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Abstract Compared to well-developed catalytic 1,2-diazidation of alkenes to produce vicinal diazides, the corresponding catalytic 1,1-diazidation of alkenes to yield geminal diazides has not been realized. Here we report an efficient approach for catalytic 1,1-diazidation of alkenes by redox-active selenium catalysis. Under mild conditions, electron-rich aryl alkenes with Z or E or Z/E mixed configuration can undergo migratory 1,1-diazidation to give a series of functionalized monoalkyl or dialkyl geminal diazides that are difficult to access by other methods. The method is also effective for the construction of polydiazides. The formed diazides are relatively safe by TGA-DSC analysis and impact sensitivity tests, and can be easily converted into various valuable molecules. In addition, interesting reactivity that geminal diazides give valuable molecules via the geminal diazidomethyl moiety as a formal leaving group in the presence of Lewis acid is disclosed. Mechanistic studies revealed that a selenenylation-deselenenylation followed by 1,2-aryl migration process is involved in the reactions, which provides a basis for the design of new reactions.

In this study, a novel electric field compressor is proposed by doping a metal-air-metal pillar in epsilon-near-zero medium within a metallic waveguide, which effectively enhances the background electric fields in a sub-wavelength air pillar with high uniformity. The field enhancement factor can be analytically determined through theoretical derivations from Maxwell’s equations, reaching its maximum value by appropriately selecting the size of the air pillar. Furthermore, the proposed compressor can achieve a tunable electric field enhancement effect within the deep sub-wavelength air pillar by adjusting the height of the air pillar through movement of two metal pillars inserted into the waveguide. Both theoretical analysis and numerical simulations are employed to validate the performance of the electric field compressor, which exhibits a wide range of tunable field enhancement effect (i.e., continuously adjustable enhancement factor between 20 and 800) with uniformity below 1.5 within the deep sub-wavelength air pillar (wherein the air volume is smaller than λ0/10 × λ0/10 × λ0/16). Finally, a practical model is proposed for the realization of the electric field compressor in the microwave range, where specially placed metal pillars and wires are incorporated into a rectangular metallic waveguide structure. The field enhancement and tunable effects of this practical model have been verified through simulations.

Abstract TRF2 is a component of shelterin, a telomere-specific protein complex that protects the ends of mammalian chromosomes from DNA damage signaling and improper repair. TRF2 functions as a homodimer and its interaction with telomeric DNA has been studied, but its full-length DNA-binding properties are unknown. This study examines TRF2’s interaction with single-DNA strands and focuses on the conformation of the TRF2-DNA complex and TRF2’s preference for DNA chirality. The results show that TRF2-DNA can switch between extended and compact conformations, indicating multiple DNA-binding modes, and TRF2’s binding does not have a strong preference for DNA supercoiling chirality when DNA is under low tension. Instead, TRF2 induces DNA bending under tension. Furthermore, both the N-terminal domain of TRF2 and the Myb domain enhance its affinity for the telomere sequence, highlighting the crucial role of multivalent DNA binding in enhancing its affinity and specificity for telomere sequence. These discoveries offer unique insights into TRF2’s interaction with telomeric DNA.

(1) Background and Objectives: Flow assessment using cardiovascular magnetic resonance (CMR) provides important implications in determining physiologic parameters and clinically important markers. However, post-processing of CMR images remains labor- and time-intensive. This study aims to assess the validity and repeatability of fully automated segmentation of phase contrast velocity-encoded aortic root plane. (2) Materials and Methods: Aortic root images from 125 patients are segmented by artificial intelligence (AI), developed using convolutional neural networks and trained with a multicentre cohort of 160 subjects. Derived simple flow indices (forward and backward flow, systolic flow and velocity) and complex indices (aortic maximum area, systolic flow reversal ratio, flow displacement, and its angle change) were compared with those derived from manual contours. (3) Results: AI-derived simple flow indices yielded excellent repeatability compared to human segmentation (p < 0.001), with an insignificant level of bias. Complex flow indices feature good to excellent repeatability (p < 0.001), with insignificant levels of bias except flow displacement angle change and systolic retrograde flow yielding significant levels of bias (p < 0.001 and p < 0.05, respectively). (4) Conclusions: Automated flow quantification using aortic root images is comparable to human segmentation and has good to excellent repeatability. However, flow helicity and systolic retrograde flow are associated with a significant level of bias. Overall, all parameters show clinical repeatability.

Aims Turbulent aortic flow makes the cardiovascular system less effective. It remains unknown if patients with heart failure with preserved ejection fraction (HFpEF) have disturbed aortic flow. This study sought to investigate advanced markers of aortic flow disturbances in HFpEF. Methods This case-controlled observational study used four-dimensional flow cardiovascular magnetic resonance derived, two-dimensional phase-contrast reformatted plane data at an orthogonal plane just above the sino-tubular junction. We recruited 10 young healthy controls (HCs), 10 old HCs and 23 patients with HFpEF. We analysed average systolic aortic flow displacement (FDsavg), systolic flow reversal ratio (sFRR) and pulse wave velocity (PWV). In a sub-group analysis, we compared old HCs versus age-gender-matched HFpEF (N=10). Results Differences were significant in mean age (P 17.7% achieved 74% sensitivity, 70% specificity for differentiating them. sFRR was notably higher in HFpEF (11±10% vs 7±6%, P 7.3% yielded 78% sensitivity, 70% specificity in differentiating these groups. In sub-group analysis, FDsavg remained distinctly elevated in HFpEF (22.4±9.7% vs 16±4.9%, P=0.029). FDsavg of >16% showed 100% sensitivity and 70% specificity (P=0.01). Similarly, sFRR remained significantly higher in HFpEF (11.3±9.5% vs 6.6±6.4%, P=0.007). A sFRR of >7.2% showed 100% sensitivity and 60% specificity (P

Abstract Osteoarthritis is a worldwide prevalent disease that imposes a significant socioeconomic burden on individuals and healthcare systems. Achieving cartilage regeneration in patients with osteoarthritis remains challenging clinically. In this work, we construct a multiple hydrogen-bond crosslinked hydrogel loaded with tannic acid and Kartogenin by polyaddition reaction as a cell-free scaffold for in vivo cartilage regeneration, which features ultra-durable mechanical properties and stage-dependent drug release behavior. We demonstrate that the hydrogel can withstand 28000 loading-unloading mechanical cycles and exhibits fast shape memory at body temperature (30 s) with the potential for minimally invasive surgery. We find that the hydrogel can also alleviate the inflammatory reaction and regulate oxidative stress in situ to establish a microenvironment conducive to healing. We show that the sequential release of tannic acid and Kartogenin can promote the migration of bone marrow mesenchymal stem cells into the hydrogel scaffold, followed by the induction of chondrocyte differentiation, thus leading to full-thickness cartilage regeneration in vivo. This work may provide a promising solution to address the problem of cartilage regeneration.

Abstract Regulation of global transcription output is important for normal development and disease, but little is known about the mechanisms involved. DNA topoisomerase I (TOP1) is an enzyme well-known for its role in relieving DNA supercoils for enabling transcription. Here, we report a non-enzymatic function of TOP1 that downregulates RNA synthesis. This function is dependent on specific DNA-interacting residues located on a conserved protein surface. A loss-of-function knock-in mutation on this surface, R548Q, is sufficient to cause hypertranscription and alter differentiation outcomes in mouse embryonic stem cells (mESCs). Hypertranscription in mESCs is accompanied by reduced TOP1 chromatin binding and change in genomic supercoiling. Notably, the mutation does not impact TOP1 enzymatic activity; rather, it diminishes TOP1-DNA binding and formation of compact protein-DNA structures. Thus, TOP1 exhibits opposing influences on transcription through distinct activities which are likely to be coordinated. This highlights TOP1 as a safeguard of appropriate total transcription levels in cells.

Abstract Background Advances in four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) have allowed quantification of left ventricular (LV) and right ventricular (RV) blood flow. We aimed to (1) investigate age and sex differences of 4D flow CMR-derived LV and RV relative flow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEiEDV) in healthy subjects; and (2) assess the effects of age and sex on these parameters. Methods We performed 4D flow analysis in 163 healthy participants (42% female; mean age 43 ± 13 years) of a prospective registry study (NCT03217240) who were free of cardiovascular diseases. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEiEDV (global, peak systolic, average systolic, average diastolic, peak E-wave, peak A-wave) for both LV and RV were analysed. Results Compared with men, women had lower median LV and RV residual volume, and LV peak and average systolic KEiEDV, and higher median values of RV direct flow, RV global KEiEDV, RV average diastolic KEiEDV, and RV peak E-wave KEiEDV. ANOVA analysis found there were no differences in flow components, peak and average systolic, average diastolic and global KEiEDV for both LV and RV across age groups. Peak A-wave KEiEDV increased significantly (r = 0.458 for LV and 0.341 for RV), whereas peak E-wave KEiEDV (r = − 0.355 for LV and − 0.318 for RV), and KEiEDV E/A ratio (r = − 0.475 for LV and − 0.504 for RV) decreased significantly, with age. Conclusion These data using state-of-the-art 4D flow CMR show that biventricular flow components and kinetic energy parameters vary significantly by age and sex. Age and sex trends should be considered in the interpretation of quantitative measures of biventricular flow. Clinical trial registration https://www.clinicaltrials.gov . Unique identifier: NCT03217240.

Objectives Severe symptomatic epidural hematoma (SSEH) is one of the most severe complications following percutaneous endoscopic unilateral laminectomy for bilateral decompression (Endo‐ULBD). Considering that this technique has been performed for a short time, no detailed reports have been recently published. Thus, it is critical to gain a better understanding of SSEH occurring in its postoperative period with regard to its incidence, possible causes, outcome, etc., in order to identify relevant management strategies. Methods Patients with spinal stenosis who had undergone Endo‐ULBD in our department from May 2019 to May 2022 were retrospectively analyzed. Of which, patients with postoperative epidural hematoma were followed‐up. The preoperative and postoperative physical conditions of each patient were recorded, and the information related to hematoma removal surgery was recorded in detail. Clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry disability index (ODI), and the results were classified into “excellent,” “good,” “fair,” or “poor” based on the modified MacNab criteria. The incidence of hematoma with different factors was calculated, and a bar graph was used to compare the difference of the indexes related to hematoma removal between cases, and a line graph was used to reflect the trend of the outcome of each patient within 6 months to evaluate the effect of the treatment. Results A total of 461 patients with spinal stenosis who underwent Endo‐ULBD were enrolled in the study. SSEH occurred in four cases, with an incidence rate of 0.87% (4/461). All these four patients underwent decompression of multiple segments, and three of them had a history of hypertension comorbid with diabetes. Notably, one patient had a past history of hypertension and coronary artery disease and was on postoperative low molecular heparin due to lower extremity venous thrombosis. According to the conditions of the four patients, three types of treatment were used. And with timely treatment, all patients recovered well. Conclusion Despite being a minimally invasive technique, postoperative epidural hematoma remains a severe complication of Endo‐ULBD. Therefore, during percutaneous endoscopic surgery, it is essential to enhance the comprehensive perioperative management of patients with Endo‐ULBD. Signs related to postoperative hematoma must be recognized and promptly managed. If necessary, satisfactory results can be achieved by using percutaneous endoscopy along the original surgical channel to remove the hematoma.

The high-altitude real-time inspection of unmanned aerial vehicles (UAVs) has always been a very challenging task. Because high-altitude inspections are susceptible to interference from different weather conditions, interference from communication signals and a larger field of view result in a smaller object area to be identified. We adopted a method that combines a UAV system scheduling platform with artificial intelligence object detection to implement the UAV automatic inspection technology. We trained the YOLOv5s model on five different categories of vehicle data sets, in which mAP50 and mAP50-95 reached 93.2% and 71.7%, respectively. The YOLOv5s model size is only 13.76 MB, and the detection speed of a single inspection photo reaches 11.26 ms. It is a relatively lightweight model and is suitable for deployment on edge devices for real-time detection. In the original DeepStream framework, we set up the http communication protocol to start quickly to enable different users to call and use it at the same time. In addition, asynchronous sending of alarm frame interception function was added and the auxiliary services were set up to quickly resume video streaming after interruption. We deployed the trained YOLOv5s model on the improved DeepStream framework to implement automatic UAV inspection.

Purpose The main objective of this study was to develop two-dimensional (2D) phase contrast (PC) methods to quantify the helicity and vorticity of blood flow in the aortic root.Methods This proof-of-concept study used four-dimensional (4D) flow cardiovascular MR (4D flow CMR) data of five healthy controls, five patients with heart failure with preserved ejection fraction and five patients with aortic stenosis (AS). A PC through-plane generated by 4D flow data was treated as a 2D PC plane and compared with the original 4D flow. Visual assessment of flow vectors was used to assess helicity and vorticity. We quantified flow displacement (FD), systolic flow reversal ratio (sFRR) and rotational angle (RA) using 2D PC.Results For visual vortex flow presence near the inner curvature of the ascending aortic root on 4D flow CMR, sFRR demonstrated an area under the curve (AUC) of 0.955, p8% for sFRR had a sensitivity of 82% and specificity of 100% for visual vortex presence. In addition, the average late systolic FD, a marker of flow eccentricity, also demonstrated an AUC of 0.909, p

BackgroundPulmonary artery (PA) strain is associated with structural and functional alterations of the vessel and is an independent predictor of cardiovascular events. The relationship of PA strain to metabolomics in participants without cardiovascular disease is unknown.MethodsIn the current study, community-based older adults, without known cardiovascular disease, underwent simultaneous cine cardiovascular magnetic resonance (CMR) imaging, clinical examination, and serum sampling. PA global longitudinal strain (GLS) analysis was performed by tracking the change in distance from the PA bifurcation to the pulmonary annular centroid, using standard cine CMR images. Circulating metabolites were measured by cross-sectional targeted metabolomics analysis.ResultsAmong n = 170 adults (mean age 71 ± 6.3 years old; 79 women), mean values of PA GLS were 16.2 ± 4.4%. PA GLS was significantly associated with age (β = −0.13, P = 0.017), heart rate (β = −0.08, P = 0.001), dyslipidemia (β = −2.37, P = 0.005), and cardiovascular risk factors (β = −2.49, P = 0.001). Alanine (β = −0.007, P = 0.01) and proline (β = −0.0009, P = 0.042) were significantly associated with PA GLS after adjustment for clinical risk factors. Medium and long-chain acylcarnitines were significantly associated with PA GLS (C12, P = 0.027; C12-OH/C10-DC, P = 0.018; C14:2, P = 0.036; C14:1, P = 0.006; C14, P = 0.006; C14-OH/C12-DC, P = 0.027; C16:3, P = 0.019; C16:2, P = 0.006; C16:1, P = 0.001; C16:2-OH, P = 0.016; C16:1-OH/C14:1-DC, P = 0.028; C18:1-OH/C16:1-DC, P = 0.032).ConclusionBy conventional CMR, PA GLS was associated with aging and vascular risk factors among a contemporary cohort of older adults. Metabolic pathways involved in PA stiffness may include gluconeogenesis, collagen synthesis, and fatty acid oxidation.

The application of the combination of unmanned aerial vehicles (UAVs) and artificial intelligence is a hot topic in the intelligent inspection of substations, and meter reading is a very challenging task. This paper proposes a method based on the combination of YOLOv6n object detection and Deeplabv3[Formula: see text] image segmentation and performs post-processing on the segmented images to obtain meter readings. First, YOLOv6n is used to detect the meter area of the aerial image and classify the meters. Second, the detected meter images are fed into the image segmentation model. The backbone network of the Deeplabv3[Formula: see text] algorithm is improved by using the MobileNetv3 network, which not only effectively extracts pointers and scales, but also makes the model more lightweight. Third, License Plate Recognition Network (LPRNet) is used to recognize digital meter images. In order to solve the problem of inaccurate pointer meter readings, to begin with, the segmented image is corroded; in addition, the circular dial area is flattened into a rectangular area by concentric circle sampling method. Finally, the meter reading is calculated by the position of the pointer, the scale and the total range of the meter. The post-processing part uses numba to optimize the inference speed. The experimental results show that in two datasets, The mean average precision of 50 (mAP50) accuracy of the YOLOv6n model using this method reached 99.71% and 98.60%, respectively, and the inference speed of a single image was 17.1[Formula: see text]ms and 13.2[Formula: see text]ms, respectively. The mean intersection over union (mIoU) of the image segmentation model reached 82.00%, 74.73%, 73.50%, 82.26% and 73.20%, respectively, and the single segmentation speed reached 33.7[Formula: see text]ms. The LPRNet model has a recognition accuracy of 99.17% and a single image inference speed of 14.7[Formula: see text]ms. At the same time, several mainstream object detection and semantic segmentation algorithms are compared. The experimental results show that the method in this paper greatly improved the accuracy and efficiency of intelligent inspection of substation meter readings.

Medical image segmentation has always been a challenging task. This paper proposes a new LUneXt medical image segmentation model based on the characteristics analysis of medical image data sets and testing of different nonlinear activation units. Both normalized activations for the original negative input image activation have good optimization capabilities for the tokenization module parameters proposed in the original UneXt model. Using different activation coefficients for different foreground and background areas has achieved better results. The experimental results of this paper on the Breast Ultrasound Images (BUSI) data set reached an intersection over union (IoU) value of 62.64%, a Dice value of 76.12%, and a single inference speed of 807.57[Formula: see text]ms. The experimental IoU value of the International Skin Imaging Collaboration (ISIC 2018) data set reached 82.95%, and the Dice value reached 90.50%. The single inference speed reached 842.58[Formula: see text]ms. The LUneXt model is more robust than other models. While improving model performance, it does not introduce higher computational complexity and does not have a major impact on the processing speed of a single image.

Aims Blood pressure (BP) is a crucial factor in cardiovascular health and can affect cardiac imaging assessments. However, standard outpatient cardiovascular MR (CMR) imaging procedures do not typically include BP measurements prior to image acquisition. This study proposes that brachial systolic BP (SBP) and diastolic BP (DBP) can be modelled using patient characteristics and CMR data.Methods In this multicentre study, 57 patients from the PREFER-CMR registry and 163 patients from other registries were used as the derivation cohort. All subjects had their brachial SBP and DBP measured using a sphygmomanometer. Multivariate linear regression analysis was applied to predict brachial BP. The model was subsequently validated in a cohort of 169 healthy individuals.Results Age and left ventricular ejection fraction were associated with SBP. Aortic forward flow, body surface area and left ventricular mass index were associated with DBP. When applied to the validation cohort, the correlation coefficient between CMR-derived SBP and brachial SBP was (r=0.16, 95% CI 0.011 to 0.305, p=0.03), and CMR-derived DBP and brachial DBP was (r=0.27, 95% CI 0.122 to 0.403, p=0.0004). The area under the curve (AUC) for CMR-derived SBP to predict SBP>120 mmHg was 0.59, p=0.038. Moreover, CMR-derived DBP to predict DBP>80 mmHg had an AUC of 0.64, p=0.002.Conclusion CMR-derived SBP and DBP models can estimate brachial SBP and DBP. Such models may allow efficient prospective collection, as well as retrospective estimation of BP, which should be incorporated into assessments due to its critical effect on load-dependent parameters.

Infantile spasms (IS) is a typical childhood epileptic disorder with generalized seizures. The sudden, frequent and complex characteristics of infantile spasms are the main causes of sudden death, severe comorbidities and other adverse consequences. Effective prediction is highly critical to infantile spasms subjects, but few related studies have been done in the past. To address this, this study proposes a seizure prediction framework for infantile spasms by combining the statistical analysis and deep learning model. The analysis is conducted on dividing the continuous scalp electroencephalograms (sEEG) into 5 phases: Interictal, Preictal, Seizure Prediction Horizon (SPH), Seizure, and Postictal. The brain network of Phase-Locking Value (PLV) of 5 typical brain rhythms is constructed, and the mechanism of epileptic changes is analyzed by statistical methods. It is found that 1) the connections between the prefrontal, occipital, and central regions show a large variability at each stage of seizure transition, and 2) 4 sub-bands of brain rhythms ( $\theta $ , $\alpha $ , $\beta $ , $\gamma $ ) are predominant. Group and individual variabilities are validated by using the Resnet18 deep model on data from 25 patients with infantile spasms, where the consistent results to statistical analyses can be observed. The optimized model achieves an average of $79.78~\%$ , $94.46\%$ , $75.46\%$ accuracy, specificity, and recall rate, respectively. The method accomplishes the analysis of the synergy between infantile spasms mechanism, model, data and algorithm, providing a guideline to build an intelligent and systematic model for comprehensive IS seizure prediction.

Development of biocompatible hydrogel adhesives with robust tissue adhesion to realize instant hemorrhage control and injury sealing, especially for emergency rescue and tissue repair, is still challenging. Herein, we report a potent hydrogel adhesive by free radical polymerization of N-acryloyl aspartic acid (AASP) in a facile and straightforward way. Through delicate adjustment of steric hindrance, the synergistic effect between interface interactions and cohesion energy can be achieved in PAASP hydrogel verified by X-ray photoelectron spectroscopy (XPS) analysis and simulation calculation compared to poly (N-acryloyl glutamic acid) (PAGLU) and poly (N-acryloyl amidomalonic acid) (PAAMI) hydrogels. The adhesion strength of the PAASP hydrogel could reach 120 kPa to firmly seal the broken organs to withstand the external force with persistent stability under physiological conditions, and rapid hemostasis in different hemorrhage models on mice is achieved using PAASP hydrogel as physical barrier. Furthermore, the paper-based Fe3+ transfer printing method is applied to construct PAASP-based Janus hydrogel patch with both adhesive and non-adhesive surfaces, by which simultaneous wound healing and postoperative anti-adhesion can be realized in gastric perforation model on mice. This advanced hydrogel may show vast potential as bio-adhesives for emergency rescue and tissue/organ repair.

Abstract Background Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes. Methods PAH patients and healthy controls from two centers were prospectively enrolled to undergo on-site cine and 4D flow CMR, and CPET within one week. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes (EDV). Phasic (peak systolic, average systolic, and peak E-wave) LV and RV blood flow KE indexed to EDV (KEIEDV) and ventricular LV and RV flow components (direct flow, retained inflow, delayed ejection flow, and residual volume) were calculated. Oxygen uptake (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were measured and recorded. Results 45 PAH patients (46 ± 11 years; 7 M) and 51 healthy subjects (46 ± 14 years; 17 M) with no significant differences in age and gender were analyzed. Compared with healthy controls, PAH had significantly lower median RV direct flow, RV delayed ejection flow, RV peak E-wave KEIEDV, peak VO2, and percentage (%) predicted peak VO2, while significantly higher median RV residual volume and VE/VCO2 slope. RV direct flow and RV residual volume were significantly associated with RV remodelling, function, peak VO2, % predicted peak VO2 and VE/VCO2 slope (all P

A novel double-physical-fields lens that can simultaneously focus acoustic and electromagnetic waves into a given region is designed based on double-physical-fields null medium, which can be realized by metal plates with subwavelength separations/thicknesses and precisely designed lengths. Numerical simulations show the proposed double-physical-fields lens can create exactly the same focusing effect for both electromagnetic and acoustic waves, i.e., the same focal spot size and efficiency at the same focal length. Four typical lens with different output surfaces are studied, which shows different focusing characteristics, e.g., noodle-shaped focal spot, tiny focal spot, and capsule-shaped focal spot. With the help of the designed double-physical-fields lens, an additional degree of freedom for control can be provided by simultaneously focusing acoustic and electromagnetic waves, which may lead to wider range of applications than single-field focusing.

Tomato fruits are rich in flavonoids. This study explores the effect of transcription factor SlNOR-like1 on the accumulation of flavonoids in tomato fruits at different ripening stages. We used ultra-pressure liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) to analyze wild-type (WT) and NOR-like1 CRISPR/Cas9-edited (NOR-like1) tomato fruits. A total of 50 flavonoid metabolites were accurately identified and determined in tomatoes. The flavonoid metabolic differences were observed among the different tomato sample groups using PCA and OPLS-DA analysis. There were 16 differential flavonoids (13 upregulated and 3 downregulated) identified between WT-GR (WT tomato at the green-ripening stage) and NOR-like1-GR (NOR-like1 tomato at the green-ripening stage), 9 differential flavonoids (six upregulated and three downregulated) identified between WT-BR3 (WT tomato at the color-breaking stage) and NOR-like1-BR3 (NOR-like1 tomato at the color-breaking stage), and 12 differential flavonoids (11 upregulated and 1 downregulated) identified between WT-BR9 (WT tomato at the red-ripening stage) and NOR-like1-BR9 (NOR-like1 tomato at the red-ripening stage). Rutin, nicotiflorin, naringenin chalcone, eriodictyol, and naringenin-7-glucoside were the five flavonoids with the highest content in the ripening stages (BR3 and BR9) in both WT and NOR-like1 tomato fruits. The overall flavonoid contents in WT tomato fruits changed little from GR to BR3 and decreased from BR3 to BR9; meanwhile, in the NOR-like1 tomato fruits, the total amounts of the flavonoids exhibited an increasing trend during all three ripening stages. The accumulation pattern of flavonoid metabolites in NOR-like1 tomato fruits differed from that in WT tomato fruits, especially in the later ripening process of BR9. The transcription factor SlNOR-like1 has an impact on the accumulation of flavonoids in tomato fruits. The results provide a preliminary basis for subsequent research into its regulatory mechanism and will be helpful for attaining future improvements in the nutritional quality and postharvest treatment of tomato fruits.

ObjectiveThe oblique lateral interbody fusion (OLIF) technique is a promising interbody fusion technique. This study summarizes the technical aspects of OLIF as a salvage surgery and the preliminary outcomes of a series of cases.Patients and methodsA retrospective review of patients with leg or back pain induced by pseudoarthrosis or adjacent segment disease after posterior lumbar interbody fusion/transforaminal lumbar interbody fusion was done. These patients underwent salvage OLIF surgeries in our institution from January 2021 to March 2022. Variables such as the demographic, clinical, surgical, and radiological characteristics of the enrolled patients were recorded and analyzed.ResultsEight patients (five females and three males; mean age 69.1 ± 5.7 years, range 63–80 years) were enrolled in this study. The mean operative time was 286.25 min (range: 230–440 min), and the estimated blood loss was 90 ml (range: 50–150 ml). Only one of the eight patients experienced a complication of lower limb motor weakness, which disappeared within 5 days after surgery. The latest data showed that the mean intervertebral space height increased from 8.36 mm preoperatively to 12.70 mm and the mean segmentary lordosis increased from 8.92° preoperatively to 15.05°. Bone fusion was achieved in all but one patient, who was followed up for only 3 months. The JOA scores Japanese Orthopaedic Association (JOA) Scores for low back pain of all patients significantly improved at the final follow-up.ConclusionOLIF provides a safe and effective salvage strategy for patients with failed posterior intervertebral fusion surgery. Patients effectively recovered intervertebral and foraminal height with no additional posterior direct decompression.

Abstract Background Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome. Methods Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEiEDV), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave. Results In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEiEDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P

AimsTo use visual mapping and bibliometrics to analyze and summarize the valuable information on laparoscopic surgery for gastric cancer (GC) obtained in the last 20 years, so as to determine the research hotspots and trends in this field.MethodsWe screened all literature on laparoscopic surgery for GC in the Web of Science published from 2000 to 2022 and analyzed the research hotspots and trends in this field using VOSviewer.ResultsA total of 2796 reports from 61 countries and regions were selected. Japanese researchers published the most papers (n=946), followed by those from China (n=747) and South Korea (n=557). Papers from Japan also had the most citations (n=21,836). Surgical Endoscopy and Other Interventional Techniques published the most reports on laparoscopic surgery for GC (n=386) and also had the highest total number of citations (n=11,076), making this journal the most authoritative in this field. Among the institutions, researchers from Seoul National University in South Korea had the highest numbers of published papers and citations. The keywords of the articles could be divided into five categories: surgical methods for GC, short-term and long-term efficacy of laparoscopic surgery, guiding role of laparoscopy in the treatment of advanced GC, diagnosis and treatment of early gastric cancer (EGC), and lymph node dissection. Keywords such as “laparoscopic proximal gastrectomy”, “surgical outcomes”, and “esophagogastric junction” have emerged recently, and relevant studies on laparoscopic surgery for adenocarcinoma of esophagogastric junction(AEG)have gradually become a hot topic and trend.ConclusionThis study adopted bibliometric analysis to identify the current research hotspots and research trends in the field of laparoscopic surgery for GC. Five main research hotspots of laparoscopic surgery for GC were also identified. Laparoscopic surgery for AEG may become an important research focus in the future.

The treatment of diabetic chronic wounds remains a global challenge due to the up-regulated inflammation response, oxidant stress, and persistent infection during healing process. Developing wound dressing materials with ideal biocompatibility, adequate mechanical strength, considerable under-water adhesion, sufficient anti-inflammation, antioxidant, and antibacterial properties is on-demand for clinical applications. In this study, we developed a bioactive skin-mimicking hydrogel band-aid through the combination of tannic acid (TA) and imidazolidinyl urea reinforced polyurethane (PMI) (TAP hydrogel) and explored its potentials in various medical applications, including hemostasis, normal skin incision, full-thickness skin wounds, and bacterial-infection skin incision on diabetic mice. TA was loaded into PMI hydrogel network to enhance the mechanical properties of TAP hydrogels through multiple non-covalent interactions (break strength: 0.28–0.64 MPa; elongation at break: 650–930%), which could resist the local stress and maintain the structural integrity of wound dressings during applications. Moreover, owing to the promising moisture-resistant adhesiveness and organ hemostasis, outstanding anti-inflammation, antibacterial, and antioxidant properties, TAP hydrogels could efficiently promote the recovery of skin incision and defects on diabetic mice. To further simulate the practical situation and explore the potential in clinical application, we also verified the treatment efficiency of TAP hydrogel in S. aureus-infected skin incision model on diabetic mice.

The gut microbiota is engaged in multiple interactions affecting host health. Bacteriocins showed the ability of impeding the growth of intestinal pathogenic bacteria and modulating gut microbiota in animals. Few studies have also discovered their regulation on human intestinal flora using an in vitro simulated system. However, little is known about their effect on gut microbiota of different enterotypes of human. This work evaluated the modification of the gut microbiota of two enterotypes (ET B and ET P) by the class IIb bacteriocin plantaricin NC8 (PLNC8) by using an in vitro fermentation model of the intestine. Gas chromatography results revealed that PLNC8 had no influence on the gut microbiota’s production of short-chain fatty acids in the subjects’ samples. PLNC8 lowered the Shannon index of ET B’ gut microbiota and the Simpson index of ET P’ gut microbiota, according to 16S rDNA sequencing. In ET B, PLNC8 enhanced the abundance of Bacteroides, Bifidobacterium, Megamonas, Escherichia-Shigella, Parabacteroides, and Lactobacillus while decreasing the abundance of Streptococcus. Prevotella_9, Bifidobacterium, Escherichia-Shigella, Mitsuokella, and Collinsella were found more abundant in ET P. The current study adds to our understanding of the impact of PLNC8 on the human gut microbiota and lays the groundwork for future research into PLNC8’s effects on human intestinal disease.

The potential of Lactiplantibacillus plantarum ZJ316 (ZJ316) as a starter culture for quality improvement and microbial community regulation in pickled mustard fermentation was elucidated in this study. Our results show that ZJ316 can deter the occurrence of nitrite peaks and maintain the nitrite content of pickled mustard at a low level (0.34 mg/kg). The headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry results indicate that ZJ316 gives a good flavor to pickled mustard. According to the 16S rDNA results, Firmicutes were the predominant microbiota after inoculation with ZJ316, and the abundances of Citrobacter, Enterobacter, and Proteus decreased simultaneously. In addition, antibacterial activity analysis showed that the supernatant of pickled mustard inoculated with ZJ316 had a significant inhibitory effect on Staphylococcus aureus D48, Escherichia coli DH5α, and Listeria monocytogenes LM1. In conclusion, L. plantarum ZJ316 has potential for use as an ideal starter in the process of vegetable fermentation.

Abstract Background Parameters of myocardial deformation may provide improved insights into right ventricular (RV) dysfunction. We quantified RV longitudinal myocardial function using a fast, semi-automated method and investigated its diagnostic and prognostic values in patients with repaired tetralogy of Fallot (rTOF) and pulmonary arterial hypertension (PAH), who respectively exemplify patients with RV volume and pressure overload conditions. Methods The study enrolled 150 patients (rTOF, n = 75; PAH, n = 75) and 75 healthy controls. RV parameters of interest were fast global longitudinal strain (GLS) and strain rates during systole (GLSRs), early diastole (GLSRe) and late diastole (GLSRa), obtained by tracking the distance from the medial and lateral tricuspid valve insertions to the RV epicardial apex on cine cardiovascular magnetic resonance (CMR). Results The RV fast GLS exhibited good agreement with strain values obtained by conventional feature tracking approach (bias − 4.9%, error limits (± 2·standard deviation) ± 4.3%) with fast GLS achieving greater reproducibility and requiring reduced analysis time. Mean RV fast GLS was reduced in PAH and rTOF groups compared to healthy controls (PAH

Salvia miltiorrhiza, known as danshen, is one of most valued medicinal plants in China. Although it has been cultivated since ancient times, an optimal culture system needs to be standardized for this important species. Here, we explored the phytochemical properties of S. miltiorrhiza with the treatments of rare earth elements (REEs) to develop an optimal tissue culture system. Four-week-old in vitro-grown S. miltiorrhiza plantlets were used as explants. The experiment was conducted in a randomized block design on a Murashige and Skoog (MS) medium containing 0.2 mg·L−1 naphthaleneacetic acid (NAA) to induce rooting at four different concentrations (50, 100, 200, and 300 μM) of REEs such as cerium (Ce), lanthanum (La), or praseodymium (Pr), respectively. Compared with all REEs at different concentrations, 100 μM Pr induced greater root length than Ce or La at any concentrations. Concomitantly, 0.38 μg tanshinone IIA/mg dry weight (DW) was observed, which was 54.84% higher than in the control. Similarly, chlorophyll content, antioxidant enzyme activity, and secondary metabolite were enhanced in rooting medium supplemented with 100 μM Pr. Therefore, this study showed that 100 μM Pr is an adequate concentration in the optimal culture system for promoting plant growth as well as enhancing secondary metabolite content in S. miltiorrhiza.

There remains a debate whether the ventricular volume within prolapsing mitral valve (MV) leaflets should be included in the left ventricular (LV) end-systolic volume, and therefore factored in LV stroke volume (SV), in cardiac magnetic resonance (CMR) assessments. This study aims to compare LV volumes during end-systolic phases, with and without the inclusion of the volume of blood on the left atrial aspect of the atrioventricular groove but still within the MV prolapsing leaflets, against the reference LV SV by four-dimensional flow (4DF). A total of 15 patients with MV prolapse (MVP) were retrospectively enrolled in this study. We compared LV SV with (LV SVMVP) and without (LV SVstandard) MVP left ventricular doming volume, using 4D flow (LV SV4DF) as the reference value. Significant differences were observed when comparing LV SVstandard and LV SVMVP (p < 0.001), and between LV SVstandard and LV SV4DF (p = 0.02). The Intraclass Correlation Coefficient (ICC) test demonstrated good repeatability between LV SVMVP and LV SV4DF (ICC = 0.86, p < 0.001) but only moderate repeatability between LV SVstandard and LV SV4DF (ICC = 0.75, p < 0.01). Calculating LV SV by including the MVP left ventricular doming volume has a higher consistency with LV SV derived from the 4DF assessment. In conclusion, LV SV short-axis cine assessment incorporating MVP dooming volume can significantly improve the precision of LV SV assessment compared to the reference 4DF method. Hence, in cases with bi-leaflet MVP, we recommend factoring in MVP dooming into the left ventricular end-systolic volume to improve the accuracy and precision of quantifying mitral regurgitation.

Tomato is abundant in alkaloids, phenolic acids, and flavonoids; however, the effect of transcription factor NOR-like1 on these metabolites in tomato is unclear. We used a combination of widely targeted metabolomics and transcriptomics to analyze wild-type tomatoes and CR-NOR-like1 tomatoes. A total of 83 alkaloids, 85 phenolic acids, and 96 flavonoids were detected with significant changes. Combined with a KEGG enrichment analysis, we revealed 16 differentially expressed genes (DEGs) in alkaloid-related arginine and proline metabolism, 60 DEGs were identified in the phenolic acid-related phenylpropane biosynthesis, and 30 DEGs were identified in the flavonoid-related biosynthesis pathway. In addition, some highly correlated differential-expression genes with differential metabolites were further identified by correlation analysis. The present research provides a preliminary view of the effects of NOR-like1 transcription factor on alkaloid, phenolic acid, and flavonoid accumulation in tomatoes at different ripening stages based on widely targeted metabolomics and transcriptomics in plants, laying the foundation for extending fruit longevity and shelf life as well as cultivating stress-resistant plants.

Cardiovascular magnetic resonance (CMR) is the reference standard for non-invasive assessment of right-sided heart function. Recent advances in CMR post-processing facilitate quantification of tricuspid annular (TA) dynamics and longitudinal strains of the right ventricle (RV) and right atrium (RA). We aimed to determine age- and sex-specific changes in CMR-derived TA dynamics, and RV and RA functional parameters in healthy Asian adults. We studied 360 healthy subjects aged 21–79 years, with 30 men and 30 women in each of the six age groups. Functional parameters of RV and RA were measured on standard four-chamber cine CMR using fast feature tracking: (1) TA peak velocities (systolic velocity S′, early diastolic velocity E′, late diastolic velocity A′) and TA plane systolic excursion (TAPSE); (2) RV global longitudinal strain (GLS) and strain rates; and (3) RA phasic longitudinal strains and strain rates. S′ and TAPSE exhibited negative correlations with age. RV GLS was significantly higher in females than in males but not associated with age in both sexes. Females had similar E′, lower A′, and higher E′/A′ ratios compared to males. Positive associations of E′ and E′/A′, and negative association of A′ with age were observed in both sexes. Females had higher RA reservoir and conduit strains compared to males. There were significantly negative and positive associations between RA conduit and booster strains, respectively, with age. Age- and sex-specific reference ranges were established, and associations revealed, for fast CMR feature tracking parameters of right heart function in a large normal Asian population.

Background: We determined the age-related changes in atrioventricular junction (AVJ) velocities and displacements by feature tracking cardiovascular magnetic resonance (FT-CMR) in a healthy community-based population. We also investigated the importance of age-matching for the identification of altered AVJ dynamics. Methods: FT-CMR was performed in 230 controls (18–78 years) and in two patient groups each consisting of 40 subjects (group 1: 23–55 years, group 2: 56–80 years). AVJ dynamic parameters, including systolic velocity Sm, early diastolic velocity Em, late diastolic velocity Am, maximal systolic excursion MAPSE and the new parameter sweep surface area velocity SSAV were measured. Results: Increasing age in the control group was significantly associated with reductions in Sm, Em, MAPSE (r = −0.40, −0.76, −0.34, all P

Crop genetics: novel gene involved in tomato ripening Chinese researchers have identified a new gene which regulates the ripening of tomatoes. Several genes known to control tomato ripening are members of the NAC family of regulators. To identify others, a team led by Daqi Fu of China Agricultural University blocked the expression of candidate NAC genes. The discovered that silencing NOR-like1 repressed ripening, leaving the tomatoes partially green. The team also engineered plants with defective copies of NOR-like1 and found that this delayed ripening and eventually resulted in partially ripe fruit and impaired seed development. RNA sequencing of these lines revealed that NOR-like1 directly regulates genes involved in ethylene synthesis, carotenoid accumluation, chlorophyll metabolism, and cell wall breakdown. These findings clearly demonstrate a key role for NOR-like1 as a positive regulator of tomato ripening and a potential tool for controlling this important process.

Vascular wall stiffness and hemodynamic parameters are potential biomechanical markers for detecting pulmonary arterial hypertension (PAH). Previous computational analyses, however, have not considered the interaction between blood flow and wall deformation. Here, we applied an established computational framework that utilizes patient-specific measurements of hemodynamics and wall deformation to analyze the coupled fluid–vessel wall interaction in the proximal pulmonary arteries (PA) of six PAH patients and five control subjects. Specifically, we quantified the linearized stiffness (E), relative area change (RAC), diastolic diameter (D), regurgitant flow, and time-averaged wall shear stress (TAWSS) of the proximal PA, as well as the total arterial resistance (Rt) and compliance (Ct) at the distal pulmonary vasculature. Results found that the average proximal PA was stiffer [median: 297 kPa, interquartile range (IQR): 202 kPa vs. median: 75 kPa, IQR: 5 kPa; P = 0.007] with a larger diameter (median: 32 mm, IQR: 5.25 mm vs. median: 25 mm, IQR: 2 mm; P = 0.015) and a reduced RAC (median: 0.22, IQR: 0.10 vs. median: 0.42, IQR: 0.04; P = 0.004) in PAH compared to our control group. Also, higher total resistance (Rt; median: 6.89 mmHg × min/l, IQR: 2.16 mmHg × min/l vs. median: 3.99 mmHg × min/l, IQR: 1.15 mmHg × min/l; P = 0.002) and lower total compliance (Ct; median: 0.13 ml/mmHg, IQR: 0.15 ml/mmHg vs. median: 0.85 ml/mmHg, IQR: 0.51 ml/mmHg; P = 0.041) were observed in the PAH group. Furthermore, lower TAWSS values were seen at the main PA arteries (MPAs) of PAH patients (median: 0.81 Pa, IQR: 0.47 Pa vs. median: 1.56 Pa, IQR: 0.89 Pa; P = 0.026) compared to controls. Correlation analysis within the PAH group found that E was directly correlated to the PA regurgitant flow (r = 0.84, P = 0.018) and inversely related to TAWSS (r = −0.72, P = 0.051). Results suggest that the estimated elastic modulus E may be closely related to PAH hemodynamic changes in pulmonary arteries.

Preformed crowns are preferred to reduce the failure risk of restoration of primary teeth, but some drawback of conventional material is still a main barrier for their clinical use. Polyether etherketone (PEEK), a tooth colored, high-performance thermoplastic polymer, has been recognized as a promising alternative to manufacture the restoration of primary teeth. However, the hydrophobic surface and low surface energy of PEEK make it hard to establish a strong and durable adhesion. In this study, we have evaluated a modification method of polydopamine (PDA) coating with plasma pretreatment for the PEEK films by physical and chemical characterization, bonding properties, and biocompatibility. The surface properties of PEEK were well-characterized by scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). The adhesive strength of the PEEK films was greatly improved without significant reduction of the proliferation rate of human gingival fibroblast cells in MTT and Live/Dead assays. Therefore, PDA coating with plasma pretreatment may give a new solution for effective clinical application of PEEK in primary performed crowns.

Abstract Freshwater stored on land is an extremely vital resource for all the terrestrial life on Earth. But our ability to record the change of land water storage is weak despite its importance. In this study, we attempt to establish a data‐driven model for simulating terrestrial water storage dynamics by relating climate forcings with terrestrial water storage anomalies (TWSAs) from the Gravity Recovery and Climate Experiment (GRACE) satellites. In the case study in Pearl River basin, China, the relationships were learned by using two ensemble learning algorithms, the Random Forest (RF) and eXtreme Gradient Boost (XGB), respectively. The TWSA in the basin was reconstructed back to past decades and compared with the TWSA derived from global land surface models. As a result, the RF and XGB algorithms both perform well and could nicely reproduce the spatial pattern and value range of GRACE observations, outperforming the land surface models. Temporal behaviors of the reconstructed TWSA time series well capture those of both GRACE and land surface models time series. A multiscale GRACE‐based drought index was proposed, and the index matches the Standardized Precipitation‐Evapotranspiration Index time series at different time scales. The case analysis for years of 1963 and 1998 indicates the ability of the reconstructed TWSA for identifying past drought and flood extremes. The importance of different input variables to the TWSA estimation model was quantified, and the precipitation of the prior 2 months is the most important variable for simulating the TWSA of the current month in the model. Results of this study highlight the great potentials for estimating terrestrial water storage dynamics from climate forcing data by using machine learning to achieve comparable results than complex physical models.

Abstract Background Abnormal left atrial (LA) function is a marker of cardiac dysfunction and adverse cardiovascular outcome, but is difficult to assess, and hence not, routinely quantified. We aimed to determine the feasibility and effectiveness of a fast method to measure long-axis LA strain and strain rate (SR) with standard cardiovascular magnetic resonance (CMR) compared to conventional feature tracking (FT) derived longitudinal strain. Methods We studied 50 normal controls, 30 patients with hypertrophic cardiomyopathy, and 100 heart failure (HF) patients, including 40 with reduced ejection fraction (HFrEF), 30 mid-range ejection fraction (HFmrEF) and 30 preserved ejection fraction (HFpEF). LA longitudinal strain and SR parameters were derived by tracking the distance between the left atrioventricular junction and a user-defined point at the mid posterior LA wall on standard cine CMR two- and four-chamber views. LA performance was analyzed at three distinct cardiac phases: reservoir function (reservoir strain ε s and strain rate SRs), conduit function (conduit strain ε e and strain rate SRe) and booster pump function (booster strain ε a and strain rate SRa). Results There was good agreement between LA longitudinal strain and SR assessed using the fast and conventional FT-CMR approaches (r = 0.89 to 0.99, p

Abstract Coptidis Rhizoma binds to the membrane receptors on hPDLSC/CMC, and the active ingredient Berberine (BER) that can be extracted from it may promote the proliferation and osteogenesis of periodontal ligament stem cells (hPDLSC). The membrane receptor that binds with BER on the cell surface of hPDLSC, the mechanism of direct interaction between BER and hPDLSC, and the related signal pathway are not yet clear. In this research, EGFR was screened as the affinity membrane receptor between BER and hPDLSC, through retention on CMC, competition with BER and by using a molecular docking simulation score. At the same time, the MAPK PCR Array was selected to screen the target genes that changed when hPDLSC was simulated by BER. In conclusion, BER may bind to EGFR on the cell membrane of hPDLSC so the intracellular ERK signalling pathways activate, and nuclear-related genes of FOS change, resulting in the effect of osteogenesis on PDLSC.

Catalytic enantioselective synthesis of trifluoromethylthiolated molecules remains a challenge. Here, the authors report a bifunctional selenide-catalyzed approach for the synthesis of structurally complex chiral trifluoromethylthiolated tetrahydronaphthalenes by merging desymmetrization and trifluoromethylthiolation.

Abstract HMGA2 belongs to the family of the high mobility group (HMG) proteins. It binds DNA via three AT-hook domains to the minor groove of adenine-thymine (AT) rich DNA. Recently, a new function of HMGA2 as a replication fork chaperone that protects stem and cancer cells from replication fork collapse induced by chemotherapeutic agents was uncovered, suggesting a previously uncharacterized binding at replication forks. In this study, we examined HMGA2 binding to four DNA structures relevant to replication forks, namely ds DNA, ss DNA, forked DNA and supercoiled DNA plectonemes. We detected HMGA2 binding to supercoiled DNA at the lowest concentration and this binding mode transiently stabilizes the supercoiled plectonemes against relaxation by type I topoisomerase. Together, these findings suggest a plausible mechanism how fork regression and collapse are attenuated by HMGA2 during replication stress, i.e. through transient stabilization of positively supercoiled plectonemes in the parental duplex.

Abstract Background A wide range of pesticides is applied for crop protection in vegetable cultivation in China. Regulation of pesticide maximum residue limits (MRLs) in vegetables is established but not fully enforced. And pesticide residues in vegetables were not well monitored. This study conducted the monitoring surveys from 2011 to 2013 to investigate the pesticides in vegetables in the northwest region of China. Methods A multi-residue gas chromatography/mass spectrometry method (GC/MS) was used in determination of pesticides in vegetable samples. The χ2 test was used to compare the concentration of pesticide residues. Results A total of 32 pesticide residues were detected in 518 samples from 20 types of vegetables in this study. 7.7% of the detected pesticide residues exceeded the MRLs. The percentages of residues that exceeded the MRLs for leafy, melon and fruit, and root vegetables were 11.2%, 5.1%, and 1.6%, respectively. There was no seasonal difference in the proportion of samples that exceeded the MRLs in different vegetables. A total of 84.3% (27/32) pesticides were detected at concentrations that exceeded MRLs. And of the 27 pesticides that exceeded the MRLs, 11 (40.7%) were banned for use in agriculture. The most frequently detected pesticides were Malathion (9.4%), Dichlorvos (8.7%), and Dimethoate (8.1%). Conclusion The observed high rate of pesticides detected and high incidence of pesticide detection exceeding their MRLs in the commonly consumed vegetables indicated that the Good Agricultural Practices (GAP) may not be well followed. The management of pesticide use and control should be improved. Well-developed training programs should be initiated to improve pesticide application knowledge for farmers.

One important index to assess left ventricular diastolic function is the quantitative measurement of atrioventricular junction (AVJ) motion in one cardiac cycle including systole and diastole. The best way to perform the measurement is to use a software tool that can conduct AVJ motion tracking from cine cardiovascular magnetic resonance (CMR) images. In this paper, a software tool for this purpose is presented by using the insight segmentation and registration toolkit (ITK), the visualization toolkit (VTK), and Qt. We propose a surface area-based tracking approach in the software tool. In the tracking approach to obtain the surface area swept by six points being tracked, we manually select six points from four-, three- and two-chamber views of CMR images. After that, we reconstruct the 3-D coordinates of the six points from image acquisition parameters extracted from DICOM files. We perform interpolation by using parametric cubic curve fitting techniques. From the curve fitting results, we finally obtain the surface areas for all time points in one cardiac cycle. The software tool has been successfully implemented. The functionality include single point-based tracking, surface area-based tracking by using 6 tracked points, generation of displacement, sweep surface area and velocity, and generation of tracking movies. From the software engineering practice, it is concluded that ITK, VTK, and Qt are very handy software systems to implement automatic image analysis functions for CMR images, such as quantitative measure of motion by visual tracking. The software tool provides a convenient and efficient way to measure AVJ motion and extends the scope of methods for ventricular function assessment.

Tomato fruit ripening is a complex process, which determines the formation of fruit quality. Many factors affect fruit ripening, including environmental conditions and genetic factors. Transcription factors (TFs) play key roles in regulating fruit ripening and quality formation. Current studies have found that the TDR4 gene is an important TF for tomato fruit ripening, but its effects on fruit metabolism and quality are less well studied. In this study, suppression of TDR4 gene expression obtained through virus-induced gene silencing (VIGS) technology resulted in an orange pericarp phenotype. Transcriptomic analysis of TDR4-silenced fruit showed changes in the expression of genes involved in various metabolic pathways, including amino acid and flavonoid biosynthesis pathways. Metabolomic analysis showed that levels of several amino acids including phenylalanine and tyrosine, and organic acids were reduced in TDR4-silenced fruit, while α-tomatine accumulated in TDR4-silenced fruit. Taken together, our RNA-seq and metabolomics analyses of TDR4-silenced fruit showed that TDR4 is involved in ripening and nutrient synthesis in tomato fruit, and is therefore an important regulator of fruit quality.

Abstract Background Long noncoding RNA (lncRNA) exerts a potential regulatory role in tumorigenesis. LncRNA NEAT1 expression remains high in osteosarcoma tissues. However, its biological mechanism in osteosarcoma remains unknown. Methods In this study, NEAT1 expression in osteosarcoma cells was detected by qRT‐PCR. Proliferative and apoptosis potentials of osteosarcoma cells were determined by CCK‐8 assay and Flow Cytometry, respectively. We identified the potential target of NEAT1 through bioinformatics and dual‐luciferase reporter gene assay. Furthermore, their interaction and functions in regulating the development of osteosarcoma were clarified by Western blot and RIP assay. Results Our results demonstrated a high expression of NEAT1 in osteosarcoma tissues and cells. Overexpression of NEAT1 markedly accelerated proliferative and reduced apoptosis potentials of osteosarcoma cells. Besides, NEAT1 could positively regulate the expression of HOXA13 by competing with miR‐34a‐5p. Conclusion These results indicated that NEAT1 participated in the development of osteosarcoma as a ceRNA to competitively bind to miR‐34a‐5p and thus mediate HOXA13 expression.

The transient build-up of DNA supercoiling during the translocation of replication forks threatens genome stability and is controlled by DNA topoisomerases (TOPs). This crucial process has been exploited with TOP poisons for cancer chemotherapy. However, pinpointing cellular determinants of the best clinical response to TOP poisons still remains enigmatic. Here, we present an integrated approach and demonstrate that endogenous and exogenous expression of the oncofetal high-mobility group AT-hook 2 (HMGA2) protein exhibited broad protection against the formation of hydroxyurea-induced DNA breaks in various cancer cells, thus corroborating our previously proposed model in which HMGA2 functions as a replication fork chaperone that forms a protective DNA scaffold at or close to stalled replication forks. We now further demonstrate that high levels of HMGA2 also protected cancer cells against DNA breaks triggered by the clinically important TOP1 poison irinotecan. This protection is most likely due to the recently identified DNA supercoil constraining function of HMGA2 in combination with exclusion of TOP1 from binding to supercoiled substrate DNA. In contrast, low to moderate HMGA2 protein levels surprisingly potentiated the formation of irinotecan-induced genotoxic covalent TOP1-DNA cleavage complexes. Our data from cell-based and several in vitro assays indicate that, mechanistically, this potentiating role involves enhanced drug-target interactions mediated by HMGA2 in ternary complexes with supercoiled DNA. Subtelomeric regions were found to be extraordinarily vulnerable to these genotoxic challenges induced by TOP1 poisoning, pointing at strong DNA topological barriers located at human telomeres. These findings were corroborated by an increased irinotecan sensitivity of patient-derived xenografts of colorectal cancers exhibiting low to moderate HMGA2 levels. Collectively, we uncovered a therapeutically important control mechanism of transient changes in chromosomal DNA topology that ultimately leads to enhanced human subtelomere stability.

Proanthocyanidins (PAs) are responsible for several health benefits of many fruits, but they could cause a generally disliked sensation of astringency. Traditional deastringency methods remove bioactive ingredients, resulting in the loss of valuable nutrients and associated health benefits. This work aimed to microencapsulate PAs from grape seeds using oxidized starch hydrogel (OSH) and mask its perceived astringency in beverages while maintaining its bioavailability. The maximum PA uptake capabilities of OSH, as well as the binding site and primary binding force between these two components, were determined. The resulting PA-OSH complex was stable under in vitro digestion, with only 1.6% of PA being released in the salivary digestion, and it has an intestine-specific release property. The reaction of PA with α-amylase in artificial saliva was substantially reduced by OSH microencapsulation, leading to 41.5% less precipitation of the salivary proteins. The sensory evaluation results showed that the microencapsulation was able to mask the astringency of PA-fortified water, as the perceived threshold of astringency increased by 3.85 times. These results proved that OSH could be used as a novel food additive to reduce the astringency of beverage products due to its hydrogel properties and ability to encapsulate phenolic compounds.

Reference values on atrial and ventricular strain from cardiovascular magnetic resonance (CMR) are essential in identifying patients with impaired atrial and ventricular function. However, reference values have not been established for Chinese subjects. One hundred and fifty healthy volunteers (75 Males/75 Females; 18–82 years) were recruited. All underwent CMR scans with images acceptable for further strain analysis. Subjects were stratified by age: Group 1, 18–44 years; Group 2, 45–59 years; Group 3, ≥60 years. Feature tracking of CMR cine imaging was used to obtain left atrial global longitudinal (LA Ell) and circumferential strains (LA Ecc) and respective systolic strain rates, left ventricular longitudinal (LV Ell), circumferential (LV Ecc) and radial strains (LV Err) and their respective strain rates, and right ventricular longitudinal strain (RV Ell) and strain rate. LA Ell and LA Ecc were 32.8 ± 9.2% and 40.3 ± 13.4%, respectively, and RV Ell was −29.3 ± 6.0%. LV Ell, LV Ecc and LV Err were −22.4 ± 2.9%, −24.3 ± 3.1%, and 79.0 ± 19.4%, respectively. LV Ell and LV Ecc were higher in females than males (P < 0.05). LA Ell, LA Ecc, and LV Ecc decreased, while LV Err increased with age (P < 0.05). LV Ell and RV Ell were not shown to be associated with age. Normal ranges for atrial and ventricular strain and strain rates are provided using CMR feature tracking in Chinese subjects.

Heart failure (HF) imposes a major global health care burden on society and suffering on the individual. About 50% of HF patients have preserved ejection fraction (HFpEF). More intricate and comprehensive measurement-focused imaging of multiple strain components may aid in the diagnosis and elucidation of this disease. Here, we describe the development of a semi-automated hyperelastic warping method for rapid comprehensive assessment of biventricular circumferential, longitudinal, and radial strains that is physiological meaningful and reproducible. We recruited and performed cardiac magnetic resonance (CMR) imaging on 30 subjects [10 HFpEF, 10 HF with reduced ejection fraction patients (HFrEF) and 10 healthy controls]. In each subject, a three-dimensional heart model including left ventricle (LV), right ventricle (RV), and septum was reconstructed from CMR images. The hyperelastic warping method was used to reference the segmented model with the target images and biventricular circumferential, longitudinal, and radial strain–time curves were obtained. The peak systolic strains are then measured and analyzed in this study. Intra- and inter-observer reproducibility of the biventricular peak systolic strains was excellent with all ICCs > 0.92. LV peak systolic circumferential, longitudinal, and radial strain, respectively, exhibited a progressive decrease in magnitude from healthy control→HFpEF→HFrEF: control (-15.5 ± 1.90, -15.6 ± 2.06, 41.4 ± 12.2%); HFpEF (-9.37 ± 3.23, -11.3 ± 1.76, 22.8 ± 13.1%); HFrEF (-4.75 ± 2.74, -7.55 ± 1.75, 10.8 ± 4.61%). A similar progressive decrease in magnitude was observed for RV peak systolic circumferential, longitudinal and radial strain: control (-9.91 ± 2.25, -14.5 ± 2.63, 26.8 ± 7.16%); HFpEF (-7.38 ± 3.17, -12.0 ± 2.45, 21.5 ± 10.0%); HFrEF (-5.92 ± 3.13, -8.63 ± 2.79, 15.2 ± 6.33%). Furthermore, septum peak systolic circumferential, longitudinal, and radial strain magnitude decreased gradually from healthy control to HFrEF: control (-7.11 ± 1.81, 16.3 ± 3.23, 18.5 ± 8.64%); HFpEF (-6.11 ± 3.98, -13.4 ± 3.02, 12.5 ± 6.38%); HFrEF (-1.42 ± 1.36, -8.99 ± 2.96, 3.35 ± 2.95%). The ROC analysis indicated LV peak systolic circumferential strain to be the most sensitive marker for differentiating HFpEF from healthy controls. Our results suggest that the hyperelastic warping method with the CMR-derived strains may reveal subtle impairment in HF biventricular mechanics, in particular despite a “normal” ventricular ejection fraction in HFpEF.