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This study aims to integrate a convolutional neural network (CNN) and the Random Forest Model into a rehabilitation assessment device to provide a comprehensive gait analysis in the evaluation of movement disorders to help physicians evaluate rehabilitation progress by distinguishing gait characteristics under different walking modes. Equipped with accelerometers and six-axis force sensors, the device monitors body symmetry and upper limb strength during rehabilitation. Data were collected from normal and abnormal walking groups. A knee joint limiter was applied to subjects to simulate different levels of movement disorders. Features were extracted from the collected data and analyzed using a CNN. The overall performance was scored with Random Forest Model weights. Significant differences in average acceleration values between the moderately abnormal (MA) and severely abnormal (SA) groups (without vehicle assistance) were observed (p < 0.05), whereas no significant differences were found between the MA with vehicle assistance (MA-V) and SA with vehicle assistance (SA-V) groups (p > 0.05). Force sensor data showed good concentration in the normal walking group and more scatter in the SA-V group. The CNN and Random Forest Model accurately recognized gait conditions, achieving average accuracies of 88.4% and 92.3%, respectively, proving that the method mentioned above provides more accurate gait evaluations for patients with movement disorders.
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Aprendizaje Profundo , Marcha , Trastornos del Movimiento , Redes Neurales de la Computación , Humanos , Trastornos del Movimiento/rehabilitación , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/fisiopatología , Marcha/fisiología , Masculino , Dispositivos de Autoayuda , Adulto , Femenino , Acelerometría/instrumentación , Acelerometría/métodos , Caminata/fisiología , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/instrumentaciónRESUMEN
Rapid and accurate realization of in situ analysis of deep-sea dissolved gases imperative to the study of ecological geology, oil and gas resource exploration, and global climate change. Herein, we report for the first time the deep-sea dissolved methane (CH4) in situ sensor based on quartz-enhanced photoacoustic and light-induced thermoelastic spectroscopy. The developed sensor system has a volume of φ120 mm × 430 mm and a power consumption of 7.6 W. The sensor, in the manner of frequency division multiplexing, is able to simultaneously measure the photoacoustic signals and light-induced thermoelastic signals, which can accurately correct laser-intensity induced influence on concentration. The spectral response of CH4 concentration varying from 0.01 to 5% is calibrated in detail based on the pressure and temperature in the application environment. The trend of the photoacoustic signal of CH4 at different water molecule (H2O) concentrations is investigated. An Allan variance analysis of several hours demonstrates a minimum detection limit of 0.21 ppm for the CH4 spectrometer. The sensor combined with the gas-liquid separation and enrichment unit is integrated into a compact marine standalone system. Since the specifically designed photoacoustic cell has a volume of only 1.2 mL, the time response for dissolved CH4 detection is reduced to 4 min. Furthermore, the sensor is successfully deployed in the vicinity of the "HaiMa" cold seeps at 1380 m underwater in the South China Sea, completing three consecutive days of measurements of dissolved CH4.
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Protein-peptide interactions (PPepIs) are vital to understanding cellular functions, which can facilitate the design of novel drugs. As an essential component in forming a PPepI, protein-peptide binding sites are the basis for understanding the mechanisms involved in PPepIs. Therefore, accurately identifying protein-peptide binding sites becomes a critical task. The traditional experimental methods for researching these binding sites are labor-intensive and time-consuming, and some computational tools have been invented to supplement it. However, these computational tools have limitations in generality or accuracy due to the need for ligand information, complex feature construction, or their reliance on modeling based on amino acid residues. To deal with the drawbacks of these computational algorithms, we describe a geometric attention-based network for peptide binding site identification (GAPS) in this work. The proposed model utilizes geometric feature engineering to construct atom representations and incorporates multiple attention mechanisms to update relevant biological features. In addition, the transfer learning strategy is implemented for leveraging the protein-protein binding sites information to enhance the protein-peptide binding sites recognition capability, taking into account the common structure and biological bias between proteins and peptides. Consequently, GAPS demonstrates the state-of-the-art performance and excellent robustness in this task. Moreover, our model exhibits exceptional performance across several extended experiments including predicting the apo protein-peptide, protein-cyclic peptide and the AlphaFold-predicted protein-peptide binding sites. These results confirm that the GAPS model is a powerful, versatile, stable method suitable for diverse binding site predictions.
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Péptidos , Sitios de Unión , Péptidos/química , Péptidos/metabolismo , Unión Proteica , Biología Computacional/métodos , Algoritmos , Proteínas/química , Proteínas/metabolismo , Aprendizaje AutomáticoRESUMEN
Liver fibrosis can cause hepatitis B virus (HBV)-associated hepatocellular carcinoma. Menstrual blood-derived mesenchymal stem cells (MenSCs) can ameliorate liver fibrosis through paracrine. Single-cell RNA sequencing (scRNA-seq) may be used to explore the roadmap of activated hepatic stellate cell (aHSC) inactivation to target liver fibrosis. This study established HBV transgenic (HBV-Tg) mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis and demonstrated that MenSCs migrated to the injured liver to improve serological indices and reduce fibrotic accumulation. RNA-bulk analysis revealed that MenSCs mediated extracellular matrix accumulation and cell adhesion. Liver parenchymal cells and nonparenchymal cells were identified by scRNA-seq in the control, CCl4, and MenSC groups, revealing the heterogeneity of fibroblasts/HSCs. A CellChat analysis revealed that diminished intercellular adhesion molecule (ICAM) signaling is vital for MenSC therapy. Specifically, Icam1 in aHSCs acted on Itgal/Itgb2 and Itgam/Itgb2 in neutrophils, causing decreased adhesion. The expression of Itgal, Itgam, and Itgb2 was higher in CCl4 group than in the control group and decreased after MenSC therapy in neutrophil clusters. The Lcn2, Pglyrp1, Wfdc21, and Mmp8 had high expression and may be potential targets in neutrophils. This study highlights interacting cells, corresponding molecules, and underlying targets for MenSCs in treating HBV-associated liver fibrosis.
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OBJECTIVE: To explore the clinical manifestations, diagnosis, pathological features and treatment of small-cell carcinoma of the prostate (SCCP). METHODS: We conducted a retrospective analysis of the clinical and pathological data of 2 cases of confirmed SCCP treated from November 2017 to March 2018, and reviewed relevant literature. RESULTS: Both the patients had the symptoms of frequent, urgent and difficult urination, with an elevated level of PSA and gradesâ ¡ï¼â ¢ enlargement of the prostate at palpation. One underwent prostate puncture biopsy and the other received transurethral 1470 laser vaporization resection of the tumor. Postoperative pathology indicated prostate adenocarcinoma accompanied by SCCP in both of the cases. One of them was treated by etoposide-platinum (EP) chemotherapy and died of systemic multiple organ failure 20 months after diagnosis, while the other underwent endocrine therapy and has lived with tumor up to the present day. CONCLUSION: The incidence rate of SCCP is low, its malignancy is high, and its prognosis is poor. The average survival of the patient is about 7 to 10 months after diagnosis. Currently there is no effective management of the dissease, except by relying on the experience of the treatment of small-cell lung cancer, with chemotherapy as the main option.
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Carcinoma de Células Pequeñas , Neoplasias de la Próstata , Humanos , Masculino , Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Pequeñas/terapia , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Etopósido/uso terapéutico , Etopósido/administración & dosificación , Anciano , Persona de Mediana Edad , Próstata/patología , Pronóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adenocarcinoma/terapia , Antígeno Prostático Específico/sangreRESUMEN
With electronic devices evolving toward portable and high-performance wearables, the constraints of complex and wet processing technologies become apparent. This study presents a scalable photolithography/chemical-free method for crafting wearable all-carbon nanotube (CNT) photodetector device arrays. Laser-assisted patterning and dry deposition techniques directly assemble gas-phase CNTs into flexible devices without any lithography or lift-off processes. The resulting wafer-scale all-CNT photodetector arrays showcase excellent uniformity, wearability, environmental stability, and notable broadband photoresponse, boasting a high responsivity of 44 AW-1 and a simultaneous detectivity of 1.9 × 109 Jones. This research provides an efficient, versatile, and scalable strategy for manufacturing wearable all-CNT device arrays, allowing widespread adoption in wearable optoelectronics and multifunctional sensors.
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The approach of shortcuts to adiabaticity enables the effective execution of adiabatic dynamics in quantum information processing with enhanced speed. Owing to the inherent trade-off between dynamical speed and the cost associated with the transitionless driving field, executing arbitrarily fast operations becomes impractical. To understand the accurate interplay between speed and energetic cost in this process, we propose theoretically and verify experimentally a new trade-off, which is characterized by a tightly optimized bound within s-parametrized phase spaces. Our experiment is carried out in a single ultracold ^{40}Ca^{+} ion trapped in a harmonic potential. By exactly operating the quantum states of the ion, we execute the Landau-Zener model as an example, where the quantum speed limit as well as the cost are governed by the spectral gap. We witness that our proposed trade-off is indeed tight in scenarios involving both initially eigenstates and initially thermal equilibrium states. Our work helps understanding the fundamental constraints in shortcuts to adiabaticity and illuminates the potential of underutilized phase spaces that have been traditionally overlooked.
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Liquid-solid contact electrification (CE) is essential to diverse applications. Exploiting its full implementation requires an in-depth understanding and fine-grained control of charge carriers (electrons and/or ions) during CE. Here, we decouple the electrons and ions during liquid-solid CE by designing binary superhydrophobic surfaces that eliminate liquid and ion residues on the surfaces and simultaneously enable us to regulate surface properties, namely work function, to control electron transfers. We find the existence of a linear relationship between the work function of superhydrophobic surfaces and the as-generated charges in liquids, implying that liquid-solid CE arises from electron transfer due to the work function difference between two contacting surfaces. We also rule out the possibility of ion transfer during CE occurring on superhydrophobic surfaces by proving the absence of ions on superhydrophobic surfaces after contact with ion-enriched acidic, alkaline, and salt liquids. Our findings stand in contrast to existing liquid-solid CE studies, and the new insights learned offer the potential to explore more applications.
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OBJECTIVES: To investigate the added value of extracellular volume fraction (ECV) and arterial enhancement fraction (AEF) derived from enhanced CT to conventional image and clinical features for differentiating between pleomorphic adenoma (PA) and atypical parotid adenocarcinoma (PCA) pre-operation. METHODS: From January 2010 to October 2023, a total of 187 cases of parotid tumors were recruited, and divided into training cohort (102 PAs and 51 PCAs) and testing cohort (24 PAs and 10 atypical PCAs). Clinical and CT image features of tumor were assessed. Both enhanced CT-derived ECV and AEF were calculated. Univariate analysis identified variables with statistically significant differences between the two subgroups in the training cohort. Multivariate logistic regression analysis with the forward variable selection method was used to build four models (clinical model, clinical model+ECV, clinical model+AEF, and combined model). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. Delong's test compared model differences, and calibration curve and decision curve analysis (DCA) assessed calibration and clinical application. RESULTS: Age and boundary were chosen to build clinical model, and to construct its ROC curve. Amalgamating the clinical model, ECV, and AEF to establish a combined model demonstrated superior diagnostic effectiveness compared to the clinical model in both the training and test cohorts (AUC = 0.888, 0.867). There was a significant statistical difference between the combined model and the clinical model in the training cohort (p = 0.0145). CONCLUSIONS: ECV and AEF are helpful in differentiating PA and atypical PCA, and integrating clinical and CT image features can further improve the diagnostic performance.
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Adenoma Pleomórfico , Medios de Contraste , Neoplasias de la Parótida , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Adenoma Pleomórfico/diagnóstico por imagen , Adenoma Pleomórfico/patología , Persona de Mediana Edad , Neoplasias de la Parótida/diagnóstico por imagen , Neoplasias de la Parótida/patología , Tomografía Computarizada por Rayos X/métodos , Diagnóstico Diferencial , Anciano , Adulto , Curva ROC , Estudios Retrospectivos , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patologíaRESUMEN
Inhibition of excessive osteoclastic activity is an efficient therapeutic strategy for many bone diseases induced by increased bone resorption, such as osteoporosis. BMS-582949, a clinical p38α inhibitor, is a promising drug in Phase II studies for treating rheumatoid arthritis. However, its function on bone resorption is largely unknown. In this study, we find that BMS-582949 represses RANKL-induced osteoclast differentiation in a dose-dependent manner. Moreover, BMS-582949 inhibits osteoclastic F-actin ring formation and osteoclast-specific gene expression. Mechanically, BMS-582949 treatment attenuates RANKL-mediated osteoclastogenesis through mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) signaling pathways without disturbing nuclear factor-κB (NF-κB) signaling. Interestingly, BMS-582949 impairs osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation (OXPHOS). Furthermore, BMS-582949 administration prevents bone loss in ovariectomized mouse mode by inhibiting both bone resorption and bone formation in vivo. Taken together, these findings indicate that BMS-582949 may be a potential and effective drug for the therapy of osteolytic diseases.
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Ratones Endogámicos C57BL , Osteoclastos , Osteogénesis , Ovariectomía , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Ratones , Ovariectomía/efectos adversos , Femenino , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteogénesis/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Resorción Ósea/prevención & control , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Células RAW 264.7 , Inhibidores de Proteínas Quinasas/farmacología , Remodelación Ósea/efectos de los fármacos , Ligando RANK/metabolismo , Diferenciación Celular/efectos de los fármacos , Relación Dosis-Respuesta a DrogaRESUMEN
Myocardial fibrosis is a pathological feature of doxorubicin-induced chronic cardiotoxicity that severely affects the prognosis of oncology patients. However, the specific cellular and molecular mediators driving doxorubicin-induced cardiac fibrosis, and the relative impact of different cell populations on cardiac fibrosis, remain unclear.This study aimed to explore the mechanism of doxorubicin-induced cardiotoxicity and myocardial fibrosis and to find potential therapeutic targets. Single-cell RNA sequencing was used to analyze the transcriptome of non-cardiomyocytes from normal and doxorubicin-induced chronic cardiotoxicity in mouse model heart tissue.We established a mouse model of doxorubicin-induced cardiotoxicity with a well-defined fibrotic phenotype. Analysis of single-cell sequencing results showed that fibroblasts were the major origin of extracellular matrix in doxorubicin-induced myocardial fibrosis. Further resolution of fibroblast subclusters showed that resting fibroblasts were converted to matrifibrocytes and then to myofibroblasts to participate in the myocardial remodeling process in response to doxorubicin treatment. Ctsb expression was significantly upregulated in fibroblasts after doxorubicin-induced.This study provides a comprehensive map of the non-cardiomyocyte landscape at high resolution, reveals multiple cell populations contributing to pathological remodeling of the cardiac extracellular matrix, and identifies major cellular sources of myofibroblasts and dynamic gene-expression changes in fibroblast activation. Finally, we used this strategy to detect potential therapeutic targets and identified Ctsb as a specific target for fibroblasts in doxorubicin-induced myocardial fibrosis.
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Cardiotoxicidad , Doxorrubicina , Fibrosis , Análisis de la Célula Individual , Doxorrubicina/efectos adversos , Animales , Ratones , Análisis de la Célula Individual/métodos , Miocardio/patología , Miocardio/metabolismo , Antibióticos Antineoplásicos/toxicidad , Antibióticos Antineoplásicos/efectos adversos , Modelos Animales de Enfermedad , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Perfilación de la Expresión Génica/métodos , Transcriptoma , Masculino , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Ratones Endogámicos C57BLRESUMEN
Retrogression and re-aging (RRA) treatment has been proven to effectively overcome the trade-off between strength and corrosion resistance. Current research focuses on the heating rate, temperature, and holding time of retrogression treatment while ignoring the retrogression cooling ways. In this paper, the effects of RRA treatment with different retrogression cooling ways on the microstructure and properties of newly developed T'/η' strengthened Al-Zn-Mg-Cu alloys were investigated by performing tests on mechanical properties, intergranular corrosion (IGC) resistance, and electrochemical corrosion behavior. The results show that the mechanical properties of samples subject to RRA treatment with water-quenching retrogression (ultimate tensile strength, yield strength, and elongation of 419.2 MPa, 370.2 MPa, and 15.9, respectively) are better than those of air-cooled and furnace-cooled samples. The corrosion resistance of water-quenching (IGC depth of 162.2 µm, corrosion current density of 0.833 × 10-5 A/cm2) and furnace-cooled samples (IGC depth of 123.7 µm, corrosion current density of 0.712 × 10-5 A/cm2) is better than that of air-cooled samples. Microstructure characterization reveals that the effect of the retrogression cooling rate on mechanical properties is related to the size of T'/η' precipitates with grains as well as the proportion of T' and η', while the difference in corrosion resistance depends on the continuity of grain boundary precipitates (GBPs). With mechanical properties, corrosion resistance, and time cost taken into consideration, it is appropriate to select water quenching for retrogression. These findings offer valuable insights for further design to achieve superior performance in various applications.
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In the precise point positioning/real-time kinematic (PPP-RTK) technique, high-precision ionospheric delay correction information is an important prerequisite for rapid PPP convergence. The commonly used ionospheric modeling approaches in the PPP-RTKs only take the trend term of the ionospheric total electron content (TEC) variations into account. As a result, the residual ionospheric delay still affects the positioning solutions. In this study, we propose a two-step regional ionospheric modeling approach that involves combining a polynomial fitting model (PFM) and a Kriging interpolation (KI) model. In the first step, a polynomial fitting method is used to model the trend term of the ionospheric TEC variations. In the second step, a KI method is used to compensate for the residual term of the ionospheric TEC variations. Datasets collected from continuously operating reference stations (CORSs) in Hunan Province, China, are used to validate the PFM/KI method by comparing with a single PFM method and a combined PFM and inverse distance weighting interpolation (IDWI) method. The experimental results show that the two-step PFM/KI modeled ionospheric delay achieves an average root mean square (RMS) error of 1.8 cm, which is improved by about 48% and 23% when compared with the PFM and PFM/IDWI methods, respectively. Regarding the positioning performance, the PPP-RTK with the PFM/KI method takes an average of 1.8 min or 4.0 min to converge to a positioning accuracy of 1.3 cm or 2.5 cm in the horizontal and vertical directions, respectively. The convergence times are decreased by about 18% and 14% in the horizontal direction and 9% and 5% in the vertical direction over the PFM and the PFM/IDWI methods, respectively.
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BACKGROUND: To evaluate the intraobserver repeatability and interobserver reproducibility of a newly developed dynamic real-time visualization 25 kHz swept-source optical coherence tomography (SS-OCT) based biometer (ZW-30, TowardPi Medical Technology Ltd, China) and compare its agreement with another SS-OCT based biometer (IOLMaster 700, Carl Zeiss Meditec AG, Jena, Germany). METHODS: Eighty-two healthy right eyes were enrolled in this prospective observational study. Measurements were repeated for three times using the ZW-30 and IOLMaster 700 in a random order. Obtained parameters included axial length (AL), central corneal thickness (CCT), aqueous depth (AQD), anterior chamber depth (ACD), lens thickness (LT), mean keratometry (Km), astigmatism magnitude (AST), vector J0, vector J45, and corneal diameter (CD). The within-subject standard deviation (Sw), test-retest (TRT) variability, coefficient of variation (CoV), and intraclass correlation coefficient (ICC) were adopted to assess the intraobserver repeatability and interobserver reproducibility. The double-angle plot was also used to display the distribution of AST. To estimate agreement, Bland-Altman plots were used. RESULTS: For the intraobserver repeatability and interobserver reproducibility, the Sw, TRT and CoV for all parameters were low. Meanwhile, the ICC values were all close to 1.000, except for the J45 (ICC = 0.887 for the intraobserver repeatability). The double-angle plot showed that the distribution of AST measured by these two devices was similar. For agreement, the Bland-Altman plots showed narrow 95% limits of agreements (LoAs) for AL, CCT, AQD, ACD, LT, Km AST, J0, J45, and CD (- 0.02 mm to 0.02 mm, - 7.49 µm to 8.08 µm, - 0.07 mm to 0.04 mm, - 0.07 mm to 0.04 mm, - 0.07 mm to 0.08 mm, - 0.16 D to 0.30 D, - 0.30 D to 0.29 D, - 0.16 D to 0.16 D, - 0.23 D to 0.13 D, and - 0.39 mm to 0.10 mm, respectively). CONCLUSIONS: The newly dynamic real-time visualization biometer exhibited excellent intraobserver repeatability and interobserver reproducibility. The two devices both based on the SS-OCT principle had similar ocular parameters measurement values and can be interchanged in clinical practice.
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BACKGROUND: Microsatellite instability (MSI) is associated with treatment response and prognosis in patients with rectal cancer (RC). However, intratumoral heterogeneity limits MSI testing in patients with RC. The authors developed a subregion radiomics model based on multiparametric MRI to preoperatively assess high-risk subregions with MSI and predict the MSI status of patients with RC. METHODS: This retrospective study included 475 patients (training cohort, 382; external test cohort, 93) with RC from two participating hospitals between April 2017 and June 2023. In the training cohort, subregion radiomic features were extracted from multiparametric MRI, which included T2-weighted, T1-weighted, diffusion-weighted, and contrast-enhanced T1-weighted imaging. MSI-related subregion radiomic features, classical radiomic features, and clinicoradiological variables were gathered to build five predictive models using logistic regression. Kaplan-Meier survival analysis was conducted to explore the prognostic information. RESULTS: Among the 475 patients [median age, 64 years (interquartile range, IQR: 55-70 years); 304 men and 171 women], the prevalence of MSI was 11.16% (53/475). The subregion radiomics model outperformed the classical radiomics and clinicoradiological models in both training [area under the curve (AUC)=0.86, 0.72, and 0.59, respectively] and external test cohorts (AUC=0.83, 0.73, and 0.62, respectively). The subregion-clinicoradiological model combining clinicoradiological variables and subregion radiomic features performed the optimal, with AUCs of 0.87 and 0.85 in the training and external test cohorts, respectively. The 3-year disease-free survival rate of MSI groups predicted based on the model was higher than that of the predicted microsatellite stability groups in both patient cohorts (training, P =0.032; external test, P =0.046). CONCLUSIONS: The authors developed and validated a model based on subregion radiomic features of multiparametric MRI to evaluate high-risk subregions with MSI and predict the MSI status of RC preoperatively, which may assist in individualized treatment decisions and positioning for biopsy.
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Inestabilidad de Microsatélites , Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias del Recto , Humanos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/genética , Neoplasias del Recto/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Pronóstico , Medición de Riesgo , RadiómicaRESUMEN
The ubiquity of dissolved organic matter (DOM) makes it encounter the released perï¬uorooctanoic acid (PFOA) in subsurface environment. However, the effect of DOM (e.g., humic acid, HA) on PFOA transport in soils and the critical influencing factors and mechanisms remain obscure. Column experiments were conducted to explore PFOA transport with the presence of different concentrations of HA in three types of soils and two types of Al oxide coated sand. Results revealed soil properties significantly regulate the effects of HA on PFOA transport, for which pore size distribution, minerals content (e.g., Al oxide) and pH were critical influencing soil-properties. For soil with large mesopore volume, pore blockage caused by HA controlled the effect of HA on PFOA transport. Large mesopore volume significantly alleviated pore blockage of HA, and led to insignificant effects of HA on PFOA transport. For soil exhibited minimum mesopore volume, Al oxide content and pH dominated the effect of HA on PFOA transport. Results from Al oxide coated sand (low mesopore volume) columns further proved that higher Al oxide content and lower pH caused more significant facilitating effect of HA on PFOA transport via site competition. Results highlighted the importance of considering pore size distribution and Al oxide content when assessing PFOA mobility capacity with co-transport with DOM in soils.
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Caprilatos , Fluorocarburos , Sustancias Húmicas , Suelo , Sustancias Húmicas/análisis , Óxidos , ArenaRESUMEN
Lymph node dissection has been a long-standing diagnostic and therapeutic strategy for metastatic cancers. However, questions over myriad related complications and survival outcomes are continuously debated. Immunotherapy, particularly neoadjuvant immunotherapy, has revolutionized the conventional paradigm of cancer treatment, yet has benefited only a fraction of patients. Emerging evidence has unveiled the role of lymph nodes as pivotal responders to immunotherapy, whose absence may contribute to drastic impairment in treatment efficacy, again posing challenges over excessive lymph node dissection. Hence, centering around this theme, we concentrate on the mechanisms of immune activation in lymph nodes and provide an overview of minimally invasive lymph node metastasis diagnosis, current best practices for activating lymph nodes, and the prognostic outcomes of omitting lymph node dissection. In particular, we discuss the potential for future comprehensive cancer treatment with effective activation of immunotherapy driven by lymph node preservation and highlight the challenges ahead to achieve this goal.
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Escisión del Ganglio Linfático , Ganglios Linfáticos , Humanos , Ganglios Linfáticos/patología , Pronóstico , Metástasis Linfática/patología , InmunoterapiaRESUMEN
Rationale: Although programmed death-ligand 1 (PD-L1) inhibitors have achieved efficacy in cancer therapy, their response rate is low. Differences in the prognosis of patients with cancer under anti-PD-L1 treatment are related to the PD-L1 level in tumors. Accurate PD-L1 detection can optimize the accuracy of tumor immunotherapy and avoid ineffective clinical diagnosis and treatments. Methods: We investigated the imaging efficiency and therapy monitoring capacity of [89Zr]Zr-DFO-KN035 immunoPET for tumors. We labeled the monodomain anti-PD-L1 antibody KN035 with the radionuclide zirconium-89 and used this tracer for PET imaging. [89Zr]Zr-DFO-KN035 uptakes in patients with PD-L1-positive tumors, including primary and metastatic tumors, as well as in normal tissues, were comparatively assessed by using positron emission tomography/computed tomography imaging. Results: In PD-L1-positive patients, [89Zr]Zr-DFO-KN035 was sensitive in tumor-targeting imaging and could detect multiple metastatic foci, including multiple bone metastases (tumor-to-muscle ratios of 7.102 and 6.118 at 55 and 120 h, respectively) and lymph-node metastases (tumor-to-muscle ratios of 11.346 and 6.542 at 55 and 120 h, respectively). The needed radioactive dose of [89Zr]Zr-DFO-KN035 (55.5-92.5 MBq) used in this study was considerably lower than that of [18F]FDG (370-555 MBq). [89Zr]Zr-DFO-KN035 monitored and predicted the site of adverse reactions in antitumor immunotherapy. Moreover, after antitumor treatment, [89Zr]Zr-DFO-KN035 enabled observational imaging for therapeutic efficacy evaluation, which can help predict patient prognosis. Conclusion: [89Zr]Zr-DFO-KN035 can be used for the diagnosis and therapy monitoring of PD-L1-positive tumors and provide noninvasive and comprehensive observations for tumor diagnostic imaging, prognosis prediction, and efficacy evaluation.
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Anticuerpos Monoclonales Humanizados , Antígeno B7-H1 , Humanos , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Línea Celular Tumoral , CirconioRESUMEN
BACKGROUND: To assess repeatability and reproducibility of corneal epithelium thickness (ET) measured by a spectral-domain optical coherence tomographer (SD-OCT)/Placido topographer (MS-39, CSO, Florence, Italy) in keratoconus (KC) population at different stages, as well as to determine the progression limits for evaluating KC progression. METHODS: A total of 149 eyes were enrolled in this study, with 29 eyes in the forme fruste keratoconus (FFKC) group, 34 eyes in the mild KC group, 40 eyes in the moderate KC group, and 46 eyes in the severe KC group. Employing the within-subject standard deviation (Sw), test-retest variability (TRT), coefficient of variation (CoV), and intraclass correlation coefficient (ICC) to evaluate intraoperator repeatability and interoperator reproducibility. RESULTS: The repeatability and reproducibility of MS-39 in patients with KC were acceptable, according to ICC values ranging from 0.732 to 0.954. However, patients with more severe KC and progressive peripheralization of the measurement points had higher TRTs but a thinning trend. The current study tended to set the cut-off values of mild KC, moderate KC, and severe KC to 4.9 µm, 5.2 µm, and 7.4 µm for thinnest epithelium thickness (TET). When differences between follow-ups are higher than those values, progression of the disease is possible. As for center epithelium thickness (CET), cut-off values for mild KC, moderate KC, and severe KC should be 2.8 µm, 4.4 µm, and 5.3 µm. This might be useful in the follow-up and diagnosis of keratoconus. CONCLUSIONS: This study demonstrated that the precision of MS-39 was reduced in measuring more severe KC patients and more peripheral corneal points. In determining disease progression, values should be differentiated between disease-related real changes and measurement inaccuracies. Due to the large difference in ET measured by MS-39 between various stages of disease progression, it is necessary to accurately grade KC patients to avoid errors in KC clinical decision-making.
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HBV-miR-3 is encoded by HBV and takes part in pathogenesis of HBV-related liver disease. Whether HBV-miR-3 has a relationship with HBV replication and is predictive of PegIFN-α treatment response is still unknown. HBV-miR-3 quantification is based on qRT-PCR. The relationship of HBV-miR-3 and HBV replication, and predictive value of HBV-miR-3 were evaluated in a cohort of 650 HBeAg positive patients from a multi-center, randomized phase III clinical trial for the study of PegIFN-a2b. HBV-miR-3 is significantly positively related to HBVDNA, HBVpgRNA, HBeAg and HBsAg at baseline and at all the different time points during PegIFN-α treatment. Both univariate regression analyses and multivariate logistic regression analyses showed HBV-miR-3 is a predictor of HBeAg seroconversion in the patients treated with PegIFN-α at weeks of 0, 12, and 24. 70.0% of patients with HBV-miR-3 < 3log at week 12 achieved HBeAg seroconversion, otherwise, with HBV-miR-3 > 6log at week 12 no patient obtained HBeAg seroconversion. Conbination of HBV-miR-3 and HBeAg is more strongly predictive of HBeAg seroconversion (83.64%) at week 12. HBV-miR-3 is new biomarker for HBV replication and positively correlated to HBV replication. HBV-miR-3 is also an early predictor of HBeAg seroconversion in the patients treated with PegIFN-α.