ELM2-SANT Domain-Containing Scaffolding Protein 1 Regulates Differentiation and Maturation of Cardiomyocytes Derived From Human-Induced Pluripotent Stem Cells.

BACKGROUND: ELMSAN1 (ELM2-SANT domain-containing scaffolding protein 1) is a newly identified scaffolding protein of the MiDAC (mitotic deacetylase complex), playing a pivotal role in early embryonic development. Studies on Elmsan1 knockout mice showed that its absence results in embryo lethality and heart malformation. However, the precise function of ELMSAN1 in heart development and formation remains elusive. To study its potential role in cardiac lineage, we employed human-induced pluripotent stem cells (hiPSCs) to model early cardiogenesis and investigated the function of ELMSAN1. METHODS AND RESULTS: We generated ELMSAN1-deficient hiPSCs through knockdown and knockout techniques. During cardiac differentiation, ELMSAN1 depletion inhibited pluripotency deactivation, decreased the expression of cardiac-specific markers, and reduced differentiation efficiency. The impaired expression of genes associated with contractile sarcomere structure, calcium handling, and ion channels was also noted in ELMSAN1-deficient cardiomyocytes derived from hiPSCs. Additionally, through a series of structural and functional assessments, we found that ELMSAN1-null hiPSC cardiomyocytes are immature, exhibiting incomplete sarcomere Z-line structure, decreased calcium handling, and impaired electrophysiological properties. Of note, we found that the cardiac-specific role of ELMSAN1 is likely associated with histone H3K27 acetylation level. The transcriptome analysis provided additional insights, indicating maturation reduction with the energy metabolism switch and restored cell proliferation in ELMSAN1 knockout cardiomyocytes. CONCLUSIONS: In this study, we address the significance of the direct involvement of ELMSAN1 in the differentiation and maturation of hiPSC cardiomyocytes. We first report the impact of ELMSAN1 on multiple aspects of hiPSC cardiomyocyte generation, including cardiac differentiation, sarcomere formation, calcium handling, electrophysiological maturation, and proliferation.

Effect of interpregnancy interval on the risk of gestational diabetes mellitus during a second pregnancy.

BACKGROUND: Interpregnancy interval (IPI) is associated with the risk of GDM in a second pregnancy. However, an optimal IPI is still need to be determined based on the characteristics of the population. This study aimed to analyze the effect of interpregnancy interval (IPI) on the risk of gestational diabetes mellitus (GDM) in the Chinese population. METHODS: We conducted a retrospective cohort study on female participants who had consecutive deliveries at Peking University Shenzhen Hospital from 2013 to 2021. The IPI was categorized into 7 groups and included into the multivariate logistic regression model with other confound factors. Analysis was also stratified based on age of first pregnancy, BMI, and history of GDM. Adjusted OR values (aOR) and 95% confidence intervals (CI) calculated. The regression coefficient of IPI months on GDM prediction risk was analyzed using a linear regression model. RESULTS: A total of 2,392 participants were enrolled. The IPI of the GDM group was significantly greater than that of the non-GDM group (P < 0.05). Compared with the 18-24 months IPI category, participants with longer IPIs (24-36 months, 36-48 months, 48-60 months, and ≥ 60 months) had a higher risk of GDM (aOR:1.585, 2.381, 2.488, and 2.565; 95% CI: 1.021-2.462, 1.489-3.809, 1.441-4.298, and 1.294-5.087, respectively). For participants aged < 30 years or ≥ 30 years or without GDM history, all longer IPIs (≥ 36 months) were all significantly associated with the GDM risk in the second pregnancy (P < 0.05), while any shorter IPIs (< 18 months) was not significantly associated with GDM risk (P > 0.05). For participants with GDM history, IPI 12-18 months, 24-36 months, 36-48 months, and ≥ 60 months were all significantly associated with the GDM risk (aOR: 2.619, 3.747, 4.356, and 5.373; 95% CI: 1.074-6.386, 1.652-8.499, 1.724-11.005, and 1.078-26.793, respectively), and the slope value of linear regression (0.5161) was significantly higher compared to participants without a history of GDM (0.1891) (F = 284.168, P < 0.001). CONCLUSIONS: Long IPI increases the risk of GDM in a second pregnancy, but this risk is independent of maternal age. The risk of developing GDM in a second pregnancy for women with GDM history is more significantly affected by IPI.

A deep semantic network-based image segmentation of soybean rust pathogens.

Introduction: Asian soybean rust is a highly aggressive leaf-based disease triggered by the obligate biotrophic fungus Phakopsora pachyrhizi which can cause up to 80% yield loss in soybean. The precise image segmentation of fungus can characterize fungal phenotype transitions during growth and help to discover new medicines and agricultural biocides using large-scale phenotypic screens. Methods: The improved Mask R-CNN method is proposed to accomplish the segmentation of densely distributed, overlapping and intersecting microimages. First, Res2net is utilized to layer the residual connections in a single residual block to replace the backbone of the original Mask R-CNN, which is then combined with FPG to enhance the feature extraction capability of the network model. Secondly, the loss function is optimized and the CIoU loss function is adopted as the loss function for boundary box regression prediction, which accelerates the convergence speed of the model and meets the accurate classification of high-density spore images. Results: The experimental results show that the mAP for detection and segmentation, accuracy of the improved algorithm is improved by 6.4%, 12.3% and 2.2% respectively over the original Mask R-CNN algorithm. Discussion: This method is more suitable for the segmentation of fungi images and provide an effective tool for large-scale phenotypic screens of plant fungal pathogens.

Cell-Cycle-Specific Autoencoding Improves Cluster Analysis of Cycling Cardiomyocytes.

BACKGROUND: Our previous analyses of cardiomyocyte single-nucleus RNA sequencing (snRNAseq) data from the hearts of fetal pigs and pigs that underwent apical resection surgery on postnatal day (P) 1 (ARP1), myocardial infarction (MI) surgery on P28 (MIP28), both ARP1 and MIP28 (ARP1MIP28), or controls (no surgical procedure or CTL) identified 10 cardiomyocyte subpopulations (clusters), one of which appeared to be primed to proliferate in response to MI. However, the clusters composed of primarily proliferating cardiomyocytes still contained noncycling cells, and we were unable to distinguish between cardiomyocytes in different phases of the cell cycle. Here, we improved the precision of our assessments by conducting similar analyses with snRNAseq data for only the 1646 genes included under the Gene Ontology term "cell cycle." METHODS: Two cardiac snRNAseq datasets, one from mice (GEO dataset number GSE130699) and one from pigs (GEO dataset number GSE185289), were evaluated via our cell-cycle-specific analytical pipeline. Cycling cells were identified via the co-expression of 5 proliferation markers (AURKB, MKI67, INCENP, CDCA8, and BIRC5). RESULTS: The cell-cycle-specific autoencoder (CSA) algorithm identified 7 cardiomyocyte clusters in mouse hearts (mCM1 and mCM3-mCM8), including one prominent cluster of cycling cardiomyocytes in animals that underwent MI or Sham surgery on P1. Five cardiomyocyte clusters (pCM1, pCM3-pCM6) were identified in pig hearts, 2 of which (pCM1 and pCM4) displayed evidence of cell cycle activity; pCM4 was found primarily in hearts from fetal pigs, while pCM1 comprised a small proportion of cardiomyocytes in both fetal hearts and hearts from ARP1MIP28 pigs during the 2 weeks after MI induction, but was nearly undetectable in all other experimental groups and at all other time points. Furthermore, pseudotime trajectory analysis of snRNAseq data from fetal pig cardiomyocytes identified a pathway that began at pCM3, passed through pCM2, and ended at pCM1, whereas pCM3 was enriched for the expression of a cell cycle activator that regulates the G1/S phase transition (cyclin D2), pCM2 was enriched for an S-phase regulator (CCNE2), and pCM1 was enriched for the expression of a gene that regulates the G2M phase transition and mitosis (cyclin B2). We also identified 4 transcription factors (E2F8, FOXM1, GLI3, and RAD51) that were more abundantly expressed in cardiomyocytes from regenerative mouse hearts than from nonregenerative mouse hearts, from the hearts of fetal pigs than from CTL pig hearts, and from ARP1MIP28 pig hearts than from MIP28 pig hearts during the 2 weeks after MI induction. CONCLUSIONS: The CSA algorithm improved the precision of our assessments of cell cycle activity in cardiomyocyte subpopulations and enabled us to identify a trajectory across 3 clusters that appeared to track the onset and progression of cell cycle activity in cardiomyocytes from fetal pigs.

High enrichment and measurement of heterocyclic aromatic hydrocarbons from environmental waters with magnetic resorcinol-formaldehyde nanocomposites coupled with high performance liquid chromatography.

Heterocyclic aromatic hydrocarbons are concerned pollutants with carcinogenic toxicity, which exist universally in various environmental matrices and have great harm to environmental and human health. In present work, magnetic resorcinol-formaldehyde composites (Fe3O4@SiO2@R-F) were fabricated via aldol condensation reaction under alkaline condition. The prepared magnetic materials were examined and analyzed with Fourier transform infrared spectroscopy and other related instruments. The Fe3O4@SiO2@R-F composites were utilized to develop an efficient magnetic solid phase extraction (MSPE) method for extracting six heteropolyclic aromatic hydrocarbons from environmental water samples including carbazole (CB), 7-methylquinoline (7-MQL), 9-methylcarbazole (9-MCB), dibenzothiophene (DBT), 4-methyldibenzothiophene (4-MDBT), and 4,6-dimethyldibenzothiophene (4,6-DMDBT). The analytes were analyzed by high performance liquid chromatography-ultraviolet variable wavelength detector (HPLC-VWD). The main factors affecting MSPE were optimized. With the optimal parameters, 9-MCB and 4-MDBT have good linearity over the concentration range of 0.1-300 µg L-1, and 7-MQL, CB, DBT and 4,6-DMDBT have good linearity over the concentration range of 0.5-300 µg L-1. The limits of detection were over the concentration range of 0.012-0.031 µg L-1. This method was successfully employed to measure real waters, and the spiked recoveries ranged from 89.4% to 99.9%. The results confirmed that the developed method was reliable, robust and could be employed as a usefully alternate way for analyzing such pollutants in waters.

Association between sodium and potassium intake levels and body compositions of Chinese college students.

BACKGROUND AND OBJECTIVES: To investigate the relationship between sodium (Na) and potassium (K) nutritional condition and body compositions in youth aiming to give target population reasonable diet recommendations. METHODS AND STUDY DESIGN: The cross-sectional study was conducted involving 512 healthy youth aged 18 to 31 years from universities in Beijing. Food frequency questionnaire (FFQ) and bioelectrical impedance analyzer (BIA) were used to collect dietary intake information and body compositions. RESULTS: There was an increasing tendency in fat-related indicators and muscle-related indicators of the dietary Na tertile group (p <0.05). Additionally, Weight, body mass index (BMI), waist circumference (WC), and muscle-related indicators increased with the dietary K tertile group (p <0.05). Across increasing tertiles of dietary Na intake, the odds ratio (OR) was increased significantly (p < 0.05) in fat-related indicators. On the contrary, with the increased dietary Na intake, the OR decreased (p < 0.05) in appendicular skeletal muscle mass index (ASMI) and body lean mass. As tertiles of dietary K intake increased, the OR in both skeletal muscle mass index (SMMI) and lean mass index (LMI) decreased. CONCLUSIONS: High dietary Na is a risk factor for abnormal lipid distribution in college students. High dietary K can maintain skeletal muscle mass and reduce the risk of obesity. Na in the diet has a greater impact on the body composition of young people than K. Low dietary Na and high dietary K still need to be strengthened in science popularization and practice among more college students.

Effect of novel botanical synergist on the effectiveness and residue behavior of prothioconazole in wheat field.

Fusarium head blight (FHB) is a critical fungal disease causes serious grain yield losses and mycotoxin contaminations. Currently, utilization of chemical fungicides is the main control method which has led to serious resistance. Development of novel synergist is an important strategy to reduce the usage of chemical fungicides and postpone the development of resistance, while natural components are interesting resources. In this study, the synergistic effect of Taxodium 'zhongshansha' essential oil (TZEO) was determined and the best synergistic ratio (SR) of 3.96 in laboratory which was observed when the weight ratio of TZEO and prothioconazole was 1 : 1 with the corresponding EC50 (half maximal effective concentration) value of Fusarium graminearum was 0.280 mg L-1. Subsequently, an increase of 6.31% on the control effect to FHB index in field test was observed when compared to the treatment with prothioconazole alone, though there was no significant difference between these treatments. Furthermore, we established an effective method to detect the mycotoxin contaminations in wheat grain with the limits of quantifications (LOQs) value of 5 µg kg-1 (DON, ZEN, 3-DON, and 15-DON) and 1 µg kg-1 (OTA) and the contents were less to the maximum residue limit (MRL) values. It was also shown that the application of 20% TZEO EW led to a 20% reduction in the use of prothioconazole, which was calculated based on the control effect values of 86.41% and 90.20% between the treatments of 30% prothioconazole OD (225 g a.i ha-1, recommend dosage) and 30% prothioconazole OD (180 g a.i ha-1) + 20% TZEO EW (225 mL ha-1), significantly. The initial residue of prothioconazole and prothioconazole-desthio was increased in the treatment with TZEO, which may play an important role in the synergistic effect on FHB. Moreover, none of the treatments posed a prothioconazole residue risk in the wheat grain and the environment. In addition, the essential oil has no any negative influence on wheat growth, which was revealed by a study of the chlorophyll content. These results provide an important botanical synergist for use with prothioconazole to control Fusarium head blight, and in-depth study to the synergistic mechanism of this oil is necessary in our future research.

Gut microbial signatures of patients with primary hepatocellular carcinoma and their healthy first-degree relatives.

AIMS: The gut microbiome has been recognized as a significant contributor to primary hepatocellular carcinoma (HCC), with mounting evidence indicating associations between bacterial components and cancers of the digestive system. METHODS AND RESULTS: Here, to characterize gut bacterial signature in patients with primary HCC and to assess the diagnostic potential of bacterial taxa for primary HCC, 21 HCC patients and 21 healthy first-degree relatives (control group) were enrolled in this study. Bacterial DNA in the fecal samples was quantified by 16S rRNA gene sequencing. We found that 743 operational taxonomic units (OTUs) were shared between patients with primary HCC and healthy controls. Of these, 197 OTUs were unique to patients with primary HCC, while 95 OTUs were unique to healthy subjects. Additionally, we observed significant differences in the abundance of Ruminococcaceae_UCG-014 and Romboutsia between patients with primary HCC and their healthy first-degree relatives. Besides, the relative abundance of Ruminococcaceae_UCG-014 and Prevotella_9 was positively correlated with physiological indicators including AST, ALT, ALB, or TBIL. Signature bacterial taxa could serve as non-invasive biomarkers, of which Romboutsia and Veillonella were identified as differential taxa in fecal samples from patients with HCC compared to healthy controls. Romboutsia showed a strong association with HCC (AUC = 0.802). Additionally, the combination of Romboutsia and Veillonella (AUC = 0.812) or the grouping of Fusobacterium, Faccalibacterium, and Peptostreptococcacae together (AUC = 0.762) exhibited promising outcomes for the diagnosis of HCC. CONCLUSIONS: The composition of gut microbes in patients with HCC was found to be significantly altered. Differential taxa Romboutsia, Veillonella, and Peptostreptococcacae could be tested for identification of HCC.

Hypoadiponectinemia-induced upregulation of microRNA449b downregulating Nrf-1 aggravates cardiac ischemia-reperfusion injury in diabetic mice.

Diabetes enhances myocardial ischemic/reperfusion (MI/R) injury via an incompletely understood mechanism. Adiponectin (APN) is a cardioprotective adipokine suppressed by diabetes. However, how hypoadiponectinemia exacerbates cardiac injury remains incompletely understood. Dysregulation of miRNAs plays a significant role in disease development. However, whether hypoadiponectinemia alters cardiac miRNA profile, contributing to diabetic heart injury, remains unclear. Methods and Results: Wild-type (WT) and APN knockout (APN-KO) mice were subjected to MI/R. A cardiac microRNA profile was determined. Among 23 miRNAs increased in APN-KO mice following MI/R, miR-449b was most significantly upregulated (3.98-fold over WT mice). Administrating miR-449b mimic increased apoptosis, enlarged infarct size, and impaired cardiac function in WT mice. In contrast, anti-miR-449b decreased apoptosis, reduced infarct size, and improved cardiac function in APN-KO mice. Bioinformatic analysis predicted 73 miR-449b targeting genes, and GO analysis revealed oxidative stress as the top pathway regulated by these genes. Venn analysis followed by luciferase assay identified Nrf-1 and Ucp3 as the two most important miR-449b targets. In vivo administration of anti-miR-449b in APN-KO mice attenuated MI/R-stimulated superoxide overproduction. In vitro experiments demonstrated that high glucose/high lipid and simulated ischemia/reperfusion upregulated miR-449b and inhibited Nrf-1 and Ucp3 expression. These pathological effects were attenuated by anti-miR-449b or Nrf-1 overexpression. In a final attempt to validate our finding in a clinically relevant model, high-fat diet (HFD)-induced diabetic mice were subjected to MI/R and treated with anti-miR-449b or APN. Diabetes significantly increased miR-449b expression and downregulated Nrf-1 and Ucp3 expression. Administration of anti-miR-449b or APN preserved cardiac Nrf-1 expression, reduced cardiac oxidative stress, decreased apoptosis and infarct size, and improved cardiac function. Conclusion: We demonstrated for the first time that hypoadiponectinemia upregulates miR-449b and suppresses Nrf-1/Ucp3 expression, promoting oxidative stress and exacerbating MI/R injury in this population. Dysregulated APN/miR-449b/oxidative stress pathway is a potential therapeutic target against diabetic MI/R injury.

eIF2α incites photoreceptor cell and retina damage by all-trans-retinal.

Dry age-related macular degeneration (AMD) and recessive Stargardt's disease (STGD1) lead to irreversible blindness in humans. The accumulation of all-trans-retinal (atRAL) induced by chaos in visual cycle is closely associated with retinal atrophy in dry AMD and STGD1 but its critical downstream signaling molecules remain ambiguous. Here, we reported that activation of eukaryotic translation initiation factor 2α (eIF2α) by atRAL promoted retinal degeneration and photoreceptor loss through activating c-Jun N-terminal kinase (JNK) signaling-dependent apoptosis and gasdermin E (GSDME)-mediated pyroptosis. We determined that eIF2α activation by atRAL in photoreceptor cells resulted from endoplasmic reticulum homeostasis disruption caused at least in part by reactive oxygen species production, and it activated JNK signaling independent of and dependent on activating transcription factor 4 and the activating transcription factor 4/transcription factor C/EBP homologous protein (CHOP) axis. CHOP overexpression induced apoptosis of atRAL-loaded photoreceptor cells through activating JNK signaling rather than inhibiting the expression of antiapoptotic gene Bcl2. JNK activation by eIF2α facilitated photoreceptor cell apoptosis caused by atRAL via caspase-3 activation and DNA damage. Additionally, we demonstrated that eIF2α was activated in neural retina of light-exposed Abca4-/-Rdh8-/- mice, a model that shows severe defects in atRAL clearance and displays primary features of human dry AMD and STGD1. Of note, inhibition of eIF2α activation by salubrinal effectively ameliorated retinal degeneration and photoreceptor apoptosis in Abca4-/-Rdh8-/- mice upon light exposure. The results of this study suggest that eIF2α is an important target to develop drug therapies for the treatment of dry AMD and STGD1.

ß-Cyclodextrin functionalized magnetic polyamine-amine dendrimers for high enrichment and effective analysis of trace bisphenolic pollutants in beverages.

Bisphenols (BPs) are typical endocrine disruptors, which can cause great effects on environmental, organisms and human health. In this study, ß-Cyclodextrin (ß-CD) functionalized polyamidoamine dendrimers-modified Fe3O4 nanomaterials (MNPs@PAMAM (G3.0)@ß-CD) were facilely synthesized. It exhibited good adsorption capacities for BPs, which was utilized to construct a sensitive tool in combination with high performance liquid chromatography for monitoring BPs such as bisphenol A (BPA), tetrabromobisphenol A (TBBPA), bisphenol S (BPS), bisphenol AF (BPAF) and bisphenol AP (BPAP) in beverage samples. The factors affecting the enrichment were examined such as generation of adsorbent, dosage of adsorbent, type and volume of eluting solvent, elution time and pH value of sample solution. The optimal parameters for enrichment was as follows: dosage of adsorbent, 60 mg; adsorption time, 50min; sample pH, pH7; elutent, 9 mL mixture of methanol and acetone(1:1); elution time, 6min; sample volume, 60 mL. The experimental results demonstrated that the adsorption conformed to pseudo-second-order kinetic model and Langmuir adsorption isotherm model. The results showed the maximum adsorption capacities of BPS, TBBPA, BPA, BPAF and BPAP were 131.80 µgg-1, 139.84 µgg-1, 157.08 µgg-1, 142.11 µgg-1 and 134.23 µgg-1, respectively. Under optimal conditions, BPS had good linear relationship over range from of 0.5-300 µgL-1, and the linear ranges of BPA, TBBPA, BPAF and BPAP ranged from 0.1 to 300 µgL-1. The limits of detection (S/N = 3) for BPs were good in range of 0.016-0.039 µgL-1. The spiked recoveries of target bisphenols (BPs) in beverages were approving over range from 92.3% to 99.2%. The established method possessed merits of easy to operate, good sensitivity, rapidness as well as environmental friendliness, and which earned great application potential for the enrichment and detection of trace BPs in practical samples.

Discrimination between progressive penumbra and benign oligemia of the diffusion-perfusion mismatch region by amide proton transfer-weighted imaging.

PURPOSE: Amide proton transfer-weighted (APTw) imaging was an effective tool to reveal the tissue acidosis of acute ischemic stroke. This study aimed to evaluate the ability of APTw MRI to distinguish progressive penumbra and benign oligemia in the diffusion-perfusion mismatch region. MATERIALS AND METHODS: 38 acute cerebral infarction patients who underwent a comprehensive MRI examination, including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), APT imaging, and a follow-up scan in one week were recruited. There were 12 DWI/PWI match cases. The DWI/PWI mismatch patients were divided into 10 progressive cases and 16 stable cases according to the lesion size on the follow-up DWI image compared to the admission scan. Three ROIs: infarction lesion, peripheral, and contralateral normal regions were measured on each subject's MTRasym map. The Friedman test was used to compare the changes of MTRasym among three different regions within each group. The Kruskal-Wallis ANOVA test was used to compare them among the same region of different groups. The correlation between the MTRasym of the peripheral region and the lesion enlargement was analyzed by the Spearman test. RESULTS: The MTRasym at the infarction lesion of all three groups showed significant decrease to the contralateral normal tissue. In the progressive mismatch group, the MTRasym at the peripheral region within the DWI/PWI mismatch showed a significant difference with the contralateral normal region and no difference with the infarct core. Whereas both the MTRasym at the peripheral region of the stable mismatch and match groups had no significant difference with the contralateral side, but the differences were significant from those of the central core. When comparing the peripheral region of three groups, the MTRasym of the progressive mismatch group showed a significant decrease to that of the stable mismatch and match groups. The MTRasym of the peripheral region showed a negative correlation with lesion enlargement. CONCLUSION: APTw imaging is promising to stratify the heterogeneous PWI/DWI mismatch region and benefit the clinical treatment.

Effect of palmitoylethanolamide on degeneration of a human-derived retinal pigment epithelial cell induced by all-trans retinal.

AIM: To study the effect of palmitoylethanolamide (PEA) on apoptosis of retinal pigment epithelial (RPE) cells induced by all-trans retinal (atRAL) and to explore the possible molecular mechanism. METHODS: CellTiter 96® Aqueous One Solution Cell Proliferation Assay (MTS) was used to detect the effect of PEA on human-derived retinal epithelial cells (ARPE-19) viability induced by atRAL. A Leica DMi8 inverted microscope was used to observe cell morphology. Reactive oxygen species (ROS) production was evaluated with 2',7'-dichlorodihydrof-luorescein diacetate (H2DCFDA) staining and fluorescence microscopy. Expression of c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), c-Jun, phosphorylated c-Jun (p-c-Jun), Bak, cleaved caspase-3, C/EBP homologous protein (CHOP), and binding (Bip) protein levels were tested by Western blot. Abca4 -/- Rdh8 -/- mice, mouse models of atRAL clearance defects which displays some symbolic characteristics of dry age-related macular degeneration (AMD) and Stargardt disease (STGD1). In the animal models, PEA was injected intraperitoneally. The full-field electroretinogram was used to detect visual function under scotopic conditions traced from mice. Optical coherence tomography showed reconstitution or thickening of the retinal pigment epithelium layer. Effect of PEA on fundus injury induced by light in Abca4-/-Rdh8-/- mice was observed by fundus photography. RESULTS: PEA ameliorated ARPE-19 cells apoptosis and inhibited ROS (including mitochondrial ROS) production induced by atRAL. PEA improved the retinal functional, prohibited both RPE and photoreceptor from death, ameliorates light-induced fundus impairment in Abca4 -/- Rdh8 -/- mice. In vitro and in vivo, PEA inhibited JNK, p-JNK, c-Jun, p-c-Jun, Bak, cleaved caspase-3, CHOP, and Bip protein levels induced by all-trans retinal in ARPE-19 cells. CONCLUSION: PEA has effect on treating RPE cells apoptosis in retinopathy caused by atRAL accumulation. PEA is a potential treatment strategy for dry AMD and STGD1. The molecular mechanism is affecting the ROS-JNK-CHOP signaling pathway partly.

Improvement of olfactory fMRI activation and hemodynamic response function curve with respiration correction.

BACKGROUND: Odor perception is highly dependent on respiration, however, the asynchronization between inspiration and odor delivery results in a decreased activation and hemodynamic response function (HRF) curve in olfactory functional MRI (fMRI). This study aimed to investigate the effect of a data post-processing method to minimize the asynchronization and consequently improve the olfactory activation and HRF curve and compare it between different TRs (3 s and 1 s). NEW METHOD: A new data post-processing method of respiration correction based on olfactory perception was investigated. COMPARISON WITH EXISTING METHODS: The odor stimuli of olfactory fMRI were mostly based on odor deliveries. But for the reason of respiration, the time of olfactory perception might be a little different. The actual onset time and duration of odor stimuli were modified based on the respiration data. RESULTS: For 3 s TR data, an increased number of activated voxels and higher HRF curves response height were obtained with the respiration correction method in the primary olfactory cortex (POC) (P = 0.034 and 0.009) and insula (P = 0.024 and 0.001), compared with the uncorrected method. But the activated voxels and response height of the anterior cingulate cortex (ACC) did not differ between uncorrected and respiration correction methods (P = 0.102 and 0.200). The time to peak of the HRF curve was shorter with the respiration correction method in all ROIs (all P < 0.05), compared with the uncorrected method. Whereas there were no significant differences between the uncorrected and corrected results for 1 s TR data. CONCLUSIONS: The post-processing method of respiration correction could effectively minimize the asynchronization between respirations and odor deliveries, and improve the activations and HRF curves for a routine 3 s TR olfactory fMRI data.

Tissue perfusion of the kurtosis/diffusion mismatch differs from the central core and peripheral regions in acute cerebral infarction patients.

BACKGROUND: Despite its wide adoption in stroke imaging, the diffusion-weighted imaging (DWI) lesion is heterogeneous. The emerging diffusion kurtosis imaging (DKI) has been postulated to resolve the graded DWI lesion. PURPOSE: To determine the perfusion characteristics of the central infarction core, kurtosis/diffusion mismatch, and peripheral regions. MATERIAL AND METHODS: Patients with acute ischemic stroke underwent DWI, DKI, and perfusion-weighted imaging (PWI) scans. The patients were divided into mean kurtosis (MK)/mean diffusivity (MD) match and mismatch groups. Perfusion parameters were measured in the MK/MD lesion and peripheral areas in the MK/MD match group. We also analyzed perfusion status in the MK/MD lesion mismatch area for the mismatch group. RESULTS: A total of 40 eligible patients (24 MK/MD match and 16 MK/MD mismatch) were enrolled in the final data analysis. The MTT and TTP progressively decreased, while the cerebral blood flow (CBF) and cerebral blood volume (CBV) increased from the central to peripheral areas. In addition, CBF in the MK/MD mismatch region was significantly higher than that in the central region (P < 0.05), but similar to the peripheral region. Furthermore, CBV in the MK/MD mismatch region did not differ significantly from that of the central region, but both were significantly lower than that of the peripheral area (P < 0.05). CONCLUSION: The MK/MD mismatch region had blood flow similar to the peripheral region but with a reduced blood volume, indicating that it was less ischemic from the infarction core, albeit insufficient collateral circulation.

Induction of ferroptosis by HO-1 contributes to retinal degeneration in mice with defective clearance of all-trans-retinal.

The accumulation of all-trans-retinal (atRAL) in photoreceptors and the retinal pigment epithelium (RPE), which is induced by chaos in visual (retinoid) cycle, is closely associated with the pathogenesis of dry age-related macular degeneration (AMD) and autosomal recessive Stargardt's disease (STGD1). Although we have reported that the induction of ferroptosis by atRAL is an important cause of photoreceptor loss, but its mechanisms still remain unclear. In this study, we identified heme oxygenase-1 (HO-1) as an inducer of photoreceptor ferroptosis elicited by atRAL. In atRAL-loaded photoreceptor cells, inhibition of Kelch-like ECH-associated protein 1 (KEAP1) at least in part by reactive oxygen species (ROS) production evoked the release of nuclear factor-erythroid 2-related factor-2 (NRF2) from KEAP1, followed by the translocation of active NRF2 into the nucleus where it promoted the transcription of the Ho-1 gene, thereby leading to HO-1 overexpression in the cytosol. A significant elevation of Fe2+ levels in photoreceptor cells resulted from activation of HO-1 by atRAL, and it facilitated ROS overproduction and then triggered ferroptotic cell death through ROS-mediated lipid peroxidation. Both treatment with HO-1 repressor Zinc protoporphyrin IX (ZnPP) and knockout of Ho-1 gene clearly rescued photoreceptor cells against ferroptosis arising from atRAL overload. Light-exposed Abca4-/-Rdh8-/- mice rapidly display severe defects in atRAL clearance, and serve as an acute model of dry AMD and STGD1. HO-1 activation was distinctly observed in neural retina of Abca4-/-Rdh8-/- mice after exposure to light, and it was visibly relieved by intraperitoneally injected ferroptosis inhibitor ferrostatin-1. More notably, intraperitoneal administration of ZnPP effectively alleviated both photoreceptor degeneration and RPE atrophy in Abca4-/-Rdh8-/- mice in response to light exposure by repressing HO-1-mediated ferroptosis. Our study suggests that HO-1 is a key factor that regulates atRAL-induced ferroptosis in photoreceptors and the RPE, and its inhibition may hold promises for the therapy of dry AMD and STGD1.

Highly efficient and simultaneous magnetic solid phase extraction of heavy metal ions from water samples with l-Cysteine modified magnetic polyamidoamine dendrimers prior to high performance liquid chromatography.

Due to the strong metal-sulfur interaction between mercapto groups and metal ions, which can be used to functionalize polyamidoamine dendrimer decorated Fe3O4 nanoparticles for high enrichment of trace heavy metal ions from waters. Based on this concept, polyamidoamine dendrimer modified Fe3O4 nanomaterials were functionalized with l-Cysteine and a new magnetic solid phase extraction for rapid adsorption and separation of Hg2+, Pb2+, Co2+ and Cd2+ from waters was established. The factors affecting extraction efficiency have been optimized. Upon the optimal parameters, the established method provided good linear ranges of 0.1-200 µg L-1 for Hg2+ and 0.05-200 µg L-1 for Pb2+, Co2+ and Cd2+, and high sensitivity with limits of detection (LOD) of 0.018 µg L-1, 0.014 µg L-1, 0.013 µg L-1 and 0.025 µg L-1 for Cd2+, Pb2+, Co2+ and Hg2+, respectively. Real water samples were utilized to validate the proposed method, and achieved results revealed that the proposed method was sensitive, effective, stable and suitable for monitoring Pb2+, Cd2+, Co2+and Hg2+ in environmental waters. This work provided a novel strategy for the simultaneous analysis of target cations in waters, and a new direction for developing decoration method of nanomaterials according to specific purpose.

COVID-19 and cardiovascular complications: updates of emergency medicine.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV-2 variants, has become a global pandemic resulting in significant morbidity and mortality. Severe cases of COVID-19 are characterized by hypoxemia, hyper-inflammation, cytokine storm in lung. Clinical studies have reported an association between COVID-19 and cardiovascular disease (CVD). Patients with CVD tend to develop severe symptoms and mortality if contracted COVID-19 with further elevations of cardiac injury biomarkers. Furthermore, COVID-19 itself can induce and promoted CVD development, including myocarditis, arrhythmia, acute coronary syndrome, cardiogenic shock, and venous thromboembolism. Although the direct etiology of SARS-CoV-2 induced cardiac injury remains unknown and under-investigated, it is suspected that it is related to myocarditis, cytokine-mediated injury, microvascular injury, and stress-related cardiomyopathy. Despite vaccinations having provided the most effective approach to reducing mortality overall, an adapted treatment paradigm and regular monitoring of cardiac injury biomarkers is critical for improving outcomes in vulnerable populations at risk for severe COVID-19. In this review, we focus on the latest progress in clinic and research on the cardiovascular complications of COVID-19 and provide a perspective of treating cardiac complications deriving from COVID-19 in Emergency Medicine.

Reliable strategy of sensitive fluorescent nanoprobe for sensing silver nanoparticles using specific carbon dots derived from mercaptoacetic acid and melamine.

Nitrogen and sulfur element co-decorated carbon nanodots (N,S-CDs) were synthesized by solid state hydrothermal method utilizing mercaptoacetic acid and melamine as the precursors. The obtained N,S-CDs had wonderful optical and chemical stability. The experimental results demonstrated that silver nanoparticles (AgNPs) could noticeably quench the fluorescence of N,S-CDs. The quenching of fluorescence signal from the presence of AgNPs may be attributed to inner filter effect. The crafted nanoprobe for sensing AgNPs was endowed with some specialties such as simplicity, excellent selectivity and sensitivity, environmental friendliness and low cost. The probe exhibited specific linearity from 0.024 to 1.77 nM, and was endowed a good limit of detection down to 0.022 nM. The experimental results demonstrated that the built probe could be an efficient tool for AgNPs detection and had a prospective application, and also provided a new direction for establishing innovative method for determining and monitoring pollutants from nanoparticles.