Genetic and molecular basis of carotenoid metabolism in cereals.

Carotenoids are vital pigments for higher plants and play a crucial function in photosynthesis and photoprotection. Carotenoids are precursors of vitamin A synthesis and contribute to human nutrition and health. However, cereal grain endosperm contains a minor carotenoid measure and a scarce supply of provitamin A content. Therefore, improving the carotenoids in cereal grain is of major importance. Carotenoid content is governed by multiple candidate genes with their additive effects. Studies on genes related to carotenoid metabolism in cereals would increase the knowledge of potential metabolic steps of carotenoids and enhance the quality of crop plants. Recognizing the metabolism and carotenoid accumulation in various staple cereal crops over the last few decades has broadened our perspective on the interdisciplinary regulation of carotenogenesis. Meanwhile, the amelioration in metabolic engineering approaches has been exploited to step up the level of carotenoid and valuable industrial metabolites in many crops, but wheat is still considerable in this matter. In this study, we present a comprehensive overview of the consequences of biosynthetic and catabolic genes on carotenoid biosynthesis, current improvements in regulatory disciplines of carotenogenesis, and metabolic engineering of carotenoids. A panoptic and deeper understanding of the regulatory mechanisms of carotenoid metabolism and genetic manipulation (genome selection and gene editing) will be useful in improving the carotenoid content of cereals.

Evaluation of morphological features: femtosecond-LASIK flap vs. SMILE cap, and the effects on corneal higher-order aberrations.

PURPOSE: The aim of this study is to evaluate morphological features of corneal flap/cap and the correlations with corneal higher-order aberrations (HOAs) changes after femtosecond laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE). METHODS: This was a retrospective study. Pre- and postoperative (1 and 3 months) corneal HOAs were assessed with Pentacam HR. The corneal flap/cap thickness at 32 points (± 1.5 mm, ± 2 mm, ± 2.5 mm, and ± 3 mm from the corneal vertex on meridian 0°/45°/90°/135°) were measured using anterior segment optical coherence tomography at 3 months postoperatively. Morphological features of corneal flap/cap including predictability (P), uniformity (U), and symmetry (S) were calculated and used for correlation analysis with corneal HOAs changes. RESULTS: Eighty-six eyes (44 patients) and ninety-six eyes (50 patients) were involved in FS-LASIK and SMILE groups, respectively. Significant thicker corneal flap/cap than the predicted was observed at each measuring point and meridian in both groups (difference > 2.225 µm, the within-subject standard deviation over 6-mm optical zone). There was no statistically significant difference in predictability of corneal flap/cap thickness, while U6 mm (P < .0001), U0 (P < .001), U45 (P = .002), U90 (P < .0001), U135 (P = .004), S6 mm (P < .0001), S0 (P < .001), and S90 (P < .0001) over 6 mm zone were less in SMILE than in FS-LASIK. The changes of corneal tHOAs, Z (3, - 1), Z (3, 1), and SA were significantly correlated with morphological features of corneal flap/cap. CONCLUSION: Both FS-LASIK and SMILE had good predictability in flap or cap thickness, while the uniformity and symmetry of SMILE cap were better than FS-LASIK flap. The quality of flap/cap was closely associated with the changes of corneal HOAs.

Glucose impairs angiogenesis and promotes ventricular remodelling following myocardial infarction via upregulation of microRNA-17.

Hyperglycaemia is known to impair angiogenesis, which may contribute to the poor prognosis of diabetic patients following myocardial infarction (MI). miR-17 has been reported to be involved in the proliferation, migration, and angiogenesis of a variety of vascular endothelial cells. However, how miR-17 regulates angiogenesis under hyperglycaemic conditions has not been reported. Thus, the aim of this study was to investigate the role of miR-17 in the impairment of angiogenesis induced by high glucose. In vitro, human umbilical vein endothelial cells (HUVECs) transfected with miR-17 mimics or inhibitors were incubated with normal-glucose or high-glucose (HG) medium. In vivo, miR-17 or negative control antagomirs were administered by tail vein injection in an MI model of streptozotocin (STZ)-induced diabetic mice. MiR-17 was upregulated, while VEGFA was downregulated in MI mice with diabetes and in HUVECs exposed to HG. The luciferase reporter gene assay confirmed that VEGFA is a target gene of miR-17. Moreover, inhibition of miR-17 prevented HG-induced VEGFA downregulation and impaired the capacity for migration and tube formation in HUVECs. Administration of miR-17 antagomirs significantly improved LV function and reduced infarct size in diabetic post-MI mice. Furthermore, the effects of diabetes-induced decreases in angiogenesis and VEGFA expression were abrogated by miR-17 antagomirs treatment in diabetic infarcted myocardium. These findings suggest that inhibition of miR-17 prevents HG-induced impairment of angiogenesis and improves cardiac function after MI by targeting VEGFA in diabetic mice.

TRAF6 mediates high glucose-induced endothelial dysfunction.

To investigate the role of tumor necrosis factor-associated factor 6 (TRAF6) in high glucose-induced endothelial cell dysfunction. Human aortic endothelial cells (HAECs) were cultured in high glucose medium, and TRAF6 expression was assayed by quantitative real-time Polymerase Chain Reaction (PCR) and western blotting. The effect of TRAF6 on in vitro endothelial cell viability, apoptosis, migration, and endothelial-monocyte adhesion was investigated by gene knockdown. The expression of TRAF6 and related adhesion molecules was assayed in a mouse streptozotocin-induced type I diabetes model. The signaling pathways associated with TRAF6 effects on endothelial cells were investigated in high glucose HAEC cultures. Culture of HAECs in high glucose medium significantly increased TRAF6 mRNA and protein expression in a time dependent manner. High glucose markedly reduced HAEC viability, apoptosis, and migration, and these effects was significantly reversed by TRAF6 knockdown. High glucose significantly increased intercellular adhesion of THP-1 monocytic cells and HAECs via upregulation of ICAM-1 and VCAM-1 expression, and TRAF6 knockdown attenuated the effect on THP-1 cell adhesion. TRAF6, ICAM-1, and VCAM-1 expression were increased in aorta tissue of mice with streptozotocin-induced diabetes. The free radical scavenger N-acetyl-L-cysteine attenuated TRAF6 expression in HAECs cultured in high glucose medium, and TRAF6 knockdown inhibited high glucose-induced IκB-α degradation and JNK phosphorylation. TRAF6 mediated high glucose-induced endothelial dysfunction via NF-κB- and AP-1-dependent signaling. Targeting TRAF6 may delay progression of vascular diseases during diabetes mellitus and atherosclerosis.

Roles of ST2, IL-33 and BNP in predicting major adverse cardiovascular events in acute myocardial infarction after percutaneous coronary intervention.

This study investigated roles of serum ST2, IL-33 and BNP in predicting major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Blood samples were collected from the included AMI patients (n = 180) who underwent PCI. All patients were divided into the MACEs and MACEs-free groups. Enzyme-linked immunosorbent assay was performed to measure serum levels of ST2, IL-33 and BNP. Severity of coronary artery lesion was evaluated by Gensini score. Pearson correlation analysis was used. A receiver operating characteristics curve was drawn to evaluate the potential roles of ST2, IL-33 and BNP in predicting MACEs, and Kaplan-Meier curve to analyse the 1-year overall survival rate. Logistic regression analysis was conducted to analyse the independent risk factors for MACEs. Compared with the MACEs-free group, the serum levels of ST2, IL-33 and BNP were significantly higher in the MACEs group. Serum levels of ST2, IL-33 and BNP were positively correlated with each other and positively correlated with Gensini score. The area under curves of ST2, IL-33 and BNP, respectively, were 0.872, 0.675 and 0.902. The relative sensitivity and specificity were, respectively, 76.27% and 85.92%, 69.49% and 58.68%, as well as, 96.61% and 77.69%. Serum levels of ST2, IL-33 and BNP were independent risk factors for MACEs. The 1-year overall survival rate was higher in AMI patients with lower serum levels of ST2, IL-33 and BNP. In conclusion, serum levels of ST2, IL-33 and BNP have potential value in predicting MACEs in AMI patients undergoing PCI.

Protective Effects of Salvianolate on Contrast-Induced Nephropathy after Primary Percutaneous Coronary Intervention: A Prospective Multicenter Randomized Controlled Trial.

OBJECTIVES: This study's aim was to evaluate the protective effects of salvianolate on contrast-induced nephropathy after primary percutaneous coronary intervention (PPCI) compared with normal saline (NS) hydration. METHODS: We enrolled patients with acute myocardial infarction who underwent PPCI in 3 centers in Shanghai. The patients were randomly assigned to the salvianolate group or the NS group. The incidence of CIN, the changes in renal function parameters, and the occurrence of adverse events after the procedure were compared between the 2 groups. We used a multivariate logistic regression analysis to determine the independent correlates of CIN after PPCI. RESULTS: A total of 484 patients were finally included in the statistical analysis. Compared with the control group, salvianolate reduced the incidence of CIN (9.1 vs. 16.3%, p = 0.018) after PPCI. The renal function parameters after PPCI in the salvianolate group were superior to those of the control group (p < 0.05). The composite adverse events rate was significantly lower in the salvianolate group within 1 month after the procedure (9.5 vs. 15.5%, p = 0.046). A higher peak of troponin I and loop diuretic therapy were the independent correlates of CIN after PPCI. CONCLUSIONS: Salvianolate reduces the incidence of CIN and protects renal function after PPCI, and the effects were superior to those of NS hydration.

Tele-rehabilitation for Type II diabetics with heart failure with preserved ejection fraction.

Objective: This study aims to determine whether tele-rehabilitation has similar effects to conventional face-to-face physical rehabilitation for diabetic patients with heart failure with preserved ejection fraction (HFpEF). Materials and methods: Demographic, laboratory, diagnostic and rehabilitation information for patients with type 2 diabetes with HFpEF were extracted from disease-specific databases. Outcome measures, including the Short Physical Performance Battery (SPPB), 6-minute walk distance, frailty status, European Quality of Life 5-Dimension 5-Level questionnaire (EQ-5D-5L) and reduction in HbA1c from admission, patients who received tele-rehabilitation therapy were compared to those received face-to-face rehabilitation. Results: In this study, 90 patients with type 2 diabetes and HFpEF using tele-rehabilitation were matched with 90 patients with type 2 diabetes and HFpEF using face-to-face physical rehabilitation. Improvements in the results of the SPPB scores, 6-min walk distance and gait speed and EQ-5D-5L were noted from the follow-up time point 3 months to 6 months in both two groups. There were no significant differences in functional tests and quality of life between the two groups. Conclusion: Our study proved that mobile-based tele-rehabilitation programs are non-inferior to face-to-face physical rehabilitation for diabetes patients after HFpEF. In addition, adherence to the telerehabilitation program showed that the novel technology was accepted well and could be an alternative to the conventional face-to-face rehabilitation program.

Trends and Disparities in the Incidence of Intraocular Foreign Bodies 1990-2019: A Global Analysis.

Objectives: This study aims to provide trends and disparities in the incidence of intraocular foreign bodies (IOFBs) from 1990 to 2019 in 204 countries by region, country, socio-demographic index (SDI), age, and sex. Methods: The global, regional and national number of incident cases as well as age-standardized incidence rate (ASIR) of IOFBs were attained from the Global Burden of Disease Study 2019 (GBD 2019). To estimate the trend of ASIR of IOFBs, the estimated annual percentage change (EAPC) was calculated from 1990 to 2019. Results: Globally, although ASIR of IOFBs decreased with an EAPC of -0.93% [95% uncertainty interval (UI) -1.1 to -0.76] from 1990 to 2019, ASIR of IOFBs increased from 2008 to 2019. From 35.79 million (95% UI 23.62-50.89) in 1990 to 46.63 million (95% UI 32.45-64.45) in 2019, the number of IOFB incident cases worldwide increased by 30.29% (95% UI 19.63-43.55). The incidence of IOFBs varied by region and country, and it was closely related to socio-economic development. Furthermore, while ASIR of IOFBs was high in the young population aged 15-49 years, we observed a significant increase in the number of IOFB incident cases in older adults when compared to other age groups. In terms of sex, males accounted for the vast majority of IOFB incident cases. Conclusions: The global ASIR of IOFBs is on the rise, with an increase in incident cases, designating IOFBs as a global health challenge. The incidence of IOFBs cases is directly related to geographic location, socio-economic status, age, sex, and other factors. Our findings could be useful for the control and prevention of IOFBs.

Optimization of determinant factors associated with the efficiency of experimental autoimmune uveitis induction in C57BL/6 mice.

Background: Experimental autoimmune uveitis (EAU) is a widely used animal model for uveitis research. The C57BL/6 mouse strain is the most commonly used mouse strain in the research of genetic modification, but C57BL/6 mice are not sufficiently susceptible to EAU induction, partly due to experimental factors. This work aims to optimize relevant factors to improve the efficiency of EAU induction in C57BL/6 mice. Methods: To induce EAU, mice were immunized via intraperitoneal injection with pertussis (PTX) and subcutaneous injection with interphotoreceptor retinoid-binding protein peptide 1-20 (IRBP1-20) emulsified with complete Freund's adjuvant (CFA). The severity of inflammation was assessed using several approaches. The relevant experimental factors were evaluated, including methods of emulsification and doses of peptide and PTX. Results: Uveitis occurred at 8-12 days after immunization and reached its peak at 18-20 days, while T helper type 17 (Th17) cells peaked earlier at 14-18 days after immunization. Based on clinical and histological scores, 500 µg of IRBP peptide was the optimal dose required to induce EAU. The PTX dose demonstrated no influence on EAU incidence, but potentially affected the severity of uveitis. A single injection of 1,000 ng of PTX induced the most severe EAU and the highest proportion of Th17 cells. Compared to extruded emulsion, sonicated emulsion produced a higher incidence, higher histological score, and a 2-day-earlier onset of EAU. Electron microscopy showed a significantly different microstructure between the 2 emulsions. Conclusions: This work optimized the protocols of EAU induction and obtained a high and stable induction rate with severe inflammation in the C57BL/6 mouse strain. Our results facilitate future experimental research involving uveitis.

Systemic immune inflammation index and system inflammation response index are potential biomarkers of atrial fibrillation among the patients presenting with ischemic stroke.

BACKGROUND: Chronic inflammatory disorders in atrial fibrillation (AF) contribute to the onset of ischemic stroke. Systemic immune inflammation index (SIII) and system inflammation response index (SIRI) are the two novel and convenient measurements that are positively associated with body inflammation. However, little is known regarding the association between SIII/SIRI with the presence of AF among the patients with ischemic stroke. METHODS: A total of 526 ischemic stroke patients (173 with AF and 353 without AF) were consecutively enrolled in our study from January 2017 to June 2019. SIII and SIRI were measured in both groups. Logistic regression analysis was used to analyse the potential association between SIII/SIRI and the presence of AF. Finally, the correlation between hospitalization expenses, changes in the National Institutes of Health Stroke Scale (NIHSS) scores and SIII/SIRI values were measured. RESULTS: In patients with ischemic stroke, SIII and SIRI values were significantly higher in AF patients than in non-AF patients (all p < 0.001). Moreover, with increasing quartiles of SIII and SIRI in all patients, the proportion of patients with AF was higher than that of non-AF patients gradually. Logistic regression analyses demonstrated that log-transformed SIII and log-transformed SIRI were independently associated with the presence of AF in patients with ischemic stroke (log-transformed SIII: odds ratio [OR]: 1.047, 95% confidence interval CI = 0.322-1.105, p = 0.047; log-transformed SIRI: OR: 6.197, 95% CI = 2.196-17.484, p = 0.001). Finally, a positive correlation between hospitalization expenses, changes in the NIHSS scores and SIII/SIRI were found, which were more significant in patients with AF (all p < 0.05). CONCLUSIONS: Our study suggests SIII and SIRI are convenient and effective measurements for predicting the presence of AF in patients with ischemic stroke. Moreover, they were correlated with increased financial burden and poor short-term prognosis in AF patients presenting with ischemic stroke.

AI-Model for Identifying Pathologic Myopia Based on Deep Learning Algorithms of Myopic Maculopathy Classification and "Plus" Lesion Detection in Fundus Images.

Background: Pathologic myopia (PM) associated with myopic maculopathy (MM) and "Plus" lesions is a major cause of irreversible visual impairment worldwide. Therefore, we aimed to develop a series of deep learning algorithms and artificial intelligence (AI)-models for automatic PM identification, MM classification, and "Plus" lesion detection based on retinal fundus images. Materials and Methods: Consecutive 37,659 retinal fundus images from 32,419 patients were collected. After excluding 5,649 ungradable images, a total dataset of 32,010 color retinal fundus images was manually graded for training and cross-validation according to the META-PM classification. We also retrospectively recruited 1,000 images from 732 patients from the three other hospitals in Zhejiang Province, serving as the external validation dataset. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, and quadratic-weighted kappa score were calculated to evaluate the classification algorithms. The precision, recall, and F1-score were calculated to evaluate the object detection algorithms. The performance of all the algorithms was compared with the experts' performance. To better understand the algorithms and clarify the direction of optimization, misclassification and visualization heatmap analyses were performed. Results: In five-fold cross-validation, algorithm I achieved robust performance, with accuracy = 97.36% (95% CI: 0.9697, 0.9775), AUC = 0.995 (95% CI: 0.9933, 0.9967), sensitivity = 93.92% (95% CI: 0.9333, 0.9451), and specificity = 98.19% (95% CI: 0.9787, 0.9852). The macro-AUC, accuracy, and quadratic-weighted kappa were 0.979, 96.74% (95% CI: 0.963, 0.9718), and 0.988 (95% CI: 0.986, 0.990) for algorithm II. Algorithm III achieved an accuracy of 0.9703 to 0.9941 for classifying the "Plus" lesions and an F1-score of 0.6855 to 0.8890 for detecting and localizing lesions. The performance metrics in external validation dataset were comparable to those of the experts and were slightly inferior to those of cross-validation. Conclusion: Our algorithms and AI-models were confirmed to achieve robust performance in real-world conditions. The application of our algorithms and AI-models has promise for facilitating clinical diagnosis and healthcare screening for PM on a large scale.

Tactile Perception Technologies and Their Applications in Minimally Invasive Surgery: A Review.

Minimally invasive surgery (MIS) has been the preferred surgery approach owing to its advantages over conventional open surgery. As a major limitation, the lack of tactile perception impairs the ability of surgeons in tissue distinction and maneuvers. Many studies have been reported on industrial robots to perceive various tactile information. However, only force data are widely used to restore part of the surgeon's sense of touch in MIS. In recent years, inspired by image classification technologies in computer vision, tactile data are represented as images, where a tactile element is treated as an image pixel. Processing raw data or features extracted from tactile images with artificial intelligence (AI) methods, including clustering, support vector machine (SVM), and deep learning, has been proven as effective methods in industrial robotic tactile perception tasks. This holds great promise for utilizing more tactile information in MIS. This review aims to provide potential tactile perception methods for MIS by reviewing literatures on tactile sensing in MIS and literatures on industrial robotic tactile perception technologies, especially AI methods on tactile images.

A seven long-noncoding RNA signature predicts prognosis of lung squamous cell carcinoma.

Aim: This study profiled differentially expressed long noncoding RNAs (lncRNAs) in lung squamous cell carcinoma (LSCC) to predict LSCC overall survival (OS) using The Cancer Genome Atlas data. Materials & methods: The RNA-seq and clinical dataset of 475 LSCC patients was retrieved from The Cancer Genome Atlas database and statistically analyzed. Results: There were 67 upregulated and 32 downregulated lncRNAs in LSCCs and 12 lncRNAs associated with OS. The seven-lncRNA signature was associated with poor OS and RP11-150O12.6 and CTA-384D8.35 were associated with better OS (p < 0.001). The seven lncRNAs-mRNA interaction network analysis showed their association with 187 protein-coding genes for cancer development, cell migration, adhesion, proliferation, apoptosis, angiogenesis and the MAPK signaling pathways. Conclusion: This seven-lncRNA signature is useful to predict LSCC OS.

Impaired Left Atrial Performance Resulting From Age-Related Arial Fibrillation Is Associated With Increased Fibrosis Burden: Insights From a Clinical Study Combining With an in vivo Experiment.

Background: Atrial fibrillation (AF) is increasingly considered an age-related degenerative disease, whose process is associated with the development of impaired left atrial (LA) performance. However, the subtle dynamic changes of LA performance in AF during aging have yet to be fully elucidated. Atrial fibrosis is a key substrate for the development of AF, but the progression of fibrosis during aging and its relationship with LA dysfunction need to be further explored. Methods: A total of 132 control individuals and 117 persistent AF patients were prospectively studied. Subjects were further stratified into three age groups (age group 1: younger than 65 years, age group 2: between 65 and 79 years old, and age group 3: older than 80 years). The two-dimensional speckle tracking imaging was carried out for analyzing the alterations in LA function underlying LA remodeling, whereas electroanatomic mapping was performed to investigate LA fibrosis burden. In animal study, aged mice and young mice served as research subjects. Echocardiography and histological staining were used to assess LA performance and fibrosis burden, respectively. Results: Echocardiography showed progressive increases in LA dimension and LA stiffness index, and progressive decreases in LA global longitudinal strain and LA strain rates with advancing age in both AF and control cohorts, which was more prominent in AF cohort. Electroanatomic mapping showed progressive decrease in mean LA voltage and progressive increases in LA surface area, low-voltage area %, and LA volume with advancing age, whereas more significant alterations were observed in AF patients. Moreover, left atrial global longitudinal strain was positively correlated with mean LA voltage, whereas LA stiffness index was negatively related to mean LA voltage. In animal experiment, increased LA size and pulmonary artery dimension as well as longer P-wave duration and more prominent LA fibrosis were found in aged mice. Conclusions: This study provides new evidence of subtle changes in structure and performance of left atrium and their association with atrial fibrosis in both AF and non-AF subjects during physiological aging. In addition, our study also provides normal values for LA structure and performance in both AF and non-AF conditions during aging. These measurements may provide an early marker for onset of AF and LA adverse remodeling.

A pilot study of prognostic value of non-invasive cardiac parameters for major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention.

The objective of this study was to determine the combination of left ventricular ejection fraction (LVEF) and individual electrocardiographic parameters related to abnormal depolarization/repolarization or baroreceptor sensitivity that had the best predictive value for major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). Patients with ACS who underwent coronary angiography and percutaneous coronary intervention (PCI) were included in this prospective study. Ventricular late potential (VLP), heart rate turbulence (HRT), heart rate variability (HRV), and T wave alternans (TWA) parameters were measured using 24 h Holter monitoring 2-4 weeks after onset of ACS. Initial and follow-up LVEF was measured by ultrasound. Patients were followed for at least 6 months to record the occurrence of MACE. Models using combinations of the individual independent prognostic factors found by multivariate analysis were then constructed to use for estimation of risk of MACE. In multivariate analysis, VLP measured as QRS duration, HRV measured as standard deviation of normal RR intervals, and followup LVEF, but none of the other parameters studied, were independent risk factors for MACE. Areas under ROC curve (AUCs) for combinations of 2 or all 3 factors ranged from 0.73 to 0.76. Combinations of any of the three independent risk factors for MACE in ACS patients with PCI improved prediction and, because these risk factors were obtained non-invasively, may have future clinical usefulness.