Rescue of cardiac dysfunction during chemotherapy in acute myeloid leukaemia by blocking IL-1α.

BACKGROUND AND AIMS: Patients with acute myeloid leukaemia (AML) suffer from severe myocardial injury during daunorubicin (DNR)-based chemotherapy and are at high risk of cardiac mortality. The crosstalk between tumour cells and cardiomyocytes might play an important role in chemotherapy-related cardiotoxicity, but this has yet to be demonstrated. This study aimed to identify its underlying mechanism and explore potential therapeutic targets. METHODS: Cardiac tissues were harvested from an AML patient after DNR-based chemotherapy and were subjected to single-nucleus RNA sequencing. Cardiac metabolism and function were evaluated in AML mice after DNR treatment by using positron emission tomography, magnetic resonance imaging, and stable-isotope tracing metabolomics. Plasma cytokines were screened in AML mice after DNR treatment. Genetically modified mice and cell lines were used to validate the central role of the identified cytokine and explore its downstream effectors. RESULTS: In the AML patient, disruption of cardiac metabolic homeostasis was associated with heart dysfunction after DNR-based chemotherapy. In AML mice, cardiac fatty acid utilization was attenuated, resulting in cardiac dysfunction after DNR treatment, but these phenotypes were not observed in similarly treated tumour-free mice. Furthermore, tumour cell-derived interleukin (IL)-1α was identified as a primary factor leading to DNR-induced cardiac dysfunction and administration of an anti-IL-1α neutralizing antibody could improve cardiac functions in AML mice after DNR treatment. CONCLUSIONS: This study revealed that crosstalk between tumour cells and cardiomyocytes during chemotherapy could disturb cardiac energy metabolism and impair heart function. IL-1α neutralizing antibody treatment is a promising strategy for alleviating chemotherapy-induced cardiotoxicity in AML patients.

Electrifying Hydroformylation Catalysts Exposes Voltage-Driven C-C Bond Formation.

Electrochemical reactions can access a significant range of driving forces under operationally mild conditions and are thus envisioned to play a key role in decarbonizing chemical manufacturing. However, many reactions with well-established thermochemical precedents remain difficult to achieve electrochemically. For example, hydroformylation (thermo-HFN) is an industrially important reaction that couples olefins and carbon monoxide (CO) to make aldehydes. However, the electrochemical analogue of hydroformylation (electro-HFN), which uses protons and electrons instead of hydrogen gas, represents a complex C-C bond-forming reaction that is difficult to achieve at heterogeneous electrocatalysts. In this work, we import Rh-based thermo-HFN catalysts onto electrode surfaces to unlock electro-HFN reactivity. At mild conditions of room temperature and 5 bar CO, we achieve Faradaic efficiencies of up to 15% and turnover frequencies of up to 0.7 h-1. This electro-HFN rate is an order of magnitude greater than the corresponding thermo-HFN rate at the same catalyst, temperature, and pressure. Reaction kinetics and operando X-ray absorption spectroscopy provide evidence for an electro-HFN mechanism that involves distinct elementary steps relative to thermo-HFN. This work demonstrates a step-by-step experimental strategy for electrifying a well-studied thermochemical reaction to unveil a new electrocatalyst for a complex and underexplored electrochemical reaction.

High-Sensitivity Differential Helmholtz Photoacoustic System Combined with the Herriott Multipass Cell and Its Application in Seed Respiration.

A highly sensitive photoacoustic detection system using a differential Helmholtz resonator (DHR) combined with a Herriott multipass cell is presented, and its implementation to sub-ppm level carbon dioxide (CO2) detection is demonstrated. Through the utilization of erbium-doped optical fiber amplifier (EDFA), the laser power was amplified to 150 mW. Within the multipass cell, a total of 22 reflections occurred, contributing to an impressive 33.6 times improvement in the system sensitivity. The normalized noise equivalent absorption coefficient (NNEA) was 8.64 × 10-11 cm-1·W·Hz-1/2 [signal-to-noise ratio, (SNR) = 1] and according to the Allan variance analysis, a minimum detection limit of 500 ppb could be achieved for CO2 at 1204 s, which demonstrates the long-term stability of the system. The system was applied to detect the respiration of rice and upland rice seeds. It is demonstrated that the system can monitor and distinguish the respiration intensity and respiration rate of different seeds in real time.

Effects of trimetazidine on cardiac function in adult cyanotic congenital heart disease patients: Protocol for a 3-month multicenter, randomized, double-blind controlled trial.

BACKGROUND: Nearly 20% Patients with cyanotic congenital heart disease (CCHD) are not able to receive surgery. These patients experience a decline in cardiac function as they age, which has been demonstrated to be associated with changes in energy metabolism in cardiomyocytes. Trimetazidine (TMZ), a metabolic regulator, is supposed to alleviate such maladaptation and reserve cardiac function in CCHD patients. METHODS: This is a randomized, double-blind, placebo-controlled clinical trial. Eighty adult CCHD patients will be recruited and randomized to the TMZ (20 mg TMZ 3 times a day for 3 months) or placebo group (placebo 3 times a day for 3 months). The primary outcome is the difference in cardiac ejection fractions (EF) measured by cardiac magnetic resonance (MRI) between baseline and after 3 months of TMZ treatment. The secondary outcomes include TMZ serum concentration, rate of cardiac events, NYHA grading, fingertip SpO2, NT-proBNP levels, 6-minute walking test (6MWT), KCCQ-CSS questionnaire score, echocardiography, ECG, routine blood examination, liver and kidney function test, blood pressure and heart rate. DISCUSSION: This trial is designed to explore whether the application of TMZ in adult CCHD patients can improve cardiac function, reduce cardiac events, and improve exercise performance and quality of life. The results will provide targeted drug therapy for CCHD patients with hypoxia and support the application of TMZ in children with CCHD.

High-definition imaging using line-illumination modulation microscopy.

The microscopic visualization of large-scale three-dimensional (3D) samples by optical microscopy requires overcoming challenges in imaging quality and speed and in big data acquisition and management. We report a line-illumination modulation (LiMo) technique for imaging thick tissues with high throughput and low background. Combining LiMo with thin tissue sectioning, we further develop a high-definition fluorescent micro-optical sectioning tomography (HD-fMOST) method that features an average signal-to-noise ratio of 110, leading to substantial improvement in neuronal morphology reconstruction. We achieve a >30-fold lossless data compression at a voxel resolution of 0.32 × 0.32 × 1.00 µm3, enabling online data storage to a USB drive or in the cloud, and high-precision (95% accuracy) brain-wide 3D cell counting in real time. These results highlight the potential of HD-fMOST to facilitate large-scale acquisition and analysis of whole-brain high-resolution datasets.

Predictive Value of the Diffusion Magnetic Resonance Imaging Technique for the Postoperative Outcome of Cervical Spondylotic Myelopathy.

BACKGROUND: Diffusion magnetic resonsance imaging (dMRI) can potentially predict the postoperative outcome of cervical spondylotic myelopathy (CSM). PURPOSE: To explore preoperative dMRI parameters to predict the postoperative outcome of CSM through multifactor correlation analysis. STUDY TYPE: Prospective. POPULATION: Post-surgery CSM patients; 102 total, 73 male (52.42 ± 10.60 years old) and 29 female (52.0 ± 11.45 years old). FIELD STRENGTH/SEQUENCE: 3.0 T/Turbo spin echo T1/T2-weighted, T2*-weighted multiecho gradient echo and dMRI. ASSESSMENT: Spinal cord function was evaluated using modified Japanese Orthopedic Association (mJOA) scoring at different time points: preoperative and 3, 6, and 12 months postoperative. Single-factor correlation and t test analyses were conducted based on fractional anisotropy (FA), mean diffusivity, intracellular volume fraction, isotropic volume fraction, orientation division index, increased signal intensity, compression ratio, age, sex, symptom duration and operation method, and multicollinearity was calculated. The linear quantile mixed model (LQMM) and the linear mixed-effects regression model (LMER) were used for multifactor correlation analysis using the combinations of the above variables. STATISTICAL TESTS: Distance correlation, Pearson's correlation, multiscale graph correlation and t tests were used for the single-factor correlation analyses. The variance inflation factor (VIF) was used to calculate multicollinearity. LQMM and LMER were used for multifactor correlation analyses. P < 0.05 was considered statistically significant. RESULTS: The single-factor correlation between all variables and the postoperative mJOA score was weak (all r < 0.3). The linear relationship was stronger than the nonlinear relationship, and there was no significant multicollinearity (VIF = 1.10-1.94). FA values in the LQMM and LMER models had a significant positive correlation with the mJOA score (r = 5.27-6.04), which was stronger than the other variables. DATA CONCLUSION: The FA value based on dMRI significantly positively correlated with CSM patient postoperative outcomes, helping to predict the surgical outcome and formulate a treatment plan before surgery. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Photoelectrochemical signal polarity transition mediated by quercetin for the detection of neuron-specific enolase.

A photoelectrochemical (PEC) biosensor with a wide linear detection range was developed for the sensitive detection of neuron-specific enolase (NSE), which was achieved by applying a photocurrent polarity transition strategy mediated by quercetin. The coupling reaction between Cr(VI) and quercetin drives the signal polarity from anodic to cathodic. When only quercetin is present in the test solution, photogenerated electrons are transferred to the electrode to generate anodic photocurrent. However, in the presence of the target, the signal probe released Cr(VI), which interacted with quercetin, and the electron transfer direction was changed to achieve signal polarity conversion. Meanwhile, protoporphyrin-sensitized Bi:SrTiO3 nanocubes were used as matrix photoactive materials to provide basic photocurrent. The doping of Bi element would adjust the bandgap of SrTiO3, and the organic-inorganic composite material exhibits good photostability and chemical stability that can maintain stable photoelectric properties over a long period of time. Such a novel signal polarity transition strategy greatly broadened the sensor detection to the range of 0.00007-170 ng mL-1 and obtained a relatively low detection limit (25 fg mL-1), which greatly improved the detection sensitivity and accuracy of the biosensor.

Dye-sensitized NiO photocathode sensor based on signal-sensitive change strategy for MC-LR detection.

A novel photoelectrochemical (PEC) sensor for the detection of microcystic toxins (MC-LR) was developed on the basis of signal-sensitive change strategy. NiO nanoarray as a basic photoactive material was grown directly on the ITO glass electrode via calcination after hydrothermal reaction, while dye N719 was used to sensitize the electrode for enhancing visible light absorption, and the first signal-on stage was obtained. In the meantime, p-type Cu2O was applied as the signal probe attached to probe DNA (DNA2) to improve the sensitivity, and the second "signal-on" stage appeared because of its synergistic effect with NiO nanoarrays. The PEC signal decreases after the target analyte MC-LR is modified on the electrode due to the stronger affinity between MC-LR and its complementary aptamer DNA; part of the Cu2O-DNA2 will dissociate from the electrode. This sensitive signal change strategy allows the detection limit of the MC-LR sensor to be as low as 1.7 pM, which offers an optional method for the sensitive and selective detection of other target molecules, with potential applications in environmental monitoring and toxin determination.

Preliminary exploration of deep learning-assisted recognition of superior labrum anterior and posterior lesions in shoulder MR arthrography.

PURPOSE: MR arthrography (MRA) is the most accurate method for preoperatively diagnosing superior labrum anterior-posterior (SLAP) lesions, but diagnostic results can vary considerably due to factors such as experience. In this study, deep learning was used to facilitate the preliminary identification of SLAP lesions and compared with radiologists of different seniority. METHODS: MRA data from 636 patients were retrospectively collected, and all patients were classified as having/not having SLAP lesions according to shoulder arthroscopy. The SLAP-Net model was built and tested on 514 patients (dataset 1) and independently tested on data from two other MRI devices (122 patients, dataset 2). Manual diagnosis was performed by three radiologists with different seniority levels and compared with SLAP-Net outputs. Model performance was evaluated by the receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), etc. McNemar's test was used to compare performance among models and between radiologists' models. The intraclass correlation coefficient (ICC) was used to assess the radiologists' reliability. p < 0.05 was considered statistically significant. RESULTS: SLAP-Net had AUC = 0.98 and accuracy = 0.96 for classification in dataset 1 and AUC = 0.92 and accuracy = 0.85 in dataset 2. In dataset 1, SLAP-Net had diagnostic performance similar to that of senior radiologists (p = 0.055) but higher than that of early- and mid-career radiologists (p = 0.025 and 0.011). In dataset 2, SLAP-Net had similar diagnostic performance to radiologists of all three seniority levels (p = 0.468, 0.289, and 0.495, respectively). CONCLUSIONS: Deep learning can be used to identify SLAP lesions upon initial MR arthrography examination. SLAP-Net performs comparably to senior radiologists.

Longitudinal changes of oxidative stress and PON1 lactonase activity and status in older pregnant women undergoing assisted reproductive technology: a prospective nested case-control study.

BACKGROUND: Childbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART. METHODS: This prospective nested case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed. RESULTS: Lactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups. CONCLUSIONS: Women with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases.

Application research of AI-assisted compressed sensing technology in MRI scanning of the knee joint: 3D-MRI perspective.

OBJECTIVE: To investigate the potential applicability of AI-assisted compressed sensing (ACS) in knee MRI to enhance and optimize the scanning process. METHODS: Volunteers and patients with sports-related injuries underwent prospective MRI scans with a range of acceleration techniques. The volunteers were subjected to varied ACS acceleration levels to ascertain the most effective level. Patients underwent scans at the determined optimal 3D-ACS acceleration level, and 3D compressed sensing (CS) and 2D parallel acquisition technology (PAT) scans were performed. The resultant 3D-ACS images underwent 3.5 mm/2.0 mm multiplanar reconstruction (MPR). Experienced radiologists evaluated and compared the quality of images obtained by 3D-ACS-MRI and 3D-CS-MRI, 3.5 mm/2.0 mm MPR and 2D-PAT-MRI, diagnosed diseases, and compared the results with the arthroscopic findings. The diagnostic agreement was evaluated using Cohen's kappa correlation coefficient, and both absolute and relative evaluation methods were utilized for objective assessment. RESULTS: The study involved 15 volunteers and 53 patients. An acceleration factor of 10.69 × was identified as optimal. The quality evaluation showed that 3D-ACS provided poorer bone structure visualization, and improved cartilage visualization and less satisfactory axial images with 3.5 mm/2.0 mm MPR than 2D-PAT. In terms of objective evaluation, the relative evaluation yielded satisfactory results across different groups, while the absolute evaluation revealed significant variances in most features. Nevertheless, high levels of diagnostic agreement (κ: 0.81-0.94) and accuracy (0.83-0.98) were observed across all diagnoses. CONCLUSION: ACS technology presents significant potential as a replacement for traditional CS in 3D-MRI knee scans, allowing thinner MPRs and markedly faster scans without sacrificing diagnostic accuracy. CLINICAL RELEVANCE STATEMENT: 3D-ACS-MRI of the knee can be completed in the 160 s with good diagnostic consistency and image quality. 3D-MRI-MPR can replace 2D-MRI and reconstruct images with thinner slices, which helps to optimize the current MRI examination process and shorten scanning time. KEY POINTS: • AI-assisted compressed sensing technology can reduce knee MRI scan time by over 50%. • 3D AI-assisted compressed sensing MRI and related multiplanar reconstruction can replace traditional accelerated MRI and yield thinner 2D multiplanar reconstructions. • Successful application of 3D AI-assisted compressed sensing MRI can help optimize the current knee MRI process.

Color-variable dual-dyed photodynamic antimicrobial polyethylene terephthalate (PET)/cotton blended fabrics.

The urgent demand for scalable, potent, color variable, and comfortable antimicrobial textiles as personal protection equipment (PPE) to help reduce infection transmission in hospitals and healthcare facilities has significantly increased since the start of the COVID-19 pandemic. Here, we explored photodynamic antimicrobial polyethylene terephthalate/cotton (TC) blended fabrics comprised of photosensitizer-conjugated cotton fibers and polyethylene terephthalate (PET) fibers dyed with disperse dyes. A small library of TC blended fabrics was constructed wherein the PET fibers were embedded with traditional disperse dyes dominating the fabric color, thereby enabling variable color expression, while the cotton fibers were covalently coupled with the photosensitizer thionine acetate as the microbicidal agent. Physical (SEM, CLSM, TGA, XPS and mechanical strength) and colorimetric (K/S and CIELab values) characterization methods were employed to investigate the resultant fabrics, and photooxidation studies with DPBF demonstrated the ability of these materials to generate reactive oxygen species (i.e., singlet oxygen) upon visible light illumination. The best results demonstrated a photodynamic inactivation of 99.985% (~ 3.82 log unit reduction, P = 0.0021) against Gram-positive S. aureus, and detection limit inactivation (99.99%, 4 log unit reduction, P ≤ 0.0001) against Gram-negative E. coli upon illumination with visible light (60 min; ~ 300 mW/cm2; λ ≥ 420 nm). Enveloped human coronavirus 229E showed a photodynamic susceptibility of ~ 99.99% inactivation after 60 min illumination (400-700 nm, 65 ± 5 mW/cm2). The presence of the disperse dyes on the fabrics showed no significant effects on the aPDI results, and furthermore, appeared to provide the photosensitizer with some measure of protection from photobleaching, thus improving the photostability of the dual-dyed fabrics. Taken together, these results suggest the feasibility of low cost, scalable and color variable thionine-conjugated TC blended fabrics as potent self-disinfecting textiles.

The low-dose colchicine in patients after non-CABG cardiac surgery: a randomized controlled trial.

BACKGROUND: Recent high-quality trials have shown that the anti-inflammatory effects of colchicine reduce the risk of cardiovascular events in patients suffering post-myocardial infarction and chronic coronary disease. The effect of colchicine in patients undergoing non-coronary artery bypass grafting (non-CABG) with cardiopulmonary bypass remains unclear. We aim to evaluate the effect of colchicine on myocardial protection in patients who underwent non-CABG cardiac surgery. METHOD: Patients were randomly assigned to colchicine or placebo groups starting 72 h before scheduled cardiac surgery and for 5 days thereafter (0.5 mg daily).The primary outcome was the level of cardiac troponin T (cTnT) at postoperative 48 h. The secondary outcomes included troponin I (cTnI) and creatine kinase-MB (CK-MB), inflammatory biomarkers (procalcitonin and interleukin-6, etc.), and adverse events (30-day mortality, stroke, ECMO and IABP use, etc.). RESULTS: A total of 132 patients underwent non-CAGB cardiac surgery, 11were excluded because of diarrhea (n = 6) and long aortic cross-clamp time > 2 h (n = 5), 59 were assigned to the colchicine group and 62 to the placebo group. Compared with the placebo group, cTnT (median: 0.3 µg/L, IQR 0.2-0.4 µg/L vs. median: 0.4 µg/L, IQR 0.3-0.6 µg/L, P < 0.01), cardiac troponin I (median: 0.9 ng/ml, IQR 0.4-1.7 ng/ml vs. median: 1.3 ng/ml, IQR 0.6-2.3 ng/ml, P = 0.02), CK-MB (median: 1.9 ng/ml, IQR 0.7-3.2 ng/ml vs. median: 4.4 ng/ml, IQR 1.5-8.2 ng/ml, P < 0.01), and interleukin-6 (median: 73.5 pg/ml, IQR 49.6-125.8 pg/ml vs. median: 101 pg/ml, IQR 57.5-164.7 pg/ml, P = 0.048) were significantly reduced in colchicine group at postoperative 48 h. For safety evaluation, the colchicine (n = 65) significantly decreased post-pericardiotomy syndrome (3.08% vs. 17.7%, P < 0.01) and increased the rate of diarrhea (9.23% vs. 0, P = 0.01) compared with the placebo group (n = 62). No significant difference was observed in other adverse events between the two groups. CONCLUSION: A short perioperative course of low-dose colchicine was effective to attenuate the postoperative biomarkers of myocardial injury and inflammation, and to decrease the postoperative syndrome compared with the placebo. Trial registration ChiCTR2000040129. Registered 22nd Nov. 2020. This trial was registered before the first participant was enrolled. http://www.chictr.org.cn/showproj.aspx?proj=64370 .

Analysis of the Chaotic Component of Photoplethysmography and Its Association with Hemodynamic Parameters.

Wearable technologies face challenges due to signal instability, hindering their usage. Thus, it is crucial to comprehend the connection between dynamic patterns in photoplethysmography (PPG) signals and cardiovascular health. In our study, we collected 401 multimodal recordings from two public databases, evaluating hemodynamic conditions like blood pressure (BP), cardiac output (CO), vascular compliance (C), and peripheral resistance (R). Using irregular-resampling auto-spectral analysis (IRASA), we quantified chaotic components in PPG signals and employed different methods to measure the fractal dimension (FD) and entropy. Our findings revealed that in surgery patients, the power of chaotic components increased with vascular stiffness. As the intensity of CO fluctuations increased, there was a notable strengthening in the correlation between most complexity measures of PPG and these parameters. Interestingly, some conventional morphological features displayed a significant decrease in correlation, indicating a shift from a static to dynamic scenario. Healthy subjects exhibited a higher percentage of chaotic components, and the correlation between complexity measures and hemodynamics in this group tended to be more pronounced. Causal analysis showed that hemodynamic fluctuations are main influencers for FD changes, with observed feedback in most cases. In conclusion, understanding chaotic patterns in PPG signals is vital for assessing cardiovascular health, especially in individuals with unstable hemodynamics or during ambulatory testing. These insights can help overcome the challenges faced by wearable technologies and enhance their usage in real-world scenarios.

An electrochemical nitric oxide generator for in-home inhalation therapy in pulmonary artery hypertension.

BACKGROUND: Inhaled NO is a selective pulmonary vasodilator proven to be therapeutic for patients with pulmonary artery hypertension (PAH). The most common NO delivery system in clinical practice is cylinder-based, but unfortunately limited by its high costs, complicated delivery, and the requirement of an extensive supply chain, leaving vast unmet medical needs globally. METHODS: To address the need for rapid, affordable, and safe production of nitric oxide (NO) for in-home inhalation therapy in patients with PAH. We developed a novel portable device to derive NO from a nitrite complex solution with a copper(II)-ligand catalyst, and further examined its effectiveness in a porcine model of PAH. This model was established by using female Bama miniature pig and induced by monocrotaline (MCT) administration. RESULTS: This generator could rapidly and safely produce therapeutic NO at concentrations ranging from 0 to 100 parts per million (ppm) with the least disproportionated nitrogen dioxide (NO2) and byproducts. It could effectively alleviate pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in piglets with PAH, without causing major physiologic disruptions. CONCLUSIONS: Our electrochemical NO generator is able to produce the desired NO doses for pulmonary vasodilation in a safe and sustainable way, with low costs, which paves the way for its subsequent clinical trials in the patient with PAH and other common cardiopulmonary conditions with a high disease burden around the world.

Tetrahedral DNA Nanoconjugates for Simultaneous Measurement of Telomerase Activity and miRNA.

In this study, a tetrahedral DNA nanostructure was first self-assembled; this was then conjugated with gold nanoparticles (AuNPs) and carbon nanodots (CDs). The fabricated nanocomposites allow simultaneous analysis of telomerase activity and miRNA with dual fluorescence channels. By further introducing an iRGD peptide sequence, the nanoconjuates can be conveniently transferred inside living cells for in situ imaging. The analytical performances and anti-jamming capabilities are excellent. Meanwhile, the materials are highly biocompatible for intracellular applications. Therefore, the proposed biosystem shows great promise as a powerful tool for quantitative analysis of the dual biomarkers. The strategy can also be further exploited as a versatile platform for in situ detection of many other targets for early disease diagnosis.

High-throughput optical sectioning via line-scanning imaging with digital structured modulation.

Optical sectioning with high-throughput, a high signal-to-noise ratio (SNR), and submicrometer resolution is crucial, but challenging, to three-dimensional visualization of large biological tissue samples. Here we propose line-scanning imaging with digital structured modulation for optical sectioning. Our method generates images with a significantly improved SNR, compared to wide-field structured illumination microscopy (WF-SIM), without residual modulation artifacts. We image a 14.5mm×11.5mm horizontal view of mouse brain tissue at a pixel resolution of 0.32µm×0.32µm in 101 s, which, compared to WF-SIM, represents a significant improvement on imaging throughput. These results provide development opportunities for high-throughput, high-resolution large-area optical imaging methods.

Lactonase activity and status of paraoxonase 1 and oxidative stress in neonates of women with gestational diabetes mellitus.

BACKGROUND: The level and lactonase activity of paraoxonase 1 (PON1) and their association with PON1 genetic variants and oxidative stress are unclear in neonates of women with gestational diabetes mellitus (GDM). METHODS: This study included 362 neonates of women with GDM and 302 control neonates. The level, lactonase activity, normalized lactonase activity (NLA), and genetic polymorphisms of PON1, serum total oxidant status (TOS), total antioxidant capacity (TAC), and malondialdehyde (MDA) were analyzed. RESULTS: The neonates of the women with GDM had significantly higher levels, lactonase activity, and NLA of PON1, higher TOS, TAC, and MDA concentrations, and relatively higher oxidative stress index than those of the control neonates. The PON1 -108C → T variation decreased the lactonase activity, level, and NLA of PON1, while the PON1 192Q → R variation decreased the PON1 NLA in a genotype-dependent manner in the two groups. Multivariable regression analysis revealed the PON1 -108C/T or 192Q/R variation, apolipoprotein (apo)A1, or apoB as significant predictors of the level, lactonase activity, and NLA of PON1. CONCLUSIONS: The lactonase activity, level, and NLA of PON1 were increased in the neonates of women with GDM. The PON1 genetic variants, abnormalities in lipoproteins, and increased oxidative stress may be associated with these changes. IMPACT: This is the first study to report the elevated level, lactonase activity, and NLA of PON1 in the neonates of women with GDM. These neonates also exhibited increased oxidative stress and an adverse glycolipid metabolic profile. We further established that the -108C/T and/or 192Q/R genetic variants of the PON1 gene, abnormalities in lipoprotein metabolism, and/or increased oxidative stress had noticeable influences on the level and activities of PON1. Whether these changes potentially cause metabolic disorders later in life remains to be determined. Therefore, the neonates born to women with GDM require further clinical follow-ups.

Why does unilateral pulsatile tinnitus occur in patients with idiopathic intracranial hypertension?

PURPOSE: To investigate the relevant factors of unilateral pulsatile tinnitus (PT) in patients with idiopathic intracranial hypertension (IIH) using CT. METHODS: CT angiography images of IIH patients with unilateral PT (n = 19), without PT (n = 13), and controls (n = 32) were reviewed. The characteristics including transverse sinus stenosis (TSS), venous outflow laterality (VOL), sigmoid sinus wall dehiscence (SSWD), and sigmoid sinus diverticulum (SSD) were quantitatively or/and qualitatively detected. VOL was compared between the symptomatic side of IIH patients with PT and the larger side of IIH patients without PT and the controls. TSS, SSWD, and SSD were compared between the symptomatic side of IIH patients with PT, and both sides of the latter two groups. RESULTS: There was no statistical difference in body mass index or cerebrospinal fluid pressure between IIH patients with and without PT. The prevalence of TSS was significantly higher in IIH patients than that in the controls (p = 0.000), but TSS had no correlation with PT within IIH patients. The prevalence of SSWD successively decreased in IIH patients with PT, without PT, and the controls, with significant differences between each two of three groups (p = 0.000, p' = 0.000, p″ = 0.031). The proportion of VOL and the prevalence of SSD were significantly larger in IIH patients with PT than in the latter groups respectively (pVOL = 0.005, p'VOL = 0.000; pSSD = 0.040, p'SSD = 0.000). All SSDs in IIH patients with PT were accompanied with SSWD. CONCLUSION: The dominant VOL and ipsilateral SSWD with/without SSD may be correlated with the occurrence of unilateral PT in IIH patients.

Personalized application of three different concentrations of iodinated contrast media in coronary computed tomography angiography.

No study has evaluated the impact of different iodinated contrast media on coronary contrast enhancement, using an injection protocol according to body surface area (BSA). Thus, the present study aimed to examine the usefulness and safety of personalized application of different iodine concentrations of contrast media in coronary computed tomographic (CT) angiography with a 2nd dual-source CT scanner in eliminating differences in coronary contrast enhancement based on a BSA-adapted injection protocol of contrast media. A total of 270 enrolled participants were randomly assigned to three groups: ioversol 320, ioversol 350 and iopromide 370 (n = 90 per group). The three groups were administered contrast media at a BSA-adjusted volume and flow rate with a fixed injection time of 15 seconds, and they subsequently received a 30-mL saline flush. All patients were scanned with a prospective electrocardiogram-gated protocol in a craniocaudal direction using a second-generation 128-slice dual-source CT system. The three iodinated contrast media used in coronary CT angiography exhibited similar diagnostic quality and safety. No significant differences were found in the contrast enhancement degrees, image quality scores, radiation doses and incidences of adverse effects among the three groups. The three contrast media used in coronary CT angiography with 320, 350 and 370 mg/mL iodine, respectively, have comparable diagnostic quality and safety. However, more large-scale, multinational, multi-centre and prospective trials are warranted.