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The use of livestock manure as agricultural soil amendments is a significant source of ammonia emissions and nitrate leaching. Anaerobic digestion of manure can yield to solid and liquid by-products usable as fertilizers that can limit these negative impacts. They could be further supplemented with plant growth-promoting microorganisms (PGPM) to improve plant growth and yield. This study investigated the impact of PGPMs and anaerobic digestates on strawberry quality and rhizospheric microbial community. Strawberry plants were grown in soils treated with PGPMs (pure culture of Azospirillum brasilenseor a commercial product with effective microorganisms) along with either liquid or solid digestate. Effects of digestates and PGPMs were evaluated by measuring plant yield and nutraceutical values, while the rhizospheric microbial community was assessed through an eDNA metabarcoding approach. Results suggest using PGPMs combined with digestates enhances plant yield, with increases of up to 40-60% in fruit yield and 9-18% in nutraceutical value, compared to the controls. The rhizospheric microbial community was influenced only by digestates. Nevertheless, these alterations have not led to significant changes in the community, thus ensuring its long-term stability. Moreover, PGPMs were not detected into the rhizospheric community. Our data pointed out that both PGPMs and digestates can represent a sustainable approach to increase strawberry plant yield. However, PGPMs require repeated inoculations in long-term projects to achieve and maintain desired outcomes. These findings emphasize the complexity of rhizospheric microbial interactions and underscore the importance of continued research to optimize agricultural practices while maintaining ecosystem stability.

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The continuous-flow, gas-phase oxidative dehydrogenation (ODH) of an actual mixture of decen-1-ol isomers (“Isorosalva” alcohol) towards the corresponding mixture of aldehydes (“Costenal” analogues, valuable ingredients in perfumes formulation) is herein reported for the first time over noble metal-free catalysts. In particular, the optimisation of the reaction conditions over a copper ferrite (Cu/Fe/O), as well as dedicated characterizations and comparisons between the fresh, the post-reaction (reduced) and regenerated (re-oxidised) catalytic material, allowed us to underline the key role of well dispersed copper oxide over a Fe-enriched spinel in promoting the selective ODH of Isorosalva alcohol. The superior catalytic activity and selectivity of CuO/γ-Fe2O3synthesized ad hocwere attributed to the very high dispersion of Cu over the support as well as to a cooperative effect between Cu and Fe species in promoting the redox cycle.

PI3K pathway plays a crucial role in dendritic cells (DCs) functions, as it regulates different cellular processes, such as maturation and cytokines production. However, the specific role of PI3K p110δ isoform in human DCs has not been thoroughly addressed. In this study, we analyze the effects of seletalisib, a potent and specific inhibitor of PI3K p110δ, on phenotype and antigen‐presenting functions of monocyte‐derived DCs undergone maturation via LPS. Seletalisib treatment reduced membrane HLA‐DR as well as CD83 and CD40 costimulatory molecules, whereas CD80 and CD86 expression was only partially affected. Additionally, DCs cultures showed reduced TNF‐α, IL‐10, and IL‐12 and increased IL‐23 secretion levels. This resulted in a reduced capacity of DCs to prime allogeneic T cells, with a strong decrease of Th1 differentiation. On the other hand, PI3K p110δ inhibitor seletalisib increased CXCR4 and CCR7 expression and augmented the DCs migration toward CCL19 and CXCL12 ligands. At molecular level, inhibition of PI3K p110δ isoform by seletalisib significantly down‐regulated the phosphorylation of AKT and other downstream signaling molecules, such as ribosomal protein S6, 4E‐BP1, and NF‐κB p65. In contrast, seletalisib did not affect p38 MAP kinase phosphorylation or TLR‐associated adapter molecule TIRAP in DCs. Our results indicate that PI3K p110δ can serve as an important regulatory signal for DCs, and selective inhibition of PI3K p110δ isoform by seletalisib could be used for the prevention of exaggerated and harmful immune responses occurring in pathologic conditions, such as autoimmune disorders. The study demonstrate that the PI3K‐δ inhibitor Seletalisib impairs maturation of DCs while increasing expression of chemokine receptor involved in DC migration toward lymph nodes

The aim of the study was to evaluate the validity and safety of Ottawa's ankle rules (OAR) in the urgency department of referral hospital in Peru.

(Abstracted from Prenat Diagn2022;42:1575–1586Methods for diagnosis of genetic abnormalities have recently undergone substantial improvement. Noninvasive prenatal testing (NIPT) is performed early in pregnancy, typically at the end of the first trimester using cell-free DNA (cfDNA) to identify 3 commonly occurring trisomies (13, 18, and 21).

The Non-centred Reticular Structure is a modular pattern developed by Cesare Leonardi (Modena, Italy, 1935) from 1983, the result of research into spatial and urban planning focusing on trees. It is a model of spatial organization seeking a balance between the spaces of people and those of trees, reconciling and promote all living forms. The Structure consists of a primary pattern of 23 irregular polygons defining the areas belonging to each stakeholder in the spatial organisation: humans, plants, animals. The sides of the polygon constitute a network of nodes (vertices) and connecting rods. The pattern may evolve in space and time, combining biomimicry and geometry, and adapts to different contexts through metamorphosis and deformations. The Structure was applied to ‘Bosco Albergati’ Park (Modena, Italy) which, 30 years after planting, represents an example of spatial organisation imitating nature. This paper presents the Structure as a tool supporting the designer in the spatial organisation of the functional design elements, and investigates its relevance in the design of current green projects.

An experimental study on how to reduce the content of singly ionized zinc vacancy (V−Zn) in ZnGeP2crystals to improve their optical quality is presented. Their electron paramagnetic resonance signal has been studied in samples treated in different ways. The data provide a scheme of the reductions that can be obtained by the different methods or by their combinations. The adding of Sn during the synthesis phase helps the production of large‐size single crystals and the reduction of the V−Zncontent. Thermal treatment and electron irradiation are then needed for further reduction. At the fluence of 2 × 1017e cm−2, the V−Zndecrease does not reach a minimum value, so with higher fluences, additional reduction of V−Zncontent is expected. The combination of Sn addition, thermal annealing, and electron irradiation is able to reduce the content of single‐ionized zinc vacancies in ZnGeP2single crystals. As the presence of these defects limits the use of ZnGeP2in nonlinear optic applications, the present method can be used to overcome the actual limitation.

To explore alternative applications of gallium(iii) oxide and co-precipitated Ga(iii)/M(ii) oxides (MMg, Ca, and Sr), we investigate the relative dehydrogenation/dehydration activity of nanostructured gallia for alcohols viaelectronic structure calculations, reactivity tests and DRIFT-IR spectroscopy. Computing the relative reaction barriers with all electron DFT and split-valence basis sets for a panel of 11 alcohols suggested dehydrogenation to be the most active process catalysed by gallia for both primary and secondary alcohols despite its fundamentally acidic behaviour, which was previously suggested to foster dehydration. A key contribution in defining the most active channel is also provided by the interaction between the alcohol carbon skeleton and gallia surface. The only deviation from the relative reactivity just discussed is found for 1-phenyl ethanol, an outcome easily rationalized by the conjugated nature of the nearly-carbocationic TS leading to styrene. Catalytic tests on methanol, ethanol, and 1- and 2-propanol at 400 °C supported the proposed relative selectivity; besides, the recorded alcohol total conversions and product yields agree well with what was proposed by the DFT reaction profiles, thus demonstrating the predictive capability of the chosen electronic structure approach. Finally, temperature programmed DRIFT spectroscopy on the aliphatic C3 alcohols was able to characterize the adsorbed reactants, intermediates, and products, fully supporting the picture described by the theoretical modelling and the reactivity tests. In conclusion, the lower acidity of Ga(iii), due to its semi-metallic nature and its larger ionic radius, compared to that of Al(iii), leads to opposite selectivity in the competition between alcohol dehydrogenation and dehydration at 400 °C, with the oxide of the latter ion being known to preferentially produce olefins.

1,6-Hexanediol is one of the most relevant building blocks originating from biomass and it transforms into adipic acid for polymer synthesis. Herein, we examine the selective oxidation of 1,6-hexanediol to adipic acid over Au-based catalysts, in the aqueous phase, under base-free conditions. Particularly, the absence of a base allows the neutralization step at the end of the reaction to be avoided. The influences of various supports (MgO, BaO, NiO, and TiO2) and substrate/gold molar ratios were studied. Under the conditions used, the leaching of Mg in the mixture of MgF2and MgO was limited by diluting the basic sites in the support. The highest selectivity to adipic acid (43%) was achieved at 110 °C under 15 bar of air in the presence of 2 wt% Au/0.6MgF2–0.4MgO.

•Fluconazole pharmacokinetics is significantly altered in critically ill burn patients.•Half-life and total body clearance were correlated to volume of distribution decrease.•High-dose fluconazole may be necessary to guarantee coverage against Candida glabrata.

Given the current prolonged life expectancy, various pathologies affect increasingly the aging subjects. Regarding the musculoskeletal apparatus, bone fragility induces more susceptibility to fractures, often not accompanied by good ability of self-repairing, in particular when critical-size defects (CSD) occur. Currently orthopedic surgery makes use of allografting and autografting which, however, have limitations due to the scarce amount of tissue that can be taken from the donor, the possibility of disease transmission and donor site morbidity. The need to develop new solutions has pushed the field of tissue engineering (TE) research to study new scaffolds to be functionalized in order to obtain constructs capable of promoting tissue regeneration and achieve stable bone recovery over time. This investigation focuses on the most important aspect related to bone tissue regeneration: the angiogenic properties of the scaffold to be used. As an innovative solution, scleral ossicles (SOs), previously characterized as natural, biocompatible and spontaneously decellularized scaffolds used for bone repair, were tested for angiogenic potential and biocompatibility. To reach this purpose, in ovoChorioallantoic Membrane Assay (CAM) was firstly used to test the angiogenic potential; secondly, in vivosubcutaneous implantation of SOs (in a rat model) was performed in order to assess the biocompatibility and the inflammatory response. Finally, thanks to the analysis of mass spectrometry (LCMSQE), the putative proteins responsible for the SO angiogenic properties were identified. Thus, a novel natural biomaterial is proposed, which is (i) able to induce an angiogenic response in vivoby subcutaneous implantation in a non-immunodeficient animal model, (ii) which does not induce any inflammatory response, and (iii) is useful for regenerative medicine application for the healing of bone CSD.

In the past years, consumers' concerns about sustainability and animal welfare have increased, strengthening the demand for eggs and meat produced through alternative and extensive farming methods. In addition, producers have also become increasingly interested in the recovery and exploitation of local breeds due to their adaptability to local environmental conditions, to valorize the biodiversity and to provide added value to typical products. Among the Italian local breeds, Romagnola has almost risked extinction and currently is reared in small-scale farms for eggs and meat production. The aim of this study was to characterize the egg quality traits of Romagnola chicken breed (RMG) compared to those obtained by a commercial hybrid (CONV). Ten laying hens of both Romagnola breed and Hy-Line Brown at 40 wk of age were housed in the same outdoor pen and fed the same commercial feed (ME 2,830 kcal/kg, CP 17.2%) for 10 wk. At 5 and 10 wk after housing, all the eggs laid in 4 consecutive days were collected and used for the determination of egg and eggshell characteristics as well as proximate composition and fatty acid profile of egg yolk. As expected, some important productive traits such as egg weight and production resulted higher in CONV chickens. However, eggs from RMG hens presented a higher yolk/egg ratio (31.1 vs. 24.9%; P < 0.01) as well as carotenoids (36.8 vs. 20.2 ppm; P < 0.01) and cholesterol content (12.8 vs. 11.7 mg/g of yolk; P < 0.01) than those laid by the conventional genotype. Moreover, yolks from RMG eggs were characterized by lower polyunsaturated fatty acid (PUFA) n-6 content (22.6 vs. 28.4%; P < 0.01) and PUFA n-6/n-3 ratio (11.3 vs. 13.5; P < 0.01) showing a healthier fatty acids profile than conventional eggs. These results highlighted several valuable egg quality traits of Romagnola chicken breed that might be exploited for the conservation and the development of this underutilized Italian pure breed.

We studied the vapour-phase oxidative dehydrogenation (ODH) of ethyl lactate with air to give ethyl pyruvate over V2O5/TiO2catalysts in a fixed-bed reactor. The nature of the vanadia species is changed by varying the vanadium surface density, and the corresponding structure of the VOxspecies was determined by XRD, UV-vis spectroscopy, XPS and H2-TPR. Monomeric and isolated vanadia species dominate at lower vanadium surface densities. As the surface density increases, two-dimensional polyvanadates and bulk-like vanadia crystallites become predominant. The activity per vanadium decreases with increasing vanadium surface density, indicating that the monomeric VOxspecies is better for pyruvate production and that the V–O–Ti bonds play an important role in the ODH of ethyl lactate. This is also confirmed by the superior catalytic performance of V2O5/TiO2compared to vanadium supported on MgO, Al2O3, ZrO2and CeO2. In situDRIFT spectroscopy coupled with mass analysis shows that the reaction can involve three possible adsorption modes of ethyl lactate on the V2O5/TiO2surface.Under anaerobic conditions, 2-hydroxypropionate forms, giving ethyl acetate as the major product. Conversely, under aerobic conditions, oxygen that is chemisorbed on V2O5/TiO2is active and easily replenished from the gas phase, converting the ethyl-propionate-2-oxide intermediate into ethyl pyruvate.

A range of organic carbonates was synthesised from dimethylcarbonate (DMC) and different alcohols by base-catalysed carbonate interchange reactions (CIRs). Dimethyl carbonate – used as a green and efficient reagent as well as the reaction solvent – was coupled to methanol-removing systems to break the reaction equilibrium and thus obtain near quantitative yields of the desired carbonates. Two different methanol-removing systems are described, one based on azeotropic distillation (reactive azeotropic distillation, RAD) and one based on methanol absorption (reactive vapour absorption, RVA). A comparison between the two systems is described and some conclusions based on reaction metrics are discussed. The methods were applied to the synthesis of aliphatic asymmetric alkyl-methyl carbonates and to the synthesis of catechol carbonate, using both homogeneous (NaOMe and trioctylmethylphosphonium methylcarbonate, P8881-MC) as well as heterogeneous (MgO) catalysts.

Recently the poultry industry faced an emerging muscle abnormality termed wooden breast (WB), the prevalence of which has dramatically increased in the past few years. Considering the incomplete knowledge concerning this condition and the lack of information on possible variations due to the intra-fillet sampling locations (superficial vs. deep position) and aging of the samples, this study aimed at investigating the effect of 7-d storage of broiler breast muscles on histology, texture, and particle size distribution, evaluating whether the sampling position exerts a relevant role in determining the main features of WB. With regard to the histological observations, severe myodegeneration accompanied by accumulation of connective tissue was observed within the WB cases, irrespective of the intra-fillet sampling position. No changes in the histological traits took place during the aging in either the normal or the WB samples. As to textural traits, although a progressive tenderization process took place during storage (P≤ 0.001), the differences among the groups were mainly detected when raw meat rather than cooked was analyzed, with the WB samples exhibiting the highest (P≤ 0.001) 80% compression values. In spite of the increased amount of connective tissue components in the WB cases, their thermally labile cross-links will account for the similar compression and shear-force values as normal breast cases when measured on cooked samples. Similarly, the enlargement of extracellular matrix and fibrosis might contribute in explaining the different fragmentation patterns observed between the superficial and the deep layer in the WB samples, with the superficial part exhibiting a higher amount of larger particles and an increase in particles with larger size during storage, compared to normal breasts.

Autoimmune skin lesions are characterized by a complex cytokine milieu and by the accumulation of plasmacytoid dendritic cells (pDCs). Granzyme B (GrB) transcript is abundant in activated pDCs, though its mechanisms of regulation and biological role are largely unknown. Here we report that IL-21 was the only T helper 1/T helper 17 cytokine able to induce the expression and secretion of GrB by pDCs and that this action was counteracted by the autocrine production of type I IFNs. In lupus erythematosus skin lesions, the percentage of GrB+pDCs directly correlated with the IL-21/MxA ratio, indicating that the interplay between these two cytokines finely tunes the levels of pDC-dependent GrB also in vivo. In lupus erythematosus, pDCs colocalized with professional cytotoxic cells at sites of epithelial damage, suggesting a role in keratinocyte killing. Accordingly, we demonstrate that supernatants of IL-21-activated pDCs promoted autologous keratinocyte killing by natural killer cells and this action was dependent on GrB. These results propose a GrB-dependent functional interaction between pDCs and natural killer cells and highlight a negative feedback regulation by type I IFNs in vitro and in vivo that may function to limit excessive tissue damage.

T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)–activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells. TSLP-induced T cells expressed CXCR5, CXCL13, ICOS, PD1, BCL6, BTLA, and SAP, among other Tfh markers. Functionally, TSLP-DC–polarized T cells induced IgE secretion by memory B cells, and this depended on IL-4Rα. TSLP-activated DCs stimulated circulating memory Tfh cells to produce IL-21 and CXCL13. Mechanistically, TSLP-induced Tfh differentiation depended on OX40-ligand, but not on ICOS-ligand. Our results delineate a pathway of human Tfh differentiation in Th2 environments.

To evaluate the effects of intrathecal morphine on pulmonary function, analgesia, and morphine plasma concentrations after cardiac surgery.

New insights on the gas-phase ammoxidation of ethanol to acetonitrile over supported vanadia catalysts were obtained by means of reactivity experiments (in ethanol ammoxidation and oxidation) as well as in situRaman and DRIFT spectroscopy. It was found that the rate-determining step during the redox process depends on the support type. In the case of V2O5/ZrO2, the V oxidation state under reaction conditions is closer to V5+, whereas with V2O5/TiO2, the reduction of V5+is faster than the re-oxidation of the corresponding reduced V species by O2; thus, the V oxidation state under steady state conditions is lower than for V2O5/ZrO2. In the latter catalyst, the more oxidized V species is responsible for ammonia activation and reaction with the intermediate acetaldehyde, leading in the end to a better acetonitrile yield than with V2O5/TiO2. It was also found that V2O5/ZrO2is more selective to acetaldehyde than V2O5/TiO2. With the former catalyst, ethanol is able to reduce V2O5only to a limited extent. Conversely, V2O5/TiO2is readily reduced by ethanol but this reduced V species is responsible for an unselective oxidation of the alcohol, giving more CO and CO2.

Skeletal metastases are a common cause of severe morbidity, reduction in quality of life and often early mortality. Consequently, improvements in therapies are necessary. Electroporation uses electric energy to alter cancer cell membrane permeability and enhance the local uptake of chemotherapeutics, thus leading to local tumor control. The aim of this study was to investigate the feasibility and safety of delivering electric field protocols causing electroporation of healthy bone and structures of clinical relevance using small and large animal models. Reversible electroporation was used in the rabbit sciatic nerve by applying 2 series of 8 pulses 100ms long at 1000 V/cm. Irreversible electroporation was used in rabbit distal femur condyles and in sheep vertebral body by applying 120 pulses 100ms long at 1750 V/cm. Any effect on surrounding sensitive structures was investigated. Reversible electroporation of sciatic nerve was associated with transient foot functional deficit that completely recovered at 30 days. Irreversible electroporation removed cells from trabeculae in the femurs of rabbits and in the vertebral body of sheep. After irreversible protocol, histology and microtomography demonstrated that the trabecular structure was maintained, the presence of new bone marrow cells, osteoblasts, and mineral apposition characterized by new trabeculae thinner than controls (P= .005) and a significant reduction in the ablated areas (−225%, P= .0219). Spinal cord, vertebral pedicles and spinal nerves showed transient edema in the absence of functional or structural alterations. Collectively, these results show that electroporation can be safely applied to bone even in the proximity of neuronal structures.

The three Ni-based metal–organic frameworks (MOFs) Ni(BDP), Ni(BPEB), and Ni3(BTP)2[H2BDP = 1,4-(4-bispyrazolyl)benzene; H2BPEB = 1,4-bis(1H-pyrazol-4-ylethynyl)benzene; H3BTP = 1,3,5-tris(1H-pyrazol-4-yl)benzene], possessing square planar, potentially accessible metal sites, were preliminarily tested as catalysts in the base-free selective oxidation of hydroxymethylfurfural to 2,5-diformylfuran (DFF). While Ni(BDP) undergoes degradation, Ni3(BTP)2is the most active of the three MOFs, yielding 27% DFF after 24 h with a selectivity close to 100% under relatively mild reaction conditions (120 °C, 30 bar O2, water as solvent). Upon flowing a model probe, in situDRIFT and FT-IR spectroscopy were employed to rationalize the different performances of Ni(BPEB) and Ni3(BTP)2in terms of adsorbate–adsorbent interactions: Not only hydrogen bonds are at work between the hydroxyl functionality of the probe and the pore walls of the MOF, but also and more importantly, bands ascribed to Ni-OR stretching are detected, denouncing the insurgence of Ni-probe interactions. The different intensity of these bands in the two cases confirms the different accessibility of the metal centers, as suggested by crystal structure analysis and catalytic tests.

This Letter relates the clear evidence of Yb^2+ formation under 2.5 MeV electron irradiation in optical fiber preforms showing a darkening of the core. We thus detected by in situ photoluminescence measurements the green emission of divalent Yb^2+ under the 355 nm excitation. Moreover, we showed the existence of two types of Yb^2+ ion species with different stabilities. We demonstrated that the radiodarkening mechanism is based on a pair association of Yb^2+ with aluminum oxygen hole center point defects.

The hydrogenation of biomass-derived molecules is a key reaction in upgrading these compounds into chemicals and fuels. The use of catalytic transfer hydrogenation, employing alcohols as hydrogen sources, offers an alternative approach to this process, avoiding the use of H2under high pressure and precious metal catalysts. In this work, the gas-phase conversion of biomass-derived furfural into furfuryl alcohol and 2-methylfuran was studied, using methanol as the H-transfer agent and MgO-based catalysts. Pure MgO was shown to reduce furfural into its corresponding unsaturated alcohol at low reaction temperatures (lower than 350 °C), thus allowing selective H-transfer from methanol to the substrate. 2-Methylfuran formation, associated with the partial rearrangement of furan rings to cyclopentanones, was observed at high temperatures. Conversely, the distribution of compounds obtained with Mg/Fe/O was significantly different, with 2-methylfuran formation prevailing when the reaction was carried out between 300 and 400 °C. In this temperature range, upon tuning the reaction conditions, a very high yield of 2-methylfuran was produced, thus indicating that the mixed oxide allows efficient sequential transfer hydrogenation/hydrogenolysis reactions. These results highlight the potential application of the H-transfer reaction over MgO-based catalysts as an efficient process for the selective de-oxygenation of biomass-derived molecules.

Emerald and alexandrite, the chromiferous varieties of beryl, Be3 Al2 [Si6 O18], and chrysoberyl, BeAl2 O4, respectively, are, as gems, of high economical and technological interest. The Cr3+ properties in natural beryl and chrysoberyl samples have been studied by mainly photoluminescence technique and electron paramagnetic resonance (EPR) as a function of Cr content (50–11370 ppm) as well as impurities, such as Fe and V. In emeralds, the Cr3+ crystal field value is linked to the Cr content and decreases when Cr increases. In chrysoberyl with low Cr content, the vanishing of Cr3+ emission from Cr3+ ions located on the inversion-symmetry site suggests a competition between Cr and V regarding chemical substitution. The Fe3+ ion substitutes efficiently on the mirror-symmetry site, with a strong impact on the Cr3+ lifetime on this site.

This study was designed to estimate genetic parameters for the following traits of Brahman cattle in Brazil: age at first calving (AFC), calving interval (CI), rebreeding (REB), and stayability (STAY). For REB, the value 1 was assigned to heifers that rebred and calved after first calving and the value 0 was assigned to heifers that failed to rebreed after first calving. Likewise, for STAY, the value 1 was assigned to cows that calved at least 3 times by the time they reach 6 yr of age; otherwise, the value 0 was assigned. A bivariate analysis was used to estimate covariances components by using linear animal model for CI and AFC and threshold animal model for REB and STAY. The mean h2were 0.10, 0.02, 0.22, and 0.10 for AFC, CI, REB, and STAY, respectively. The genetic correlations were –0.13 between AFC and CI, –0.35 between AFC and REB, –0.57 between AFC and STAY, and 0.32 between REB and STAY, which reveal that cows that remain productive for longer periods in the herd also start breeding younger and present greater chances to REB. The selection of Brahman cattle for reproductive traits, such as AFC, CI, REB, and STAY, will render low magnitude and long-term responses.