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1.
Artículo en Inglés | MEDLINE | ID: mdl-39255119

RESUMEN

We propose and study a novel cross-reality environment that seamlessly integrates a monoscopic 2D surface (an interactive screen with touch and pen input) with a stereoscopic 3D space (an augmented reality HMD) to jointly host spatial data visualizations. This innovative approach combines the best of two conventional methods of displaying and manipulating spatial 3D data, enabling users to fluidly explore diverse visual forms using tailored interaction techniques. Providing such effective 3D data exploration techniques is pivotal for conveying its intricate spatial structures-often at multiple spatial or semantic scales-across various application domains and requiring diverse visual representations for effective visualization. To understand user reactions to our new environment, we began with an elicitation user study, in which we captured their responses and interactions. We observed that users adapted their interaction approaches based on perceived visual representations, with natural transitions in spatial awareness and actions while navigating across the physical surface. Our findings then informed the development of a design space for spatial data exploration in cross-reality. We thus developed cross-reality environments tailored to three distinct domains: for 3D molecular structure data, for 3D point cloud data, and for 3D anatomical data. In particular, we designed interaction techniques that account for the inherent features of interactions in both spaces, facilitating various forms of interaction, including mid-air gestures, touch interactions, pen interactions, and combinations thereof, to enhance the users' sense of presence and engagement. We assessed the usability of our environment with biologists, focusing on its use for domain research. In addition, we evaluated our interaction transition designs with virtual and mixed-reality experts to gather further insights. As a result, we provide our design suggestions for the cross-reality environment, emphasizing the interaction with diverse visual representations and seamless interaction transitions between 2D and 3D spaces.

2.
Front Plant Sci ; 15: 1425798, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39309179

RESUMEN

Introduction: Clubroot disease is a devastating soil borne disease caused by infection with Plasmodiophora brassicae, which primarily affects cruciferous plants. The microbial diversity of the soil is an essential indicator of its quality. Methods: This study measured the physicochemical properties of the soil to study the effect of its microbial diversity on the infection of oilseed rape with P. brassicae. High-throughput sequences of the soil bacteria and fungi in the inter-root soils of P. brassicae were analyzed under different treatment conditions. Results: In the study, it was found that the efficiency of strain X216 in preventing and controlling the root disease of rapeseed was positively correlated with the amount of solution used to irrigate the root system. The results of the greenhouse and field trials showed that the efficiency of strain X216 against the root disease of rapeseed was 43.16% in the field and 62.14% in the greenhouse. Proteobacteria, Chloroflexi, Rozellomycota, and Basidiomycota are critical phylum in the development of clubroot disease. The application of biocontrol increased the relative abundance of Actinobacteria, Bacillus, Mesorhizobium, Mycobacterium, Streptomyces and Filobasidium, which affected the structure and abundance of microbial communities. A principal coordinate analysis showed that the microbial structure in the soil varied substantially in the bacterial community, and there was no significant difference in soil structure in the fungal community. Discussion: The occurrence of clubroot disease affected the structure of inter-root microbial community composition in the soil, which resulted in a decrease in its community diversity. The application of the biocontrol bacterium X216 increased the soil microbial diversity. It effectively reduced the occurrence of P. brassicae, and this study provides a basis to study the microbial diversity in cruciferous crops.

3.
Clin Transl Oncol ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39240303

RESUMEN

PURPOSE: The aim of this study is to investigate the expression of TET3 in prostate cancer and its effect on the efficacy of anti-androgen therapy (ADT). METHODS: The expression of TET3 in 1965 cases of prostate cancer and 493 cases of normal prostate tissues were analyzed. The CIBERSORT algorithm evaluated the abundance of 22 tumor-infiltrating immune cells in 497 prostate cancers. Subsequently, the expression of TET3 in prostate cancer TAMs was analyzed using 21,292 cells from single-cell RNA sequencing (scRNAseq). In addition, the trajectory of the differentiation process was reconstructed based on pseudotime analysis. Sensitivity prediction of prostate cancers to ADT was evaluated based on GDSC2 and CTRP databases. Another dataset GSE111177 was employed for further analysis. RESULTS: TET3 was over-expressed in prostate cancer, and the expression of TET3 in metastatic prostate cancer was higher than that in non-metastatic prostate cancer. The scRNAseq analysis of prostate cancer showed that TET3 was mainly expressed in TAM. TET3 expressed in early and active TAMs, with the activation of signaling pathways such as energy metabolism, cell communication, and cytokine production. Prostate cancer in TET3 high expression group was more sensitive to ADT drugs such as Bicalutamide and AZD3514, and was also more sensitive to chemotherapy drugs such as Cyclophosphamide, Paclitaxel, and Vincristine, and MAPK pathway inhibitors of Docetaxel and Dabrafenib. CONCLUSIONS: The efficacy of ADT in prostate cancer is related to the expression of TET3 in TAMs, and TET3 may be a potential therapeutic target for coordinating ADT.

4.
Sci Rep ; 14(1): 20577, 2024 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232239

RESUMEN

Chloroplast (cp) genome sequences have been extensively used for phylogenetic and evolutionary analyses, as many have been sequenced in recent years. Identification of Quercus is challenging because many species overlap phenotypically owing to interspecific hybridization, introgression, and incomplete lineage sorting. Therefore, we wanted to gain a better understanding of this genus at the level of the maternally inherited chloroplast genome. Here, we sequenced, assembled, and annotated the cp genomes of the threatened Quercus marlipoensis (160,995 bp) and Q. kingiana (161,167 bp), and mined these genomes for repeat sequences and codon usage bias. Comparative genomic analyses, phylogenomics, and selection pressure analysis were also performed in these two threatened species along with other species of Quercus. We found that the guanine and cytosine content of the two cp genomes were similar. All 131 annotated genes, including 86 protein-coding genes, 37 transfer RNA genes, and 8 ribosomal RNA genes, had the same order in the two species. A strong A/T bias was detected in the base composition of simple sequence repeats. Among the 59 synonymous codons, the codon usage pattern of the cp genomes in these two species was more inclined toward the A/U ending. Comparative genomic analyses indicated that the cp genomes of Quercus section Ilex are highly conserved. We detected eight highly variable regions that could be used as molecular markers for species identification. The cp genome structure was consistent and different within and among the sections of Quercus. The phylogenetic analysis showed that section Ilex was not monophyletic and was divided into two groups, which were respectively nested with section Cerris and section Cyclobalanopsis. The two threatened species sequenced in this study were grouped into the section Cyclobalanopsis. In conclusion, the analyses of cp genomes of Q. marlipoensis and Q. kingiana promote further study of the taxonomy, phylogeny and evolution of these two threatened species and Quercus.


Asunto(s)
Especies en Peligro de Extinción , Evolución Molecular , Genoma del Cloroplasto , Filogenia , Quercus , Quercus/genética , Genoma del Cloroplasto/genética , Uso de Codones , Cloroplastos/genética
5.
Artículo en Inglés | MEDLINE | ID: mdl-39255122

RESUMEN

Steering is a fundamental task in interactive Virtual Reality (VR) systems. Prior work has demonstrated that movement direction can significantly influence user behavior in the steering task, and different interactive environments (VEs) can lead to various behavioral patterns, such as tablets and PCs. However, its impact on VR environments remains unexplored. Given the widespread use of steering tasks in VEs, including menu adjustment and object manipulation, this work seeks to understand and model the directional effect with a focus on barehand interaction, which is typical in VEs. This paper presents the results of two studies. The first study was conducted to collect behavioral data with four categories: movement time, average movement speed, success rate, and reenter times. According to the results, we examined the effect of movement direction and built the SθModel. We then empirically evaluated the model through the data collected from the first study. The results proved that our proposed model achieved the best performance across all the metrics (r 2 > 0.95), with more than 15% improvement over the original Steering Law in terms of prediction accuracy. Next, we further validated the SθModel by another study with the change of device and steering direction. Consistent with previous assessments, the model continues to exhibit optimal performance in both predicting movement time and speed. Finally, based on the results, we formulated design recommendations for steering tasks in VEs to enhance user experience and interaction efficiency.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39255157

RESUMEN

Authentication in digital security relies heavily on text-based passwords, even with other available methods like biometrics and graphical passwords. While virtual reality (VR) keyboards are typically invisible to onlookers, the presence of inconspicuous sensors, including accelerometers, gyroscopes, and barometers, poses a potential risk of unauthorized observation and recording. Traditional defense shoulder-surfing attack methods typically involve breaking apart the Qwerty layout, which destroys the user's inherent familiarity with the layout. This research addresses the need for secure password entry in VR environments while retaining the Qwerty layout. We explore three keyboard-related position alteration strategies to ensure security while mitigating the decline in user experience. These strategies involve moving the entire keyboard, cursor, and keys. Our theoretical study assesses the effectiveness of these strategies against shoulder-surfing attacks. Two user studies, employing ray-based and position-based text entry methods, respectively, evaluate the practical effectiveness of the three strategies in resisting shoulder-surfing attacks, as well as their impact on typing performance and user experience. Our findings demonstrate that the three strategies achieve shoulder-surfing attack resistance comparable to a random layout keyboard. Moreover, compared to a random layout, the two strategies involving the movement of the entire keyboard and the repositioning of keys support faster entry rates and enhanced user experience.

7.
Artículo en Inglés | MEDLINE | ID: mdl-39255139

RESUMEN

The use of Virtual Reality (VR) technology, especially in medical rehabilitation, has expanded to include tactile cues along with visual stimuli. For patients with upper limb hemiplegia, tangible handles with haptic stimuli could improve their ability to perform daily activities. Traditional VR controllers are unsuitable for patient rehabilitation in VR, necessitating the design of specialized tangible handles with integrated tracking devices. Besides, matching tactile stimulation with corresponding virtual visuals could strengthen users' embodiment (i.e., owning and controlling virtual bodies) in VR, which is crucial for patients' training with virtual hands. Haptic stimuli have been shown to amplify the embodiment in VR, whereas the effect of partial tactile stimulation from tangible handles on embodiment remains to be clarified. This research, including three experiments, aims to investigate how partial tactile feedback of tangible handles impacts users' embodiment, and we proposed a design concept called TouchMark for partial tactile stimuli that could help users quickly connect the physical and virtual worlds. To evaluate users' tactile and comfort perceptions when grasping tangible handles in a non-VR setting, various handles with three partial tactile factors were manipulated in Study 1. In Study 2, we explored the effects of partial feedback using three forms of TouchMark on the embodiment of healthy users in VR, with various tangible handles, while Study 3 focused on similar investigations with patients. These handles were utilized to complete virtual food preparation tasks. The tactile and comfort perceptions of tangible handles and users' embodiment were evaluated in this research using questionnaires and interviews. The results indicate that TouchMark with haptic line and ring forms over no stimulation would significantly enhance users' embodiment, especially for patients. The low-cost and innovative TouchMark approach may assist users, particularly those with limited VR experience, in achieving the embodiment and enhancing their virtual interactive experience.

8.
Medicine (Baltimore) ; 103(35): e39369, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39213232

RESUMEN

BACKGROUND: This study aims to evaluate the therapeutic efficacy of combined treatment with pulsed electromagnetic fields (PEMFs) and platelet-rich plasma (PRP) injection in improving pain and functional mobility among patients with early-stage knee osteoarthritis (KOA). We hypothesize that this combined therapy can yield superior treatment outcomes. METHODS: Based on the different treatment regimens, we divided 48 patients diagnosed with Kellgren-Lawrence grades I-III KOA into 3 groups: the PRP group, the PEMFs group, and the PRP + PEMFs group. Each subtype of KOA patients was randomly assigned to different treatment groups. In the PRP group, patients received intra-articular injections of leukocyte-rich platelet-rich plasma once a month for 3 consecutive months. In the PEMFs group, patients receive low-frequency PEMFs irradiation therapy with a frequency of 30 Hz and intensity of 1.5 mT, once daily, 5 times a week, for a consecutive treatment period of 12 weeks. In the PRP + PEMFs group, patients receive both of the aforementioned treatment protocol. The treatment effects on patients are evaluated at baseline and at weeks 4, 8, and 12 post-treatment. Assessment parameters include visual analog scale for pain, Western Ontario and McMaster Universities Osteoarthritis Index, Lequesne Index score, and knee joint range of motion. RESULTS: From the 4th to the 12th week of treatment, the visual analog scale scores, Western Ontario and McMaster Universities Osteoarthritis Index scores, and Lequesne index scores of patients in all 3 groups gradually decreased, while knee joint mobility gradually increased (P < .05). At weeks 4, 8, and 12 after treatment, the PRP combined with PEMFs group showed significantly better scores compared to the PRP group and the PEMFs group, with statistically significant differences (P < .05). A total of 7 patients experienced adverse reactions such as knee joint swelling, low-grade fever, and worsening knee joint pain after treatment, all of which disappeared within 1 week after treatment. The incidence of complications did not differ significantly among the 3 groups (P = .67). CONCLUSION: PRP, PEMFs, and the combination of PRP and PEMFs therapy all effectively alleviate knee joint pain and improve joint function. However, compared to single treatment modalities, the combined therapy of PRP and PEMFs demonstrates more pronounced efficacy.


Asunto(s)
Magnetoterapia , Osteoartritis de la Rodilla , Plasma Rico en Plaquetas , Humanos , Osteoartritis de la Rodilla/terapia , Masculino , Femenino , Persona de Mediana Edad , Terapia Combinada , Magnetoterapia/métodos , Anciano , Resultado del Tratamiento , Dimensión del Dolor , Inyecciones Intraarticulares
9.
Fitoterapia ; 178: 106160, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39098734

RESUMEN

Patrinia punctiflora is a medical and edible Chinese herb with high nutritional and medicinal value. The continuing study of its chemical constituents led to the isolation of six iridoids, which were previously unreported compounds, patriscabioins PU (1-6). Their structures were characterized and confirmed with NMR (1D & 2D), HRMS, IR and UV. Among them, compound 5 was screened to evaluate its insulin resistance activity on an IR-HepG-2 cell model. Compound 5 had no cytotoxicity compared with the control group and could promote glucose uptake in IR-HepG-2 cells. Through further mechanism studies, the undescribed compound 5 could increase the expression levels of PI-3 K, p-AKT, GLUT4 and p-GSK3ß proteins. Moreover, the expression of PEPCK and G6Pase proteins, which are key gluconeogenic enzymes, was also inhibited. Thus, compound 5 promotes the transfer of GLUT4 to the plasma membrane by activating the PI-3 K/AKT signaling pathway, at the same time, promotes glycogen synthesis and inhibits the onset of gluconeogenesis, which in turn ameliorates insulin resistance.


Asunto(s)
Resistencia a la Insulina , Iridoides , Patrinia , Humanos , Células Hep G2 , Iridoides/farmacología , Iridoides/aislamiento & purificación , Iridoides/química , Patrinia/química , Estructura Molecular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Transducción de Señal/efectos de los fármacos , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Gluconeogénesis/efectos de los fármacos , Glucosa/metabolismo , China , Fosfatidilinositol 3-Quinasas/metabolismo
10.
RSC Adv ; 14(35): 25301-25306, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39139243

RESUMEN

Silicon quantum dots (SiQDs) and carbon quantum dots (CQDs) are renowned for their outstanding applications in fluorescence imaging and biosensing. However, their small size poses significant challenges in terms of preparation, collection, and purification. Polyhedral oligomeric silsesquioxanes (POSS), an organic-inorganic nanohybrid with a cage-like structure, has recently attracted considerable attention due to its excellent biocompatibility. In this research, we utilize the encapsulating properties of POSS to improve the optical property of SiQDs/CQDs through an in situ synthesis strategy, resulting in the production of blue-emitting POSS-SiQDs, green-emitting POSS-G-CNDs, and red-emitting POSS-R-CNDs. By examining their structural and optical characteristics, it is found that these hybrid materials exhibit excellent luminescent properties, biocompatibility and cell membrane permeability. This facilitates multicolor intracellular imaging and underscores their successful application in biological imaging. Our study presents a novel approach to synthesize POSS-QDs composite nanomaterials with new perspectives in biological imaging and medical diagnostics.

11.
Nat Commun ; 15(1): 7200, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39168997

RESUMEN

Intermetallic compounds (IMCs) with ordered atomic structure have gained great attention as nanocatalysts for its enhanced activity and stability. Although the reliance of IMC preparation on high-temperature annealing is well known, a comprehensive understanding of the formation mechanisms of IMCs in this process is currently lacking. Here, we employ aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (AC-HAADF-STEM) to track the formation process of IMCs on carbon supports during in-situ annealing, by taking PtFe as a case study within an industry-relevant impregnation synthesis framework. We directly discern five different stages at the atomic level: initial atomic precursors; Pt cluster formation; Pt-Fe disordered alloying; structurally ordered Pt3Fe formation, and final Pt3Fe-PtFe IMC conversion. In particular, we find that the crucial role of high-temperature annealing resides in facilitating the diffusion of Fe towards Pt, enabling the creation of alloys with the targeted stoichiometric ratio, which in turn provides the thermodynamic driving force for the disorder-to-order transition.

12.
Artículo en Inglés | MEDLINE | ID: mdl-39208039

RESUMEN

Prior work has shown that frame rate significantly influences user behavior in fast-response tasks in 2D and 3D contexts. However, its impact on a steering task, which involves navigating an object along a path from the start to the end, remains relatively unexplored, especially in the context of virtual reality (VR). This task is considered a typical non-fast-response activity, as it does not demand rapid reactions within a limited time frame. Our work aims to understand and model users' steering behavior and predict movement time with different task complexities and frame rates in VR environments. We first conducted a user study to collect user behavior in a steering task with four factors: frame rate, path length, width, and radius of curvature. Based on the results, we then quantified the effects of frame rate and built two predictive models. Our models exhibited the best fit ([Formula: see text]) and over 17% improvement in prediction accuracy for movement time compared to existing models. Our models' robustness was further validated by applying them to predict steering performance with different VR tasks and frame rates. The two models keep the best predictability for both movement time and speed.

13.
Front Oncol ; 14: 1427341, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39091914

RESUMEN

Testicular tumors represent a common form of solid tumor in young men, with choriocarcinoma of the testis being a rare, non-granulomatous germ cell tumor. It accounts for less than 0.3% of all testicular germ cell tumors. Pelvic and pulmonary metastases originating from testicular choriocarcinoma are exceptionally uncommon in men. This study describes a case of a 27-year-old male diagnosed with testicular choriocarcinoma, presenting initially with nausea, vomiting, and abdominal pain. Furthermore, this review encompasses cases of testiclar choriocarcinoma in individuals aged 30 years and below, both in China and internationally, over the past 20 years.

14.
Nat Prod Res ; : 1-9, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39086211

RESUMEN

Phytochemical investigation of Gynostemma pentaphyllum led to the purification of five novel dammarane-type triterpene isolates, gypenosides B1 - B5 (1-5). Their structures were determined through comprehensive 1D and 2D NMR spectroscopic analyses and HRESIMS data. Of note, 1-3 are inseparable mixtures of epimers due to their unstable nature, and a total of eight dammarane-type triterpene saponins were identified. Additionally, the protective activities of these new compounds against PC12 cell injury induced by hypoxia were evaluated.

15.
Games Health J ; 13(4): 297-304, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38985574

RESUMEN

Objective: Following the initial measures taken to manage the repercussions of the COVID-19 pandemic, mental health conditions have become a critical concern. Mental health has become a foremost priority not only for health care providers but also for many other organizations, such as educational institutions, companies, and government agencies. A significant proportion of the Australian population having experienced mental disorders highlights the need for effective interventions. Those with pre-existing mental health issues experienced particularly pronounced effects. Among these challenges, advancements in technology offer new possibilities for mental health support. Videogames have shown effectiveness in mitigating symptoms of depression. Previous research has shown that game interface preferences correlate with players' emotional responses. This study aims to use MoodJumper, a game we designed, developed, and evaluated to examine the choice of game preferences in individuals with depressive symptoms. Materials and Methods: A pilot study was carried out after obtaining the Human Ethics committee's approval (n = 20). The participants were asked to fill out a Patient Health Questionnaire-9 (PHQ-9) questionnaire. They then played with the MoodJumper game for 20-30 minutes. Upon completing the game session, they were asked to fill out a questionnaire regarding their experience. Results: The results indicate a nonsignificant correlation between music preference, the direction of movement, and depressive symptoms meaning no significant relationship was found between depressive symptoms and chosen settings. However, a significant negative correlation was found between decision-making ability regarding game preferences and Patient Health Questionnaire-9 scores showing the difficulty of choosing preferred settings when having depressive symptoms. Conclusion: This contribution paves the way for designing and evaluating more impactful game experiences for individuals with mental health challenges.


Asunto(s)
COVID-19 , Depresión , Juegos de Video , Humanos , Proyectos Piloto , Juegos de Video/psicología , Juegos de Video/estadística & datos numéricos , Depresión/psicología , Masculino , Femenino , Adulto , COVID-19/psicología , Australia , Encuestas y Cuestionarios , SARS-CoV-2 , Persona de Mediana Edad
16.
Biochem Pharmacol ; 226: 116338, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38848780

RESUMEN

ITFG2, as an immune-modulatory intracellular protein that modulate the fate of B cells and negatively regulates mTORC1 signaling. ITFG2 is highly expressed in the heart, but its pathophysiological function in heart disease is unclear. In this study, we found that in MI mice, overexpression of ITFG2 via an AAV9 vector significantly reduced the infarct size and ameliorated cardiac function. Knockdown of endogenous ITFG2 by shRNA partially aggravated ischemia-induced cardiac dysfunction. In cardiac-specific ITFG2 transgenic (TG) mice, myocardial infarction size was smaller, eject fraction (EF) and fractional shortening (FS) was higher compared to those in wild-type (WT) mice, suggesting ITFG2 reversed cardiac dysfunction induced by MI. In hypoxic neonatal cardiomyocytes (NMCMs), overexpression of ITFG2 maintained mitochondrial function by increasing intracellular ATP production, reducing ROS levels, and preserving the mitochondrial membrane potential (MMP). Overexpression of ITFG2 reversed the mitochondrial respiratory dysfunction in NMCMs induced by hypoxia. Knockdown of endogenous ITFG2 by siRNA did the opposite. Mechanism, ITFG2 formed a complex with NEDD4-2 and ATP 5b and inhibited the binding of NEDD4-2 with ATP 5b leading to the reduction ubiquitination of ATP 5b. Our findings reveal a previously unknown ability of ITFG2 to protect the heart against ischemic injury by interacting with ATP 5b and thereby regulating mitochondrial function. ITFG2 has promise as a novel strategy for the clinical management of MI.


Asunto(s)
Mitocondrias Cardíacas , Infarto del Miocardio , Miocitos Cardíacos , Animales , Masculino , Ratones , Células Cultivadas , Ratones Endogámicos C57BL , Ratones Transgénicos , Mitocondrias Cardíacas/metabolismo , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/inmunología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología
17.
Clin Hemorheol Microcirc ; 87(4): 405-413, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38848169

RESUMEN

This study aims to elucidate the effect of alprostadil (ALP) plus cilostazol (CIL) on the treatment outcomes and inflammatory factors in patients with lower extremity arteriosclerosis obliterans (LEASO) receiving evidence-based care. Firstly, 130 patients with LEASO were selected from February 2020 to February 2023 and then randomly divided into two groups with 65 patients each. Excluding the dropouts, 59 patients in the control group (6 cases of dropout) received ALP and 62 patients in the research group (3 cases of dropout) received ALP plus CIL. Both groups were cared for in accordance with the evidence-based care model. Treatment outcomes, arteriosclerosis indexes (blood flow of dorsalis pedis artery [DPA], ankle-brachial index [ABI] and toe-brachial index [TBI]), hemorheological parameters (erythrocyte aggregation index [EAI], erythrocyte deformation index [EDI], high blood viscosity [HBV] and haematocrit [HCT]), inflammatory factors (interleukin [IL]-6, IL-8 and tumour necrosis factor [TNF]-α) and complications (nausea, diarrhoea, headache and transaminase elevation) were compared between the control and research groups. Results show that the overall response rate was markedly higher in the research group (90.32%) than in the control group (74.58%). Additionally, the blood flow of DPA, ABI and TBI in the research group significantly increased after the treatment and were higher than those in the control group. Meanwhile, the EAI, EDI, HBV, HCT, IL-6, IL-8 and TNF-α were significantly lower. The two groups did not differ markedly in the complication rate. The above findings suggest that ALP plus CIL is effective for patients with LEASO receiving evidence-based care. It can significantly improve arteriosclerosis indexes and hemorheological parameters while inhibiting serum inflammatory responses, with some certain safety.


Asunto(s)
Alprostadil , Arteriosclerosis Obliterante , Cilostazol , Extremidad Inferior , Humanos , Cilostazol/uso terapéutico , Masculino , Femenino , Arteriosclerosis Obliterante/tratamiento farmacológico , Persona de Mediana Edad , Extremidad Inferior/irrigación sanguínea , Alprostadil/uso terapéutico , Anciano , Resultado del Tratamiento , Quimioterapia Combinada
18.
Acta Pharmacol Sin ; 45(7): 1425-1437, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38839936

RESUMEN

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.


Asunto(s)
Fibrosis , Ratones Endogámicos C57BL , Infarto del Miocardio , Animales , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Ratones , Masculino , Proteínas Señalizadoras YAP/metabolismo , Fibroblastos/metabolismo , Citidina/análogos & derivados , Citidina/farmacología , Ratones Noqueados , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Acetiltransferasa E N-Terminal/metabolismo , Vía de Señalización Hippo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Células Cultivadas , Transducción de Señal , Acetiltransferasas N-Terminal/metabolismo , Miocardio/patología , Miocardio/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo
19.
Se Pu ; 42(6): 564-571, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-38845517

RESUMEN

Protein phosphorylation plays an important role in cellular signaling and disease development. Advances in mass spectrometry-based proteomics have enabled qualitative and quantitative phosphorylation studies as well as in-depth biological explorations for biomarker discovery and signaling pathway analysis. However, the dynamic changes that occur during phosphorylation and the low abundance of target analytes render direct analysis difficult because mass spectral detection offers no selectivity, unlike immunoassays such as Western blot and enzyme-linked immunosorbent assay (ELISA). The present study aimed to solve one of the key problems in the specific and efficient isolation of phosphorylated peptides. A method based on a magnetic carbon nitride composite coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was developed for the enrichment and analysis of phosphopeptides with low abundance in complex samples. Magnetic carbon nitride composite was synthesized and characterized by electron microscopy, infrared spectroscopy, and X-ray diffractometry. The composite showed a well-distributed two-dimensional layered structure and functional groups with excellent paramagnetic performance. Two classical phosphoproteins, namely, α- and ß-caseins, were selected as model phosphorylated samples to assess the performance of the proposed enrichment technique. The magnetic carbon nitride composite exhibited high selectivity and sensitivity for phosphopeptide enrichment. The limit of detection was determined by MALDI-TOF-MS analysis to be 0.1 fmol. The selectivity of the method was investigated using the digest mixtures of α-casein, ß-casein, and bovine serum albumin (BSA) with different mass ratios (1∶1∶1000, 1∶1∶2000, and 1∶1∶5000). Direct analysis of the samples revealed the dominance of spectral signals from the abundant peptides in BSA. After enrichment with the magnetic carbon nitride composite, the high concentration of background proteins was washed away and only the signals of the phosphopeptides were captured. The signals from the casein proteins were clearly observed with little background noise, indicating the high selectivity of the composite material. The robustness of the method was tested by assessing the reusability of the same batch of magnetic carbon nitride materials over 20 cycles of enrichment. The composite showed nearly the same enrichment ability even after several cycles of reuse, demonstrating its potential applicability for a large number of clinical samples. Finally, the method was applied to the analysis of phosphopeptides from several commonly used phosphoprotein-containing samples, including skimmed milk digest, human serum, and human saliva; these samples are significant in the analysis of food quality, disease biomarkers, and liquid biopsies for cancer. Without enrichment, no phosphopeptide was detected because of the high abundance of nonphosphopeptide materials dominating the spectral signals obtained. After pretreatment with the developed magnetic carbon nitride composite, most of the phosphosites were identified with high selectivity and sensitivity via MALDI-TOF-MS. These results revealed the practicality of the developed approach for clinical applications. In addition, our method may potentially be employed for phosphoproteomics with real complex biological samples.


Asunto(s)
Nitrilos , Fosfopéptidos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Fosfopéptidos/análisis , Fosfopéptidos/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Nitrilos/química , Caseínas/química , Caseínas/análisis , Fosforilación , Proteómica/métodos , Magnetismo
20.
Cell Mol Neurobiol ; 44(1): 50, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856921

RESUMEN

In recent years, spatial transcriptomics (ST) research has become a popular field of study and has shown great potential in medicine. However, there are few bibliometric analyses in this field. Thus, in this study, we aimed to find and analyze the frontiers and trends of this medical research field based on the available literature. A computerized search was applied to the WoSCC (Web of Science Core Collection) Database for literature published from 2006 to 2023. Complete records of all literature and cited references were extracted and screened. The bibliometric analysis and visualization were performed using CiteSpace, VOSviewer, Bibliometrix R Package software, and Scimago Graphica. A total of 1467 papers and reviews were included. The analysis revealed that the ST publication and citation results have shown a rapid upward trend over the last 3 years. Nature Communications and Nature were the most productive and most co-cited journals, respectively. In the comprehensive global collaborative network, the United States is the country with the most organizations and publications, followed closely by China and the United Kingdom. The author Joakim Lundeberg published the most cited paper, while Patrik L. Ståhl ranked first among co-cited authors. The hot topics in ST are tissue recognition, cancer, heterogeneity, immunotherapy, differentiation, and models. ST technologies have greatly contributed to in-depth research in medical fields such as oncology and neuroscience, opening up new possibilities for the diagnosis and treatment of diseases. Moreover, artificial intelligence and big data drive additional development in ST fields.


Asunto(s)
Bibliometría , Transcriptoma , Humanos , Transcriptoma/genética , Publicaciones , Animales
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