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The European Union’s Green Deal emphasises the importance of improving the efficiency of the energy sector in its countries, which is why the issues involved are relevant in both scientific and practical terms. The article sets out the hypothesis that conveying the state of the economic efficiency of energy development by grades does not reflect the real situation. Instead of ranks, it is proposed to form homogeneous groups of some countries based on non-linear data normalisation instead of today’s universally used linearisation. Grouping the euro area countries in the European Union on the basis of the value of the cost-effectiveness indicator for the energy development of their industrial sector confirmed the appropriateness of the proposed method-ology. In this way, three groups of countries were formed according to the level of cost-effectiveness achieved. The proposed methodology for grouping countries is universal and can be used for international comparisons of any kind.

Prostate cancer (PCa) is a common and fatal type of cancer in men. Metastatic PCa (mPCa) is a major factor contributing to its lethality, although the mechanisms remain poorly understood. PTEN is one of the most frequently deleted genes in mPCa. Here we show a frequent genomic co-deletion of PTEN and STAT3 in liquid biopsies of patients with mPCa. Loss of Stat3 in a Pten -null mouse prostate model leads to a reduction of LKB1/pAMPK with simultaneous activation of mTOR/CREB, resulting in metastatic disease. However, constitutive activation of Stat3 led to high LKB1/pAMPK levels and suppressed mTORC1/CREB pathway, preventing mPCa development. Metformin, one of the most widely prescribed therapeutics against type 2 diabetes, inhibits mTORC1 in liver and requires LKB1 to mediate glucose homeostasis. We find that metformin treatment of STAT3/AR-expressing PCa xenografts resulted in significantly reduced tumor growth accompanied by diminished mTORC1/CREB, AR and PSA levels. PCa xenografts with deletion of STAT3/AR nearly completely abrogated mTORC1/CREB inhibition mediated by metformin. Moreover, metformin treatment of PCa patients with high Gleason grade and type 2 diabetes resulted in undetectable mTORC1 levels and upregulated STAT3 expression. Furthermore, PCa patients with high CREB expression have worse clinical outcomes and a significantly increased risk of PCa relapse and metastatic recurrence. In summary, we have shown that STAT3 controls mPCa via LKB1/pAMPK/mTORC1/CREB signaling, which we have identified as a promising novel downstream target for the treatment of lethal mPCa.

Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa patients has failed to provide therapeutic benefit. Here we show that genetic inactivation of Stat3 or IL-6 signalling in a Pten -deficient PCa mouse model accelerates cancer progression leading to metastasis. Mechanistically, we identify p19 ARF as a direct Stat3 target. Loss of Stat3 signalling disrupts the ARF–Mdm2–p53 tumour suppressor axis bypassing senescence. Strikingly, we also identify STAT3 and CDKN2A mutations in primary human PCa. STAT3 and CDKN2A deletions co-occurred with high frequency in PCa metastases. In accordance, loss of STAT3 and p14 ARF expression in patient tumours correlates with increased risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be prognostic markers to stratify high from low risk PCa patients. Our findings challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3 inhibition. IL6-STAT3 signaling is activated in prostate cancer, however inhibiting this pathway has not lead to a survival advantage in patients. Here, Pencik et al. show that loss of the IL6-STAT3 axis in mice and humans leads to metastasis due to loss of ARF, unravelling STAT3 and ARF as potential prognostic markers in prostate cancer.

Prostate cancer (PCa) has a broad spectrum of clinical behavior; hence, biomarkers are urgently needed for risk stratification. Here, we aim to find potential biomarkers for risk stratification, by utilizing a gene co‐expression network of transcriptomics data in addition to laser‐microdissected proteomics from human and murine prostate FFPE samples. We show up‐regulation of oxidative phosphorylation (OXPHOS) in PCa on the transcriptomic level and up‐regulation of the TCA cycle/OXPHOS on the proteomic level, which is inversely correlated to STAT3 expression. We hereby identify gene expression of pyruvate dehydrogenase kinase 4 ( PDK4 ), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging, and PSA level. Therefore, low PDK4 is a promising marker for PCa with dismal prognosis. Synopsis Transcriptomic and proteomic analyses in prostate cancer (PCa) reveal high TCA/OXPHOS activity and low PDK4 expression in low STAT3 tumors. PDK4 is a promising independent predictor of biochemical recurrence in PCa. Low STAT3 tumors show enhanced TCA/OXPHOS and ribosome activity in a gene co‐expression network and in transcriptomic and proteomic analyses. Enhanced ribosome‐ and metabolic activity is found in mice with a deletion of Pten and Stat3 in the prostate epithelium. Low STAT3 is associated with low PDK4 expression. PDK4 is an important regulator of TCA/OXPHOS. Analysis of patient data indicates that low PDK4 correlates with earlier biochemical recurrence in PCa. Graphical Abstract Transcriptomic and proteomic analyses in prostate cancer (PCa) reveal high TCA/OXPHOS activity and low PDK4 expression in low STAT3 tumors. PDK4 is a promising independent predictor of biochemical recurrence in PCa.

Background Prostate cancer ranks as the second most frequently diagnosed cancer in men worldwide. Recent research highlights the crucial roles IL6ST-mediated signaling pathways play in the development and progression of various cancers, particularly through hyperactivated STAT3 signaling. However, the molecular programs mediated by IL6ST/STAT3 in prostate cancer are poorly understood. Methods To investigate the role of IL6ST signaling, we constitutively activated IL6ST signaling in the prostate epithelium of a Pten -deficient prostate cancer mouse model in vivo and examined IL6ST expression in large cohorts of prostate cancer patients. We complemented these data with in-depth transcriptomic and multiplex histopathological analyses. Results Genetic cell-autonomous activation of the IL6ST receptor in prostate epithelial cells triggers active STAT3 signaling and significantly reduces tumor growth in vivo. Mechanistically, genetic activation of IL6ST signaling mediates senescence via the STAT3/ARF/p53 axis and recruitment of cytotoxic T-cells, ultimately impeding tumor progression. In prostate cancer patients, high IL6ST mRNA expression levels correlate with better recurrence-free survival, increased senescence signals and a transition from an immune-cold to an immune-hot tumor. Conclusions Our findings demonstrate a context-dependent role of IL6ST/STAT3 in carcinogenesis and a tumor-suppressive function in prostate cancer development by inducing senescence and immune cell attraction. We challenge the prevailing concept of blocking IL6ST/STAT3 signaling as a functional prostate cancer treatment and instead propose cell-autonomous IL6ST activation as a novel therapeutic strategy.

We aimed to identify novel markers for aggressive prostate cancer in a STAT3-low proteomics-derived dataset of mitochondrial proteins by immunohistochemical analysis and correlation with transcriptomic data and biochemical recurrence in a STAT3 independent PCa cohort. Formalin-fixed paraffin-embedded tissue (FFPE) sample selection for proteomic analysis and tissue-microarray (TMA) generation was conducted from a cohort of PCa patients. Retrospective data analysis was performed with the same cohort. 153 proteins differentially expressed between STAT3-low and STAT3-high samples were identified. Out of these, 46 proteins were associated with mitochondrial processes including oxidative phosphorylation (OXPHOS), and 45 proteins were upregulated, including NDUFS1/ATP5O. In a STAT3 independent PCa cohort, high expression of NDUFS1/ATP5O was confirmed by immunocytochemistry (IHC) and was significantly associated with earlier biochemical recurrence (BCR). mRNA expression levels for these two genes were significantly higher in intra-epithelial neoplasia and in PCa compared to benign prostate glands. NDUFS1/ATP5O levels are increased both at the mRNA and protein level in aggressive PCa. Our results provide evidence that NDUFS1/ATP5O could be used to identify high-risk PCa patients.

Since publication of the article, the authors became aware that Figure 6(A,D) contained errors in the bands and loading controls. The newly compiled Figure 6A and 6D is given below.Since publication of the article, the authors became aware that Figure 6(A,D) contained errors in the bands and loading controls. The newly compiled Figure 6A and 6D is given below.

Purpose This paper presents life cycle assessment of planned mass production of the thermal insulation blocks (TIB) made of thermal insulation composite material (TICM) from secondary raw materials—glass and plastic. This material is being developed at Brno University of Technology, Faculty of Civil Engineering for use in structural details of (especially low energy or passive) buildings subjected to higher compressive loads. Two production modes depending on the quality of the input materials are compared. Methods The assessment is conducted using GaBi 4 software tool with inbuilt Ecoinvent database. The results of the assessment are presented in individual impact categories according to used characterization model (CML 2001—Dec. 07). All the necessary energy and material flows are specified in detail for the purpose of the assessment. Cut-off allocation method is used for allocating the environmental impacts of recycled materials. Part of the assessment is sensitivity analysis of one variable parameter—amount of TIB produced per year. Results and discussion The results of the assessment show decisive impact of used electricity source on the overall results—86.2 and 94.3 %, respectively, for both production modes. This is closely connected with quality of used secondary raw materials and design of the production line. Use of higher-quality materials, as well as changes of the designed production line can reduce the overall environmental impacts by almost 30 %. Conclusions The results show possible improvements in the planned mass production of the TIB. They also find that further investigation will be required before the start of mass production, especially in connection with improving the environmental impacts of used electricity sources.

Over the past three decades, an exponentially growing body on elements and actors of the concept of an entrepreneurial university has emerged. Compared to its western European counterparts, however, the idea of the third role of the university has only recently been implemented in Central and Eastern European countries, and thus both research and entrepreneurial practice grapple with empirical results. In this paper, we attempt to fill this gap while adopting a case study approach to examine the issue of what resources a prominent technical university operating in the emerging market of the Czech Republic transfers to academic ventures to utilise and commercialise university research results. Within a survey, nine academic founders and two university representatives were interviewed to assess the role of university resources in facilitating academic entrepreneurship. Our research results suggest that creating infrastructure to foster the third role of universities in an emerging market is a complex and long-term issue. Formal institutions embedded in the intra-university organisational structure, such as knowledge transfer offices and entrepreneurial centres, need to be equipped with sufficient resources and competences. Skilled people with their own network of contacts to intra-university departments and external environment represented by regional incubators, venture capital providers, business angel associations, and experienced entrepreneurs should be involved in the process of creating and increasing capacity. Furthermore, the upcoming agenda should undoubtedly acknowledge the significant role of entrepreneurship education with a focus on talent recognition and entrepreneurship training to impact the entrepreneurial intentions of researchers and students. Overall, we also conclude that the motivation of academics to commercialise their inventions could be positively affected by the applied concepts of assessing their performance. Finally, this study shows that measures at all management levels have to be adopted to create a vital organisational culture that will be in alignment with the vision of entrepreneurial university. The novelty of this paper is twofold. First, the study provides a useful methodological concept of data collection as the multi-level approach was applied for studying the phenomenon of entrepreneurial university. Furthermore, the research findings have valuable implications for university authorities, as well as national and local policy makers, in creating growth programmes and supporting the entrepreneurial mindset.

The prefabricated roller blind lintels have become common solution, particularly for the single-leaf masonry structures without external thermal insulation system. These lintels, representing simple system solution, are designed to interrupt thermal bridges in a place of above the window lintel and simultaneously to provide sufficient reliability of load transfer. The actual outdoor blinds contribute to increase the thermal stability in the room in summer and winter season. They prevent overheating of the room in the summer months and reduce heat transmission through a window in the winter. This paper is focused on the design and numerical modelling of the prefabricated roller blind carrier lintels solutions. Methods of elimination of the thermal bridge are demonstrated on the example of a real produced prefabricated lintel. At the same time this paper deals with its structural analysis. Analyses were carried out using the method of numerical modelling, using finite element method and computing software ANSYS.