Genomic prediction and selection response for grain yield in safflower.

In plant breeding programs, multiple traits are recorded in each trial, and the traits are often correlated. Correlated traits can be incorporated into genomic selection models, especially for traits with low heritability, to improve prediction accuracy. In this study, we investigated the genetic correlation between important agronomic traits in safflower. We observed the moderate genetic correlations between grain yield (GY) and plant height (PH, 0.272-0.531), and low correlations between grain yield and days to flowering (DF, -0.157-0.201). A 4%-20% prediction accuracy improvement for grain yield was achieved when plant height was included in both training and validation sets with multivariate models. We further explored the selection responses for grain yield by selecting the top 20% of lines based on different selection indices. Selection responses for grain yield varied across sites. Simultaneous selection for grain yield and seed oil content (OL) showed positive gains across all sites with equal weights for both grain yield and oil content. Combining g×E interaction into genomic selection (GS) led to more balanced selection responses across sites. In conclusion, genomic selection is a valuable breeding tool for breeding high grain yield, oil content, and highly adaptable safflower varieties.

Psychological stress and coping strategies among frontline healthcare workers supporting patients with coronavirus disease 2019: a retrospective study and literature review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak might have a psychological impact on frontline healthcare workers. However, the effectiveness of coping strategies was less reported. OBJECTIVES: We aimed to investigate the sources of stress and coping strategies among frontline healthcare workers fighting against COVID-19. We also performed a literature review regarding the effects of coping methods on psychological health in this population. METHODS: We included frontline healthcare workers who completed an online survey using self-made psychological stress questionnaires in a cross-sectional study. We evaluated the association between potential factors and high-stressed status using a logistic regression model. We performed the principal component analysis with varimax rotation for factor analysis. We also performed a systematic review of published randomized controlled studies that reported the effects of coping methods on psychological health in COVID-19 healthcare workers. RESULTS: We included 107 [32 (29-36) years] respondents in the final analysis, with a response rate of 80.5%. A total of 41 (38.3%) respondents were high-stressed. Compared with the low-stressed respondents, those with high-stress were less likely to be male (46.3% versus 72.7%, p = 0.006), nurses (36.6% versus 80.3%, p < 0.001), and more likely to have higher professional titles (p = 0.008). The sources of high-stress in frontline healthcare workers were categorized into 'work factor', 'personal factor', and 'role factor'. A narrative synthesis of the randomized controlled studies revealed that most of the coping methods could improve the psychological stress in healthcare workers during the COVID-19 pandemic. CONCLUSION: Our findings suggest that some frontline healthcare workers experienced psychological stress during the early pandemic. Effective coping strategies are required to help relieve the stress in this population.

Benefit of Introgression Depends on Level of Genetic Trait Variation in Cereal Breeding Programmes.

We investigated the benefit from introgression of external lines into a cereal breeding programme and strategies that accelerated introgression of the favourable alleles while minimising linkage drag using stochastic computer simulation. We simulated genomic selection for disease resistance and grain yield in two environments with a high level of genotype-by-environment interaction (G × E) for the latter trait, using genomic data of a historical barley breeding programme as the base generation. Two populations (existing and external) were created from this base population with different allele frequencies for few (N = 10) major and many (N ~ 990) minor simulated disease quantitative trait loci (QTL). The major disease QTL only existed in the external population and lines from the external population were introgressed into the existing population which had minor disease QTL with low, medium and high allele frequencies. The study revealed that the benefit of introgression depended on the level of genetic variation for the target trait in the existing cereal breeding programme. Introgression of external resources into the existing population was beneficial only when the existing population lacked variation in disease resistance or when minor disease QTL were already at medium or high frequency. When minor disease QTL were at low frequencies, no extra genetic gain was achieved from introgression. More benefit in the disease trait was obtained from the introgression if the major disease QTL had larger effect sizes, more selection emphasis was applied on disease resistance, or more external lines were introgressed. While our strategies to increase introgression of major disease QTL were generally successful, most were not able to completely avoid negative impacts on selection for grain yield with the only exception being when major introgression QTL effects were very large. Breeding programmes are advised to carefully consider the level of genetic variation in a trait available in their breeding programme before deciding to introgress germplasms.

Topical Application of Tetrandrine Nanoemulsion Promotes the Expansion of CD4+Foxp3+ Regulatory T Cells and Alleviates Imiquimod-Induced Psoriasis in Mice.

There is compelling evidence that CD4+Foxp3+ regulatory T cells (Tregs) are indispensable in the inhibition of autoimmune inflammatory responses, including psoriasis. Recently, we showed that systemically treatment with tetrandrine (TET), a two-pore channel inhibitor identified from the Chinese herb Stephania tetrandra S. Moor, could promote the proliferative expansion of Tregs in mice through stimulation of TNF-TNFR2 interaction. We thus hypothesized that topical administration of TET might also expand Tregs and consequently inhibit psoriasis. To this end, we developed a TET nanoemulsion and examined its effect on the expansion of Tregs after topical administration on mouse psoriasis induced by imiquimod. The result of our experiment showed that topical treatment with TET nanoemulsion markedly increased the proportion and number of Tregs in the spleen, as well as TNFR2 and Ki-67 expression by Tregs, in WT and TNFR1 KO mice, but not in TNFR2 KO mice. Consequently, TET nanoemulsion potently inhibited IL-17-expressing cells in the spleen and lymph nodes of imiquimod-treated WT mice, accompanied by decreased serum levels of IL-17A, INF-γ, and TNF and their mRNA levels in the flamed lesion. Importantly, TET nanoemulsion treatment markedly inhibited the development of psoriasis-like disease in WT and TNFR1 KO mice but not in TNFR2 KO mice. Therefore, our study indicates that the topical administration of TET could also stimulate the expansion of Tregs through the TNF-TNFR2 pathway. This effect of TET and its analogs may be useful in the treatment of inflammatory skin diseases such as psoriasis.

Enhanced uptake and anti-maturation effect of celastrol-loaded mannosylated liposomes on dendritic cells for psoriasis treatment.

Psoriasis is an autoimmune skin disease in which dendritic cells (DCs) trigger the progression of psoriasis by complex interactions with keratinocytes and other immune cells. In the present study, we aimed to load celastrol, an anti-inflammatory ingredient isolated from Chinese herbs, on mannosylated liposomes to enhance DC uptake as well as to induce DC tolerance in an imiquimod-induced psoriasis-like mouse model. Mannose was grafted onto liposomes to target mannose receptors on DCs. The results demonstrated that compared with unmodified liposomes, DCs preferred to take up more fluorescence-labeled mannosylated liposomes. After loading celastrol into mannose-modified liposomes, they effectively inhibited the expression of maturation markers, including CD80, CD86 and MHC-II, on DCs both in vitro and in vivo. Additionally, after intradermal injection with a microneedle, celastrol-loaded mannose-modified liposomes (CEL-MAN-LPs) achieved a superior therapeutic effect compared with free drug and celastrol-loaded unmodified liposomes in the psoriasis mouse model in terms of the psoriasis area and severity index, histology evaluation, spleen weight, and expression of inflammatory cytokines. In conclusion, our results clearly revealed that CEL-MAN-LPs was an effective formulation for psoriasis treatment and suggested that this treatment has the potential to be applied to other inflammatory diseases triggered by activated DCs.

The Therapeutic Effect of Tacrolimus in a Mouse Psoriatic Model is Associated with the Induction of Myeloid-derived Suppressor Cells.

Objectives: Topical administration of Tacrolimus (TAC) is efective in the treatment of psoriasis in human patients and in mouse models. Previously, we showed that, though promoting the proliferative expansion of CD4+Foxp3+ regulatory T cells (Tregs), TNFR2 was protective in mouse psoriasis model. We thus examined the role of TNFR2 signal in the efect of TAC in the treatment of mouse psoriasis. Methods: To this end, psoriasis was induced in WT, or TNFR1 KO, or TNFR2 KO mice, and the psoriatic mice were treated with or without IMQ. Results: The results showed that TAC treatment potently inhibited the development of psoriasis in WT and TNFR1 KO mice, but not in TNFR2 KO mice. However, the treatment of TAC failed to induce the expansion of Tregs in psoriatic mice. In addition to playing a decisive role in the activation of Tregs, TNFR2 stimulates the generation and activation of myeloid-derived suppressor cells (MDSCs). This led us to found that the topical treatment with TAC markedly increased the number of MDSCs in the spleen of WT and TNFR1 KO mice, but not in TNFR2 KO mice. Consequently, TAC potently decreased serum levels of IL-17A, INF-γ, and TNF and their mRNA levels in the inflamed skin lesion. Conclusion: Therefore, our study for the first time found that the therapeutic efect of TAC in psoriasis is associated with the expansion of MDSCs in a TNFR2-dependent manner.

Differential role of TNFR1 and TNFR2 in the development of imiquimod-induced mouse psoriasis.

Tumor necrosis factor alpha (TNF) has been implicated in the pathogenesis of psoriasis and anti-TNF therapeutics are used in the treatment of psoriasis in the clinic. However, considerable proportion of patients fail to respond to anti-TNF treatment. Furthermore, anti-TNF therapy induces de novo development of psoriasis in some patients with other type of autoimmune disorders. Therefore, further understanding of the role of TNF-TNFR signaling in pathogenesis of psoriasis remains a critical to devise safer and more effective treatment. In this study, it is shown that in imiquimod-induced mouse psoriasis model, TNF receptor type 1 (TNFR1) deficiency inhibited the development of skin diseases. In sharp contrast, TNF receptor type 2 (TNFR2) deficiency led to more severe psoriasis that was associated with increased Th1 and Th17 responses and reduced number of CD4+ Foxp3+ regulatory T cells (Tregs). Importantly, adoptive transfer of WT Tregs was able to attenuate inflammatory responses in imiquimod-treated TNFR2-/- mice, suggestive of a role of malfunctioned Tregs in mice deficient in TNFR2. RNA sequencing data revealed that Tregs deficient in TNFR2 exhibited down-regulation of different biological processes linked to proliferative expansion. Taken together, our study clearly indicated that TNFR1 was pathogenic in mouse psoriasis. In contrast, through boosting the proliferative expansion of Tregs, TNFR2 was protective in this model. The data thus suggest that TNFR1-specific antagonist or TNFR2-specific agonist may be useful in the treatment of patients with psoriasis.

Uptake and trafficking of different sized PLGA nanoparticles by dendritic cells in imiquimod-induced psoriasis-like mice model.

Psoriasis is an autoimmune inflammatory disease, where dendritic cells (DCs) play an important role in its pathogenesis. In our previous work, we have demonstrated that topical delivery of curcumin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) could treat Imiquimod (IMQ)-induced psoriasis-like mice. The objective of this study is to further elucidate biofate of PLGA NPs after intradermal delivery including DCs uptake, and their further trafficking in psoriasis-like mice model by using fluorescence probes. Two-sized DiO/DiI-loaded PLGA NPs of 50 ± 4.9 nm (S-NPs) and 226 ± 7.8 nm (L-NPs) were fabricated, respectively. In vitro cellular uptake results showed that NPs could be internalized into DCs with intact form, and DCs preferred to uptake larger NPs. Consistently, in vivo study showed that L-NPs were more captured by DCs and NPs were firstly transported to skin-draining lymph nodes (SDLN), then to spleens after 8 h injection, whereas more S-NPs were transported into SDLN and spleens. Moreover, FRET imaging showed more structurally intact L-NPs distributed in skins and lymph nodes. In conclusion, particle size can affect the uptake and trafficking of NPs by DCs in skin and lymphoid system, which needs to be considered in NPs tailing to treat inflammatory skin disease like psoriasis.

Making the most of all data: Combining non-genotyped and genotyped potato individuals with HBLUP.

Using genomic information to predict phenotypes can improve the accuracy of estimated breeding values and can potentially increase genetic gain over conventional breeding. In this study, we investigated the prediction accuracies achieved by best linear unbiased prediction (BLUP) for nine potato phenotypic traits using three types of relationship matrices pedigree ABLUP, genomic GBLUP, and a hybrid matrix (H) combining pedigree and genomic information (HBLUP). Deep pedigree information was available for >3000 different potato breeding clones evaluated over four years. Genomic relationships were estimated from >180,000 informative SNPs generated using a genotyping-by-sequencing transcriptome (GBS-t) protocol for 168 cultivars, many of which were parents of clones. Two validation scenarios were implemented, namely "Genotyped Cultivars Validation" (a subset of genotyped lines as validation set) and "Non-genotyped 2009 Progenies Validation". Most of the traits showed moderate to high narrow sense heritabilities (range 0.22-0.72). In the Genotyped Cultivars Validation, HBLUP outperformed ABLUP on prediction accuracies for all traits except early blight, and outperformed GBLUP for most of the traits except tuber shape, tuber eye depth and boil after-cooking darkening. This is evidence that the in-depth relationship within the H matrix could potentially result in better prediction accuracy in comparison to using A or G matrix individually. The prediction accuracies of the Non-genotyped 2009 Progenies Validation were comparable between ABLUP and HBLUP, varying from 0.17-0.70 and 0.18-0.69, respectively. Better prediction accuracy and less bias in prediction using HBLUP is of practical utility to breeders as all breeding material is ranked on the same scale leading to improved selection decisions. In addition, our approach provides an economical alternative to utilize historic breeding data with current genotyped individuals in implementing genomic selection.

Fructo-oligosaccharides from Morinda officinalis remodeled gut microbiota and alleviated depression features in a stress rat model.

BACKGROUND: Inulin-type fructo-oligosaccharides (FOSs) purified from Morinda officinalis How., an effective oral antidepressant for mild to moderate depression, have a largely unknown efficacy and poor bioavailability. PURPOSE: Therefore, the microbiota-gut-brain axis was used to investigate the antidepressive properties of FOSs at the interface of the gut microbiota (GM). STUDY DESIGN AND METHODS: FOSs was introduced via intragastric gavage to rats exposed to chronic unpredictable mild stress (CUMS), and the antidepressive effects were investigated through behavioral tests, intestinal morphology and corticosterone levels. Bacterial genomic DNA was extracted from feces, and the GM was profiled for using enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis, partial least squares-discriminant analysis (PLS-DA) and 16S rRNA gene pyrosequencing. RESULTS: It was observed that FOSs alleviated depression-like behaviors and repaired intestinal epithelia damages. FOSs treatment lowered corticosterone levels in the plasma and urine of the model rats. Moreover, the GM compositions of normal and model rats were distantly clustered and were mainly related to the disappearance of beneficial bacteria (e.g., Acinetobacter, Barnesiella, Coprococcus, Dialister, Lactobacillus, and Paenibacillus) and appearance of depression-associated bacteria (e.g., Anaerostipes, Oscillibacter, Proteobacteria, and Streptococcus) in depressive rats. Interestingly, the dysbiosis in depressive rats' gut was reinstated with FOSs treatments. Notably, FOSs promoted the abundance of the bacterial phylum Cyanobacteria, a group of bacteria known for the secretion of pharmacologically important metabolites, such as H2S, that exhibit antidepressant-like properties. Apparently, FOSs-induced modulation of GM was more antidepressive compared to a component of FOSs, degrees of polymerization (DP) 5, and fluoxetine, the standard antidepressant drug. CONCLUSION: In conclusion, this study implied that antidepressant efficacy of FOSs was inseparable from and strongly associated with the modulation of the host' s GM.

Boosting Genetic Gain in Allogamous Crops via Speed Breeding and Genomic Selection.

Breeding schemes that utilize modern breeding methods like genomic selection (GS) and speed breeding (SB) have the potential to accelerate genetic gain for different crops. We investigated through stochastic computer simulation the advantages and disadvantages of adopting both GS and SB (SpeedGS) into commercial breeding programs for allogamous crops. In addition, we studied the effect of omitting one or two selection stages from the conventional phenotypic scheme on GS accuracy, genetic gain, and inbreeding. As an example, we simulated GS and SB for five traits (heading date, forage yield, seed yield, persistency, and quality) with different genetic architectures and heritabilities (0.7, 0.3, 0.4, 0.1, and 0.3; respectively) for a tall fescue breeding program. We developed a new method to simulate correlated traits with complex architectures of which effects can be sampled from multiple distributions, e.g. to simulate the presence of both minor and major genes. The phenotypic selection scheme required 11 years, while the proposed SpeedGS schemes required four to nine years per cycle. Generally, SpeedGS schemes resulted in higher genetic gain per year for all traits especially for traits with low heritability such as persistency. Our results showed that running more SB rounds resulted in higher genetic gain per cycle when compared to phenotypic or GS only schemes and this increase was more pronounced per year when cycle time was shortened by omitting cycle stages. While GS accuracy declined with additional SB rounds, the decline was less in round three than in round two, and it stabilized after the fourth SB round. However, more SB rounds resulted in higher inbreeding rate, which could limit long-term genetic gain. The inbreeding rate was reduced by approximately 30% when generating the initial population for each cycle through random crosses instead of generating half-sib families. Our study demonstrated a large potential for additional genetic gain from combining GS and SB. Nevertheless, methods to mitigate inbreeding should be considered for optimal utilization of these highly accelerated breeding programs.

Loading of water-insoluble celastrol into niosome hydrogels for improved topical permeation and anti-psoriasis activity.

Psoriasis is a severe disfiguring skin disease affecting approximately 3% of people worldwide and negatively affecting their daily lives. The pathogenesis of psoriasis is complicated, and typical therapeutic strategies for psoriasis mainly focus on anti-inflammation. Considering the side effects, withdrawal rebound, high cost, and many other disadvantages of existing treatments, we developed a new topical therapeutic formulation consisting of niosomes loaded with celastrol, a triterpenoid extracted from Tripterygium. Celastrol niosomes were prepared by the thin film hydration method and probe sonication. The niosomes were composed of Span 20, Span 60, and cholesterol at a weight ratio of 3:1:1. The particle size of the niosomes was approximately 147 nm, with yield of up to 90%. Celastrol niosomes showed improved in vitro permeation ability compared to the raw drug. In our in vivo study, celastrol niosomes effectively alleviated erythema and scaling on the dorsal skin of psoriasis mouse models. Spleen weight and the levels of cytokines, including IL-22, IL-23, and IL-17, decreased after the treatment, indicating the high therapeutic potential of this formulation for psoriasis. In conclusion, encapsulation of celastrol by niosomes increased the water-solubility and permeation of celastrol into the skin, significantly improving its anti-psoriasis activity in mice.

Comparison of normal versus imiquimod-induced psoriatic skin in mice for penetration of drugs and nanoparticles.

BACKGROUND: As an immune-mediated skin disease, psoriasis encounters therapeutic challenges on topical drug development due to the unclear mechanism, and complicated morphological and physiological changes in the skin. METHODS: In this study, imiquimod-induced psoriatic mouse skin (IMQ-psoriatic skin) was chosen as the in vitro pathological model to explore the penetration behaviors of drugs and nanoparticles (NPs). RESULTS: Compared with normal skin, significantly higher penetration and skin accumulation were observed in IMQ-psoriatic skin for all the three model drugs. When poorly water-soluble curcumin was formulated as NPs that were subsequently loaded in gel, the drug's penetration and accumulation in both normal and IMQ-psoriatic skins were significantly improved, in comparison with that of the curcumin suspension. Interestingly, the NPs' size effect, in terms of their penetration and accumulation behaviors, was more pronounced for IMQ-psoriatic skin. Furthermore, by taking three sized FluoSpheres® as model NPs, confocal laser scanning microscopy demonstrated that the penetration pathways of NPs no longer followed the hair follicles channels, instead they were more widely distributed in the IMQ-psoriatic skin. CONCLUSION: In conclusion, the alternation of the IMQ-psoriatic skin structure will lead to the enhanced penetration of drug and NPs, and should be considered in topical drug formulation and further clinical practice for psoriasis therapy.

Insights into population genetics and evolution of polyploids and their ancestors.

We have developed the first comprehensive simulator for polyploid genomes (PolySim) and demonstrated its value by performing large-scale simulations to examine the effect of different population parameters on the evolution of polyploids. PolySim is unlimited in terms of ploidy, population size or number of simulated loci. Our process considered the evolution of polyploids from diploid ancestors, polysomic inheritance, inbreeding, recombination rate change in polyploids and gene flow from lower to higher ploidies. We compared the number of segregating single nucleotide polymorphisms, minor allele frequency, heterozygosity, R2 and average kinship relatedness between different simulated scenarios, and to real data from polyploid species. As expected, allotetraploid populations showed no difference from their ancestral diploids when population size remained constant and there was no gene flow or multivalent (MV) pairing between subgenomes. Autotetraploid populations showed significant differences from their ancestors for most parameters and diverged from their ancestral populations faster than allotetraploids. Autotetraploids can have significantly higher heterozygosity, relatedness and extended linkage disequilibrium compared with allotetraploids. Interestingly, autotetraploids were more sensitive to increasing selfing rate and decreasing population size. MV formation can homogenize allotetraploid subgenomes, but this homogenization requires a higher MV rate than previously proposed. Our results can be considered as the first building block to understand polyploid population evolutionary dynamics. PolySim can be used to simulate a wide variety of polyploid organisms that mimic empirical populations, which, in combination with quantitative genetics tools, can be used to investigate the power of genomewide association, genomic selection or breeding programme designs in these species.

Psoriasis therapy by Chinese medicine and modern agents.

Psoriasis is a chronic, painful, disfiguring and non-contagious skin disease that has globally affected at least 200 million patients. In general, mild to moderate psoriasis patients will be treated by chemical drugs or Chinese medicine, while targeting systemic biological drugs have been successfully developed with good efficacy but high cost burden to patients with severe psoriasis. Since the underlying mechanisms of psoriasis are not well understood, in this review, psoriasis pathogenesis and clinical therapeutic principles by modern medicine and Chinese medicine are extensively described. Based on the data from the China Food and Drug Administration, the majority of chemical drugs are utilized as the topical formulations, while Chinese medicines are mainly delivered by an oral route, suggesting that the market for topical preparations of Chinese medicine to treat psoriasis is worth to exploration. Moreover, considering the unique clinical therapeutic theory and successful clinical application of Chinese medicine in the treatment of psoriasis, we believe that development of new small molecule drugs based on Chinese medicine will be a promising strategy to reduce therapeutic costs and improve safety for psoriatic patients.

Mitigation of inbreeding while preserving genetic gain in genomic breeding programs for outbred plants.

KEY MESSAGE: Heuristic genomic inbreeding controls reduce inbreeding in genomic breeding schemes without reducing genetic gain. Genomic selection is increasingly being implemented in plant breeding programs to accelerate genetic gain of economically important traits. However, it may cause significant loss of genetic diversity when compared with traditional schemes using phenotypic selection. We propose heuristic strategies to control the rate of inbreeding in outbred plants, which can be categorised into three types: controls during mate allocation, during selection, and simultaneous selection and mate allocation. The proposed mate allocation measure GminF allocates two or more parents for mating in mating groups that minimise coancestry using a genomic relationship matrix. Two types of relationship-adjusted genomic breeding values for parent selection candidates ([Formula: see text]) and potential offspring ([Formula: see text]) are devised to control inbreeding during selection and even enabling simultaneous selection and mate allocation. These strategies were tested in a case study using a simulated perennial ryegrass breeding scheme. As compared to the genomic selection scheme without controls, all proposed strategies could significantly decrease inbreeding while achieving comparable genetic gain. In particular, the scenario using [Formula: see text] in simultaneous selection and mate allocation reduced inbreeding to one-third of the original genomic selection scheme. The proposed strategies are readily applicable in any outbred plant breeding program.

Genetic Gain and Inbreeding from Genomic Selection in a Simulated Commercial Breeding Program for Perennial Ryegrass.

Genomic selection (GS) provides an attractive option for accelerating genetic gain in perennial ryegrass () improvement given the long cycle times of most current breeding programs. The present study used simulation to investigate the level of genetic gain and inbreeding obtained from GS breeding strategies compared with traditional breeding strategies for key traits (persistency, yield, and flowering time). Base population genomes were simulated through random mating for 60,000 generations at an effective population size of 10,000. The degree of linkage disequilibrium (LD) in the resulting population was compared with that obtained from empirical studies. Initial parental varieties were simulated to match diversity of current commercial cultivars. Genomic selection was designed to fit into a company breeding program at two selection points in the breeding cycle (spaced plants and miniplot). Genomic estimated breeding values (GEBVs) for productivity traits were trained with phenotypes and genotypes from plots. Accuracy of GEBVs was 0.24 for persistency and 0.36 for yield for single plants, while for plots it was lower (0.17 and 0.19, respectively). Higher accuracy of GEBVs was obtained for flowering time (up to 0.7), partially as a result of the larger reference population size that was available from the clonal row stage. The availability of GEBVs permit a 4-yr reduction in cycle time, which led to at least a doubling and trebling genetic gain for persistency and yield, respectively, than the traditional program. However, a higher rate of inbreeding per cycle among varieties was also observed for the GS strategy.