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Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to a lack of appropriate human models. Here, we engineered human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity. A CRISPRi screen of genes associated with Tau pathobiology identified over 500 genetic modifiers of seeding-induced Tau propagation, including retromer VPS29 and genes in the UFMylation cascade. In progressive supranuclear palsy (PSP) and Alzheimer's Disease (AD) brains, the UFMylation cascade is altered in neurofibrillary-tangle-bearing neurons. Inhibiting the UFMylation cascade in vitro and in vivo suppressed seeding-induced Tau propagation. This model provides a robust platform to identify novel therapeutic strategies for 4R tauopathy.
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Células Madre Pluripotentes Inducidas , Neuronas , Tauopatías , Proteínas tau , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Proteínas tau/metabolismo , Tauopatías/metabolismo , Tauopatías/patología , Neuronas/metabolismo , Neuronas/patología , Animales , Ratones , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/genética , Encéfalo/metabolismo , Encéfalo/patología , Parálisis Supranuclear Progresiva/metabolismo , Parálisis Supranuclear Progresiva/patología , Parálisis Supranuclear Progresiva/genética , Diferenciación Celular , Mutación , AutofagiaRESUMEN
Adventitious root (AR) formation plays an important role in vegetatively propagated plants. Cytokinin (CK) inhibits AR formation, but the molecular mechanisms driving this process remain unknown. In this study, we confirmed that CK content is related to AR formation and further revealed that a high auxin/CK ratio was beneficial to AR formation in apple (Malus domestica). A correlation between expression of CK-responsive TEOSINTE BRANCHED1, CYCLOIDEA, and PCF17 (MdTCP17) and AR formation in response to CK was identified, and overexpression of MdTCP17 in transgenic apple inhibited AR formation. Yeast two-hybrid, bimolecular fluorescence complementation, and co-immunoprecipitation assays revealed an interaction between MdTCP17 and WUSCHEL-RELATED HOMEOBOX11 (MdWOX11), and a significant correlation between the expression of MdWOX11 and AR ability. Overexpression of MdWOX11 promoted AR primordium formation in apple, while interference of MdWOX11 inhibited AR primordium production. Moreover, a positive correlation was found between MdWOX11 and LATERAL ORGAN BOUNDARIES DOMAIN29 (MdLBD29) expression, and yeast one-hybrid, dual luciferase reporter, and ChIP-qPCR assays verified the binding of MdWOX11 to the MdLBD29 promoter with a WOX-box element in the binding sequence. Furthermore, MdTCP17 reduced the binding of MdWOX11 and MdLBD29 promoters, and coexpression of MdTCP17 and MdWOX11 reduced MdLBD29 expression. Together, these results explain the function and molecular mechanism of MdTCP17-mediated CK inhibition of AR primordium formation, which could be used to improve apple rootstocks genetically.
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Citocininas , Malus , Citocininas/metabolismo , Malus/genética , Malus/metabolismo , Saccharomyces cerevisiae/metabolismo , Raíces de Plantas/metabolismo , Ácidos Indolacéticos/metabolismo , Regulación de la Expresión Génica de las Plantas/genéticaRESUMEN
Micropeptides encoded by short open reading frames (sORFs) within long noncoding RNAs (lncRNAs) are beginning to be discovered and characterized as regulators of biological and pathological processes. Here, we find that lncRNA Dleu2 encodes a 17-amino-acid micropeptide, which we name Dleu2-17aa, that is abundantly expressed in T cells. Dleu2-17aa promotes inducible regulatory T (iTreg) cell generation by interacting with SMAD Family Member 3 (Smad3) and enhancing its binding to the Foxp3 conserved non-coding DNA sequence 1 (CNS1) region. Importantly, the genetic deletion of Dleu2-17aa in mice by start codon mutation impairs iTreg generation and worsens experimental autoimmune encephalomyelitis (EAE). Conversely, the exogenous supplementation of Dleu2-17aa relieves EAE. Our findings demonstrate an indispensable role of Dleu2-17aa in maintaining immune homeostasis and suggest therapeutic applications for this peptide in treating autoimmune diseases.
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Encefalomielitis Autoinmune Experimental , ARN Largo no Codificante , Animales , Ratones , Autoinmunidad , Péptidos/metabolismo , ARN Largo no Codificante/genética , Linfocitos T Reguladores/metabolismoRESUMEN
Psoriasis is a common inflammatory skin disorder with no cure. Mesenchymal stem cells (MSCs) have immunomodulatory properties for psoriasis, but the therapeutic efficacies varied, and the molecular mechanisms were unknown. In this study, we improved the efficacy by enhancing the immunomodulatory effects of umbilical cord-derived MSCs (UC-MSCs). UC-MSCs stimulated by TNF-α and IFN-γ exhibited a better therapeutic effect in a mouse model of psoriasis. Single-cell RNA sequencing revealed that the stimulated UC-MSCs overrepresented a subpopulation expressing high tryptophanyl-tRNA synthetase 1 (WARS1). WARS1-overexpressed UC-MSCs treat psoriasis-like skin inflammation more efficiently than control UC-MSCs by restraining the proinflammatory macrophages. Mechanistically, WARS1 maintained a RhoA-Akt axis and governed the immunomodulatory properties of UC-MSCs. Together, we identify WARS1 as a master regulator of UC-MSCs with enhanced immunomodulatory capacities, which paves the way for the directed modification of UC-MSCs for escalated therapeutic efficacy.
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Inmunomodulación , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/inmunología , Animales , Ratones , Humanos , Trasplante de Células Madre Mesenquimatosas/métodos , Triptófano-ARNt Ligasa/genética , Psoriasis/inmunología , Psoriasis/terapia , Modelos Animales de Enfermedad , Análisis de la Célula Individual , Análisis de Secuencia de ARN , Cordón Umbilical/citología , Cordón Umbilical/inmunología , Ratones Endogámicos C57BL , Células CultivadasRESUMEN
The cutting technique is extensively used in tea breeding, with key emphasis on promoting the growth of adventitious roots (ARs). Despite its importance in tea cultivation, the mechanisms underlying AR development in tea remain unclear. In this study, we demonstrated the essential role of auxins in the initiation and progression of AR and established that the application of exogenous 1-naphthaleneacetic acid-enhanced AR formation in tissue-cultured seedlings and cuttings. Then, we found that the auxin-responsive transcription factor CsSPL9 acted as a negative regulator of AR development by reducing the levels of free indole-3-acetic acid (IAA) in tea plants. Furthermore, we identified CsGH3.4 as a downstream target of CsSPL9, which was activated by direct binding to its promoter. CsGH3.4 also inhibited AR development and maintained low levels of free IAA. Thus, these results revealed the inhibitory effect of the auxin-responsive CsSPL9-CsGH3.4 module on AR development by reducing free IAA levels in tea. These findings have significant theoretical and practical value for enhancing tea breeding practices.
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Camellia sinensis , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos , Proteínas de Plantas , Raíces de Plantas , Factores de Transcripción , Ácidos Indolacéticos/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Raíces de Plantas/genética , Camellia sinensis/crecimiento & desarrollo , Camellia sinensis/genética , Camellia sinensis/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Ácidos Naftalenoacéticos/farmacología , Plantones/crecimiento & desarrollo , Plantones/genética , Plantones/metabolismo , Regiones Promotoras GenéticasRESUMEN
Asthenoteratozoospermia, defined as reduced sperm motility and abnormal sperm morphology, is a disorder with considerable genetic heterogeneity. Although previous studies have identified several asthenoteratozoospermia-associated genes, the etiology remains unknown for the majority of affected men. Here, we performed whole-exome sequencing on 497 unrelated men with asthenoteratozoospermia and identified DNHD1 bi-allelic variants from eight families (1.6%). All detected variants were predicted to be deleterious via multiple bioinformatics tools. Hematoxylin and eosin (H&E) staining revealed that individuals with bi-allelic DNHD1 variants presented striking abnormalities of the flagella; transmission electron microscopy (TEM) further showed flagellar axoneme defects, including central pair microtubule (CP) deficiency and mitochondrial sheath (MS) malformations. In sperm from fertile men, DNHD1 was localized to the entire flagella of the normal sperm; however, it was nearly absent in the flagella of men with bi-allelic DNHD1 variants. Moreover, abundance of the CP markers SPAG6 and SPEF2 was significantly reduced in spermatozoa from men harboring bi-allelic DNHD1 variants. In addition, Dnhd1 knockout male mice (Dnhd1â/â) exhibited asthenoteratozoospermia and infertility, a finding consistent with the sperm phenotypes present in human subjects with DNHD1 variants. The female partners of four out of seven men who underwent intracytoplasmic sperm injection therapy subsequently became pregnant. In conclusion, our study showed that bi-allelic DNHD1 variants cause asthenoteratozoospermia, a finding that provides crucial insights into the biological underpinnings of this disorder and should assist with counseling of affected individuals.
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Alelos , Astenozoospermia/genética , Axonema/genética , Dineínas/genética , Flagelos/genética , Predisposición Genética a la Enfermedad , Mutación , Animales , Astenozoospermia/diagnóstico , Axonema/patología , Biología Computacional/métodos , Análisis Mutacional de ADN , Modelos Animales de Enfermedad , Flagelos/patología , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , Infertilidad Masculina/genética , Masculino , Ratones , Ratones Noqueados , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Linaje , Fenotipo , Análisis de Semen , Cola del Espermatozoide/patología , Cola del Espermatozoide/ultraestructura , Secuenciación del ExomaRESUMEN
Respiratory viral infections remain a leading cause of morbidity and mortality. Using a murine model of human metapneumovirus (HMPV), we identified recruitment of a C1q-expressing inflammatory monocyte population concomitant with viral clearance by adaptive immune cells. Genetic ablation of C1q led to reduced CD8+ T cell function. Production of C1q by a myeloid lineage was necessary to enhance CD8+ T cell function. Activated and dividing CD8+ T cells expressed a C1q receptor, gC1qR. Perturbation of gC1qR signaling led to altered CD8+ T cell IFN-γ production, metabolic capacity, and cell proliferation. Autopsy specimens from fatal respiratory viral infections in children demonstrated diffuse production of C1q by an interstitial population. Humans with severe COVID-19 infection also demonstrated upregulation of gC1qR on activated and rapidly dividing CD8+ T cells. Collectively, these studies implicate C1q production from monocytes as a critical regulator of CD8+ T cell function following respiratory viral infection. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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Autophagy plays a pivotal role in physiology and pathophysiology, including cancer. Mechanisms of autophagy dysregulation in cancer remain elusive. Loss of function of TRIM28, a multifunction protein, is seen in familial kidney malignancy, but the mechanism by which TRIM28 contributes to the etiology of kidney malignancy is unclear. In this study, we show TRIM28 retards kidney cancer cell proliferation through inhibiting autophagy. Mechanistically, we find TRIM28 promotes ubiquitination and proteasome-mediated degradation of transcription factor TFE3, which is critical for autophagic gene expression. Genetic activation of TFE3 due to gene fusion is known to cause human kidney malignancy, but whether and how transcription activation by TFE3 involves chromatin changes is unclear. Here, we find another mode of TFE3 activation in human renal carcinoma. We find that TFE3 is constitutively localized to the cell nucleus in human and mouse kidney cancer, where it increases autophagic gene expression and promotes cell autophagy as well as proliferation. We further uncover that TFE3 interacts with and recruits histone H3K27 demethylase KDM6A for autophagic gene upregulation. We reveal that KDM6A contributes to expression of TFE3 target genes through increasing H3K4me3 rather than demethylating H3K27. Collectively, in this study, we identify a functional TRIM28-TFE3-KDM6A signal axis, which plays a critical role in kidney cancer cell autophagy and proliferation.
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Carcinoma de Células Renales , Neoplasias Renales , Proteína 28 que Contiene Motivos Tripartito , Animales , Humanos , Ratones , Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Carcinoma de Células Renales/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Histona Demetilasas/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Proteína 28 que Contiene Motivos Tripartito/genética , Proteína 28 que Contiene Motivos Tripartito/metabolismoRESUMEN
The growing trend of bilingual education between Chinese and English has contributed to a rise in the number of early bilingual children, who were exposed to L2 prior to formal language instruction of L1. The L2-L1 transfer effect in an L1-dominant environment has been well established. However, the threshold of L2 proficiency at which such transfer manifests remains unclear. This study investigated the behavioral and neural processes involved when manipulating phonemes in an auditory phonological task to uncover the transfer effect in young bilingual children. Sixty-two first graders from elementary schools in Taiwan were recruited in this study (29 Chinese monolinguals, 33 Chinese-English bilinguals). The brain activity was measured using fNIRS (functional near-infrared spectroscopy). Bilingual children showed right lateralization to process Chinese and left lateralization to process English, which supports more on the accommodation effect within the framework of the assimilation-accommodation hypothesis. Also, compared to monolinguals, bilingual children showed more bilateral frontal activation in Chinese, potentially reflecting a mixed influence from L2-L1 transfer effects and increased cognitive load of bilingual exposure. These results elucidate the developmental adjustments in the neural substrates associated with early bilingual exposure in phonological processing, offering valuable insights into the bilingual learning process.
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Multilingüismo , Niño , Humanos , Lingüística , ChinaRESUMEN
Hydrogen peroxide (H2O2) overexpressed in mitochondria has been regarded as a key biomarker in the pathological processes of various diseases. However, there is currently a lack of suitable mitochondria-targetable near-infrared (NIR) probes for the visualization of H2O2 in multiple diseases, such as PM2.5 exposure-induced lung injury, hepatic ischemia-reperfusion injury (HIRI), nonalcoholic fatty liver (NAFL), hepatic fibrosis (HF), and malignant tumor tissues containing clinical cancer patient samples. Herein, we conceived a novel NIR fluorescent probe (HCy-H2O2) by introducing pentafluorobenzenesulfonyl as a H2O2 sensing unit into the NIR hemicyanine platform. HCy-H2O2 exhibits good sensitivity and selectivity toward H2O2, accompanied by a remarkable "turn-on" fluorescence signal at 720 nm. Meanwhile, HCy-H2O2 has stable mitochondria-targetable ability and permits monitoring of the up-generated H2O2 level during mitophagy. Furthermore, using HCy-H2O2, we have successfully observed an overproduced mitochondrial H2O2 in ambient PM2.5 exposure-induced lung injury, HIRI, NAFL, and HF models through NIR fluorescence imaging. Significantly, the visualization of H2O2 has been achieved in both tumor-bear mice as well as surgical specimens of cancer patients, making HCy-H2O2 a promising tool for cancer diagnosis and imaging-guided surgery.
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Colorantes Fluorescentes , Peróxido de Hidrógeno , Mitocondrias , Imagen Óptica , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Peróxido de Hidrógeno/metabolismo , Animales , Mitocondrias/metabolismo , Mitocondrias/química , Ratones , Humanos , Lesión Pulmonar/diagnóstico por imagen , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/metabolismo , Rayos InfrarrojosRESUMEN
Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.
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In order to improve the safety of spacecraft, the research on artificial neural network and digital twin technology based on, to our best knowledge, a novel fiber Bragg grating (FBG) sensor array is proposed for intelligent sensing monitoring of spacecraft on-orbit collisions. Femtosecond FBG arrays were fabricated on the novel oxide-doped fiber by point-by-point writing technique. The femtosecond FBG is analyzed using the time-dependent perturbation theory of quantum mechanics. The FBG array can achieve high-temperature measurement of 1100 °C and large strain measurement of 15000 µÎµ. The sensing arrays were deployed on the surface of the spacecraft. Constructed the multi-layer perceptron neural network structure and convolutional neural network structure. 1200 samples were trained. Conducted model accuracy testing. The accuracy rate is above 98%, and accuracy verification has been implemented. The digital twin model was designed based on various data such as strain and temperature of the spacecraft structure under impact monitored by FBG sensors. A precise mapping has been formed between the physical entities of spacecraft and digital twins. Empower spacecraft with functions such as self-monitoring, judgment, and response. To ensure the stable and safe operation of spacecraft.
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Compared to the integer-order vector field, the fractional-order vector field has an additional degree of control freedom, which will bring rich photophysical properties and what we believe to be novel nonlinear optical phenomena. In this work, we theoretically and experimentally investigate the focusing, propagation, and spatial self-phase modulation (SSPM) of fractional-order linearly polarized vector fields (FLPVFs). It is shown that the weak focusing field of FLPVF exhibits an asymmetric intensity distribution. Intriguingly, its state of polarization (SoP) has a hybrid polarization distribution. When this focused FLPVF propagates to the far field in free space, its SoP degenerates into a localized linearly polarization distribution. However, after the focused FLPVF passes through an isotropic nonlinear Kerr medium, its SoP exhibits a hybrid polarization distribution. Additionally, unlike the self-diffraction intensity pattern of integer-order linearly polarized vector field (ILPVF) with a concentric multi-ring structure, the SSPM pattern of FLPVF is a symmetry broken self-diffraction intensity pattern. The presented work provides a nonlinear optics approach for manipulating both the SoP and intensity distributions of the light field.
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A kind of curved long-period fiber grating(CLPFG) engraved by CO2 laser based on oxide-doped fiber was designed to monitor the structural integrity of propellant. The mechanical damage characteristics of the propellant were analyzed. The sensor model is constructed and the refractive index modulation characteristics of the CLPFG are analyzed. The strain coupling characteristics and the strain transfer efficiency of the interface between the CLPFG and the propellant are clarified. Propellant modules with implanted CLPFG were fabricated. The novel grating sensor has been effectively coated and structurally packaged. Conducted experiments on strain and temperature of propellant modules. The large strain measurement of propellant from 0 µÎµ to 24000 µÎµ is realized. Solved the thorny problem of large strain measurement for propellants. In addition, the temperature discrimination measurement in the temperature range of 30 â to 250 â can be realized. Sensor exhibit extremely high stability characteristics and has good compatibility with propellants. The sensor implantation and extraction structure has been designed to improve the survival rate of the sensor inside the solid rocket motors (SRM). Sensors can accurately measure the mechanical and thermal state parameters of propellants, providing effective data support for the health management of SRM.
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In this study, a novel method that can detect carbon dioxide (CO2) concentration and realize temperature immunity based on only one fiber Bragg grating (FBG) is proposed. The outstanding contribution lies in solving the temperature crosstalk issue of FBG and ensuring the accuracy of detection results under the condition of anti-temperature interference. To achieve immunity to temperature interference without changing the initial structure of FBG, the optical fiber cladding of FBG and adjacent optical fiber cladding at both ends of FBG are modified by a polymer coating. Moreover, a universal immune temperature demodulation algorithm is derived. The experimental results demonstrate that the temperature response sensitivity of the improved FBG is controlled within the range of 0.00407â nm/°C. Compared with the initial FBG (the temperature sensitivity of the initial FBG is 0.04â nm/°C), it decreases by nearly 10 times. Besides, the gas response sensitivity of FBG reaches 1.6 pm/ppm and has overwhelmingly ideal linearity. The detection error results manifest that the gas concentration error in 20 groups of data does not exceed 3.16â ppm. The final reproducibility research shows that the difference in detection sensitivity between the two sensors is 0.08 pm/ppm, and the relative error of linearity is 1.07%. In a word, the proposed method can accurately detect the concentration of CO2 gas and is efficiently immune to temperature interference. The sensor we proposed has the advantages of a simple production process, low cost, and satisfactory reproducibility. It also has the prospect of mass production.
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BACKGROUND: The association between the triglyceride-glucose (TyG) index and subclinical left ventricular (LV) systolic dysfunction in obese patients remains unclear. This study aimed to investigate the relationship between the TyG index and LV global longitudinal strain (GLS) in obese patients. METHODS: A total of 1028 obese patients from January 2019 to January 2024 were included in the present study. Clinical parameters and biochemical and echocardiographic data were obtained from the participants. LV GLS was obtained from the GE EchoPAC workstation for evaluating subclinical LV function. The TyG index was calculated as Ln (fasting TG [mg/dL] × fasting glucose [mg/dL]/2). LV GLS was compared between obese patients with a high TyG index and those with a low TyG index. RESULTS: Obese patients with a high TyG index had greater incidences of hypertension, diabetes mellitus and hyperlipidaemia. The LV GLS was significantly lower in the high TyG index group than in the low TyG index group (P = 0.01). After adjusting for sex, age, body mass index, heart rate, hypertension, diabetes mellitus, dyslipidaemia, blood urea nitrogen, serum creatinine, LV mass and LV hypertrophy, the TyG index remained an independent risk indicator related to an LV GLS < 20% (OR: 1.520, 95% CI: 1.040 to 2.221; P = 0.031). CONCLUSIONS: We concluded that an increase in the TyG index is independently associated with subclinical LV systolic dysfunction in obese patients.
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Enfermedades Asintomáticas , Biomarcadores , Glucemia , Obesidad , Triglicéridos , Disfunción Ventricular Izquierda , Función Ventricular Izquierda , Humanos , Masculino , Femenino , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/epidemiología , Obesidad/diagnóstico , Obesidad/sangre , Obesidad/fisiopatología , Obesidad/epidemiología , Obesidad/complicaciones , Persona de Mediana Edad , Triglicéridos/sangre , Glucemia/metabolismo , Biomarcadores/sangre , Adulto , Factores de Riesgo , Medición de Riesgo , Sístole , Anciano , Estudios Transversales , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
Kidney renal clear cell carcinoma (KIRC) is a highly immune-infiltrated kidney cancer with the highest mortality rate and the greatest potential for invasion and metastasis. Solute carrier family 11 member1 (SLC11A1) is a phagosomal membrane protein located in monocytes and plays a role in innate immunity, autoimmune diseases, and infection, but its expression and biological role in KIRC is still unknown. In this study, we sought to investigate the potential value of SLC11A1 according to tumor growth and immune response in KIRC. TIMER and UALCAN database was used to analyze the expression feature and prognostic significance of SLC11A1 and its correlation with immune-related biomarkers in KIRC. Proliferation, migration, and invasion were measured using colony formation, EdU, and transwell assays. Role of SLC11A1 on KIRC tumor growth was examined by the xenograft tumor model in vivo. Effects of KIRC cells on macrophage polarization and the proliferation and apoptosis of CD8+ T cells were analyzed using flow cytometry assays. Herein, SLC11A1 was highly expressed in KIRC tissues and cell lines. SLC11A1 downregulation repressed KIRC cell proliferation, migration, invasion, macrophage, and lymphocyte immunity in vitro, as well as hindered tumor growth in vivo. SLC11A1 is significantly correlated with immune cell infiltration and immune-related biomarkers. In KIRC patients, SLC11A1 is highly expressed and positively correlated with the immune-related factors CCL2 and PD-L1. SLC11A1 induced CCL2 and PD-L1 expression, thereby activating the JAK/STAT3 pathway. SLC11A1 deficiency constrained KIRC cell malignant phenotypes and immune response via regulating CCL2 and PD-L1-mediated JAK/STAT3 pathway, providing a promising therapeutic target for KIRC treatment.
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Carcinoma de Células Renales , Proteínas de Transporte de Catión , Proliferación Celular , Neoplasias Renales , Microambiente Tumoral , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/metabolismo , Humanos , Neoplasias Renales/patología , Neoplasias Renales/inmunología , Neoplasias Renales/genética , Animales , Línea Celular Tumoral , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Ratones , Movimiento Celular , Progresión de la Enfermedad , Ratones Desnudos , Linfocitos T CD8-positivos/inmunología , Apoptosis , Femenino , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Masculino , Transducción de Señal , Invasividad Neoplásica , Regulación Neoplásica de la Expresión Génica , Ratones Endogámicos BALB CRESUMEN
AIMS: To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S). MATERIALS AND METHODS: Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months. RESULTS: Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A1c (HbA1c) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years. CONCLUSIONS: In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally.
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Diabetes Mellitus Tipo 1 , Cetoacidosis Diabética , Niño , Humanos , Adulto Joven , Adulto , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Cetoacidosis Diabética/epidemiología , Estudios Retrospectivos , Estudios Prospectivos , China/epidemiología , Sistema de RegistrosRESUMEN
BACKGROUND: Dual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records. METHODS: This study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups. RESULTS: The study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn't affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups. CONCLUSIONS: RFID tag witnessing doesn't negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist's confidence.
Asunto(s)
Transferencia de Embrión , Fertilización In Vitro , Dispositivo de Identificación por Radiofrecuencia , Flujo de Trabajo , Humanos , Femenino , Fertilización In Vitro/métodos , Embarazo , Estudios Retrospectivos , Transferencia de Embrión/métodos , Dispositivo de Identificación por Radiofrecuencia/métodos , Laboratorios , Adulto , Masculino , Índice de Embarazo , Resultado del EmbarazoRESUMEN
The temperature dependence of the dynamic contact angles (DCAs) of water on a metallic surface remains unclear, especially under elevated pressures. Here in this work, the advancing and receding contact angles (RCAs), as well as the contact angle hysteresis (CAH), of water on stainless-steel 316 (SS316) surfaces were studied using the dynamic sessile drop method for temperatures up to 300 °C and pressures up to 10 MPa. It was found that the temperature dependence of the DCAs exhibits a different pattern as compared to the piecewise linear decline of static contact angles. The advancing contact angle (ACA) remains nearly constant and does not decrease until the temperature becomes close to the saturated temperature. The decrease in ACA is attributed to evaporation, which reduces the advancement of energy barrier. The RCA linearly declines below 120 °C and remains stable above 120 °C. The increasing temperature enhances the pinning effect and changes the droplet receding mode. Under all pressures tested, the CAH demonstrates a "increase-constant-decrease" trilinear relationship with temperature. Furthermore, the mean solid surface entropy and solid-gas interfacial tension of SS316 were estimated to be 0.1152 mJ/(m2·°C) and 61.49 mJ/m2, respectively.