attraction strength and, at the same time, decreases with the increasing intra-polymer attraction strength. For adsorbed polymers with large intra-polymer attraction strength, we also find an adsorption-induced structural transition from a three-dimensional compact globule to a two-dimensional compacted pancake with an increasing fraction of adsorption sites. Anomalous sub-diffusion is observed for the adsorbed polymer diffusion on heterogeneous surfaces, in contrast to the normal diffusion on a homogeneous surface. The polymer on heterogeneous surfaces shows larger fluctuation in the total surface attraction energy and a longer waiting time.

Enhanced sugar accumulation and regulated plant hormone signalling genes contribute to cold tolerance in hypoploid Saccharum spontaneum.

BACKGROUND: Wild sugarcane Saccharum spontaneum plants vary in ploidy, which complicates the utilization of its germplasm in sugarcane breeding. Investigations on cold tolerance in relation to different ploidies in S. spontaneum may promote the exploitation of its germplasm and accelerate the improvement of sugarcane varieties. RESULTS: A hypoploid clone 12-23 (2n = 54) and hyperploid clone 15-28 (2n = 92) of S. spontaneum were analysed under cold stress from morphological, physiological, and transcriptomic perspectives. Compared with clone 15-28, clone 12-23 plants had lower plant height, leaf length, internode length, stem diameter, and leaf width; depressed stomata and prominent bristles and papillae; and thick leaves with higher bulliform cell groups and thicker adaxial epidermis. Compared with clone 15-28, clone 12-23 showed significantly lower electrical conductivity, significantly higher water content, soluble protein content, and superoxide dismutase activity, and significantly higher soluble sugar content and peroxidase activity. Under cold stress, the number of upregulated genes and downregulated genes of clone 12-23 was higher than clone 15-28, and many stress response genes and pathways were affected and enriched to varying degrees, particularly sugar and starch metabolic pathways and plant hormone signalling pathways. Under cold stress, the activity of 6-phosphate glucose trehalose synthase, trehalose phosphate phosphatase, and brassinosteroid-signalling kinase and the content of trehalose and brassinosteroids of clone 12-23 increased. CONCLUSIONS: Compared with hyperploid clone 15-28, hypoploid clone 12-23 maintained a more robust osmotic adjustment system through sugar accumulation and hormonal regulation, which resulted in stronger cold tolerance.

Terahertz magneto-optical effect of wafer-scale La: yttrium iron garnet single-crystal film with low loss and high permittivity.

The wafer-scale La:YIG single crystal thick films were fabricated on a three-inch gadolinium gallium garnet (GGG) substrate by liquid phase epitaxy method. The terahertz (THz) optical and magneto-optical properties of La:YIG film were demonstrated by THz time domain spectroscopy (THz-TDS). The results show that a high refractive index of approximately 4.09 and a low absorption coefficient of 10-50 cm-1 from 0.1 to 1.6 THz for this La:YIG film. Moreover, the THz Faraday rotation effect of La:YIG film was measured by the orthogonal polarization detection method in THz-TDS system, which can be actively manipulated by a weak longitudinal magnetic field of up to 0.155 T. With 5 samples stacked together, the Faraday rotation angle varies linearly from -15° to 15°, and the Verdet constant of La:YIG is about 100 °/mm/T within the saturation magnetization. This magneto-optical single crystal thick film with large area shows low loss, high permittivity and strong magneto-optical effect in the THz regime, which will be widely used in magneto-optical polarization conversion, nonreciprocal phase shifter and isolator for THz waves.

Characterization of a Saccharum spontaneum with a basic chromosome number of x = 10 provides new insights on genome evolution in genus Saccharum.

KEY MESSAGE: A novel tetraploid S. spontaneum with basic chromosome x = 10 was discovered, providing us insights in the origin and evolution in Saccharum species. Sugarcane (Saccharum spp., Poaceae) is a leading crop for sugar production providing 80% of the world's sugar. However, the genetic and genomic complexities of this crop such as its high polyploidy level and highly variable chromosome numbers have significantly hindered the studies in deciphering the genomic structure and evolution of sugarcane. Here, we developed the first set of oligonucleotide (oligo)-based probes based on the S. spontaneum genome (x = 8), which can be used to simultaneously distinguish each of the 64 chromosomes of octaploid S. spontaneum SES208 (2n = 8x = 64) through fluorescence in situ hybridization (FISH). By comparative FISH assay, we confirmed the chromosomal rearrangements of S. spontaneum (x = 8) and S. officinarum (2n = 8x = 80), the main contributors of modern sugarcane cultivars. In addition, we examined a S. spontaneum accession, Np-X, with 2n = 40 chromosomes, and we found that it was a tetraploid with the unusual basic chromosome number of x = 10. Assays at the cytological and DNA levels demonstrated its close relationship with S. spontaneum with basic chromosome number x = 8 (the most common accessions in S. spontaneum), confirming its S. spontaneum identity. Population genetic structure and phylogenetic relationship analyses between Np-X and 64 S. spontaneum accessions revealed that Np-X belongs to the ancient Pan-Malaysia group, indicating a close relationship to S. spontaneum with basic chromosome number of x = 8. This finding of a tetraploid S. spontaneum with basic chromosome number of x = 10 suggested a parallel evolution path of genomes and polyploid series in S. spontaneum with different basic chromosome numbers.

Caspase-Independent Pathway is Related to Nilotinib Cytotoxicity in Cultured Cardiomyocytes.

BACKGROUND/AIMS: Cardiotoxicity is a predominant side-effect of nilotinib during chronic myeloid leukemia treatment. The underlying molecular mechanism remains unclear. The role of autophagy and mitochondrial signaling was investigated in nilotinib-treated cardiac H9C2 cells. METHODS: Cytotoxicity was assessed using Cell Death Detection kit. Immunoblot and immunofluorescence staining was performed, and cathepsin B and caspase3 activity was assessed in nilotinib-treated H9C2 cells with or without distinct pathway inhibitor or specific siRNA. RESULTS: Nilotinib time- and dose-dependently induced H9C2 apoptosis, which was not completely prevented by the pan caspase inhibitor z-VAD-fmk. Following nilotinib treatment, mitochondrial membrane potential decreased significantly accompanied with remarkable morphological changes. Nuclear translocation of mitochondrial apoptosis inducing factor (AIF) and increased p53 was detected in nilotinib-treated cells. AIF knockdown prevented nilotinib-induced increase of p53 and apoptosis. Additionally, increased cathepsin B activity was detected, and inhibition of cathepsin B by CA-074Me prevented nilotinib-induced apoptosis and nuclear translocation of AIF. Moreover, increased Atg5 and transition of LC3-I to LC3-II was revealed following nilotinib treatment. Increased cathepsin B activity and apoptosis by nilotinib was significantly prohibited by specific autophagy inhibitor bafilomycin A and Atg5 knockdown. CONCLUSION: Our findings demonstrate that nilotinib increases autophagy and cathepsin B activity, leading to mitochondrial AIF release and nuclear translocation, which is responsible for p53 and apoptosis induction in H9C2 cells.

Association of interleukin-6 methylation in leukocyte DNA with serum level and the risk of ischemic heart disease.

Background Interleukin-6 (IL-6), a multifunctional cytokine, plays an important role in the development of ischemic heart disease (IHD), and DNA hypomethylation of 2 CpGs, located downstream in the proximity of the IL-6 gene promoter, has been associated with risk factor for IHD. This study was to examine the association of blood leukocyte DNA methylation of the 2 CpGs in IL-6 with the risk of IHD and the serum IL-6 level. Methods IL-6 methylation levels of 582 cases and 673 controls were measured using the bisulfite pyrosequencing technology. Serum level of IL-6 was measured using enzyme-linked immunosorbent assay. Results The IL-6 methylation was significantly lower in IHD cases than in the controls, irrespective of CpG site. After multivariate adjustment, lower (< median) average IL-6 methylation was associated with an increased risk of IHD (OR 1.57, 95% CI 1.22-2.02, p < 0.001). Average IL-6 methylation level was inversely associated with serum IL-6 level (ß = -1.02 pg/mL per increase in IL-6 methylation, p = 0.002) among IHD cases. This significant relationship was not observed among controls. Conclusions DNA hypomethylation of IL-6 gene measured in blood leukocytes was associated with increased risk of IHD. IL-6 demethylation may upregulate its expression, whereby exerting its risk effect on the development of IHD.

Inhibition of Autophagy Increases Proliferation Inhibition and Apoptosis Induced by the PI3K/mTOR Inhibitor NVP-BEZ235 in Breast Cancer Cells.

BACKGROUND: The phosphoinositide 3 kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) pathway is a complicated intracellular pathway which leads to cell growth and tumor proliferation and plays a significant role in breast cancer. Multiple compounds targeting this pathway are being evaluated in clinical trials. NVP-BEZ235, a novel and orally available dual PI3K/mTOR inhibitor, showed great antitumor effect and provided a therapy strategy in breast cancer. METHODS: In this study, we detect the effect of NVP-BEZ235 on cell viability, apoptosis, and autophagy in a breast cancer cell line. We also test the effect of NVP-BEZ235 on the expression of PI3K/AKT/mTOR pathway proteins p-AKT, p-mTOR, and p-70S6K. RESULTS: The results showed that the PI3K/AKT/mTOR proteins p-AKT, p-mTOR, and p-70S6K were obviously suppressed by NVP-BEZ235. NVP-BEZ235 inhibited cell proliferation and induced apoptosis and autophagy in breast cancer cells. In combination with autophagy inhibitors or autophagy gene knockdown, enhanced growth inhibition and apoptosis was induced by NVP-BEZ235 in MCF-7 cells. CONCLUSIONS: This study provides a novel treatment strategy that PI3K/AKT/mTOR pathway inhibitors in combination with autophagy inhibitors lead to further apoptosis in breast cancer cells.

Adiponectin Gene Polymorphisms are Associated with Increased Risk of Colorectal Cancer.

BACKGROUND: This meta-analysis investigates the associations of adiponectin (ADIPOQ) genetic polymorphisms with the susceptibility to colorectal cancer (CRC). MATERIAL AND METHODS: 2 reviewers independently searched 6 databases - PubMed, Cochrane Library, Ovid, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases - to identify published studies relevant to adiponectin gene polymorphisms and CRC. Studies retrieved from database searches were screened using our stringent inclusion and exclusion criteria. Full texts of the selected studies were accessed and related data was extracted using a standardized data extraction form. Comprehensive Meta-analysis 2.0 software was used for statistical analyses. RESULTS: A total of 188 studies were initially retrieved from database search, and 6 studies were eventually selected, through a rigorous screening process, for inclusion in this meta-analysis. The 6 studies contained a total of 1897 patients (Asians: 1190; white: 707) with CRC in case group and 2475 healthy controls (Asians: 1325; white: 1150) in the control group. Results of the current meta-analysis revealed that the rs2241766 T>G single-nucleotide polymorphisms (SNP) increase the risk of CRC; rs1501299 G>T under dominant model was associated with increased risk of CRC; and rs266729 C>G SNP under allele model conferred an increased risk of CRC. CONCLUSIONS: Our meta-analysis strongly suggests that the ADIPOQ rs2241766 T>G, rs1501299 G>T, and rs266729 C>G SNPs correlate with an increased risk of CRC.

Genetic association between cyclin D1 polymorphism and breast cancer susceptibility.

Cyclin D1 polymorphism has been reported to be associated with risk of breast cancer, but the published studies have yielded controversial results. This study was undertaken to derive a precise risk estimate for the cyclin D1 polymorphism associated with breast cancer risk. We performed a search of EMBASE, PubMed, and Web of Science. In total, data from 18 publications were pooled and the association was assessed by odds ratios (ORs) with 95 % confidence intervals (CIs). This analysis showed that there was no obvious association between the cyclin D1 polymorphism and breast cancer risk in any of the analyzed genetic model. We found the same negative association in stratified analyses by ethnicity, source of controls, and sample size. Our meta-analysis provides an estimate that the presence of cyclin D1 polymorphism may not confer susceptibility to breast cancer.

High-speed and broadband terahertz wave modulators based on large-area graphene field-effect transistors.

We present a broadband terahertz wave modulator with improved modulation depth and switch speed by cautiously selecting the gate dielectric materials in a large-area graphene-based field-effect transistor (GFET). An ultrathin Al2O3 film (∼60 nm) is deposited by an atomic-layer-deposition technique as a high-k gate dielectric layer, which reduces the Coulomb impurity scattering and cavity effect, and thus greatly improves the modulation performance. Our modulator has achieved a modulation depth of 22% and modulation speed of 170 kHz in a frequency range from 0.4 to 1.5 THz, which is a large improvement in comparison to its predecessor of SiO2-based GFET.