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Multidrug resistance (MDR) is a major factor in the failure of many forms of tumor chemotherapy. Development of a specific ligand for MDR-reversal would enhance the intracellular accumulation of therapeutic agents and effectively improve the tumor treatments. Here, an aptamer was screened against a doxorubicin (DOX)-resistant human hepatocellular carcinoma cell line (HepG2/DOX) via cell-based systematic evolution of ligands by exponential enrichment. A 50 nt truncated sequence termed d3 was obtained with high affinity and specificity for HepG2/DOX cells. Multidrug resistance protein 1 (MDR1) is determined to be a possible recognition target of the selected aptamer. Aptamer d3 binding was revealed to block the MDR of the tumor cells and increase the accumulation of intracellular anticancer drugs, including DOX, vincristine, and paclitaxel, which led to a boost to the cell killing of the anticancer drugs and lowering their survival of the tumor cells. The aptamer d3-mediated MDR-reversal for effective chemotherapy was further verified in an in vivo animal model, and combination of aptamer d3 with DOX significantly improved the suppression of tumor growth by treating a xenograft HepG2/DOX tumor in vivo. This work demonstrates the feasibility of a therapeutic DNA aptamer as a tumor MDR-reversal agent, and combination of the selected aptamer with chemotherapeutic drugs shows great potential for liver cancer treatments.
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Antineoplásicos , Resistencia a Antineoplásicos , Animales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Resistencia a Múltiples Medicamentos , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Quimioterapia Combinada , Línea Celular TumoralRESUMEN
The cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway is instrumental to antitumor immunity, yet the underlying molecular and cellular mechanisms are complex and still unfolding. A new paradigm suggests that cancer cells' cGAS-synthesized cGAMP can be transferred to tumor-infiltrating immune cells, eliciting STING-dependent IFN-ß response for antitumor immunity. Nevertheless, how the tumor microenvironment may shape this process remains unclear. In this study, we found that extracellular ATP, an immune regulatory molecule widely present in the tumor microenvironment, can potentiate cGAMP transfer, thereby boosting the STING signaling and IFN-ß response in murine macrophages and fibroblasts. Notably, genetic ablation or chemical inhibition of murine volume-regulation anion channel LRRC8/volume-regulated anion channel (VRAC), a recently identified cGAMP transporter, abolished ATP-potentiated cGAMP transfer and STING-dependent IFN-ß response, revealing a crucial role of LRRC8/VRAC in the cross-talk of extracellular ATP and cGAMP. Mechanistically, ATP activation of the P2X family receptors triggered Ca2+ influx and K+ efflux, promoting reactive oxygen species production. Moreover, ATP-evoked K+ efflux alleviated the phosphorylation of VRAC's obligate subunit LRRC8A/SWELL1 on S174. Mutagenesis studies indicated that the phosphorylation of S174 on LRRC8A could act as a checkpoint for VRAC in the steady state and a rheostat of ATP responsiveness. In an MC38-transplanted tumor model, systemically blocking CD39 and ENPP1, hydroxylases of extracellular ATP and cGAMP, respectively, elevated antitumor NK, NKT, and CD8+ T cell responses and restrained tumor growth in mice. Altogether, this study establishes a crucial role of ATP in facilitating LRRC8/VRAC transport cGAMP in the tumor microenvironment and provides new insight into harnessing cGAMP transfer for antitumor immunity.
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Adenosina Trifosfato , Proteínas de la Membrana , Nucleótidos Cíclicos , Microambiente Tumoral , Animales , Nucleótidos Cíclicos/metabolismo , Ratones , Adenosina Trifosfato/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/inmunología , Microambiente Tumoral/inmunología , Interferón beta/metabolismo , Interferón beta/inmunología , Ratones Endogámicos C57BL , Humanos , Transducción de Señal/inmunología , Ratones Noqueados , Línea Celular Tumoral , Cationes/metabolismo , Neoplasias/inmunología , Neoplasias/metabolismo , Nucleotidiltransferasas/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismoRESUMEN
Maintaining genomic stability is a prerequisite for proliferating NPCs to ensure genetic fidelity. Though histone arginine methylation has been shown to play important roles in safeguarding genomic stability, the underlying mechanism during brain development is not fully understood. Protein arginine N-methyltransferase 5 (PRMT5) is a type II protein arginine methyltransferase that plays a role in transcriptional regulation. Here, we identify PRMT5 as a key regulator of DNA repair in response to double-strand breaks (DSBs) during NPC proliferation. Prmt5F/F; Emx1-Cre (cKO-Emx1) mice show a distinctive microcephaly phenotype, with partial loss of the dorsal medial cerebral cortex and complete loss of the corpus callosum and hippocampus. This phenotype is resulted from DSBs accumulation in the medial dorsal cortex followed by cell apoptosis. Both RNA sequencing and in vitro DNA repair analyses reveal that PRMT5 is required for DNA homologous recombination (HR) repair. PRMT5 specifically catalyzes H3R2me2s in proliferating NPCs in the developing mouse brain to enhance HR-related gene expression during DNA repair. Finally, overexpression of BRCA1 significantly rescues DSBs accumulation and cell apoptosis in PRMT5-deficient NSCs. Taken together, our results show that PRMT5 maintains genomic stability by regulating histone arginine methylation in proliferating NPCs.
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Células-Madre Neurales , Reparación del ADN por Recombinación , Animales , Ratones , Arginina/metabolismo , Reparación del ADN , Inestabilidad Genómica , Genómica , Histonas/genética , Histonas/metabolismo , Células-Madre Neurales/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismoRESUMEN
Antenna, as a converter, could receive and convert signals from the outside world flexibly. Inspired by the behavior of antennas receiving external signals, we developed a pH-stimulated and aptamer-anchored Y-shaped DNA nanoantenna (termed pH-Apt-YNA) for sensitive and specific sensing of tumor extracellular pH gradients. The nanoantenna consisted of three functional nucleic acid sequences, an I-strand, Apt-Y-R and Y-L-G, where the I-strand endowed the DNA nanoantenna with the ability to receive and convert signals, the Apt-Y-R containing an aptamer fragment gave the DNA nanoantenna the ability to specifically anchor target tumor cells, and the complementarity of Y-L-G with the other two sequences ensured the stability of the DNA nanoantenna. Initially, the DNA nanoantenna was in a "silent" state, and rhodamine green was close to BHQ2, leading to suppressed signal emission. When the DNA nanoantenna anchored on the surface of target cancer cells through the aptamer recognition domain, the I-strand tended to fold into a hairpin-contained i-motif tetramer structure owing to the extracellular low pH stimuli, resulting in the DNA nanoantenna changing into an "active" state. In the meantime, rhodamine green moved far away from BHQ2, resulting in a strong signal output. The results demonstrate that the pH-Apt-YNA presents a sensitive pH sensing capacity within a narrow pH range of 6.2-7.4 and exhibits excellent specificity for the imaging of target cancer cell extracellular pH. Based on these advantages, we therefore anticipate that our facile design of the DNA nanoantenna with sensitive responsiveness provides a new way and great promise in the application of sensing pH-related physiological and pathological processes.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Neoplasias , Humanos , Fuerza Protón-Motriz , ADN/química , Rodaminas/química , Oligonucleótidos , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodosRESUMEN
The purpose of this study was to explore the relationship between the MYCN gene, serum neuron-specific enolase (NSE), urinary vanillylmandelic acid (VMA) levels, and neuroblastoma pathological features and prognosis. Ninety-four children with neuroblastoma treated in the hospital were selected to compare the differences in MYCN gene amplification, serum NSE, and urinary VMA levels in children with different clinicopathological features and prognoses. The proportion of children with MYCN gene copy number ≥10 in INSS stage 3-4 was higher than that of children with INSS stage 1-2 (P < 0.05); the proportion of children with MYCN gene copy number ≥10 in high-risk children in the COG risk stratification was higher than that of children with intermediate and low risk (P < 0.05); the serum NSE of children aged >12 months higher than that of children aged ≤12 months (P < 0.05); serum NSE of children with tumors >500 cm3 higher than that of children with tumors ≤500 cm3 (P < 0.05); serum NSE and urinary VMA of children with INSS staging of stages 3-4 were higher than that of children with stages 1 to 2 (P < 0.05); serum NSE and urinary VMA in children with lymph node metastasis were higher than that of children without lymph node metastasis (P < 0.05); serum NSE of children with MYCN gene copy number ≥10 was higher than that of children without lymph node metastasis (P < 0.05); the proportion of children with MYCN gene copy number ≥10 who died, and the percentages of serum NSE and urinary VMA were higher than those of the surviving children (P < 0.05). MYCN gene amplification and serum NSE and urinary VMA levels were related to the age, tumor size, INSS stage, COG stage, lymph node metastasis, and prognosis of the children with neuroblastoma.
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Proteína Proto-Oncogénica N-Myc , Neuroblastoma , Fosfopiruvato Hidratasa , Ácido Vanilmandélico , Humanos , Neuroblastoma/genética , Neuroblastoma/sangre , Neuroblastoma/orina , Neuroblastoma/patología , Proteína Proto-Oncogénica N-Myc/genética , Masculino , Femenino , Pronóstico , Lactante , Preescolar , Fosfopiruvato Hidratasa/sangre , Fosfopiruvato Hidratasa/genética , Fosfopiruvato Hidratasa/orina , Ácido Vanilmandélico/orina , Ácido Vanilmandélico/sangre , Estadificación de Neoplasias , Dosificación de Gen , Niño , Amplificación de Genes , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/orinaRESUMEN
Proflavine (PF), an acridine DNA intercalating agent, has been widespread applied as an anti-microbial and topical antiseptic agent due to its ability to suppress DNA replication. On the other hand, various studies show that PF intercalation to DNA can increase photogenotoxicity and has potential chances to induce carcinomas of skin appendages. However, the effects of PF intercalation on the photophysical and photochemical properties of DNA have not been sufficiently explored. In this study, the excited state dynamics of the PF intercalated d(GC)9 ⢠d(GC)9 and d(AT)9 ⢠d(AT)9 DNA duplex are investigated in an aqueous buffer solution. Under 267 nm excitation, we observed ultrafast charge transfer (CT) between PF and d(GC)9 ⢠d(GC)9 duplex, generating a CT state with an order of magnitude longer lifetime compared to that of the intrinsic excited state reported for the d(GC)9 ⢠d(GC)9 duplex. In contrast, no excited state interaction was detected between PF and d(AT)9 ⢠d(AT)9. Nevertheless, a localized triplet state with a lifetime over 5 µs was identified in the PF-d(AT)9 ⢠d(AT)9 duplex.
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Sustancias Intercalantes , Proflavina , Proflavina/química , Análisis Espectral , Sustancias Intercalantes/química , ADN/químicaRESUMEN
Microglia migrate to the cerebral cortex during early embryonic stages. However, the precise mechanisms underlying microglia migration remain incompletely understood. As an extracellular matrix protein, Netrin-1 is involved in modulating the motility of diverse cells. In this paper, we found that Netrin-1 promoted microglial BV2 cell migration in vitro. Mechanism studies indicated that the activation of GSK3ß activity contributed to Netrin-1-mediated microglia migration. Furthermore, Integrin α6/ß1 might be the relevant receptor. Single-cell data analysis revealed the higher expression of Integrin α6 subunit and ß1 subunit in microglia in comparison with classical receptors, including Dcc, Neo1, Unc5a, Unc5b, Unc5c, Unc5d, and Dscam. Microscale thermophoresis (MST) measurement confirmed the high binding affinity between Integrin α6/ß1 and Netrin-1. Importantly, activation of Integrin α6/ß1 with IKVAV peptides mirrored the microglia migration and GSK3 activation induced by Netrin-1. Finally, conditional knockout (CKO) of Netrin-1 in radial glial cells and their progeny led to a reduction in microglia population in the cerebral cortex at early developmental stages. Together, our findings highlight the role of Netrin-1 in microglia migration and underscore its therapeutic potential in microglia-related brain diseases.
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Movimiento Celular , Microglía , Netrina-1 , Netrina-1/metabolismo , Netrina-1/genética , Microglía/metabolismo , Animales , Ratones , Ratones Noqueados , Corteza Cerebral/metabolismo , Corteza Cerebral/citología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Línea Celular , Integrina beta1/metabolismo , Integrina beta1/genéticaRESUMEN
Mechanically interlocked molecules (MIMs) are promising platforms for developing functionalized artificial molecular machines. The construction of chiral MIMs with appealing circularly polarized luminescence (CPL) properties has boosted their potential application in biomedicine and the optical industry. However, there is currently little knowledge about the CPL emission mechanism or the emission dynamics of these related MIMs. Herein, we demonstrate that time-resolved circularly polarized luminescence (TRCPL) spectroscopy combined with transient absorption (TA) spectroscopy offers a feasible approach to elucidate the origins of CPL emission in pyrene-functionalized topologically chiral [2]catenane as well as in a series of pyrene-functionalized chiral molecules. For the first time, direct evidence differentiating the chiroptical signals originating from either topological (local state emission) or Euclidean chirality (excimer state emission) in these pyrene-functionalized chiral molecules has been discovered. Our work not only establishes a novel and ideal approach to study CPL mechanism, but also provides a theoretical foundation for the rational design of novel chiral materials in the future.
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ABSTRACT: Histiocytic sarcoma is a tumor of the lymphohematopoietic system characterized by macrophage morphology and immunophenotype. Here, we report FDG PET/CT images of a 50-year-old man with coexisting histiocytic sarcoma of the liver and spleen. Images showed multiple enhanced uptake lesions of FDG in both the liver and spleen. Ultimately, histiocytic sarcoma was confirmed by the biopsy histopathology.
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Sarcoma Histiocítico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Masculino , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Sarcoma Histiocítico/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Bazo/diagnóstico por imagen , Bazo/patología , Hígado/diagnóstico por imagen , Hígado/patologíaRESUMEN
Gilvocarcin V (GV) is a natural antibiotic exhibiting excellent antitumor activities and remarkably low toxicity in near-ultraviolet or visible light-dependent treatment. Notwithstanding, the [2 + 2] cycloaddition reaction between GV and thymine has been proven to be the key for its function in photodynamic therapy, and crucial mechanistic details about such a reaction are poorly understood. In this study, the electronic relaxation pathways and photoaddition reaction are characterized by femto- to nanosecond time-resolved spectroscopy combined with quantum chemical calculation. Our results reveal that ultrafast intersystem crossing (<3 ps) leads to the population of a local triplet excited state in DNA-intercalated GV. Such a state can further induce the formation of a biradical state, which is identified as the important reactive precursor for photoaddition between GV and thymine. The overall photoaddition quantum efficiency is determined to be 11.57 ± 1.0%. These results are essential to the elucidation of the DNA photoaddition mechanism of C-aryl glycoside-based artificial photocytotoxic agents and could help further development of those medicines.
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Cumarinas , Glicósidos , Timina , Timina/química , ADN/química , AntibacterianosRESUMEN
PURPOSE: Engagement in self-injurious thoughts and behaviors (SITBs) is associated with low help-seeking intentions. Nevertheless, prior research has primarily relied on cross-sectional data, leaving uncertainties about the longitudinal dynamics between SITBs and help-seeking intentions. This study aims to investigate the longitudinal relationship between SITBs and help-seeking intentions for them. METHOD: A one-year interval follow-up investigation was conducted among 1788 Chinese students (71.5% girls, Mage = 19.5). Changes in help-seeking intentions were initially analyzed among four SITBs transition groups. Subsequently, a cross-lagged model was employed to explore the possible bidirectional associations. RESULTS: 232 participants (12.90%) experienced changes in SITBs, while 65 participants (3.60%) exhibited sustained SITBs between two measurement time points. Changes in help-seeking intentions varied across SITBs transition groups. Participants whose SITBs faded 1 year later showed a significant increase in help-seeking intentions, whereas those who experienced newly developed SITBs across two measurement time points demonstrated a significant decline. The cross-lagged analysis revealed that help-seeking intentions negatively predicted the subsequent risk of experiencing SITBs. CONCLUSIONS: Greater help-seeking intentions predicted decreased SITBs 1 year later. Changes in help-seeking intentions serve as a valuable indicator for distinguishing between different types of SITBs transition. These findings underscore the importance of implementing prevention and intervention strategies targeted at enhancing help-seeking intentions to reduce SITBs.
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BACKGROUND: Glucocorticoids are widely used in inhalation aerosol therapy for wheezing diseases. This study aims to explore guardians' knowledge and attitude towards inhaled corticosteroids (ICS) aerosol therapy and the medication compliance of children with wheezing diseases in China. METHODS: This cross-sectional study enrolled guardians of children with wheezing diseases at the First Hospital Affiliated to Shaoyang College between October 2022 and February 2023. A self-administered questionnaire was developed to collect demographic information of the participants and evaluate their knowledge and attitude towards ICS aerosol therapy. The 8-item Morisky Medication Adherence Scale was used to assess the medication compliance of children. RESULTS: A total of 506 valid questionnaires were collected. 260 (51.38%) participants were guardians of a ≤ 3-year-old child and 327 (64.62%) were children's mothers. The knowledge, attitude, and medication compliance scores of all participants were 12.61 ± 5.78, 20.95 ± 2.37, and 4.69 ± 2.18, respectively. Multivariate logistic regression showed that knowledge scores [OR = 1.053, 95% CI (confidence interval): 1.017-1.090, P = 0.003], attitude scores (OR = 1.121, 95% CI: 1.030-1.219, P = 0.008), guardians of children aged 4-6 years (OR = 0.385, 95% CI: 0.242-0.612, P < 0.001), and grandparents of children (OR = 2.633, 95% CI: 1.104-6.275, P = 0.029) were independently associated with children's medication compliance. CONCLUSIONS: In conclusion, guardians of children with wheezing diseases in China had insufficient knowledge, unsatisfactory attitude, and poor medication compliance towards ICS aerosol therapy. TRIAL REGISTRATION: Retrospectively registered.
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The existence of the oxidation/reduction interface can promote the performance of a photocatalyst, due to its effect on the separation of photogenerated carriers and the surface reactivity. However, it is difficult to construct two sets of oxidation/reduction interfaces in a single crystal and compare their separation efficiency for photogenerated carriers. Introducing a high proportion of active facets into the co-exposed facets is even more challenging. Herein, a hollow anatase TiO2 tetrakaidecahedron (HTT) with two sets of oxidation/reduction interfaces ({001}/{101} and {001}/{110}) is synthesized by directional chemical etching. Theoretical and experimental results indicate that the {001}/{110} interface is a dominant oxidation/reduction interface, showing a better promotion on the separation of photogenerated carriers than the {001}/{101} interface. In the HTT, the ratio of dominant {001}/(110) is increased and the proportion of the active {110} facet is about 40% (generally about 15%). Therefore, the HTT shows excellent catalytic activity for photocatalytic reductive (hydrogen production) and oxidative (selective oxidation of sulfides) reactions. The HTT also demonstrates favorable photocatalytic activity for the cross-dehydrogenative coupling reaction, where both photogenerated electrons and photogenerated holes are involved, further verifying its high separation efficiency of photogenerated carriers and surface reactivity. This work provides an important guideline for developing advanced structures with a predetermined interface toward desired applications.
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Purpose: Humanistic caring in clinical practice is important for quality care and patient satisfaction. This study aimed to assess patient satisfaction with humanistic care for emergency patients in China and its associated factors. Methods: From October 2023 to December 2023, a multi-center cross-sectional survey was conducted across 28 provinces and 87 hospitals in China, using a sampling method for inpatients in emergency department. Patient satisfaction with humanistic care was evaluated by a self-developed questionnaire with 32 items across 6 dimensions. Stepwise multiple linear regression was used to explore associated factors. Results: A total of 3,003 valid questionnaires were successfully collected, with an effective rate of 86.05%. The emergency patients' total mean humanistic caring satisfaction score was 4.67 ± 0.66. Age, medical insurance type, specialized emergency department visited, waiting times, whether had accompanied person, hospital level, and hospital type are correlated factors (P < 0.05) regarding humanistic caring satisfaction. The correlation analysis showed perceived value, and its three dimensions were moderately correlated with humanistic caring satisfaction. The multiple linear regression showed waiting time (ß = -0.219, P < 0.05), whether had accompanied person (ß = -0.192, P < 0.05), hospital level (ß = -0.137, P < 0.05), functional value (ß = 0.197, P < 0.05), and emotional value (ß = 0.418, P < 0.05) were strong predictors. Conclusion: Hospitals at all levels should improve patients' perceived value, shorten waiting times, and provide caregivers with improved humanistic care in the emergency department.
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Servicio de Urgencia en Hospital , Humanismo , Satisfacción del Paciente , Humanos , Estudios Transversales , China , Femenino , Masculino , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , Adulto , Encuestas y Cuestionarios , Servicio de Urgencia en Hospital/estadística & datos numéricos , Anciano , Hospitales , Adolescente , Adulto JovenRESUMEN
Wearable sweat sensors have achieved rapid development since they hold great potential in personalized health monitoring. However, a typical difficulty in practical processes is the control of working conditions for biorecognition elements, e.g., pH level and ionic strength in sweat may decrease the affinity between analytes and recognition elements. Here, we developed a wearable sensing device for cortisol detection in sweat using an aptamer as the recognition element. The device integrated functions of sweat collection, reagent prestorage, and signal conversion. Especially, the components of prestored reagents were optimized according to the inherent characteristics of sweat samples and electrodes, which allowed us to keep optimal conditions for aptamers. The sweat samples were transferred from the inlet of the device to the reagent prestored chamber, and the dry preserved reagents were rehydrated with sweat and then arrived at the aptamer-modified electrodes. Sweat samples of volunteers were analyzed by the wearable sensing device, and the results showed a good correlation with those of the ELISA kit. We believe that this convenient and reliable wearable sensing device has significant potential in self-health monitoring.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Hidrocortisona , Sudor , Dispositivos Electrónicos Vestibles , Sudor/química , Hidrocortisona/análisis , Humanos , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Electrodos , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Indicadores y Reactivos/químicaRESUMEN
OBJECTIVES: To investigate PET/CT registration and quantification accuracy of thoracic lesions of a single 30-second deep-inspiration breath-hold (DIBH) technique with a total-body PET (TB-PET) scanner, and compared with free-breathing (FB) PET/CT. METHODS: 137 of the 145 prospectively enrolled patients finished a routine FB-300 s PET/CT exam and a 30-second DIBH TB-PET with chest to pelvis low dose CT. The total-body FB-300 s, FB-30 s, and DIBH-30 s PET images were reconstructed. Quantitative assessment (SUVmax and SUVmean of lung and other organs), PET/CT registration assessment and lesion analysis (SUVmax, SUVpeak, SUVmean and tumor-background ratio) were compared with Wilcoxon signed-rank tests. RESULTS: The SUVmax and SUVmean of the lung with DIBH-30 s were significantly lower than those with FB. The distances of the liver dome between PET and CT were significantly smaller with DIBH-30 s than with FB. 195 assessable lesions in 106 patients were included, and the detection sensitivity was 97.9 % and 99.0 % in FB-300 s, and DIBH-30 s, respectively. For both small co-identified lesions (n = 86) and larger co-identified lesions with a diameter ≥ 1 cm (n = 91), the lesion SUVs were significantly greater with DIBH-30 s than with FB-300 s. Regarding lesion location, the differences of the SUVs for the lesions in the lower thorax area (n = 97, p < 0.001) were significant between DIBH-30 s and FB-300 s, while these differences were not statistically significant in the upper thorax (n = 80, p > 0.05). The lesion tumor-to-surrounding-background ratio (TsBR) was significantly increased, both in the upper and lower thorax. CONCLUSION: The TB DIBH PET/CT technique is feasible in clinical practice. It reduces the background lung uptake and achieves better registration and lesion quantification, especially in the lower thorax.
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Contencion de la Respiración , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Sensibilidad y Especificidad , Imagen de Cuerpo Entero , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Imagen de Cuerpo Entero/métodos , Adulto , Estudios Prospectivos , Anciano de 80 o más Años , Reproducibilidad de los Resultados , Neoplasias Torácicas/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , InhalaciónRESUMEN
OBJECTIVE: Electroconvulsive therapy (ECT) is endorsed as a principal treatment approach for major depressive disorder (MDD) worldwide. Despite prior studies highlighting potential short-term cognitive deficits post-ECT, the debate regarding its long-term implications persists. This study endeavors to elucidate the reasons for this contention using an evidence-based approach. METHODS: This investigation, meticulously aligned with PRISMA guidelines, was prospectively enlisted on PROSPERO (CRD42023439259). A comprehensive search was performed across various databases, including PubMed, Cochrane Library, Web of Science, Embase, SCOPUS, PsycINFO, CINAHL Plus, and OpenGrey. This review, traversing the literature from inception until June 2023, encapsulated 10 studies (five RCTs and five quasi-experimental studies) involving a cohort of 868 individuals diagnosed with major depressive disorder. RESULTS: The meta-analysis revealed that the persistent discourse on ECT-induced long-term cognitive impairment chiefly emanates from the inadequacies in the specificity and sensitivity of conventional assessment instruments. Conversely, subgroup analyses showed that cognitive impairment in ECT, as gauged by the nascent assessment tool, Electroconvulsive Therapy Cognitive Assessment (ECCA) (SMD = -0.94, 95 % CI [-1.33, -0.54], p < 0.00001), exerted a detrimental influence on the long-term trajectory of individuals with MDD. Notably, there was an adverse effect of ECT on the subdomain of long-term learning cognitive abilities in patients with MDD (SMD = -0.37, 95 % CI [-0.55, -0.18], p < 0.0001). Contrarily, memory (SMD = 0.16, 95 % CI [-0.02, 0.34], p = 0.08), attention (SMD = 0.23, 95 % CI [-0.07, 0.54], p = 0.14), language (SMD = -0.10, 95 % CI [-0.25, 0.05], p = 0.19), spatial perception, and orientation (SMD = -0.04, 95 % CI [-0.28, 0.20], p = 0.75) exhibited no significant detriments. Intriguingly, ECT showed favorable effects on executive function and processing speed among patients with MDD (SMD = 0.52, 95 % CI [0.29, 0.74], p < 0.00001). CONCLUSION: This meta-analysis underscores ECCA's superior sensitivity of the ECCA compared to the MMSE or MoCA in detecting cognitive changes in patients with post-ECT MDD. Following Electroconvulsive Therapy (ECT), deterioration was observed in overall cognitive function and learning capabilities, while memory, attention, language, and spatial perception remained stable. Notably, enhancements were discerned in executive function and processing speed, which not only augmented academic perspectives but also steered the formulation of international clinical guidelines, accentuating the progressive role of ECT in the therapeutic approach to MDD.
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Disfunción Cognitiva , Trastorno Depresivo Mayor , Terapia Electroconvulsiva , Humanos , Cognición , Disfunción Cognitiva/etiología , Disfunción Cognitiva/terapia , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/psicología , Terapia Electroconvulsiva/efectos adversos , Función EjecutivaRESUMEN
Transmembrane ion transport modality has received a widespread attention due to its apoptotic activation toward anticancer cell activities. In this study, G-quadruplex-based potassium-specific transmembrane channels have been developed to facilitate the intracellular K+ efflux, which perturbs the cellular ion homeostasis thereby inducing cancer cell apoptosis. Cholesterol-tag, a lipophilic anchor moiety, serves as a rudiment for the G-quadruplex immobilization onto the membrane, while G-quadruplex channel structure as a transport module permits ion binding and migration along the channels. A c-Myc sequence tagged with two-cholesterol is designed as a representative lipophilic G-quadruplex, which forms intramolecular parallel G-quadruplex with three stacks of G-quartets (Ch2-Para3). Fluorescence transport assay demonstrates Ch2-Para3 a high transport activity (EC50 = 10.9 × 10-6 m) and an ion selectivity (K+/Na+ selectivity ratio of 84). Ch2-Para3 mediated K+ efflux in cancer cells is revealed to purge cancer cells through K+ efflux-mediated cell apoptosis, which is confirmed by monitoring the changes in membrane potential of mitochondria, leakage of cytochrome c, reactive oxygen species yield, as well as activation of a family of caspases. The lipophilic G-quadruplex exhibits obvious antitumor activity in vivo without systemic toxicity. This study provides a functional scheme aimed at generating DNA-based selective artificial membrane channels for the purpose of regulating cellular processes and inducing cell apoptosis, which shows a great promising for anticancer therapy in the future.
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Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeATac1 neurons) are activated during aggressive behaviors in male mice. We identified MeATac1 neurons as a key mediator of aggression and found that MeATac1âventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits.
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Objectives: This study aimed to identify the key elements and develop a formation mechanism model of quality geriatric care behavior for nursing assistants. Methods: This qualitative research employed the strategy of grounded theory proposed by Strauss and Corbin. Furthermore, the data was collected by participatory observation and semi-structured interviews. A total of 12 nursing managers, 63 nursing assistants, and 36 older people from 9 nursing homes in 6 cities were interviewed, whereas for the observatory survey, participants were recruited from 2 nursing homes. Results: The comparative and analysis process revealed 5 key elements of quality geriatric care behavior, including holistic care, personalized care, respect, positive interaction, and empowerment. Based on the Capability-Opportunity-Motivation-Behavior (COM-B) model, key elements and the 3 stages of quality geriatric care behavior (negative behavior cognition stage, practice exchange run-in stage, and positive behavior reinforcement stage), the theoretical framework of the formation mechanism was established. Conclusion: The results indicated that nursing assistants' capabilities, motivation, and organizational and environmental support are vital for quality care behaviors. The theoretical framework established in this study provides theoretical support and practical reference to policymakers, institutional administrators, and healthcare professionals for improving nursing assistant's care behaviors.