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1.
Front Microbiol ; 15: 1355599, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38706966

RESUMEN

The emergence of anti-influenza drug-resistant strains poses a challenge for influenza therapy due to mutations in the virus's surface protein. Recently, there has been increasing interest in combination therapy consisting of two or more drugs as a potential alternative approach, aiming to enhance therapeutic efficacy. In this study, we investigated a novel synergistic therapy with a vertical effect using a single-domain VL-HA1-specific antibody against H1N1/PR8 and a horizontal effect using an RNA catalytic antibody with broad-spectrum influenza antiviral drug. We isolated a single-domain VL-HA1-specific (NVLH8) antibody binding to the virus particles showing a neutralizing activity against influenza virus A, specifically H1N1/PR8, as determined by the reduction in plaque number and lower viral HA protein expression in vitro. The neutralizing antibody likely prevented the viral entry, specifically at the viral genome-releasing step. Additionally, the 3D8 scFv hydrolyzed viral RNAs in the cytoplasm, including mRNA, vRNA, and cRNA in MDCK cells. The combined treatment of neutralizing antibodies for a vertical effect and 3D8 scFv for a horizontal effect produced a synergistic effect providing a novel approach against viral diseases when compared with a single treatment. Our results indicated that combining treatment, in particular two proteins exhibiting different mechanisms of action increased the antiviral activity against the influenza virus.

2.
Sci Rep ; 14(1): 6847, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38514797

RESUMEN

Entangled coherent states play pivotal roles in various fields such as quantum computation, quantum communication, and quantum sensing. We experimentally demonstrate the generation of entangled coherent states with the two-dimensional motion of a trapped ion system. Using Raman transitions with appropriate detunings, we simultaneously drive the red and blue sidebands of the two transverse axes of a single trapped ion and observe multi-periodic entanglement and disentanglement of its spin and two-dimensional motion. Then, by measuring the spin state, we herald entangled coherent states of the transverse motions of the trapped ion and observe the corresponding modulation in the parity of the phonon distribution of one of the harmonic oscillators. Lastly, we trap two ions in a linear chain and realize Mølmer-Sørensen gate using two-dimensional motion.

3.
Sci Transl Med ; 16(737): eadf4601, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38446899

RESUMEN

Patients with cancer undergoing chemotherapy frequently experience a neurological condition known as chemotherapy-related cognitive impairment, or "chemobrain," which can persist for the remainder of their lives. Despite the growing prevalence of chemobrain, both its underlying mechanisms and treatment strategies remain poorly understood. Recent findings suggest that chemobrain shares several characteristics with neurodegenerative diseases, including chronic neuroinflammation, DNA damage, and synaptic loss. We investigated whether a noninvasive sensory stimulation treatment we term gamma entrainment using sensory stimuli (GENUS), which has been shown to alleviate aberrant immune and synaptic pathologies in mouse models of neurodegeneration, could also mitigate chemobrain phenotypes in mice administered a chemotherapeutic drug. When administered concurrently with the chemotherapeutic agent cisplatin, GENUS alleviated cisplatin-induced brain pathology, promoted oligodendrocyte survival, and improved cognitive function in a mouse model of chemobrain. These effects persisted for up to 105 days after GENUS treatment, suggesting the potential for long-lasting benefits. However, when administered to mice 90 days after chemotherapy, GENUS treatment only provided limited benefits, indicating that it was most effective when used to prevent the progression of chemobrain pathology. Furthermore, we demonstrated that the effects of GENUS in mice were not limited to cisplatin-induced chemobrain but also extended to methotrexate-induced chemobrain. Collectively, these findings suggest that GENUS may represent a versatile approach for treating chemobrain induced by different chemotherapy agents.


Asunto(s)
Deterioro Cognitivo Relacionado con la Quimioterapia , Disfunción Cognitiva , Humanos , Animales , Ratones , Cisplatino/efectos adversos , Cognición , Daño del ADN , Modelos Animales de Enfermedad
4.
NPJ Vaccines ; 9(1): 68, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555379

RESUMEN

Human cytomegalovirus (CMV) is the most common infectious cause of complications post-transplantation, while a CMV vaccine for transplant recipients has yet to be licensed. Triplex, a multiantigen Modified Vaccinia Ankara (MVA)-vectored CMV vaccine candidate based on the immunodominant antigens phosphoprotein 65 (pp65) and immediate-early 1 and 2 (IE1/2), is in an advanced stage of clinical development. However, its limited genetic and expression stability restricts its potential for large-scale production. Using a recently developed fully synthetic MVA (sMVA) platform, we developed a new generation Triplex vaccine candidate, T10-F10, with different sequence modifications for enhanced vaccine stability. T10-F10 demonstrated genetic and expression stability during extensive virus passaging. In addition, we show that T10-F10 confers comparable immunogenicity to the original Triplex vaccine to elicit antigen-specific T cell responses in HLA-transgenic mice. These results demonstrate improvements in translational vaccine properties of an sMVA-based CMV vaccine candidate designed as a therapeutic treatment for transplant recipients.

5.
Commun Med (Lond) ; 4(1): 19, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38366141

RESUMEN

BACKGROUND: Although the mpox global health emergency caused by mpox virus (MPXV) clade IIb.1 has ended, mpox cases are still reported due to low vaccination coverage and waning immunity. COH04S1 is a clinically evaluated, multiantigen COVID-19 vaccine candidate built on a fully synthetic platform of the highly attenuated modified vaccinia Ankara (MVA) vector, representing the only FDA-approved smallpox/mpox vaccine JYNNEOS. Given the potential threat of MPXV resurgence and need for vaccine alternatives, we aimed to assess the capacity COH04S1 and its synthetic MVA (sMVA) backbone to confer MPXV-specific immunity. METHODS: We evaluated orthopoxvirus-specific and MPXV cross-reactive immune responses in samples collected during a Phase 1 clinical trial of COH04S1 and in non-human primates (NHP) vaccinated with COH04S1 or its sMVA backbone. MPXV cross-reactive immune responses in COH04S1-vaccinated healthy adults were compared to responses measured in healthy subjects vaccinated with JYNNEOS. Additionally, we evaluated the protective efficacy of COH04S1 and sMVA against mpox in mpox-susceptible CAST/EiJ mice. RESULTS: COH04S1-vaccinated individuals develop robust orthopoxvirus-specific humoral and cellular responses, including cross-reactive antibodies to MPXV-specific virion proteins as well as MPXV cross-neutralizing antibodies in 45% of the subjects. In addition, NHP vaccinated with COH04S1 or sMVA show similar MPXV cross-reactive antibody responses. Moreover, MPXV cross-reactive humoral responses elicited by COH04S1 are comparable to those measured in JYNNEOS-vaccinated subjects. Finally, we show that mice vaccinated with COH04S1 or sMVA are protected from lung infection following challenge with MPXV clade IIb.1. CONCLUSIONS: These results demonstrate the capacity of sMVA vaccines to elicit cross-reactive and protective orthopox-specific immunity against MPXV, suggesting that COH04S1 and sMVA could be developed as bivalent or monovalent mpox vaccine alternatives against MPXV.


Mpox is an ilness caused by the mpox virus (MPXV) that belongs to the poxvirus family. The 2022-2023 mpox outbreak highlights the need to develop effective vaccines against MPXV. We have developed a COVID-19 vaccine using as scaffold chemically synthesized genetic material of a highly attenuated and safe poxvirus vector. This scaffold is the same present in a vaccine that has been approved and is given to prevent mpox. Here, we show that healthy human volunteers or monkeys vaccinated with this COVID-19 vaccine generated a robust immune response against MPXV, similar to that generated by the mpox vaccine with the same scaffold. This COVID-19 vaccine is also able to protect mice from infection caused by the MPXV strain isolated from the recent mpox outbreak. This COVID-19 vaccine in a poxvirus scaffold might be an additional tool to curtail mpox outbreaks.

6.
J Gynecol Oncol ; 35(2): e66, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38330382

RESUMEN

In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.


Asunto(s)
Neoplasias Endometriales , Neoplasias de los Genitales Femeninos , Neoplasias Ováricas , Neoplasias del Cuello Uterino , Femenino , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Endometriales/tratamiento farmacológico
7.
Nature ; 627(8002): 149-156, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38418876

RESUMEN

The glymphatic movement of fluid through the brain removes metabolic waste1-4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease5-8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer's disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.


Asunto(s)
Enfermedad de Alzheimer , Amiloide , Encéfalo , Líquido Cefalorraquídeo , Líquido Extracelular , Ritmo Gamma , Sistema Glinfático , Animales , Ratones , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/prevención & control , Amiloide/metabolismo , Acuaporina 4/metabolismo , Astrocitos/metabolismo , Encéfalo/citología , Encéfalo/metabolismo , Encéfalo/patología , Líquido Cefalorraquídeo/metabolismo , Modelos Animales de Enfermedad , Líquido Extracelular/metabolismo , Sistema Glinfático/fisiología , Interneuronas/metabolismo , Péptido Intestinal Vasoactivo/metabolismo , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Estimulación Eléctrica
8.
Cell Host Microbe ; 32(2): 244-260.e11, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38198924

RESUMEN

Although early life colonization of commensal microbes contributes to long-lasting immune imprinting in host tissues, little is known regarding the pathophysiological consequences of postnatal microbial tuning of cutaneous immunity. Here, we show that postnatal exposure to specific skin commensal Staphylococcus lentus (S. lentus) promotes the extent of atopic dermatitis (AD)-like inflammation in adults through priming of group 2 innate lymphoid cells (ILC2s). Early postnatal skin is dynamically populated by discrete subset of primed ILC2s driven by microbiota-dependent induction of thymic stromal lymphopoietin (TSLP) in keratinocytes. Specifically, the indole-3-aldehyde-producing tryptophan metabolic pathway, shared across Staphylococcus species, is involved in TSLP-mediated ILC2 priming. Furthermore, we demonstrate a critical contribution of the early postnatal S. lentus-TSLP-ILC2 priming axis in facilitating AD-like inflammation that is not replicated by later microbial exposure. Thus, our findings highlight the fundamental role of time-dependent neonatal microbial-skin crosstalk in shaping the threshold of innate type 2 immunity co-opted in adulthood.


Asunto(s)
Dermatitis Atópica , Linfopoyetina del Estroma Tímico , Humanos , Adulto , Recién Nacido , Inmunidad Innata , Linfocitos , Citocinas/metabolismo , Piel/metabolismo , Inflamación
9.
Neuron ; 112(2): 201-208.e4, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-37944516

RESUMEN

Despite recent advancements in identifying engram cells, our understanding of their regulatory and functional mechanisms remains in its infancy. To provide mechanistic insight into engram cell functioning, we introduced a novel local microcircuit labeling technique that enables the labeling of intraregional synaptic connections. Utilizing this approach, we discovered a unique population of somatostatin (SOM) interneurons in the mouse basolateral amygdala (BLA). These neurons are activated during fear memory formation and exhibit a preference for forming synapses with excitatory engram neurons. Post-activation, these SOM neurons displayed varying excitability based on fear memory retrieval. Furthermore, when we modulated these SOM neurons chemogenetically, we observed changes in the expression of fear-related behaviors, both in a fear-associated context and in a novel setting. Our findings suggest that these activated SOM interneurons play a pivotal role in modulating engram cell activity. They influence the expression of fear-related behaviors through a mechanism that is dependent on memory cues.


Asunto(s)
Complejo Nuclear Basolateral , Interneuronas , Ratones , Animales , Interneuronas/fisiología , Memoria/fisiología , Neuronas/fisiología , Complejo Nuclear Basolateral/fisiología , Somatostatina/metabolismo
10.
J Control Release ; 365: 703-715, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38016489

RESUMEN

Recently, CRISPR proteins have been recognized as promising candidates for drug development. However, there is still a lack of substances with the appropriate sensitivity and stability for targeted drug delivery systems. 89Zr is a radioactive isotope that emits positrons, allowing real-time in vivo tracking with proven safety. In this study, we confirmed that labeling with 89Zr did not compromise the functionality of CRISPR proteins during in vivo behavioral imaging. Furthermore, we demonstrated the therapeutic efficacy of the CRISPR interference system in a mouse model of liver fibrosis, highlighting the theragnostic potential of isotope-labeled CRISPR proteins. The findings of this research could contribute to various aspects of ongoing clinical studies exploring the in vivo applications of CRISPR proteins.


Asunto(s)
Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Tomografía de Emisión de Positrones , Ratones , Animales , Tomografía de Emisión de Positrones/métodos , Circonio , Radioisótopos , Distribución Tisular , Marcaje Isotópico
11.
J Gynecol Oncol ; 35(2): e18, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37921602

RESUMEN

OBJECTIVE: To assess the frequency of regular uptake of national cervical cancer screening (CCS) program and identify associated factors among Korean women. METHODS: This study is a fundamental investigation that employs openly accessible public data of Korea through secondary data analysis. A cohort of 4,663 women from the 2007-2012 Korean National Health and Nutrition Examination Survey, was followed up for up to 12 years (2007-2018) to obtain the frequency of national CCS. Compliance level with CCS was categorized, and an ordinal logistic regression model was employed to investigate the contributing factors. RESULTS: The regular uptake of CCS in South Korea was low at 18.9%. The trend of regular screening showed significant association with various factors, including age (40-59 years), household income (100%-150% bracket), occupation (service workers), place of residence (small to medium sized cities), education level (middle school graduates), marital status (married), and possession of private insurance. Moreover, individuals with a history of non-cervical cancer or carcinoma in situ of the cervix, a family history of cervical cancer, or a higher frequency of general check-ups demonstrated a stronger adherence to regular CCS uptake. CONCLUSION: Our findings revealed that regular participation in CCS in Korea was lower than anticipated, with factors such as socioeconomic status, personal history of gynecologic issue, and frequency of general health check-ups playing influential roles. However, further research, including an exploration of unexamined psychological barriers to screening, is necessary to gain a better understanding the reasons behind the reduced rates of regular CCS among Korean women.


Asunto(s)
Neoplasias del Cuello Uterino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Encuestas Nutricionales , Detección Precoz del Cáncer , Tamizaje Masivo , República de Corea/epidemiología
12.
Proc Natl Acad Sci U S A ; 120(52): e2309786120, 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38109550

RESUMEN

Many sub-Neptune exoplanets have been believed to be composed of a thick hydrogen-dominated atmosphere and a high-temperature heavier-element-dominant core. From an assumption that there is no chemical reaction between hydrogen and silicates/metals at the atmosphere-interior boundary, the cores of sub-Neptunes have been modeled with molten silicates and metals (magma) in previous studies. In large sub-Neptunes, pressure at the atmosphere-magma boundary can reach tens of gigapascals where hydrogen is a dense liquid. A recent experiment showed that hydrogen can induce the reduction of Fe[Formula: see text] in (Mg,Fe)O to Fe[Formula: see text] metal at the pressure-temperature conditions relevant to the atmosphere-interior boundary. However, it is unclear whether Mg, one of the abundant heavy elements in the planetary interiors, remains oxidized or can be reduced by H. Our experiments in the laser-heated diamond-anvil cell found that heating of MgO + Fe to 3,500 to 4,900 K (close to or above their melting temperatures) in an H medium leads to the formation of Mg[Formula: see text]FeH[Formula: see text] and H[Formula: see text]O at 8 to 13 GPa. At 26 to 29 GPa, the behavior of the system changes, and Mg-H in an H fluid and H[Formula: see text]O were detected with separate FeH[Formula: see text]. The observations indicate the dissociation of the Mg-O bond by H and subsequent production of hydride and water. Therefore, the atmosphere-magma interaction can lead to a fundamentally different mineralogy for sub-Neptune exoplanets compared with rocky planets. The change in the chemical reaction at the higher pressures can also affect the size demographics (i.e., "radius cliff") and the atmosphere chemistry of sub-Neptune exoplanets.

13.
Sci Adv ; 9(50): eadi6096, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38100581

RESUMEN

Giant impact-driven redox processes in the atmosphere and magma ocean played crucial roles in the evolution of Earth. However, because of the absence of rock records from that time, understanding these processes has proven challenging. Here, we present experimental results that simulate the giant impact-driven reactions between iron and volatiles (H2O and CO2) using x-ray free electron laser (XFEL) as fast heat pump and structural probe. Under XFEL pump, iron is oxidized to wüstite (FeO), while volatiles are reduced to H2 and CO. Furthermore, iron oxidation proceeds into formation of hydrides (γ-FeHx) and siderite (FeCO3), implying redox boundary near 300-km depth. Through quantitative analysis on reaction products, we estimate the volatile and FeO budgets in bulk silicate Earth, supporting the Theia hypothesis. Our findings shed light on the fast and short-lived process that led to reduced atmosphere, required for the emergence of prebiotic organic molecules in the early Earth.

14.
Sensors (Basel) ; 23(21)2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37960551

RESUMEN

In multi-cat households, monitoring individual cats' various behaviors is essential for diagnosing their health and ensuring their well-being. This study focuses on the defecation and urination activities of cats, and introduces an adaptive cat identification architecture based on deep learning (DL) and machine learning (ML) methods. The architecture comprises an object detector and a classification module, with the primary focus on the design of the classification component. The DL object detection algorithm, YOLOv4, is used for the cat object detector, with the convolutional neural network, EfficientNetV2, serving as the backbone for our feature extractor in identity classification with several ML classifiers. Additionally, to address changes in cat composition and individual cat appearances in multi-cat households, we propose an adaptive concept drift approach involving retraining the classification module. To support our research, we compile a comprehensive cat body dataset comprising 8934 images of 36 cats. After a rigorous evaluation of different combinations of DL models and classifiers, we find that the support vector machine (SVM) classifier yields the best performance, achieving an impressive identification accuracy of 94.53%. This outstanding result underscores the effectiveness of the system in accurately identifying cats.


Asunto(s)
Aprendizaje Automático , Redes Neurales de la Computación , Algoritmos , Monitoreo Fisiológico , Máquina de Vectores de Soporte
15.
Polymers (Basel) ; 15(22)2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-38006167

RESUMEN

The use of mixed matrix membranes (MMMs) comprising metal-organic frameworks (MOFs) for the separation of CO2 from flue gas has gained recognition as an effective strategy for enhancing gas separation efficiency. When incorporating porous materials like MOFs into a polymeric matrix to create MMMs, the combined characteristics of each constituent typically manifest. Nevertheless, the inadequate dispersion of an inorganic MOF filler within an organic polymer matrix can compromise the compatibility between the filler and matrix. In this context, the aspiration is to develop an MMM that not only exhibits optimal interfacial compatibility between the polymer and filler but also delivers superior gas separation performance, specifically in the efficient extraction of CO2 from flue gas. In this study, we introduce a modification technique involving the grafting of poly(ethylene glycol) diglycidyl ether (PEGDE) onto a UiO-66-NH2 MOF filler (referred to as PEG-MOF), aimed at enhancing its compatibility with the 6FDA-durene matrix. Moreover, the inherent CO2-philic nature of PEGDE is anticipated to enhance the selectivity of CO2 over N2 and CH4. The resultant MMM, incorporating 10 wt% of PEG-MOF loading, exhibits a CO2 permeability of 1671.00 Barrer and a CO2/CH4 selectivity of 22.40. Notably, these values surpass the upper bound reported by Robeson in 2008.

16.
Exp Mol Med ; 55(11): 2461-2472, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37919422

RESUMEN

Despite advances in cancer therapy, the clinical outcome of patients with gastric cancer remains poor, largely due to tumor heterogeneity. Thus, finding a hidden vulnerability of clinically refractory subtypes of gastric cancer is crucial. Here, we report that chemoresistant gastric cancer cells rely heavily on endocytosis, facilitated by caveolin-1, for survival. caveolin-1 was highly upregulated in the most malignant stem-like/EMT/mesenchymal (SEM)-type gastric cancer cells, allowing caveolin-1-mediated endocytosis and utilization of extracellular proteins via lysosomal degradation. Downregulation of caveolin-1 alone was sufficient to induce cell death in SEM-type gastric cancer cells, emphasizing its importance as a survival mechanism. Consistently, chloroquine, a lysosomal inhibitor, successfully blocked caveolin-1-mediated endocytosis, leading to the marked suppression of tumor growth in chemorefractory gastric cancer cells in vitro, including patient-derived organoids, and in vivo. Together, our findings suggest that caveolin-1-mediated endocytosis is a key metabolic pathway for gastric cancer survival and a potential therapeutic target.


Asunto(s)
Caveolina 1 , Neoplasias Gástricas , Humanos , Caveolina 1/genética , Caveolina 1/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Regulación hacia Abajo , Endocitosis
17.
J Clin Med ; 12(19)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37834898

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the efficacy of scoring balloon angioplasty for drug-coated balloon (DCB) treatment in percutaneous coronary intervention. BACKGROUND: The scoring balloon angioplasty may play a pivotal role in enhancing the outcomes of DCB treatment. METHODS: A total of 259 patients (278 lesions) with coronary artery disease successfully treated with DCB were retrospectively enrolled. The mean age of the patients was 62.2 ± 11.1 years, and the majority of patients were men (68.7%). The study's endpoint was defined as achieving an optimal angiographic result, which consisted of Thrombolysis in Myocardial Infarction (TIMI) flow grade 3, residual diameter stenosis ≤ 30%, and dissection less than type C after the procedure. RESULTS: Angioplasty was performed for 61 lesions with a scoring balloon and 217 lesions with a non-scoring balloon. All lesions were TIMI flow grade 3 except two lesions in the non-scoring balloon group. The scoring balloon group had a higher prevalence of residual diameter stenosis ≤ 30% (68.9% vs. 39.6%, p < 0.001), while severe dissection, defined as type C or greater, was observed less frequently (9.8% vs. 31.8%, p = 0.001). Moreover, the scoring balloon group achieved a superior rate of optimal angiographic results (60.7% vs. 28.6%, p < 0.001). In multivariable analysis, scoring balloon (OR: 3.08 [95% confidence interval, 1.47-6.58], p = 0.003) and DCB balloon-to-artery ratios (OR: 5.46 [95% confidence interval, 1.43-21.93], p = 0.014) were independent factors in the increasing rate of optimal angiographic result. CONCLUSIONS: The application of a scoring balloon catheter for lesion preparation, aiming to make them suitable for DCB treatment, was associated with a decreased risk of severe dissection and a greater occurrence of optimal angiographic outcomes compared with non-scoring balloon angioplasty.

18.
Int J Mol Sci ; 24(20)2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37894829

RESUMEN

Endometrial receptivity is a complex process that prepares the uterine endometrium for embryo implantation; insufficient endometrial receptivity is one of the causes of implantation failure. Here, we analyzed the microRNA expression profiles of exosomes derived from both receptive (RL95-2) and non-receptive (AN3-CA) endometrial epithelial cell (EEC) lines to identify exosomal miRNAs closely linked to endometrial receptivity. Among the 466 differentially expressed miRNAs, miR-205-5p was the most highly expressed in exosomes secreted from receptive RL95-2 cells. miR-205-5p, enriched at the adhesive junction, was closely related to endometrial receptivity. ZEB1, a transcriptional repressor of E-cadherin associated with endometrial receptivity, was identified as a direct target of miR-205-5p. miR-205-5p expression was significantly lower in the endometrial tissues of infertile women than in that of non-infertile women. In vivo, miR-205-5p expression was upregulated in the post-ovulatory phase, and its inhibitor reduced embryo implantation. Furthermore, administration of genetically modified exosomes overexpressing miR-205-5p mimics upregulated E-cadherin expression by targeting ZEB1 and improved spheroid attachment of non-receptive AN3-CA cells. These results suggest that the miR-205-5p/ZEB1/E-cadherin axis plays an important role in regulating endometrial receptivity. Thus, the use of exosomes harboring miR-205-5p mimics can be considered a potential therapeutic approach for improving embryo implantation.


Asunto(s)
Infertilidad Femenina , MicroARNs , Femenino , Humanos , Cadherinas/genética , Cadherinas/metabolismo , Implantación del Embrión/genética , Endometrio/metabolismo , Infertilidad Femenina/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo
19.
Front Plant Sci ; 14: 1225409, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37810377

RESUMEN

Recent advancements in deep learning have brought significant improvements to plant disease recognition. However, achieving satisfactory performance often requires high-quality training datasets, which are challenging and expensive to collect. Consequently, the practical application of current deep learning-based methods in real-world scenarios is hindered by the scarcity of high-quality datasets. In this paper, we argue that embracing poor datasets is viable and aims to explicitly define the challenges associated with using these datasets. To delve into this topic, we analyze the characteristics of high-quality datasets, namely, large-scale images and desired annotation, and contrast them with the limited and imperfect nature of poor datasets. Challenges arise when the training datasets deviate from these characteristics. To provide a comprehensive understanding, we propose a novel and informative taxonomy that categorizes these challenges. Furthermore, we offer a brief overview of existing studies and approaches that address these challenges. We point out that our paper sheds light on the importance of embracing poor datasets, enhances the understanding of the associated challenges, and contributes to the ambitious objective of deploying deep learning in real-world applications. To facilitate the progress, we finally describe several outstanding questions and point out potential future directions. Although our primary focus is on plant disease recognition, we emphasize that the principles of embracing and analyzing poor datasets are applicable to a wider range of domains, including agriculture. Our project is public available at https://github.com/xml94/EmbracingLimitedImperfectTrainingDatasets.

20.
Opt Express ; 31(21): 33787-33798, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37859151

RESUMEN

Excess micromotion is detrimental to accurate qubit control of trapped ions, thus measuring and minimizing it is crucial. In this paper, we present a simple approach for measuring and suppressing excess micromotion of trapped ions by leveraging the existing laser-driven qubit transition scheme combined with direct scanning of dc voltages. The compensation voltage is deduced by analyzing the Bessel expansion of a scanned qubit transition rate. The method provides a fair level of sensitivity for practical quantum computing applications, while demanding minimal deviation of trap condition. By accomplishing compensation of excess micromotion in the qubit momentum-excitation direction, the scheme offers an additional avenue for excess micromotion compensation, complementing existing compensation schemes.

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