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1.
Clin Epigenetics ; 16(1): 94, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39026267

ABSTRACT

INTRODUCTION: Walking stands as the most prevalent physical activity in the daily lives of individuals and is closely associated with physical functioning and the aging process. Nonetheless, the precise cause-and-effect connection between walking and aging remains unexplored. The epigenetic clock emerges as the most promising biological indicator of aging, capable of mirroring the biological age of the human body and facilitating an investigation into the association between walking and aging. Our primary objective is to investigate the causal impact of walking with epigenetic age acceleration (EAA). METHODS: We conducted a two-sample two-way Mendelian randomization (MR) study to investigate the causal relationship between walking and EAA. Walking and Leisure sedentary behavior data were sourced from UK Biobank, while EAA data were gathered from a total of 28 cohorts. The MR analysis was carried out using several methods, including the inverse variance weighted (IVW), weighted median, MR-Egger, and robust adjusted profile score (RAPS). To ensure the robustness of our findings, we conducted sensitivity analyses, which involved the MR-Egger intercept test, Cochran's Q test, and MR-PRESSO, to account for and mitigate potential pleiotropy. RESULTS: The IVW MR results indicate a significant impact of usual walking pace on GrimAge (BETA = - 1.84, 95% CI (- 2.94, - 0.75)), PhenoAge (BETA = - 1.57, 95% CI (- 3.05, - 0.08)), Horvath (BETA = - 1.09 (- 2.14, - 0.04)), and Hannum (BETA = - 1.63, 95% CI (- 2.70, - 0.56)). Usual walking pace is significantly associated with a delay in epigenetic aging acceleration (EAA) (P < 0.05). Moreover, the direction of effect predicted by the gene remained consistent across RAPS outcomes and sensitivity MR analyses. There is a lack of robust causal relationships between other walking conditions, such as walking duration and walking frequency, on EAA (P > 0.05). CONCLUSION: Our evidence demonstrates that a higher usual walking pace is associated with a deceleration of the acceleration of all four classical epigenetic clocks acceleration.


Subject(s)
Aging , Epigenesis, Genetic , Mendelian Randomization Analysis , Walking , Humans , Mendelian Randomization Analysis/methods , Walking/physiology , Epigenesis, Genetic/genetics , Aging/genetics , Aging/physiology , Female , Male , Aged , Middle Aged , United Kingdom , Sedentary Behavior , DNA Methylation/genetics
2.
MedComm (2020) ; 5(8): e642, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39036342

ABSTRACT

The poor prognosis observed in elderly individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a serious clinical burden and the underlying mechanism is unclear, which necessities detailed investigation of disease characteristics and research for efficient countermeasures. To simulate lethal coronavirus disease 2019 (COVID-19) in senescent human patients, 80-week-old male hamsters are intranasally inoculated with different doses of SARS-CoV-2 Omicron BA.5 variant. Exposure to a low dose of the Omicron BA.5 variant results in early activation of the innate immune response, followed by rapid viral clearance and minimal lung damage. However, a high dose of BA.5 results in impaired interferon signaling, cytokine storm, uncontrolled viral replication, and severe lung injury. To decrease viral load and reverse the deterioration of COVID-19, a new bio-mimic decoy called CoVR-MV is used as a preventive or therapeutic agent. Administration of CoVR-MV as a preventive or therapeutic intervention in the early stages of infection can effectively suppress viral load, regulate the immune response, and rescue animals from death and critical illness. These findings underscore the risk associated with SARS-CoV-2 Omicron BA.5 exposure in senescent hamsters and highlight the importance of early intervention to prevent disease progression.

3.
Biomed Environ Sci ; 37(6): 617-627, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38988112

ABSTRACT

Objective: The aim of this study was to explore the role and mechanism of ferroptosis in SiO 2-induced cardiac injury using a mouse model. Methods: Male C57BL/6 mice were intratracheally instilled with SiO 2 to create a silicosis model. Ferrostatin-1 (Fer-1) and deferoxamine (DFO) were used to suppress ferroptosis. Serum biomarkers, oxidative stress markers, histopathology, iron content, and the expression of ferroptosis-related proteins were assessed. Results: SiO 2 altered serum cardiac injury biomarkers, oxidative stress, iron accumulation, and ferroptosis markers in myocardial tissue. Fer-1 and DFO reduced lipid peroxidation and iron overload, and alleviated SiO 2-induced mitochondrial damage and myocardial injury. SiO 2 inhibited Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes, while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion: Iron overload-induced ferroptosis contributes to SiO 2-induced cardiac injury. Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO 2 cardiotoxicity, potentially via modulation of the Nrf2 pathway.


Subject(s)
Disease Models, Animal , Ferroptosis , Iron Overload , Mice, Inbred C57BL , Myocytes, Cardiac , Silicon Dioxide , Silicosis , Animals , Ferroptosis/drug effects , Male , Mice , Iron Overload/metabolism , Silicon Dioxide/toxicity , Silicosis/metabolism , Silicosis/drug therapy , Silicosis/pathology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Deferoxamine/pharmacology , Phenylenediamines/pharmacology , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Oxidative Stress/drug effects , Iron/metabolism , Cyclohexylamines/pharmacology
4.
Heart Rhythm ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38997056

ABSTRACT

BACKGROUND: Prior studies have investigated cardiac anatomy and clinical parameters as predictors for pulmonary vein and non-pulmonary vein triggers. OBJECTIVES: To assess the link between the descending aorta to left inferior pulmonary vein (Dao-LIPV) distance and the occurrence of triggers and drivers in atrial fibrillation (AF) ablation procedures. METHODS: Drug-refractory AF patients who underwent first-time index catheter ablation from January 2010 to December 2019 were retrospectively assembled. The Dao-LIPV distance was measured from pre-ablation pulmonary vein computed tomography. Patients were categorized based on the presence of LIPV triggers and/or drivers. Multivariate logistic regression was used to identify risk factors. RESULTS: A total of 886 consecutive patients with drug-refractory AF were studied, and 63 (7.1%) patients were identified to have LIPV triggers and/or drivers. The Dao-LIPV distance had a better predictive performance (AUC: 0.70) compared to persistent AF (AUC: 0.57). Multivariate logistic regression analysis showed that Dao-LIPV distance ≤ 2.5 mm (Odds ratio [OR] 3.96 [95% CI 2.15-7.29], p <0.001) and persistent AF (OR 1.73 [95% CI 1.02-2.94], p=0.044) were independent predictors for the presence of LIPV triggers and/or drivers. A risk score model was established to predict the probability of LIPV triggers or drivers with persistent AF (10.2%), Dao-LIPV distance ≤ 2.5mm (11.4%), and both (15.0%). CONCLUSIONS: The close proximity of the Dao-LIPV was correlated to the presence of LIPV triggers or drivers. We developed a risk score model indicating that persistent AF and Dao-LIPV distances ≤ 2.5mm significantly increase the risk of LIPV triggers/drivers, aiding electrophysiologists in preparing for and performing catheter ablation more effectively.

5.
iScience ; 27(7): 110208, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39015149

ABSTRACT

The emergence of SARS-CoV-2 variants raises concerns about the efficacy of existing COVID-19 vaccines and therapeutics. Previously, we identified a conserved cryptic class 5 epitope of SARS-CoV-2 receptor binding domain (RBD) by two cross-neutralizing antibodies 7D6 and 6D6. Intriguingly, this site remains resistant to substantial mutations occurred in ever-changing SARS-CoV-2 subvariants. As compared to class 3 antibody S309, 6D6 maintains broad and consistent neutralizing activities against SARS-CoV-2 variants. Furthermore, 6D6 effectively protected hamster from the virulent Beta strain. Sequence alignment of approximately 6 million documented SARS-CoV-2 isolates revealed that 6D6 epitope maintains an exceptionally high conservation rate (99.92%). Structural analysis demonstrated that all 33 mutations accumulated in XBB.1.5 since the original strain do not perturb the binding 6D6 to RBD, in line with the sequence analysis throughout the antigenicity evolution of SARS-CoV-2. These findings suggest the potential of this epitope serving as a critical determinant for vaccines and therapeutic design.

6.
Article in English | MEDLINE | ID: mdl-39043158

ABSTRACT

INTRODUCTION: It's crucial to utilize combination therapy for IgAN patients to reduce proteinuria and maintain stable kidney function. We demonstrate the safety and efficacy of low-dose spironolactone in management of IgAN patients. METHODS: Adult IgAN patients treated with spironolactone were evaluated. Patients were separated into two categories according to whether 24h-proteinuria was reduced by more than 20% after two-months of spironolactone treatment compared to baseline levels. RESULTS: 88 patients were analyzed and 24h-proteinuria decreased from 0.93g to 0.70 g (p<0.001) after two-months of treatment with spironolactone, accompanied by a slight decrease in EPI-eGFR from 75.7 to 73.9 mL/min/1.73 m2 (p = 0.033). Intriguingly, 47 patients in effective MRA group showed less endocapillary hypercellularity (p = 0.040). In ineffective group, 18 patients discontinued MRA treatment because of 24h-proteinuria increased from 0.83 g to 1.04 g, while the other 23 patients were continued with spironolactone and proteinuria decreased to 0.57 g in the sixth month (p = 0.001). Furthermore, 12 patients with persistent high proteinuria during prednisone therapy, were added with spironolactone. 24-proteinuria were dropped from 0.95 g to 0.73 g at the second month, and to 0.50 g at the sixth month. CONCLUSIONS: In our study, we confirmed spironolactone's efficacy in reducing urine protein excretion in IgA nephropathy patients within two months of treatment. However, response varied among patients, with those showing endocapillary proliferation (E1) in renal biopsies having poor spironolactone responsiveness. Administering mineralocorticoid receptor antagonists (MRAs) to patients with eGFR over 30 ml/min did not result in hyperkalemia, indicating the treatment's safety. Key Words:IgA Nephrology, Proteinuria, Spironolactone, Renal function.

7.
Psych J ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39048100

ABSTRACT

Guanxi, a distinctive Chinese concept, reflects a shared vision of relationships and connections that include mutual understanding, trust, and a deep bond between individuals. Recognized for its potency in shaping the relationships that facilitate business undertakings and access to key resources, Guanxi is postulated as a potential mediator in the nexus between organizational justice and contextual work performance. The depth of Guanxi, intertwined with Chinese culture and values, may be perceived differently across age groups. Specifically, as Chinese millennials usually interact with global paradigms, generational disparities might emerge in valuing these traditional constructs. This study delves into how the dimensions of Guanxi-Ganqing (emotional connection), Renqing (reciprocity), and Xinren (loyalty)-mediate the relationship between organizational justice and contextual work performance, with chronological age as a moderator. The present study includes a convenience sample of 630 Chinese employees, aged 22-67 years, who participated in a quantitative online survey. The findings endorse the mediation role of Guanxi. The total influence of justice was found to be significant, as well as the indirect impacts, that were statistically salient. Although the age-moderated mediation was not wholly substantiated, the age-specific indirect effects of Renqing and Xinren did present significant variances between millennials and those above 42 years. The relevance of this study extends beyond the academic field, shedding light on the cultural dynamics at play within Chinese organizational settings. By unveiling the relationships between Guanxi, organizational justice, and performance, and by elucidating the age-specific variations therein, this research provides insights for organizational leaders and human resource professionals. Based on these findings, businesses can craft targeted interventions that capitalize on the strengths of Guanxi, ensuring fair practices and enhancing performance across diverse age groups. Further, recognizing the unique attributes and values of different generational cohorts can aid in fostering a harmonious, culturally attuned, and efficient workplace environment.

8.
Bioelectrochemistry ; 160: 108782, 2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39053177

ABSTRACT

This study is the first to investigate the effects of external resistance and electrolyte concentration on the performance of a bioelectro-Fenton (BEF) system, involving measurements of power density, H2O2 generation, and bisphenol A (BPA) removal efficiency. With optimized operating conditions (external resistance of 1.12 kΩ and cathodic NaCl concentration of 1,657 mg/L), the BEF system achieved a maximum power density of 38.59 mW/m2, which is about 3.5 times higher than with 1 kΩ external resistance and no NaCl. This system featured a 71.7 % reduction in total internal resistance. The optimized BEF also accelerated the oxygen reduction reaction rate, increasing H2O2 generation by 4.4 times compared to the unoptimized system. Moreover, it exhibited superior BPA degradation performance, removing over 99 % of BPA within 14 hs, representing a 1.1 to 3.3-fold improvement over the unoptimized BEF. By the fifth cycle (70 h), the optimized BEF still removed 70 % of BPA. Optimizing the operating conditions significantly increased the abundance of electrochemically active bacteria (Pseudomonadaceae) from 2.2 % to 20 %, facilitating rapid acclimation. The study demonstrates the strong potential of an optimized BEF system for removing persistent pollutants.

9.
Front Endocrinol (Lausanne) ; 15: 1384953, 2024.
Article in English | MEDLINE | ID: mdl-38836233

ABSTRACT

Background: Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme involved in kidney disease, yet its regulation in diabetic kidney disease (DKD) remains inadequately understood. Objective: Therefore, we investigated the changes of NAD+ levels in DKD and the underlying mechanism. Methods: Alternations of NAD+ levels and its biosynthesis enzymes were detected in kidneys from streptozotocin-induced diabetic mouse model by real-time PCR and immunoblot. The distribution of NAD+ de novo synthetic enzymes was explored via immunohistochemical study. NAD+ de novo synthetic metabolite was measured by LC-MS. Human data from NephroSeq were analyzed to verify our findings. Results: The study showed that NAD+ levels were decreased in diabetic kidneys. Both mRNA and protein levels of kynurenine 3-monooxygenase (KMO) in NAD+ de novo synthesis pathway were decreased, while NAD+ synthetic enzymes in salvage pathway and NAD+ consuming enzymes remained unchanged. Further analysis of human data suggested KMO, primarily expressed in the proximal tubules shown by our immunohistochemical staining, was consistently downregulated in human diabetic kidneys. Conclusion: Our study demonstrated KMO of NAD+ de novo synthesis pathway was decreased in diabetic kidney and might be responsible for NAD+ reduction in diabetic kidneys, offering valuable insights into complex regulatory mechanisms of NAD+ in DKD.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , NAD , Animals , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , NAD/metabolism , Humans , Mice , Diabetes Mellitus, Experimental/metabolism , Male , Mice, Inbred C57BL , Disease Models, Animal , Kidney/metabolism , Kidney/pathology
10.
Ibrain ; 10(2): 164-171, 2024.
Article in English | MEDLINE | ID: mdl-38915949

ABSTRACT

This study aimed to provide a recommendable protocol for the preparation of brain cryosections of rats to reduce and avoid ice crystals. We have designed five different dewatering solutions (Scheme 1: dehydrate with 15%, 20%, and 30% sucrose-phosphate-buffered saline solution; Scheme 2: 20% sucrose and 30% sucrose; Scheme 3: 30% sucrose; Scheme 4: 10%, 20%, and 30% sucrose; and Scheme 5: the tissue was dehydrated with 15% and 30% sucrose polyacetate I until it sank to the bottom, followed by placement in 30% sucrose polyacetate II) to minimize the formation of ice crystals. Cryosections from different protocols were stained with Nissl staining and compared with each other by density between cells and the distance of intertissue spaces. The time required for the dehydration process from Scheme 1 to Scheme 5 was 24, 23, 24, 24, and 33 h, respectively. Density between cells gradually decreased from Scheme 1 to Scheme 5, and the distance of intertissue spaces was differentiated and irregular in different schemes according to the images of Nissl staining. We recommend the dewatering method of Scheme 4 (the brain tissues were dehydrated in 10%, 20% and 30% sucrose solution in turn until the tissue samples were completely immersed in the solution and then immersed in the next concentration solution for dehydration).

11.
Virulence ; 15(1): 2362748, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38860453

ABSTRACT

Rad6 functions as a ubiquitin-conjugating protein that regulates cellular processes in many fungal species. However, its role in filamentous entomopathogenic fungi remains poorly understood. This study characterizes Rad6 in Beauveria bassiana, a filamentous fungus widely employed as a critical fungicide globally. The results demonstrate a significant association between Rad6 and conidial properties, heat shock response, and UV-B tolerance. Concurrently, the mutant strain exhibited heightened sensitivity to oxidative stress, cell wall interfering agents, DNA damage stress, and prolonged heat shock. Furthermore, the absence of Rad6 significantly extended the median lethal time (LT50) of Galleria mellonella infected by B. bassiana. This delay could be attributed to reduced Pr1 proteases and extracellular cuticle-degrading enzymes, diminished dimorphic transition rates, and dysregulated antioxidant enzymes. Additionally, the absence of Rad6 had a more pronounced effect on genetic information processing, metabolism, and cellular processes under normal conditions. However, its impact was limited to metabolism in oxidative stress. This study offers a comprehensive understanding of the pivotal roles of Rad6 in conidial and hyphal stress tolerance, environmental adaptation, and the pathogenesis of Beauveria bassiana.


Subject(s)
Beauveria , Fungal Proteins , Spores, Fungal , Animals , Beauveria/pathogenicity , Beauveria/genetics , Beauveria/physiology , Fungal Proteins/genetics , Fungal Proteins/metabolism , Heat-Shock Response , Hyphae/growth & development , Moths/microbiology , Oxidative Stress , Spores, Fungal/genetics , Stress, Physiological , Ubiquitin-Conjugating Enzymes/metabolism , Ubiquitin-Conjugating Enzymes/genetics , Virulence
12.
Angew Chem Int Ed Engl ; : e202408321, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926096

ABSTRACT

exo-6b2-Methyl-substituted pentabenzocorannulene (exoPBC-Me) was synthesized by the palladium-catalyzed cyclization of 1,2,3-triaryl-1H-cyclopenta[l]phenanthrene. Its bowl-shaped geometry with an sp3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X-ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen-doped analogs with intact π-conjugated backbones (see the main text), exo-PBC-Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250-620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO-LUMO gap (2.01 eV). exo-PBC-Me formed polar crystals where all bowl-in-bowl stacking with close π···π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp3 carbon atom in the backbone.

13.
J Mater Chem B ; 12(26): 6394-6409, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38855886

ABSTRACT

This study develops a composite bone graft of CaO-MgO-SiO2 glass-ceramic and CaSO4 [abbreviated as (CMS)3-x(CS)x] via the sponge replication technique with weight fractions of x = 0, 1, 1.5, 2, and 3. The (CMS)1.5(CS)1.5 composite displays a superior degradability and, a suitable compressive strength of ∼3 MPa, and excellent cell proliferation and differentiation. The in vivo rat femur test in the hybrid-pore (CMS)1.5(CS)1.5 composite granules achieves a higher rate of bone formation, which is ∼2.7 times better than that of the commercial HAP/ß-TCP at 12 weeks. Improved expressions of osteocyte and mature osteocyte marker genes, namely (Spp1, Dmp1, and Fgf23), were observed in the (CMS)1.5(CS)1.5 group, indicating a faster differentiation into mature bone tissue. The ions release of (CMS)1.5(CS)1.5 through the ERK1/2 signaling pathway promotes osteogenic differentiation. The high bone generation rate can be attributed to faster active ions release and modified surface topography. This work highlights an excellent bone graft candidate for clinical applications in orthopedic surgery.


Subject(s)
Ceramics , Osteogenesis , Ceramics/chemistry , Animals , Osteogenesis/drug effects , Rats , Cell Differentiation/drug effects , Calcium Compounds/chemistry , Rats, Sprague-Dawley , Cell Proliferation/drug effects , Oxides/chemistry , Silicon Dioxide/chemistry , Male , Bone Substitutes/chemistry , Bone Substitutes/pharmacology , Bone Transplantation/methods , Magnesium Oxide/chemistry , Surface Properties , Femur
14.
Microbiome ; 12(1): 84, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725076

ABSTRACT

BACKGROUND: Emergence of antibiotic resistance in bacteria is an important threat to global health. Antibiotic resistance genes (ARGs) are some of the key components to define bacterial resistance and their spread in different environments. Identification of ARGs, particularly from high-throughput sequencing data of the specimens, is the state-of-the-art method for comprehensively monitoring their spread and evolution. Current computational methods to identify ARGs mainly rely on alignment-based sequence similarities with known ARGs. Such approaches are limited by choice of reference databases and may potentially miss novel ARGs. The similarity thresholds are usually simple and could not accommodate variations across different gene families and regions. It is also difficult to scale up when sequence data are increasing. RESULTS: In this study, we developed ARGNet, a deep neural network that incorporates an unsupervised learning autoencoder model to identify ARGs and a multiclass classification convolutional neural network to classify ARGs that do not depend on sequence alignment. This approach enables a more efficient discovery of both known and novel ARGs. ARGNet accepts both amino acid and nucleotide sequences of variable lengths, from partial (30-50 aa; 100-150 nt) sequences to full-length protein or genes, allowing its application in both target sequencing and metagenomic sequencing. Our performance evaluation showed that ARGNet outperformed other deep learning models including DeepARG and HMD-ARG in most of the application scenarios especially quasi-negative test and the analysis of prediction consistency with phylogenetic tree. ARGNet has a reduced inference runtime by up to 57% relative to DeepARG. CONCLUSIONS: ARGNet is flexible, efficient, and accurate at predicting a broad range of ARGs from the sequencing data. ARGNet is freely available at https://github.com/id-bioinfo/ARGNet , with an online service provided at https://ARGNet.hku.hk . Video Abstract.


Subject(s)
Bacteria , Neural Networks, Computer , Bacteria/genetics , Bacteria/drug effects , Bacteria/classification , Drug Resistance, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , High-Throughput Nucleotide Sequencing/methods , Computational Biology/methods , Genes, Bacterial/genetics , Drug Resistance, Microbial/genetics , Humans , Deep Learning
15.
Front Cardiovasc Med ; 11: 1306055, 2024.
Article in English | MEDLINE | ID: mdl-38689859

ABSTRACT

Introduction: Signal-averaged electrocardiography (SAECG) provides diagnostic and prognostic information regarding cardiac diseases. However, its value in other nonischemic cardiomyopathies (NICMs) remains unclear. This study aimed to investigate the role of SAECG in patients with NICM. Methods and results: This retrospective study included consecutive patients with NICM who underwent SAECG, biventricular substrate mapping, and ablation for ventricular arrhythmia (VA). Patients with baseline ventricular conduction disturbances were excluded. Patients who fulfilled at least one SAECG criterion were categorized into Group 1, and the other patients were categorized into Group 2. Baseline and ventricular substrate characteristics were compared between the two groups. The study included 58 patients (39 men, mean age 50.4 ± 15.5 years), with 34 and 24 patients in Groups 1 and 2, respectively. Epicardial mapping was performed in eight (23.5%) and six patients (25.0%) in Groups 1 and 2 (p = 0.897), respectively. Patients in Group 1 had a more extensive right ventricular (RV) low-voltage zone (LVZ) and scar area than those in Group 2. Group 1 had a larger epicardial LVZ than Group 2. Epicardial late potentials were more frequent in Group 1 than in Group 2. There were more arrhythmogenic foci within the RV outflow tract in Group 1 than in Group 2. There was no significant difference in long-term VA recurrence. Conclusion: In our NICM population, a positive SAECG was associated with a larger RV endocardial scar, epicardial scar/late potentials, and a higher incidence of arrhythmogenic foci in the RV outflow tract.

16.
Cell Mol Biol Lett ; 29(1): 68, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730334

ABSTRACT

BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.


Subject(s)
Actins , Meiosis , Oocytes , cdc42 GTP-Binding Protein , Animals , Oocytes/metabolism , Mice , Female , Actins/metabolism , Actins/genetics , cdc42 GTP-Binding Protein/metabolism , cdc42 GTP-Binding Protein/genetics , Phosphorylation , Spindle Apparatus/metabolism
17.
Angew Chem Int Ed Engl ; : e202405017, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38749917

ABSTRACT

The controllable anchoring of multiple metal single-atoms (SAs) into a single support exhibits scientific and technological opportunities, while marrying the concentration-complex multimetallic SAs and high-entropy SAs (HESAs) into one SAC system remains a substantial challenge. Here, we present a substrate-mediated SAs formation strategy to successfully fabricate a library of multimetallic SAs and HESAs on MoS2 and MoSe2 supports, which can precisely control the doping location of SAs. Specially, the contents of SAs can continuously increase until the accessible Mo atoms on TMDs carriers are completely replaced by SAs, thus allowing the of much higher metal contents. In-depth mechanistic study shows that the well-controlled synthesis of multimetallic SAs and HESAs is realized by controlling the reversible redox reaction occurred on the TMDs/TM ion interface. As a proof-of-concept application, a variety of SAs-TMDs were applied to hydrogen evolution reaction. The optimized HESAs-TMDs (Pt,Ru,Rh,Pd,Re-MoSe2) delivers a much higher activity and durability than state of-the-art Pt. Thus, our work will broaden the family of single-atom catalysts and provide a new guideline for the rational design of high-performance single-atom catalysts.

18.
Heliyon ; 10(7): e28111, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38596035

ABSTRACT

This study develops an efficient approach for precise channel frame detection in complex backgrounds, addressing the critical need for accurate drone navigation. Leveraging YOLACT and group regression, our method outperforms conventional techniques that rely solely on color information. We conducted extensive experiments involving channel frames placed at various angles and within intricate backgrounds, training the algorithm to effectively recognize them. The process involves initial edge image detection, noise reduction through binarization and erosion, segmentation of channel frame line segments using the Hough Transform algorithm, and subsequent classification via the K-means algorithm. Ultimately, we obtain the regression line segment through linear regression, enabling precise positioning by identifying intersection points. Experimental validations validate the robustness of our approach across diverse angles and challenging backgrounds, making significant advancements in UAV applications.

19.
Development ; 151(6)2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38546043

ABSTRACT

The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility.


Subject(s)
M Phase Cell Cycle Checkpoints , Meiosis , Animals , Female , Mice , Anaphase-Promoting Complex-Cyclosome/genetics , Anaphase-Promoting Complex-Cyclosome/metabolism , Oocytes/metabolism , Ubiquitins/metabolism
20.
Nat Commun ; 15(1): 2174, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38467627

ABSTRACT

When electrons moving in two dimensions (2D) are subjected to a strong uniform magnetic field, they form flat bands called Landau levels (LLs). LLs can also arise from pseudomagnetic fields (PMFs) induced by lattice distortions. In three-dimensional (3D) systems, there has been no experimental demonstration of LLs  as a type of flat band thus far. Here, we report the experimental realization of a flat 3D LL in an acoustic crystal. Starting from a lattice whose bandstructure exhibits a nodal ring, we design an inhomogeneous distortion corresponding to a specific pseudomagnetic vector potential (PVP). This distortion causes the nodal ring states to break up into LLs, including a zeroth LL that is flat along all three directions. These findings suggest the possibility of using nodal ring materials to generate 3D flat bands, allowing access to strong interactions and other attractive physical regimes in 3D.

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