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In this work, we describe the complex formation and radiochemistry of the cyclen-based chelator DOTI-Me bearing four methylimidazole arms. Radiolabeling properties were evaluated for 52g Mn, 64 Cu, 68 Ga, 111 In, 161 Tb, and 177 Lu, and DOTI-Me showed distinct differences to the structurally related H 4 DOTA. While radiochemical conversions (RCCs) for 52g Mn and 111 In were comparable to those of H 4 DOTA, DOTI-Me was not suited for 68 Ga. Conversely, quantitative RCCs were achieved for 64 Cu at ambient temperature, while elevated temperatures were required for complexation with H 4 DOTA. For 161 Tb and 177 Lu, good but not quantitative RCCs were obtained with DOTI-Me. With the exemption of 68 Ga 3+ , radiolabeled complexes showed high stability in ligand challenge experiments and in human serum. X-ray analysis of the nonradioactive complexes revealed the formation of 8-coordinate Mn 2+ and In 3+ DOTI-Me complexes. Cu 2+ adopted a unique distorted square-pyramidal 2 + 3 with the neutral DOTI-Me ligand and a Jahn-Teller distorted 4 + 2 coordination geometry for the diprotonated H 2 DOTI-Me 2+ cation, respectively. For Zn 2+ , the complex with HDOTI-Me + showed a distorted 4 + 3 pentagonal bipyramidal geometry. Summarizing, the ligand DOTI-Me may be an interesting alternative to H 4 DOTA for 52g Mn, 64 Cu, 111 In, 161 Tb, and 177 Lu, covering diagnostic as well as therapeutic radionuclides. Further studies of targeted radiopharmaceuticals based on the DOTI-Me scaffold in combination with the set of radiometals presented herein are thus warranted.

The impact of dietary fiber on intestinal T cell development is poorly understood. Here we show that a low fiber diet reduces MHC-II antigen presentation by small intestinal epithelial cells (IECs) and consequently impairs development of CD4 + CD8αα + intraepithelial lymphocytes (DP IELs) through changes to the microbiota. Dietary fiber supports colonization by Segmented Filamentous Bacteria (SFB), which induces the secretion of IFNγ by type 1 innate lymphoid cells (ILC1s) that lead to MHC-II upregulation on IECs. IEC MHC-II expression caused either by SFB colonization or exogenous IFNγ administration induced differentiation of DP IELs. Finally, we show that a low fiber diet promotes overgrowth of Bifidobacterium pseudolongum, and that oral administration of B. pseudolongum reduces SFB abundance in the small intestine. Collectively we highlight the importance of dietary fiber in maintaining the balance among microbiota members that allow IEC MHC-II antigen presentation and define a mechanism of microbiota-ILC-IEC interactions participating in the development of intestinal intraepithelial T cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Androgen insensitivity syndrome (AIS) is one of the most common Disorders of Sexual Differentiation (DSDs). AIS is characterized by an X-linked recessive inheritance pattern associated with variants in the androgen receptor (AR) gene that affects the masculinization process in individuals with XY karyotype. Here, we report a neonatal case of a very early diagnosis of complete AIS due to a novel variant in the AR gene. In the present case, after the clinical evaluation, the infant has undergone the following tests: biochemical analyses, including newborn screening workflow, karyotype analysis, and Next-Generation Sequencing (NGS) panel of 50 genes involved in DSDs. The NGS analysis identified a missense variant, c.2108C>A, in the AR gene. According to a cytogenetic analysis, the patient presented a 46, XY karyotype, thus the resulting hemizygote for the AR gene variant. The variant is not currently described in the literature nor in the ClinVar database. However, according to computational models, the variant could have a pathogenetic effect. This clinical case reveals a novel variant of the AR gene with a possible pathogenetic effect associated with AIS and highlights the importance of a multidisciplinary approach for the timely diagnosis and appropriate follow-up of the patient.

The neutral holmium(III) oxalate octadecahydrate {[Ho 2 (ox) 3 (H 2 O) 6 ]·12H 2 O} n of mixed hexagonal/decagonal (6 3 ·10 3 ) 3D net topology shows important changes in the magnetocaloric efficiency upon dehydration/rehydration by heating and water vapor exposition to give the holmium(III) oxalate decahydrate {[Ho 2 (ox) 3 (H 2 O) 6 ]·4H 2 O} n of hexagonal (6 3 ) 2D net topology through the intermediacy of the elusive amorphous anhydrous compound {Ho 2 (ox) 3 } n .

Up to approximately 70% of cancer survivors report persistent deficits in memory, attention, speed of information processing, multi-tasking, and mental health functioning, a series of symptoms known as "brain fog." The severity and duration of such effects can vary depending on age, cancer type, and treatment regimens. In particular, every year, hundreds of thousands of patients worldwide undergo radiotherapy (RT) for primary brain tumors and brain metastases originating from extracranial tumors. Besides its potential benefits in the control of tumor progression, recent studies indicate that RT reprograms the brain tumor microenvironment inducing increased activation of microglia and astrocytes and a consequent general condition of neuroinflammation that in case it becomes chronic could lead to a cognitive decline. Furthermore, radiation can induce endothelium reticulum (ER) stress directly or indirectly by generating reactive oxygen species (ROS) activating compensatory survival signaling pathways in the RT-surviving fraction of healthy neuronal and glial cells. In particular, the anomalous accumulation of misfolding proteins in neuronal cells exposed to radiation as a consequence of excessive activation of unfolded protein response (UPR) could pave the way to neurodegenerative disorders. Moreover, exposure of cells to ionizing radiation was also shown to affect the normal proteasome activity, slowing the degradation rate of misfolded proteins, and further exacerbating ER-stress conditions. This compromises several neuronal functions, with neuronal accumulation of ubiquitinated proteins with a consequent switch from proteasome to immunoproteasome that increases neuroinflammation, a crucial risk factor for neurodegeneration. The etiology of brain fog remains elusive and can arise not only during treatment but can also persist for an extended period after the end of RT. In this review, we will focus on the molecular pathways triggered by radiation therapy affecting cognitive functions and potentially at the origin of so-called "brain fog" symptomatology, with the aim to define novel therapeutic strategies to preserve healthy brain tissue from cognitive decline., 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., (Copyright © 2024 Marino, Bedeschi, Vaccari, Cambiaghi and Tesei.)