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3D printing has been widely used for on-demand prototyping of complex three-dimensional structures. In biomedical applications, PEDOT:PSS has emerged as a promising material in versatile bioelectronics due to its tissue-like mechanical properties and suitable electrical properties. However, previously developed PEDOT:PSS inks have not been able to fully utilize the advantages of commercial 3D printing due to its long post treatment times, difficulty in high aspect ratio printing, and low conductivity. We propose a one-shot strategy for the fabrication of PEDOT:PSS ink that is able to simultaneously achieve on-demand biocompatibility (no post treatment), structural integrity during 3D printing for tall three-dimensional structures, and high conductivity for rapid-prototyping. By using ionic liquid-facilitated PEDOT:PSS colloidal stacking induced by a centrifugal protocol, a viscoplastic PEDOT:PSS-ionic liquid colloidal (PILC) ink was developed. PILC inks exhibit high-aspect ratio vertical stacking, omnidirectional printability for generating suspended architectures, high conductivity (~286 S/cm), and high-resolution printing (~50 µm). We demonstrate the on-demand and versatile applicability of PILC inks through the fabrication of 3D circuit boards, on-skin physiological signal monitoring e-tattoos, and implantable bioelectronics (opto-electrocorticography recording, low voltage sciatic nerve stimulation and recording from deeper brain layers via 3D vertical spike arrays).
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Materiales Biocompatibles , Coloides , Conductividad Eléctrica , Líquidos Iónicos , Poliestirenos , Impresión Tridimensional , Líquidos Iónicos/química , Coloides/química , Materiales Biocompatibles/química , Animales , Poliestirenos/química , Ratas , Tinta , Polímeros/química , Tiofenos/química , Neuronas/fisiología , Compuestos Bicíclicos Heterocíclicos con Puentes/químicaRESUMEN
BACKGROUND: On June 30, 2021, China received certification from the World Health Organization for malaria elimination. However, this certification does not signify the absence of malaria within China. Due to the increasing frequency of international exchanges and collaborations, the threat of imported malaria persists in China. Consequently, the prevention and control of imported malaria have become a primary focus for our country to maintain its malaria elimination status. CASE SUMMARY: Herein, we present a case report of a 53-year-old Chinese man who worked in Africa for nearly two years. He was diagnosed with malaria in the Democratic Republic of the Congo between November 19 and November 23, 2022. After receiving effective treatment with oral antimalarial drugs, his condition improved, allowing him to return to China. He was later admitted to our hospital on January 12, 2023, during the coronavirus disease 2019 pandemic in Huangshi, China. Through a thorough evaluation of the patient's symptoms, clinical signs, imaging and laboratory test results, and epidemiological data, he was rapidly diagnosed with severe cerebral malaria. The patient underwent successful treatment through a series of intensive care unit interventions. CONCLUSION: The successful treatment of this imported case of severe cerebral malaria provides a valuable reference for managing patients with similar malaria infections and has significant clinical implications.
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NiFe layered double hydroxide (LDH) with abundant heterostructures represents a state-of-the-art electrocatalyst for the alkaline oxygen evolution reaction (OER). Herein, NiFe LDH/Fe2O3 nanosheet arrays have been fabricated by facile combustion of corrosion-engineered NiFe foam (NFF). The in situ grown, self-supported electrocatalyst exhibited a low overpotential of 248 mV for the OER at 50 mA cm-2, a small Tafel slope of 31 mV dec-1, and excellent durability over 100 h under the industrial benchmarking 500 mA cm-2 current density. A balanced Ni and Fe composition under optimal corrosion and combustion contributed to the desirable electrochemical properties. Comprehensive ex-situ analyses and operando characterizations including Fourier-transformed alternating current voltammetry (FTACV) and in situ Raman demonstrate the beneficial role of modulated interfacial electron transfer, dynamic atomic structural transformation to NiOOH, and the high-valence active metal sites. This study provides a low-cost and easy-to-expand way to synthesize efficient and durable electrocatalysts.
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Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-ß1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-ß1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-ß1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 µM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-ß1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 µM) downregulated TGF-ß1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 (ATG5) gene silencing decreased the TGF-ß1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-ß1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis.
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Autofagia , Células Epiteliales , Transición Epitelial-Mesenquimal , NADPH Oxidasa 4 , Estrés Oxidativo , Especies Reactivas de Oxígeno , Transducción de Señal , Factor de Crecimiento Transformador beta1 , Humanos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Autofagia/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , NADPH Oxidasa 4/metabolismo , NADPH Oxidasa 4/genética , Transducción de Señal/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Peritoneo/patología , Pirazolonas , PiridonasRESUMEN
High-temperature piezoelectric materials, which enable the accurate and reliable sensing of physical parameters to guarantee the functional operation of various systems under harsh conditions, are highly demanded. To this end, both large piezoelectricity and high Curie temperature are pivotal figures of merit (FOMs) for high-temperature piezoceramics. Unfortunately, despite intensive pursuits, it remains a formidable challenge to unravel the inverse correlation between these FOMs. Herein, a conceptual material paradigm of multiscale structural engineering was proposed to address this dilemma. The synergistic effects of phase structure reminiscent of a polymorphic phase boundary and refined domain morphology simultaneously contribute to a large piezoelectric coefficient d33 of 30.3 pC/N and a high Curie temperature TC of 740 °C in (LiCeNd) codoped Na0.5Bi2.5Nb2O9 (NBN-LCN) ceramics. More encouragingly, the system has exceptional thermal stability and is nonsusceptible to mechanical loading. This study not only demonstrates that the high-performance and robust NBN-LCN high-temperature piezoceramics hold great potential for implements under harsh conditions but also opens an avenue for integrating antagonistic properties for the enhancement of the collective performance in functional materials.
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BACKGROUND: Recently, a growing number of adolescents have been afflicted with mental disorders, with annual morbidity rates on the rise. This trend has been exacerbated by the global coronavirus disease 2019 (COVID-19) pandemic, leading to a surge in suicide and self-harm rates among this demographic. AIM: To investigate the impact of the COVID-19 pandemic on adolescent bipolar disorder (BD), along with the underlying factors contributing to heightened rates of suicide and self-harm among adolescents. METHODS: A comprehensive statistical analysis was conducted utilizing clinical interviews and self-reports obtained from patients or their guardians. Diagnostic criteria for BDs were based on the Diagnostic and statistical manual of mental disorders, international classification of diseases-11, and the National institute of mental health research domain criteria. Statistical analyses were performed using SPSS 26.0 software, with significance set at P < 0.05. RESULTS: A cohort of 171 adolescents diagnosed with BD between January 1, 2018, and December 31, 2022, was included in the analysis. The gender distribution was 2.8:1 (female to male), with ages ranging from 11 to 18 years old. Major factors contributing to adolescent BDs included familial influences, academic stress, genetic predisposition and exposure to school-related violence. Notably, a significant increase in suicide attempts and self-harm incidents was observed among adolescents with BD during the COVID-19 pandemic. Statistical analysis indicated that the pandemic exacerbated familial discord and heightened academic stress, thereby amplifying the prevalence of suicidal behavior and self-harm among adolescents. CONCLUSION: The COVID-19 pandemic has exacerbated familial tensions and intensified the incidence of suicide and self-harm among adolescents diagnosed with BD. This study underscores the urgent need for societal, familial and educational support systems to prioritize the well-being of adolescents and offers valuable insights and guidelines for the prevention, diagnosis and treatment of adolescent BDs.
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The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56 years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9 years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.
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Corticoesteroides , Everolimus , Rechazo de Injerto , Trasplante de Corazón , Inmunosupresores , Sistema de Registros , Humanos , Everolimus/administración & dosificación , Everolimus/uso terapéutico , Trasplante de Corazón/efectos adversos , Persona de Mediana Edad , Masculino , Femenino , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , República de Corea/epidemiología , Rechazo de Injerto/prevención & control , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Resultado del Tratamiento , Supervivencia de Injerto , Estudios RetrospectivosRESUMEN
DEAD box helicase 41 (DDX41) mutations are the most prevalent predisposition to familial myelodysplastic syndrome (MDS). However, the precise roles of these variants in the pathogenesis of MDS have yet to be elucidated. Here, we discovered a novel mechanism by which DDX41 contributes to R-loop-induced DNA damage responses (DDR) in cooperation with the m6A-METTL complex (MAC) and YTHDC1 using DDX41 knockout (KO) and DDX41 knock-in (KI, R525H, Y259C) cell lines as well as primary samples from MDS patients. Compared to wild type (WT), DDX41 KO and KI led to increased levels of m6A RNA methylated R-loop. Interestingly, we found that DDX41 regulates m6A/R-loop levels by interacting with MAC components. Further, DDX41 promoted the recruitment of YTHDC1 to R-loops by promoting the binding between METTL3 and YTHDC1, which was dysregulated in DDX41-deficient cells, contributing to genomic instability. Collectively, we demonstrated that DDX41 plays a key role in the physiological control of R-loops in cooperation with MAC and YTHDC1. These findings provide novel insights into how defects in DDX41 influence MDS pathogenesis and suggest potential therapeutic targets for the treatment of MDS.
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ARN Helicasas DEAD-box , Metiltransferasas , Mutación , Síndromes Mielodisplásicos , Factores de Empalme de ARN , Humanos , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Síndromes Mielodisplásicos/metabolismo , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Estructuras R-Loop , Daño del ADN , Unión Proteica , Proteínas del Tejido NerviosoRESUMEN
Dual immunoglobulin domain-containing cell adhesion molecule (DICAM) is a type I transmembrane protein that presents in various cells including renal tubular cells. This study evaluated the expression and protective role of DICAM in renal tubular cell injury. HK-2 cells were incubated and treated with lipopolysaccharide (LPS, 30 µg/mL) or hydrogen peroxide (H2O2, 100 µM) for 24 h. To investigate the effect of the gene silencing of DICAM, small interfering RNA of DICAM was used. Additionally, to explain its role in cellular response to injury, DICAM was overexpressed using an adenoviral vector. DICAM protein expression levels significantly increased following treatment with LPS or H2O2 in HK-2 cells. In response to oxidative stress, DICAM showed an earlier increase (2-4 h following treatment) than neutrophil gelatinase-associated lipocalin (NGAL) (24 h following treatment). DICAM gene silencing increased the protein expression of inflammation-related markers, including IL-1ß, TNF-α, NOX4, integrin ß1, and integrin ß3, in H2O2-induced HK-2 cell injury. Likewise, in the LPS-induced HK-2 cell injury, DICAM knockdown led to a decrease in occludin levels and an increase in integrin ß3, IL-1ß, and IL-6 levels. Furthermore, DICAM overexpression followed by LPS-induced HK-2 cell injury resulted in an increase in occludin levels and a decrease in integrin ß1, integrin ß3, TNF-α, IL-1ß, and IL-6 levels, suggesting an alleviating effect on inflammatory responses. DICAM was elevated in the early stage of regular tubular cell injury and may protect against renal tubular injury through its anti-inflammatory properties. DICAM has a potential as an early diagnostic marker and therapeutic target for renal cell injury.
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A comprehensive understanding of the characteristics of biochar released-dissolved organic matter (BDOM) derived from an invasive plant and its impact on the binding behavior of pharmaceuticals is essential for the application of biochar, yet has received less attention. In this study, the binding behavior of BDOM pyrolyzed at 300-700 °C with sulfathiazole, acetaminophen, chloramphenicol (CAP), and carbamazepine (CMZ) was investigated based on a multi-analytical approach. Generally, the pyrolysis temperature exhibited a more significant impact on the spectral properties of BDOM and pharmaceutical binding behavior than those of the molecular weight. With increased pyrolysis temperature, the dissolved organic carbon decreased while the proportion of the protein-like substance increased. The highest binding capacity towards the drugs was observed for the BDOM pyrolyzed at 500 °C with the molecular weight larger than 0.3 kDa. Moreover, the protein-like substance exhibited higher susceptive and released preferentially during the dialysis process and also showed more sensitivity and bound precedingly with the pharmaceuticals. The active binding points were the aliphatic C-OH, amide II N-H, carboxyl CO, and phenolic-OH on the tryptophan-like substance. Furthermore, the binding affinity of the BDOM pyrolyzed at 500 °C was relatively high with the stability constant (logKM) of 4.51 ± 0.52.
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Materia Orgánica Disuelta , Pirólisis , Temperatura , Peso Molecular , Carbón Orgánico/química , Sustancias Húmicas/análisis , Proteínas , Preparaciones FarmacéuticasRESUMEN
INTRODUCTION: Children receiving extracorporeal membrane oxygenation are prone to delirium. This case report describes the nursing care of a child with delirium who received venoarterial extracorporeal membrane oxygenation. Relevant interventions and precautions are also discussed. CLINICAL FINDINGS: A 6-year-old girl was admitted to the pediatric intensive care unit with a 2-day history of vomiting and fever. The child underwent cannulation for venoarterial extracorporeal membrane oxygenation. DIAGNOSIS: The child was diagnosed with acute fulminant myocarditis, cardiac shock, and ventricular arrhythmia. INTERVENTIONS: On the third day of extracorporeal membrane oxygenation, bedside nurses began using the Cornell Assessment of Pediatric Delirium to assess the child for delirium symptoms. The team of physicians and nurses incorporated a nonpharmacologic delirium management bundle into pediatric daily care. Delirium screening, analgesia and sedation management, sleep promotion, and family participation were implemented. OUTCOMES: During the 18 days of pediatric intensive care unit hospitalization, the child had 6 days of delirium: 1.5 days of hypoactive delirium, 1.5 days of hyperactive delirium, and 3 days of mixed delirium. The child was successfully discharged home on hospital day 22. CONCLUSION: Caring for a child with delirium receiving venoarterial extracorporeal membrane oxygenation required multidimensional nursing capabilities to prevent and reduce delirium while ensuring safe extracorporeal membrane oxygenation. This report may assist critical care nurses caring for children under similar circumstances.
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Delirio , Oxigenación por Membrana Extracorpórea , Niño , Femenino , Humanos , Arritmias Cardíacas , Delirio/diagnóstico , Oxigenación por Membrana Extracorpórea/métodos , Choque CardiogénicoRESUMEN
BACKGROUND: Non-small cell lung cancer (NSCLC) remains at the forefront of new cancer cases, and there is an urgent need to find new treatments or improve the efficacy of existing therapies. In addition to the application in the field of cerebrovascular diseases, recent studies have revealed that tanshinone IIA (Tan IIA) has anticancer activity in a variety of cancers. PURPOSE: To investigate the potential anticancer mechanism of Tan IIA and its impact on immunotherapy in NSCLC. METHODS: Cytotoxicity and colony formation assays were used to detect the Tan IIA inhibitory effect on NSCLC cells. This research clarified the mechanisms of Tan IIA in anti-tumor and programmed death-ligand 1 (PD-L1) regulation by using flow cytometry, transient transfection, western blotting and immunohistochemistry (IHC) methods. Besides, IHC was also used to analyze the nuclear factor of activated T cells 1 (NFAT2) expression in NSCLC clinical samples. Two animal models including xenograft mouse model and Lewis lung cancer model were used for evaluating tumor suppressive efficacy of Tan IIA. We also tested the efficacy of Tan IIA combined with programmed cell death protein 1 (PD-1) inhibitors in Lewis lung cancer model. RESULTS: Tan IIA exhibited good NSCLC inhibitory effect which was accompanied by endoplasmic reticulum (ER) stress response and increasing Ca2+ levels. Moreover, Tan IIA could suppress the NFAT2/ Myc proto oncogene protein (c-Myc) signaling, and it also was able to control the Jun Proto-Oncogene(c-Jun)/PD-L1 axis in NSCLC cells through the c-Jun N-terminal kinase (JNK) pathway. High NFAT2 levels were potential factors for poor prognosis in NSCLC patients. Finally, animal experiments data showed a stronger immune activation phenotype, when we performed treatment of Tan IIA combined with PD-1 monoclonal antibody. CONCLUSION: The findings of our research suggested a novel mechanism for Tan IIA to inhibit NSCLC, which could exert anti-cancer effects through the JNK/NFAT2/c-Myc pathway. Furthermore, Tan IIA could regulate tumor PD-L1 levels and has the potential to improve the efficacy of PD-1 inhibitors.
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Abietanos , Carcinoma de Pulmón de Células no Pequeñas , Estrés del Retículo Endoplásmico , Neoplasias Pulmonares , Factores de Transcripción NFATC , Abietanos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Animales , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ratones , Factores de Transcripción NFATC/metabolismo , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Proto-Oncogenes Mas , Antígeno B7-H1/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Receptor de Muerte Celular Programada 1 , Inmunoterapia/métodos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Células A549 , Ratones Desnudos , Ratones Endogámicos BALB C , Proteínas Proto-Oncogénicas c-myc/metabolismo , Masculino , FemeninoRESUMEN
Amorphous potassium sodium niobate (KNN) films were synthesized at 300 °C through the radio frequency magnetron sputtering method and subsequently crystallized by post-annealing at 700 °C in various alkali element atmospheres (Na and K). The as-deposited film is notably deficient in alkali metal elements, particularly K, whereas the loss of alkali elements in the films can be replenished through annealing in an alkali element atmosphere. By adjusting the molar ratio of Na and K in the annealing atmosphere, the ratio of Na/K in the resultant film varied, consequently suggesting the efficiency of this method on composition regulation of KNN films. Meanwhile, we also found that the physical characteristics of the films also underwent differences with the change of an annealing atmosphere. The films annealed in a high Na atmosphere exhibit large dielectric losses with limited piezoelectric vibration behavior, while annealing in a high K atmosphere reduces the dielectric losses and enhances the piezoelectric behavior. Furthermore, the results of vibration measurement demonstrated that the film annealed in a mixed powder of 25% Na2CO3 and 75% K2CO3 exhibits an optimal vibration displacement of ~400 pm under the sinusoidal excitation voltage of 8 V. This approach of altering the composition of KNN films through post-annealing may introduce the new concept of property design of KNN as well as other similar films.
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BACKGROUND: Video-assisted thoracoscopic (VATS) lung resections are increasingly popular and localization techniques are necessary to aid resection. We describe our experience with hybrid operating room (OR) cone-beam computed tomography (CT) assisted pre-operative and intra-operative lesion localization of lung nodules for VATS wedge resections, including our novel workflow using the hybrid OR cone-beam CT to re-evaluate patients who have undergone pre-operative localization for those who are unsuitable for intra-operative localization. METHODS: Retrospective analysis of all consecutive patients with small (≤ 20 mm), deep (≥ 10 mm distance from pleura) and/or predominantly ground-glass nodules selected for lesion localization in the Interventional Radiology suite followed by re-evaluation with cone-beam CT in the hybrid OR (pre-operative), or in the hybrid OR alone (intra-operative), prior to intentional VATS wedge performed by a single surgeon at our centre from January 2017 to December 2021. RESULTS: 30 patients with 36 nodules underwent localization. All nodules were successfully resected with a VATS wedge resection, although 10% of localizations had hookwire or coil dislodgement. The median effective radiation dose in the pre-operative group was 10.4 mSV including a median additional radiation exposure of 0.9 mSV in the hybrid OR for reconfirmation of hookwire or coil position prior to surgery (p = 0.87). The median effective radiation dose in the intra-operative group was 3.2 mSV with a higher mean rank than the intra-operative group, suggesting a higher radiation dose (p = 0.01). CONCLUSIONS: We demonstrate that our multidisciplinary approach utilizing the hybrid OR is safe and effective. Intra-operative localization is associated with lower radiation doses. Routine use of cone-beam CT to confirm the position of the physical marker prior to surgery in the hybrid OR helps mitigate consequences of localization failure with only a modest increase in radiation exposure.
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Neoplasias Pulmonares , Nódulo Pulmonar Solitario , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Quirófanos , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/cirugía , Tomografía Computarizada por Rayos X/métodos , Cirugía Torácica Asistida por Video/métodos , Pulmón/cirugíaRESUMEN
Metal immunotherapy is a novel adjuvant immunotherapy. Mn2+ can activate STING-a type I IFN response protein-that promotes innate immunity and increases anti-tumor activity by promoting macrophage phagocytosis. IL-12, a cytokine that increases the antigen-presenting ability to promote effector T-cell activation, has potent antitumor activity, albeit with severe adverse effects. In this study, we observed that the combination of Mn2+ and IL-12 has a better antitumor effect and possibly reflects a better safety profile, providing a novel approach and theoretical basis for safe and rapid cancer treatment.
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Manganeso , Neoplasias , Femenino , Humanos , Manganeso/farmacología , Microambiente Tumoral , Interleucina-12 , InmunoterapiaRESUMEN
The rise of multidrug resistant fungal infections highlights the need to identify and develop novel antifungal agents. Occidiofungin is a nonribosomally synthesized glycolipopeptide that has a unique mechanism of action, disrupting actin-mediated functions and inducing cellular apoptosis. Antifungal activity has been observed in vitro against various fungal species, including multidrug resistant Candida auris, and in vivo efficacy has been demonstrated in a murine vulvovaginal candidiasis model. Occidiofungin, a cyclic glycolipopeptide, is composed of eight amino acids and in previous studies, an asparagine residue was assigned at position 7 (ASN7). In this study, new structural variants of occidiofungin have been characterized which have aspartic acid (ASP7), glutamine (GLN7), or glutamic acid (GLU7) at position 7. The side chain of the ASP7 variant contains the only terminal carboxylic acid in the peptide and provides a useful site for selective chemical modifications. Analogues were synthesized at the ASP7 position and tested for antifungal activity. These analogues were shown to be more active as compared to the ASP7 variant against a panel of Candida species. The naturally occurring variants of occidiofungin with a side chain containing a carboxylic acid at the seventh amino acid position can be used to develop semisynthetic analogues with enhanced therapeutic properties.
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Antifúngicos , Burkholderia , Glicopéptidos , Péptidos Cíclicos , Ratones , Animales , Antifúngicos/química , Burkholderia/química , Ácidos Carboxílicos , Pruebas de Sensibilidad MicrobianaRESUMEN
Structural engineering and hybridization of heterogeneous 2D materials can be effective for advanced supercapacitor. Furthermore, architectural design of electrodes particularly with vertical construction of structurally anisotropic graphene nanosheets, can significantly enhance the electrochemical performance. Herein, MXene-derived TiO2 nanocomposites hybridized with vertical graphene is synthesized via CO2 laser irradiation on MXene/graphene oxide nanocomposite film. Instantaneous photon energy by laser irradiation enables the formation of vertical graphene structures on nanocomposite films, presenting the controlled anisotropy in free-standing film. This vertical structure enables improved supercapacitor performance by forming an open structure, increasing the electrolyte-electrode interface, and creating efficient electron transport path. In addition, the effective oxidation of MXene nanosheets by instantaneous photon energy leads to the formation of rutile TiO2 . TiO2 nanoparticles directly generated on graphene enables the effective current path, which compensates for the low conductivity of TiO2 and enables the functioning of an effective supercapacitor by utilizing its pseudocapacitive properties. The resulting film exhibits excellent specific areal capacitance of 662.9 mF cm-2 at a current density of 5 mA cm-2 . The film also shows superb cyclic stability during 40 000 repeating cycles, maintaining high capacitance. Also, the pseudocapacitive redox reaction kinetics is evaluated, showing fast redox kinetics with potential for high-performance supercapacitor applications.
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This study aimed to investigate the chemical constituents in the water extract of the whole herb of Hedyotis scandens by silica gel, ODS, and MCI column chromatographies together with preparative high-performance liquid chromatography(HPLC). The structures of isolated constituents were identified by NMR, HR-ESI-MS, etc. Thirteen compounds were isolated and identified as methyl 4-benzoyloxy-3-methoxybenzeneacetate(1), 4-benzoyloxy-3-methoxybenzeneacetic acid(2), 3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(3), salicylic acid(4), 3-hydroxy-4-methoxypyridine(5), syringic acid(6), hydroxycinnamic acid(7),(R)-6-methyl-4,6-bis(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde(8), 1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(9), 1H-indole-3-carboxaldehyde(10), isoscopoletin(11), syringaresinol(12), and pinoresinol(13). Among them, compounds 1 and 2 were new phenolic acid compounds, compounds 3-5, 8-11, and 13 were isolated from this genus for the first time, and compounds 6, 7, and 12 were obtained from H. scandens for the first time. The activity test showed that compounds 1 and 10 had a certain inhibitory effect on Mycobacterium smegmatis, with MIC_(50) values of 58.5 and 33.3 µg·mL~(-1), respectively.
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Medicamentos Herbarios Chinos , Hedyotis , Hedyotis/química , Medicamentos Herbarios Chinos/química , Espectroscopía de Resonancia Magnética , Ácido SalicílicoRESUMEN
Direct seawater electrolysis (DSE) for hydrogen production, using earth-abundant seawater as the feedstock and renewable electricity as the driving source, paves a new opportunity for flexible energy conversion/storage and smooths the volatility of renewable energy. Unfortunately, the complex environments of seawater impose significant challenges on the design of DSE catalysts, and the practical performance of many current DSE catalysts remains unsatisfactory on the device level. However, many studies predominantly concentrate on the development of electrocatalysts for DSE without giving due consideration to the specific devices. To mitigate this gap, the most recent progress (mainly published within the year 2020-2023) of DSE electrocatalysts and devices are systematically evaluated. By discussing key bottlenecks, corresponding mitigation strategies, and various device designs and applications, the tremendous challenges in addressing the trade-off among activity, stability, and selectivity for DSE electrocatalysts by a single shot are emphasized. In addition, the rational design of the DSE electrocatalysts needs to align with the specific device configuration, which is more effective than attempting to comprehensively enhance all catalytic parameters. This work, featuring the first review of this kind to consider rational catalyst design in the framework of DSE devices, will facilitate practical DSE development.