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Strongly-correlated transition-metal oxides are widely known for their various exotic phenomena. This is exemplified by rare-earth nickelates such as LaNiO3, which possess intimate interconnections between their electronic, spin, and lattice degrees of freedom. Their properties can be further enhanced by pairing them in hybrid heterostructures, which can lead to hidden phases and emergent phenomena. An important example is the LaNiO3/LaTiO3 superlattice, where an interlayer electron transfer has been observed from LaTiO3 into LaNiO3 leading to a high-spin state. However, macroscopic emergence of magnetic order associated with this high-spin state has so far not been observed. Here, by using muon spin rotation, x-ray absorption, and resonant inelastic x-ray scattering, direct evidence of an emergent antiferromagnetic order with high magnon energy and exchange interactions at the LaNiO3/LaTiO3 interface is presented. As the magnetism is purely interfacial, a single LaNiO3/LaTiO3 interface can essentially behave as an atomically thin strongly-correlated quasi-2D antiferromagnet, potentially allowing its technological utilization in advanced spintronic devices. Furthermore, its strong quasi-2D magnetic correlations, orbitally-polarized planar ligand holes, and layered superlattice design make its electronic, magnetic, and lattice configurations resemble the precursor states of superconducting cuprates and nickelates, but with an Sâ1 spin state instead.
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Post-transplantation immune rejection remains an important factor for transplant patients. However, conventional immunosuppressants are associated with substantial adverse effects. Natural immunosuppressants present a promising alternative to conventional counterparts, boasting exceptional biological activity, minimal toxicity and reduced side effects. We identified carvacrol as a prospective immunosuppressive agent following T cell proliferation experiment and validated carvacrol's immunosuppressive efficacy in the murine allogeneic skin graft model. T cell proliferation assay was used to screen natural small molecule compounds and the immunosuppressive effect of compounds was evaluated in MHC-mismatched murine allogeneic skin graft model. H&E and immunohistochemical staining were applied to evaluate the pathological grade. Furthermore, flow cytometry was uitlized to analyse the immunophenotype changes of immune cells. Western blotting and q-PCR were used to detect the expression of key molecules in macrophages. In vitro, carvacrol demonstrates significant inhibition of the proliferation of CD4+ T and CD8+ T cells. It notably reduces inflammatory factor expression within the allografts, suppresses T cell differentiation toward Th1 phenotype and expansion. Furthermore, carvacrol prominently hinders M1-type macrophages polarization by activating Wnt signaling. Notably, the anti-rejection efficacy of carvacrol was significantly weakened upon the removal of macrophages in mice using chlorophosphate liposomes. Carvacrol could significantly inhibit T cell proliferation, alleviate graft rejection and has outstanding toxicological safety. The molecular mechanism of the anti-rejection effect of carvacrol is closely related to its mediating activation of macrophage Wnt pathway, inhibiting M1 polarization and inducing T cell differentiation.
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Materials demonstrating positive thermal expansion (PTE) or negative thermal expansion (NTE) are quite common, whereas those exhibiting zero thermal expansion (ZTE) are notably scarce. In this work, we identify the mechanical descriptors, namely in-plane tensile stiffness and out-of-plane bending stiffness, that can effectively classify PTE and NTE 2D crystals. By utilizing high throughput calculations and the state-of-the-art symbolic regression method, these descriptors aid in the discovery of ZTE or 2D Invar monolayers with the linear thermal expansion coefficient (LTEC) within ±2 × 10-6 K-1 in the middle range of temperatures. Additionally, the descriptors assist the discovery of large PTE and NTE 2D monolayers with the LTEC larger than ±15 × 10-6 K-1, which are so-called 2D anti-Invar monolayers. Advancing our understanding of materials with exceptionally low or high thermal expansion is of substantial scientific and technological interest, particularly in the development of next-generation electronics at the nanometer or even Ångstrom scale.
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Inspired by biological channels, achieving precise separation of ion/water and ion/ion requires finely tuned pore sizes at molecular dimensions and deliberate exposure of charged groups. Covalent organic frameworks (COFs), a class of porous crystalline materials, offer well-defined nanoscale pores and diverse structures, making them excellent candidates for nanofluidic channels that facilitate ion and water transport. In this study, we perform molecular simulations to investigate the structure and kinetics of water and ions confined within the typical COFs with varied exposure of charged groups. The COFs exhibit vertically arrayed nanochannels, enabling diffusion coefficients of water molecules within COFs to remain within the same order of magnitude as in the bulk. The motion of water molecules manifests in two distinct modes, creating a mobile hydration layer around acid groups. The ion diffusion within COFs displays a notable disparity between monovalent (M+) and divalent (M2+) cations. As a result, the selectivity of M+/M2+ can exceed 100, while differentiation among M+ is less pronounced. In addition, our simulations indicate a high rejection (R > 98%) in COFs, indicating their potential as ideal materials for desalination. The chemical flexibility of COFs indicates that would hold significant promise as candidates for advanced artificial ion channels and separation membranes.
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Strongly correlated materials respond sensitively to external perturbations such as strain, pressure, and doping. In the recently discovered superconducting infinite-layer nickelates, the superconducting transition temperature can be enhanced via only ~ 1% compressive strain-tuning with the root of such enhancement still being elusive. Using resonant inelastic x-ray scattering (RIXS), we investigate the magnetic excitations in infinite-layer PrNiO2 thin films grown on two different substrates, namely SrTiO3 (STO) and (LaAlO3)0.3(Sr2TaAlO6)0.7 (LSAT) enforcing different strain on the nickelates films. The magnon bandwidth of PrNiO2 shows only marginal response to strain-tuning, in sharp contrast to the enhancement of the superconducting transition temperature Tc in the doped superconducting samples. These results suggest the bandwidth of spin excitations of the parent compounds is similar under strain while Tc in the doped ones is not, and thus provide important empirics for the understanding of superconductivity in infinite-layer nickelates.
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Glucocorticoid-induced osteoporosis (GIOP) is the common reason for secondary osteoporosis. Dendrobine (DEN) is the major biologically active component of Dendrobium officinale with anti-inflammatory and antiaging properties. Whether DEN could alleviate osteogenic inhibition in GIOP rats is still unknown. The influence on osteogenic function caused by DEN on dexamethasone-treated bone marrow mesenchymal stem cells and rats was observed. The in vitro results showed that DEN reversed the inhibition of osteogenic differentiation by dexamethasone. Moreover, DEN supplementation attenuated dexamethasone-induced bone loss in vivo. DEN activated JNK and p38 MAPK pathways and restrained GR nuclear translocation, which could be prevented by the JNK (SP600125) or p38 (SB203580) pathway inhibitor. This study verified that DEN alleviated dexamethasone-induced nuclear translocation of GR, and inhibition of osteogenesis via JNK and p38 pathways, laying the foundation for DEN as a therapeutic agent for GIOP.
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Glucocorticoides , Células Madre Mesenquimatosas , Osteogénesis , Osteoporosis , Ratas Sprague-Dawley , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Humanos , Masculino , Ratas , Diferenciación Celular/efectos de los fármacos , Dexametasona/efectos adversos , Glucocorticoides/efectos adversos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismo , Osteoporosis/inducido químicamente , Osteoporosis/prevención & control , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Extractos Vegetales/farmacología , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genéticaRESUMEN
In recent years, the exercise behavior of Chinese adolescents has been on the decline, which is extremely detrimental to their physical and mental health development. However, few studies have explored the mechanisms by which exercise cognition influences Chinese adolescents' exercise behavior. The present study aimed to investigate the relationship between exercise cognition and exercise behavior among Chinese adolescents and the mediating role of satisfying basic psychological needs for exercise. The study consisted of 996 adolescents (44.6% males, 55.4% females) between the ages of 12 and 15 (M = 13.34, SD = 1.059). Participants' exercise behaviors and the satisfaction of basic psychological needs for exercise data were collected via surveys. Structure equation modeling (SEM) was performed to examine the direct and indirect effects. The results were as follows: (1) adolescents' perceptions of exercise were significantly associated with exercise behavior and (2) the mediation model suggests that the satisfaction of basic psychological needs for exercise is an important mechanism by which exercise cognition influences the occurrence of exercise behavior. Therefore, it is crucial to help adolescents form good exercise cognition. Schools, families, and society should take responsibility for adolescents' formation of good exercise cognition and satisfy adolescents' basic psychological needs for exercise so as to enhance adolescents' exercise behaviors and thereby develop good exercise habits.
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OBJECTIVE: We aimed to investigate the neural mechanisms underlying the inhibitory function performance of maritime Search and Rescue (SAR) personnel in states of physical exhaustion. BACKGROUND: SAR missions pose serious challenges to the cognitive function of SAR personnel, especially in extreme environments and physical exhaustion. It is important to understand SAR personnel's cognitive performance and neural activity under exhaustion to improve the efficiency of task execution and ensure work safety. METHOD: Twenty-six maritime SAR personnel were recruited to simulate boat operations until they reached a self-imposed state of exhaustion. The exhaustion state was monitored by maximum heart rate and subjective fatigue scale. Two event-related potentials, N200 and P300, were measured during a Go-Nogo task before and after a session of acute exhaustive tasks. RESULTS: After exhaustion, a marked reduction in accuracy, a notable increase in N200 amplitude, and a substantial decline in P300 amplitude under the Nogo condition were observed compared to the baseline phase. Pre- and post-exhaustion comparisons using standardized low-resolution brain electromagnetic tomography revealed reduced activations in the right middle temporal gyrus's N200 component after exhaustion in SAR personnel during the Nogo condition. CONCLUSION: The results suggest that acute physical exhaustion significantly impacts the inhibition ability of SAR personnel, prolonging the conflict monitoring phase and weakening the response inhibition phase. These findings provide valuable insights into how physical exhaustion affects cognitive functions critical to the safety and effectiveness of SAR operations, and can inform strategies to improve training and equipment to enhance performance under extreme conditions.
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Electroencefalografía , Potenciales Evocados , Fatiga , Inhibición Psicológica , Humanos , Masculino , Adulto , Adulto Joven , Fatiga/fisiopatología , Potenciales Evocados/fisiología , Frecuencia Cardíaca/fisiología , Encéfalo/fisiología , Femenino , Desempeño Psicomotor/fisiologíaRESUMEN
BACKGROUND: The purpose of this study was to investigate the effect of tumor size and differentiation grade on long term survival in patients with early-stage lung adenocarcinoma (LUAD) after lobectomy and segmentectomy. PATIENTS AND METHODS: Patients with stage T1-2N0M0 LUAD who underwent lobectomy and segmentectomy were identified from the Surveillance, Epidemiology, and End Results database. Patients were stratified as grade I (well differentiated), grade II (moderately differentiated), and grade III/IV (poorly differentiated/undifferentiated) carcinomas. The effect of tumor size on overall survival (OS) and lung cancer-specific survival (LCSS) was evaluated using the multivariate Cox regression model, including the interaction between tumor size, type of surgery, and tumor differentiation grade. The inverse probability of treatment weighting method was used to adjust for bias between the groups. RESULTS: A total of 19,857 patients were identified, including 18,759 (94.4%) who underwent lobectomy and 1098 (5.5%) who underwent segmentectomy. A three-way interaction among tumor size, differentiation grade, and type of surgery was observed in the overall cohort. After stratifying by differentiation grade, plots of interaction revealed that lobectomy was associated with improved survival compared with segmentectomy when the tumor size exceeded 23 mm for grade I LUAD and 14 mm for grade II LUAD. No interaction was observed between the studied factors in grade III/IV carcinomas. CONCLUSIONS: This study interpreted the interaction between tumor size and type of surgery on long-term survival in patients with early stage LUAD and established a tumor size threshold beyond which lobectomy provided survival benefits compared with segmentectomy.
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Physical activity (PA) is widely recognized as crucial for human health, yet the low level of PA in adolescents continues to raise major concerns. This study aims to validate the Chinese version of the Social Support Scale for Exercise (SE) and establish its reliability among Chinese adolescents. A cross-sectional study was conducted on two primary and two secondary schools in central China. Students were recruited using a random cluster sampling method, and written informed consent was provided after they were briefed on the purpose of the study. The standard forward-backward translation was applied to translate the English version of the SE into Chinese. The Social Support Scale used in this study consists of two factors: family support and friend support. Data were analyzed using Mplus 8 for the CFA, composite reliability (CR), average variance extracted (AVE), and intra-class correlation coefficients (ICC) were calculated. A total of 1422 students (boys = 838, girls = 604) with a mean age of 11 years (SD = 1.6) participated in the study. The measurement model of the translated social support scale fit the data well: CFI = .935; TLI = .929; SRMR = .038; RMSEA = .053, with a 90% confidence interval of (.051, .056; RMSEA p < .001). The composite reliability values of .935 for family support and .948 for friend support were acceptable. The intra-class correlation coefficients (ICC) based on test-retest were .928 for family support, and .904 for friend support. Hence, the Chinese version of the SE was valid and reliable, its implementation will provide researchers with a valuable tool to comprehensively assess Chinese adolescents' exercise-related social support and help develop targeted and effective interventions to improve their physical activity levels.
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Ejercicio Físico , Psicometría , Apoyo Social , Humanos , Masculino , Femenino , China , Ejercicio Físico/psicología , Adolescente , Psicometría/métodos , Estudios Transversales , Niño , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Estudiantes/psicologíaRESUMEN
The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.
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Aprendizaje Profundo , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/antagonistas & inhibidores , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/metabolismo , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Animales , Descubrimiento de Drogas , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , RatonesRESUMEN
Our minds represent miscellaneous objects in the physical world metaphorically in an abstract and complex high-dimensional object space, which is implemented in a two-dimensional surface of the ventral temporal cortex (VTC) with topologically organized object selectivity. Here we investigated principles guiding the topographical organization of object selectivities in the VTC by constructing a hybrid Self-Organizing Map (SOM) model that harnesses a biologically inspired algorithm of wiring cost minimization and adheres to the constraints of the lateral wiring span of human VTC neurons. In a series of in silico experiments with functional brain neuroimaging and neurophysiological single-unit data from humans and non-human primates, the VTC-SOM predicted the topographical structure of fine-scale category-selective regions (face-, tool-, body-, and place-selective regions) and the boundary in large-scale abstract functional maps (animate vs. inanimate, real-word small-size vs. big-size, central vs. peripheral), with no significant loss in functionality (e.g., categorical selectivity and view-invariant representations). In addition, when the same principle was applied to V1 orientation preferences, a pinwheel-like topology emerged, suggesting the model's broad applicability. In summary, our study illustrates that the simple principle of wiring cost minimization, coupled with the appropriate biological constraint of lateral wiring span, is able to implement the high-dimensional object space in a two-dimensional cortical surface.
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Lóbulo Temporal , Humanos , Lóbulo Temporal/fisiología , Animales , Simulación por Computador , Modelos Neurológicos , Algoritmos , Neuronas/fisiología , Redes Neurales de la Computación , Imagen por Resonancia Magnética , Mapeo EncefálicoRESUMEN
Extracting lithium from salt-lake brines critically relies on the separation of Li+ and Mg2+, which could combat the lithium shortage. However, designing robust sieving membrane with high Li+/Mg2+ selectivity in the long-time operation has remained highly challenging. Here, we demonstrate a bioinspired congener-welded crystalline carbon nitride membrane that can accomplish efficient and stable monovalent ion sieving over divalent Mg ion. The crystalline carbon nitrides have uniform and narrow pore size to reject the large hydrated Mg2+ and rich ligating sites to facilitate an almost barrierless Li+ transport as suggested by ab initio simulations. These crystals were then welded by vapor-deposited congeners, i.e., amorphous polymer carbon nitride, which have similar composition and chemistry with the crystals, forming intimate and compatible crystal/polymer interface. As a result, our membrane can sieve out highly dilute Li+ (0.002 M) from concentrated Mg2+ (1.0 M) with a high selectivity of 1708, and can be continuously operated for 10 days.
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14 novel pleuromutilin derivatives were designed and synthesized as inhibitors against Staphylococcus aureus (S. aureus). The modification was focused on the C22 position of pleuromutilin. We conducted the characterization, in vitro and in vivo biological assessment of the compounds. Compound 18 exhibited the best antibacterial effect against MRSA (MIC = 0.015 µg/mL, MBC = 0.125 µg/mL). Compound 18 was further studied by time-kill kinetic and post-antibiotic effect (PAE) approaches. Besides, most compounds exhibited low cytotoxicity to RAW 264.7 cells. Compound 18 displayed decent bactericidal activity in vivo (-0.51 log10 CFU/mL). Molecular docking study indicated that compound 18 could be located stably at the ribosome (ΔGb = -7.30 kcal/mol). The results revealed that compound 18 might be further developed into a novel antibiotic.
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Antibacterianos , Diterpenos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Pleuromutilinas , Compuestos Policíclicos , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Diterpenos/farmacología , Diterpenos/química , Ratones , Animales , Estructura Molecular , Células RAW 264.7 , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Diseño de Fármacos , Staphylococcus aureus/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
Heated effluent injection, cold hypolimnetic water inputs from dams, and extreme weather events can lead to unpredictable temperature fluctuations in natural waters, impacting fish performance and fitness. We hypothesized that fish exposed to such unpredictable fluctuations would exhibit weaker growth and enhanced thermal tolerance compared to predictable conditions. Qingbo (Spinibarbus sinensis) was selected as the experimental subject in this study. The qingbo were divided into a constant temperature group (C, 22 ± 0.5 °C), a predictable temperature fluctuation group (PF, 22 ± 4 °C, first warming, then cooling within a day) and an unpredictable temperature fluctuation group (UF, 22 ± 4 °C, the order of warming or cooling is random). After 40 days of temperature acclimation, the growth, metabolic rate, spontaneous activity, thermal tolerance, plasma cortisol concentration and liver hsp70 level of the fish were measured. Unexpectedly, neither the PF nor the UF group showed decreased growth compared to the C group. This could be attributed to the fact that temperature variation did not lead to a substantial increase in basic energy expenditure. Furthermore, feeding rates increased due to temperature fluctuations, although the difference was not significant. Both the PF and UF groups exhibited increased upper thermal tolerance, but only the UF group exhibited improved lower thermal tolerance and higher liver hsp70 levels compared to the C group. The qingbo that experienced unpredictable temperature fluctuations had the best thermal tolerance among the 3 groups, which might have occurred because they had the highest level of hsp70 expression. This may safeguard fish against the potential lethal consequences of extreme temperatures in the future. These findings suggested that qingbo exhibited excellent adaptability to both predictable and unpredictable temperature fluctuations, which may be associated with frequent temperature fluctuations in its natural habitat.
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Aclimatación , Temperatura , Animales , Aclimatación/fisiología , Termotolerancia , Hidrocortisona/sangre , Hidrocortisona/metabolismo , Hígado/metabolismo , Hígado/fisiología , Proteínas HSP70 de Choque Térmico/metabolismo , Metabolismo Basal , Metabolismo EnergéticoRESUMEN
BACKGROUND: Longer times between diagnosis and treatments of cancer patients have been estimated as effects of the COVID-19 pandemic. However, relatively few studies attempted to estimate actual delay to treatment at the patient level. OBJECTIVE: To assess changes in delays to first treatment and surgery among newly diagnosed patients with localized breast cancer (BC) during the COVID-19 pandemic. METHODS: We used data from the PAPESCO-19 multicenter cohort study, which included patients from 4 French comprehensive cancer centers. We measured the delay to first treatment as the number of days between diagnosis and the first treatment regardless of whether this was neoadjuvant chemotherapy or surgery. COVID-19 pandemic exposure was estimated with a composite index that considered both the severity of the pandemic and the level of lockdown restrictions. We ran generalized linear models with a log link function and a gamma distribution to model the association between delay and the pandemic. RESULTS: Of the 187 patients included in the analysis, the median delay to first treatment was 42 (IQR:32-54) days for patients diagnosed before and after the start of the 1st lockdown (N = 99 and 88, respectively). After adjusting for age and centers of inclusion, a higher composite pandemic index (> = 50 V.S. <50) had only a small, non-significant effect on times to treatment. Longer delays were associated with factors other than the COVID-19 pandemic. CONCLUSION: We found evidence of no direct impact of the pandemic on the actual delay to treatment among patients with localized BC.
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Neoplasias de la Mama , COVID-19 , Tiempo de Tratamiento , Humanos , COVID-19/epidemiología , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/epidemiología , Persona de Mediana Edad , Tiempo de Tratamiento/estadística & datos numéricos , Anciano , Francia/epidemiología , Adulto , Pandemias , SARS-CoV-2/aislamiento & purificación , Estudios de CohortesRESUMEN
Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA. In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance. Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function. In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer.
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Neoplasias de la Mama , Doxorrubicina , Resistencia a Antineoplásicos , Exosomas , Regulación Neoplásica de la Expresión Génica , MicroARNs , Receptor Notch1 , Humanos , Exosomas/metabolismo , Exosomas/genética , MicroARNs/genética , MicroARNs/metabolismo , Doxorrubicina/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Células MCF-7 , Femenino , Receptor Notch1/metabolismo , Receptor Notch1/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
Heterostructures from complex oxides allow one to combine various electronic and magnetic orders as to induce new quantum states. A prominent example is the coupling between superconducting and magnetic orders in multilayers from high-Tc cuprates and manganites. A key role is played here by the interfacial CuO2 layer whose distinct properties remain to be fully understood. Here, we study with resonant inelastic X-ray scattering the magnon excitations of this interfacial CuO2 layer. In particular, we show that the underlying antiferromagnetic exchange interaction at the interface is strongly suppressed to J≈70 meV, when compared with J≈130 meV for the CuO2 layers away from the interface. Moreover, we observe an anomalous momentum dependence of the intensity of the interfacial magnon mode and show that it suggests that the antiferromagnetic order is accompanied by a particular kind of orbital order that yields a so-called altermagnetic state. Such a 2D altermagnet has recently been predicted to enable new spintronic applications and superconducting proximity effects.
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Slower perceptual alternations, a notable perceptual effect observed in psychiatric disorders, can be alleviated by antidepressant therapies that affect serotonin levels in the brain. While these phenomena have been well documented, the underlying neurocognitive mechanisms remain to be elucidated. Our study bridges this gap by employing a computational cognitive approach within a Bayesian predictive coding framework to explore these mechanisms in depression. We fitted a prediction error (PE) model to behavioral data from a binocular rivalry task, uncovering that significantly higher initial prior precision and lower PE led to a slower switch rate in patients with depression. Furthermore, serotonin-targeting antidepressant treatments significantly decreased the prior precision and increased PE, both of which were predictive of improvements in the perceptual alternation rate of depression patients. These findings indicated that the substantially slower perception switch rate in patients with depression was caused by the greater reliance on top-down priors and that serotonin treatment's efficacy was in its recalibration of these priors and enhancement of PE. Our study not only elucidates the cognitive underpinnings of depression, but also suggests computational modeling as a potent tool for integrating cognitive science with clinical psychology, advancing our understanding and treatment of cognitive impairments in depression.