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The present study investigated the sweetness interaction and the sensory characteristics of a novel glycosylated rebaudioside A (g-reb_A) when mixed with other sweeteners. Binary sweetener mixtures were formulated by mixing g-reb_A with four types of sweeteners (sucrose, aspartame, acesulfame-K, saccharin). The sweetness potencies of sweeteners were measured at various concentrations. G-reb_A was mixed with each of the four other sweeteners at the concentration ratio of 35:65 or 50:50 to match the sweetness of a 10% sucrose solution. A generic descriptive analysis was conducted to evaluate the binary samples compared to the 10% sucrose solution. Most binary mixtures exhibited an additive effect on sweetness. A marginal sweetness synergistic effect was observed when g-reb_A was mixed with sucrose at the 50:50 ratio. The sensory characteristics of the binary mixture depended on the type of sweetener mixed with g-reb_A. Mixtures of g-reb_Aacesulfame-K or g-reb_Asaccharin elicited significantly higher bitter taste than the other binary mixtures.

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Solid-state polymer dielectrics offer an exceptional dielectric breakdown, but require an enhanced energy density to be competitive with alternative electrolyte-based energy storage technologies. Therefore, this research introduces conductive titanium carbonitride (TiCN) nanoparticles in a polyvinylidene fluoride (PVDF) matrix to obtain flexible percolation-based nanodielectrics by ultrasonication-based suspension processing and hot pressing. Well-dispersed TiCN nanoparticles in PVDF were obtained for a wide range of filler volume fractions, and an exceptional peak in the dielectric constant equal to 1130 (0.1 Hz) and 29 (10 kHz) was observed near the percolation threshold (9.2 vol %). The enhanced dielectric constant was ascribed to massive interfacial polarization occurring, resulting from Maxwell-Wagner-Sillars (MWS) polarization and a nanocapacitor mechanism that are dominant at low and high frequencies, respectively. An improvement by 30% in the energy density (0.042 Wh kg-1) compared with the neat PVDF matrix was achieved for the PVDF/TiCN nanodielectrics. The first successful uniform deposition of a nanometer-thin (3 nm) silica (SiO2) shell via the Stöber process on TiCN nanoparticles significantly suppressed the dielectric losses near percolation for the PVDF/TiCN@SiO2 nanodielectrics by more than 1 order of magnitude while offering dielectric constants of 34 (0.1 Hz) and 10 (10 kHz). This study demonstrates the potential of hybrid (core-shell) percolation-based dielectrics for an improved capacitive dielectric performance by an integrated dielectric characterization approach that simultaneously optimizes the dielectric constant, loss tangent, breakdown strength, and energy density.

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The hippocampus primarily functions through a canonical trisynaptic circuit, comprised of dentate granule cells and CA1-CA3 pyramidal neurons (PNs), which exhibit significant heterogeneity along the dorsoventral axis. Among these, CA PNs are known to project beyond the hippocampus into various limbic areas, critically influencing cognitive and affective behaviors. Despite accumulating evidence of these extrahippocampal projections, the specific topological patterns-particularly variations among CA PN types and between their dorsal and ventral subpopulations within each type-remain to be fully elucidated. In this study, we utilized cell type-specific Cre mice injected with fluorescent protein-expressing AAVs to label each CA PN type distinctly. This method further enabled the dual-fluorescence labeling of dorsal and ventral subpopulations using EGFP and tdTomato, respectively, allowing a comprehensive comparison of their axonal projections in an animal. Our findings demonstrate that CA1 PNs predominantly form unilateral projections to the frontal cortex (PFC), amygdala (Amy), nucleus accumbens (NAc), and lateral septum (LS), unlike CA2 and CA3 PNs making bilateral innervation to the LS only. Moreover, the innervation patterns especially within LS subfields differ according to the CA PN type and their location along the dorsoventral axis of the hippocampus. This detailed topographical mapping provides the neuroanatomical basis of the underlying functional distinctions among CA PN types.

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AIM: To analyse and describe the trends concerning nurse-parent partnerships in South Korean research, presenting their implications in paediatric care and guiding future directions for partnership research. DESIGN: A scoping review. METHODS: The scoping review was conducted according to the framework outlined by Arksey and O'Malley. This review method consists of five stages: (1) identifying a research question, (2) identifying relevant studies, (3) selecting relevant studies, (4) charting the data extraction and (5) collating, summarizing and reporting the results. The studies reviewed were searched from electronic databases. RESULTS: Thirty studies were analysed for general characteristics, type of research method and findings from quantitative and qualitative research. Among the quantitative research, factors associated with partnerships, such as self-efficacy, quality of care and coping, were commonly associated with nurse-parent partnerships regardless of parent-, child- and nurse-related factors. The intervention methods included active parental participation and the development of educational materials. In the review of qualitative research, parents and paediatric nurses experienced that even when both groups occupied the same environment simultaneously, a disparity existed between the paediatric nurses' and parents' perceptions of their partnership experiences. IMPLICATIONS FOR THE PROFESSION: Strengthening nurse-parent partnerships is crucial in improving health outcomes and quality of life for paediatric patients in South Korea. Effective collaboration, emphasizing mutual respect, effective communication, and shared decision-making, is essential in paediatric nursing care. This requires ongoing research, including both parents and a multidisciplinary approach to build supportive relationships across various age groups. Recognizing parents as key members of the care team, with valuable insights and contributions, enhances care quality. Additionally, enhancing paediatric nurses' self-efficacy, empowerment, and communication skills through continuous education is vital to improving parents' perceived quality of nursing. Partnership-centred practices not only boost care quality but also fortify the bond between healthcare providers and families, promoting better health outcomes. NO PATIENT OR PUBLIC CONTRIBUTION: This work did not incorporate patient or public contributions, as its methodology was centred on a scoping review approach.

Asunto(s)

Padres , Humanos , República de Corea , Padres/psicología , Relaciones Profesional-Familia , Niño , Investigación Cualitativa

RESUMEN

Introduction: Humanized mouse models to recapitulate human biological systems still have limitations, such as the onset of lethal graft-versus-host disease (GvHD), a variable success rate, and the low accessibility of total body irradiation (TBI). Recently, mice modified with the CD47-SIRPA axis have been studied to improve humanized mouse models. However, such trials have been rarely applied in NOD mice. In this study, we created a novel mouse strain, NOD-CD47nullRag2nullIL-2rγnull (RTKO) mice, and applied it to generate humanized mice. Methods: Four-week-old female NOD-Rag2nullIL-2rγnull (RID) and RTKO mice pre-conditioned with TBI or busulfan (BSF) injection were used for generating human CD34+ hematopoietic stem cell (HSC) engrafted humanized mice. Clinical signs were observed twice a week, and body weight was measured once a week. Flow cytometry for human leukocyte antigens was performed at intervals of four weeks or two weeks, and mice were sacrificed at 48 weeks after HSC injection. Results: For a long period from 16 to 40 weeks post transplantation, the percentage of hCD45 was mostly maintained above 25% in all groups, and it was sustained the longest and highest in the RTKO BSF group. Reconstruction of human leukocytes, including hCD3, was also most prominent in the RTKO BSF group. Only two mice died before 40 weeks post transplantation in all groups, and there were no life-threatening GvHD lesions except in the dead mice. The occurrence of GvHD has been identified as mainly due to human T cells infiltrating tissues and their related cytokines. Discussion: Humanized mouse models under all conditions applied in this study are considered suitable models for long-term experiments based on the improvement of human leukocytes reconstruction and the stable animal health. Especially, RTKO mice pretreated with BSF are expected to be a valuable platform not only for generating humanized mice but also for various immune research fields.

Asunto(s)

Busulfano , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas , Ratones Endogámicos NOD , Ratones Noqueados , Acondicionamiento Pretrasplante , Animales , Busulfano/farmacología , Humanos , Ratones , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Células Madre Hematopoyéticas/metabolismo , Femenino , Subunidad gamma Común de Receptores de Interleucina/genética , Subunidad gamma Común de Receptores de Interleucina/deficiencia , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/inmunología , Modelos Animales de Enfermedad , Irradiación Corporal Total

RESUMEN

Emotional eating, which refers to eating in response to emotional states, is prevalent in early childhood. Executive function (EF) and sleep problems are related to preschoolers' self-regulatory abilities during the day and night and have been reported to be associated with their emotional eating. These associations can be stronger in emotionally stressful situations, such as controlling feeding practices. This study explored the role of preschoolers' EF and sleep problems as child characteristics, as well as maternal feeding practices as environmental factors influencing emotional eating during the preschool period. Participants included 363 Korean mothers with preschoolers aged 3- to 5-years old (190 boys, 173 girls). Mothers reported on their own feeding practices, and preschoolers' EF, sleep problems, and emotional eating. Results indicated that preschoolers' EF was negatively associated with emotional over- and undereating, and this association was stronger when mothers applied more pressure to eat. Maternal monitoring had a similar effect, with emotional overeating exerting a greater impact with low levels of maternal monitoring. Finally, maternal pressure to eat moderated the influence of preschoolers' sleep problems on emotional overeating, with higher pressure to eat predicting a stronger relationship between sleep problems and emotional overeating. These findings suggest that maternal feeding practices, which are relatively modifiable, should be considered an important element in intervention programs aimed at preventing emotional eating in preschool children.

Asunto(s)

Emociones , Conducta Alimentaria , Madres , Humanos , Preescolar , Femenino , Masculino , Conducta Alimentaria/psicología , Madres/psicología , República de Corea , Trastornos del Sueño-Vigilia/psicología , Función Ejecutiva , Adulto , Relaciones Madre-Hijo/psicología , Responsabilidad Parental/psicología , Ingestión de Alimentos/psicología , Hiperfagia/psicología , Conducta Infantil/psicología , Encuestas y Cuestionarios

RESUMEN

This study conducted the development of an advanced risk assessment algorithm system and safety management strategies using pesticide residue monitoring data from soils. To understand the status of pesticide residues in agricultural soils, monitoring was performed on 116 types of pesticides currently in use across 300 soil sites. The analysis of the monitoring results, alongside the physicochemical properties of the pesticides, led to the selection of soil half-life as a critical component in residue analysis. The use of Toxicity Exposure Ratio (TER) and Risk Quotient (RQ) for environmental risk assessment, based on monitoring data, presents limitations due to its single-component, conservative approach, which does not align with actual field conditions. Therefore, there is a necessity for a risk assessment process applicable in real-world scenarios. In this research, an efficient and accurate risk assessment algorithm system, along with a safety management model, was developed. Using the physicochemical properties of pesticides (such as soil half-life), monitoring results, and toxicity data, cluster analysis and Principal Component Analysis (PCA) validation identified four pesticides: boscalid, difenoconazole, fluquinconazole, and tebuconazole. The k-mean cluster analysis selected three priority management sites where the contribution of these four pesticides to the RQ was between 94-99 %, showing similar results to the RQ calculated for all pesticides. Predictions made with the developed model for the time required for soil half-life based RQ to drop below 1 at these priority sites showed only a 1-9 day difference between the four pesticides of concern and all pesticides, indicating comparable outcomes. The scenario of replacing high-risk pesticides with those of lower risk demonstrated that the RQ could be consistently maintained at about 50 % level. The results of this study suggest that through monitoring, evaluation, and management, effective and accurate environmental safety management of pesticides in soil can be achieved.

Asunto(s)

Agricultura , Algoritmos , Monitoreo del Ambiente , Residuos de Plaguicidas , Contaminantes del Suelo , Suelo , Medición de Riesgo , Residuos de Plaguicidas/análisis , Contaminantes del Suelo/análisis , Monitoreo del Ambiente/métodos , Suelo/química , Triazoles/análisis , Triazoles/toxicidad , Semivida , Análisis de Componente Principal , Plaguicidas/análisis , Análisis por Conglomerados , Administración de la Seguridad

RESUMEN

This study investigated the effects of various binary sweetener mixtures on sweetness enhancement and their interactions with sweet or bitter taste receptors, focusing on sensory perception and receptor activity. Acesulfame K or saccharin was mixed with allulose, aspartame, erythritol, fructose, glucose, or sucrose to match a target sucrose sweetness. The effects of the mixtures on sweet and bitter taste receptors (in the human embryonic kidney -293 cells) and sensory taste intensities were evaluated. Sweetness enhancement at the sweet taste receptor level was observed in some cases, with several monosaccharides reducing the acesulfame K- or saccharin-induced bitter taste receptor activity. Combining acesulfame K or saccharin with any of the six sweeteners perceptually enhanced sweetness (60% âˆ¼ 100% in 50:50 ratio), correlating with a reduction in inherent bitterness (-35% âˆ¼ -63% in 50:50 ratio). This finding suggests that sweetness perception likely increased because the monosaccharides mitigate the activation of bitter receptors caused by high-potency sweeteners.

Asunto(s)

Receptores Acoplados a Proteínas G , Edulcorantes , Papilas Gustativas , Percepción del Gusto , Gusto , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Percepción del Gusto/efectos de los fármacos , Papilas Gustativas/metabolismo , Papilas Gustativas/efectos de los fármacos , Células HEK293 , Sacarina/farmacología , Tiazinas

RESUMEN

Cervical length (CL) measurement using transvaginal ultrasound is an effective screening tool to assess the risk of preterm birth. An adequate assessment of CL is crucial, however, manual sonographic CL measurement is highly operator-dependent and cumbersome. Therefore, a reliable and reproducible automatic method for CL measurement is in high demand to reduce inter-rater variability and improve workflow. Despite the increasing use of artificial intelligence techniques in ultrasound, applying deep learning (DL) to analyze ultrasound images of the cervix remains a challenge due to low signal-to-noise ratios and difficulties in capturing the cervical canal, which appears as a thin line and with extremely low contrast against the surrounding tissues. To address these challenges, we have developed CL-Net, a novel DL network that incorporates expert anatomical knowledge to identify the cervix, similar to the approach taken by clinicians. CL-Net captures anatomical features related to CL measurement, facilitating the identification of the cervical canal. It then identifies the cervical canal and automatically provides reproducible and reliable CL measurements. CL-Net achieved a success rate of 95.5% in recognizing the cervical canal, comparable to that of human experts (96.4%). Furthermore, the differences between the CL measurements of CL-Net and ground truth were considerably smaller than those made by non-experts and were comparable to those made by experts (median 1.36 mm, IQR 0.87-2.82 mm, range 0.06-6.95 mm for straight cervix; median 1.31 mm, IQR 0.61-2.65 mm, range 0.01-8.18 mm for curved one).

RESUMEN

This study addresses the prevalent issue of meat species authentication and adulteration through a chemometrics-based approach, crucial for upholding public health and ensuring a fair marketplace. Volatile compounds were extracted and analyzed using headspace-solid-phase-microextraction-gas chromatography-mass spectrometry. Adulterated meat samples were effectively identified through principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA). Through variable importance in projection scores and a Random Forest test, 11 key compounds, including nonanal, octanal, hexadecanal, benzaldehyde, 1-octanol, hexanoic acid, heptanoic acid, octanoic acid, and 2-acetylpyrrole for beef, and hexanal and 1-octen-3-ol for pork, were robustly identified as biomarkers. These compounds exhibited a discernible trend in adulterated samples based on adulteration ratios, evident in a heatmap. Notably, lipid degradation compounds strongly influenced meat discrimination. PCA and PLS-DA yielded significant sample separation, with the first two components capturing 80% and 72.1% of total variance, respectively. This technique could be a reliable method for detecting meat adulteration in cooked meat.

RESUMEN

Two-dimensional (2D) topological insulators (TIs) or quantum spin Hall (QSH) insulators, characterized by insulating 2D electronic band structures and metallic helical edge states protected by time-reversal symmetry, offer a platform for realizing the quantum spin Hall effect, making them promising candidates for future spintronic devices and quantum computing. However, observing a high-temperature quantum spin Hall effect requires large-gap 2D TIs, and only a few 2D systems have been experimentally confirmed to possess this property. In this study, we employ first-principles calculations, combined with a structural search based on an evolutionary algorithm, to predict a class of 2D QSH insulators in hafnium halides, namely, HfF, HfCl, and HfBr with sizable band gaps of 0.12, 0.19, and 0.38 eV. Their topological nontrivial nature is confirmed by a Z2 invariant which equals to 1 and the presence of gapless edge states. Furthermore, the QSH effect in these materials remains robust under biaxial tensile strain of up to 10%, and the use of h-BN as a substrate effectively preserves the QSH states in these materials. Our findings pave the way for future theoretical and experimental investigations of 2D hafnium halides and their potential for realizing the QSH effect.

RESUMEN

Bone homeostasis is maintained by an intricate balance between osteoclasts and osteoblasts, which becomes disturbed in osteoporosis. Metallothioneins (MTs) are major contributors in cellular zinc regulation. However, the role of MTs in bone cell regulation has remained unexplored. Single-cell RNA sequencing analysis discovered that, unlike the expression of other MT members, the expression of MT3 was unique to osteoclasts among various macrophage populations and was highly upregulated during osteoclast differentiation. This unique MT3 upregulation was validated experimentally and supported by ATAC sequencing data analyses. Downregulation of MT3 by gene knockdown or knockout resulted in excessive osteoclastogenesis and exacerbated bone loss in ovariectomy-induced osteoporosis. Transcriptome sequencing of MT3 knockdown osteoclasts and gene set enrichment analysis indicated that the oxidative stress and redox pathways were enriched, which was verified by MT3-dependent regulation of reactive oxygen species (ROS). In addition, MT3 deficiency increased the transcriptional activity of SP1 in a manner dependent on intracellular zinc levels. This MT3-zinc-SP1 axis was crucial for the control of osteoclasts, as zinc chelation and SP1 knockdown abrogated the promotion of SP1 activity and osteoclastogenesis by MT3 deletion. Moreover, SP1 bound to the NFATc1 promoter, and overexpression of an inactive SP1 mutant negated the effects of MT3 deletion on NFATc1 and osteoclastogenesis. In conclusion, MT3 plays a pivotal role in controlling osteoclastogenesis and bone metabolism via dual axes involving ROS and SP1. The present study demonstrated that MT3 elevation is a potential therapeutic strategy for osteolytic bone disorders, and it established for the first time that MT3 is a crucial bone mass regulator.

Asunto(s)

Metalotioneína 3 , Osteoclastos , Osteogénesis , Osteoporosis , Animales , Osteoporosis/metabolismo , Osteoporosis/genética , Osteoporosis/patología , Osteoporosis/etiología , Osteogénesis/genética , Ratones , Osteoclastos/metabolismo , Metalotioneína 3/metabolismo , Diferenciación Celular/genética , Femenino , Regulación de la Expresión Génica , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción Sp1/metabolismo , Factor de Transcripción Sp1/genética , Zinc/metabolismo , Factores de Transcripción NFATC/metabolismo , Factores de Transcripción NFATC/genética , Metalotioneína/metabolismo , Metalotioneína/genética , Ratones Noqueados

RESUMEN

Sleep quality often deteriorates with age, and insomnia among the elderly increases the risks of both physical and psychiatric disorders. To elucidate the mechanisms and identify useful diagnostic biomarkers for insomnia in the elderly, the current study investigated the associations of waking brain activity patterns with susceptibility to stress-induced insomnia (sleep reactivity) and dysfunctional beliefs about sleep, major factors precipitating and maintaining insomnia, respectively. Forty-five participants aged 60 years or older with insomnia completed self-reported measures assessing depression, anxiety, sleep quality, dysfunctional beliefs about sleep, and sleep reactivity. Participants were then examined by quantitative electroencephalography (qEEG) during wakefulness, and spectral analysis was conducted to examine associations of regional frequency band power with these insomnia-precipitating and -maintaining factors. Dysfunctional beliefs about sleep were significantly correlated with higher beta/high-beta frequency band powers, while sleep reactivity was correlated with higher theta and delta frequency band powers. These findings suggest that sleep reactivity of older adults is associated with widespread cortical deactivation leading to poor stress coping, while their dysfunctional beliefs about sleep are associated with hyperactivation which is related to cognitive processes. These associations suggest that cognitive inflexibility and maladaptive stress-coping contribute to insomnia among the elderly.

Asunto(s)

Electroencefalografía , Trastornos del Inicio y del Mantenimiento del Sueño , Vigilia , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Vigilia/fisiología , Sueño/fisiología , Anciano de 80 o más Años , Ondas Encefálicas/fisiología

RESUMEN

Due to the constraints of the COVID-19 pandemic, conducting sensory evaluations requiring direct interactions became challenging. In response, researchers have been motivated to devise non-face-to-face testing methods as alternatives. This study aimed to compare two non-face-to-face home-use tests (HUT) with the traditional face-to-face central location test (CLT). Both HUTs involved online recruitment and sample delivery to participants' homes. One HUT provided a written protocol with no direct interaction (contactless HUT; C-HUT), whereas the other included an online meeting with a researcher for live guidance (online HUT; O-HUT). Four coffee samples were evaluated on the basis of liking and sensory and emotional attributes. The comparison between CLT and O-HUT showed RV coefficients of 0.92, 0.93, and 0.98 (P < 0.05) for liking and sensory and emotional attributes, respectively. In addition, based on the RV coefficient, the CLT results showed a significantly greater similarity to those of O-HUT compared to those of C-HUT. The O-HUT also outperformed the C-HUT in its ability to significantly discriminate between samples. Hence, real-time interactions between researchers and participants, as facilitated by O-HUT, may be more suitable in certain scenarios compared to C-HUT, which relies solely on a written protocol. Overall, these findings suggest that C-HUT and O-HUT are suitable methods for collecting sensory data and overcoming geographic and face-to-face contact limitations, providing greater flexibility, and reducing the time and cost associated with traditional sensory evaluations.

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COVID-19 , Café , Comportamiento del Consumidor , Humanos , Café/química , Masculino , Femenino , Adulto , COVID-19/epidemiología , Adulto Joven , Gusto , Persona de Mediana Edad , SARS-CoV-2 , Emociones , Preferencias Alimentarias , Internet

RESUMEN

BACKGROUND: Insects encounter various environmental stresses, in response to which they generate reactive oxygen species (ROS). Superoxide dismutase (SOD) is an antioxidant metalloenzyme that scavenges superoxide radicals to prevent oxidative damage. OBJECTIVE: To investigate expressions of SODs under oxidative stress in Tenebrio molitor. METHODS: Here, we investigated the transcriptional expression of SODs by pesticide and heavy metals in Tenebrio moltior. First, we searched an RNA-Seq database for T. molitor SOD (TmSOD) genes and identified two SOD isoforms (TmSOD1-iso1 and iso2). We examined their activities under developmental stage, tissue-specific, and various types (pesticide and heavy metal) of oxidative stress by using qPCR. RESULTS: Our results revealed two novel forms of TmSODs. These TmSODs had a copper/zinc superoxide dismutase domain, active site, Cu2+ binding site, Zn2+ binding site, E-class dimer interface, and P-class dimer interface. TmSODs (TmSOD1-iso1 and iso2) were expressed in diverse developmental phases and tissues. Pesticides and heavy metals caused an upregulation of these TmSODs. CONCLUSION: Our findings suggest that the two TmSODs have different functions in T. molitor, providing insights into the detoxification ability of T. molitor.

Asunto(s)

Estrés Oxidativo , Superóxido Dismutasa , Tenebrio , Animales , Tenebrio/genética , Tenebrio/enzimología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Proteínas de Insectos/química , Metales Pesados/metabolismo , Simulación por Computador , Plaguicidas/metabolismo

RESUMEN

This study aimed to develop synthetic Claudin18.2 (CLDN18.2) chimeric antigen receptor (CAR)-T (CAR-T) cells as a treatment for advanced gastric cancer using lentiviral vector genetic engineering technology that targets the CLDN18.2 antigen and simultaneously overcomes the immunosuppressive environment caused by programmed cell death protein 1 (PD-1). Synthetic CAR T cells are a promising approach in cancer immunotherapy but face many challenges in solid tumors. One of the major problems is immunosuppression caused by PD-1. CLDN18.2, a gastric-specific membrane protein, is considered a potential therapeutic target for gastric and other cancers. In our study, CLDN18.2 CAR was a second-generation CAR with inducible T-cell costimulatory (CD278), and CLDN18.2-PD1/CD28 CAR was a third-generation CAR, wherein the synthetic PD1/CD28 chimeric-switch receptor (CSR) was added to the second-generation CAR. In vitro, we detected the secretion levels of different cytokines and the killing ability of CAR-T cells. We found that the secretion of cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) secreted by three types of CAR-T cells was increased, and the killing ability against CLDN18.2-positive GC cells was enhanced. In vivo, we established a xenograft GC model and observed the antitumor effects and off-target toxicity of CAR-T cells. These results support that synthetic anti-CLDN18.2 CAR-T cells have antitumor effect and anti-CLDN18.2-PD1/CD28 CAR could provide a promising design strategy to improve the efficacy of CAR-T cells in advanced gastric cancer.

Asunto(s)

Antígenos CD28 , Claudinas , Ingeniería Genética , Vectores Genéticos , Inmunoterapia Adoptiva , Receptor de Muerte Celular Programada 1 , Receptores Quiméricos de Antígenos , Linfocitos T , Animales , Humanos , Ratones , Antígenos CD28/genética , Antígenos CD28/inmunología , Línea Celular Tumoral , Claudinas/genética , Claudinas/metabolismo , Citocinas/metabolismo , Vectores Genéticos/genética , Inmunoterapia Adoptiva/métodos , Interferón gamma/metabolismo , Lentivirus/genética , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/inmunología , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/inmunología , Neoplasias Gástricas/terapia , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/genética , Linfocitos T/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

PURPOSE: We aimed to develop and investigate positional reproducibility using a fixation device (Unity Brain tumor Immobilization Device [UBID]) in patients with brain tumor undergoing magnetic resonance (MR)-guided radiation therapy (RT) with a 1.5 Tesla (T) MR-linear accelerator (MR-LINAC) to evaluate its feasibility in clinical practice and report representative cases of patients with central nervous system (CNS) tumor. MATERIALS AND METHODS: Quantitative analysis was performed by comparing images obtained by placing only the MR phantom on the couch with those obtained by placing UBID next to the MR phantom. Twenty patients who underwent RT for CNS tumors using 1.5T MR-LINAC between June and October 2022 were retrospectively analyzed. Among them, 5 did not use UBID, whereas 15 used UBID. The positional reproducibility of UBID was evaluated using the median interfractional and intrafractional errors in the first 10 fractions. RESULTS: Each MR quality factor of the MR phantom with UBID satisfied the criteria presented by Elekta. Median values of median shifts in the mediolateral, anteroposterior, and craniocaudal axes for interfractional errors were 2.98, 2.35, and 1.40 mm, respectively. For intrafractional errors, the median values were 0.05, 0.03, and 0.06 mm, respectively. The median values of the median rotations in pitch, roll, and yaw for both interfractional and intrafractional rotations were 0.00°. One patient diagnosed with an optic nerve sheath meningioma received RT with motion monitoring during irradiation. In 2 patients, changes in the tumor cavity and residual lesions were observed in the MRI obtained using 1.5T MR-LINAC on the day of the first treatment and immediately before the 21st fraction, respectively; therefore, offline/online adaptation was performed. CONCLUSIONS: The reproducible and immobile UBID is clinically feasible in patients with CNS tumors receiving RT with 1.5T MR-LINAC. Based on our initial experience, we developed a workflow for 1.5T MR-LINAC treatment of CNS tumors.

Asunto(s)

Inmovilización , Imagen por Resonancia Magnética , Radioterapia Guiada por Imagen , Humanos , Masculino , Femenino , Radioterapia Guiada por Imagen/métodos , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Adulto , Estudios Retrospectivos , Anciano , Inmovilización/instrumentación , Inmovilización/métodos , Neoplasias del Sistema Nervioso Central/radioterapia , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Fantasmas de Imagen

RESUMEN

Retinoic acid (RA), derived from vitamin A (retinol), plays a crucial role in modulating neuroplasticity within the adult brain. Perturbations in RA signaling have been associated with memory impairments, underscoring the necessity to elucidate RA's influence on neuronal activity, particularly within the hippocampus. In this study, we investigated the cell type and sub-regional distribution of RA-responsive granule cells (GCs) in the mouse hippocampus and delineated their properties. We discovered that RA-responsive GCs tend to exhibit a muted response to environmental novelty, typically remaining inactive. Interestingly, chronic dietary depletion of RA leads to an abnormal increase in GC activation evoked by a novel environment, an effect that is replicated by the localized application of an RA receptor beta (RARß) antagonist. Furthermore, our study shows that prolonged RA deficiency impairs spatial discrimination-a cognitive function reliant on the hippocampus-with such impairments being reversible with RA replenishment. In summary, our findings significantly contribute to a better understanding of RA's role in regulating adult hippocampal neuroplasticity and cognitive functions.

RESUMEN

Dimensional confinement has shown to be an effective strategy to tune competing degrees of freedom in complex oxides. Here, we achieved atomic layered growth of trigonal vanadium sesquioxide (V2O3) by means of oxygen-assisted molecular beam epitaxy. This led to a series of high-quality epitaxial ultrathin V2O3 films down to unit cell thickness, enabling the study of the intrinsic electron correlations upon confinement. By electrical and optical measurements, we demonstrate a dimensional confinement-induced metal-insulator transition in these ultrathin films. We shed light on the Mott-Hubbard nature of this transition, revealing a vanishing quasiparticle weight as demonstrated by photoemission spectroscopy. Furthermore, we prove that dimensional confinement acts as an effective out-of-plane stress. This highlights the structural component of correlated oxides in a confined architecture, while opening an avenue to control both in-plane and out-of-plane lattice components by epitaxial strain and confinement, respectively.

RESUMEN

BACKGROUND: The human upper respiratory tract (URT) microbiome, like the gut microbiome, varies across individuals and between health and disease states. However, study-to-study heterogeneity in reported case-control results has made the identification of consistent and generalizable URT-disease associations difficult. RESULTS: In order to address this issue, we assembled 26 independent 16S rRNA gene amplicon sequencing data sets from case-control URT studies, with approximately 2-3 studies per respiratory condition and ten distinct conditions covering common chronic and acute respiratory diseases. We leveraged the healthy control data across studies to investigate URT associations with age, sex, and geographic location, in order to isolate these associations from health and disease states. CONCLUSIONS: We found several robust genus-level associations, across multiple independent studies, with either health or disease status. We identified disease associations specific to a particular respiratory condition and associations general to all conditions. Ultimately, we reveal robust associations between the URT microbiome, health, and disease, which hold across multiple studies and can help guide follow-up work on potential URT microbiome diagnostics and therapeutics.

Asunto(s)

Microbiota , ARN Ribosómico 16S , Sistema Respiratorio , Humanos , Microbiota/genética , ARN Ribosómico 16S/genética , Sistema Respiratorio/microbiología , Enfermedades Respiratorias/microbiología , Estudios de Casos y Controles , Masculino , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Femenino