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To better understand the migration behavior of plastic fragments in the environment, development of rapid non-destructive methods for in-situ identification and characterization of plastic fragments is necessary. However, most of the studies had focused only on colored plastic fragments, ignoring colorless plastic fragments and the effects of different environmental media (backgrounds), thus underestimating their abundance. To address this issue, the present study used near-infrared spectroscopy to compare the identification of colored and colorless plastic fragments based on partial least squares-discriminant analysis (PLS-DA), extreme gradient boost, support vector machine and random forest classifier. The effects of polymer color, type, thickness, and background on the plastic fragments classification were evaluated. PLS-DA presented the best and most stable outcome, with higher robustness and lower misclassification rate. All models frequently misinterpreted colorless plastic fragments and its background when the fragment thickness was less than 0.1mm. A two-stage modeling method, which first distinguishes the plastic types and then identifies colorless plastic fragments that had been misclassified as background, was proposed. The method presented an accuracy higher than 99% in different backgrounds. In summary, this study developed a novel method for rapid and synchronous identification of colored and colorless plastic fragments under complex environmental backgrounds.
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Monitoreo del Ambiente , Aprendizaje Automático , Plásticos , Espectroscopía Infrarroja Corta , Espectroscopía Infrarroja Corta/métodos , Monitoreo del Ambiente/métodos , Plásticos/análisis , Análisis de los Mínimos Cuadrados , Análisis Discriminante , ColorRESUMEN
Accurate and fast extraction of step parameters from video recordings of gait allows for richer information to be obtained from clinical tests such as Timed Up and Go. Current deep-learning methods are promising, but lack in accuracy for many clinical use cases. Extracting step parameters will often depend on extracted landmarks (keypoints) on the feet. We hypothesize that such keypoints can be determined with an accuracy relevant for clinical practice from video recordings by combining an existing general-purpose pose estimation method (OpenPose) with custom convolutional neural networks (convnets) specifically trained to identify keypoints on the heel. The combined method finds keypoints on the posterior and lateral aspects of the heel of the foot in side-view and frontal-view images from which step length and step width can be determined for calibrated cameras. Six different candidate convnets were evaluated, combining three different standard architectures as networks for feature extraction (backbone), and with two different networks for predicting keypoints on the heel (head networks). Using transfer learning, the backbone networks were pre-trained on the ImageNet dataset, and the combined networks (backbone + head) were fine-tuned on data from 184 trials of older, unimpaired adults. The data was recorded at three different locations and consisted of 193 k side-view images and 110 k frontal-view images. We evaluated the six different models using the absolute distance on the floor between predicted keypoints and manually labelled keypoints. For the best-performing convnet, the median error was 0.55 cm and the 75% quartile was below 1.26 cm using data from the side-view camera. The predictions are overall accurate, but show some outliers. The results indicate potential for future clinical use by automating a key step in marker-less gait parameter extraction.
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PURPOSE: The role of tumor resection remains undetermined in treating primary central nervous system lymphomas (PCNSLs). This study aimed to clarify the impact of tumor resection on survival and functional outcomes, and to identify subgroups benefiting from resection. METHODS: We retrospectively reviewed records from 2010 to 2021 for PCNSL diagnosed at Chang Gung Memorial Hospital, Linkou. Patients were categorized by extent of resection: gross total resection (GTR), partial resection (PR), and biopsy. Univariate and multivariate analyses were performed to identify prognostic factors for survival and functional outcomes. Subgroup analysis was conducted to characterize patients who benefit from tumor resection. RESULTS: Of 88 patients, 12 had GTR, 25 had PR, and 51 received biopsy. GTR correlated with longer progression free survival (PFS) (HR 0.25, p=0.039), remaining significant in multivariate analysis (adjusted HR 0.09, p=0.004). In solitary PCNSLs, GTR also independently predicted longer PFS (adjusted HR 0.13, p= 0.023). Patients with dominant tumors measuring ≥ 3â¯cm trended towards improved overall survival (OS) with cytoreductive surgery versus biopsy (median survival 38.6 months vs 22.3 months, p=0.083). Age ≥ 60 years (adjusted OR 16.9, p = 0.008) and preoperative Karnofsky Performance Scale ≤ 70 (adjusted OR 4.97, p = 0.049) predicted poorer functional outcomes, while radiation therapy (adjusted OR 0.10, p = 0.033) was protective. CONCLUSIONS: GTR significantly improved PFS in treating PCNSLs, particularly in solitary cases. For patients with dominant tumors measuring ≥ 3â¯cm, cytoreductive surgery may improve OS. Neither cytoreductive surgery nor GTR correlated with poor functional outcomes.
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To address the issues of ZVI's susceptibility to oxidation and aggregation, ball milling and Na2S·9H2O modification were employed on ZVI to enhance its efficiency in removing Cr(VI) from effluent. The characterization results expressed that S-mZVIbm had mesoporous and macroporous structures, enabling successful capture of Cr(VI). Moreover, S-mZVIbm had the highest adsorption capacity for Cr(VI) (350.04 mg/g) at pH = 2.00 and reached kinetic equilibrium within 420 min. Furthermore, the adsorption of Cr(VI) by S-mZVIbm conformed to the Avrami-fractional-order model, demonstrated that the adsorption process indicated a complex multi-adsorption process. Meanwhile, the adsorption also fit to Langmuir and Sips models, suggesting monolayer-level adsorption with heterogeneous sites located on S-mZVIbm. The S-mZVIbm could enhance Cr(VI) adsorption through various synergistic mechanisms, such as electrostatic interaction, chemical precipitation, surface complexation, and reduction. Overall, this research presented an innovative perspective for the modification of ZVI, and S-mZVIbm could be widely applied in the practical remediation of wastewater containing Cr(VI).
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Asymmetric optical transmission (AOT) has been an enduring hot topic of interest in various fields, including optical communication, information processing, and so on. Particularly, the development of reciprocal micro-nanostructures achieving AOT further facilitates and accelerates the miniaturization and integration of traditional optical components. However, most of these optical components merely consider a single AOT band and transmission in a specified direction, limiting the development of their versatile functions. In this paper, we theoretically propose an all-dielectric metamaterial consisting of a nanograting and a defective multilayer photonic crystal, exhibiting multi-band and bidirectional multiplexing AOT. More specifically, the proposed metamaterial demonstrates both narrowband and wideband AOT for incidence from the nanograting to the photonic crystal, and a completely different narrowband AOT for the opposite incidence, namely, from the photonic crystal to the nanograting. These distinctive AOT spectral features are achieved by matching the diffraction effect of the nanograting with the special energy band of the defective multilayer photonic crystal. Remarkably, the device exhibits a transmittance difference of up to 0.974 and a contrast ratio of up to 0.997 (transmittance ratio of up to 673), with a transmission bandwidth of 62.7 nm for incident light with a wavelength of 624 nm illuminating from the nanograting to the defective multilayer photonic crystal. Furthermore, the bandwidth and number of transmission bands can be flexibly tuned by changing the polarization angle of the incident light, showcasing its excellent polarization multiplexing characteristics. The designed metamaterial provides an effective strategy for the realization of versatile AOT devices and is conducive to expanding the application scenarios of AOT devices.
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Background: Testicular germ cell tumor (TGCT) is a type of tumor with relatively lower incidence but being more prevalent in young men. The expression of programmed cell death ligand 1 (PD-L1) serves as a potential biomarker for predicting the survival outcomes of other tumors. Some studies discovered higher prevalence of PD-L1 in TGCT patients who achieved favorable treatment outcomes, while other studies showed lower or absent expression of PD-L1 in TGCT with the better prognosis as well. Therefore, in order to address this controversy and clarify the association between the expression of PD-L1 and pathological features and prognosis of TGCT, this meta-analysis was conducted. Methods: A comprehensive literature search was performed using following search terms: "testis", "testicle", "testicular", "cancer", "carcinoma", "tumor", "neoplasm", "programmed cell death ligand 1", "programmed death ligand 1", "PD-L1", "PDL1", "B7 homolog 1", "B7-H1", "B7H1" and "CD274". Relevant studies were retrieved according to the inclusion criteria from reputable databases including PubMed, Embase, Web of Science, Cochrane Library and China National Knowledge Infrastructure (CNKI). These studies investigated the expression of PD-L1 in both tumor cells and tumor infiltrating immune cells (TIICs) in TGCT. The overall proportion of PD-L1 positivity was assessed using R programming. Pooled hazard ratio (HR) and odds ratio (OR) with corresponding 95% confidence interval (CI) were calculated using Revman software to evaluate the involvement of PD-L1 expression in TGCT. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality assessment of included studies. Sensitivity analysis and publication bias evaluation were subsequently performed. Results: A total of eight eligible studies compromising 1,589 patients diagnosed with TGCT were finally included in this study. PD-L1 positivity was detected in 31% and 41% of TGCT patients' tumor cells and TIICs, respectively. The pooled data demonstrated a significant association between elevated PD-L1 expression levels in TIICs and a favorable prognosis characterized by the reduced disease progression and relapse events (HR =0.21, 95% CI: 0.13-0.33). Furthermore, PD-L1+ TIICs exhibited higher prevalence rates in seminoma (OR =2.11, 95% CI: 1.57-2.84) and embryonal carcinoma (OR =6.23, 95% CI: 2.42-16.02) patients. Notably, PD-L1 expression in TIICs displayed a tendency to increase in TGCT patients with lower stages or without lymph node metastasis. Conclusions: PD-L1 expression was observed in choriocarcinoma tumor cells, while yolk sac tumor and teratoma tumor cells exhibited lower or absent expression of PD-L1. Conversely, PD-L1 expression in TIICs was associated with seminoma and embryonal carcinoma, which was more commonly observed in TGCT patients with lower stages and better prognosis, thereby providing a theoretical foundation for the application of immunotherapy in relapsed/refractory TGCT patients.
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This study proposes a new method to evaluate the effectiveness of orebody grade estimations, drawing upon the analysis of existing evaluation methods for grade estimation. This new approach addresses factors such as uneven sampling and asymmetric estimation range, which are challenging to overcome with existing evaluation techniques. The core principle of this method involves documenting how frequently individual samples are used during grade estimation and calculating the total distance weights for each sample. Subsequently, the usage frequency and total weight of the samples are standardized, and these standardized values are weighted based on the sample grades. A comparison is made between the weighted sample grades and the estimated grades, with the closeness between the two serving as a metric for assessing the effectiveness of the estimation. This study compares the new evaluation method to the direct comparison and cross-validation methods, examining the effectiveness of grade estimation using the inverse distance weighting (IDW) method. The findings revealed that: (1) The new evaluation method theoretically accounts for the systematic deviation between the statistical measures of estimated and sample grades resulting from uneven sample distribution, offering a fresh approach for enhancing the effectiveness of orebody grade estimation. (2) In the grade estimation of experimental Fe samples, the frequency of usage and the sum of distance weights were unequal. This inequality significantly contributes to the systematic deviation between the estimated and sample grades. (3) Comparing the new evaluation method to others confirms the stability and reliability of the new approach for evaluating the effectiveness of orebody grade estimation. This novel method demonstrates theoretical advantages and practical utility. (4) The deviation between the estimated grades and the statistical results of sample grades is influenced by the distribution pattern of sample grades, the spatial relationship between samples and estimation blocks, and the inherent systematic error associated with the IDW method. This systematic error cannot be overlooked.
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Evaluación Educacional , Humanos , Evaluación Educacional/métodosRESUMEN
OBJECTIVES: This study explored the mechanisms by which physical activity was associated with depressive symptoms in multi-ethnic (Han, Yi and Tibetan) adolescents in southwest China. The mediating role of insomnia in the association of physical activity with depressive symptoms, the moderating role of resilience in this mediation model and the moderating role of parental absence in the moderated mediation model were also examined. DESIGN: A cross-sectional survey. SETTING: In southwest China (Sichuan Province and Tibet Autonomous Region). PARTICIPANTS: 3195 adolescents from a school-based survey conducted between April and October 2020. METHODS: There were 3143 valid samples in this study (47.2% males with mean age=12.88±1.68 years). Structural equation models were developed to estimate the direct and mediating effect, and the moderating effect. Multigroup comparison was performed to examine the differences and similarities of the moderated mediation model across three parental absence subgroups: (1) both parents present, (2) one parent absent and (3) both parents absent. RESULTS: As hypothesised, physical activity was significantly and positively associated with the reduction of depressive symptoms in adolescents. Insomnia partially mediated the effect of physical activity on depressive symptoms. In addition, resilience moderated the direct and indirect effects of physical activity (through insomnia) on depressive symptoms. Finally, the multigroup comparison indicated the moderating effect of parental absence on the moderated mediation model. CONCLUSIONS: Physical activity was associated with alleviating insomnia symptoms among adolescents, thus correlating with the improvement of their depressive symptoms. Resilience was associated with enhancing the beneficial effects of physical activity, further improving depressive symptoms among adolescents, especially those with both absent parents. It is evident that physical activity interventions should be further incorporated into public health programmes to foster the physical and mental health of left-behind adolescents in southwest China.
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Depresión , Ejercicio Físico , Padres , Resiliencia Psicológica , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Masculino , Adolescente , Femenino , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Estudios Transversales , Depresión/epidemiología , Depresión/psicología , China/epidemiología , Ejercicio Físico/psicología , Padres/psicología , NiñoRESUMEN
Peritumoral hepatocytes are critical components of the liver cancer microenvironment, However, the role of peritumoral hepatocytes in the local tumor immune interface and the underlying molecular mechanisms have not been elucidated. YTHDF2, an RNA N6-methyladenosine (m6A) reader, is critical for liver tumor progression. The function and regulatory roles of YTHDF2 in peritumoral hepatocytes are unknown. This study demonstrated that oxaliplatin (OXA) upregulated m6A modification and YTHDF2 expression in hepatocytes. Studies using tumor-bearing liver-specific Ythdf2 knockout mice revealed that hepatocyte YTHDF2 suppresses liver tumor growth through CD8+ T cell recruitment and activation. Additionally, YTHDF2 mediated the response to immunotherapy. Mechanistically, OXA upregulated YTHDF2 expression by activating the cGAS-STING signaling pathway and consequently enhanced the therapeutic outcomes of immunotherapeutic interventions. Ythdf2 stabilized Cx3cl1 transcripts in an m6A-dependent manner, regulating the interplay between CD8+ T cells and the progression of liver malignancies. Thus, this study elucidated the novel role of hepatocyte YTHDF2, which promotes therapy-induced antitumor immune responses in the liver. The findings of this study provide valuable insights into the mechanism underlying the therapeutic benefits of targeting YTHDF2.
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Linfocitos T CD8-positivos , Quimiocina CX3CL1 , Hepatocitos , Neoplasias Hepáticas , Oxaliplatino , Proteínas de Unión al ARN , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Animales , Quimiocina CX3CL1/metabolismo , Quimiocina CX3CL1/genética , Hepatocitos/metabolismo , Ratones , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Humanos , Oxaliplatino/farmacología , Microambiente Tumoral/inmunología , Ratones Noqueados , Regulación Neoplásica de la Expresión Génica , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Antineoplásicos/farmacologíaRESUMEN
Ontologies play a pivotal role in knowledge representation across various artificial intelligence domains, serving as foundational frameworks for organizing data and concepts. However, the construction and evolution of ontologies frequently lead to logical contradictions that undermine their utility and accuracy. Typically, these contradictions are addressed using an Integer Linear Programming (ILP) model, which traditionally treats all formulas with equal importance, thereby neglecting the distinct impacts of individual formulas within minimal conflict sets. To advance this method, we integrate cooperative game theory to compute the Shapley value for each formula, reflecting its marginal contribution towards resolving logical contradictions. We further construct a graph-based representation of the ontology, enabling the extension of Shapley values to Myerson values. Subsequently, we introduce a Myerson-weighted ILP model that employs a lexicographic approach to eliminate logical contradictions in ontologies. The model ensures the minimum number of formula deletions, subsequently applying Myerson values to guide the prioritization of deletions. Our comparative analysis across 18 ontologies confirms that our approach not only preserves more graph edges than traditional ILP models but also quantifies formula contributions and establishes deletion priorities, presenting a novel approach to ILP-based contradiction resolution.
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Radiomics offers a noninvasive avenue for predicting clinicopathological factors. However, thorough investigations into a robust breast cancer outcome-predicting model and its biological significance remain limited. This study develops a robust radiomic model for prognosis prediction, and further excavates its biological foundation and transferring prediction performance. We retrospectively collected preoperative dynamic contrast-enhanced MRI data from three distinct breast cancer patient cohorts. In FUSCC cohort (n = 466), Lasso was used to select features correlated with patient prognosis and multivariate Cox regression was utilized to integrate these features and build the radiomic risk model, while multiomic analysis was conducted to investigate the model's biological implications. DUKE cohort (n = 619) and I-SPY1 cohort (n = 128) were used to test the performance of the radiomic signature in outcome prediction. A thirteen-feature radiomic signature was identified in the FUSCC cohort training set and validated in the FUSCC cohort testing set, DUKE cohort and I-SPY1 cohort for predicting relapse-free survival (RFS) and overall survival (OS) (RFS: p = 0.013, p = 0.024 and p = 0.035; OS: p = 0.036, p = 0.005 and p = 0.027 in the three cohorts). Multiomic analysis uncovered metabolic dysregulation underlying the radiomic signature (ATP metabolic process: NES = 1.84, p-adjust = 0.02; cholesterol biosynthesis: NES = 1.79, p-adjust = 0.01). Regarding the therapeutic implications, the radiomic signature exhibited value when combining clinical factors for predicting the pathological complete response to neoadjuvant chemotherapy (DUKE cohort, AUC = 0.72; I-SPY1 cohort, AUC = 0.73). In conclusion, our study identified a breast cancer outcome-predicting radiomic signature in a multicenter radio-multiomic study, along with its correlations with multiomic features in prognostic risk assessment, laying the groundwork for future prospective clinical trials in personalized risk stratification and precision therapy.
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Escalating energy demands of self-independent on-skin/wearable electronics impose challenges on corresponding power sources to offer greater power density, permeability, and stretchability. Here, a high-efficient breathable and stretchable monolithic hybrid triboelectric-piezoelectric-electromagnetic nanogenerator-based electronic skin (TPEG-skin) is reported via sandwiching a liquid metal mesh with two-layer topological insulator-piezoelectric polymer composite nanofibers. TPEG-skin concurrently extracts biomechanical energy (from body motions) and electromagnetic radiations (from adjacent appliances), operating as epidermal power sources and whole-body self-powered sensors. Topological insulators with conductive surface states supply notably enhanced triboelectric and piezoelectric effects, endowing TPEG-skin with a 288 V output voltage (10 N, 4 Hz), â¼3 times that of state-of-the-art devices. Liquid metal meshes serve as breathable electrodes and extract ambient electromagnetic pollution (±60 V, ±1.6 µA cm-2). TPEG-skin implements self-powered physiological and body motion monitoring and system-level human-machine interactions. This study provides compatible energy strategies for on-skin/wearable electronics with high power density, monolithic device integration, and multifunctionality.
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Cell type identification is an indispensable analytical step in single-cell data analyses. To address the high noise stemming from gene expression data, existing computational methods often overlook the biologically meaningful relationships between genes, opting to reduce all genes to a unified data space. We assume that such relationships can aid in characterizing cell type features and improving cell type recognition accuracy. To this end, we introduce scPriorGraph, a dual-channel graph neural network that integrates multi-level gene biosemantics. Experimental results demonstrate that scPriorGraph effectively aggregates feature values of similar cells using high-quality graphs, achieving state-of-the-art performance in cell type identification.
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Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Humanos , Redes Neurales de la Computación , RNA-Seq/métodos , Biología Computacional/métodos , Algoritmos , Programas Informáticos , Análisis de Expresión Génica de una Sola CélulaRESUMEN
BACKGROUND: Autoimmune pancreatitis (AIP) is a chronic form of pancreatitis characterized by diffused enlargement of the pancreas and irregular stenosis of the main pancreatic duct. Some studies have reported that AIP can cause hemorrhage of gastric varices (GV) related to portal hypertension (PH). However, such cases are rare. In addition, the association of PH with AIP is unclear. At the same time, the efficacy and duration of glucocorticoid therapy is also controversial. CASE SUMMARY: In this case, we reported a case of GV in pancreatic PH associated with AIP. Enhanced abdominal computed tomography (CT) suggested splenic vein (SV) and superior mesenteric vein (SMV) thromboses. The patient received a long-term glucocorticoid therapy, that the initial dose of 40 mg is reduced weekly by 5 mg, and then reduced to 5 mg for long-term maintenance. CT and gastroscopic examination after 8 mo of treatment indicated that SV and SMV were recanalized, pancreatic stiffness and swelling were ameliorated, and the GV almost completely disappeared. CONCLUSION: Long-term glucocorticoid therapy can alleviate the development of GV in patients with AIP and has potential reversibility.
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BACKGROUND: Our study utilized the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) to analyze and study the adverse event (AEs) signals of second-generation antipsychotic drug lumateperone, providing a reference for clinical safety monitoring in the treatment of schizophrenia. METHODS: The International Dictionary of Medical Terminology (version 26.0) was used to standardize the preferred system organ category (SOC) and preferred terminology (PT) for adverse drug events (ADE) data related to lumateperone. ADE signals were classified and described using four algorithms: reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian confidence-propagation neural network (BCPNN) and Multinomial gamma-poisson shrinkage (MGPS). RESULT: Among the 2542 case reports collected from the FAERS database, 1762 reports with lumateperone as a 'principal suspect(PS)' AEs were identified. Lumateperone-induced AEs occurred in 26 system organ categories (SOC). A total of 118 significant disproportionate preferred terms (PTs) meeting the requirements of 4 algorithms were retained, and unexpected major events, such as burning sensation, tremor, migraine etc. may also occur. The median time to onset of lumateperone-related adverse events was 9 days (interquartile range [IQR] 2-31.25 days), and most AEs occurred within the first 10 days and 1 month after initiation of lumateperone therapy. CONCLUSION: Our research may provide a better understanding of the potential adverse events that may be caused by lumateperone and those not recorded in the drug instructions, providing valuable signals for clinical use.
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Developing robust metal-based monolithic catalysts with efficient oxygen activation capacity is crucial for thermal catalytic treatment of volatile organic compound (VOC) pollution. Two-dimensional (2D) metal oxides are alternative thermal catalysts, but their traditional loading strategies on carriers still face challenges in practical applications. Herein, we propose a novel in situ molten salt-loading strategy that synchronously enables the construction of 2D Co3O4 and its growth on Fe foam for the first time to yield a unique monolithic catalyst named Co3O4/Fe-S. Compared to the Co3O4 nanocube-loaded Fe foam, Co3O4/Fe-S exhibits a significantly improved catalytic performance with a temperature reduction of 44 °C at 90% toluene conversion. Aberration-corrected scanning transmission electron microscopy and theoretical calculation suggest that Co3O4/Fe-S possesses abundant 2D Co3O4/Fe3O4 composite interfaces, which promote the construction of active sites (oxygen vacancy and Co3+) to boost oxygen activation and toluene chemisorption, thereby accelerating the transformation of reaction intermediates through Langmuir-Hinshelwood (L-H) and Mars-van Krevelen (MvK) mechanisms. Moreover, the growth mechanism reveals that 2D Co3O4/Fe3O4 composite interfaces are generated in situ in molten salt, inducing the growth of 2D Co3O4 onto the surface lattice of 2D Fe3O4. This study provides new insights into enhancing oxygen activation and opens an unprecedented avenue in preparing efficient monolithic catalysts for VOC oxidation.
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Oxidación-Reducción , Oxígeno , Tolueno , Catálisis , Tolueno/química , Oxígeno/química , Compuestos Orgánicos Volátiles/química , Cobalto/química , Óxidos/químicaRESUMEN
BACKGROUND: Cervical spine fracture-dislocations in patients with ankylosing spondylitis (AS) are mostly unstable and require surgery. However, osteoporosis, one of the comorbidities for AS, could lead to detrimental prognoses. There are few accurate assessments of bone mineral density in AS patients. AIM: To analyze Hounsfield units (HUs) for assessing bone mineral density in AS patients with cervical fracture-dislocation. METHODS: The HUs from C2 to C7 of 51 patients obtained from computed tomography (CT) scans and three-dimensional reconstruction of the cervical spine were independently assessed by two trained spinal surgeons and statistically analyzed. Inter-reader reliability and agreement were assessed by interclass correlation coefficient. RESULTS: The HUs decreased gradually from C2 to C7. The mean values of the left and right levels were significantly higher than those in the middle. Among the 51 patients, 25 patients (49.02%) may be diagnosed with osteoporosis, and 16 patients (31.37%) may be diagnosed with osteopenia. CONCLUSION: The HUs obtained by cervical spine CT are feasible for assessing bone mineral density with excellent agreement in AS patients with cervical fracture-dislocation.
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Genomic instability stands out as a pivotal hallmark of cancer, and PARP inhibitors (PARPi) emerging as a groundbreaking class of targeted therapy drugs meticulously crafted to inhibit the repair of DNA single-strand breaks(SSB) in tumor cells. Currently, PARPi have been approved for the treatment of ovarian cancer, pancreatic cancer, breast cancer, and prostate cancer characterized by homologous recombination(HR) repair deficiencies due to mutations in BRCA1/2 or other DNA repair associated genes and acquiring the designation of breakthrough therapy. Nonetheless, PARPi exhibit limited efficacy in the majority of HR-proficient BRCA1/2 wild-type cancers. At present, the synergistic approach of combining PARPi with agents that induce HR defects, or with chemotherapy and radiotherapy to induce substantial DNA damage, significantly enhances the efficacy of PARPi in BRCA wild-type or HR-proficient patients, supporting extension the use of PARPi in HR proficient patients. Therefore, we have summarized the effects and mechanisms of the combined use of drugs with PARPi, including the combination of PARPi with HR defect-inducing drugs such as ATRi, CHKi, HR indirectly inducing drugs like VEGFRi, CDKi, immune checkpoint inhibitors and drugs instigating DNA damage such as chemotherapy or radiotherapy. In addition, this review discusses several ongoing clinical trials aimed at analyzing the clinical application potential of these combined treatment strategies.
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Background: Observational studies and clinical trials suggest associations between immune cells, inflammatory factors, serum metabolites, and hepatic cancer. However, the causal relationships between these factors and hepatic cancer remain to be established. Objective: To explore the causal relationships between immune cells, inflammatory factors, serum metabolites, and hepatic cancer. Methods: This study employed comprehensive two-sample Mendelian randomization (MR) utilizing publicly available genetic data (GWAS) to analyze causal relationships between 731 immune cell traits, 91 inflammatory factors, 1400 serum metabolites, and hepatic cancer. The primary analysis used inverse variance-weighted (IVW) MR, with additional sensitivity tests to assess the validity of causal relationships. Results: After correction for heterogeneity and horizontal pleiotropy, in exploring the causal relationships between immune cell groups and hepatic cancer, we found that Terminally Differentiated CD4-CD8- T cell %T cell was negatively associated with hepatic cancer, serving as a protective factor, while Effector Memory CD4-CD8- T cell %CD4-CD8- T cell was positively associated with hepatic cancer, acting as a risk factor. In investigating the causal relationships between inflammatory factors and hepatic cancer, C-C motif chemokine 19 levels were positively associated with hepatic cancer, representing a risk factor, while Interleukin-10 levels were negatively associated with hepatic cancer, acting as a protective factor. Regarding the causal relationships between serum metabolites and hepatic cancer, (N(1) + N(8))-acetylspermidine levels were negatively associated with hepatic cancer, serving as a protective factor, while 1-(1-enyl-palmitoyl)-GPC (p-16:0) levels were positively associated with hepatic cancer, acting as a risk factor. Conclusion: Our MR analysis indicates causal relationships between immune cells, inflammatory factors, serum metabolites, and hepatic cancer. However, further validation is needed to assess the potential of these immune cells, inflammatory factors, and serum metabolites as preventive or therapeutic targets for hepatic cancer.
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Most of the antiviral drugs in the market are designed to target viral proteins directly. They are generally considered safe for human use. However, they also suffer from several inherent limitations, in particular, narrow-spectrum antiviral profiles and liability to drug resistance. The other strategy for antiviral drug development is targeting host factors, which are highly involved at different stages in the viral life cycle. In contrast to direct-acting antiviral agents, host-targeting antiviral ones normally exhibit broad-spectrum antiviral properties along with a much higher genetic barrier to drug resistance. Cyclin-dependent kinases (CDKs) represent one such host factor. In this review, we summarized a number of CDK inhibitors (CDKIs) of varied chemical scaffolds with demonstrated antiviral activity. Challenges and issues associated with the repurposing of CDKIs as antiviral agents were also discussed.