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1.
Arthritis Res Ther ; 26(1): 92, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38725078

RESUMEN

OBJECTIVE: The macrophage activation syndrome (MAS) secondary to systemic lupus erythematosus (SLE) is a severe and life-threatening complication. Early diagnosis of MAS is particularly challenging. In this study, machine learning models and diagnostic scoring card were developed to aid in clinical decision-making using clinical characteristics. METHODS: We retrospectively collected clinical data from 188 patients with either SLE or the MAS secondary to SLE. 13 significant clinical predictor variables were filtered out using the Least Absolute Shrinkage and Selection Operator (LASSO). These variables were subsequently utilized as inputs in five machine learning models. The performance of the models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), F1 score, and F2 score. To enhance clinical usability, we developed a diagnostic scoring card based on logistic regression (LR) analysis and Chi-Square binning, establishing probability thresholds and stratification for the card. Additionally, this study collected data from four other domestic hospitals for external validation. RESULTS: Among all the machine learning models, the LR model demonstrates the highest level of performance in internal validation, achieving a ROC-AUC of 0.998, an F1 score of 0.96, and an F2 score of 0.952. The score card we constructed identifies the probability threshold at a score of 49, achieving a ROC-AUC of 0.994 and an F2 score of 0.936. The score results were categorized into five groups based on diagnostic probability: extremely low (below 5%), low (5-25%), normal (25-75%), high (75-95%), and extremely high (above 95%). During external validation, the performance evaluation revealed that the Support Vector Machine (SVM) model outperformed other models with an AUC value of 0.947, and the scorecard model has an AUC of 0.915. Additionally, we have established an online assessment system for early identification of MAS secondary to SLE. CONCLUSION: Machine learning models can significantly improve the diagnostic accuracy of MAS secondary to SLE, and the diagnostic scorecard model can facilitate personalized probabilistic predictions of disease occurrence in clinical environments.


Asunto(s)
Lupus Eritematoso Sistémico , Aprendizaje Automático , Síndrome de Activación Macrofágica , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Femenino , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/etiología , Estudios Retrospectivos , Masculino , Adulto , Persona de Mediana Edad , Diagnóstico Precoz , Curva ROC
2.
Proc Natl Acad Sci U S A ; 121(18): e2310283121, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38669183

RESUMEN

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.


Asunto(s)
Proteínas Portadoras , Polaridad Celular , Proteínas de la Membrana , Columna Vertebral , Pez Cebra , Animales , Pez Cebra/genética , Pez Cebra/embriología , Humanos , Ratones , Polaridad Celular/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Columna Vertebral/anomalías , Columna Vertebral/metabolismo , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Escoliosis/genética , Escoliosis/congénito , Escoliosis/metabolismo , Vía de Señalización Wnt/genética , Predisposición Genética a la Enfermedad , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Femenino
3.
Toxicol Sci ; 199(1): 108-119, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38445754

RESUMEN

Carbamazepine (CBZ) has been identified in the aquatic environment as an emerging contaminant. Its immune effect across generations at environmentally relevant concentrations is little known. We aim to elucidate the effects of CBZ on the immune system in zebrafish (Danio rerio), hypothesizing the effects caused by CBZ exposure in the parental generation can be passed on to its offspring, leading to impairment of innate immune function and defense against pathogen weakened. A suite of bioassays (including a test with added lipopolysaccharide) was used to measure the effects of environmentally relevant levels of CBZ (1, 10, and 100 µg/l) on zebrafish at multiple biological levels, and across 2 successive generations (21 days exposure for F0; 5 and 21 days exposure or nonexposure for F1). The results showed that CBZ affected homeostasis in the immune system, caused liver vacuolization, increased the inflammation-related microbiota proportion in gut, and decreased reproduction, by induction of oxidative stress and modulation of Toll-like receptors (TLR) signaling pathway on gut-liver axis. The effects of exposure to CBZ over 21 days in F0 could be passed to the next generation. Intergenerational effects on TLR and antioxidant defense system were also observed in nonexposed F1 at 5 days post-fertilization (5 dpf), but diminished at 21 dpf. The finding provided evidence to unravel immune response by gut-liver axis mediated and oxidative stress under 4 test conditions. The study has raised a potential concern about the multigenerational immune effects of environmental pollutants and calls for a focus on the risk of synergetic pathogen infection.


Asunto(s)
Carbamazepina , Hígado , Transducción de Señal , Receptores Toll-Like , Contaminantes Químicos del Agua , Pez Cebra , Animales , Pez Cebra/inmunología , Carbamazepina/toxicidad , Receptores Toll-Like/metabolismo , Transducción de Señal/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/inmunología , Hígado/metabolismo , Contaminantes Químicos del Agua/toxicidad , Estrés Oxidativo/efectos de los fármacos , Femenino , Inmunidad Innata/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Relación Dosis-Respuesta a Droga , Reproducción/efectos de los fármacos
4.
J Multidiscip Healthc ; 17: 937-947, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38455274

RESUMEN

Background: This study aims to investigate the knowledge, attitudes, and practices (KAP) among patients with systemic lupus erythematosus (SLE) toward disease management and biologic therapy. Methods: This cross-sectional study was conducted between April 20, 2023, and May 5, 2023, among patients with SLE at Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology. A self-designed questionnaire was developed to collect demographic information of SLE patients and assess their KAP. Results: A total of 463 SLE patients participated. The mean scores for knowledge, attitudes, and practices were 8.52 ± 2.36 (possible range: 0-11), 39.40 ± 3.38 (possible range: 11-55), and 27.10 ± 6.29 (possible range: 8-40), respectively. The path analysis demonstrated a significant and positive association between knowledge and attitudes, as indicated by a path coefficient of 0.455 (p < 0.001), and a significant and positive relationship between knowledge and practices, with a path coefficient of 0.709 (p < 0.001). Conclusion: Patients with SLE exhibited insufficient knowledge, negative attitudes, and poor practices.

5.
Br J Radiol ; 97(1156): 812-819, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38366622

RESUMEN

OBJECTIVE: To demonstrate that a T2 periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) technique using deep learning reconstruction (DLR) will provide better image quality and decrease image noise. METHODS: From December 2020 to March 2021, 35 patients examined cervical spine MRI were included in this study. Four sets of images including fast spin echo (FSE), original PROPELLER, PROPELLER DLR50%, and DLR75% were quantitatively and qualitatively reviewed. We calculated the signal-to-noise ratio (SNR) of the spinal cord and sternocleidomastoid (SCM) muscle and the contrast-to-noise ratio (CNR) of the spinal cord by applying region-of-interest at the spinal cord, SCM muscle, and background air. We evaluated image noise with regard to the spinal cord, SCM, and back muscles at each level from C2-3 to C6-7 in the 4 sets. RESULTS: At all disc levels, the mean SNR values for the spinal cord and SCM muscles were significantly higher in PROPELLER DLR50% and DLR75% compared to FSE and original PROPELLER images (P < .0083). The mean CNR values of the spinal cord were significantly higher in PROPELLER DLR50% and DLR75% compared to FSE at the C3-4 and 4-5 levels and PROPELLER DLR75% compared to FSE at the C6-7 level (P < .0083). Qualitative analysis of image noise on the spinal cord, SCM, and back muscles showed that PROPELLER DLR50% and PROPELLER DLR75% images showed a significant denoising effect compared to the FSE and original PROPELLER images. CONCLUSION: The combination of PROPELLER and DLR improved image quality with a high SNR and CNR and reduced noise. ADVANCES IN KNOWLEDGE: Motion-insensitive imaging technique (PROPELLER) increased the image quality compared to conventional FSE images. PROPELLER technique with a DLR reduced image noise and improved image quality.


Asunto(s)
Aprendizaje Profundo , Humanos , Aumento de la Imagen/métodos , Artefactos , Imagen por Resonancia Magnética/métodos , Vértebras Cervicales/diagnóstico por imagen , Resultado del Tratamiento
6.
Nat Commun ; 15(1): 1838, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418810

RESUMEN

Plastic crystals as barocaloric materials exhibit the large entropy change rivalling freon, however, the limited pressure-sensitivity and large hysteresis of phase transition hinder the colossal barocaloric effect accomplished reversibly at low pressure. Here we report reversible colossal barocaloric effect at low pressure in two-dimensional van-der-Waals alkylammonium halides. Via introducing long carbon chains in ammonium halide plastic crystals, two-dimensional structure forms in (CH3-(CH2)n-1)2NH2X (X: halogen element) with weak interlayer van-der-Waals force, which dictates interlayer expansion as large as 13% and consequently volume change as much as 12% during phase transition. Such anisotropic expansion provides sufficient space for carbon chains to undergo dramatic conformation disordering, which induces colossal entropy change with large pressure-sensitivity and small hysteresis. The record reversible colossal barocaloric effect with entropy change ΔSr ~ 400 J kg-1 K-1 at 0.08 GPa and adiabatic temperature change ΔTr ~ 11 K at 0.1 GPa highlights the design of novel barocaloric materials by engineering the dimensionality of plastic crystals.

7.
Elife ; 132024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38240312

RESUMEN

Out of the several hundred copies of rRNA genes arranged in the nucleolar organizing regions (NOR) of the five human acrocentric chromosomes, ~50% remain transcriptionally inactive. NOR-associated sequences and epigenetic modifications contribute to the differential expression of rRNAs. However, the mechanism(s) controlling the dosage of active versus inactive rRNA genes within each NOR in mammals is yet to be determined. We have discovered a family of ncRNAs, SNULs (Single NUcleolus Localized RNA), which form constrained sub-nucleolar territories on individual NORs and influence rRNA expression. Individual members of the SNULs monoallelically associate with specific NOR-containing chromosomes. SNULs share sequence similarity to pre-rRNA and localize in the sub-nucleolar compartment with pre-rRNA. Finally, SNULs control rRNA expression by influencing pre-rRNA sorting to the DFC compartment and pre-rRNA processing. Our study discovered a novel class of ncRNAs influencing rRNA expression by forming constrained nucleolar territories on individual NORs.


Asunto(s)
Región Organizadora del Nucléolo , Precursores del ARN , Humanos , Animales , Región Organizadora del Nucléolo/genética , Región Organizadora del Nucléolo/metabolismo , Precursores del ARN/genética , Precursores del ARN/metabolismo , Nucléolo Celular/genética , Nucléolo Celular/metabolismo , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , Cromosomas Humanos/metabolismo , ARN no Traducido/genética , ARN no Traducido/metabolismo , Mamíferos/genética
8.
Elife ; 122024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38277211

RESUMEN

Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than fivefold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the PAX1 gene. Here, we sought to define the roles of PAX1 and newly identified AIS-associated genes in the developmental mechanism of AIS. In a genetic study of 10,519 individuals with AIS and 93,238 unaffected controls, significant association was identified with a variant in COL11A1 encoding collagen (α1) XI (rs3753841; NM_080629.2_c.4004C>T; p.(Pro1335Leu); p=7.07E-11, OR = 1.118). Using CRISPR mutagenesis we generated Pax1 knockout mice (Pax1-/-). In postnatal spines we found that PAX1 and collagen (α1) XI protein both localize within the intervertebral disc-vertebral junction region encompassing the growth plate, with less collagen (α1) XI detected in Pax1-/- spines compared to wild-type. By genetic targeting we found that wild-type Col11a1 expression in costal chondrocytes suppresses expression of Pax1 and of Mmp3, encoding the matrix metalloproteinase 3 enzyme implicated in matrix remodeling. However, the latter suppression was abrogated in the presence of the AIS-associated COL11A1P1335L mutant. Further, we found that either knockdown of the estrogen receptor gene Esr2 or tamoxifen treatment significantly altered Col11a1 and Mmp3 expression in chondrocytes. We propose a new molecular model of AIS pathogenesis wherein genetic variation and estrogen signaling increase disease susceptibility by altering a PAX1-COL11a1-MMP3 signaling axis in spinal chondrocytes.


Adolescent idiopathic scoliosis (AIS) is a twisting deformity of the spine that occurs during periods of rapid growth in children worldwide. Children with severe cases of AIS require surgery to stop it from getting worse, presenting a significant financial burden to health systems and families. Although AIS is known to cluster in families, its genetic causes and its inheritance pattern have remained elusive. Additionally, AIS is known to be more prevalent in females, a bias that has not been explained. Advances in techniques to study the genetics underlying diseases have revealed that certain variations that increase the risk of AIS affect cartilage and connective tissue. In humans, one such variation is near a gene called Pax1, and it is female-specific. The extracellular matrix is a network of proteins and other molecules in the space between cells that help connect tissues together, and it is particularly important in cartilage and other connective tissues. One of the main components of the extracellular matrix is collagen. Yu, Kanshour, Ushiki et al. hypothesized that changes in the extracellular matrix could affect the cartilage and connective tissues of the spine, leading to AIS. To show this, the scientists screened over 100,000 individuals and found that AIS is associated with variants in two genes coding for extracellular matrix proteins. One of these variants was found in a gene called Col11a1, which codes for one of the proteins that makes up collagen. To understand the relationship between Pax1 and Col11a1, Yu, Kanshour, Ushiki et al. genetically modified mice so that they would lack the Pax1 gene. In these mice, the activation of Col11a1 was reduced in the mouse spine. They also found that the form of Col11a1 associated with AIS could not suppress the activation of a gene called Mmp3 in mouse cartilage cells as effectively as unmutated Col11a1. Going one step further, the researchers found that lowering the levels of an estrogen receptor altered the activation patterns of Pax1, Col11a1, and Mmp3 in mouse cartilage cells. These findings suggest a possible mechanism for AIS, particularly in females. The findings of Yu, Kanshour, Ushiki et al. highlight that cartilage cells in the spine are particularly relevant in AIS. The results also point to specific molecules within the extracellular matrix as important for maintaining proper alignment in the spine when children are growing rapidly. This information may guide future therapies aimed at maintaining healthy spinal cells in adolescent children, particularly girls.


Asunto(s)
Escoliosis , Masculino , Animales , Niño , Ratones , Humanos , Femenino , Adolescente , Escoliosis/genética , Metaloproteinasa 3 de la Matriz/genética , Columna Vertebral , Factores de Transcripción/genética , Colágeno/genética , Variación Genética , Colágeno Tipo XI/genética
9.
J Leukoc Biol ; 115(4): 633-646, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38066571

RESUMEN

Oncolytic virotherapy is an innovative approach for cancer treatment. However, recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment (TME) after oncolysis-mediated local inflammation leads to tumor resistance to the therapy. Using the murine malignant mesothelioma model, we demonstrated that the in situ vaccinia virotherapy recruited primarily polymorphonuclear MDSCs (PMN-MDSCs) into the TME, where they exhibited strong suppression of cytotoxic T lymphocytes in a reactive oxygen species-dependent way. Single-cell RNA sequencing analysis confirmed the suppressive profile of PMN-MDSCs at the transcriptomic level and identified CXCR2 as a therapeutic target expressed on PMN-MDSCs. Abrogating PMN-MDSC trafficking by CXCR2-specific small molecule inhibitor during the vaccinia virotherapy exhibited enhanced antitumor efficacy in 3 syngeneic cancer models, through increasing CD8+/MDSC ratios in the TME, activating cytotoxic T lymphocytes, and skewing suppressive TME into an antitumor environment. Our results warrant clinical development of CXCR2 inhibitor in combination with oncolytic virotherapy.


Asunto(s)
Células Supresoras de Origen Mieloide , Viroterapia Oncolítica , Vaccinia , Animales , Ratones , Línea Celular Tumoral , Células Supresoras de Origen Mieloide/patología , Linfocitos T Citotóxicos , Microambiente Tumoral , Vaccinia/patología , Virus Vaccinia
10.
J Clin Invest ; 134(2)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-37962965

RESUMEN

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity, affecting millions of adolescents worldwide, but it lacks a defined theory of etiopathogenesis. Because of this, treatment of AIS is limited to bracing and/or invasive surgery after onset. Preonset diagnosis or preventive treatment remains unavailable. Here, we performed a genetic analysis of a large multicenter AIS cohort and identified disease-causing and predisposing variants of SLC6A9 in multigeneration families, trios, and sporadic patients. Variants of SLC6A9, which encodes glycine transporter 1 (GLYT1), reduced glycine-uptake activity in cells, leading to increased extracellular glycine levels and aberrant glycinergic neurotransmission. Slc6a9 mutant zebrafish exhibited discoordination of spinal neural activities and pronounced lateral spinal curvature, a phenotype resembling human patients. The penetrance and severity of curvature were sensitive to the dosage of functional glyt1. Administration of a glycine receptor antagonist or a clinically used glycine neutralizer (sodium benzoate) partially rescued the phenotype. Our results indicate a neuropathic origin for "idiopathic" scoliosis, involving the dysfunction of synaptic neurotransmission and central pattern generators (CPGs), potentially a common cause of AIS. Our work further suggests avenues for early diagnosis and intervention of AIS in preadolescents.


Asunto(s)
Escoliosis , Animales , Humanos , Adolescente , Escoliosis/genética , Escoliosis/diagnóstico , Escoliosis/cirugía , Glicina/genética , Pez Cebra , Transmisión Sináptica
11.
J Comput Biol ; 31(1): 41-57, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38010500

RESUMEN

Intratumoral heterogeneity and the presence of cancer stem cells are challenging issues in cancer therapy. An appropriate quantification of the stemness of individual cells for assessing the potential for self-renewal and differentiation from the cell of origin can define a measurement for quantifying different cell states, which is important in understanding the dynamics of cancer evolution, and might further provide possible targeted therapies aimed at tumor stem cells. Nevertheless, it is usually difficult to quantify the stemness of a cell based on molecular information associated with the cell. In this study, we proposed a stemness definition method with one-class Hadamard kernel support vector machine (OCHSVM) based on single-cell RNA sequencing (scRNA-seq) data. Applications of the proposed OCHSVM stemness are assessed by various data sets, including preimplantation embryo cells, induced pluripotent stem cells, or tumor cells. We further compared the OCHSVM model with state-of-the-art methods CytoTRACE, one-class logistic regression, or one-class SVM methods with different kernels. The computational results demonstrate that the OCHSVM method is more suitable for stemness identification using scRNA-seq data.


Asunto(s)
Neoplasias , Máquina de Vectores de Soporte , Humanos , Neoplasias/genética , Diferenciación Celular , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos
13.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(6): 1111-1117, 2023 Dec 18.
Artículo en Chino | MEDLINE | ID: mdl-38101797

RESUMEN

Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.


Asunto(s)
Anemia , Lupus Eritematoso Sistémico , Vasculitis por Lupus del Sistema Nervioso Central , Síndrome de Activación Macrofágica , Humanos , Femenino , Adulto , Rituximab/uso terapéutico , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/tratamiento farmacológico , Síndrome de Activación Macrofágica/etiología , Estudios Retrospectivos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Fiebre/tratamiento farmacológico , Eritema/complicaciones , Eritema/tratamiento farmacológico , Hormonas/uso terapéutico , Alopecia/complicaciones , Alopecia/tratamiento farmacológico , Triglicéridos/uso terapéutico , Ferritinas/uso terapéutico
15.
Mater Today Bio ; 23: 100793, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37766900

RESUMEN

A pillar dishe for subculture of 3D cultured cells on hydrogel spots (Matrigel and alginate) have been developed. Cells cultured in 3D in an extracellular matrix (ECM) can retain their intrinsic properties, but cells cultured in 2D lose their intrinsic properties as the cells stick to the bottom of the well. Previously, cells and ECM spots were dispensed on a conventional culture dish for 3D cultivation. However, as the spot shape and location depended on user handling, pillars were added to the dish to realize uniform spot shape and stable subculture, supporting 3D cell culture-based high-throughput screening (HTS). Matrigel and alginate were used as ECMs during 6-passage subculture. The growth rate of lung cancer cell (A549) was higher on Matrigel than on alginate. Cancer cell was subcultured in three dimensions in the proposed pillar dish and used for drug screening and differential gene expression analysis. Interestingly, stemness markers, which are unique characteristics of lung cancer cells inducing drug resistance, were upregulated in 3D-subcultured cells compared with those in 2D-subcultured cells. Additionally, the PI3K/Akt/mTOR, VEGFR1/2, and Wnt pathways, which are promising therapeutic targets for lung cancer, were activated, showing high drug sensitivity under 3D-HTS using the 3D-subcultured cells.

16.
Mar Environ Res ; 191: 106170, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37708617

RESUMEN

In context of testing, screening and monitoring of endocrine-disrupting (ED) type of environmental pollutants, tunicates could possibly represent a particularly interesting group of bioindicator organisms. These primitive chordates are already important model organisms within developmental and genomics research due to their central position in evolution and close relationship to vertebrates. The solitary ascidians, such as the genus Ciona spp. (vase tunicates), could possibly be extra feasible as ED bioindicators. They have a free-swimming, tadpole-like larval stage that develops extremely quickly (<20 h under favorable conditions), has a short life cycle (typically 2-3 months), are relatively easy to maintain in laboratory culture, have fully sequenced genomes, and transgenic embryos with 3D course data of the embryo ontogeny are available. In this article, we discuss possible roles of Ciona spp. (and other solitary ascidians) as ecotoxicological bioindicator organisms in general but perhaps especially for effect studies of contaminants with presumed endocrine disrupting modes of action.


Asunto(s)
Ciona intestinalis , Ciona , Disruptores Endocrinos , Animales , Biomarcadores Ambientales , Disruptores Endocrinos/toxicidad
17.
Chemistry ; 29(66): e202301771, 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-37665775

RESUMEN

Qubits are the basic unit of quantum information and computation. To realize quantum computing and information processing, the decoherence times of qubits must be long enough. Among the studies of molecule-based electron spin qubits, most of the work focused on the ions with the spin S=1/2, where only single-bit gates can be constructed. However, quantum operations require the qubits to interact with each other, so people gradually carry out relevant research in ions or systems with S>1/2 and multilevel states. In this work, a two-dimensional (2D) oxygen-coordinated GdIII NaI -based oxamato supramolecular coordination framework, Na[Gd(4-HOpa)4 (H2 O)] ⋅ 2H2 O (1, 4-HOpa=N-4-hydroxyphenyloxamate), was selected as a possible carrier of qubit. The field-induced slow magnetic relaxation shows this system has phonon bottleneck (PB) effect at low temperatures with a very weak magnetic anisotropy. The pulse electron paramagnetic resonance studies show the spin-lattice and spin-spin relaxation times are T1 =1.66 ms at 4 K and Tm =4.25 µs at 8 K for its diamagnetically diluted sample (1Gd0.12 %). It suggested that the relatively long decoherence time is mainly ascribed to its near isotropic and the PB effect from resonance phonon trapped for pure sample, while the dilution further improves its qubit performance.

18.
Angew Chem Int Ed Engl ; 62(42): e202309852, 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37635684

RESUMEN

Conventional solid electrolyte frameworks typically consist of anions such as sulphur, oxygen, chlorine, and others, leading to inherent limitations in their properties. Despite the emergence of sulphide, oxide, and halide-based solid electrolytes for all-solid-state batteries, their utilization is hampered by issues, including the evolution of H2 S gas, the need for expensive elements, and poor contact. Here, we first introduce Prussian Blue analogue (PBA) open-framework structures as a solid electrolyte that demonstrates appreciable Na+ conductivity (>10-2 mS cm-1 ). We delve into the relationship between Na+ conductivity and the lattice parameter of N-coordinated transition metal, which is attributed to the reduced interaction between Na+ and the framework, corroborated by the distribution of relaxation times and density functional theory calculations. Among the five PBAs studied, Mn-PBA have exhibited the highest Na+ conductivity of 9.1×10-2 mS cm-1 . Feasibility tests have revealed that Mn-PBA have maintained a cycle retention of 95.1 % after 80cycles at 30 °C and a C-rate of 0.2C. Our investigation into the underlying mechanisms that play a significant role in governing the conductivity and kinetics of these materials contributes valuable insights for the development of alternative strategies to realize all-solid-state batteries.

19.
Adv Mater ; 35(38): e2303199, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37395728

RESUMEN

The majority of waste-heat energy exists in the form of low-grade heat (<100 °C), which is immensely difficult to convert into usable energy using conventional energy-harvesting systems. Thermally regenerative electrochemical cycles (TREC), which integrate battery and thermal-energy-harvesting functionalities, are considered an attractive system for low-grade heat harvesting. Herein, the role of structural vibration modes in enhancing the efficacy of TREC systems is investigated. How changes in bonding covalency, influenced by the number of structural water molecules, impact the vibration modes is analyzed. It is discovered that even small amounts of water molecules can induce the A1g stretching mode of cyanide ligands with strong structural vibration energy, which significantly contributes to a larger temperature coefficient (ɑ) in a TREC system. Leveraging these insights, a highly efficient TREC system using a sodium-ion-based aqueous electrolyte is designed and implemented. This study provides valuable insights into the potential of TREC systems, offering a deeper understanding of the intrinsic properties of Prussian Blue analogs regulated by structural vibration modes. These insights open up new possibilities for enhancing the energy-harvesting capabilities of TREC systems.

20.
Sci Rep ; 13(1): 11679, 2023 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-37468491

RESUMEN

For the comprehensive evaluation of metal artifact reduction (MAR) technique, not only the removal of metal artifacts but also the evaluation of the area restored by MAR is required. We propose a method to comprehensively evaluate the effect by MAR in this study. We have conducted the computed tomography scan to acquire both the evaluation image and the reference image for the full-reference based evaluation. The evaluation image and reference image were reconstructed into 24 image sets according to the tube potentials, image reconstruction method, and use of the MAR technique. Images of two different positions were selected according to the distance from metal and material (bone, tissue) distribution, and bone and tissue were automatically segmented in both evaluation and reference images. The values of full width at half the maximum (FWHM) and centroid were extracted after Gaussian modeling of each segmented region. Then, we computed four evaluation metrics (FWHMNM: non-MAR to non-metal ratio of FWHM, FWHMM: MAR to non-metal ratio of FWHM, CENTNM: non-MAR to non-metal ratio of centroid, CENTM: MAR to non-metal ratio of centroid), and the MAR image and non-MAR image were compared. The overlap ratio automatically segmented from the evaluation image and reference image were position 1 (bone: 99.61%, tissue: 99.23%) with 80 kVp, position 1 (bone: 99.32%, tissue: 99.56%) with 120 kVp, position 2 (bone: 99.20%, tissue: 99.73%) with 80 kVp, and position 2 (bone: 99.23%, tissue: 99.67%) with 120 kVp. The FWHMNM showing the change of image pixel value by metal artifact was calculated as (bone: 1.32-1.46, tissue: 1.08-1.16) at 80 kVp and (bone: 1.19-1.27, tissue: 1.02-1.05) at 120 kVp. More metal artifacts occurred at 80 kVp tube potential. Regardless of the tube potential and image reconstruction method, the MAR showed an overall artifact reduction effect (1 < FWHMM < FWHMNM). However, distortion of pixel values occurred due to the MAR in regions where metal artifacts were high in proximity to metal (1 < FWHMNM < FWHMM). Overall, the average value of the medium was maintained (CENTM: 0.98-1.03) after MAR application, but there was a change of image value in region around the metal (CENTM: 0.97-1.11). In this study, we propose a new method to evaluate the effect of metal artifacts and MAR technique using full-reference based method. Metal artifacts, effect of MAR technique, and side-effect caused by MAR technique were quantitatively analyzed through proposed method. There are some limitations in applying it to clinical imaging since our method is a reference-based evaluation. However, our experimental results were important for understanding the effects of the MAR technique and its functional properties.


Asunto(s)
Artefactos , Procesamiento de Imagen Asistido por Computador , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos , Metales , Fantasmas de Imagen , Tomografía Computarizada por Rayos X/métodos
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