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Abstract The availability of static tiny optical devices is mandatory to reduce the complexity of optical paths that typically use dynamic optical components and/or many standard elements for the generation of complex states of light, leading to unprecedented levels of miniaturization and compactness of optical systems. In particular, the design of flat and integrated optical elements capable of multiple vector beams generation with high resolution in the visible and infrared range is very attractive in many fields, from life science to information and communication technology. In this regard, we propose dual-functional transmission dielectric metalenses that act simultaneously on the dynamic and geometric phases in order to manipulate independently right-handed and left-handed circularly polarized states of light and generate focused vector beams in a compact and versatile way. In the specific, starting from the mathematical fundamentals for the compact generation of vector beams using dual-functional optical elements, we provide the numerical algorithms for the computation of metaoptics and apply those techniques to the design and fabrication of silicon metalenses which are able to generate and focus different vector beams in the telecom infrared, depending on the linear polarization state in input. This approach provides new integrated optics for applications in the fields of high-resolution microscopy, optical manipulation, and optical communications, both in the classical and single-photon regimes.

Abstract COVID-19 vaccines have dramatically reduced rates of severe infection requiring hospitalization. However, SARS-CoV-2 variants have reduced vaccine effectiveness at preventing any symptomatic infection. This real-world study analyzed binding and neutralizing antibodies generated after complete vaccination and boosting across three vaccine platforms. Binding antibodies decayed most slowly in people under 60 with hybrid immunity. Neutralizing antibodies against Omicron BA.1 were reduced compared to other variants. The anamnestic anti-spike IgG response to the first boost was more pronounced than after the second boost. Monitoring of the effects of SARS-CoV-2 mutations on disease severity and the effectiveness of therapeutics is warranted.

Abstract Background AMBRA1 is an intrinsically disordered protein, working as a scaffold molecule to coordinate, by protein-protein interaction, many cellular processes, including autophagy, mitophagy, apoptosis and cell cycle progression. The zebrafish genome contains two ambra1 paralogous genes (a and b), both involved in development and expressed at high levels in the gonads. Characterization of the zebrafish paralogous genes mutant lines generated by CRISPR/Cas9 approach showed that ambra1b knockout leads to an all-male population. Results We demonstrated that the silencing of the ambra1b gene determines a reduction of primordial germ cells (PGCs), a condition that, in the zebrafish, leads to the development of all-male progeny. PGC reduction was confirmed by knockdown experiments and rescued by injection of ambra1b and human AMBRA1 mRNAs, but not ambra1a mRNA. Moreover, PGC loss was not rescued by injection with human AMBRA1 mRNA mutated in the CUL4-DDB1 binding region, thus suggesting that interaction with this complex is involved in PGC protection from loss. Results from zebrafish embryos injected with murine Stat3 mRNA and stat3 morpholino suggest that Ambra1b could indirectly regulate this protein through CUL4-DDB1 interaction. According to this, Ambra1 +/− mice showed a reduced Stat3 expression in the ovary together with a low number of antral follicles and an increase of atretic follicles, indicating a function of Ambra1 in the ovary of mammals as well. Moreover, in agreement with the high expression of these genes in the testis and ovary, we found significant impairment of the reproductive process and pathological alterations, including tumors, mainly limited to the gonads. Conclusions By exploiting ambra1a and ambra1b knockout zebrafish lines, we prove the sub-functionalization between the two paralogous zebrafish genes and uncover a novel function of Ambra1 in the protection from excessive PGC loss, which seems to require binding with the CUL4-DDB1 complex. Both genes seem to play a role in the regulation of reproductive physiology.

Resumo Este artigo analisa sistemas de inteligência artificial como agentes temporalizadores em uma história mais do que humana. Engaja-se em uma discussão interdisciplinar abrangendo a sociologia dos algoritmos, a ética informacional e a filosofia da mente para, com base na teoria da história, avaliar como a onipresença da automação adiciona novas dimensões ao estudo da condição histórica contemporânea. O argumento diz que a temporalização artificial se origina da simulação da linguagem natural por meio de algoritmos de aprendizado. O artigo esclarece isso através de uma descrição em código e uma demonstração em imagem técnica, ilustrando a 'renderização' ou 'digitalização' de experiências humanas em padrões de dados, posteriormente replicados ou atualizados por agentes artificiais. Esse processo destaca a vetorização e manipulação estatística da experiência e representa o que denomino "computação necessária". Em contraste, o texto sugere que uma "computação contingente", capaz de produzir algo novo, transcende o mero discurso técnico. Assim, enfatiza-se o papel da ética e transparência na gestão de dados e no treinamento de sistemas de IA, cruciais para compreender a Inteligência Artificial como um campo histórico aberto a formas cognitivas potencialmente não-humanas.

No Brasil, o estado de Mato Grosso é o principal produtor de soja, sua produção colabora com cerca de 29% da produção nacional. A produtividade das plantas de soja está relacionada, dentre outras atividades, com o manejo correto de doenças, essa eficiência no manejo fúngico ocorre principalmente quando se tem conhecimento das características do microrganismo alvo. Portanto, o objetivo deste trabalho foi avaliar a sensibilidade de Colletotrichum plurivorum e Colletotrichum truncatum a fungicidas disponíveis no mercado. Foram realizados ensaios em placas de Petri, com os fungicidas homogeneizados em meio de cultura batata-dextrose-ágar (BDA) e posterior incubação em incubadora com Demanda Bioquímica de Oxigênio (BOD). Avaliou-se o crescimento micelial diariamente, esporulação e germinação de esporos. Os ensaios comprovaram que C. plurivorum e C. truncatum possuem sensibilidade diferente aos ingredientes ativos estudados, sendo que C. plurivorum apresenta maior sensibilidade aos produtos. O fungicida Mancozebe e a associação Azoxistrobina + Mancozebe + Protioconazol proporcionaram eficiente controle no desenvolvimento de C. truncatum. Os fungicidas Picoxistrobina + Benzovindiflupir e Azoxistrobina + Mancozebe + Protioconazol, promoveram maior eficiência no controle de C. plurivorum.

Introdução: Sabe-se que o programa de Stewardship é uma importante ferramenta para manejar a resistência bacteriana e sua principal estratégia é tratar o paciente com o antimicrobiano (ATM) certo, na dose certa e no tempo certo. Entre os profissionais atuantes no Stewardship, cabe ao farmacêutico clínico avaliar a prescrição médica, acompanhar os exames laboratoriais e protocolos institucionais e realizar intervenções relacionadas ao uso de medicamentos. Objetivo: Identificar as intervenções realizadas pelo farmacêutico relacionadas ao uso de ATM em prescrições de pacientes adultos de um hospital de nível terciário de Londrina no ano de 2022, categorizando as intervenções e demonstrar o papel do farmacêutico no programa de Stewardship. Métodos: Estudo realizado em um hospital de nível terciário, as intervenções farmacêuticas relacionadas a ATM realizadas no período de 2022, foram classificadas conforme a ferramenta PRAT (identificação do problema relacionado a terapia antimicrobiana) baseada na classificação de problemas relacionados a medicamentos, sendo categorizadas como intervenções relacionadas a indicação, efetividade ou segurança. Resultados: Foram avaliadas 22069 prescrições e realizadas 1843 intervenções farmacêuticas relacionadas aos ATM, sendo 45% relacionadas à segurança (potencial de reação adversa ou toxicidade), 38% à efetividade (questionamento do efeito terapêutico antiinfecioso), 10% à indicação (necessidade ou não do antimicrobiano ou à indicação ou não do uso de acordo com parâmetros clínicos e laboratoriais) e 7% que não se enquadram nas categorias anteriores. As principais intervenções realizadas foram referentes às interações medicamento-medicamento (31%), sendo realizado o reaprazamento dos medicamentos para resolução do problema. A dose prescrita está relacionada a 24% dos problemas encontrados, sendo realizado o ajuste da dose como intervenção, seguido por prescrição de medicamento desnecessário (11%), sendo sugerido então a suspensão do ATM. Problemas relacionados a frequência, intervalo de administração, são de 8% e problemas relacionados a administração do medicamento são 7%. Conclusão: Evidenciou-se que a análise criteriosa da prescrição pelo farmacêutico clínico e suas intervenções são fundamentais para garantir a segurança do paciente e para a efetividade do seu tratamento, contribuindo então para o uso racional de ATM que, redução da resistência bacteriana, o principal objetivo de um programa de Stewardship.

A hidroxiureia (HU) é um medicamento que aumenta os níveis de hemoglobina fetal nos eritrócitos, diminuindo complicações clínicas como vasoclusão, hemólise e inflamação sistêmica associadas à anemia falciforme (AF). Contudo, a HU interfere em aspectos essenciais do nicho hematopoiético, como a proliferação, a renovação e a diferenciação das células-tronco e progenitoras hematopoéticas (CTPHs). Isso limita as perspectivas de sucesso em procedimentos como o transplante de células-tronco e a terapia gênica, que são as únicas abordagens terapêuticas curativas. Considerando a falta de estudos na caracterização detalhada das CTPHs na AF, este estudo avaliou a integridade imunofenotípica das populações de CTPHs circulantes em pacientes com AF, tratados (HU, n = 10) ou não (CT, n = 7) com HU. Para tanto, as células mononucleares do sangue periférico (PBMC) de pacientes e doadores saudáveis (HD, n = 5) foram isoladas por gradiente de densidade e avaliadas por citometria de fluxo, utilizando um painel de anticorpos específico para CTPHs, além das moléculas CD49d e CD235a. A análise estatística foi conduzida por meio do teste de Kruskal-Wallis e do teste de comparações múltiplas de Dunn (p < 0.05). A contagem total de células viáveis CD34 é maior nos grupos com AF, sendo que o grupo HU apresentou a maior mediana. Os níveis de células CD34CD49d são maiores entre os pacientes dos grupos CT e HU. No que diz respeito ao compartimento de progenitores hematopoiéticos multipotentes (HMC), também foram observadas diferenças significativas na contagem total entre pacientes tratados com HU e controles (p < 0.01). As HMCs positivas para CD49d são mais frequentes no grupo CT, enquanto CD235a é mais presente no grupo HU. Ao analisar especificamente as células-tronco hematopoiéticas (HSC), observou-se que, diferentemente dos pacientes, os indivíduos controle não apresentam essas populações no sangue periférico, indicando que a presença dessas células na circulação é uma característica inerente à AF. Além disso, a mediana da quantidade de células HSCs positivas para CD49d e CD235a também é maior nos grupos CT e HU do que no grupo HD. Tendo em vista que o CD49d é um marcador de adesão e cinética hematopoiética, sua presença em maior quantidade nas células-tronco indica uma hematopoiese possivelmente ineficaz. Já a presença do CD235a junto ao marcador CD34 está relacionada com uma diferenciação celular acelerada. Esses achados evidenciam uma heterogeneidade imunofenotípica nas CTPHs nos indivíduos com AF e, principalmente, uma contribuição da HU para essas alterações. Além disso, mostram que parte das células envolvidas na hematopoiese desses indivíduos pode estar comprometida e, portanto, inadequada para terapias que envolvam edição gênica. Nas próximas etapas, ensaios para avaliação da capacidade de proliferação e diferenciação in vitro dessas populações e grupos de pacientes deverão ser executados para testar a funcionalidade das células sob a influência da HU. Financiamento: FUNDHERP, CTC/FAPESP (2013/08135-2), FAPESP (2022/09643-0), INCTC/CNPq (465539/2014-9).

Introduction: Hydroxyurea, the 1st line treatment for SCD, induces HbF, inhibiting polymerization of mutant HbS and cell sickling. However, laboratory tests that assess HbF induction do not quantify the % of effectively protected RBCs (%pRBC), i.e. those with HbF content (cHbF)>10 pg/RBC. While chromatography (HPLC) determines the HbF% among blood Hb (HbF%), classical flow cytometry (cFC) provides the % HbF+ RBCs (Fcell%), including RBCs with very little HbF. We have developed an unprecedented method of quantitative CF (qFC) that uses an internal cellular control, composed of samples of umbilical cord blood (UCB) and adult blood with known mean HbF contents (MCHbF), allowing the distribution of cHbF/RBC in the population is determined, including the %pRBC. Aim: Validate the method and demonstrate its potential clinical application in SCD. Methods: The MCHbF of 9 UCB samples were pre-calculated, multiplying the HbF% by the respective MCH obtained with a hematological analyzer, and compared with the MCHbF derived by qFC, in order to evaluate the correlation and linearity of the method. A total of 40 samples from 29 SCD (SS) patients had their hematimetric indices and %pRBC determined. From these, %Fcell (n = 27) and HbF% (n = 15) were obtained, totaling 12 samples characterized by all methods, which were evaluated for correlation between themselves and with hematimetric data. Hb10% had %Fcell>99%. In contrast, %pRBC correlated strongly and linearly across all HbF% (r = 0.89, p < 0.0001). In line, both HbF% and %pRBC showed significant positive correlations with RBC counts, Hb, and hematocrit (Hct); and negative correlations with the % reticulocytes (%Ret) and Red Cell Distribution Width (RDW). However, %Fcell correlated only with Hct. Considering all 27 samples evaluated, %Fcell correlated further only with Hb and RDW; however, %pRBC was further correlated positively with MCHC, and negatively with WB cells, Ret No, and % immature Ret. Correlations improved for all 40 samples. The potential of %pRBC to predict high-risk patients was much higher (AUC=0.969, p < 0.0001) than that of %Fcell (AUC=0.873, p = 0.0019), with a sensitivity of 94.4% and a specificity of 88.9%, for %pRBC

We report Zika virus (ZIKV) vertical transmission in 130 infants born to PCR+ mothers at the time of the Rio de Janeiro epidemic of 2015-2016. Serum and urine collected from birth through the first year of life were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM Zika MAC-ELISA. Four hundred and seven specimens are evaluated; 161 sera tested by PCR and IgM assays, 85 urines by PCR. Sixty-five percent of children (N = 84) are positive in at least one assay. Of 94 children tested within 3 months of age, 70% are positive. Positivity declines to 33% after 3 months. Five children are PCR+ beyond 200 days of life. Concordance between IgM and PCR results is 52%, sensitivity 65%, specificity 40% (positive PCR results as gold standard). IgM and serum PCR are 61% concordant; serum and urine PCR 55%. Most children (65%) are clinically normal. Equal numbers of children with abnormal findings (29 of 45, 64%) and normal findings (55 of 85, 65%) have positive results, p = 0.98. Earlier maternal trimester of infection is associated with positive results (p = 0.04) but not clinical disease (p = 0.98). ZIKV vertical transmission is frequent but laboratory confirmed infection is not necessarily associated with infant abnormalities.

The new nopine genus Roddenberryus gen. nov. is erected to include in total five species: three new species, R. kirk gen. et sp. nov. (male and female) from Costa Rica, R. spock gen. et sp. nov. (female) from Campeche, Mexico and R. mccoy gen. et sp. nov. (male) from Baja California Sur, Mexico, as well as two species previously misplaced in Caponina Simon, i.e., R. sargi (Pickard-Cambridge, 1899) gen. et comb. nov. from Guatemala and R. pelegrina (Bryant, 1940) gen. et comb. nov. from Cuba. A male specimen reported as C. sargi Pickard-Cambridge from Costa Rica by E. Kritscher (1957) is assigned to Roddenberryus kirk together with one female collected at the same locality. The new genus is characterized by the distally projected endites and a triangular, projected labium, a conformation unique among nopines; also by a triangular, very short, scaly gladius, serrula with interspersed multiple tooth rows, and a tarsal organ with strongly projected margins. Roddenberryus shares with Tarsonops Chamberlin the cracked tarsi and metatarsi, with multiple adesmatic joints intertwined on the cuticle and an unusual internal respiratory system with both posterior tracheae fused in a single trunk.

We describe an enzymatic fuel cell (EFC) that can electrooxidize glucose completely. The EFC contains the hybrid Ni@Pt-CNT/OxOx bioanode, composed of a bimetallic composite catalyst (Ni@Pt-CNT) and the enzyme oxalate oxidase (OxOx), which can cleave carbon-carbon bonds. Ni@Pt-CNT/OxOx displayed 3-fold higher catalytic activity in the presence than in the absence of glucose (1.3 and 0.4 mA cm−2, respectively), indicating that Ni@Pt-CNT and OxOx acted synergistically. Electrochemical impedance spectroscopy showed that Ni@Pt-CNT/OxOx had higher charge transfer resistance and double layer capacitance than Ni@Pt-CNT. Long-term bulk electrolysis (18 h) revealed that the EFC operating with Ni@Pt-CNT/OxOx presented better current density and stability than the electrochemical cell operating with Ni@Pt-CNT, so deep glucose electrooxidation generated energy. The glucose oxidation products detected by HPLC-UV/RID confirmed that glucose was fully electrooxidized, and that 24 electrons were harvested from it. The hybrid Ni@Pt-CNT/OxOx bioanode developed herein could be used in cascade reactions, to provide an EFC with promising application in self-powered electronic devices.

The objective of this perspective paper is to present and discuss how systemic innovations can deliver a step change in the way food is produced in Europe. The production of healthy, safe and affordable food can contribute toward a just transition to net zero carbon (C) for Europe. A systemic and cross sectorial approach can contribute to climate mitigation by transfer of atmospheric CO2 to the terrestrial biosphere using low trophic species (LTS), including plants, seaweed and mussels (i.e. C sequestration) and increasing organic C stocks in soils and vegetation biomass (i.e. C storage). Innovative combinations of technologies applied to LTS, processed animal protein, new crops, and diversified and integrated production systems can link the high primary productivity rates of the marine environment to the C storage capability of the terrestrial food sector. Furthermore, the important roles of both private and public sector actors and better use of systemic approaches to further elucidate the multi-dimensional and multi-level interplays in complex food systems needs consideration. This can pave the way for linking and scaling up C-neutral marine and terrestrial food production systems into a future sustainable and circular bioeconomy. This systems-based approach can address some of the challenges associated with the current farming systems, as interdisciplinary research on aquaculture innovation can support the development of a resilient and sustainable food system. Examples of technologies provided include: a custom configured and digital user-oriented co-creation approach for Responsible Research and Innovation (RRI), a WebGIS tool on soil C storage, innovative composting methods, advanced breeding methods, new machinery for low greenhouse gas diversified orchard farming, AI model systems to improve decision support systems in management of soil, vertical farming, and animal feeding.

The pericellular matrix (PCM) is a specialized extracellular matrix that surrounds cells. Interactions with the PCM enable the cells to sense and respond to mechanical signals, triggering a proper adaptive response. Collagen VI is a component of muscle and tendon PCM. Mutations in collagen VI genes cause a distinctive group of inherited skeletal muscle diseases, and Ullrich congenital muscular dystrophy (UCMD) is the most severe form. In addition to muscle weakness, UCMD patients show structural and functional changes of the tendon PCM. In this study, we investigated whether PCM alterations due to collagen VI mutations affect the response of tendon fibroblasts to mechanical stimulation. By taking advantage of human tendon cultures obtained from unaffected donors and from UCMD patients, we analyzed the morphological and functional properties of cellular mechanosensors. We found that the length of the primary cilia of UCMD cells was longer than that of controls. Unlike controls, in UCMD cells, both cilia prevalence and length were not recovered after mechanical stimulation. Accordingly, under the same experimental conditions, the activation of the Hedgehog signaling pathway, which is related to cilia activity, was impaired in UCMD cells. Finally, UCMD tendon cells exposed to mechanical stimuli showed altered focal adhesions, as well as impaired activation of Akt, ERK1/2, p38MAPK, and mechanoresponsive genes downstream of YAP. By exploring the response to mechanical stimulation, for the first time, our findings uncover novel unreported mechanistic aspects of the physiopathology of UCMD-derived tendon fibroblasts and point at a role for collagen VI in the modulation of mechanotransduction in tendons.

Neonatal calf diarrhoea (NCD) poses a significant health challenge in cattle herds, resulting in considerable economic losses and antimicrobial use. In response to the escalating threat of antimicrobial resistance, viable alternatives are imperative, aligning with European policies. This study evaluated the in-milk supplementation of the chestnut and quebracho tannin extract in preweaning calves on performance, diarrhoea occurrence, Cryptosporidium spp. shedding, protein digestibility, and intestinal health. Twenty newborn calves were divided, after colostrum administration, into two experimental groups for 30 days as follows: the control (CTRL) was fed with whole milk and solid feed, and tannins (TAN) were fed whole milk supplemented with 6/g day of tannin extract and solid feed. Faecal samples were collected on days 0, 3, 7, 14, and 30 for the evaluation of Cryptosporidium oocyst shedding and protein digestibility. Faecal consistency was evaluated during the sampling using the faecal score scale (0–3 scale, considering diarrhoea > 1). The results showed a significant reduction in diarrhoea frequency in the TAN compared to the CTRL group (p < 0.05) over 30 days of the trial. The prevalence of Cryptosporidium spp. was generally low (12%), considering all analysed samples. Protein digestibility revealed comparable values for the TAN and CTRL groups, suggesting that tannins did not negatively affect milk protein availability. In conclusion, the in-milk supplementation of 6/g day of the chestnut and quebracho tannin extract could be considered a valuable functional feed additive to decrease NCD occurrence, thus supporting animal health and decreasing antibiotic use in livestock.

Recent data in a nonhuman primate model showed that infants postnatally infected with Zika virus (ZIKV) were acutely susceptible to high viremia and neurological damage, suggesting the window of vulnerability extends beyond gestation. In this pilot study, we addressed the susceptibility of two infant rhesus macaques born healthy to dams infected with Zika virus during pregnancy. Passively acquired neutralizing antibody titers dropped below detection limits between 2 and 3 months of age, while binding antibodies remained detectable until viral infection at 5 months. Acute serum viremia was comparatively lower than adults infected with the same Brazilian isolate of ZIKV (n = 11 pregnant females, 4 males, and 4 non-pregnant females). Virus was never detected in cerebrospinal fluid nor in neural tissues at necropsy two weeks after infection. However, viral RNA was detected in lymph nodes, confirming some tissue dissemination. Though protection was not absolute and our study lacks an important comparison with postnatally infected infants born to naïve dams, our data suggest infants born healthy to infected mothers may harbor a modest but important level of protection from postnatally acquired ZIKV for several months after birth, an encouraging result given the potentially severe infection outcomes of this population.

Abstract Background Maintaining healthy mitochondria is mandatory for muscle viability and function. An essential surveillance mechanism targeting defective and harmful mitochondria to degradation is the selective form of autophagy called mitophagy. Ambra1 is a multifaceted protein with well‐known autophagic and mitophagic functions. However, the study of its role in adult tissues has been extremely limited due to the embryonic lethality caused by full‐body Ambra1 deficiency. Methods To establish the role of Ambra1 as a positive regulator of mitophagy, we exploited in vivo overexpression of a mitochondria‐targeted form of Ambra1 in skeletal muscle. To dissect the consequence of Ambra1 inactivation in skeletal muscle, we generated muscle‐specific Ambra1 knockout (Ambra1fl/fl:Mlc1f‐Cre) mice. Mitochondria‐enriched fractions were obtained from muscles of fed and starved animals to investigate the dynamics of the mitophagic flux. Results Our data show that Ambra1 has a critical role in the mitophagic flux of adult murine skeletal muscle and that its genetic inactivation leads to mitochondria alterations and myofibre remodelling. Ambra1 overexpression in wild‐type muscles is sufficient to enhance mitochondria clearance through the autophagy‐lysosome system. Consistently with this, Ambra1‐deficient muscles display an abnormal accumulation of the mitochondrial marker TOMM20 by +76% (n = 6–7; P

The capacity of utilising a single cell protein (SCP) ingredient coming from Corynebacterium glutamicum was assessed on adult grey mullet (Mugil cephalus) reared in captive conditions. The experiment was carried out using triplicate groups of grey mullet of 68 g average initial body weight. Three diets, SCP0, SCP10 and SCP20 with increasing inclusion of SCP (0%, 10% and 20%) in substitution of soybean, poultry and fish meal were formulated to contain 30% protein, 10% fat and 18.5 Mj/kg feed of digestible energy. After 113 days, fish fed SCP diets presented significantly lower growth performance and a significant lower activity of the alkaline proteases and aminopeptidases compared to fish fed diet without SCP inclusion. Gut microbiota appeared modulated by SCP inclusion being dominated at the phylum level by Fusobacteria in fish fed SCP0 (51.1%), while in fish fed SCP10 (67.3%) and SCP20 (53.2%) Proteobacteria was dominant. Data evinces a deficiency in the protein utilisation as a cause of the poor growth performance in fish fed the SCP diets. A hypothesis has been proposed that an incomplete SCP cell-wall lysis accounts for this outcome because of the particular organisation of the digestive system of grey mullet (which lack of an acidic stomach digestion) and the failing in the development of a functional gizzard (no access to sand in captive conditions). Even though the outcomes of this research were quite unexpected, they will improve our knowledge on the digestive system of flathead grey mullet and provide some theoretical basis for an improved development of low FM and SBM aquafeed for the species.

Nowadays functional ingredients have a significant potential for improving current low fish meal (FM) aquafeed formulation in sustaining growth and enhancing animal robustness for Mediterranean aquaculture. Among them, nucleotides (NT) and nucleic acids (NA) drew attention for their application in the last two decades. NT are organic molecules involved in many life-supporting pathways, and are the building blocks of NA, which stand as genetic repositories. NT are naturally present in organic ingredients, and among them FM is known to be one of the highest NT sources. When this NT source is seriously limited, fish might be under the minimum NT requirements, especially in fast growing life stages of carnivorous species. Hence, a trial on European sea bass juveniles was carried out, testing two dietary FM levels (FM10, FM20 as 10% and 20% FM, respectively) supplemented with 500 mg kg-1 yeast-originate NT or NA dose over 80 days. Thereafter, fish were exposed to one week of sub-optimal thermal and dissolved oxygen condition (30°C and 4.0 mg/L O2) to further explore the effect of NT and NA inclusion on immune response and gut microbiome alteration. At the end of the growth period NT increased feed intake at both FM dietary levels. FM20 combined with NA and NT further improved growth performance, enhancing lipid efficiency and increased anti-inflammatory TGF-β. After sub-optimal environmental conditions both NT and NA exerted prebiotic functions on gut microbiome by promoting beneficial lactic acid bacteria such as Weissella and Leuconostoc. At the same time NT in 10% FM diet increased the abundance of Bacillus taxon. In conclusion, the combination of NT/NA included at 500 mg kg-1 was able to promote growth when included in 20% FM level, assuming higher nutritional NT requirement when combined with 10% FM. On the other hand, NT/NA added in 10% FM upregulate proinflammatory IL-1β and favor beneficial gut bacterial taxa.