Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanical Aspects of Angiogenesis

Simple Summary The formation of new blood vessels from already existing ones is a process of high clinical relevance, since it is of great importance for both physiological and pathological processes. In regard to tumors, the process is crucial, since it ensures the supply with nutrients and the growth of the tumor. The influence of mechanical factors on this biological process is an emerging field. Until now, the shear force of the blood flow has been considered the main mechanical parameter during angiogenesis. This review article provides an overview of further mechanical cues, with particular focus on the surrounding extracellular matrix impacting the cell behavior and, thus, regulating angiogenesis. This underlines the enormous importance of the mechanical properties of the extracellular matrix on cell biological processes and shows how changing the mechanics of the extracellular matrix could be used as a possible therapeutic approach in cancer therapy. Abstract Angiogenesis is of high clinical relevance as it plays a crucial role in physiological (e.g., tissue regeneration) and pathological processes (e.g., tumor growth). Besides chemical signals, such as VEGF, the relationship between cells and the extracellular matrix (ECM) can influence endothelial cell behavior during angiogenesis. Previously, in terms of the connection between angiogenesis and mechanical factors, researchers have focused on shear forces due to blood flow. However, it is becoming increasingly important to include the direct influence of the ECM on biological processes, such as angiogenesis. In this context, we focus on the stiffness of the surrounding ECM and the adhesion of cells to the ECM. Furthermore, we highlight the mechanical cues during the main stages of angiogenesis: cell migration, tip and stalk cells, and vessel stabilization. It becomes clear that the different stages of angiogenesis require various chemical and mechanical cues to be modulated by/modulate the stiffness of the ECM. Thus, changes of the ECM during tumor growth represent additional potential dysregulations of angiogenesis in addition to erroneous biochemical signals. This awareness could be the basis of therapeutic approaches to counteract specific processes in tumor angiogenesis.
Incidence, Outcomes and Sex-Related Disparities in Pneumonia: A Matched-Pair Analysis with Data from Spanish Hospitals (2016–2019)

(1) Background: the purpose of this study is to analyze the incidence and in-hospital mortality (IHM) of community-acquired pneumonia (CAP) needing hospital admission and hospital-acquired pneumonia (HAP) in Spain (2016–2019). (2) Methods: using the Spanish Register of Specialized Care-Basic Minimum Database, we estimated the incidence of CAP and HAP. We matched each woman with a man with an identical age, according to comorbidities. (3) Results: we analyzed 518,838 cases of CAP and 38,705 cases of HAP, and 5192 ventilator-associated HAPs (13.4%). The incidence of CAP increased over time in both men (from 384.5 to 449.8 cases/105 population) and women (from 244.9 to 301.2 cases/105 population). Men showed a 47% higher adjusted incidence of CAP than women. The incidence of HAP increased over time in both men (from 302.3 to 342.2 cases/105 population) and women (from 139.2 to 167.6 cases/105 population). Men showed a 98% higher adjusted incidence of HAP than women. IHM was higher in men admitted for CAP than in women (12.9% vs. 12.2%; p < 0.001), but not in men who developed HAP (28.9% vs. 28.0%; p = 0.107). Men admitted for CAP (OR: 1.13; 95% CI: 1.10–1.15) and men who developed HAP (OR: 1.05; 95% CI: 1.01–1.10) had higher IHM than women. (4) Conclusions: men had higher incidence rates of CAP and HAP than women. Men admitted for CAP and men who developed HAP had higher IHM than women.
Oral and Topical Anti-Inflammatory and Antipyretic Potentialities of Araucaria bidiwillii Shoot Essential Oil and Its Nanoemulsion in Relation to Chemical Composition

Different parts of Araucaria bidiwillii (bunya pin) trees, such as nuts, seeds, bark, and shoots, are widely used in cooking, tea, and traditional medicines around the world. The shoots essential oil (EO) has not yet been studied. Herein, the chemical profile of A. bidiwillii shoots EO (ABSEO) was created by GC–MS analysis. Additionally, the in vivo oral and topical anti-inflammatory effect against carrageenan-induced models, as well as antipyretic potentiality of ABSEO and its nanoemulsion were evaluated. Forty-three terpenoid components were identified and categorized as mono- (42.94%), sesqui- (31.66%), and diterpenes (23.74%). The main compounds of the ABSEO were beyerene (20.81%), α-pinene (16.21%), D-limonene (14.22%), germacrene D (6.69%), β-humulene (4.14%), and sabinene (4.12%). The ABSEO and its nanoemulsion exhibited significant inflammation suppression in carrageenan-induced rat paw edema model, in both oral (50 and 100 mg/kg) and topical (5% in soyabean oil) routes, compared to the control and reference drugs groups. All the results demonstrated the significant inflammation reduction via the inflammatory cytokines (IL-1β and IL8), nitrosative (NO), and prostaglandin E2 (PGE2) supported by the histopathological studies and immunohistochemical assessment of MMP-9 and NF-κβ levels in paw tissues. Moreover, the oral administration of ABSEO and its nanoemulsion (50 and 100 mg/kg) exhibited antipyretic activity in rats, demonstrated by the inhibition of hyperthermia induced by intramuscular injection of brewer’s yeast. These findings advised that the use of ABSEO and its nanoemulsion against numerous inflammatory and hyperthermia ailments that could be attributed to its active constituents.
A Wind Tunnel Experimental Study of Icing on NACA0012 Aircraft Airfoil with Silicon Compounds Modified Polyurethane Coatings

Ice formation on the aerodynamic surfaces of an aircraft is regarded as a major problem in the aerospace industry. Ice accumulation may damage parts, sensors and controllers and alter the aerodynamics of the airplane, leading to a range of undesired consequences, including flight delays, emergency landings, damaged parts and increased energy consumption. There are various approaches to reducing ice accretion, one of them being the application of icephobic coatings. In this work, commercially available polyurethane-based coatings were modified and deposited on NACA 0012 aircraft airfoils. A hybrid modification of polyurethane (PUR) topcoats was adopted by the addition of nanosilica and three-functional spherosilicates (a variety of silsesqioxane compound), which owe their unique properties to the presence of three different groups. The ice accretion on the manufactured nanocomposites was determined in an icing wind tunnel. The tests were performed under three different icing conditions: glaze ice, rime ice and mixed ice. Furthermore, the surface topography and wetting behavior (static contact angle and contact angle hysteresis) were investigated. It was found that the anti-icing properties of polyurethane nanocomposite coatings strongly depend on the icing conditions under which they are tested. Moreover, the addition of nanosilica and spherosilicates enabled the reduction of accreted ice by 65% in comparison to the neat topcoat.
Delineating the Switch between Senescence and Apoptosis in Cervical Cancer Cells under Ciclopirox Treatment

Simple Summary Novel treatment options for cervical cancer are urgently required. Ciclopirox (CPX), an iron chelator, has shown promising anti-tumorigenic potential in several preclinical tumor models, including cervical cancer cells. In these cells, CPX can induce apoptosis, a form of cell death, or senescence, an irreversible cellular growth arrest. These different phenotypic outcomes may influence therapy response. Here, we show that the decision of cervical cancer cells to induce apoptosis or senescence is strongly dependent on glucose availability: CPX induces apoptosis under limited glucose availability, whereas under increased glucose supply, CPX treatment results in senescence. Further, we link the pro-apoptotic and pro-senescent activities of CPX to its capacity to block oxidative phosphorylation and to chelate iron, respectively. In addition, we show that the combined treatment of CPX and glycolysis inhibitors blocks the proliferation of cervical cancer cells in a synergistic manner. Collectively, we provide novel insights into the anti-proliferative activities of CPX in cervical cancer cells, elucidate the cellular decision between apoptosis or senescence induction, and provide a rationale to combine CPX with glycolysis inhibitors. Abstract The iron-chelating drug ciclopirox (CPX) may possess therapeutic potential for cancer treatment, including cervical cancer. As is observed for other chemotherapeutic drugs, CPX can induce senescence or apoptosis in cervical cancer cells which could differently affect their therapy response. The present study aims to gain insights into the determinants which govern the switch between senescence and apoptosis in cervical cancer cells. We performed proteome analyses, proliferation studies by live-cell imaging and colony formation assays, senescence and apoptosis assays, and combination treatments of CPX with inhibitors of oxidative phosphorylation (OXPHOS) or glycolysis. We found that CPX downregulates OXPHOS factors and facilitates the induction of apoptosis under limited glucose availability, an effect which is shared by classical OXPHOS inhibitors. Under increased glucose availability, however, CPX-induced apoptosis is prevented and senescence is induced, an activity which is not exerted by classical OXPHOS inhibitors, but by other iron chelators. Moreover, we show that the combination of CPX with glycolysis inhibitors blocks cervical cancer proliferation in a synergistic manner. Collectively, our results reveal that the phenotypic response of cervical cancer cells towards CPX is strongly dependent on glucose availability, link the pro-apoptotic and pro-senescent activities of CPX to its bifunctionality as an OXPHOS inhibitor and iron chelator, respectively, and provide a rationale for combining CPX with glycolysis inhibitors.
Nucleolin Aptamer N6L Reprograms the Translational Machinery and Acts Synergistically with mTORi to Inhibit Pancreatic Cancer Proliferation

Simple Summary Pancreatic cancer is an aggressive disease characterized by its invasiveness, rapid progression, and resistance to conventional therapy. There is a need to identify new molecules to improve current therapies. The aim of this study was to analyze how the pancreatic cancer cells react to the treatment with an inhibitor of nucleolin, N6L. To this end, we analyzed how the translation was affected in the cells during the treatment. We discovered that in response to N6L, a signaling pathway called the mTOR pathway was activated and was involved in the activation of translation of a subset of mRNA that could be involved in the resistance of the cells to the treatment. Indeed, we showed that the combined action of inhibitors of the mTOR pathway with N6L synergistically inhibited the cancer cells’ proliferation. We propose that this new combination of molecules could be a novel therapeutic option for pancreatic cancer. Abstract We previously showed that N6L, a pseudopeptide that targets nucleolin, impairs pancreatic ductal adenocarcinoma (PDAC) growth and normalizes tumor vessels in animal models. In this study, we analyzed the translatome of PDAC cells treated with N6L to identify the pathways that were either repressed or activated. We observed a strong decrease in global protein synthesis. However, about 6% of the mRNAs were enriched in the polysomes. We identified a 5′TOP motif in many of these mRNAs and demonstrated that a chimeric RNA bearing a 5‘TOP motif was up-regulated by N6L. We demonstrated that N6L activates the mTOR pathway, which is required for the translation of these mRNAs. An inhibitory synergistic effect in PDAC cell lines, including patient-derived xenografts and tumor-derived organoids, was observed when N6L was combined with mTOR inhibitors. In conclusion, N6L reduces pancreatic cells proliferation, which then undergoes translational reprogramming through activation of the mTOR pathway. N6L and mTOR inhibitors act synergistically to inhibit the proliferation of PDAC and human PDX cell lines. This combotherapy of N6L and mTOR inhibitors could constitute a promising alternative to treat pancreatic cancer.
Intranasal Administration of Codium fragile Polysaccharide Elicits Anti-Cancer Immunity against Lewis Lung Carcinoma

Natural polysaccharides have shown promising effects on the regulation of immunity in animals. In this study, we examined the immune stimulatory effect of intranasally administered Codium fragile polysaccharides (CFPs) in mice. Intranasal administration of CFPs in C57BL/6 mice induced the upregulation of surface activation marker expression in macrophages and dendritic cells (DCs) in the mediastinal lymph node (mLN) and the production of interleukin-6 (IL-6), IL-12p70, and tumor necrosis factor-α in bronchoalveolar lavage fluid. Moreover, the number of conventional DCs (cDCs) was increased in the mLNs by the upregulation of C-C motif chemokine receptor 7 expression, and subsets of cDCs were also activated following the intranasal administration of CFP. In addition, the intranasal administration of CFPs promoted the activation of natural killer (NK) and T cells in the mLNs, which produce pro-inflammatory cytokines and cytotoxic mediators. Finally, daily administration of CFPs inhibited the infiltration of Lewis lung carcinoma cells into the lungs, and the preventive effect of CFPs on tumor growth required NK and CD8 T cells. Furthermore, CFPs combined with anti-programmed cell death-ligand 1 (PD-L1) antibody (Ab) improved the therapeutic effect of anti-PD-L1 Ab against lung cancer. Therefore, these data demonstrated that the intranasal administration of CFP induced mucosal immunity against lung cancer.
NOTCH3 rs1043996 Polymorphism Is Associated with the Occurrence of Alcoholic Liver Cirrhosis Independently of PNPLA3 and TM6SF2 Polymorphisms

Alcoholic liver cirrhosis (ALC) is the most common indication for liver transplantation (LT) in Croatia and presents a risk factor for the development of hepatocellular carcinoma (HCC). However, genetic susceptibility has not yet been systematically studied. We aimed to investigate the contribution of the risk polymorphisms PNPLA3 rs738409, EGF rs4444903, TM6SF2 rs58542926, MTHFR rs1801133, previously identified in other populations and, additionally, the contribution of Notch-related polymorphisms (NOTCH1 rs3124591, NOTCH3 rs1043996 and rs1044116, NOTCH4 rs422951). The study included 401 patients. The ALC group consisted of 260 LT candidates, 128 of whom had histopathologically confirmed HCC, and 132 of whom were without HCC. The control group included 141 patients without liver disease. Genotyping was performed by PCR using Taqman assays. The patients’ susceptibility to ALC was significantly associated with PNPLA3 rs738409, TM6SF2 rs58542926, and NOTCH3 rs1043996 polymorphisms. These polymorphisms remained significantly associated with ALC occurrence in a logistic regression model, even after additional model adjustment for sex and age. Cirrhotic patients with the PNPLA3 GG genotype demonstrated higher activity of ALT aminotransferases than patients with CC or CG genotypes. The susceptibility to the development of HCC in ALC was significantly associated with PNPLA3 rs738409 and EGF rs4444903 polymorphisms, and logistic regression confirmed these polymorphisms as independent predictors.
A New Perspective on Adsorbent Materials Based Impregnated MgSiO3 with Crown Ethers for Palladium Recovery

The study of new useful, efficient and selective structures for the palladium ions’ recovery has led to the development of a new series of macromolecules. Thus, this study presents a comparative behavior of two crown benzene ethers that modify the magnesium silicate surface used as adsorbent for palladium. These crown ethers are dibenzo18-crown-6 (DB18C6) and dibenzo 30-crown-10 (DB30C10). The obtained materials were characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDX) and Fourier-transform infrared spectroscopy (FT-IR). The specific surface area (BET) and point of zero charge (PZC) of the two materials were determined. The palladium ions’ recovery from synthetic aqueous solutions studies aimed to establish the adsorption mechanism. For this desideratum, the kinetic, equilibrium and thermodynamic studies show that MgSiO3-DB30C10 have a higher adsorption capacity (35.68 mg g−1) compared to MgSiO3-DB18C6 (21.65 mg g−1). Thermodynamic studies highlight that the adsorption of Pd(II) on the two studied materials are spontaneous and endothermic processes. The positive values of the entropy (ΔS0) suggest that the studied adsorption processes show a higher disorder at the liquid/solid interface. Desorption studies were also performed, and it was found that the degree of desorption was 98.3%.
Inhibition of Wnt/β-Catenin Signaling Sensitizes Esophageal Cancer Cells to Chemoradiotherapy

The standard treatment of locally advanced esophageal cancer comprises multimodal treatment concepts including preoperative chemoradiotherapy (CRT) followed by radical surgical resection. However, despite intensified treatment approaches, 5-year survival rates are still low. Therefore, new strategies are required to overcome treatment resistance, and to improve patients’ outcome. In this study, we investigated the impact of Wnt/β-catenin signaling on CRT resistance in esophageal cancer cells. Experiments were conducted in adenocarcinoma and squamous cell carcinoma cell lines with varying expression levels of Wnt proteins and Wnt/β-catenin signaling activities. To investigate the effect of Wnt/β-catenin signaling on CRT responsiveness, we genetically or pharmacologically inhibited Wnt/β-catenin signaling. Our experiments revealed that inhibition of Wnt/β-catenin signaling sensitizes cell lines with robust pathway activity to CRT. In conclusion, Wnt/β-catenin activity may guide precision therapies in esophageal carcinoma patients.
Woody encroachment of grasslands: Near‐surface thermal implications assessed through the lens of an astronomical event

Abstract Temperature has long been understood as a fundamental condition that influences ecological patterns and processes. Heterogeneity in landscapes that is structured by ultimate (climate) and proximate (vegetation, topography, disturbance events, and land use) forces serve to shape thermal patterns across multiple spatio‐temporal scales. Thermal landscapes of grasslands are likely shifting as woody encroachment fragments these ecosystems and studies quantifying thermal fragmentation in grassland systems resulting from woody encroachment are lacking. We utilized the August 21st, 2017, solar eclipse to mimic a rapid sunrise/sunset event across a landscape characterized as a grassland to experimentally manipulate levels of solar radiation in the system. We then quantified changes in near‐surface temperatures resulting from changes in solar radiation levels during the eclipse. Temperatures were monitored across three grassland pastures in central Oklahoma that were characterized by different densities (low, medium, and high) of Juniperus virginiana to understand the impact of woody encroachment on diurnal temperature patterns and thermal heterogeneity in a grassland's thermal landscape. The largest temperature range across sites that occurred during the eclipse was in the mixed grass vegetation. Similarly, the largest change in thermal heterogeneity occurred in the grassland with the lowest amount of woody encroachment. Thermal heterogeneity was lowest in the highly encroached grassland, which also experienced the lowest overall change in thermal heterogeneity during the eclipse. Time series models suggested that solar radiation was the most influential factor in predicting changes in thermal heterogeneity as opposed to ambient temperature alone. These results suggest that highly encroached grasslands may experience lower diurnal variability of temperatures at the cost of a decrease in the overall thermal heterogeneity of that landscape. It appears that fine‐scale spatio‐temporal thermal variation is largely driven by solar radiation, which can be influenced by vegetation heterogeneity inherent within a landscape.
Evaluation of Comprehensive Gene Expression and NK Cell-Mediated Killing in Glioblastoma Cell Line-Derived Spheroids

Simple Summary Glioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults. Despite standard treatment, including surgery, chemotherapy, and radiotherapy, it is associated with poor survival. Immunotherapy is a promising alternative for patients with GBM. Natural killer (NK) cells are possible promising targets in GBM treatment because of their potent cytotoxic effect. We previously reported that highly activated and ex vivo-expanded NK cells, or genuine induced NK cells (GiNK), exert a greatly cytotoxic effect on GBM cells. In this study, we investigated the potential of NK cell-based immunotherapy for GBM, which we evaluated using an ex vivo three-dimensional GBM cell-derived spheroid model. Our results indicated that the NK cells had an anti-tumor effect on the spheroid models. Our findings could lead to the development of future NK cell-based immunotherapies for GBM. Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor, with a dismal prognosis. Natural killer (NK) cells are large granular lymphocytes with natural cytotoxicity against tumor cells, and they should be established for the novel treatment of patients with GBM. We previously reported highly activated, and ex vivo-expanded NK cells derived from human peripheral blood, designated genuine induced NK cells (GiNK), which were induced by specific culture conditions and which exerted a cytotoxic effect on GBM cells via apoptosis. Here, we comprehensively summarize the molecular characteristics, especially focusing on the expression of stem cell markers, extracellular matrix markers, chemokines, chemokine receptors, and NK receptor ligands of spheroids derived from GBM cell lines as compared with that of two-dimensional (2D) adherent GBM cells via microarray. The spheroid had upregulated gene expression of stem cell markers, extracellular matrix markers, chemokines, chemokine receptors, and NK cell inhibitory receptor ligands compared with the 2D adherent GBM cells. Preclinical evaluation of the NK cells was performed via an ex vivo 3D spheroid model derived from GBM cell lines. In the model, the NK cells accumulated and infiltrated around the spheroids and induced GBM cell death. Flow cytometry-based apoptosis detection clearly showed that the NK cells induced GBM cell death via apoptosis. Our findings could provide pivotal information for NK cell-based immunotherapy for patients with GBM.