Paclitaxel is an antineoplastic agent widely used to treat several solid tumor types. The primary mechanism of action of paclitaxel is based on microtubule stabilization inducing cell-cycle arrest. ...Here, we use several tumor models to show that paclitaxel not only induces tumor cell-cycle arrest, but also promotes antitumor immunity.
, paclitaxel reprogrammed M2-polarized macrophages to the M1-like phenotype in a TLR4-dependent manner, similarly to LPS. Paclitaxel also modulated the tumor-associated macrophage (TAM) profile in mouse models of breast and melanoma tumors; gene expression analysis showed that paclitaxel altered the M2-like signature of TAMs toward an M1-like profile. In mice selectively lacking TLR4 on myeloid cells, for example, macrophages (LysM-Cre
/TLR4
), the antitumor effect of paclitaxel was attenuated. Gene expression analysis of tumor samples from patients with ovarian cancer before and after treatment with paclitaxel detected an enrichment of genes linked to the M1 macrophage activation profile (IFNγ-stimulated macrophages). These findings indicate that paclitaxel skews TAMs toward an immunocompetent profile via TLR4, which might contribute to the antitumor effect of paclitaxel and provide a rationale for new combination regimens comprising paclitaxel and immunotherapies as an anticancer treatment.
This study provides new evidence that the antitumor effect of paclitaxel occurs in part via reactivation of the immune response against cancer, guiding tumor-associated macrophages toward the M1-like antitumor phenotype.
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In the early 2000s, the first articles regarding the calculation of NMR parameters for natural products appeared in the literature. Since then, modelling 1H and 13C chemical shifts and spin–spin ...coupling constants for this class of compounds has experienced a remarkable increase in precision, accessibility, and application, leading to considerable advances in the field. More recently, significant contributions from several authors have led to continuous growth in this research field, updating and broadening the simulation of NMR parameters, in particular with the application of new techniques for data treatment. Nowadays, such studies are routinely found in the high impact literature. In this review, we intend to cover the general guidelines and the main advances in NMR calculations of natural products published since 2012. We intend to address the bottlenecks of quantum chemical calculations of NMR parameters, including mathematical definitions, updates, and a discussion of relevant examples, and to highlight novel tools, for example DU8+, CP3, DP4, DP4+ and J-DP4. We will cover all aspects of NMR simulation focusing on natural products, from the fundamentals to the new computational toolboxes available, combining advanced quantum chemical calculations with complex upstream data processing and machine learning.
Volcanic clouds pose significant threats to air traffic, human health, and economic activity, making early detection and monitoring crucial. Accurate determination of eruptive source parameters is ...crucial for forecasting and implementing preventive measures. This review article aims to identify the most common remote sensing methods for monitoring volcanic clouds. To achieve this, we conducted a systematic literature review of scientific articles indexed in the Web of Science database published between 2010 and 2022, using multiple query strings across all fields. The articles were reviewed based on research topics, remote sensing methods, practical applications, case studies, and outcomes using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our study found that satellite-based remote sensing approaches are the most cost-efficient and accessible, allowing for the monitoring of volcanic clouds at various spatial scales. Brightness temperature difference is the most commonly used method for detecting volcanic clouds at a specified temperature threshold. Approaches that apply machine learning techniques help overcome the limitations of traditional methods. Despite the constraints imposed by spatial and temporal resolution and optical limitations of sensors, multiplatform approaches can overcome these limitations and improve accuracy. This study explores various techniques for monitoring volcanic clouds, identifies research gaps, and lays the foundation for future research.
Several sets of reference regions have been used in the literature for the regional synthesis of observed and modelled climate and climate change information. A popular example is the series of ...reference regions used in the Intergovernmental Panel on Climate Change (IPCC) Special Report on Managing the Risks of Extreme Events and Disasters to Advance Climate Adaptation (SREX). The SREX regions were slightly modified for the Fifth Assessment Report of the IPCC and used for reporting subcontinental observed and projected changes over a reduced number (33) of climatologically consistent regions encompassing a representative number of grid boxes. These regions are intended to allow analysis of atmospheric data over broad land or ocean regions and have been used as the basis for several popular spatially aggregated datasets, such as the Seasonal Mean Temperature and Precipitation in IPCC Regions for CMIP5 dataset.
•Overall lifestyle worsened after several months of the COVID-19 pandemic.•Rates of depression and anxiety remained similar during the study period.•Previous mental disease was independently ...associated with an unhealthier lifestyle.•Depression, anxiety and alcohol abuse were associated with unhealthier lifestyles.
This study aimed to compare self-reported changes on lifestyle behaviors during two phases of the COVID-19 pandemic in Spain, and to evaluate clinical and sociodemographic factors associated with lifestyles.
Two cross-sectional web surveys were conducted during lockdown (April 15-May 15, 2020) and seven months later (November 16-December 16, 2020). Lifestyle behaviors were self-reported by a multidimensional scale (SMILE-C). Two separate samples of respondents were analyzed. A multivariate regression model was performed to evaluate the association of SMILE-C scores with demographic and clinical variables.
The sample comprised, 3412 participants from the first survey (S1) and in the S1 and 3635 from the second (S2). SMILE-C score decreased across surveys (p < 0.001). The rates of positive screenings for depression and anxiety were similar between the surveys, whereas those for alcohol abuse decreased (p < 0.001). Most participants in S2 reported that their lifestyle had not changed compared to those before the pandemic. Variables independently associated with an unhealthier lifestyle were working as an essential worker, lower educational level, previous mental disease, worse self-rated health, totally/moderate changes on diet, sleep or social support, as well as positive screenings for alcohol abuse, anxiety and depression.
The cross-sectional design and recruitment by non-probabilistic methods limit inferring causality and the external validity of the results.
Overall lifestyle worsened seven months after the lockdown in Spain. Several demographic and clinical factors were associated with lifestyle scores. The contribution of common mental disorders to unhealthier lifestyles should be considered in order to prevent the negative impact of the pandemic.
A new linear trinuclear Co(II)
complex with a formula of {Co(μ-L)}
Co has been prepared by self-assembly of Co(II) ions and the N
O
-tripodal Schiff base ligand H
L, which is obtained from the ...condensation of 1,1,1-tris(aminomethyl)ethane and salicylaldehyde. Single X-ray diffraction shows that this compound is centrosymmetric with triple-phenolate bridging groups connecting neighboring Co(II) ions, leading to a paddle-wheel-like structure with a pseudo-
axis lying in the Co-Co-Co direction. The Co(II) ions at both ends of the Co(II)
molecule exhibit distorted trigonal prismatic CoN
O
geometry, whereas the Co(II) at the middle presents an elongated trigonal antiprismatic CoO
geometry. The combined analysis of the magnetic data and theoretical calculations reveal strong easy-axis magnetic anisotropy for both types of Co(II) ions (|
| values higher than 115 cm
) with the local anisotropic axes lying on the pseudo-
axis of the molecule. The magnetic exchange interaction between the middle and ends Co(II) ions, extracted by using either a Hamiltonian accounting for the isotropic magnetic coupling and ZFS or the Lines' model, was found to be medium to strong and antiferromagnetic in nature, whereas the interaction between the external Co(II) ions is weak antiferromagnetic. Interestingly, the compound exhibits slow relaxation of magnetization and open hysteresis at zero field and therefore SMM behavior. The significant magnetic exchange coupling found for {Co(μ-L)}
Co is mainly responsible for the quenching of QTM, which combined with the easy-axis local anisotropy of the Co
ions and the collinearity of their local anisotropy axes with the pseudo-
axis favors the observation of SMM behavior at zero field.
A new linear trinuclear Co(II)3 complex with a formula of {Co(μ-L)}2Co has been prepared by self-assembly of Co(II) ions and the N3O3-tripodal Schiff base ligand H3L, which is obtained from the ...condensation of 1,1,1-tris(aminomethyl)ethane and salicylaldehyde. Single X-ray diffraction shows that this compound is centrosymmetric with triple-phenolate bridging groups connecting neighboring Co(II) ions, leading to a paddle-wheel-like structure with a pseudo-C3 axis lying in the Co-Co-Co direction. The Co(II) ions at both ends of the Co(II)3 molecule exhibit distorted trigonal prismatic CoN3O3 geometry, whereas the Co(II) at the middle presents an elongated trigonal antiprismatic CoO6 geometry. The combined analysis of the magnetic data and theoretical calculations reveal strong easy-axis magnetic anisotropy for both types of Co(II) ions (|D| values higher than 115 cm-1) with the local anisotropic axes lying on the pseudo-C3 axis of the molecule. The magnetic exchange interaction between the middle and ends Co(II) ions, extracted by using either a Hamiltonian accounting for the isotropic magnetic coupling and ZFS or the Lines' model, was found to be medium to strong and antiferromagnetic in nature, whereas the interaction between the external Co(II) ions is weak antiferromagnetic. Interestingly, the compound exhibits slow relaxation of magnetization and open hysteresis at zero field and therefore SMM behavior. The significant magnetic exchange coupling found for {Co(μ-L)}2Co is mainly responsible for the quenching of QTM, which combined with the easy-axis local anisotropy of the CoII ions and the collinearity of their local anisotropy axes with the pseudo-C3 axis favors the observation of SMM behavior at zero field.
Background Recent research shows that both pediatric and adult patients with eosinophilic esophagitis (EoE) experience esophageal remodeling marked by increased collagen deposition in which TGF-β ...plays an important role. However, limited data are available on the intensity and reversibility of fibrous remodeling in adults with EoE. Objective We sought to analyze differences in collagen deposition in the lamina propria (LP) and profibrogenic cytokine gene expression along with other changes induced by prolonged treatment with fluticasone propionate in adults with EoE. Methods Ten adults given consecutive diagnoses of EoE were studied prospectively. Deep esophageal biopsy specimens were obtained before and after 1 year of treatment with fluticasone propionate. Collagen deposition in the LP was assessed in tissue sections with the aid of the Masson trichrome technique. IL5 , TGFB1 , fibroblast growth factor 9 (FGF9) , and CCL18 gene expression was quantified through real-time PCR. EoE results were compared among samples from 10 adult patients with gastroesophageal reflux disease and 10 control subjects with healthy esophagi. Results Patients with EoE showed a significant increase in subepithelial collagen deposition; this correlated positively with eosinophil density in the LP and the patient’s age. Prolonged steroid treatment induced a nonsignificant reduction in subepithelial fibrosis, which remained significantly higher than in control subjects. Profibrogenic cytokine gene expression also increased in patients with EoE, with IL5 ( P < .001), FGF9 ( P = .005), and CCL18 ( P = .008) all significantly upregulated. After 1 year of treatment, a reduction was observed in gene expression; for CCL18 expression, this decrease was statistically significant ( P < .001). Conclusions Esophageal remodeling is associated with upregulated gene expression of profibrogenic cytokines in adults with EoE. Prolonged treatment with fluticasone propionate leads to a nonsignificant reduction in subepithelial collagen deposition accompanied by downregulation of profibrogenic cytokine gene expression, with that of CCL18 being especially significant.
The over-exploitation of coastal aquifers has led to seawater intrusion issues in many parts of the globe; this problem, which is associated with water recharge deficit and anthropogenic pollution, ...represents the main source of groundwater degradation in Santiago Island in the Republic of Cape Verde’s archipelago. Brackish groundwater for agriculture and human consumption is being provided to several areas on Santiago Island as the only type of available water. Chemical and isotopic data obtained in three main groundwater systems were used in the characterization of the groundwater resources and in the identification of the main source responsible for their degradation. The obtained results indicate water–rock interaction as the major process responsible for the groundwater quality reflecting its lithological composition. Carbonatite dissolution can be partially responsible for the calcium increase along the groundwater flow path. Isotopic data (δ2H, δ18O; 3H and 14C) combined with the water chemistry provided a wide characterization of the groundwater recharge and identification of salinization processes (like seawater intrusion and marine aerosols dissolution in different sectors of the island). In the eastern part of Santiago Island, a different isotopic pattern (2H-18O) was observed in the groundwater samples, which was likely ascribed to different climate conditions. Carbon-14 determinations indicate apparent groundwater ages between 3.5 and 5.1 ka BP.
A well-functioning monetary transmission mechanism is critical for monetary policy. As the Dominican Republic recently adopted an inflation targeting regime, it is even more relevant to guarantee ...that changes in the monetary policy rates are quickly and fully reflected in retail rates, to eventually influence aggregate demand and inflation. This paper estimates the interest rate pass-through of the monetary policy rate to retail rates and explores asymmetries in the adjustment. We find evidence of complete pass-through to retail rates, confirming the effectiveness of the monetary policy transmission mechanism. However, our results also suggest a faster pass-through to lending rates than to deposit rates and asymmetric adjustments of short-term rates, as deposit rates respond faster to policy rate cuts and lending rates respond faster to policy rate hikes. Measures to enhance competition in the financial system could help to achieve a symmetric adjustment of retail rates.
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