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Glioblastoma (GBM) is an aggressive brain tumor characterized by an immunosuppressive tumor microenvironment (TME), which contributes to treatment resistance and disease progression. Background: Tumor-associated macrophages (TAMs), comprising both resident microglia and bone marrow–derived macrophages, play a central role in supporting tumor growth, angiogenesis, and immune evasion. Most TAMs adopt an M2-like immunosuppressive phenotype, making them a promising target for immunomodulatory strategies in GBM. Method: According to PRISMA guidelines, we conducted a systematic literature review and recruited eligible studies focused on therapeutic approaches targeting TAMs in GBM, emphasizing mechanisms of action, efficacy, and challenges. Data extraction focused on therapeutic classes, outcomes, and TAM-related biomarkers. Results: We identified 30 studies meeting the inclusion criteria. These therapies are categorized into three main strategies: inhibition of TAM recruitment, enhancement of TAM-mediated phagocytosis, and reprogramming of TAMs. Combination strategies, including TAM-targeting with checkpoint inhibitors, nanoparticles, and oncolytic viruses, show synergistic effects in preclinical models. Conclusions: Targeting TAMs represents a multifaceted strategy for GBM treatment. Current evidence underscores the need for combination approaches integrating TAM modulation with existing standard-of-care therapies. Clinical translation remains limited due to challenges such as TAM heterogeneity, plasticity, immunosuppressive therapies, and restricted drug delivery across the blood–brain barrier. Future directions should highlight personalized treatments based on detailed TME profiling. Combining TAM-targeted therapies with agents modulating metabolic or immune pathways, and leveraging advanced delivery systems and spatial transcriptomics may improve efficacy.

PurposeTo identify radiological features distinguishing adamantinomatous craniopharyngioma (ACP) from papillary craniopharyngioma (PCP) and assess their impact on pituitary-hypothalamic-axis dysfunction and post-surgery recurrence.MethodsMRIs of 80 patients (48 with ACP, 32 with PCP) were analyzed for tumor topography, size, cystic-solid composition, peritumoral edema, signal intensity, and CT for calcification patterns. Volumes, normalized signal intensity minimum (nT2min) and maximum (nT1Max) values were measured from T2 and T1-weighted images, respectively. These variables were correlated with pituitary-hypothalamic-axis dysfunction and surgical outcomes.ResultsThere were no significant topographic differences between ACP and PCP (P > 0.85). ACP tumors had larger volumes (4992.2 ± 5195.5 mm³ vs. 814.4 ± 1023 mm³), a predominant cystic component, lower nT2min values (42.57% vs. 55.55%), higher nT1Max values (273.25% vs. 216.67%), and more peripheral calcifications (P < 0.001). In ACP lower nT2min and higher nT1Max values correlated with incomplete surgical excision (nT2min: P < 0.001, r = -0.607; nT1Max: P < 0.001, r = 0.817) while only lower nT2min values correlated with higher recurrence likelihood (nT2min: P < 0.001, r = -0.485). Regardless of histotype, tumors invading the third ventricle floor were more likely to show peritumoral edema (P < 0.001), hypothalamic infiltration (P < 0.001), and dysfunction (P = 0.013).ConclusionTumor location relative to the third ventricle and associated parenchymal changes are independent predictors of hypothalamic dysfunction, regardless of tumor histotype. ACP’s cystic composition characterized by a higher concentration of thick or proteinaceous material and peripheral calcifications predict poorer surgical outcomes.

Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs’ aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs.

Background and Objectives: The temporoparietal fascia flap (TPFF) has recently emerged as an option for skull base reconstruction in endoscopic transnasal surgery when vascularized nasal flaps are not available. This study provides a systematic literature review of its use in skull base surgery and describes a novel cohort of patients. Methods: PRISMA guidelines were used for the review. Patients undergoing skull base reconstruction with TPFF in our center from May 2022 to April 2024 were retrospectively included. Data were collected on pre- and post-operative clinical and radiological features, histology, surgical procedures, and complications. Results: Sixteen articles were selected, comprising 42 patients who underwent TPFF reconstruction for treatment of complex skull base pathologies. In total, 5 of 358 patients (0.9%) who underwent tumor resection via endoscopic transanal surgery in the study period in our institution required TPFF. All had been previously treated with surgery and radiation therapy for different pathologies (three chordomas, one giant pituitary neuroendocrine tumor (PitNET), and one sarcoma). Post-operative complications included CSF leak, which resolved after flap revision, and an internal carotid artery pseudoaneurysm requiring endovascular embolization. Conclusions: TPFF is an effective option for skull base reconstruction in complex cases and should be part of the armamentarium of the skull base surgeon.

Adeno-associated viral (AAV) vector-based gene therapy is gaining foothold as treatment for genetic neurological diseases with encouraging clinical results. Nonetheless, dose-dependent adverse events have emerged in recent clinical trials through mechanisms that remain unclear. We have modelled here the impact of AAV transduction in cell models of the human central nervous system (CNS), taking advantage of induced pluripotent stem cells. Our work uncovers vector-induced innate immune mechanisms that contribute to cell death. While empty AAV capsids were well tolerated, the AAV genome triggered p53-dependent DNA damage responses across CNS cell types followed by the induction of inflammatory responses. In addition, transgene expression led to MAVS-dependent activation of type I interferon responses. Formation of DNA damage foci in neurons and gliosis were confirmed in murine striatum upon intraparenchymal AAV injection. Transduction-induced cell death and gliosis could be prevented by inhibiting p53 or by acting downstream on STING- or IL-1R-mediated responses. Together, our work identifies innate immune mechanisms of vector sensing in the CNS that can potentially contribute to AAV-associated neurotoxicity. Costa-Verdera et. al describe a mechanism by which AAV vector genomes activate P53-mediated signalling in CNS cells involving downstream STING activation and pro-inflammatory responses. Inhibition of either P53 or STING prevented target-cell apoptosis and inflammatory signalling.

We report in this paper the muography of an archaeological site located in the highly populated “Sanità” district in the center of Naples, ten meters below the current street level. Several detectors capable of detecting muons - high energy charged particles produced by cosmic rays in the upper layers of atmosphere - were installed underground at the depth of 18 m, to measure the muon flux over several weeks. By measuring the differential flux with our detectors in a wide angular range, we have produced a radiographic image of the upper layers. Despite the architectural complexity of the site, we have clearly observed the known structures as well as a few unknown ones. One of the observed new structures is compatible with the existence of a hidden, currently inaccessible, burial chamber.

In plants, hypoxia can be induced by submergence, and the lack of oxygen impairs mitochondrial respiration, thus affecting the plant's energy status. Hypoxia has major effects on gene expression; these changes induce key responses that help meet the needs of the stressed plant. However, little is known about the possible role of RNA signaling in the regulation of gene expression under limited oxygen availability. Here, we report the contribution of ARGONAUTE1 (AGO1) to hypoxia-induced gene regulation in Arabidopsis (Arabidopsis thaliana). Submergence induced changes in levels of the microRNAs miR2936 and miR398, but this had no obvious effects on their putative target mRNA levels. However, we found that ago1-27 plants are intolerant to submergence and transcriptome analysis identified genes whose regulation requires functional AGO1. Analysis of mutants affected in various branches of RNA signaling highlighted the convergence of AGO1 signaling with the AGO4-dependent RNA-directed DNA methylation (RdDM) pathway. AGO4-dependent RdDM represses the expression of HOMOLOG OF RPW8 4 (HR4) and alters its response to submergence. Remarkably, methylation of the second exon of HR4 is not only reduced in ago4-1 but also in plants overexpressing a constitutively stable version of the oxygen sensor RELATED TO APETALA2 12 (RAP2.12), indicating convergence of oxygen signaling with epigenetic regulation of gene expression. Therefore, our results identify a role for AGO1 and AGO4 RNA-silencing pathways in low-oxygen signaling in Arabidopsis.

Exposure to high light intensity (HL) and cold treatment (CT) induces reddish pigmentation in Azolla filiculoides, an aquatic fern. Nevertheless, how these conditions, alone or in combination, influence Azolla growth and pigment synthesis remains to be fully elucidated. Likewise, the regulatory network underpinning the accumulation of flavonoids in ferns is still unclear. Here, we grew A. filiculoides under HL and/or CT conditions for 20 days and evaluated the biomass doubling time, relative growth rate, photosynthetic and non-photosynthetic pigment contents, and photosynthetic efficiency by chlorophyll fluorescence measurements. Furthermore, from the A. filiculoides genome, we mined the homologs of MYB, bHLH, and WDR genes, which form the MBW flavonoid regulatory complex in higher plants, to investigate their expression by qRT-PCR. We report that A. filiculoides optimizes photosynthesis at lower light intensities, regardless of the temperature. In addition, we show that CT does not severely hamper Azolla growth, although it causes the onset of photoinhibition. Coupling CT with HL stimulates the accumulation of flavonoids, which likely prevents irreversible photoinhibition-induced damage. Although our data do not support the formation of MBW complexes, we identified candidate MYB and bHLH regulators of flavonoids. Overall, the present findings are of fundamental and pragmatic relevance to Azolla’s biology.

Drought stress poses a significant threat to olive cultivation in Mediterranean regions. This study investigated the resilience and functional adaptation of root-associated and rhizosphere soil microorganisms of four olive cultivars under contrasting water regimes (irrigated vs. drought) across seasons. Using a combination of amplicon-targeted metagenomics, phylogenetic analysis, and text mining of the scientific literature, we identified a conserved core microbiome and revealed that drought stress significantly alters the structure of root-associated—but not rhizosphere soil—bacterial communities. Potential functional profiling indicated that drought conditions enriched for genes involved in stress response pathways, including branched-chain amino acid transport, glutathione S-transferase activity, thioredoxin reductase, and chemotaxis. Text mining co-occurrence networks highlighted strong associations between some key bacterial genera and plant growth-promoting functions like phytohormone production and biocontrol. Furthermore, we identified Solirubrobacter, Microvirga, and Pseudonocardia as the primary contributors to these drought-resilience functions. The stability of the soil microbiome suggests functional redundancy, whereas the restructuring of the root endophytic compartment indicates active plant selection for beneficial microbes. Our findings provide a foundation for developing tailored microbial consortia (SynComs) to enhance drought tolerance in olive trees and support sustainable agriculture in water-limited environments.

Azolla spp. are floating ferns used for centuries as biofertilizers to enrich the soil with inorganic nitrogen and improve rice yields. However, the molecular interactions between Azolla and co-cultivated rice plants only recently started to be thoroughly investigated. In this study, we exploited an experiment in which rice plants were grown together with Azolla by maintaining a low and constant concentration of inorganic nitrogen. We employed a combination of non-targeted metabolomics, chemometrics, and molecular networking to dissect the impact of Azolla co-cultivation on the metabolome of rice roots- and leaves, as well as to annotate the metabolites released by Azolla into the growing medium. Our analyses showed that Azolla can synthesize and release a broad range of metabolites in the culture medium, mainly comprising small peptides (i.e., di- and tri-peptides) and flavonoids, that may have stimulated the rice plant growth. We also observed a systemic response in the upregulation of rice metabolites, first in the roots and then in the leaves. Metabolomics analysis indicated that during the first stages of co-cultivation, the impact of Azolla on rice mainly resulted in the accumulation of small peptides, lipids and carbohydrates in roots, as well as flavonoid glycosides and carbohydrates in leaves. Consistent with these results, transcriptomics analysis of rice roots indicated significant changes in the expressions of genes coding for small peptide and lipid transporters and genes involved in the pathways of amino acid salvage and biosynthesis. Overall, our study provides new insights into Azolla’s beneficial and growth-promoting effects on rice. Understanding the molecular mechanisms by which Azolla functions as a biostimulant in rice co-culture will facilitate the development of more sustainable and environmentally friendly techniques to increase yields.