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OBJECTIVE: Studies have shown that electroacupuncture (EA) can alleviate cognitive impairments from Alzheimer's disease (AD) by regulating the expression of adenosine monophosphate-activated protein kinase (AMPK), but the specific mechanism involved remains to be elucidated. Therefore, this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial dynamics. METHODS: The four-month-old transgenic mice with amyloid precursor protein (APP)/presenilin 1 (PS1) and AMPKα1-subunit conditional knockout (AMPKα1-cKO) were used for experiments. To evaluate the effects of EA treatment on cognitive function, the T-maze and Morris water maze were used. In addition, chemical exchange saturation transfer, thioflavin staining, transmission electron microscopy, mitochondrial membrane potential, and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 mice. RESULTS: Both APP/PS1 mice and AMPKα1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment. Inactivation of the AMPK/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) pathway increased pathological amyloid-ß (Aß) deposition and aggravated the dysfunction in mitochondrial dynamics. In addition, EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1α pathway, specifically by reducing pathological Aß deposition, normalizing energy metabolism, protecting the structure and function of mitochondria, increasing the levels of mitochondrial fusion proteins, and downregulating the expression of fission proteins. However, the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by AMPKα1 knockout. CONCLUSION: The regulation of hippocampal mitochondrial dynamics and reduction in Aß deposition via the AMPK/PGC-1α pathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice. Please cite this article as: Jia WW, Lin HW, Yang MG, Dai YL, Ding YY, Xu WS, Wang SN, Cao YJ, Liang SX, Wang ZF, Chen C, Liu WL. Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer's disease by regulating hippocampal mitochondrial dynamics. J Integr Med. 2024; Epub ahead of print.
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Drought is one of the most important abiotic stresses, and seriously threatens plant development and productivity. Increasing evidence indicates that chromatin remodelers are pivotal for plant drought response. However, molecular mechanisms of chromatin remodelers-mediated plant drought responses remain obscure. In this study, we found a novel interactor of BRM called BRM-associated protein involved in drought response (BAPID), which interacted with SWI/SNF chromatin remodeler BRM and drought-induced transcription factor Di19. Our findings demonstrated that BAPID acted as a positive drought regulator since drought tolerance was increased in BAPID-overexpressing plants, but decreased in BAPID-deficient plants, and physically bound to PR1, PR2, and PR5 promoters to mediate expression of PR genes to defend against dehydration stress. Genetic approaches demonstrated that BRM acted epistatically to BAPID and Di19 in drought response in Arabidopsis. Furthermore, the BAPID protein-inhibited interaction between BRM and Di19, and suppressed the inhibition of BRM on the Di19-PR module by mediating the H3K27me3 deposition at PR loci, thus changing nucleosome accessibility of Di19 and activating transcription of PR genes in response to drought. Our results shed light on the molecular mechanism whereby the BAPID-BRM-Di19-PRs pathway mediates plant drought responses. We provide data improving our understanding of chromatin remodeler-mediated plant drought regulation network.
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TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.
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Linfoma de Células B Grandes Difuso , Proteína p53 Supresora de Tumor , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Humanos , Proteína p53 Supresora de Tumor/genética , Pronóstico , Mutación Missense/genética , Mutación/genética , Microambiente Tumoral/genética , Masculino , Femenino , Factores de Riesgo , Persona de Mediana EdadRESUMEN
Coumarins are natural products with benzopyran ring as the parent nucleus. Numerous coumarin derivatives exhibit a variety of pharmacological activities, including antibacterial, anti-inflammatory, antitumor, anti-coagulant, anti-osteoporotic, and insecticidal activities. Therefore, they play an important role in both medicine and agriculture. The development and utilization of coumarin derivatives have attracted increasing attention. The advancement of gene sequencing technology and the rapid progress in synthetic bio-logy have led to significant advancement in the biosynthesis of coumarin derivatives, and has received increasing attention from global researchers. This paper presents a comprehensive overview of the key biosynthesis-related enzymes of coumarin derivatives, such as cytochrome P450 enzyme(CYP450), prenyltransferase(PT), UDP-glucosyltransferase(UGT). Additionally, the pharmacological activities of these enzymes, including anti-tumor, anti-inflammatory, antioxidant, and antibacterial activities, are systematically summarized. This review aims to provide a valuable reference for the biosynthesis of coumarin derivatives and further exploration of their medicinal potential.
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Cumarinas , Cumarinas/química , Cumarinas/farmacología , Cumarinas/metabolismo , Humanos , Animales , Dimetilaliltranstransferasa/metabolismo , Dimetilaliltranstransferasa/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Glucosiltransferasas/genética , Glucosiltransferasas/metabolismoRESUMEN
Within the past decade, single domain antibodies (sdAbs) have been recognized as unique affinity binding reagents that can be tailored for performance in a variety of immunoassay formats. Luminex MagPlex color-coded magnetic microspheres provide a high-throughput platform that enables multiplexed immunoassays. We developed a MagPlex bead-based assay for the detection of SARS-CoV-2, using sdAbs against SARS-CoV-2 nucleocapsid (N) protein in which we engineered the sdAb capture reagents to orient them on the beads. The oriented sdAbs provided an increase in sensitivity over randomly oriented sdAbs for samples of N diluted in buffer, which also translated into better detection of SARS-CoV-2 in clinical samples. We assessed the specificity of the assay by examining seasonal coronavirus clinical samples. In summary, we provide a proof-of-concept that a bead-based assay using sdAbs to detect SARS-CoV-2 is feasible and future research combining it with other sdAb-coated beads that can detect other viruses may provide a useful diagnostic tool.
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Anticuerpos Antivirales , COVID-19 , Proteínas de la Nucleocápside de Coronavirus , SARS-CoV-2 , Anticuerpos de Dominio Único , Humanos , SARS-CoV-2/inmunología , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/virología , Anticuerpos de Dominio Único/inmunología , Anticuerpos Antivirales/inmunología , Inmunoensayo/métodos , Proteínas de la Nucleocápside de Coronavirus/inmunología , Prueba Serológica para COVID-19/métodos , Fosfoproteínas/inmunología , Sensibilidad y Especificidad , MicroesferasRESUMEN
CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-TSCM) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies.
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Antígenos CD19 , Antígenos CD20 , Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Antígenos CD19/inmunología , Humanos , Antígenos CD20/inmunología , Antígenos CD20/genética , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/genética , Animales , Ratones , Ingeniería Celular/métodos , Linfocitos T/inmunología , Línea Celular TumoralRESUMEN
Electrocatalytic CO2 reduction (eCO2R) in acid holds promise in renewable electricity-powered CO2 utilization with high efficiency, but the hydrogen evolution reaction (HER) often prevails and results in a low eCO2R selectivity. Here, using cobalt phthalocyanine/Ketjen black (CoPc/KB) as the model catalysts, we systematically study the effect of active site density, operational current density, and hydrated cations on the acidic eCO2R selectivity and decipher it through the componential dynamics of electric double layer (EDL). The optimal CoPc-4/KB demonstrates a near-unity CO Faradaic efficiency from 50 to 400 mA cm-2 and superb operational stability (>120 h) at 100 mA cm-2. Aided by in situ Raman and infrared spectroscopies, we reveal that the proper cations establish an electrostatic shield for mitigating bulk H+ penetration and mediate the interfacial water structure for suppressing HER. This study should elicit further profound thinking on robust eCO2R system design from the perspective of multiphasic and dynamic EDL.
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BACKGROUND: The association between the triglyceride-glucose (TyG) index and clinical outcomes in patients with both coronary artery disease (CAD) and psoriasis is unclear. This study investigated the association between the TyG index and major adverse cardiovascular events (MACE) in patients with both CAD and psoriasis. METHODS: This retrospective cohort study included patients diagnosed with both CAD and psoriasis who underwent coronary angiography at the Fuwai Hospital, Beijing, China, between January 2017 and May 2022. The study endpoint was the occurrence of MACE or end of follow-up time. Multivariate Cox proportional analysis and restricted cubic splines (RCS) were used to determine the association between the TyG index and MACE. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold value of the TyG index for predicting MACE. RESULTS: This study enrolled 293 patients with both CAD and psoriasis, including 258 (88.1%) males with a mean age of 58.89 ± 9.61 years. Patients were divided into four groups based on the TyG quartiles: Q1 (N = 74), Q2 (N = 73), Q3 (N = 73), and Q4 (N = 73). After adjusting for the potential confounders, the TyG index was independently associated with MACE, both as a continuous variable (HR = 1.53, 95% CI = 1.03-2.28, P = 0.035) and as a categorical variable (Q1: reference; Q2: HR = 1.85, 95% CI = 0.88-3.87, P = 0.105; Q3: HR = 2.39, 95% CI = 1.14-5.00, P = 0.021; Q4: HR = 2.19, 95% CI = 1.001-4.81, P = 0.0497; P for trend = 0.039). RCS analysis showed an linear association between the TyG index and MACE (P-overall = 0.027, P-non-linear = 0.589). ROC curve analysis showed that the TyG index of ≥ 8.73 was the optimal threshold value (area under the ROC curve = 0.60, 95% CI 0.53-0.67). TyG index ≥ 8.73 was significantly associated with MACE (HR = 2.10, 95% CI = 1.32-3.34, P = 0.002). After adjustment for confounders, the TyG index showed independent association with MACE (HR = 2.00, 95% CI = 1.17-3.42, P = 0.011). CONCLUSIONS: The TyG index showed a positive linear correlation with MACE in patients with both CAD and psoriasis. The TyG index of ≥ 8.73 might be the optimal threshold for predicting MACE.
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In this study, an active film composed of gallic acid (GA), chitosan (CS), and cellulose nanocrystals (CNC) was prepared using a solution casting method and synergistic photodynamic inactivation (PDI) technology. Characterization of the film showed that the CS-CNC-GA composite film had high transparency and UV-blocking ability. The addition of GA (0.2 %-1.0 %) significantly enhanced the mechanical properties, water resistance, and thermal stability of the film. The tensile strength increased up to 46.30 MPa, and the lowest water vapor permeability was 1.16 × e-12 g/(cm·s·Pa). The PDI-treated CS-CNC-GA1.0 composite film exhibited significantly enhanced antibacterial activity, with inhibition zone diameters of 31.83 mm against Staphylococcus aureus and 21.82 mm against Escherichia coli. The CS-CNC-GA composite film also showed good antioxidant activity. Additionally, the CS-CNC-GA1.0 composite film generated a large amount of singlet oxygen under UV-C light irradiation. It was found that using the CS-CNC-GA1.0 composite film for packaging and storage of oysters at 4 °C effectively delayed the increase in pH, total colony count, and lipid oxidation in oysters. In conclusion, the CS-CNC-GA composite film based on PDI technology has great potential for applications in the preservation of aquatic products.
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Antibacterianos , Celulosa , Quitosano , Ácido Gálico , Ácido Gálico/química , Ácido Gálico/farmacología , Quitosano/química , Celulosa/química , Antibacterianos/farmacología , Antibacterianos/química , Antioxidantes/química , Antioxidantes/farmacología , Escherichia coli/efectos de los fármacos , Embalaje de Alimentos/métodos , Staphylococcus aureus/efectos de los fármacos , Nanopartículas/química , Permeabilidad , Nanocompuestos/química , Resistencia a la Tracción , Rayos UltravioletaRESUMEN
BACKGROUND: Left bundle branch area pacing includes left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP), which is effective in patients with dyssynchronous heart failure (DHF). However, the basic mechanisms are unknown. OBJECTIVES: This study aimed to compare LBBP with LVSP and explore potential mechanisms underlying the better clinical outcomes of LBBP. METHODS: A total of 24 beagles were assigned to the following groups: 1) control group; 2) DHF group, left bundle branch ablation followed by 6 weeks of AOO pacing at 200 ppm; 3) LBBP group, DHF for 3 weeks followed by 3 weeks of DOO pacing at 200 ppm; and 4) LVSP with the same interventions in the LBBP group. Metrics of electrocardiogram, echocardiography, hemodynamics, and expression of left ventricular proteins were evaluated. RESULTS: Compared with LVSP, LBBP had better peak strain dispersion (44.67 ± 1.75 ms vs 55.50 ± 4.85 ms; P < 0.001) and hemodynamic effect (dP/dtmax improvement: 27.16% ± 7.79% vs 11.37% ± 4.73%; P < 0.001), whereas no significant differences in cardiac function were shown. The altered expressions of proteins in the lateral wall vs septum in the DHF group were partially reversed by LBBP and LVSP, which was associated with the contraction and adhesion process, separately. CONCLUSIONS: The animal study demonstrated that LBBP offered better mechanical synchrony and improved hemodynamics than LVSP, which might be explained by the reversed expression of contraction proteins. These results supported the potential superiority of left bundle branch area pacing with the capture of the conduction system in DHF model.
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The purple nonsulfur bacteria, Rhodospirillum rubrum, is recognized as a potential strain for PHAs bioindustrial processes since they can assimilate a broad range of carbon sources, such as syngas, to allow reduction of the production costs. In this study, we comparatively analyzed the biomass and PHA formation behaviors of R. rubrum under 100% CO and 50% CO gas atmosphere and found that pure CO promoted the PHA synthesis (PHA content up to 23.3% of the CDW). Hydrogen addition facilitated the uptake and utilization rates of CO and elevated 3-HV monomers content (molar proportion of 3-HV up to 9.2% in the presence of 50% H2). To elucidate the genetic events culminating in the CO assimilation process, we performed whole transcriptome analysis of R. rubrum grown under 100% CO or 50% CO using RNA sequencing. Transcriptomic analysis indicated different CO2 assimilation strategy was triggered by the presence of H2, where the CBB played a minor role. An increase in BCAA biosynthesis related gene abundance was observed under 50% CO condition. Furthermore, we detected the α-ketoglutarate (αKG) synthase, converting fumarate to αKG linked to the αKG-derived amino acids synthesis, and series of threonine-dependent isoleucine synthesis enzymes were significantly induced. Collectively, our results suggested that those amino acid synthesis pathways represented a key way for carbon assimilation and redox potential maintenance by R. rubrum growth under syngas condition, which could partly replace the PHA production and affect its monomer composition in copolymers. Finally, a fed-batch fermentation of the R. rubrum in a 3-l bioreactor was carried out and proved H2 addition indeed increased the PHA accumulation rate, yielding 20% ww-1 PHA production within six days.
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Carbono , Fermentación , Redes y Vías Metabólicas , Polihidroxialcanoatos , Rhodospirillum rubrum , Rhodospirillum rubrum/metabolismo , Rhodospirillum rubrum/genética , Polihidroxialcanoatos/biosíntesis , Polihidroxialcanoatos/metabolismo , Carbono/metabolismo , Monóxido de Carbono/metabolismo , Dióxido de Carbono/metabolismo , Hidrógeno/metabolismo , Biomasa , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión GénicaRESUMEN
BACKGROUND: The combined association of physical activity (PA) and alcohol use (AU) with long-term mortality is yet to be investigated. METHODS: For the current study, 12,621 participants aged ≥ 20 years were enrolled from the National Health and Nutrition Examination Survey (1999-2004). The study endpoint was all-cause mortality. Cox proportional hazards regression models were used to examine the combined effect of PA and AU on long-term mortality. RESULTS: The study population was divided into young (< 60 years, N = 8,258) and old (≥ 60 years, N = 4,363) groups. The median follow-up time was 203 months. In both young and old group, sedentary lifestyle combined with even minimal AU were associated with elevated risk of death (all P < 0.05). In young group, the integration of high volume AU with any degree of PA, including sedentary PA (HR = 2.35, 95% CI 1.24-4.44, P = 0.009), low PA (HR = 1.64, 95% CI 1.01-2.68, P = 0.047), and moderate-to-vigorous PA (HR = 1.99, 95% CI 1.03-3.84, P = 0.041), was associated with an increased risk of mortality. This relationship persisted as significant after adjusting for potential confounders (all P < 0.05). In old group, combining moderate-to-vigorous PA and low volume AU (HR = 0.59, 95% CI 0.37-0.94, P = 0.027) was associated with a reduction in mortality. After adjustment, the combination of moderate-to-vigorous PA and low volume AU was independently associated with favorable prognostic outcomes (all P < 0.05). CONCLUSIONS: In both age groups, combining sedentary lifestyle with even minimal AU was a risk factor for death. In young group, combining any level of PA with high volume AU was associated with increased mortality. In old group, combining moderate-to-vigorous PA with low volume AU was related to reduced mortality.
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Consumo de Bebidas Alcohólicas , Mortalidad , Encuestas Nutricionales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/mortalidad , Mortalidad/tendencias , Anciano , Factores de Edad , Ejercicio Físico , Conducta Sedentaria , Modelos de Riesgos Proporcionales , Adulto Joven , Factores de Riesgo , Estudios de SeguimientoRESUMEN
OBJECTIVES: Delirium is a significant health concern in acute stroke patients. We aim to systematically summarize existing evidence to conduct a meta-analysis to quantify the occurrence and risk factors for delirium after acute stroke. METHOD: PubMed, EMBASE and MEDLINE were searched from inception to Feb. 2023 for prospective observational studies that reported the incidence or prevalence of post-stroke delirium and/or evaluated potential risk factors. The search strategy was created using controlled vocabulary terms and text words for stroke and delirium. We performed a meta-analysis of the estimates for occurrence and risk factors using random-effects models. Meta-regression and subgroup meta-analyses were conducted to explore the sources of heterogeneity. Study quality and quality of evidence were assessed using the customized Newcastle-Ottawa Scale and GRADE, respectively. RESULTS: Forty-nine studies that enrolled 12383 patients were included. The pooled occurrence rate of post-stroke delirium was 24.4â¯% (95â¯%CI, 20.4â¯%-28.9â¯%, I2=96.2â¯%). The pooled occurrence of hyperactive, hypoactive, and mixed delirium was 8.5â¯%, 5.7â¯% and 5.0â¯%, respectively. Study location, delirium assessment method and stroke type independently affected the heterogeneity of the pooled estimate of delirium. Statistically significant risk factors were older age, low education level, cigarette smoking, alcohol drinking, atrial fibrillation, lower ADL level, higher pre-stroke mRS score, premorbid cognitive impairment or dementia, aphasia, total anterior circulation impairment, higher National Institute of Health Stroke Scale score and infection. CONCLUSIONS: Delirium affected 1 in 4 acute stroke patients, although reported rates may depend on assessment method and stroke type. Timely prevention, recognition and intervention require prioritizing patients with dominant risk factors.
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PURPOSE: To analyse the types of chairside CAD/CAM all-ceramic restorations and the color range of all-ceramic materials used so as to provide reference for the application of clinical chairside all-ceramic restoration and the color selection of all-ceramic materials. METHODS: IPS e.max CAD prostheses and related data were collected from January 2021 to December 2021 from the Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The number and type of restorations and the color of materials were investigated and analyzed by descriptive statistics. RESULTS: A total of 1 374 restorations were included, of which 624 were crown restorations, accounting for 45.41% of the total restorations. 516 cases were veneer, accounting for 37.55%; 219 were inlays, accounting for 15.94%; fixed bridges were all adhesive bridges, with the least number with only 15 cases, accounting for 1.09%. In terms of the selection of restoration materials, the use rate of low-transparent(LT) ceramic blocks was significantly higher than that of other transparent ceramic blocks. A was the most frequently used ceramic color. The most frequently used porcelain blocks for veneers were LTA2 and LTA1; for inlay were LTA3; for crowns were LTA2 and LTA3. The blocks used in the fixed bridges were all LT, and A3 color was the majority. CONCLUSIONS: Chairside CAD/CAM all-ceramic prostheses made of IPS e.max CAD materials have been widely used in clinical practice. The types of prostheses include veneer, inset, crown and fixed bridge. The most commonly used IPS e.max CAD blocks are LTA2, LTA3 and LTA1. These findings have certain guiding significance for the clinical restoration decision and the reserve of porcelain blocks in primary hospitals.
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Cerámica , Diseño Asistido por Computadora , Coronas , Cerámica/química , Diseño de Prótesis Dental/métodos , Porcelana Dental/química , Color , Humanos , Coronas con Frente Estético , Incrustaciones/métodos , Restauración Dental Permanente/métodosRESUMEN
BACKGROUND: Traditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative. PURPOSE: To assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical-imaging parameters with deep learning (DL) features from preoperative MR images. STUDY TYPE: Retrospective/prospective. POPULATION: 354 pathologically confirmed STS patients (226 low-grade, 128 high-grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low-grade, 6 high-grade) were enrolled into prospective validation cohort. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/Unenhanced T1-weighted and fat-suppressed-T2-weighted. ASSESSMENT: DL features were extracted from MR images using a parallel ResNet-18 model to construct DL signature. Clinical-imaging characteristics included age, gender, tumor-node-metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS-T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical-imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression-free survival (PFS) in retrospective cohorts, with an average follow-up of 23 ± 22 months. STATISTICAL TESTS: Logistic regression, Cox regression, Kaplan-Meier curves, log-rank test, area under the receiver operating characteristic curve (AUC)ï¼and decision curve analysis. A P-value <0.05 was considered significant. RESULTS: The AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk-stratify patients and assess PFS. DATA CONCLUSION: The DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans. TECHNICAL EFFICACY: Stage 2.
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Diffuse large B-cell lymphoma (DLBCL), accounts for 30-40% of newly diagnosed lymphomas, has an overall cure rate of approximately 60%. Despite previous reports suggesting a negative prognostic association between CCND3 mutations and Burkitt lymphoma, their prognostic implications in DLBCL remain controversial. To investigate this, we evaluated CCND3 mutation status in 2059 DLBCL patient samples from four database (integrated cohort) and additional 167 DLBCL patient samples in our center (JSPH cohort). The mutation was identified in 5.5% (113/2059) of the cases in the integrated cohort, with 86% (97/113) found in exon 5. Furthermore, P284, R271, I290 and Q276 are described as CCND3 mutation hotspots. CCND3 mutation was associated with decreased overall survival (OS) in the integrated cohort (P = 0.0407). Further subgroup analysis revealed that patients diagnosed as EZB subtype DLBCL by LymphGen algorithm with CCND3 mutations had poorer OS than patients diagnosed as EZB subtype without CCND3 mutations (P = 0.0140). Using the next-generation sequencing (NGS) in the JSPH cohort, it was found that both cell cycle and DNA replication pathways were highly upregulated in patients with CCND3 mutations. Our results suggest that CCND3 mutations can serve as a novel prognostic factor in DLBCL pathogenesis. Consequently, the development of personalized therapeutic strategies for DLBCL patients with CCND3 mutations might enhance their prognosis.
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The biodiversity of grasslands is important for ecosystem function and health. The protection and mana-gement of grassland biodiversity requires the collection of the information on plant diversity. Hyperspectral remote sensing, with its unique advantages of extensive coverage and high spectral resolution, offers a new solution for long-term monitoring of plant diversity. We first reviewed the development history of hyperspectral remote sensing technology, emphasized its advantages in monitoring grassland plant diversity, and further analyzed its specific applications in this field. Finally, we discussed the challenges faced by hyperspectral remote sensing technology in its applications, such as the complexity of data processing, accuracy of algorithms, and integration with ground-based remote sensing data, and proposes prospects for future research directions. With the advancement of remote sensing technology and the integrated application of multi-source data, hyperspectral remote sensing would play an increasingly important role in grassland ecological monitoring and biodiversity conservation, which could provide scientific basis and technical support for global ecological protection and sustainable development.
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Biodiversidad , Monitoreo del Ambiente , Pradera , Tecnología de Sensores Remotos , Tecnología de Sensores Remotos/métodos , Monitoreo del Ambiente/métodos , Conservación de los Recursos Naturales/métodos , Imágenes Hiperespectrales/métodos , Ecosistema , Poaceae/crecimiento & desarrolloRESUMEN
BACKGROUND: It remains unclear whether the time interval between total thyroidectomy and radioactive iodine (RAI) therapy influences clinical outcomes in papillary thyroid carcinoma (PTC). This study aims to evaluate the impact of the timing to initiate RAI therapy on the response in PTC patients. METHODS: We retrospectively included 405 patients who underwent total thyroidectomy and subsequent RAI therapy at two tertiary hospitals in southwest China. Patients were categorized into two groups based on the interval between thyroidectomy and initial RAI therapy, that is, an early group (interval ≤90 days, n â =â 317) and a delayed group (interval >90 days, n â =â 88). Responses to RAI therapy were classified as excellent, indeterminate, biochemical incomplete, or structural incomplete. Univariate and multivariate analyses were conducted to identify factors associated with a nonexcellent response. RESULTS: Excellent responses were observed in 77.3% of the early group and 83.0% of the delayed group ( P â =â 0.252). No significant impact of RAI therapy timing was also observed across all American Thyroid Association risk classification categories. These findings persisted when patients were analyzed separately according to RAI dose (intermediate-dose group: 3.7 GBq [ n â =â 332]; high-activity group: ≥5.5 GBq [ n â =â 73]), further subdivided by the timing of RAI therapy. Multivariate analysis identified lymph node dissection, RAI dose, and stimulated thyroglobulin as independent risk factors for excellent response ( P â <â 0.05). CONCLUSION: The timing of initial RAI therapy following surgery did not significantly affect outcomes in patients with PTC.
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Radioisótopos de Yodo , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Radioisótopos de Yodo/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Persona de Mediana Edad , Cáncer Papilar Tiroideo/radioterapia , Cáncer Papilar Tiroideo/cirugía , Adulto , Resultado del Tratamiento , Factores de Tiempo , Tiroidectomía , Anciano , Carcinoma Papilar/radioterapia , Carcinoma Papilar/patología , Adulto Joven , AdolescenteRESUMEN
Cardiovascular disease (CVD) remains the leading cause of death worldwide. Patients often fail to recognize the early signs of CVDs, which display irregularities in cardiac contractility and may ultimately lead to heart failure. Therefore, continuously monitoring the abnormal changes in cardiac contractility may represent a novel approach to long-term CVD surveillance. Here, a zero-power consumption and implantable bias-free cardiac monitoring capsule (BCMC) is introduced based on the triboelectric effect for cardiac contractility monitoring in situ. The output performance of BCMC is improved over 10 times with nanoparticle self-adsorption method. This device can be implanted into the right ventricle of swine using catheter intervention to detect the change of cardiac contractility and the corresponding CVDs. The physiological signals can be wirelessly transmitted to a mobile terminal for analysis through the acquisition and transmission module. This work contributes to a new option for precise monitoring and early diagnosis of CVDs.