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1.
Artículo en Inglés | MEDLINE | ID: mdl-39208046

RESUMEN

Combining LiDAR points and images for robust semantic segmentation has shown great potential. However, the heterogeneity between the two modalities (e.g. the density, the field of view) poses challenges in establishing a bijective mapping between each point and pixel. This modality alignment problem introduces new challenges in network design and data processing for cross-modal methods. Specifically, 1) points that are projected outside the image planes; 2) the complexity of maintaining geometric consistency limits the deployment of many data augmentation techniques. To address these challenges, we propose a cross-modal knowledge imputation and transition approach. First, we introduce a bidirectional feature fusion strategy that imputes missing image features and performs cross-modal fusion simultaneously. This allows us to generate reliable predictions even when images are missing. Second, we propose a Uni-to-Multi modal Knowledge Distillation (U2MKD) framework, leveraging the transfer of informative features from a single-modality teacher to a cross-modality student. This overcomes the issues of augmentation misalignment and enables us to train the student effectively. Extensive experiments on the nuScenes, Waymo, and SemanticKITTI datasets demonstrate the effectiveness of our approach. Notably, our method achieves an 8.3 mIoU gain over the LiDAR-only baseline on the nuScenes validation set and achieves state-of-the-art performance on the three datasets.

2.
Sensors (Basel) ; 24(15)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39124014

RESUMEN

Given the challenges associated with the low accuracy, complexity of the equipment, and poor interference resistance observed in current wireless multipath channel measurements, this study introduces a novel algorithm called KFSC-WRELAX. This algorithm integrates techniques involving pseudorandom noise (PN) sequences, Kalman filtering (KF), sliding correlation, and weighted Fourier transform combined with the RELAXation (WRELAX) algorithm. An m-sequence is employed as the probing sequence for channel detection. The effectiveness of the KFSC-WRELAX algorithm is demonstrated through both simulation experiments and corridor testing, showing that it can accurately determine the delays in various paths with robust performance at a signal-to-noise ratio (SNR) of -5 dB or higher.

3.
Heliyon ; 10(14): e34600, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39149038

RESUMEN

Objective: The aim of this study was to elucidate the genetic pathways associated with Moyamoya disease (MMD) and Moyamoya syndrome (MMS), compare the functional activities, and validate relevant related genes in an independent dataset. Methods: We conducted a comprehensive search for genetic studies on MMD and MMS across multiple databases and identified related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analyses were performed for these genes. Commonly shared genes were selected for further validation in the independent dataset, GSE189993. The Sangerbox platform was used to perform statistical analysis and visualize the results. P<0.05 indicated a statistically significant result. Results: We included 52 MMD and 51 MMS-related publications and identified 126 and 51 relevant genes, respectively. GO analysis for MMD showed significant enrichment in cytokine activity, cell membrane receptors, enzyme binding, and immune activity. A broader range of terms was enriched for MMS. KEGG pathway analysis for MMD highlighted immune and cellular activities and pathways related to MMS prominently featured inflammation and metabolic disorders. Notably, nine overlapping genes were identified and validated. The expressions of RNF213, PTPN11, and MTHFR demonstrated significant differences in GSE189993. A combined receiver operating characteristic curve showed high diagnostic accuracy (AUC = 0.918). Conclusions: The findings indicate a close relationship of MMD with immune activity and MMS with inflammation, metabolic processes and other environmental factors in a given genetic background. Differentiating between MMD and MMS can enhance the understanding of their pathophysiology and inform the strategies for their diagnoses and treatment.

4.
Neurology ; 103(5): e209776, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39116372

RESUMEN

BACKGROUND AND OBJECTIVES: Anxiety and depression have implications for ischemic stroke recovery. This study explored the association of genetically predicted anxiety and depression with functional outcome after ischemic stroke using Mendelian randomization (MR) approach. METHODS: Independent genetic variants associated with anxiety and depression at genome-wide significance level (p < 5 × 10-8) were obtained from large-scale genome-wide association studies (Nmax = 1,306,354). Genetic results of poststroke outcome were obtained from Genetics of Ischemic Stroke Functional Outcome meta-analysis (N = 6,021). Three months after ischemic stroke event, the functional outcome was appraised with the modified Rankin Scale (mRS) score, and a mRS >2 was defined as worse functional outcome. Odds ratios (ORs) and 95% CIs are reported for the association of genetically predicted anxiety and depression with functional outcome after ischemic stroke. The inverse-variance weighted method was adopted to pool estimates. Alternative MR methods such as the weighted median and MR using the Robust Adjusted Profile Score were used as sensitivity analyses. The intercept of MR-Egger regression was also adopted to assess pleiotropy. The heterogeneity among variants was assessed by I2 and Q statistics. RESULTS: Genetic liability to depression was associated with worse functional outcome after stroke (mRS 3-6, OR 2.30; 95% CI 1.18-4.49, p = 0.015). Sensitivity analyses produced consistent results. The bidirectional MR analysis indicates that poststroke outcome did not influence liability to depression (OR 1.01, 95% CI 0.99-1.03; p = 0.436). By comparison, genetic liability to anxiety was not related with poststroke outcome (OR 1.03; 95% CI 0.71-1.50; p = 0.869). Analyses in models without adjustment for stroke severity also indicated that genetic liability to depression was related with poor functional outcome after ischemic stroke (OR 2.54; 95% CI 1.41-4.58; p = 0.002). No evidence of heterogeneity or directional pleiotropy was observed (p > 0.05). DISCUSSION: Our MR study provides evidence to support detrimental effects of depression on ischemic stroke functional outcome. Future studies are warranted to explore whether clinical intervention on depression can ameliorate functional outcome after ischemic stroke.


Asunto(s)
Ansiedad , Depresión , Estudio de Asociación del Genoma Completo , Accidente Cerebrovascular Isquémico , Análisis de la Aleatorización Mendeliana , Humanos , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/psicología , Accidente Cerebrovascular Isquémico/complicaciones , Depresión/genética , Depresión/etiología , Depresión/epidemiología , Ansiedad/genética , Ansiedad/etiología , Recuperación de la Función
5.
Angew Chem Int Ed Engl ; : e202410514, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38966937

RESUMEN

Organic scintillators are praised for their abundant element reserves, facile preparation procedures, and rich structures. However, the weak X-ray attenuation ability and low exciton utilization efficiency result in unsatisfactory scintillation performance. Herein, a new family of highly efficient organic phosphonium halide salts with thermally activated delayed fluorescence (TADF) are designed by innovatively adopting quaternary phosphonium as the electron acceptor, while dimethylamine group and halide anions (I-) serve as the electron donor. The prepared butyl(2-[2-(dimethylamino)phenyl]phenyl)diphenylphosphonium iodide (C4-I) exhibits bright blue emission and an ultra-high photoluminescence quantum yield (PLQY) of 100 %. Efficient charge transfer is realized through the unique n-π and anion-π stacking in solid-state C4-I. Photophysical studies of C4-I suggest that the incorporation of I accounts for high intersystem crossing rate (kISC) and reverse intersystem crossing rate (kRISC), suppressing the intrinsic prompt fluorescence and enabling near-pure TADF emission at room temperature. Benefitting from the large Stokes shift, high PLQY, efficient exciton utilization, and remarkable X-ray attenuation ability endowed by I, C4-I delivers an outstanding light yield of 80721 photons/MeV and a low limit of detection (LoD) of 22.79 nGy ⋅ s-1. This work would provide a rational design concept and open up an appealing road for developing efficient organic scintillators with tunable emission, strong X-ray attenuation ability, and excellent scintillator performance.

6.
Plant Physiol Biochem ; 212: 108787, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38850731

RESUMEN

Continuous cropping obstacles poses significant challenges for melon cultivation, with autotoxicity being a primary inducer. Suberization of cells or tissues is a vital mechanism for plant stress response. Our study aimed to elucidate the potential mechanism of root suberization in melon's response to autotoxicity. Cinnamic acid was used to simulate autotoxicity. Results showed that autotoxicity worsened the root morphology and activity of seedlings. Significant reductions were observed in root length, diameter, surface area, volume and fork number compared to the control in the later stage of treatment, with a decrease ranging from 20% to 50%. The decrease in root activity ranged from 16.74% to 29.31%. Root suberization intensified, and peripheral suberin deposition became more prominent. Autotoxicity inhibited phenylalanineammonia-lyase activity, the decrease was 50% at 16 h. The effect of autotoxicity on cinnamylalcohol dehydrogenase and cinnamate 4-hydroxylase activity showed an initial increase followed by inhibition, resulting in reductions of 34.23% and 44.84% at 24 h, respectively. The peroxidase activity only significantly increased at 24 h, with an increase of 372%. Sixty-three differentially expressed genes (DEGs) associated with root suberization were identified, with KCS, HCT, and CYP family showing the highest gene abundance. GO annotated DEGs into nine categories, mainly related to binding and catalytic activity. DEGs were enriched in 27 KEGG pathways, particularly those involved in keratin, corkene, and wax biosynthesis. Seven proteins, including C4H, were centrally positioned within the protein interaction network. These findings provide insights for improving stress resistance in melons and breeding stress-tolerant varieties.


Asunto(s)
Cucurbitaceae , Raíces de Plantas , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Cucurbitaceae/genética , Cucurbitaceae/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fenilanina Amoníaco-Liasa/metabolismo , Fenilanina Amoníaco-Liasa/genética , Cinamatos/farmacología , Cinamatos/metabolismo , Transcinamato 4-Monooxigenasa/metabolismo , Transcinamato 4-Monooxigenasa/genética , Plantones/efectos de los fármacos , Plantones/genética , Oxidorreductasas de Alcohol
7.
Micromachines (Basel) ; 15(6)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38930687

RESUMEN

A molecular pump is the core component of vacuum systems in portable mass spectrometers and other analytical instruments. The forms of the existing molecular pumps mainly are the combinations of vertical bleed and compression channel, which have the shortcomings of heavy mass and large volume, which seriously restricts the application and development of portable mass spectrometers. Aiming at the problems of low strength and insufficient pumping performance under the miniaturization constraints (mass of 1.8 kg; exhaust diameter of 25 mm) of molecular pumps, a compound pump consisting of a horizontal bleed channel and multi-stage spiral compression channel is proposed. The pumping principle of the compound molecular pump is analyzed to obtain its preliminary structural size parameters. The test particle Monte Carlo method is presented for establishing an aerodynamic model for a high-speed small compound molecular pump, which can be used to investigate the pumping performance of bleed blades and compression channels in a thin air environment. On the basis of the aerodynamic model, the NNIA multi-objective optimization algorithm is presented to optimize the structural parameters of the compound molecular pump. After structural parameter optimization, the maximum flow rate and compression ratio of the compound molecular pump are increased by 13.6% and 41.6%, respectively. The experimental results of the pumping performance show that the predicted data of the aerodynamic model are in good agreement with the experimental data, with an error of 12-27%. Namely, the established aerodynamic model has high accuracy and the optimized structural parameters of the compound molecular pump can provide basic conditions for the large-scale application and promotion of portable mass spectrometers.

8.
Int Arch Allergy Immunol ; 185(9): 827-835, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38763133

RESUMEN

INTRODUCTION: Although microRNA (miR)-150-5p participates in the progression of renal fibrosis, its mechanism of action remains elusive. METHODS: A mouse model of unilateral ureteral obstruction was used. The in vitro renal fibrosis model was established by stimulating human kidney 2 (HK-2) cells with transforming growth factor beta 1 (TGF-ß1). The expression profiles of miR-150-5p, zinc finger E-box binding homeobox 1 (ZEB1), and other fibrosis- and epithelial-mesenchymal transition (EMT)-linked proteins were determined using Western blot and quantitative reverse transcription polymerase chain reaction. The relationship between miR-150-5p and ZEB1 in HK-2 cells was confirmed by a dual-luciferase reporter assay. RESULTS: Both in vivo and in vitro renal fibrosis models revealed reduced miR-150-5p expression and elevated ZEB1 level. A significant decrease in E-cadherin levels, as well as increases in alpha smooth muscle actin (α-SMA) and collagen type I (Col-I) levels, was seen in TGF-ß1-treated HK-2 cells. The overexpression of miR-150-5p ameliorated TGF-ß1-mediated fibrosis and EMT. Notably, miR-150-5p acts by directly targeting ZEB1. A significant reversal of the inhibitory impact of miR-150-5p on TGF-ß1-mediated fibrosis and EMT in HK-2 cells was observed upon ZEB1 overexpression. CONCLUSION: MiR-150-5p suppresses TGF-ß1-induced fibrosis and EMT by targeting ZEB1 in HK-2 cells, providing helpful insights into the therapeutic intervention of renal fibrosis.


Asunto(s)
Células Epiteliales , Transición Epitelial-Mesenquimal , Fibrosis , Túbulos Renales , MicroARNs , Homeobox 1 de Unión a la E-Box con Dedos de Zinc , MicroARNs/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Transición Epitelial-Mesenquimal/genética , Animales , Ratones , Humanos , Células Epiteliales/metabolismo , Línea Celular , Túbulos Renales/patología , Túbulos Renales/metabolismo , Modelos Animales de Enfermedad , Enfermedades Renales/patología , Enfermedades Renales/etiología , Enfermedades Renales/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Masculino , Obstrucción Ureteral/patología , Obstrucción Ureteral/complicaciones , Regulación de la Expresión Génica
9.
Environ Geochem Health ; 46(6): 193, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38696028

RESUMEN

Microplastics (MPs) and copper (Cu) pollution coexist widely in cultivation environment. In this paper, polyvinyl chloride (PVC) were used to simulate the MPs exposure environment, and the combined effects of MPs + Cu on the germination of perilla seeds were analyzed. The results showed that low concentrations of Cu promoted seed germination, while medium to high concentrations exhibited inhibition and deteriorated the morphology of germinated seeds. The germination potential, germination index and vitality index of 8 mg • L-1 Cu treatment group with were 23.08%, 76.32% and 65.65%, respectively, of the control group. The addition of low concentration PVC increased the above indicators by 1.27, 1.15, and 1.35 times, respectively, while high concentration addition led to a decrease of 65.38%, 82.5%, and 66.44%, respectively. The addition of low concentration PVC reduced the amount of PVC attached to radicle. There was no significant change in germination rate. PVC treatment alone had no significant effect on germination. MPs + Cu inhibited seed germination, which was mainly reflected in the deterioration of seed morphology. Cu significantly enhanced antioxidant enzyme activity, increased reactive oxygen species (ROS) and MDA content. The addition of low concentration PVC enhanced SOD activity, reduced MDA and H2O2 content. The SOD activity of the Cu2+8 + PVC10 group was 4.05 and 1.35 times higher than that of the control group and Cu treatment group at their peak, respectively. At this time, the CAT activity of the Cu2+8 + PVC5000 group increased by 2.66 and 1.42 times, and the H2O2 content was 2.02 times higher than the control. Most of the above indicators reached their peak at 24 h. The activity of α-amylase was inhibited by different treatments, but ß-amylase activity, starch and soluble sugar content did not change regularly. The research results can provide new ideas for evaluating the impact of MPs + Cu combined pollution on perilla and its potential ecological risk.


Asunto(s)
Cobre , Germinación , Perilla , Cloruro de Polivinilo , Semillas , Germinación/efectos de los fármacos , Cobre/toxicidad , Semillas/efectos de los fármacos , Perilla/efectos de los fármacos , Microplásticos/toxicidad , Tamaño de la Partícula , Especies Reactivas de Oxígeno/metabolismo , Malondialdehído/metabolismo , Contaminantes del Suelo/toxicidad
10.
Plant J ; 119(2): 814-827, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38739690

RESUMEN

Several dwarf and semi-dwarf genes have been identified in barley. However, only a limited number have been effectively utilized in breeding programs to cultivate lodging resistant varieties. This is due to the common association of dwarf and semi-dwarf traits with negative effects on malt quality. In this study, we employed gene editing to generate three new haplotypes of sdw1/denso candidate gene gibberellin (GA) 20-oxidase2 (GA20ox2). These haplotypes induced a dwarfing phenotype and enhancing yield potential, and promoting seed dormancy, thereby reducing pre-harvest sprouting. Moreover, ß-amylase activity in the grains of the mutant lines was significantly increased, which is beneficial for malt quality. The haplotype analysis revealed significant genetic divergence of this gene during barley domestication and selection. A novel allele (sdw1.ZU9), containing a 96-bp fragment in the promoter region of HvGA20ox2, was discovered and primarily observed in East Asian and Russian barley varieties. The 96-bp fragment was associated with lower gene expression, leading to lower plant height but higher germination rate. In conclusion, HvGA20ox2 can be potentially used to develop semi-dwarf barley cultivars with high yield and improved malt quality.

11.
Chemosphere ; 359: 142149, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38685334

RESUMEN

Global climate change as well as human activities have been reported to increase the frequency and severity of both salinization and harmful algal blooms (HABs) in many freshwater systems, but their co-effect on benthic invertebrates has rarely been studied. This study simultaneously examined the joint toxicity of salinity and different cyanobacterial diets on the behavior, development, select biomarkers, and partial life cycle of Chironomus pallidivittatus (Diptera). High concentrations of salts (e.g., 1 g/L Ca2+ and Mg2+) and toxic Microcystis had synergistic toxicity, inhibiting development, burrowing ability and causing high mortality of C. pallidivittatus, especially for the Mg2+ treatment, which caused around 90% death. Low Ca2+ concentration (e.g., 0.01 g/L) promoted larval burrowing ability and inhibited toxin accumulation, which increased the tolerance of Chironomus to toxic Microcystis. However, low Mg2+ concentration (e.g., 0.01 g/L) was shown to inhibit the behavior, development and increase algal toxicity to Chironomus. Toxic Microcystis resulted in microcystin (MC) accumulation, inhibited the burrowing ability of larvae, and increased the proportion of male adults (>50%). The combined toxicity level from low to high was verified by the weight of evidence and the grey TOPSIS model, which integrated five lines of evidence to increase the risk assessment accuracy and efficiency. This is the first study that provided insights into ecological risk arising from the joint effect of salinity and harmful algae on benthic organisms. We suggest that freshwater salinization and HABs should be considered together when assessing ecological threats that arise from external stress.


Asunto(s)
Chironomidae , Agua Dulce , Floraciones de Algas Nocivas , Salinidad , Animales , Chironomidae/efectos de los fármacos , Chironomidae/fisiología , Microcystis/efectos de los fármacos , Microcystis/fisiología , Larva/efectos de los fármacos , Microcistinas/toxicidad , Cianobacterias/fisiología
12.
Vet Microbiol ; 293: 110091, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38626624

RESUMEN

Mastitis in dairy cows is mainly caused by bacteria, in which Staphylococcus aureus appears frequently. Epithelial cells, as a major physical barrier of mammary gland, play an important role in preventing mastitis in dairy cows. Our previous study reported that Rab11fip4 (an effector of Rab11) was significantly changed in response to stimulation by S. aureus. So, in this study, the role of Rab11A in phagocytosis of bovine mammary epithelial cells (MAC-T) against S. aureus was evaluated. First, changes of Rab11A and Rab11fip4 were analyzed in response to S. aureus by immunofluorescence and western blotting. Subsequently, the effects of Rab11A and Rab11fip4 on proliferation of S. aureus, as well as formation and function of late endosomes (LEs) and lysosomes (LYSs) were investigated. The results showed that, after infection, Rab11A and Rab11fip4 were recruited to phagosomes containing S. aureus. Rab11A promoted bacterial clearance and rescues the destruction of LEs and LYSs by S. aureus, whereas Rab11fip4 did the opposite. These findings provide new insights into phagocytosis and control of S. aureus in host cells, thus lay the foundation to elucidate the pathogenesis of S. aureus in bovine mastitis.


Asunto(s)
Células Epiteliales , Mastitis Bovina , Fagocitosis , Infecciones Estafilocócicas , Staphylococcus aureus , Proteínas de Unión al GTP rab , Animales , Bovinos , Proteínas de Unión al GTP rab/metabolismo , Proteínas de Unión al GTP rab/genética , Staphylococcus aureus/fisiología , Femenino , Células Epiteliales/microbiología , Infecciones Estafilocócicas/veterinaria , Infecciones Estafilocócicas/microbiología , Mastitis Bovina/microbiología , Glándulas Mamarias Animales/microbiología , Endosomas/metabolismo , Endosomas/microbiología , Lisosomas/metabolismo , Lisosomas/microbiología , Línea Celular , Fagosomas/microbiología
13.
Research (Wash D C) ; 7: 0338, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38464498

RESUMEN

Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.

14.
IEEE Trans Image Process ; 33: 1838-1852, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38451755

RESUMEN

Weakly supervised point cloud semantic segmentation methods that require 1% or fewer labels with the aim of realizing almost the same performance as fully supervised approaches have recently attracted extensive research attention. A typical solution in this framework is to use self-training or pseudo-labeling to mine the supervision from the point cloud itself while ignoring the critical information from images. In fact, cameras widely exist in LiDAR scenarios, and this complementary information seems to be highly important for 3D applications. In this paper, we propose a novel cross-modality weakly supervised method for 3D segmentation that incorporates complementary information from unlabeled images. We design a dual-branch network equipped with an active labeling strategy to maximize the power of tiny parts of labels and to directly realize 2D-to-3D knowledge transfer. Afterward, we establish a cross-modal self-training framework, which iterates between parameter updating and pseudolabel estimation. In the training phase, we propose cross-modal association learning to mine complementary supervision from images by reinforcing the cycle consistency between 3D points and 2D superpixels. In the pseudolabel estimation phase, a pseudolabel self-rectification mechanism is derived to filter noisy labels, thus providing more accurate labels for the networks to be fully trained. The extensive experimental results demonstrate that our method even outperforms the state-of-the-art fully supervised competitors with less than 1% actively selected annotations.

15.
Epidemiol Health ; 46: e2024005, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38404113

RESUMEN

OBJECTIVES: Atrial fibrillation (AF) contributes to stroke development and progression. We aimed to quantify the mediating role of AF in the causal associations between a wide range of risk factors and stroke via a Mendelian randomization (MR) framework. METHODS: We assessed the associations of 108 traits with stroke and its subtypes in a 2-sample univariable MR approach, then conducted a bidirectional MR analysis between these 108 traits and AF to evaluate the presence and direction of their causal associations. Finally, to further investigate the extent to which AF mediated the effects of eligible traits on stroke, we applied multivariable and 2-step MR techniques in a mediation analysis where outcomes were restricted to stroke types causally affected by AF (any stroke [AS], any ischemic stroke [AIS], and cardioembolic stroke [CES]). RESULTS: Among 108 traits, 42 were putatively causal for at least 1 stroke type; of these 42 traits, 20 that had no bidirectional relationship with AF were retained. Finally, 33 associations of 15 eligible traits were examined in the mediation analysis. The mediation analyses for AS, AIS, and CES each included 11 eligible traits. After AF adjustment, the direct effects of all traits on CES were attenuated to null (all p>0.05), while the associations with AS and AIS persisted for most traits (AF-mediated proportion: from 6.6% [95% confidence interval, 2.7 to 0.6] to 52.0% [95% confidence interval, 39.8 to 64.3]). CONCLUSIONS: The causal associations between all eligible traits and CES were largely mediated through AF, while most traits affected AS and AIS independently of AF.


Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/epidemiología , Fibrilación Atrial/genética , Análisis de la Aleatorización Mendeliana , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Causalidad , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple
16.
Neurology ; 102(3): e208080, 2024 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-38181322

RESUMEN

BACKGROUND AND OBJECTIVES: To investigate the causal relationships of abdominal adiposity (waist-to-hip ratio [WHR]) and overall adiposity (body mass index [BMI]) with functional outcome after ischemic stroke using Mendelian randomization. METHODS: Genetic instruments for WHR and BMI were obtained from the largest available genome-wide association studies meta-analysis of the Genetic Investigation of ANthropometric Traits consortium and the UK Biobank (N max = 806,834). Functional outcome after ischemic stroke was assessed using the modified Rankin Scale (mRS) score at 3-month after stroke onset, with mRS >2 (mRS 3-6) defined as an unfavorable functional outcome. Corresponding genetic estimates for an unfavorable functional outcome were extracted from the Genetics of Ischemic Stroke Functional Outcome network (N = 6,021). We applied a random-effects inverse variance weighted method as our main analysis. RESULTS: Genetically predicted higher WHR (per 0.09 ratio units) was associated with unfavorable functional outcome after ischemic stroke (mRS 3-6, OR = 1.48; 95% CI = 1.03-2.13; p = 0.033). The results remained directionally consistent in sensitivity analyses. Conversely, genetically predicted BMI (per 4.8 kg/m2) was not associated with unfavorable functional outcome after ischemic stroke (OR = 1.01; 95% CI = 0.75-1.36; p = 0.937). DISCUSSION: This study provides genetic evidence supporting the hypothesis that abdominal adiposity has a detrimental effect on functional recovery after ischemic stroke.


Asunto(s)
Adiposidad , Accidente Cerebrovascular Isquémico , Humanos , Adiposidad/genética , Estudio de Asociación del Genoma Completo , Obesidad , Obesidad Abdominal
17.
Eur Stroke J ; 9(1): 235-243, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37905729

RESUMEN

INTRODUCTION: The role of serum uric acid (UA) levels in the functional recovery of ischemic stroke remains uncertain. To evaluate whether UA could predict clinical outcomes in patients with ischemic stroke. PATIENTS AND METHODS: A three-stage study design was employed, combining a large-scale prospective cohort study, a meta-analysis and a Mendelian randomization (MR) analysis. Firstly, we conducted a cohort study using data from the Nanjing Stroke Registry Program (NSRP) to assess the association between UA levels and 3-month functional outcomes in ischemic stroke patients. Secondly, the meta-analysis was conducted to integrate currently available cohort evidence. Lastly, MR analysis was utilized to explore whether genetically determined UA had a causal link to the functional outcomes of ischemic stroke using summary data from the CKDGen and GISCOME datasets. RESULTS: In the first stage, the cohort study included 5631 patients and found no significant association between UA levels and functional outcomes at 3 months after ischemic stroke. In the second stage, the meta-analysis, including 10 studies with 14,657 patients, also showed no significant association between UA levels and stroke prognosis. Finally, in the third stage, MR analysis using data from 6165 patients in the GISCOME study revealed no evidence of a causal relationship between genetically determined UA and stroke functional outcomes. DISCUSSION AND CONCLUSION: Our comprehensive triangulation approach found no significant association between UA levels and functional outcomes at 3 months after ischemic stroke.


Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Ácido Úrico , Accidente Cerebrovascular Isquémico/genética , Estudios de Cohortes , Estudios Prospectivos , Análisis de la Aleatorización Mendeliana , Pronóstico , Accidente Cerebrovascular/epidemiología
18.
IEEE Trans Pattern Anal Mach Intell ; 46(7): 4551-4566, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38133979

RESUMEN

Information Bottleneck (IB) provides an information-theoretic principle for multi-view learning by revealing the various components contained in each viewpoint. This highlights the necessity to capture their distinct roles to achieve view-invariance and predictive representations but remains under-explored due to the technical intractability of modeling and organizing innumerable mutual information (MI) terms. Recent studies show that sufficiency and consistency play such key roles in multi-view representation learning, and could be preserved via a variational distillation framework. But when it generalizes to arbitrary viewpoints, such strategy fails as the mutual information terms of consistency become complicated. This paper presents Multi-View Variational Distillation (MV 2D), tackling the above limitations for generalized multi-view learning. Uniquely, MV 2D can recognize useful consistent information and prioritize diverse components by their generalization ability. This guides an analytical and scalable solution to achieving both sufficiency and consistency. Additionally, by rigorously reformulating the IB objective, MV 2D tackles the difficulties in MI optimization and fully realizes the theoretical advantages of the information bottleneck principle. We extensively evaluate our model on diverse tasks to verify its effectiveness, where the considerable gains provide key insights into achieving generalized multi-view representations under a rigorous information-theoretic principle.

19.
Ann Clin Lab Sci ; 53(5): 749-759, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37945011

RESUMEN

OBJECTIVE: To verify whether miR-150-5p modulates the development of renal fibrosis and its mechanism. METHODS: Transforming growth factor (TGF)-ß1 was implemented on HK-2 cells to construct a renal fibrosis in vitro model. Inhibition of autophagy was performed on HK-2 cells by treating with 3-methyladenine (3-MA, an inhibitor of autophagy). HK-2 cells experienced transfection by miR-150-5p mimics/inhibitor and pcDNA-ß-catenin plasmids, and the negative controls. Dual luciferase reporter gene assay was applied to validate the relationship between miR-150-5p and ß-catenin. Cell apoptosis exploration was implemented by flow cytometry assay. The level detection of CoII, α-SMA, miR-150-5p and ß-catenin was executed by real-time quantitative reverse transcription-polymerase chain reaction. The expression of CoII, α-SMA, LC3I, LC3II, Bax, Cleaved Caspase 3, Beclin 1, Bcl-2 and ß-catenin proteins was monitored by western blot. RESULTS: Autophagy was inhibited in TGF-ß1-induced HK-2 cells. MiR-150-5p alleviated fibrosis, enhanced autophagy, and inhibited apoptosis in TGF-ß1-induced HK-2 cells. ß-catenin was a target of miR-150-5p. Autophagy inhibition or ß-catenin partially counteracted miR-150-5p effect on TGF-ß1-induced fibrosis in HK-2 cells. CONCLUSIONS: MiR-150-5p alleviates renal tubular epithelial cell fibrosis by activating autophagy via ß-catenin signaling.


Asunto(s)
Enfermedades Renales , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , beta Catenina/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Fibrosis , Enfermedades Renales/metabolismo , Células Epiteliales/metabolismo , Autofagia/genética
20.
Sci Data ; 10(1): 616, 2023 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-37696871

RESUMEN

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) through epigenetic manipulation. While the essential role of miRNA in reprogramming and maintaining pluripotency is well studied, little is known about the functions of miRNA from exosomes in this context. To fill this research gap,we comprehensively obtained the 17 sets of cellular mRNA transcriptomic data with 3.93 × 1010 bp raw reads and 18 sets of exosomal miRNA transcriptomic data with 2.83 × 107 bp raw reads from three categories of human somatic cells: peripheral blood mononuclear cells (PBMCs), skin fibroblasts(SFs) and urine cells (UCs), along with their derived iPSCs. Additionally, differentially expressed molecules of each category were identified and used to perform gene set enrichment analysis. Our study provides sets of comparative transcriptomic data of cellular mRNA and exosomal miRNA from three categories of human tissue with three individual biological controls in studies of iPSCs generation, which will contribute to a better understanding of donor cell variation in functional epigenetic regulation and differentiation bias in iPSCs.


Asunto(s)
Exosomas , Células Madre Pluripotentes Inducidas , MicroARNs , Humanos , Epigénesis Genética , Leucocitos Mononucleares , MicroARNs/genética , ARN Mensajero , Transcriptoma
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