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Glioma is a type of tumor that starts in the glial cells of the brain or spine. Since the 1800s, when the disease was first named, its survival rates have always been unsatisfactory. Despite great advances in molecular biology and traditional treatment methods, many questions regarding cancer occurrence and the underlying mechanism remain to be answered. In this study, we assessed the protein structural features of 20 oncogenes and 20 anti-oncogenes via protein structure and dynamic analysis methods and 3D structural and systematic analyses of the structure-function relationships of proteins. All of these results directly indicate that unfavorable group proteins show more complex structures than favorable group proteins. As the tumor cell microenvironment changes, the balance of oncogene-related and anti-oncogene-related proteins is disrupted, and most of the structures of the two groups of proteins will be disrupted. However, more unfavorable group proteins will maintain and refold to achieve their correct shape faster and perform their functions more quickly than favorable group proteins, and the former thus support cancer development. We hope that these analyses will help promote mechanistic research and the development of new treatments for glioma.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Glioma/genética , Glioma/metabolismo , Glioma/patología , Oncogenes , Microambiente TumoralRESUMEN
Currently, no therapy is proven to effectively improve heart failure with preserved ejection fraction (HFpEF). Although stem cell therapy has demonstrated promising results in treating ischemic heart disease, the effectiveness of treating HFpEF with human umbilical cord mesenchymal stem cells (hucMSCs) remains unclear. To answer this question, we administered hucMSCs intravenously (i.v.), either once or repetitively, in a mouse model of HFpEF induced by a high-fat diet and NG-nitroarginine methyl ester hydrochloride. hucMSC treatment improved left ventricular diastolic dysfunction, reduced heart weight and pulmonary edema, and attenuated cardiac modeling (inflammation, interstitial fibrosis, and hypertrophy) in HFpEF mice. Repeat hucMSC administration had better outcomes than a single injection. In vitro, hucMSC culture supernatants reduced maladaptive remodeling in neonatal-rat cardiomyocytes. Ribonucleic acid sequencing and protein level analysis of left ventricle (LV) tissues suggested that hucMSCs activated the protein kinase B (Akt)/forkhead box protein O1 (FoxO1) signaling pathway to treat HFpEF. Inhibition of this pathway reversed the efficacy of hucMSC treatment. In conclusion, these findings indicated that hucMSCs could be a viable therapeutic option for HFpEF.
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Solar-driven interfacial evaporation (SDIE) is a highly promising approach to achieve sustainable desalination and tackle the global freshwater crisis. Despite advancements in this field, achieving balanced thermal localization and salt resistance remains a challenge. Herein, the study presents a 3D hierarchical porous ceramic platform for SDIE applications. The utilized alumina foam ceramics (AFCs) exhibit remarkable corrosion resistance and chemical stability, ensuring a prolonged operational lifespan in seawater or brines. The millimeter-scale air-filled pores in AFCs prevent thermal losses through conduction with bulk water, resulting in heat-localized interfaces. The hydrophilic nature of macroporous AFC skeletons facilitates rapid water replenishment on the evaporating surface for effective salt-resistant desalination. Benefiting from its self-radiation adsorption and side-assisted evaporation capabilities, the AFC-based evaporators exhibit high indoor evaporation rates of 2.99 and 3.54 kg m-2 h-1 under one-sided and three-sided illumination under 1.0 sun, respectively. The AFC-based evaporator maintains a high evaporation rate of ≈2.77 kg m-2 h-1 throughout the 21-day long-term test. Furthermore, it achieves a daily water productivity of ≈10.44 kg m-2 in outdoor operations. This work demonstrates the potential of 3D hierarchical porous ceramics in addressing the trade-off between heat localization and salt resistance, and contributes to the development of durable solar steam generators.
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Mycorrhizae are ubiquitous symbioses established between fungi and plant roots. Orchids, in particular, require compatible mycorrhizal fungi for seed germination and protocorm development. Unlike arbuscular mycorrhizal fungi, which have wide host ranges, orchid mycorrhizal fungi are often highly specific to their host orchids. However, the molecular mechanism of orchid mycorrhizal symbiosis is largely unknown compared to that of arbuscular mycorrhizal and rhizobial symbiosis. Here, we report that an endophytic Sebacinales fungus, Serendipita indica, promotes seed germination and the development of protocorms into plantlets in several epiphytic Epidendroideae orchid species (6 species in 2 genera), including Dendrobium catenatum, a critically endangered orchid with high medicinal value. Although plant-pathogen interaction and high meristematic activity can induce the hypoxic response in plants, it has been unclear whether interactions with beneficial fungi, especially mycorrhizal ones, also involve the hypoxic response. By studying the symbiotic relationship between D. catenatum and S. indica, we determined that hypoxia-responsive genes, such as those encoding alcohol dehydrogenase (ADH), are highly induced in symbiotic D. catenatum protocorms. In situ hybridization assay indicated that the ADH gene is predominantly expressed in the basal mycorrhizal region of symbiotic protocorms. Additionally, the ADH inhibitors puerarin and 4-methylpyrazole both decreased S. indica colonization in D. catenatum protocorms. Thus, our study reveals that S. indica is widely compatible with orchids and that ADH and its related hypoxia-responsive pathway are involved in establishing successful symbiotic relationships in germinating orchids.
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Basidiomycota , Dendrobium , Micorrizas , Orchidaceae , Simbiosis , Dendrobium/genética , Semillas , Micorrizas/fisiología , Basidiomycota/fisiología , Orchidaceae/genética , FilogeniaRESUMEN
In this paper, we propose an optomechanical scheme for generating mechanical squeezing over the 3 dB limit, with the mechanical mirror being driven by a strong and linear harmonic force. In contrast to parametric mechanical driving, the linearly driven force shakes the mechanical mirror periodically oscillating at twice the mechanical eigenfrequency with large amplitude, where the mechanical mirror can be dissipatively stabilized by the engineered cavity reservoir to a dynamical squeezed steady state with a maximum degree of squeezing over 8 dB. The mechanical squeezing of more than 3 dB can be achieved even for a mechanical thermal temperature larger than 100 mK. The scheme can be implemented in a cascaded optomechanical setup, with potential applications in engineering continuous variable entanglement and quantum sensing.
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BACKGROUND: To explore the impact of ARGs on the prognosis of NSCLC, and its correlation with clinicopathological parameters and immune microenvironment. Preliminary research on the biological functions of CEBPA in NSCLC. METHODS: Using consensus clustering analysis to identify molecular subtypes of ARGs in NSCLC patients; employing LASSO regression and multivariate Cox analysis to select 7 prognostic risk genes and construct a prognostic risk model; validating independent prognostic factors of NSCLC using forest plot analysis; analyzing immune microenvironment correlations using ESTIMATE and ssGSEA; assessing correlations between prognostic risk genes via qPCR and Western blot in NSCLC; measuring mRNA and protein expression levels of knocked down and overexpressed CEBPA in NSCLC using CCK-8 and EdU assays; evaluating the effects of knocked down and overexpressed CEBPA on cell proliferation using Transwell experiments; examining the correlation of CEBPA with T cells and B cells using mIHC analysis. RESULTS: Consensus clustering analysis identified three molecular subtypes, suggesting significant differential expression of these ARGs in NSCLC prognosis and clinical pathological parameters. There was significant differential expression between the two risk groups in the prognostic risk model, with P < 0.001. The risk score of the prognostic risk model was also P < 0.001. CEBPA exhibited higher mRNA and protein expression levels in NSCLC cell lines. Knockdown of CEBPA significantly reduced mRNA and protein expression levels of CEBPB, YWHAZ, ABL1, and CDK1 in H1650 and A549 cells. siRNA-mediated knockdown of CEBPA markedly inhibited proliferation, migration, and invasion of NSCLC cells, whereas overexpression of CEBPA showed the opposite trend. mIHC results indicated a significant increase in CD3 + CD4+, CD3 + CD8+, and CD20 + cell counts in the high CEBPA expression group. CONCLUSIONS: The risk score of the prognostic risk model can serve as an independent prognostic factor, guiding the diagnosis and treatment of NSCLC. CEBPA may serve as a potential tumor biomarker and immune target, facilitating further exploration of the biological functions and immunological relevance in NSCLC.
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BACKGROUND: Inflamed endothelial cells (ECs) trigger atherogenesis, especially at arterial regions experiencing disturbed blood flow. UCP2 (Uncoupling protein 2), a key mitochondrial antioxidant protein, improves endothelium-dependent relaxation in obese mice. However, whether UCP2 can be regulated by shear flow is unknown, and the role of endothelial UCP2 in regulating inflammation and atherosclerosis remains unclear. This study aims to investigate the mechanoregulation of UCP2 expression in ECs and the effect of UCP2 on endothelial inflammation and atherogenesis. METHODS: In vitro shear stress simulation system was used to investigate the regulation of UCP2 expression by shear flow. EC-specific Ucp2 knockout mice were used to investigate the role of UCP2 in flow-associated atherosclerosis. RESULTS: Shear stress experiments showed that KLF2 (Krüppel-like factor 2) mediates fluid shear stress-dependent regulation of UCP2 expression in human aortic and human umbilical vein ECs. Unidirectional shear stress, statins, and resveratrol upregulate whereas oscillatory shear stress and proinflammatory stimuli inhibit UCP2 expression through altered KLF2 expression. KLF2 directly binds to UCP2 promoter to upregulate its transcription in human umbilical vein ECs. UCP2 knockdown induced expression of genes involved in proinflammatory and profibrotic signaling, resulting in a proatherogenic endothelial phenotype. EC-specific Ucp2 deletion promotes atherogenesis and collagen production. Additionally, we found endothelial Ucp2 deficiency aggravates whereas adeno-associated virus-mediated EC-Ucp2 overexpression inhibits carotid atherosclerotic plaque formation in disturbed flow-enhanced atherosclerosis mouse model. RNA-sequencing analysis revealed FoxO1 (forkhead box protein O1) as the major proinflammatory transcriptional regulator activated by UCP2 knockdown, and FoxO1 inhibition reduced vascular inflammation and disturbed flow-enhanced atherosclerosis. We showed further that UCP2 level is critical for phosphorylation of AMPK (AMP-activated protein kinase), which is required for UCP2-induced inhibition of FoxO1. CONCLUSIONS: Altogether, our studies uncover that UCP2 is novel mechanosensitive gene under the control of fluid shear stress and KLF2 in ECs. UCP2 expression is critical for endothelial proinflammatory response and atherogenesis. Therapeutic strategies enhancing UCP2 level may have therapeutic potential against atherosclerosis.
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Aterosclerosis , Placa Aterosclerótica , Proteína Desacopladora 2/metabolismo , Animales , Aterosclerosis/genética , Aterosclerosis/metabolismo , Células Cultivadas , Endotelio/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inflamación/genética , Inflamación/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones , Placa Aterosclerótica/metabolismo , Estrés MecánicoRESUMEN
OBJECTIVES: To evaluate the application of black-blood CT (BBCT) in carotid artery wall imaging and its accuracy in disclosing stenosis rate and plaque burden of carotid artery. METHODS: A total of 110 patients underwent contrast-enhanced CT scan with two phases, and BBCT images were obtained using contrast-enhancement (CE)-boost technology. Two radiologists independently scored subjective image quality on black-blood computerized tomography (BBCT) images using a 4-point scale and then further analyzed plaque types. The artery stenosis rate on BBCT was measured and compared with CTA. The plaque burden on BBCT was compared with that on high-resolution intracranial vessel wall MR imaging (VW-MR imaging). The kappa value and intraclass correlation coefficient (ICC) were used for consistency analysis. The diagnostic accuracy of BBCT for stenosis rate and plaque burden greater than 50% was evaluated by AUC. RESULTS: The subjective image quality scores of BBCT had good consistency between the two readers (ICC = 0.836, p < 0.001). BBCT and CTA had a good consistency in the identification of stenosis rate (p < 0.001). There was good consistency between BBCT and VW-MR in diagnosis of plaque burden (p < 0.001). As for plaque burden over 50%, BBCT had good sensitivity (93.10%) and specificity (73.33%), with an AUC of 0.950 (95%CI 0.838-0.993). Compared with CTA, BBCT had higher consistency with VW-MR in disclosing low-density plaques and mixed plaques (ICC = 0.931 vs 0.858, p < 0.001). CONCLUSIONS: BBCT can not only display the carotid artery wall clearly but also accurately diagnose the stenosis rate and plaque burden of carotid artery. CLINICAL RELEVANCE STATEMENT: Black-blood CT, as a novel imaging technology, can assist clinicians and radiologists in better visualizing the structure of the vessel wall and plaques, especially for patients with contraindication to MRI. KEY POINTS: ⢠Black-blood CT can clearly visualize the carotid artery wall and plaque burden. ⢠Black-blood CT is superior to conventional CTA with more accurate diagnosis of the carotid stenosis rate and plaque burden features.
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Estenosis Carotídea , Placa Aterosclerótica , Humanos , Angiografía por Resonancia Magnética/métodos , Constricción Patológica , Arterias Carótidas/diagnóstico por imagen , Estenosis Carotídea/diagnóstico por imagen , Placa Aterosclerótica/diagnóstico , Tomografía Computarizada por Rayos X/métodosRESUMEN
Periodontitis, the second most common oral disease, is primarily initiated by inflammatory responses and osteoclast differentiation, in which the MAPK signaling pathway and mitochondrial function play important roles. 3-methyl-1H-indol-1-yl dimethylcarbamodithioate (3o), a hybrid of indole and dithiocarbamate, was first synthesized by our group. It has shown anti-inflammatory activity against lipopolysaccharide-induced acute lung injury. However, it is not known if 3o can exert effects in periodontitis. In vitro study: LPS-induced macrophage inflammation initiation and a receptor activator of nuclear factor κB ligand-stimulated osteoclast differentiation model were established. Cell viability, inflammatory cytokines, osteoclast differentiation, the MAPK signaling pathway, and mitochondrial function before and after treatment with 3o were investigated. In vivo study: Alveolar bone resorption, inflammatory cytokine expression, osteoclast differentiation, and the underlying mechanisms were assessed in mice with periodontitis. Inflammatory cytokine expression and osteoclast differentiation appeared downregulated after 3o treatment. 3o inhibited the MAPK signaling pathway and restored mitochondrial function, including mitochondrial reactive oxygen species, mitochondrial membrane potential, and ATP production. Meanwhile, 3o reduced inflammation activation and bone resorption in mice with periodontitis, reflected by the decreased expression of inflammatory cytokines and osteoclasts, implying that 3o inhibited the MAPK signaling pathway and the mitochondrial oxidative DNA damage marker 8-OHdG. These results highlight the protective role of 3o in periodontitis in mice and reveal an important strategy for preventing periodontitis.
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Indoles , Sistema de Señalización de MAP Quinasas , Mitocondrias , Osteoclastos , Periodontitis , Animales , Mitocondrias/efectos de los fármacos , Periodontitis/tratamiento farmacológico , Ratones , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Indoles/farmacología , Indoles/uso terapéutico , Diferenciación Celular/efectos de los fármacos , Citocinas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Lipopolisacáridos/farmacología , Pérdida de Hueso Alveolar/tratamiento farmacológico , Ratones Endogámicos C57BL , Células RAW 264.7RESUMEN
Seven new meroterpenoids, paraphaeones A-G (1-7), and two new polyketides, paraphaeones H-I (8-9), along with eight known compounds (10-17), were isolated from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1. The structures of 1-9 were identified through the analysis of 1H, 13C, and 2D NMR spectra, assisted by HR-ESI-MS data. Compounds 1 and 7 exhibited a dose-dependent decrease in lactate dehydrogenase levels, with IC50 values of 1.78 µM and 1.54 µM, respectively. Moreover, they inhibited the secretion of IL-1ß and CASP-1, resulting in a reduction in the activity levels of NLRP3 inflammasomes. Fluorescence microscopy results indicated that compound 7 concentration-dependently attenuated cell pyroptosis. Additionally, compounds 4 and 7 showed potential inhibitory effects on the severe acute respiratory syndrome coronavirus-2 main protease (SARS-CoV-2 Mpro), with IC50 values of 10.8 ± 0.9 µM and 12.9 ± 0.7 µM, respectively.
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Ascomicetos , Proteasas 3C de Coronavirus , Policétidos , SARS-CoV-2 , Terpenos , Policétidos/química , Policétidos/farmacología , Policétidos/aislamiento & purificación , Ascomicetos/química , Humanos , Terpenos/química , Terpenos/farmacología , Terpenos/aislamiento & purificación , SARS-CoV-2/efectos de los fármacos , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Proteasas 3C de Coronavirus/química , Estructura Molecular , Antivirales/farmacología , Antivirales/química , Antivirales/aislamiento & purificación , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Relación Estructura-Actividad , Tratamiento Farmacológico de COVID-19 , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificaciónRESUMEN
PURPOSE: Patients on oral anticancer agent (OAA) therapies have the autonomy to manage their cancer treatments in home settings. However, patients may not have adequate knowledge, confidence, or ability to effectively manage OAA-related consequences, which can significantly impact their treatment and health outcomes. This study aims to identify the associations between medication beliefs, patient activation, and self-rated health (SRH) among oncology patients taking OAAs and explore the potential mediation effects of patient activation on the relationship between medication beliefs and SRH. METHODS: A secondary data analysis was conducted on cross-sectional data from 114 patients who were diagnosed with breast, colorectal, lung, or prostate cancer. Patients completed a self-reported survey including items of SRH, Beliefs about Medicines Questionnaire (BMQ), and Patient Activation Measure (PAM-13). Descriptive statistics, bivariate correlation, hierarchical multiple linear regression, and mediation analysis were conducted. RESULTS: The results indicate that patients taking OAAs have ambivalent attitudes toward medication. Both medication necessity (r = - 0.27) and concerns (r = - 0.21) were negatively associated with SRH, while patient activation was positively associated with SRH (r = 0.38). Patient activation had a negative association with medication concerns (r = - 0.36) and fully mediated the relationship between medication concerns and SRH in patients taking OAAs (indirect effect = - 0.154, 95% confidence interval, - 0.276 to - 0.060). CONCLUSION: The findings highlight the significance of activating patients to better understand and manage their OAAs. It is crucial for oncology professionals to provide multifaceted interventions to promote patient activation with an effort to mitigate the negative impact of medication beliefs on patient-perceived health outcomes.
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Antineoplásicos , Conocimientos, Actitudes y Práctica en Salud , Neoplasias , Participación del Paciente , Humanos , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Anciano , Neoplasias/tratamiento farmacológico , Neoplasias/psicología , Encuestas y Cuestionarios , Administración Oral , Participación del Paciente/psicología , Participación del Paciente/métodos , Autoinforme , Adulto , Anciano de 80 o más AñosRESUMEN
PURPOSE: Oncology patients often struggle to manage their medications and related adverse events during transitions of care. They are expected to take an active role in self-monitoring and timely reporting of their medication safety events or concerns to clinicians. The purpose of this study was to explore the factors influencing oncology patients' willingness to report adverse events or concerns related to their medication after their transitions back home. METHODS: A qualitative interview study was conducted with adult patients with breast, prostate, lung, or colorectal cancer who experienced care transitions within the previous year. A semi-structured interview guide was developed to understand patients' perceptions of reporting mediation-related safety events or concerns from home. All interviews were conducted via phone calls, recorded, and transcribed for thematic data analysis. RESULTS: A total of 41 individuals participated in the interviews. Three main themes and six subthemes emerged, including patients' perceived relationship with clinicians (the quality of communication and trust in clinicians), perceived severity of adverse medication events (perceived severe vs. non-severe events), and patient activation in self-management (self-efficacy in self-management and engagement in monitoring health outcomes). CONCLUSION: The patient-clinician relationship significantly affects patients' reporting behaviors, which can potentially interact with other factors, including the severity of adverse events. It is important to engage oncology patients in medication safety self-reporting from home by enhancing health communication, understanding patients' perceptions of severe events, and promoting patient activation. By addressing these efforts, healthcare providers should adopt a more patient-centered approach to enhance the overall quality and safety of oncological care.
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Neoplasias , Investigación Cualitativa , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias/tratamiento farmacológico , Neoplasias/psicología , Adulto , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/psicología , Relaciones Médico-Paciente , Entrevistas como Asunto , Comunicación , Antineoplásicos/efectos adversos , Anciano de 80 o más Años , Automanejo/métodos , Participación del Paciente/métodos , Participación del Paciente/psicologíaRESUMEN
Welan gum, a natural polysaccharide produced by Sphingomonas sp. ATCC 31555, has attracted considerable attention in the scientific community due to its desirable properties. However, challenges, such as high viscosity, residual bacterial cells, carotenoids, and protein complexation, hinder the widespread application of welan gum. In this study, we established a method for the extraction and purification of welan gum using a synergistic approach with lysozyme and alkaline protease. Lysozyme hydrolysis conditions were optimized by applying response surface methodology, and the best results for bacterial cell removal were achieved at 11 000 U/g, 44 °C, and pH 9 after 3 h of treatment. Subsequently, we evaluated protein hydrolysis through computer simulation and identified alkaline protease as the most suitable enzyme. Through experimental investigations, we found that the optimal conditions for alkaline protease hydrolysis were 7500 U/g, 50 °C, pH 10, and 600 rpm. These conditions resulted in a sugar recovery rate of 76.1%, carotenoid removal rate of 89.5%, bacterial removal rate of 95.2%, and protein removal rate of 87.3% after 3 h of hydrolysis. The purified welan gum exhibited high transparency and purity. Structural characterization and antioxidant activity evaluation revealed that enzymatically purified welan gum has potential application prospects. Our study provides valuable insights into the optimal method for the enzymatic extraction and purification of welan gum. Such a method is conducive to the development of the multiple potential applications of welan gum. KEY POINTS: ⢠A novel process for the synergistic purification of welan gum using lysozyme and alkaline protease was established. ⢠In silico virtual digestion was employed to select the purification enzyme. ⢠Welan gum with high transparency and purity was obtained.
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Proteínas Bacterianas , Muramidasa , Simulación por Computador , CarotenoidesRESUMEN
BACKGROUND: Deep venous thrombosis (DVT) after spinal surgery has recently attracted increasing attention. Patients with spinal metastases who undergo decompression with fixation are at a high risk of developing DVT. D-dimer levels indicate the risk of DVT, and the purpose of our study was to investigate D-dimer levels as a predictor of DVT perioperatively. METHODS: We prospectively evaluated 100 patients with spinal metastases. D-dimer tests were performed twice: once before surgery and one day postoperatively. DVT was diagnosed by duplex ultrasonographic assessment of both lower extremities. Pulmonary embolisms (PEs) were diagnosed using multidetector computed tomography and pulmonary angiography. Perioperative serum D-dimer levels were compared between the DVT (+) and DVT (-) groups. The cutoff value of the D-dimer level was calculated using receiver operating characteristic analysis. RESULTS: Preoperative and postoperative DVT prevalences were 8.0% (8/100) and 6.6% (6/91), respectively, and none of the patients developed PE. Before surgery, there was no significant differences in D-dimer levels between the pre-DVT (+) and pre-DVT (-) groups. After surgery, the D-dimer level one-day postoperatively for the post-DVT (+) group (17.6 ± 11.8 mg/L) was significantly higher than that of the post-DVT (-) group (5.0 ± 4.7 mg/L). The cutoff value of the postoperative D-dimer level was 9.51(mg/L), and the sensitivity and specificity for the optimum threshold were 83.3% and 89.4%, respectively. CONCLUSIONS: Our findings suggest that preoperative D-dimer level may not be a predictor of DVT. Preoperative ultrasound examinations should be routinely performed in patients with spinal metastases. Postoperative D-dimer levels greater than 9.51(mg/L) are a predictive factor for the early diagnosis of DVT after spine surgery. TRIAL REGISTRATION: Our study was registered on Chinese Clinical Trial Registry (No.ChiCTR2000029737). Registered 11 February 2020 - Retrospectively registered, https://www.chictr.org.cn/index.aspx.
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Descompresión Quirúrgica , Productos de Degradación de Fibrina-Fibrinógeno , Neoplasias de la Columna Vertebral , Trombosis de la Vena , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Femenino , Masculino , Trombosis de la Vena/sangre , Trombosis de la Vena/etiología , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/epidemiología , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Descompresión Quirúrgica/efectos adversos , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/sangre , Adulto , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Embolia Pulmonar/sangre , Embolia Pulmonar/etiología , Embolia Pulmonar/diagnóstico , Valor Predictivo de las Pruebas , Biomarcadores/sangreRESUMEN
Teleosts live in aquatic habitats, where they encounter ionic and acid-base fluctuations as well as infectious pathogens. To protect from these external challenges, the teleost epidermis is composed of living cells, including keratinocytes and ionocytes that maintain body fluid ionic homeostasis, and mucous cells that secret mucus. While ionocyte progenitors are known to be specified by Delta-Notch-mediated lateral inhibition during late gastrulation and early segmentation, it remains unclear how epidermal mucous cells (EMCs) are differentiated and maintained. Here, we show that Delta/Jagged-mediated activation of Notch signaling induces the differentiation of agr2-positive (agr2+) EMCs in zebrafish embryos during segmentation. We demonstrated that agr2+ EMCs contain cytoplasmic secretory granules and express muc5.1 and muc5.2. Reductions in agr2+ EMC number were observed in mib mutants and notch3 MOs-injected notch1a mutants, while increases in agr2+ cell number were detected in notch1a- and X-Su(H)/ANK-overexpressing embryos. Treatment with γ-secretase inhibitors further revealed that Notch signaling is required during bud to 15 hpf for the differentiation of agr2+ EMCs. Increased agr2+ EMC numbers were also observed in jag1a-, jag1b-, jag2a- and dlc-overexpressing, but not jag2b-overexpressing embryos. Meanwhile, reductions in agr2+ EMC numbers were detected in jag1a morphants, jag1b mutants, jag2a mutants and dlc morphants, but not jag2b mutants. Reduced numbers of pvalb8-positive epidermal cells were also observed in mib or jag2a mutants and jag1a or jag1b morphants, while increased pvalb8-positive epidermal cell numbers were detected in notch1a-overexpressing, but not dlc-overexpressing embryos. BrdU labeling further revealed that the agr2+ EMC population is maintained by proliferation. Cell lineage experiments showed that agr2+ EMCs are derived from the same ectodermal precursors as keratinocytes or ionocytes. Together, our results indicate that specification of agr2+ EMCs in zebrafish embryos is induced by DeltaC/Jagged-dependent activation of Notch1a/3 signaling, and the cell population is maintained by proliferation.
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Desarrollo Embrionario/genética , Proteínas de Homeodominio/genética , Proteína Jagged-1/genética , Proteína Jagged-2/genética , Proteínas del Tejido Nervioso/genética , Receptor Notch1/genética , Proteínas de Pez Cebra/genética , Animales , Proteínas de Unión al Calcio/genética , Diferenciación Celular/genética , Ectodermo/crecimiento & desarrollo , Epidermis/crecimiento & desarrollo , Queratinocitos/citología , Queratinocitos/metabolismo , Moco/metabolismo , Proteínas Mutantes/genética , Receptores Notch/genética , Transducción de Señal/genética , Pez Cebra/genética , Pez Cebra/crecimiento & desarrolloRESUMEN
BACKGROUND: Actively engaging patients with cancer and their families in monitoring and reporting medication safety events during care transitions is indispensable for achieving optimal patient safety outcomes. However, existing patient self-reporting systems often cannot address patients' various experiences and concerns regarding medication safety over time. In addition, these systems are usually not designed for patients' just-in-time reporting. There is a significant knowledge gap in understanding the nature, scope, and causes of medication safety events after patients' transition back home because of a lack of patient engagement in self-monitoring and reporting of safety events. The challenges for patients with cancer in adopting digital technologies and engaging in self-reporting medication safety events during transitions of care have not been fully understood. OBJECTIVE: We aim to assess oncology patients' perceptions of medication and communication safety during care transitions and their willingness to use digital technologies for self-reporting medication safety events and to identify factors associated with their technology acceptance. METHODS: A cross-sectional survey study was conducted with adult patients with breast, prostate, lung, or colorectal cancer (N=204) who had experienced care transitions from hospitals or clinics to home in the past 1 year. Surveys were conducted via phone, the internet, or email between December 2021 and August 2022. Participants' perceptions of medication and communication safety and perceived usefulness, ease of use, attitude toward use, and intention to use a technology system to report their medication safety events from home were assessed as outcomes. Potential personal, clinical, and psychosocial factors were analyzed for their associations with participants' technology acceptance through bivariate correlation analyses and multiple logistic regressions. RESULTS: Participants reported strong perceptions of medication and communication safety, positively correlated with medication self-management ability and patient activation. Although most participants perceived a medication safety self-reporting system as useful (158/204, 77.5%) and easy to use (157/204, 77%), had a positive attitude toward use (162/204, 79.4%), and were willing to use such a system (129/204, 63.2%), their technology acceptance was associated with their activation levels (odds ratio [OR] 1.83, 95% CI 1.12-2.98), their perceptions of communication safety (OR 1.64, 95% CI 1.08-2.47), and whether they could receive feedback after self-reporting (OR 3.27, 95% CI 1.37-7.78). CONCLUSIONS: In general, oncology patients were willing to use digital technologies to report their medication events after care transitions back home because of their high concerns regarding medication safety. As informed and activated patients are more likely to have the knowledge and capability to initiate and engage in self-reporting, developing a patient-centered reporting system to empower patients and their families and facilitate safety health communications will help oncology patients in addressing their medication safety concerns, meeting their care needs, and holding promise to improve the quality of cancer care.
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Tecnología Digital , Neoplasias , Adulto , Masculino , Humanos , Estudios Transversales , Transferencia de Pacientes , Encuestas y Cuestionarios , Neoplasias/tratamiento farmacológicoRESUMEN
Nature regulates cellular interactions through the cell-surface molecules and plasma membranes. Despite advances in cell-surface engineering with diverse ligands and reactive groups, modulating cell-cell interactions through scaffolds of the cell-binding cues remains a challenging endeavor. Here, we assembled peptide nanofibrils on live cell surfaces to present the ligands that bind to the target cells. Surprisingly, with the same ligands, reducing the thermal stability of the nanofibrils promoted cellular interactions. Characterizations of the system revealed a thermally induced fibril disassembly and reassembly pathway that facilitated the complexation of the fibrils with the cells. Using the nanofibrils of varied stabilities, the cell-cell interaction was promoted to different extents with free-to-bound cell conversion ratios achieved at low (31%), medium (54%), and high (93%) levels. This study expands the toolbox to generate desired cell behaviors for applications in many areas and highlights the merits of thermally less stable nanoassemblies in designing functional materials.
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Nanofibras , Nanofibras/química , Ligandos , Péptidos/químicaRESUMEN
Environmental DNA (eDNA) metabarcoding is an emerging tool for monitoring biological communities in aquatic ecosystems. The selection of bioinformatic pipelines significantly impacts the results of biodiversity assessments. However, there is currently no consensus on the appropriate bioinformatic pipelines for fish community analysis in eDNA metabarcoding. In this study, we compared three bioinformatic pipelines (Uparse, DADA2, and UNOISE3) using real and mock (constructed with 15/30 known fish) communities to investigate the differences in biological interpretation during the data analysis process in eDNA metabarcoding. Performance evaluation and diversity analyses revealed that the choice of bioinformatic pipeline could impact the biological results of metabarcoding experiments. Among the three pipelines, the operational taxonomic units (OTU)-based pipeline (Uparse) showed the best performance (sensitivity: 0.6250 ± 0.0166; compositional similarity: 0.4000 ± 0.0571), the highest richness (25-102) and minimal inter-group differences in alpha diversity. It suggested the OTU-based pipeline possessed superior capability in fish diversity monitoring compared to ASV/ZOTU-based pipeline. Additionally, the Bray-Curtis distance matrix achieved the highest discriminative effect in the PCoA (43.3%-53.89%) and inter-group analysis (P < 0.01), indicating it was better at distinguishing compositional differences or specific genera of fish community at different sampling sites than other distance matrices. These findings provide new insights into fish community monitoring through eDNA metabarcoding in estuarine environments.
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OBJECTIVES: To investigate the utilization of mobility device, whether age and gender-related use disparities exist, and whether falls can further explain use disparities over time among Chinese older adults in need of devices. METHODS: Community-dwelling older adults who needed mobility devices and completed four waves of the China Health and Retirement Survey 2011-2018 were included (N = 1,302). A categorical variable was created to represent respondents' intersectionality of age (50-64, 65-74, and ≥75 years) and gender (men vs. women). RESULTS: The baseline prevalence of device use was 18.2 % (n = 237). Overall, the device use increased over time. Intersectionality-wise, oldest-old women were 1.53 times more likely than youngest-old men to use devices over time. Respondents with falls were more likely to use devices over time. CONCLUSIONS: Older adults with mobility impairment, especially the oldest-old women and those with falls, lag in mobility devices utilization, suggesting future tailored interventions to support these populations.
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Accidentes por Caídas , Vida Independiente , Limitación de la Movilidad , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Accidentes por Caídas/estadística & datos numéricos , Accidentes por Caídas/prevención & control , China , Dispositivos de Autoayuda/estadística & datos numéricos , Factores Sexuales , Anciano de 80 o más Años , Factores de Edad , Encuestas y CuestionariosRESUMEN
OBJECTIVES: This study aimed to provide a universal and reliable reference system quantifying temporomandibular joint (TMJ) morphological and positional changes. METHODS: Large field-of-view (FOV) cone-beam computed tomography (CBCT) images (20 TMJs) from 10 preorthognathic surgery patients and limited FOV CBCT images (40 TMJs) from 20 splint therapy-treated patients with temporomandibular disorders were collected. TMJ-specific reference system including a TMJ horizontal reference plane (TMJHP) and a local coordinate system (TMJCS) was constructed with landmarks on cranial base. Its application for TMJ measurements and its spatial relationship to common Frankfort horizontal plane (FHP) and maxillofacial coordinate system (MFCS) were evaluated. RESULTS: Five relevant landmarks were selected to optimally construct TMJ-specific reference system. General parallelism between TMJHP and FHP was demonstrated by minimal angular and constant distance deviation (1.714â ±â 0.811º; 2.925â ±â 0.817 mm). Additionally, tiny axial orientational deviations (0.181â ±â 6.805º) suggested TMJCS rivaled MFCS. Moreover, small deviations in orientations and distances (1.232â ±â 0.609º; 0.310â ±â 0.202 mm) indicated considerable reliability for TMJCS construction, with intraclass correlation coefficients (ICCs) ranging from 0.999 to 1.000. Lastly, slight discrepancies in translations and rotations revealed high reliability for condylar positional and morphological measurements (ICC, 0.918-0.999). LIMITATIONS: TMJ-specific reference system was merely tested in two representative FOVs. CONCLUSIONS: This study provides a universal and reliable reference system for TMJ assessment that is applicable to both limited and large FOV CBCT. It would improve comparability among diverse studies and enable comprehensive evaluations of TMJ positional and morphological changes during TMJ-related treatment follow-up such as splint therapy and disease progression.