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Tumour cells have exquisite flexibility in reprogramming their metabolism in order to support tumour initiation, progression, metastasis and resistance to therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosynthetic and redox status to sustain the increased energetic demand of the cells. Over the last decades, the cancer metabolism field has seen an explosion of new biochemical technologies giving more tools than ever before to navigate this complexity. Within a cell or a tissue, the metabolites constitute the direct signature of the molecular phenotype and thus their profiling has concrete clinical applications in oncology. Metabolomics and fluxomics, are key technological approaches that mainly revolutionized the field enabling researchers to have both a qualitative and mechanistic model of the biochemical activities in cancer. Furthermore, the upgrade from bulk to single-cell analysis technologies provided unprecedented opportunity to investigate cancer biology at cellular resolution allowing an in depth quantitative analysis of complex and heterogenous diseases. More recently, the advent of functional genomic screening allowed the identification of molecular pathways, cellular processes, biomarkers and novel therapeutic targets that in concert with other technologies allow patient stratification and identification of new treatment regimens. This review is intended to be a guide for researchers to cancer metabolism, highlighting current and emerging technologies, emphasizing advantages, disadvantages and applications with the potential of leading the development of innovative anti-cancer therapies.

[...]in osteoarthritis,Gong et al.reported that Paeonol protects chondrocytes from interleukin-1β-induced ferroptosis via the AMPK/Nrf2/GPX4 pathway. By preserving mitochondrial function and reducing oxidative stress, Paeonol not only prevented chondrocyte death but also attenuated inflammatory responses, offering a disease-modifying potential for osteoarthritis management. B33C22001060002); by the Brazilian agencies The National Council for Scientific and Technological Development - CNPq (312114/2025-7), the Coordination for the Improvement of Higher Education Personnel - CAPES (88881.083661/2024-01) and the INCT/Excitotoxicity and Neuroprotection (408446/2024-2); by the National Natural Science Foundation of China (82574906, 82274408, 82104873), the Preparatory discipline leader training program of Shanghai TCM Integrated hospital (RCPY0071) and, the open research project of the rural revitalization collaborative technical service center of Anhui province (Huangshan University) (XCZXZD2403). Conflict of interest 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.

Since the beginning of the SARS-CoV-2 pandemic, COVID-19 appeared as a unique disease with unconventional tissue and systemic immune features. Here we show a COVID-19 immune signature associated with severity by integrating single-cell RNA-seq analysis from blood samples and broncho-alveolar lavage fluids with clinical, immunological and functional ex vivo data. This signature is characterized by lung accumulation of naïve lymphoid cells associated with a systemic expansion and activation of myeloid cells. Myeloid-driven immune suppression is a hallmark of COVID-19 evolution, highlighting arginase-1 expression with immune regulatory features of monocytes. Monocyte-dependent and neutrophil-dependent immune suppression loss is associated with fatal clinical outcome in severe patients. Additionally, our analysis shows a lung CXCR6 + effector memory T cell subset is associated with better prognosis in patients with severe COVID-19. In summary, COVID-19-induced myeloid dysregulation and lymphoid impairment establish a condition of ‘immune silence’ in patients with critical COVID-19. Integrated studies of matched tissue sites and cell types in COVID-19 patients are important to define the immune mechanisms of pathology. Here, the authors describe an immune signature in fatal COVID-19 patients harmonizing single-cell RNA sequencing of blood and matched BAL cells with deep clinical, immunological and functional data.

Interleukin-4-induced-1 (IL4i1) is an amino acid oxidase secreted from immune cells. Recent observations have suggested that IL4i1 is pro-tumorigenic via unknown mechanisms. As IL4i1 has homologs in snake venoms (L-amino acid oxidases [LAAO]), we used comparative approaches to gain insight into the mechanistic basis of how conserved amino acid oxidases regulate cell fate and function. Using mammalian expressed recombinant proteins, we found that venom LAAO kills cells via hydrogen peroxide generation. By contrast, mammalian IL4i1 is non-cytotoxic and instead elicits a cell protective gene expression program inhibiting ferroptotic redox death by generating indole-3-pyruvate (I3P) from tryptophan. I3P suppresses ferroptosis by direct free radical scavenging and through the activation of an anti-oxidative gene expression program. Thus, the pro-tumor effects of IL4i1 are likely mediated by local anti-ferroptotic pathways via aromatic amino acid metabolism, arguing that an IL4i1 inhibitor may modulate tumor cell death pathways.

Data-driven approaches and calibration techniques for mathematical models, starting from observed data, are attracting more and more interest in the field of civil engineering. Among them, evolutionary polynomial regression (EPR) is an artificial intelligence (AI) technique that combines genetic algorithms (GAs) and regression strategies. However, the difficulties and uncertainties inherent in the method have pointed out how the implementation of proper computational methods together with the use of recent and qualified databases of experimental data are essential to carry out reliable formulations. In this framework, this paper explores a new robust EPR approach able to remove potential outliers and leverage points often occurring in biased dataset and simultaneously accounting for the effects of probabilistic uncertainties. Uncertainties are incorporated in the EPR methodology by adopting the direct perturbation method. In particular, it is shown the importance to set the parameters representative of experimental and analytical dispersions on the basis of the characteristics of the database in terms of homogeneity. With this purpose, two different case-studies are analyzed, dealing with the shear capacity of RC beams without stirrups and the compressive strength of cement-based mortar specimens, respectively. Finally, the best capacity equations are selected and discussed.

Structural Topology Optimisation (STO) plays a critical role in computational engineering, enabling the creation of material-efficient, performance-driven structures. However, dynamic STO workflows, particularly those involving time-varying or seismic excitations, are often inaccessible to architects and engineers due to their reliance on standalone solvers, large-scale data handling, and advanced programming skills. This paper introduces a Computer-Aided Design (CAD)-embedded, time-dependent STO framework built upon a modular, adjoint-based optimisation core integrated into a Visual Programming Language (VPL) interface. Implemented within a parametric CAD environment through a custom C# component, the framework embeds a MATLAB-based solver to support geometry definition, boundary condition control, and dynamic finite element analysis under harmonic and seismic loading. The resulting Graphical User Interface (GUI) lowers technical barriers by enabling users to iteratively configure STO parameters, manage meshing, and visualise real-time results. Case studies on tall building façades under earthquake excitation validate the framework’s ability to minimise displacement at targeted Degrees of Freedom (DOFs), dynamically adapt material distributions, and enhance structural resilience. By bridging high-fidelity computational methods with accessible visual workflows, the proposed system advances the integration of dynamic STO into both architectural and engineering practice.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with an overall 5-year survival rate of less than 8%. New evidence indicates that PDAC cells release pro-inflammatory metabolites that induce a marked alteration of normal hematopoiesis, favoring the expansion and accumulation of myeloid-derived suppressor cells (MDSCs). We report here that PDAC patients show increased levels of both circulating and tumor-infiltrating MDSC-like cells.MethodsThe frequency of MDSC subsets in the peripheral blood was determined by flow cytometry in three independent cohorts of PDAC patients (total analyzed patients, n = 117). Frequency of circulating MDSCs was correlated with overall survival of PDAC patients. We also analyzed the frequency of tumor-infiltrating MDSC and the immune landscape in fresh biopsies. Purified myeloid cell subsets were tested in vitro for their T-cell suppressive capacity.ResultsCorrelation with clinical data revealed that MDSC frequency was significantly associated with a shorter patients’ overall survival and metastatic disease. However, the immunosuppressive activity of purified MDSCs was detectable only in some patients and mainly limited to the monocytic subset. A transcriptome analysis of the immunosuppressive M-MDSCs highlighted a distinct gene signature in which STAT3 was crucial for monocyte re-programming. Suppressive M-MDSCs can be characterized as circulating STAT3/arginase1-expressing CD14+ cells.ConclusionMDSC analysis aids in defining the immune landscape of PDAC patients for a more appropriate diagnosis, stratification and treatment.

Core vaccinations and specific antibody titer evaluations are strongly recommended worldwide by all the vaccination guidelines. Virus neutralization (VN) is considered the gold standard for measuring antibody titer against canine distemper virus, but it is complex and time consuming, and the use of in-clinics tests would allow to obtain quicker results. The aim of this study was to evaluate the agreement of the commercial in-clinics VacciCheck test compared to VN. A total of 106 canine sera were analyzed using both methods. The best agreement was obtained using a protective threshold of ≥1:32. VacciCheck showed 95.5% sensitivity, 87.2% specificity, and 92.5% accuracy. The Cohen’s kappa coefficient between methods was 0.84 (CI 95% 0.73 to 0.95), revealing an optimal agreement between the two methods (p = 0.0073). The evaluation of discordant results reveal that most samples had less than 1.5 dilution difference, and that usually did not affect the classification as protected or non-protected. Results also suggest that, in dubious cases, especially when a protective result is expected, retesting is advisable. In conclusion, VacciCheck may be considered as a reliable instrument that may help the clinician in identifying the best vaccine protocol, avoiding unnecessary vaccination, and thus reducing the incidence of adverse effects.

Immunosuppression is a hallmark of tumor progression, and treatments that inhibit or deplete monocytic myeloid-derived suppressive cells could promote anti-tumor immunity. c-FLIP is a central regulator of caspase-8-mediated apoptosis and necroptosis. Here we show that low-dose cytotoxic chemotherapy agents cause apoptosis linked to c-FLIP down-regulation selectively in monocytes. Enforced expression of c-FLIP or viral FLIP rescues monocytes from cytotoxicity and concurrently induces potent immunosuppressive activity, in T cell cultures and in vivo models of tumor progression and immunotherapy. FLIP-transduced human blood monocytes can suppress graft versus host disease. Neither expression of FLIP in granulocytes nor expression of other anti-apoptotic genes in monocytes conferred immunosuppression, suggesting that FLIP effects on immunosuppression are specific to monocytic lineage and distinct from death inhibition. Mechanistically, FLIP controls a broad transcriptional program, partially by NF-κB activation. Therefore, modulation of FLIP in monocytes offers a means to elicit or block immunosuppressive myeloid cells. Signaling and transcriptional regulation of MDSC activity remains largely undefined. Here the authors show that monocytic MDSC immunosuppression is triggered by c-FLIP and requires NFκB, implicate this axis in cancer prognosis and response to therapy, and employ ectopic FLIP to treat immunopathology.

In the world of structural design, in most cases, there is a need to control the shape of structural elements and—at the same time—the performance that each one can achieve. With the evolution of structural analysis tools, nowadays it is possible not only to have an immediate investigation of the structure’s performance, but also to search for the best shape by imposing geometric constraints. The aim of this paper is to present an innovative methodology called the performative structural design optimization (PSDO) method, based on the use of algorithm-aided design (AAD). The proposed approach deals with an emptied voided beam; starting from the parameterization of a large-span beam, the search method for the most performing shape is accomplished by multi-objective evolutionary algorithms (MOEAs). The obtained results are characterized by a double optimization: the structure achieved by the hypervolume estimation algorithm for multi-objective optimization (HypE Reduction) (OCTOPUS) represents the starting shape for the application of form-finding, giving so the possibility to obtain different feasible solutions from a single study and to choose the best one in terms of structural behavior.