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AbstractWho influenced whom during the 2008 crisis? Did academic economists shape central bankers’ attitudes towards fiscal policy, or did central bankers impose their agenda? In an attempt to answer these questions, we analyse established attitudes and yearly topics found in speeches by bankers from six central banks and in working papers published by academic economists. Methodologically, both attitudes and topics are reconstructed through textual analysis. The results show that context matters. [ABSTRACT FROM AUTHOR]

The NFE2L2 gene of the redox-sensitive transcription factor NRF2 is a target of miR-155 microRNA. In the present work, a transfection of miR-155 imitator (mimic) was performed into dacarbazine-resistant B16 melanoma cells. It was determined that, under the influence of miR-155 microRNA mimic, the expression level of NRF2 encoded by the NFE2L2 decreases in melanoma cells both in conditions of oxidative stress and without it. A decrease in the level of NRF2 was accompanied by a decrease in the viability of dacarbazine-resistant melanoma cells. Thus, miR-155-mediated activation of NRF2, which regulates the intensity of antioxidant processes in the cell, can be associated with the preservation of viability and development of drug resistance of tumor cells. The latter can be used to overcome chemoresistance in the treatment of oncological diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Melanoma, a severe form of skin cancer, poses significant health risks due to its aggressive nature and potential for metastasis. The role of two-pore channel 2 (TPC2) in the development and progression of melanoma remains poorly understood. This study aims to investigate the impact of TPC2 knockout (KO) on melanoma-derived tumors, focusing on tumour growth and related toxicity in the organism. Methods The study utilized CHL-1 and B16 melanoma cell lines with TPC2 KO to assess the changes in proliferation dynamics. Methods included real-time monitoring of cell proliferation using the xCELLigence system, in vivo tumour growth assays in mice, histopathological analyses, inflammation marker assessment, and quantitative PCR (qPCR) for gene expression analysis Results TPC2 KO was found to significantly alter the proliferation dynamics of CHL-1 and B16 melanoma cells. The in vivo studies demonstrated reduced tumor growth in TPC2 KO cell-derived tumors. However, a notable increase in tumor-related toxicity in affected organs, such as the liver and spleen, was observed, indicating a complex role of TPC2 in melanoma pathology. Conclusions The loss of TPC2 function in melanoma cells leads to reduced tumour growth but exacerbates tumour-related toxicity in the organism. These findings highlight the dual role of TPC2 in melanoma progression and its potential as a therapeutic target. Further research is needed to fully understand the mechanisms underlying these effects and to explore TPC2 as a treatment target in melanoma. Graphical Abstract

Aim: This report proposes using the Hill model to assess the benchmark dose, the 50% lethal dose, the cooperativity and the dissociation constant while analyzing cell viability data using nanomaterials to evaluate the antitumor potential while combined with radiofrequency therapy. Materials & methods: A nanocomposite was synthesized (graphene oxide–polyethyleneimine–gold) and the viability was evaluated using two tumor cell lines, namely LLC-WRC-256 and B16-F10. Results: Our findings demonstrated that while the nanocomposite is biocompatible against the LLC-WRC-256 and B16-F10 cancer cell lines in the absence of radiofrequency, the application of radiofrequency enhances the cell toxicity by orders of magnitude. Conclusion: This result points to prospective studies with the tested cell lines using tumor animal models. [ABSTRACT FROM AUTHOR]

Background: Melanoma, a severe form of skin cancer, poses significant health risks due to its aggressive nature and potential for metastasis. The role of two-pore channel 2 (TPC2) in the development and progression of melanoma remains poorly understood. This study aims to investigate the impact of TPC2 knockout (KO) on melanoma-derived tumors, focusing on tumour growth and related toxicity in the organism. Methods: The study utilized CHL-1 and B16 melanoma cell lines with TPC2 KO to assess the changes in proliferation dynamics. Methods included real-time monitoring of cell proliferation using the xCELLigence system, in vivo tumour growth assays in mice, histopathological analyses, inflammation marker assessment, and quantitative PCR (qPCR) for gene expression analysis Results: TPC2 KO was found to significantly alter the proliferation dynamics of CHL-1 and B16 melanoma cells. The in vivo studies demonstrated reduced tumor growth in TPC2 KO cell-derived tumors. However, a notable increase in tumor-related toxicity in affected organs, such as the liver and spleen, was observed, indicating a complex role of TPC2 in melanoma pathology. Conclusions: The loss of TPC2 function in melanoma cells leads to reduced tumour growth but exacerbates tumour-related toxicity in the organism. These findings highlight the dual role of TPC2 in melanoma progression and its potential as a therapeutic target. Further research is needed to fully understand the mechanisms underlying these effects and to explore TPC2 as a treatment target in melanoma. [ABSTRACT FROM AUTHOR]

The issue of reliability and the cost of failure or maintenance costs of renewable energy sources, including wind farms, is becoming increasingly important, especially as the volume of electricity supply from such installations increases.

Anti-tumor activity of Tremella fuciformis polysaccharides (TFPS) has been widely reported, but its mechanism remains poorly understood. In this study, we established an in vitro co-culture system (B16 melanoma cells and RAW 264.7 macrophage-like cells) to explore the potential anti-tumor mechanism of TFPS. Based on our results, TFPS exhibited no inhibition on the cell viability of B16 cells. However, significant apoptosis was observed when B16 cells were co-cultured with TFPS-treated RAW 264.7 cells. We further found that mRNA levels of M1 macrophage markers including iNOS and CD80 were significantly upregulated in TFPS-treated RAW 264.7 cells, while M2 macrophage markers such as Arg-1 and CD 206 remained unchanged. Besides, the migration, phagocytosis, production of inflammatory mediators (NO, IL-6 and TNF-α), and protein expression of iNOS and COX-2 were markedly enhanced in TFPS-treated RAW 264.7 cells. Network pharmacology analysis indicated that MAPK and NF-κB signaling pathways may be involved in M1 polarization of macrophages, and this hypothesis was verified by Western blot. In conclusion, our research demonstrated that TFPS induced apoptosis of melanoma cells by promoting M1 polarization of macrophages, and suggested TFPS may be applied as an immunomodulatory for cancer therapy. [ABSTRACT FROM AUTHOR]

The Great Recession that followed the financial crisis of 2007 is not only the largest economic crisis after the Great Depression of the 1930s, it also signals a crisis of economics as a discipline. This is not only the consequence of the inadequacy of mainstream macroeconomics, and specifically the Dynamic Stochastic General Equilibrium (DSGE) workhorse model, to forecast such a huge event, or at least to detect the worrying tendencies towards it. Even more relevant is the choice to explicitly avoid the modeling of large crises (that for someone is a motivation for not attacking pre-crisis DSGE models focused on the analysis of small deviations from the steady-state), so denying the intrinsic nature of capitalism, a system that necessarily proceeds through cycles and (extended) crises. The replies of the DSGE approach to critics have led to extensions regarding for instance the role of financial frictions, heterogeneous agents, and bounded rationality (though typically in the form of quasi-rational expectations). The alternative paradigm of agent-based (AB) macroeconomics can take into account all these elements at once within an evolutionary modeling framework based on heterogeneity and interaction, so capable to endogenously reproduce complex dynamics, from small fluctuations to large crises, due to innovation and industrial dynamics, rising inequality and financial instability, and so on. The integration between AB macroeconomics and the (post-Keynesian) stock–flow consistent approach represents a promising way for the future development of this research field. [ABSTRACT FROM AUTHOR]

The modeling of chimeric antigen receptor (CAR) T cell therapies has been mostly focused on immunodeficient models. However, there are many advantages in studying CAR-T cell biology in an immunocompetent setting. We generated a fully murine CAR targeting CD105 (endoglin), a component of the TGFβ receptor expressed on the surface of certain solid tumors and acute leukemias. CD105-targeted CAR-T cells can be grown from various murine backgrounds, tracked in vivo by congenic marks, and be activated by CD105 in isolation or expressed by tumor cells. CD105-targeted CAR-T cells were toxic at higher doses but proved safe in lower doses and modestly effective in treating wild-type B16 melanoma-bearing mice. CAR-T cells infiltrating the tumor expressed high levels of exhaustion markers and exhibited metabolic insufficiencies. We also generated a human CD105 CAR, which was efficacious in treating human melanoma and acute myeloid leukemia in vivo. Our work details a new murine model of CAR-T cell therapy that can be used from immunologists to further our understanding of CAR-T cell biology. We also set the foundation for further exploration of CD105 as a possible human CAR-T cell target.

Tumor-associated tertiary lymphoid structures are ectopic lymphoid aggregates that have considerable morphological, cellular, and molecular similarity to secondary lymphoid organs, particularly lymph nodes. Tumor vessels expressing peripheral node addressin (PNAd) are hallmark features of these structures. Previous work from our laboratory demonstrated that PNAd is displayed on intratumoral vasculature of murine tumors, and its expression is controlled by the engagement of lymphotoxin-a3, secreted by effector CD8 T cells, with tumor necrosis factor receptors (TNFR) on tumor endothelial cells (TEC). The goals of the present work were: 1) to identify differences in expression of genes encoding the scaffolding proteins and glycosyl transferases associated with PNAd biosynthesis in TEC and lymph node blood endothelial cells (LN BEC); and 2) to determine which of these PNAd associated components are regulated by TNFR signaling. We found that the same genes encoding scaffolding proteins and glycosyl transferases were upregulated in PNAd+ LN BEC and PNAd+ TEC relative to their PNAdneg counterparts. The lower level of PNAd expression on TEC vs LN BEC was associated with relatively lower expression of these genes, particularly the carbohydrate sulfotransferase Chst4. Loss of PNAd on TEC in the absence of TNFR signaling was associated with lack of upregulation of these same genes. A small subset of PNAd+ TEC remaining in the absence of TNFR signaling showed normal upregulation of a subset of these genes, but reduced upregulation of genes encoding the scaffolding proteins podocalyxin and nepmucin, and carbohydrate sulfotransferase Chst2. Lastly, we found that checkpoint immunotherapy augmented both the fraction of TEC expressing PNAd and their surface level of this ligand. This work points to strong similarities in the regulation of PNAd expression on TEC by TNFR signaling and on LN BEC by lymphotoxin-b receptor signaling, and provides a platform for the development of novel strategies that manipulate PNAd expression on tumor vasculature as an element of cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Tumor-associated tertiary lymphoid structures are ectopic lymphoid aggregates that have considerable morphological, cellular, and molecular similarity to secondary lymphoid organs, particularly lymph nodes. Tumor vessels expressing peripheral node addressin (PNAd) are hallmark features of these structures. Previous work from our laboratory demonstrated that PNAd is displayed on intratumoral vasculature of murine tumors, and its expression is controlled by the engagement of lymphotoxin-α3, secreted by effector CD8 T cells, with tumor necrosis factor receptors (TNFR) on tumor endothelial cells (TEC). The goals of the present work were: 1) to identify differences in expression of genes encoding the scaffolding proteins and glycosyl transferases associated with PNAd biosynthesis in TEC and lymph node blood endothelial cells (LN BEC); and 2) to determine which of these PNAd associated components are regulated by TNFR signaling. We found that the same genes encoding scaffolding proteins and glycosyl transferases were upregulated in PNAd+ LN BEC and PNAd+ TEC relative to their PNAdneg counterparts. The lower level of PNAd expression on TEC vs LN BEC was associated with relatively lower expression of these genes, particularly the carbohydrate sulfotransferase Chst4. Loss of PNAd on TEC in the absence of TNFR signaling was associated with lack of upregulation of these same genes. A small subset of PNAd+ TEC remaining in the absence of TNFR signaling showed normal upregulation of a subset of these genes, but reduced upregulation of genes encoding the scaffolding proteins podocalyxin and nepmucin, and carbohydrate sulfotransferase Chst2. Lastly, we found that checkpoint immunotherapy augmented both the fraction of TEC expressing PNAd and their surface level of this ligand. This work points to strong similarities in the regulation of PNAd expression on TEC by TNFR signaling and on LN BEC by lymphotoxin-β receptor signaling, and provides a platform for the development of novel strategies that manipulate PNAd expression on tumor vasculature as an element of cancer immunotherapy.

Gauss' 1809 discussion of least squares, which can be viewed as the beginning of mathematical statistics, is reviewed. The general consensus seems to be that Gauss' arguments are at fault, but we show that his reasoning is in fact correct, given his self-imposed restrictions, and persuasive without these restrictions. [ABSTRACT FROM AUTHOR]

Anti-tumor activity of Tremella fuciformis polysaccharides (TFPS) has been widely reported, but its mechanism remains poorly understood. In this study, we established an in vitro co-culture system (B16 melanoma cells and RAW 264.7 macrophage-like cells) to explore the potential anti-tumor mechanism of TFPS. Based on our results, TFPS exhibited no inhibition on the cell viability of B16 cells. However, significant apoptosis was observed when B16 cells were co-cultured with TFPS-treated RAW 264.7 cells. We further found that mRNA levels of M1 macrophage markers including iNOS and CD80 were significantly upregulated in TFPS-treated RAW 264.7 cells, while M2 macrophage markers such as Arg-1 and CD 206 remained unchanged. Besides, the migration, phagocytosis, production of inflammatory mediators (NO, IL-6 and TNF-α), and protein expression of iNOS and COX-2 were markedly enhanced in TFPS-treated RAW 264.7 cells. Network pharmacology analysis indicated that MAPK and NF-κB signaling pathways may be involved in M1 polarization of macrophages, and this hypothesis was verified by Western blot. In conclusion, our research demonstrated that TFPS induced apoptosis of melanoma cells by promoting M1 polarization of macrophages, and suggested TFPS may be applied as an immunomodulatory for cancer therapy.

Melanoma is an aggressive skin cancer with a high rate of metastasis to other organs. Recent studies specified the overexpression of V-domain Ig suppressor of T-cell activation (VISTA) and Aryl Hydrocarbon Receptor (AHR) in melanoma. Metformin shows anti-tumor activities in several cancer types. However, the mechanism is unclear. This study aims to investigate the inhibitory effect of metformin on VISTA via AHR in melanoma cells (CHL-1, B16) and animal models. VISTA and AHR levels were assessed by qPCR, Western blot, immunofluorescence microscope, flow cytometry, and immunohistochemistry. Here, metformin significantly decreased VISTA and AHR levels in vitro and in vivo. Furthermore, metformin inhibited all AHR-regulated genes. VISTA levels were dramatically inhibited by AHR modulations using shRNA and αNF, confirming the central role of AHR in VISTA. Finally, melanoma cells were xenografted in C57BL/6 and nude mice. Metformin significantly reduced the tumor volume and growth rate. Likewise, VISTA and AHR-regulated protein levels were suppressed in both models. These findings demonstrate for the first time that VISTA is suppressed by metformin and identified a new regulatory mechanism through AHR. The data suggest that metformin could be a new potential therapeutic strategy to treat melanoma patients combined with targeted immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

The modeling of chimeric antigen receptor (CAR) T cell therapies has been mostly focused on immunodeficient models. However, there are many advantages in studying CAR-T cell biology in an immunocompetent setting. We generated a fully murine CAR targeting CD105 (endoglin), a component of the TGFß receptor expressed on the surface of certain solid tumors and acute leukemias. CD105-targeted CART cells can be grown from various murine backgrounds, tracked in vivo by congenic marks, and be activated by CD105 in isolation or expressed by tumor cells. CD105-targeted CAR-T cells were toxic at higher doses but proved safe in lower doses and modestly effective in treating wild-type B16 melanomabearing mice. CAR-T cells infiltrating the tumor expressed high levels of exhaustion markers and exhibited metabolic insufficiencies. We also generated a human CD105 CAR, which was efficacious in treating human melanoma and acute myeloid leukemia in vivo. Our work details a new murine model of CAR-T cell therapy that can be used from immunologists to further our understanding of CAR-T cell biology. We also set the foundation for further exploration of CD105 as a possible human CAR-T cell target. [ABSTRACT FROM AUTHOR]

This study advances research on entrepreneurial orientation and business performance by assessing, prioritizing, ranking, and evaluating decision choices among entrepreneurial orientation attributes that influence small and medium scale enterprise performance in Nigeria. Data were gathered through the multi-criteria decision-making (MCDM) tool called analytic hierarchy process (AHP) based questionnaire administered to practicing entrepreneurs in Lagos State, Nigeria. The population of the study consists of all the firms (mainly small and medium scale businesses) registered by Lagos Chamber of Commerce, totalling 1766 at the time of this study. The sample size was calculated through Yamane formula, while entrepreneurs managing the sampled firms were the respondents carefully selected for the study through a random sampling procedure. Data collected were analysed through descriptive statistics and analytic hierarchy process procedures for eliciting the consistency ratio, consistency index, Lambda Max, local and global priority values for an effective policy decision. The priorities were established in line with the AHP framework using pairwise comparisons and judgment of entrepreneurs. The results revealed the preference of entrepreneurial orientation dimension that influenced business performance most based on pairwise experiences and trade-off of different attributes. This study explores the application of AHP methodology for measuring complex entrepreneurial decision-making process for enhancing business performance. Thus, the AHP revealed a potential research method in computing weights and chasing MCDM process.

Focal thermal therapy (Heat), cryosurgery (Cryo) and irreversible electroporation (IRE) are increasingly used to treat cancer. However, local recurrence and systemic spread are persistent negative outcomes. Nevertheless, emerging work with immunotherapies (i.e., checkpoint blockade or dendritic cell (DC) vaccination) in concert with focal therapies may improve outcomes. To understand the role of focal therapy in priming the immune system for immunotherapy, an in vitro model of T cell response after exposure to B16 melanoma cell lysates after lethal exposures was designed. Exposure included: Heat (50 °C, 30 min), Cryo (−80 °C, 30 min) and IRE (1250 V/cm, 99 pulses, 50 µs pulses with 1 Hz intervals). After viability assessment (CCK-8 assay), cell lysates were collected and assessed for protein release (BCA assay), protein denaturation (FTIR-spectroscopy), TRP-2 antigen release (western blot), and T cell activation (antigen-specific CD8 T cell proliferation). Results showed IRE released the most protein and antigen (TRP-2), followed by Cryo and Heat. In contrast, Cryo released the most native (not denatured) protein, compared to IRE and Heat. Finally, IRE dramatically outperformed both Cryo and Heat in T cell activation while Cryo modestly outperformed Heat. This study demonstrates that despite all focal therapies ability to destroy cells, the ‘quantity’ (i.e., amount) and ‘quality’ (i.e., molecular state) of tumor protein (including antigen) released can dramatically change the ensuing priming of the immune system. This suggests protein-based metrics whereby focal therapies can be designed to prime the immune system in concert with immunotherapies to eventually achieve improved and durable cancer treatment in vivo.

Malignant melanoma is an aggressive cancer with a poor prognosis despite numerous advances in therapeutic strategies. Quercetin is a plant-derived flavonoid suggested to have potent anticancer properties. Quercetin has no demonstrable toxicity in humans, further supporting the possibility of using quercetin therapeutically. We chose to investigate quercetin efficacy against B16 murine melanoma cells and identify the mechanisms of anticancer activity. Treatment of B16 melanoma cells with 50 μg/mL quercetin resulted in a 75% reduction in viability from 6 through 48 h post-treatment. The reduction in cancer cell viability was comparable to or greater than what was observed with etoposide, an established chemotherapeutic. Specifically, we found Quercetin reduced the proliferation of B16 melanoma cells at 48 h as much or more than etoposide. Although quercetin reduced the proportion of cells in the S and G2/M stages of the cell cycle, this could largely be explained by an increase in the subG1 population in quercetin-treated cells (suggesting apoptosis). Quercetin-induced apoptosis was confirmed by flow cytometry analysis of Annexin V+ cells. Collectively, our findings demonstrate quercetin reduces proliferation and induces apoptosis of B16 melanoma cells in vitro. [ABSTRACT FROM AUTHOR]

Objective: As one member of the histone deacetylase inhibitor (HDACi) family, Sodium butyrate (NaB) was found out that could be used as a differentiation inducer of much cancer cell. But its effects on tumor microenvironment cells are not well recognized. The goal of this research is to investigate the effect of NaB on B16 melanoma and analysis its relevant mechanism. Methods: We observed the effect of sodium butyrate on B16 melanoma in vivo and in vitro. MTT method was performed to detect cell apoptosis rate after treatment. Tumor associated macrophage infiltration condition was detected by flow cytometry. Western-blotting and immunohistochemical method were used to detect the expression of tumor associated macrophage cytokines. Results: A certain concentration of sodium butyrate could effectively inhibit B16 melanoma growth in vivo and in vitro. Compared with the control group (45.00 ± 3.43%), macrophage differentiation in the 1.0g / kg group (37.54 ± 2.34%), 2.0g / kg group (41.62 ± 3.10%) and 3.0g / kg group (29.28 ± 4.42%) group were all inhibited to varying degrees. The inhibitory effect was most significant in the 5.0 g / kg group (19.92 ± 4.80%), and the difference was statistically significant (P <0.01).At the same time we observed the relevant macrophage factors were down-regulated compared to the control. Conclusion: Sodium butyrate could effectively inhibit B16 melanoma growth through suppressing tumor associated macrophage proliferation and reduce relevant pro-tumor macrophage factors expression, which may help to promote the clinical study of melanoma epigenetic therapy. [ABSTRACT FROM AUTHOR]

Was ist das geld(-ordnungs)theoretische Anliegen der Freiburger Schule? Wie entstand es und worauf zielt die hier vorgestellte Geldordnungstheorie ab? Diese Fragen werden in dem vorliegenden Beitrag dogmenhistorisch untersucht und ordnungsökonomisch eingeordnet. Es wird gezeigt, dass die Gründungsgeneration der Freiburger Schule um Walter Eucken unterschiedliche Geldordnungsvorschläge vorlegte, um eine Geldverfassung institutionell so auszugestalten, dass sie das Leistungskriterium der Geldwertstabilität langfristig erfüllen kann. Die Geldsystemtheorie Euckens und ihre Rückbindung an die Kapitaltheorie liefern den theoretischen Ausgangspunkt der Geldordnungstheorie. Die Zeitgebundenheit dieser Theorie und der konkreten Vorschläge widersprechen ihrer Rekonstruktion, um sie für die aktuelle Debatte um die Reform der EWU wieder einzuführen. Wer an dieser Frage interessiert ist, wird in diesem Beitrag keine Antworten finden. This article illustrates the emergence and key insights of the monetary thought in the Freiburg School of Economics – the intellectual root of ordoliberalism. It shows that capital theory shaped the Freiburg School's approach to monetary theory. Nevertheless, the monetary regime proposals by the founding generation of the Freiburg School were remarkably diverse ranging from a powerful central bank to a Free-Banking regime. The proposals are discussed from the perspective of monetary order theory. With this perspective, the Freiburg School analyzed predicted outcomes of hypothetical monetary constitutions tacitly assuming methodological individualism and rational choice of actors to finally evaluate if predictability in the value of money could be expected. Eucken's monetary institutionalism adopted key insights from the discussion in the 1930's Chicago School of Economics while his capital theory remained in the statist world of Böhm-Bawerk tradition. [ABSTRACT FROM AUTHOR]

With the rapid growth of the wireless communication industry, humans are extensively exposed to electromagnetic fields (EMF) comprised of radiofrequency (RF). The skin is considered the primary target of EMFs given its outermost location. Recent evidence suggests that extremely low frequency (ELF)-EMF can improve the efficacy of DNA repair in human cell-lines. However, the effects of EMF-RF on DNA damage remain unknown. Here, we investigated the impact of EMF-long term evolution (LTE, 1.762 GHz, 8 W/kg) irradiation on DNA double-strand break (DSB) using the murine melanoma cell line B16 and the human keratinocyte cell line HaCaT. EMF-LTE exposure alone did not affect cell viability or induce apoptosis or necrosis. In addition, DNA DSB damage, as determined by the neutral comet assay, was not induced by EMF-LTE irradiation. Of note, EMF-LTE exposure can attenuate the DNA DSB damage induced by physical and chemical DNA damaging agents (such as ionizing radiation (IR, 10 Gy) in HaCaT and B16 cells and bleomycin (BLM, 3 μM) in HaCaT cells and a human melanoma cell line MNT-1), suggesting that EMF-LTE promotes the repair of DNA DSB damage. The protective effect of EMF-LTE against DNA damage was further confirmed by attenuation of the DNA damage marker γ-H2AX after exposure to EMF-LTE in HaCaT and B16 cells. Most importantly, irradiation of EMF-LTE (1.76 GHz, 6 W/kg, 8 h/day) on mice in vivo for 4 weeks reduced the γ-H2AX level in the skin tissue, further supporting the protective effects of EMF-LTE against DNA DSB damage. Furthermore, p53, the master tumor-suppressor gene, was commonly upregulated by EMF-LTE irradiation in B16 and HaCaT cells. This finding suggests that p53 plays a role in the protective effect of EMF-LTE against DNA DSBs. Collectively, these results demonstrated that EMF-LTE might have a protective effect against DNA DSB damage in the skin, although further studies are necessary to understand its impact on human health.

Despite continuous advances in therapy, cancer remains a deadly disease. Over the past years, gas plasma technology emerged as a novel tool to target tumors, especially skin. Another promising anticancer approach are nanoparticles. Since combination therapies are becoming increasingly relevant in oncology, both gas plasma treatment and nanoparticle exposure were combined. A series of nanoparticles were investigated in parallel, namely, silica, silver, iron oxide, cerium oxide, titanium oxide, and iron-doped titanium oxide. For gas plasma treatment, the atmospheric pressure argon plasma jet kINPen was utilized. Using three melanoma cell lines, the two murine non-metastatic B16F0 and metastatic B16F10 cells and the human metastatic B-Raf mutant cell line SK-MEL-28, the combined cytotoxicity of both approaches was identified. The combined cytotoxicity of gas plasma treatment and nanoparticle exposure was consistent across all three cell lines for silica, silver, iron oxide, and cerium oxide. In contrast, for titanium oxide and iron-doped titanium oxide, significantly combined cytotoxicity was only observed in B16F10 cells.

We study a cyclic Leibniz rule, which provides a systematic approach to lattice supersymmetry, using a numerical method with a transfer matrix. The computation is carried out in |${\cal N}=2$| supersymmetric quantum mechanics with the |$\phi^6$| interaction for weak and strong couplings. The computed energy spectra and supersymmetric Ward–Takahashi identities are compared to those obtained from another lattice action. We find that a model with the cyclic Leibniz rule behaves similarly to the continuum theory compared to the other lattice action. [ABSTRACT FROM AUTHOR]

The paper concentrates on the evaluation of the Global Innovation Index, the Summary Innovation Index and the Innovation Output Indicator. For the purpose of this article, the PROFIT (PROperty- FITting) method, an extension of the multidimensional scaling (MDS), was applied. The ultimate goal of MDS techniques is to produce a geometric map that illustrates the underlying structure of complex phenomena such as the innovation performance of the EU countries. Cluster analysis, conducted with the use of Ward's method provided an objective view of the division of the EU countries based on their selected characteristics. The final result is a two-dimensional map illustrating the structure of innovation performance. The main conclusion drawn from the analysis is the explanation of distance between single indices in a spatial map and their role in distinguishing specific groups of the EU countries from the perspective of innovation performance. [ABSTRACT FROM AUTHOR]

Cytotoxic flavonoids of Murraya tetramera were investigated in this study. A novel flavonoid and twelve known flavonoids, including seven flavones (1–7), three flavanones (8–10), and three chalcones (11–13) were isolated from the leaves and twigs of Murraya tetramera. Chemical structures were elucidated by NMR combined with MS spectral analysis, and the new compound (6) was confirmed as 3′,5′-dihydroxy-5,6,7,4′-tetramethoxyflavone. Furthermore, all the isolated flavonoids were evaluated for their cytotoxicities against murine melanoma cells (B16), and human breast cancer cells (MDA-MB-231) by CCK-8 assay. Among them, compounds 7, 13, and 5 exhibited potent cytotoxic activities against B16 cell lines (IC50 = 3.87, 7.00 and 8.66 μg/mL, respectively). Compounds 5, 13, and 12 displayed potent cytotoxicities against MDA-MB-231 cell lines (IC50 = 3.80, 5.95 and 7.89 μg/mL, respectively). According to the correlation of the structure and activity analysis, 5-hydroxyl and 8-methoxyl substituents of the flavone, 8-methoxyl substituent of the flavanone, and 3′,5′-methoxyl substituents of the chalcone could be critical factors of the high cytotoxicity. The results indicated that the active flavonoids have potential to be developed as leading compounds for treating cancers.

Background and Objectives: Tumours are often low immunogenic. The role of complement, an innate immune defence system, in tumour control has begun to be elucidated, but findings are conflicting. A role for properdin, an amplifier of complement activation, in tumour control has recently been implicated. Materials and Methods: Properdin-deficient and congenic wildtype mice were injected subcutaneously with B16F10 melanoma cells. Tumour mass and chemokine profile were assessed. The frequencies of CD45+CD11b+ Gr-1+ cells were determined from tumours and spleens, and CD206+ F4/80+ cells were evaluated in spleens. Sera were analysed for C5a, sC5b-9, and CCL2. Results: Whilst there was no difference in tumour growth at study endpoint, properdin-deficient mice had significantly fewer myeloid-derived suppressor cells (MDSCs) in their tumours and spleens. Splenic M2 type macrophages and serum levels of C5a, sC5b-9, and CCL2 were decreased in properdin-deficient compared to wildtype mice. Conclusions: The presence of intact complement amplification sustains an environment that lessens potential anti-tumour responses.

Methotrexate (MTX) which is one of the longest-used cytostatics, belongs to the group of antimetabolites and is used for treatment in different types of cancer as well as during autoimmune diseases. MTX can act as a modulator enable to create the optimal environment to generate the specific anti-tumor immune response. A novel system for MTX delivery is its conjugation with high-molecular-weight carriers such as hydroxyethyl starch (HES), a modified amylopectin-based polymer applied in medicine as a colloidal plasma volume expander. Such modification prolongs the plasma half-life of the HES-MTX nanoconjugate and improves the distribution of the drug in the body. In the current study, we focused on evaluating the dose-dependent therapeutic efficacy of chemotherapy with HES-MTX nanoconjugate compared to the free form of MTX, and examining the time-dependent changes in the local and systemic anti-tumor immune response induced by this therapy. To confirm the higher effectiveness of HES-MTX in comparison to MTX, we analyzed its action using murine MC38 colon carcinoma and B16 F0 melanoma tumor models. It was noted that HES-MTX at a dose of 20 mg/kg b.w. was more effective in tumor growth inhibition than MTX in both tumor models. One of the main differences between the two analyzed tumor models concerned the kinetics of the appearance of the immunomodulation. In MC38 tumors, the beneficial change in the tumor microenvironment (TME) landscape, manifested by the depletion of pro-tumor immune cells, and increased influx of cells with strong anti-tumor activity was noted already 3 days after HES-MTX administration, while in B16 F0 model, these changes occurred 10 days after the start of therapy. Thus, the immunomodulatory potential of the HES-MTX nanoconjugate may be closely related to the specific immune cell composition of the TME, which combined with additional treatment such as immunotherapies, would enhance the therapeutic potential of the nanoconjugate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (AJCR Copyright © 2023.)

Melanoma is a highly invasive and metastatic malignant skin tumor with poor prognosis. Although several widely studied pure melanoma cell lines are available, the precise mechanism underlying transformation of melanocyte to melanoma remains unclear. Long non‐coding RNAs (lncRNAs) represent a vast category of non‐coding RNA molecules, and increasing evidence suggests that lncRNAs are crucial for various biological processes, including those in the skin. Herein, lncRNA sequencing was performed on an Illumina HiSeq platform to identify lncRNAs expressed differently in murine B16 melanoma cells compared to normal mouse melanocytes. Using four computational approaches, 2319 lncRNAs were expressed in both normal melanocytes and B16 cells, with 373 being differentially expressed at a significant level. Of these, 136 lncRNAs were upregulated and 237 were downregulated. KEGG analyses revealed that 467 genes were target genes in the Wnt signalling pathway, TGF‐beta signalling pathway, MAPK signalling pathway, NF‐kappa B signalling pathway, melanoma and several other cancer‐related regulatory pathways. From among the differentially expressed lncRNAs, lnc‐13317.1 was found to play a role in the cell cycle in melanoma by targeting BRCA1. Thus, lnc‐13317.1 might have therapeutic potential in melanoma treatment. The lncRNA profile described here highlights the importance of elucidating the exact function of these lncRNAs in the transformation of melanoma. Lnc‐13317.1 might have therapeutic potential in melanoma treatment by targeting BRCA1. [ABSTRACT FROM AUTHOR]

During the first decades of the twentieth century, Italian economist Francesco Coletti (1866–1940) was recognised as an authority on emigration and agricultural economics. We intend to focus here on Coletti's early career to understand how he rapidly managed to secure an enviable reputation. We examine Coletti's interventions on economic semiology and measurement of national wealth. We then move on to a series of theoretical debates (notably on Marx's theory of value) to which Coletti made significant contributions. Finally, we survey Coletti's fieldwork in agriculture and emigration, topics that allowed for connecting theoretical issues, methodological constraints, and empirical data. [ABSTRACT FROM AUTHOR]

Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a strong CD8+ T cell response to antigenic cargo. Therapeutic treatment of murine B16-ovalbumin (B16-OVA) melanoma with archaeosome-OVA eliminates small subcutaneous solid tumors; however, they eventually resurge despite an increased frequency of circulating and tumor infiltrating OVA-CD8+ T cells. Herein, a number of different approaches were evaluated to improve responses, including dose number, interval, and the combination of vaccine with checkpoint inhibitors. Firstly, we found that tumor protection could not be enhanced by repetitive and/or delayed boosting to maximize the CD8+ T cell number and/or phenotype. The in vivo cytotoxicity of vaccine-induced OVA-CD8+ T cells was impaired in tumor-bearing mice. Additionally, tumor-infiltrating OVA-CD8+ T cells had an increased expression of programmed cell death protein-1 (PD-1) compared to other organ compartments, suggesting impaired function. Combination therapy of tumor-bearing mice with the vaccine archaeosome-OVA, and α-CTLA-4 administered concurrently as well as α-PD-1 and an α-PD-L1 antibody administered starting 9 days after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18), significantly enhanced survival. Following multi-combination therapy ~70% of mice had rapid tumor recession, with no detectable tumor mass after >80 days in comparison to a median survival of 17-22 days for untreated or experimental groups receiving single therapies. Overall, archaeosomes offer a powerful platform for delivering cancer antigens when used in combination with checkpoint inhibitor immunotherapies. [ABSTRACT FROM AUTHOR]

Five new oleanane-type saponins 1- 5 together with a known saponin 6 and a steroidal glycoside 7 were isolated from Polaskia chichipe Backbg., and their structures were determined from their 1D and 2D NMR and HRFABMS spectral data. The six isolated saponins 1- 6 were tested for their effects on the melanogenesis of B16 melanoma 4A5 cells. Compound 1 exerted an inhibitory effect at 100 μM whereas compound 3 promoted melanogenesis at the same concentration, even though these two compounds contain the same aglycon structure. The dose-dependent activities of compounds 1 and 3 on melanin synthesis were investigated. [ABSTRACT FROM AUTHOR]

Mathematics and determinism may seem two very different topics, especially when mathematics is associated with the social sciences and economics. Nonetheless, this has not always been the case. In 1873 a curious debate took place in Paris between a young Léon Walras and Pierre Emile Levasseur concerning the compatibility of mathematics, economics, and free will. It was the consequence of a Laplacian view of mathematics that Walras inherited from physics, a view that associated mathematics with a peculiar philosophical conception. We reconstruct the historical context of the debate, the particular view of mathematics that lead to it, and then analyse the attitudes of Cournot, Walras, and Levasseur on the issue. We show that the mathematisation of economics was deeply influenced by how physicists understood mathematics. [ABSTRACT FROM PUBLISHER]

We analyse international trade in a Pasinetti–Ricardo growth model in the world economy scenario in which several small trading countries coexist and international commodity prices are determined by the interplay of supply and demand amongst them. We demonstrate that all the trading countries eventually reach the stationary state, though this process is not monotonic and the dynamics of capital and population may actually push some countries towards the stationary state and others away from it. We also use our model to assess an argument which Malthus employed in the second edition ofAn Essay on the Principle of Population(1803) to support a policy of agricultural protectionism. [ABSTRACT FROM PUBLISHER]

Various non-economic factors, like social, cultural, psychologic and others strongly affect the decision-making related to the management of personal consumption expenditure (PCE) in households and often compromise its efficiency. PCE management tools and methods currently used by households are not helpful either as rational distribution of funds among the purchases is usually out of their scope. Therefore, rational use of resources still remains a challenging task for many households. The goal of this study is to analyse the PCE management process in households and the obstacles preventing its efficiency. Methods used in the article comprise: comparative and critical analysis methods; vector analysis tools. The paper identifies shortcomings of currently used PCE management methods and tools and introduces a system of quantitative criteria enabling objective evaluation of consumption alternatives. The use of quantitative criteria limits the influence of subjective, non-economic factors on consumption-related resource management in households and can positively affect its efficiency. The criteria are justified theoretically and the benefits from their use demonstrated with some practical evidence. [ABSTRACT FROM AUTHOR]