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HIGHLIGHTS Insect meal can replace soy in hen diets without harming egg quality or production Insect-based feed supports circular economy by recycling food waste into high-value animal protein Eggs from insect-fed hens maintain quality even after 21 days, supporting food shelf-life

Internal combustion engines are a well-established, efficient and dispatchable solution for distributed power generation and they are widely used in various sectors including grid balancing, data centers and combined heat and power systems. Current research efforts focus on further increasing efficiency, enabling decarbonization through renewable fuels and improving responsiveness to electricity demand in the presence of variable renewable energy sources. In this context, the free-piston linear generator (FPLG) stands out as a highly promising technology, as it directly converts piston motion into electricity, offering high efficiency, reduced mechanical complexity and seamless grid integration. Initially explored for its high-efficiency potential with homogeneous charge compression ignition combustion at extreme compression ratios, opposed-piston FPLGs are now commercially available for distributed power generation, delivering global efficiencies exceeding 45%, near-zero emissions and multi-fuel capability. Building on the detailed studies conducted by Svrcek and co-authors, this work investigates the power-generation potential of low-temperature homogeneous combustion using CFD simulations with detailed chemical kinetics. First, rapid compression machine (RCM) experiments with methane were reproduced in simulations to validate the proposed methodology and to consolidate experimental findings on the maximum achievable efficiency. Subsequently, an extensive RCM simulation campaign supported the identification of optimal operating conditions in terms of air–fuel ratio using methane as fuel. The RCM results enabled the definition of a preliminary methane-fueled opposed-piston FPLG configuration. Full-cycle simulations including gas exchange, mixing and combustion demonstrated an indicated efficiency of 58% at an equivalence ratio ϕ=0.5 and a compression ratio of 50. The key novelties of this study are the development of a novel RCM-2 configuration that more closely reproduces the dynamic behavior of an opposed-piston FPLG including air-spring effects and the introduction of a divided intake port strategy to simultaneously reduce fuel slip and mitigate knocking behaviour through charge stratification. The simulation results for the proposed configuration confirm the potential of opposed-piston FPLGs for high-efficiency power generation and highlight key parameters affecting performance and emissions formation.

Myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML) are increasingly recognized to exhibit immune dysregulation, which can occasionally present with autoinflammatory manifestations. We describe four patients with MDS/AML harboring p53 mutations and a complex karyotype who developed inflammatory serositis without infectious correlation. All patients showed clinical improvement following corticosteroid therapy.

Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events.

Neuronal innervation of the pancreas has historically been characterized using marker‐based classification and physiological studies, but its transcriptomic landscape remains only partially explored. A detailed molecular profile of pancreatic sensory neurons could provide insights into their role in health and disease, particularly in pancreatic ductal adenocarcinoma (PDAC), where neural remodeling influences tumor progression and pain signaling. Wild‐type and PDAC mice were injected with the retrotracer Fast Blue into pancreatic or cancerous tissue. Dorsal root ganglia were dissociated, and Fast Blue‐positive sensory neurons were isolated, lysed, and analyzed using single‐cell RNA sequencing. Data were validated using immunofluorescence, organoid cultures and qPCR. We performed transcriptomic profiling of sensory neurons innervating the pancreatic head and tail under normal and cancer conditions. Our analysis identified neurofilament‐containing neurons as the predominant sensory subtype in both contexts, while non‐peptidergic neurons were underrepresented in tumor‐associated innervation. Differential gene expression analysis revealed a unique subset of genes upregulated in sensory neurons innervating pancreatic tumors, many linked to mitochondrial activity. Further validation also revealed the presence of transcripts transferred via extracellular vesicles (including the Pdx1‐CreERT2 transgene from the KPC mouse model), suggesting a novel mechanism of tumor–neuron interaction. Our findings provide a detailed characterization of pancreatic and pancreatic ductal adenocarcinoma sensory innervation. We identified tumor‐derived RNA within sensory neurons in the PDAC mouse model, suggesting an extracellular vesicle–mediated RNA transfer mechanism that may remodel sensory signaling and open new prospects for diagnostic and therapeutic innovation in PDAC. Impact statement Transcriptomic profiling of pancreatic sensory neurons reveals shifts in neuronal populations, tumor‐specific mitochondrial gene upregulation, and potential extracellular vesicle–mediated transcript transfer. Circulating tumor transcripts in KPC mice provide a reference for pancreatic innervation, tumor–nerve interactions, and therapeutic targets. Pancreatic sensory neurons innervating healthy and PDAC tissue were retrogradely labeled and profiled by single‐cell RNA sequencing. Tumor‐associated innervation showed a dominant neurofilament‐positive subtype, altered mitochondrial gene signatures, and reduced non‐peptidergic neurons. Transcriptomic and imaging analyses revealed tumor‐derived RNA within sensory neurons, supporting extracellular vesicle–mediated tumor–neuron communication in pancreatic cancer.

Chronic lymphocytic leukemia (CLL) is a dynamic malignancy in which intraclonal subfractions differ in activation history and responsiveness to microenvironmental signals. Here, we investigated the expression and inducibility of IL-12 family receptor subunits (IL-23R, IL-12Rβ1, IL-12Rβ2) and the related receptor complexes in recirculating CLL cells, with a focus on CXCR4/CD5-defined fractions: the proliferative fraction (PF; CXCR4dim/CD5bright; most recently divided, tissue-emigrated cells) and the resting fraction (RF; CXCR4bright/CD5dim; older, quiescent cells). At baseline, IL-12Rβ1 was enriched in the PF and was associated with a higher proportion of cells expressing IL-23R and IL-12R receptor complexes. Concomitantly, RT-qPCR disclosed higher IL-12Rβ1 mRNA levels. Following antigen-independent activation with CpG or CpG + IL-15, there was a marked increase in IL-23R and IL-12Rβ1 but not in IL-12Rβ2 surface expression, resulting in preferential upregulation of the IL-23R complex over the IL-12R complex. Fraction-specific analyses showed stronger induction of IL-23R and IL-23R complex expression in PF compared with RF. These findings identify an intraclonal bias toward IL-23 responsiveness in the CLL cells with a phenotype of recently divided, tissue-emigrated cells and suggest the IL-23/IL-23R axis as a potential therapeutic target.

The engagement of the B cell receptor (BcR) on the surface of leukemic cells represents a key event in chronic lymphocytic leukemia (CLL) since it can lead to the maintenance and expansion of the neoplastic clone. This notion was initially suggested by observations of the CLL BcR repertoire and of correlations existing between certain BcR features and the clinical outcomes of single patients. Based on these observations, tyrosine kinase inhibitors (TKIs), which block BcR signaling, have been introduced in therapy with the aim of inhibiting CLL cell clonal expansion and of controlling the disease. Indeed, the impressive results obtained with these compounds provided further proof of the role of BcR in CLL. In this article, the key steps that led to the determination of the role of BcR are reviewed, including the features of the CLL cell repertoire and the fine mechanisms causing BcR engagement and cell signaling. Furthermore, we discuss the biological effects of the engagement, which can lead to cell survival/proliferation or apoptosis depending on certain intrinsic cell characteristics and on signals that the micro-environment can deliver to the leukemic cells. In addition, consideration is given to alternative mechanisms promoting cell proliferation in the absence of BcR signaling, which can explain in part the incomplete effectiveness of TKI therapies. The role of the BcR in determining clonal evolution and disease progression is also described. Finally, we discuss possible models to explain the selection of a special BcR set during leukemogenesis. The BcR may deliver activation signals to the cells, which lead to their uncontrolled growth, with the possible collaboration of other still-undefined events which are capable of deregulating the normal physiological response of B cells to BcR-delivered stimuli.

Background/Objectives: The immunoglobulin heavy-chain variable (IGHV) gene repertoire represents a characteristic feature of chronic lymphocytic leukemia (CLL), although its configuration is not well defined at the early disease stages. The IGHV repertoire of a cohort of early CLL patients was analyzed and compared to that of a “real-world” reference cohort. Methods: Patients from the O-CLL1 observational protocol, which enrolled only Binet stage A cases within twelve months from diagnosis, were studied. IGHV/IGHJ rearrangements were sequenced and annotated following ERIC recommendations, and stereotyped subsets were assigned using ARResT/AssignSubsets. The repertoire features were compared with the dataset of a real-world cohort of patients with heterogeneous staging (CTR cohort) and with published early-diagnosis series. Results: IGHV and IGHJ gene distributions and HCDR3-length profiles in O-CLL1 closely mirrored those of CTR, indicating that the BcR IG repertoire at diagnosis is already defined rather than being selected during disease progression. Mutated IGHV (M-CLL) predominated, with a frequency of stereotyped BcR IG comparable to that of other early-diagnosis cohorts. However, within this conserved framework, subset #4 was over-represented among M-CLL from O-CLL without an increased overall IGHV4-34 gene usage, suggestive of a selective expansion rather than a recombinational bias. Subset #4 cases retained canonical HCDR3 motifs and showed time-to-first-treatment like other M-CLL, likely reflecting the younger age structure of O-CLL1. Conclusions: Early-diagnosis CLL displays a biased IGHV repertoire with stereotyped configurations characteristic of CLL, including subsets that are rare in the normal B-cell repertoire. These findings support a central role for antigen-driven selection in shaping CLL evolution.

Background B cell receptor Immunoglobulin (BcR IG) repertoire of Chronic Lymphocytic Leukemia (CLL) is characterized by the expression of quasi-identical BcR IG. These are observed in approximately 30% of patients, defined as stereotyped receptors and subdivided into subsets based on specific VH CDR3 aa motifs and phylogenetically related IGHV genes. Although relevant to CLL ontogeny, the distribution of CLL-biased stereotyped immunoglobulin rearrangements (CBS-IG) in normal B cells has not been so far specifically addressed using modern sequencing technologies. Here, we have investigated the presence of CBS-IG in splenic B cell subpopulations (s-BCS) and in CD5 + and CD5 − B cells from the spleen and peripheral blood (PB). Methods Fractionation of splenic B cells into 9 different B cell subsets and that of spleen and PB into CD5 + and CD5 − cells were carried out by FACS sorting. cDNA sequences of BcR IG gene rearrangements were obtained by NGS. Identification of amino acidic motifs typical of CLL stereotyped subsets was carried out on IGHV1-carrying gene sequences and statistical evaluation has been subsequently performed to assess stereotypes distribution. Results CBS-IG represented the 0.26% average of IGHV1 genes expressing sequences, were detected in all of the BCS investigated. CBS-IG were more abundant in splenic and circulating CD5 + B (0.57%) cells compared to CD5 − B cells (0.17%). In all instances, most CBS IG did not exhibit somatic hypermutation similar to CLL stereotyped receptors. However, compared to CLL, they exhibited a different CLL subset distribution and a broader utilization of the genes of the IGHV1 family. Conclusions CBS-IG receptors appear to represent a part of the “public” BcR repertoire in normal B cells. This repertoire is observed in all BCS excluding the hypothesis that CLL stereotyped BcR accumulate in a specific B cell subset, potentially capable of originating a leukemic clone. The different relative representation of CBS-IG in normal B cell subgroups suggests the requirement for additional selective processes before a full transformation into CLL is achieved.

The European Roller Coracias garrulus has suffered greatly from breeding habitat loss due to the renovation of old farmhouses and rural buildings and changing agricultural practices that took place extensively across Europe in the last decades. As a consequence, this species experienced a significant decline, and local extinctions of breeding populations were recorded in several European countries. We investigated nest sites and nesting area selection by the Italian Roller population during the breeding period (May–August) between 2016 and 2018. We collected 711 points from field surveys and used four types of point pattern analysis to detect space-time patterns of nest site and nesting area selection. We found that: (a) the spatial distribution of selected (i.e., occupied) nest sites was significantly nonrandom (p < 0.01) for all years and months; (b) only 2.6% of the selected nest sites was located within parks or reserves; (c) there were significant (p < 0.01) latitudinal, longitudinal, and altitudinal shifts of selected nest sites between May and August; (d) the geographical barycentres of selected nest sites shifted northward by about 80 km per month from May (southernmost barycentre) to August (northernmost barycentre); (e) four main nesting areas (7886 km2 in total) occurred in central and southern Italy, whose utilization by the European Rollers differed between months but not between years; (f) the detected nesting areas corresponded mainly to non-irrigated arable lands (41.22% of their extent) and natural grasslands (12.80%). Our results are useful to support conservation strategies for the breeding sites of this farmland species, which is not a regular visitor to protected areas in Italy.