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In insects, rapidly evolving primary sex-determining signals are transduced by a conserved regulatory module controlling sexual differentiation. In the agricultural pest Ceratitis capitata (Mediterranean fruit fly, or Medfly), we identified a Y-linked gene, Maleness-on-the-Y (MoY), encoding a small protein that is necessary and sufficient for male development. Silencing or disruption of MoY in XY embryos causes feminization, whereas overexpression of MoY in XX embryos induces masculinization. Crosses between transformed XY females and XX males give rise to males and females, indicating that a Y chromosome can be transmitted by XY females. MoY is Y-linked and functionally conserved in other species of the Tephritidae family, highlighting its potential to serve as a tool for developing more effective control strategies against these major agricultural insect pests.

Laboratory tests play a crucial role in the diagnostic process for both adults and children. Indeed, they are essential for evaluating health status and formulating effective treatment strategies in the presence of disease. However, in the case of pediatrics, distinct physiological and developmental features of children should be taken into account when compared to adults. Consequently, it is necessary to consider some factors, such as reference intervals that vary significantly at different stages of development due to sexual development, cerebral maturation, and biological and environmental influences; furthermore, it must be considered that extremely small volumes of biological samples are often necessary to obtain accurate laboratory results. Finally, timely test results are critical, especially for pediatric conditions that are treatable when diagnosed early. This review article provides a comprehensive overview of advanced diagnostic technologies, including rapid next-generation sequencing and complex point-of-care testing, within the context of pediatric laboratory medicine. Special attention is given to diagnostic tools that support neonatal and pediatric intensive care units, with a focus on how innovative technologies, particularly those utilizing artificial intelligence algorithms, can accelerate diagnostic workflows.

Less than 5% of the DNA sequence encodes for proteins, and the remainder encodes for non-coding RNAs (ncRNAs). Among the members of the ncRNA family, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play a pivotal role in the insurgence and progression of several cancers, including leukemia. Thought to have different molecular mechanisms, both miRNAs and lncRNAs act as epigenetic factors modulating gene expression and influencing hematopoietic differentiation, proliferation and immune system function. Here, we discuss the most recent findings on the main molecular mechanisms by which miRNAs and lncRNAs are involved in the pathogenesis and progression of pediatric T acute lymphoblastic leukemia (T-ALL), pointing out their potential utility as therapeutic targets and as biomarkers for early diagnosis, risk stratification and prognosis. miRNAs are involved in the pathogenesis of T-ALL, acting both as tumor suppressors and as oncomiRs. By contrast, to the best of our knowledge, the literature highlights lncRNAs as acting only as oncogenes in this type of cancer by inhibiting apoptosis and promoting cell cycle and drug resistance. Additionally, here, we discuss how these molecules could be detected in the plasma of T-ALL patients, highlighting that lncRNAs may represent a new class of promising accurate and sensitive biomarkers in these young patients. Thus, the unveiling of the aberrant signature of circulating and intracellular levels of lncRNAs could have great clinical utility for obtaining a more accurate definition of prognosis and uncovering novel therapeutic strategies against T-ALL in children. However, further investigations are needed to better define the standard methodological procedure for their quantification and to obtain their specific targeting in T-ALL pediatric patients.

Burn injuries are a significant cause of morbidity and mortality in pediatric populations. Our study aims to provide an in-depth overview of the current emergency treatment strategies for dermal injuries in children. While advances in burn care have led to improved outcomes for patients with dermal injuries, there remains considerable variability in treatment approaches, and numerous opportunities exist to enhance patient care through the adoption of novel therapies and more effective management of healthcare resources. Children with severe burns often experience profound physiological changes that can result in a range of complications, including infections, fluid and metabolism imbalance due to increased catabolism and protein requirements. Our systematic review focuses on emergency treatment approaches that have demonstrated direct application in pediatric burn care. To this aim, we consulted the scientific databases PubMed, Embase, Web of Science, and Cochrane Library, selecting n  = 6 studies that outline the emergency therapeutic approach used in the pediatric setting after a burn, highlighting the most widely adopted techniques and their clinical applications. Study selection was guided by defined eligibility criteria; only original articles published in English that investigated emergency interventions in pediatric populations (0 to 17 years) were considered. Studies were excluded if they involved subjects over 17 years of age, focused on conditions unrelated to burns, employed in vitro or in vivo models, or were review articles. Through a comprehensive examination of these approaches, our study aims to identify areas for improvement and potential advancements in pediatric burn management, suggesting possible future approaches based on Advanced therapy medicinal products (ATMPs) storage approaches.

In the last decades, the colonization of Mediterranean Europe and of other temperate regions by Aedes albopictus created an unprecedented nuisance problem in highly infested areas and new public health threats due to the vector competence of the species. The Sterile Insect Technique (SIT) and the Incompatible Insect Technique (IIT) are insecticide-free mosquito-control methods, relying on mass release of irradiated/manipulated males, able to complement existing and only partially effective control tools. The validation of these approaches in the field requires appropriate experimental settings, possibly isolated to avoid mosquito immigration from other infested areas, and preliminary ecological and entomological data. We carried out a 4-year study in the island of Procida (Gulf of Naples, Italy) in strict collaboration with local administrators and citizens to estimate the temporal dynamics, spatial distribution, and population size of Ae . albopictus and the dispersal and survival of irradiated males. We applied ovitrap monitoring, geo-spatial analyses, mark-release-recapture technique, and a citizen-science approach. Results allow to predict the seasonal (from April to October, with peaks of 928–9,757 males/ha) and spatial distribution of the species, highlighting the capacity of Ae . albopictus population of Procida to colonize and maintain high frequencies in urban as well as in sylvatic inhabited environments. Irradiated males shown limited ability to disperse (mean daily distance travelled <60m) and daily survival estimates ranging between 0.80 and 0.95. Overall, the ecological characteristics of the island, the acquired knowledge on Ae . albopictus spatial and temporal distribution, the high human and Ae . albopictus densities and the positive attitude of the resident population in being active parts in innovative mosquito control projects provide the ground for evidence-based planning of the interventions and for the assessment of their effectiveness. In addition, the results highlight the value of creating synergies between research groups, local administrators, and citizens for affordable monitoring (and, in the future, control) of mosquito populations.

Background Females of the Mediterranean fruit fly Ceratitis capitata (Medfly) are major agricultural pests, as they lay eggs into the fruit crops of hundreds of plant species. In Medfly, female sex determination is based on the activation of Cctransformer (Cctra). A maternal contribution of Cctra is required to activate Cctra itself in the XX embryos and to start and epigenetically maintain a Cctra positive feedback loop, by female-specific alternative splicing, leading to female development. In XY embryos, the male determining Maleness-on-the-Y gene (MoY) blocks this activation and Cctra produces male-specific transcripts encoding truncated CcTRA isoforms and male differentiation occurs. Results With the aim of inducing frameshift mutations in the first coding exon to disrupt both female-specific and shorter male-specific CcTRA open reading frames (ORF), we injected Cas9 ribonucleoproteins (Cas9 and single guide RNA, sgRNA) in embryos. As this approach leads to mostly monoallelic mutations, masculinization was expected only in G1 XX individuals carrying biallelic mutations, following crosses of G0 injected individuals. Surprisingly, these injections into XX-only embryos led to G0 adults that included not only XX females but also 50% of reverted fertile XX males. The G0 XX males expressed male-specific Cctra transcripts, suggesting full masculinization. Interestingly, out of six G0 XX males, four displayed the Cctra wild type sequence. This finding suggests that masculinization by Cas9-sgRNA injections was independent from its mutagenic activity. In line with this observation, embryonic targeting of Cctra in XX embryos by a dead Cas9 (enzymatically inactive, dCas9) also favoured a male-specific splicing of Cctra, in both embryos and adults. Conclusions Our data suggest that the establishment of Cctra female-specific autoregulation during the early embryogenesis has been repressed in XX embryos by the transient binding of the Cas9-sgRNA on the first exon of the Cctra gene. This hypothesis is supported by the observation that the shift of Cctra splicing from female to male mode is induced also by dCas9. Collectively, the present findings corroborate the idea that a transient embryonic inactivation of Cctra is sufficient for male sex determination.

The Mediterranean fruitfly Ceratitis capitata (medfly) is an invasive agricultural pest of high economic impact and has become an emerging model for developing new genetic control strategies as an alternative to insecticides. Here, we report the successful adaptation of CRISPR-Cas9-based gene disruption in the medfly by injecting in vitro pre-assembled, solubilized Cas9 ribonucleoprotein complexes (RNPs) loaded with gene-specific single guide RNAs (sgRNA) into early embryos. When targeting the eye pigmentation gene white eye ( we ), a high rate of somatic mosaicism in surviving G0 adults was observed. Germline transmission rate of mutated we alleles by G0 animals was on average above 52%, with individual cases achieving nearly 100%. We further recovered large deletions in the we gene when two sites were simultaneously targeted by two sgRNAs. CRISPR-Cas9 targeting of the Ceratitis ortholog of the Drosophila segmentation paired gene ( Ccprd ) caused segmental malformations in late embryos and in hatched larvae. Mutant phenotypes correlate with repair by non-homologous end-joining (NHEJ) lesions in the two targeted genes. This simple and highly effective Cas9 RNP-based gene editing to introduce mutations in C. capitata will significantly advance the design and development of new effective strategies for pest control management.

The Mediterranean fruitfly Ceratitis capitata (medfly) is an invasive agricultural pest of high economical impact and has become an emerging model for developing new genetic control strategies as alternative to insecticides. Here, we report the successful adaptation of CRISPR-Cas9-based gene disruption in the medfly by injecting in vitro pre-assembled Cas9 ribonucleoparticles (RNP) loaded with gene-specific sgRNAs into early embryos. When targeting the eye pigmentation white eye (we), a high rate of somatic mosaicism was observed in surviving G0 adults. Germline transmission of mutated we alleles was found in the progeny of more than 70% of G0 flies. Large deletions were recovered in the we gene when two sites were simultaneously targeted by duplex sgRNAs. CRISPR-Cas9 targeting of the Ceratitis ortholog of the Drosophila segmentation paired gene (Ccprd) caused segmental malformations in late embryos and irregular muscular contractions in hatched larvae. Mutant phenotypes correlate with presence of non-homologous end joining (NHEJ) lesions in the two targeted genes. This simple and highly effective method for gene editing together with the availability of genome and transcriptome sequences will significantly advance our knowledge on gene function and regulation in Ceratitis as well as improve design and development of new effective strategies for pest control management.

In insects, rapidly evolving primary sex-determining signals are transduced by a conserved regulatory module producing sex-specific proteins that direct sexual differentiation1-4. In the agricultural pest Ceratitis capitata (medfly), a Y-linked Maleness factor (M) is thought to repress the autoregulatory splicing of transformer (Cctra), which is required in XX individuals to establish and maintain female sex determination5,6. Despite the sequencing of the medfly genome, its M factor has remained elusive7. Here, we report the identification of a Y-linked gene, Maleness-on the-Y (MoY), and show that it encodes a small and novel protein which is both necessary and sufficient for medfly male sex determination. CRISPR-induced MoY mutants can develop into fertile XY females and expression of MoY in XX individuals can produce fertile males. indicating that, irrespective of its karyotype, sexual fate of the germline follows that of the soma. In contrast to the molecular diversity of the Y-linked M factors isolated in related or within the same dipteran species8-11, we found Y-linked MoY orthologues in seven other Tephritid species spanning ~111 millions of years of evolution, and confirmed their male determining function in the olive fly (Bactrocera oleae) and the oriental fruit fly (Bactrocera dorsalis). Interestingly, in contrast to M factors of other dipteran species, MoY ectopic embryonic expression fully masculinized XX individuals. MoY evolutionary conservation in a large number of important agricultural pests12 widely distributed over four continents, will facilitate the development of transferable genetic control strategies in these species, for example sterile male release or sex-ratio-distorting gene drives.

Background and Objectives: The human brain presents a functional asymmetry for every cognitive function, and it is possible that sexual hormones could have an impact on it. Visual–spatial attention, one of the most lateralized functions and one that is mainly dependent on the right hemisphere, represents a sentinel for functional cerebral asymmetry (FCA). The aim of this study was to evaluate whether menopausal hormone therapy (MHT) or phytoestrogens could modulate FCA in postmenopausal women. Materials and Methods: We enrolled postmenopausal women who were taking MHT or soy isoflavones or receiving no therapy and asked them to perform the line bisection test at study enrollment and after 18 and 36 months. Results: Ninety women completed the follow-up. At zero time, women who had not been subjected to therapy showed a leftward deviation (F = −3.0), whereas, after 36 months, the test results showed a rightward deviation (F = 4.5; p < 0.01). Women taking MHT showed a leftward deviation at the start (F = −3.0) and a persistent leftward deviation after 36 months (F = −4.0; p = 0.08). Conversely, women taking soy isoflavones started with a leftward deviation (F = −3.0) that became rightward (F = 3.0), with a significant difference shown after 36 months (p < 0.01). Conclusions: Our data suggest that hormonal modulation improves the interplay between the two hemispheres and reduces FCA. We propose, therefore, that the functions of the right hemisphere are mainly affected by aging and that this could be one of the reasons why the right hemisphere is more susceptible to the effects of MHT.