Eimeria parasites that damage the host’s intestinal system, resulting in poor nutrition absorption, reduced growth, and often death. Increasing evidence from recent studies indicates that immune-based strategies such as the use of recombinant vaccines and various dietary immunomodulating feed additives can improve host defense against intracellular parasitism and reduce intestinal damage due to inflammatory responses induced by parasites. Therefore, a comprehensive understanding of the complex interactions between the host immune system, gut microbiota, enteroendocrine system, and parasites that contribute to the outcome of coccidiosis is necessary to develop logical strategies to control coccidiosis in the post-antibiotic era. Most important for vaccine development is the need to understand the protective role of the local intestinal immune response and the identification of various effector molecules which mediate anti-coccidial activity against intracellular parasites. This review summarizes the current understanding of the host immune response to coccidiosis in poultry and discusses various non-antibiotic strategies which are being developed for coccidiosis control. A better understanding of the basic immunobiology of pertinent host–parasite interactions in avian coccidiosis will facilitate the development of effective anti-Eimeria strategies to mitigate the negative effects of coccidiosis.Coccidiosis is an avian intestinal disease caused by several distinct species of  Coccidiosis is a major enteric infection of poultry that is estimated to cost more than USD 14.5 billion annual losses globally . TherefoEimeria lifecycle, intestinal immune response, and the intricate interaction between parasites and the gut microbiome is required for the effective application of new immunotherapeutics including vaccines in commercial practice. Therefore, this review will provide the current knowledge on the host immune response to coccidiosis in poultry and discuss the efficacy of various Eimeria vaccine candidate antigens in protecting chickens against coccidiosis. Moreover, alternative countermeasures such as hyperimmune antibodies, antimicrobial peptides, prebiotics, and probiotics will be discussed. In response to these concerns, the demand for cost-effective and safe anticoccidial vaccines is rapidly increasing. Immunological approaches can provide an alternative method to prevent the spread of coccidiosis while avoiding the shortcomings of conventional measures. Immunologic approaches include vaccination with recombinant vaccines, immunostimulation with cytokines, and antibiotic alternatives to improve host innate immunity using antimicrobial host peptides such as NK-lysin . HoweverEimeria species and there are seven different Eimeria spp.  that undergo intracellular development in a site-specific manner. Each Eimeria spp. infects a specific region of the intestine, for example, E. tenella infects caecum whereas E. acervulina targets duodenum [Eimeria spp., E. necatrix, and E. tenella are classified as highly pathogenic in poultry [Eimeria infect the gastrointestinal tract which is the primary organ responsible for digestion and nutrient absorption. Therefore, coccidiosis results in serious economic consequences due to inefficient feed utilization, impaired growth rate, high mortality, and a temporary reduction in egg production. In addition, infection with certain Eimeria spp., especially E. maxima, is the primary risk factor for necrotic enteritis since coccidiosis compromises gut integrity allowing the proliferation of toxinogenic Clostridium perfringens [Coccidiosis is caused by pathogenic duodenum . Among t poultry , but allfringens ,9,10. Eimeria and, through an unknown mechanism, it invades specific sites in the gut epithelium to undergo first intracellular development and release merozoites through the merogony cycle by asexual reproduction. One sporozoite produces approximately 1000 merozoites and this process can be repeated two to four times. After the asexual lifecycle, the gametogony stage of the sexual reproduction cycle begins, during which male and female gametes form. Fertilization of the male and female gametes results in the formation of zygotes encased by thick outer walls which develop into unsporulated oocysts that shed onto the litter in the feces. Eimeria parasites show high host-specificity, although no information is available on the mechanism of host specificity. Many factors such as genetics, sex, nutrition, biochemistry, and immunity play a role and interaction between these factors dictates the outcome of coccidiosis [Eimeria life cycle suggest distinct antigenic diversity among Eimeria spp., which is essential for vaccine development. Although most infectious diseases affecting the poultry industry have been effectively controlled using various methods [Eimeria parasites to retain their infectivity for a long time. The use of vaccines is considered the most practical and safe method to control coccidiosis in poultry, and many types of vaccines using whole parasites, either live or attenuated, have been developed.Coccidiosis is initiated upon the ingestion of sporulated oocysts that contain four sporocysts by chickens. As oocysts travel down the gastrointestinal track, physical grinding and/or gut digestive enzymes break the oocyst wall to release four sporocysts with two sporozoites each per sporulated oocyst. Sporozoite is the invasive form of cidiosis . Each su methods ,12,13, cThe most fundamental function of the gut is to digest food through masticatory movement and absorb nutrients into the bloodstream. Thus, the intestinal epithelium is constantly in contact with resident microorganisms and food and is constantly exposed to a wide range of potential pathogenic microorganisms. The mucosal immune system is composed of mucosal-associated lymphoid tissues (MALTs) of the mammary glands, genital tract, respiratory tract, and intestine . Among tEimeria is also an intestinal parasite, the first line of defense against coccidiosis starts in GALT. GALT serves three major functions in host defense against coccidia infection: antigen processing and immunogenic epitope presentation, the release of intestinal antibodies, and the activation of cell-mediated immunity [The MALT of chickens is well developed , and theimmunity . GALT isimmunity ,18. Hostimmunity . Antigenimmunity . GALT coimmunity . The gastrointestinal epithelium is mostly covered with a protective mucus gel composed of glycoproteins produced by goblet cells, and this mucous layer acts as a physical barrier against pathogen invasion . FurtherAdaptive immunity includes humoral and cell-mediated immune (CMI) responses, which are mediated by soluble antibodies and T lymphocytes, respectively. Both responses play important roles against extracellular and intracellular antigens, with CMI response predominantly involved in host defense against intracellular pathogens.+ (cluster of differentiation 4+) helper T cells (TH) and CD8+ cytotoxic T cells (TC). Mammals and chickens are critically dependent on CD4+ TH cells in adaptive immunity [The CMI response against intracellular antigens mainly targets exogenous antigens that have entered cells via the endocytic pathway or endogenous antigens produced within the cell, such as viral proteins and residues that result from the neoplastic transformation of the cell . T cellsimmunity . The actimmunity . In thisimmunity . Eimeria-infected chickens [+ and CD8+ T lymphocytes contribute differently to primary and secondary Eimeria infections. Following coccidiosis, increasing amounts of T cells secreting interferon (IFN)-γ [Eimeria parasite development in cells [Eimeria-infected chickens using lymphocyte-specific immune reagents demonstrated the relevance of different T cell subpopulations in mediating the anticoccidial innate immune response after exposure to Eimeria infection [Eimeria parasites undergo intracellular development [E. vermiformis-infected mice, αβ T cells play an important role in the memory response to murine coccidiosis since the TCRβ−/− mice were highly susceptible to secondary infection of E. vermiformis and remained highly susceptible to subsequent infections, unlike intact mice [Initial studies have found that T cells play a crucial role in mediating anti-coccidial immunity in chickens . Many cychickens ,31. In achickens  demonstr (IFN)-γ , an immuin cells . Flow cynfection . Since celopment , the rolelopment . In E. vact mice . Similaract mice .Eimeria infection through IFN-γ secretion. The observation of subpopulations of NK cells that mediate spontaneous cytotoxicity in chicken intestinal IEL suggests that they are an important component of intestinal immunity [Eimeria-infected chickens and showed that coccidiosis markedly reduced NK cell activity in splenic lymphocytes and intestinal IEL during the early stages of infection. However, approximately one week after the primary infection, NK cell activity recovered to normal levels, and in the early stages of secondary infection, splenic and intestinal IEL NK cell activity significantly increased. Although local host response depends on the species of Eimeria [CMI responses are involved in both the antigen-specific and non-specific activation of T lymphocytes, macrophages, and natural killer (NK) cells . Cytotoximmunity . The preimmunity , thymus immunity , peripheimmunity , bursa oimmunity , and intimmunity . NK cellimmunity  investig Eimeria , these rE. tenella, E. maxima, and E. acervulina showed protective immunity compared with non-immunized chickens. The cecal tonsils, Peyer’s patches, and spleens of immunized and Eimeria-infected chickens showed an enhanced Th1 immune response. In addition, exosome-immunized chickens showed greater body weight gain, reduced oocyst output, and lower mortality compared with non-immunized chickens. Besides this efficacy against coccidiosis, recent studies have demonstrated that exosomes are useful tools in developing vaccines against other pathogens [Dendritic cells (DCs) are antigen-presenting cells (APCs) with a unique ability to induce both innate and highly antigen-specific acquired immunity  through athogens ,55. Various cytokines and chemokines that play a role in coccidiosis infection have been characterized. They include IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, 17, and IL-18, IFN-γ, transforming growth factor (TGF)-β1–4, tumor necrosis factor (TNF)-α, TNF-α superfamily 15 (TNFSF15), and lipopolysaccharide-induced TNF-α factor (LITAF) ,56,57. TEimeria. In mice, the role of IFN-γ has been well characterized as essential during intestinal parasite infection [E. acervulina infection [E. tenella-infected chickens. Upregulated expression of IFN-γ was detected in spleens, cecal tonsils, and in IELs post primary and secondary E. tenella infections [Eimeria-stimulated peripheral blood lymphocytes from chickens infected with coccidiosis. Subsequently, IFN-γ was found to be produced by mitogen or antigen-stimulated specific T cells that are present in the blood of chickens infected with Eimeria [E. acervulina. The results demonstrated that chickens treated with recombinant IFN-γ had significantly increased body weight gain compared with that of the control chickens [E. tenella into chicken cells in vitro. [E. acervulina infection [Among the cytokines involved in coccidiosis, IFN-γ is a representative immunomodulator and has received the most attention because of its direct inhibitory effect on the intracellular development of nfection ,69. Genenfection . A consinfection . Similarfections . Breed efections  demonstr Eimeria . On the  Eimeria ,73. Chicchickens . In addin vitro. . A similE. maxima and E. tenella, highly upregulated expression of IL-1β was found in the duodenum, jejunum, and cecum post primary infection [Eimeria-infected chickens by a chicken macrophage microarray [The structurally homologous proteins IL-1β and IL-18 are notable cytokines involved in the initial inflammatory response. IL-1β induces chemokine production, which promotes the recruitment of inflammatory cells at the inflammation site , and IL-nfection ,77. In acroarray . E. acervulina, increased expression levels of IL-2 were observed after primary and secondary infections [E. acervulina infection, the expression of IL-2 was decreased in chickens infected with E. tenella. Whether this difference is attributed to cytokine responses induced by these two different species of Eimeria in the different areas of gut or if there are other unknown factors that contribute to different cytokine responses remains to be studied [E. acervulina infection was demonstrated in a recombinant vaccination experiment where chickens vaccinated with 3-1E recombinant protein showed enhanced protection upon challenge infection when the recombinant protein was given with IL-2 [A major cytokine involved in CMI response is IL-2, which is a potent growth factor that stimulates the proliferation of chicken T lymphocytes and the activation of NK cells. Sundick and Gill-Dixon  cloned tfections . Followi studied . The impith IL-2 .E. tenella, indicating the possibility that IL-6 plays a role in acquired immunity [E. acervulina, E. maxima, or E. tenella [IL-6 is an important cytokine responsible for the final maturation of B cells that produce antibodies and is mainly produced by endothelial cells, macrophages, and T cells . IL-6 primmunity . Moreove tenella .Eimeria infection, IL-10 plays a significant role in downregulating harmful inflammatory responses. When comparing two different chicken lines with different coccidiosis susceptibility, susceptible chickens (line 15I) showed greater expression levels of IL-10 in the spleen and gut compared to the resistant chickens (line C.B12) following E. maxima infection [E. tenella-infected chickens [E. acervulina or E. tenella infection by qRT-PCR. One possible theory explains the role of IL-10 in coccidiosis infection: Eimeria spp. may have evolved to induce IL-10 secretion in the host by stimulating Treg cells to facilitate the invasion of parasites into chicken epithelial cells. Furthermore, IL-10 suppresses the IFN-γ-related Th1 response which plays an important role in protective immunity against intracellular parasitic infection. Morris et al. [Eimeria-infected chickens. These results suggest the important roles of Treg cells and IL-10 in the regulation of protective immunity against coccidiosis. IL-10 is an anti-inflammatory cytokine that downregulates the inflammatory Th1 response by inhibiting the secretion of pro-inflammatory cytokines, such as IL-1β, TNF-α, and IL-6 . In micenfection . Similarchickens . Compares et al.  showed tE. tenella sporozoites and merozoites in chicken macrophage cells after primary infection. However, TNF production was not observed following secondary infections [E. tenella infection, indicating the involvement of TNF in coccidiosis pathogenesis [TNF is primarily produced by activated macrophages but also by other cells such as NK cells, mast cells, and antigen-stimulated T cells . The rolfections . An in vogenesis .Eimeria sporozoites [E. tenella and in the jejunum following E. maxima infection [Chemokines are important mediators that induce host defense mechanisms by facilitating the migration of leukocytes to inflammation sites . These prozoites . In addinfection .E. tenella and found significant dysbiosis in cecal microbiota. E. tenella infection reduced the levels of nonpathogenic bacteria including Lactobacillus and Faecalibacterium and increased the levels of pathogenic bacteria such as Clostridium, Lysinibacillus, and Escherichia. Similar changes in fecal microbiota were observed in several commercial chicken spp.  indicating that dysbiosis in the gut was directly induced by E. tenella infection [Ruminococcaceae, function to generate energy and nutrients by decomposing non-starch polysaccharides into simple sugars [Faecalibacterium aids in the fermentation of these sugars and produces butyrate and essential amino acids, which play an important role in relieving chronic inflammation and reducing damage from E. tenella infection [The gut microbiota is a complex ecosystem that influences the physiological response of the host, including their immune development and function, nutrition and metabolism, and pathogen exclusion . One of nfection ,101. Mice sugars . Faecalinfection . E. maxima and Clostridium perfringens, increasing Clostridium sensu stricto 1, Escherichia Shigella, and Weissella populations and decreasing Lactobacillus populations were seen in the jejunum [Lactobacillus spp., affects microbial diversity and disrupts significant metabolic processes that provide energy and sources or carbon [Lactobacillus reuteri, which produces an antimicrobial substance called reuteri, can lead to the proliferation of other bacterial species, resulting in the loss of host defense capabilities [Lactobacillus spp. significantly inhibited the invasion of E. tenella sporozoites in Madin-Darby bovine kidney cells [E. tenella infection on cecal microbiota in specific-pathogen-free chickens and observed a reduction in potentially beneficial bacteria . These bacteria inhibit the proliferation of conditional pathogenic bacteria through substances with broad-spectrum antimicrobial activity and reduce the production of harmful substances, such as endotoxins [Escherichia−Shigella, Enterococcus, Bacillus, and Staphylococcus, have been detected in the cecum of E. tenella-infected chicks [In a necrotic enteritis (NE) disease model using the coinfection of  jejunum . The redr carbon . In addibilities . For exaey cells . Cui et ey cells  investigdotoxins . In contd chicks ,107. Eimeria parasites compromises intestinal integrity and affects nutrient absorption by reducing the function of the intestinal barrier and leads to a bacterial imbalance affecting bacterial-dependent metabolic processes in the gastrointestinal tract. Consequently, an intestinal bacterial imbalance increases the risk of susceptibility to other diseases by disrupting the gut homeostasis of the host [Eimeria parasites and the gut microbiota and the effects of coccidiosis on host physiological responses, including nutrient absorption and local immunity.Dysbiosis associated with coccidiosis increases host susceptibility to other pathogens. Infection with the host . Due to Eimeria strains or anticoccidial drugs such as diclazuril, toltrazuril, and ionophores [Eimeria strains, have generated increased interest in recombinant vaccines as an alternative strategy to control coccidiosis [Eimeria antigens have been identified as effective anticoccidial vaccine candidates, but there are not yet commercially available recombinant vaccines in the market [Eimeria proteins identified as anticoccidial agents target surface and internal parasite antigens , 14-3-3 protein, ubiquitin-conjugating enzyme domain-containing protein (UCE), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), by comparing the amino acid sequences of three Eimeria spp. . Lin et al. [E. tenella and evaluated its protective effect in chickens infected with E. maxima and E. tenella. Chickens immunized with recombinant EF-1α exhibited greater body weight gain, improved serum antibody production against EF-1α, and decreased fecal oocyst shedding post Eimeria challenge with either E. maxima or E. tenella compared to the unimmunized chickens.Liu et al.  identifin et al.  cloned tE. acervulina and E. maxima in chickens infected with E. tenella, E. acervulina, E. maxima, or a mix of these. Chickens vaccinated with recombinant GAPDH showed an enhanced proportion of CD4+ and CD8+ T lymphocytes, increased cytokine secretion , and a greater IgG antibody production compared to the non-immunized chickens. In addition, vaccination increased weight gain, decreased fecal oocyst shedding, and mitigated gut lesions compared to the non-immunized chickens. Tian et al.  evaluateEimeria spp. that infect domestic fowl [The highly immunogenic protein SO7 is a refractory body protein that contains an epitope commonly shared among all tic fowl . Chickentic fowl . In another in vivo trial, chickens vaccinated with recombinant SO7 protein showed a significant reduction in oocyst output and increased weight gain compared with non-vaccinated chickens . In addiEimeria parasites are important components of the oocyst wall and potential vaccine candidates as transmission-blocking vaccines against coccidiosis [E. maxima-infected chickens [E. necatrix (Engam22) which showed 97.7% identity to that of Etgam22 of E. tenella and this antigen was recognized in serum from chickens immunized with E. necatrix, E. tenella, and E. maxima. Furthermore, the Etgam22 antigen of E. tenella was an ortholog of E. necatrix gametocytes, indicating a potential target for future recombinant subunit vaccines against coccidiosis. The immunoprophylactic efficacy of recombinant gametocyte antigen 22 from E. tenella (EtGam22) was evaluated in chickens following E. tenella infection [E. tenella surface antigens 4 (EtSAG4) and showed that the EtSAG4 recombinant protein induced a significant (p < 0.05) protective immunity based on IgY and IFN-γ production, body weight gain, and reduced oocyst output in E. tenella-infected Cobb broilers. However, the DNA vaccine (pEGFP-N1-EtSAG4 plasmids) induced much higher levels of protection against E. tenella than the EtSAG4 recombinant antigen vaccination.Two gametocyte antigens (GAM56 and GAM82) from the sexual stages of cidiosis ,121. Chichickens ,122,123.chickens . Liu et chickens  cloned anfection . Vaccinanfection  developeE. tenella and was found in both merozoites and sporozoites of E. acervulina and E. maxima [Eimeria challenge. In addition, improved serum antibody levels of IgG and higher cytokine production than in non-immunized chickens were observed [E. acervulina against coccidiosis in combination with plasmid carrying a gene encoding IL-1, IL-2, IL-6, IL-8, IL-15, IL-16, IL-17, IL-18, or IFN-γ. The outcome of the study demonstrated that the 3-1E in ovo vaccination elicited protective immunity against E. acervulina infection as measured by decreased fecal oocyst output and a lower body weight loss than in non-immunized chickens. Moreover, the co-injection of the 3-1E vaccine with a plasmid expressing a chicken cytokine such as IL-2, IL-15, IL-17, IL-18, or IFN-γ further enhanced vaccine efficacy [Profilin, also called 3-1E, is one of the most widely evaluated subunit vaccine candidates ,113,128.. maxima . The 3-1. maxima  and indu. maxima . In seveobserved ,130,131.efficacy . In a reefficacy  demonstrE. acervulina were demonstrated by Ding et al. [E. coli (BL21) showed a 36% reduction in fecal oocyst shedding, decreased intestinal lesion scores, and increased body weight gains in comparison with the non-immunized chickens. Subsequent studies have demonstrated that defined antigens, such as apical membrane antigen 1 (AMA1) and immune mapped Protein-1 (IMP1) from E. maxima, are potential vaccine candidates [E. maxima infection [E. maxima challenge was observed following vaccination with transgenic E. tenella oocysts expressing the AMA1 and IMP1 antigens of E. maxima in a broiler chicken model of coccidiosis [The protective effects of α-tubulin protein from g et al. . Chickenndidates ,134,135.cidiosis .Eimeria protein to protect against coccidiosis. Furthermore, variations in Eimeria strains as well as the high cost of producing multiple strains of Eimeria parasites will be limiting factors. Therefore, novel strategies to improve the efficacy of recombinant vaccination need to be developed in order for recombinant vaccine approaches to be successful in the field when it comes to vaccinating against coccidiosis [In comparison to using live and attenuated parasite vaccines, recombinant antigens are safe and more immunogenic since they are selected on the basis of their ability to induce various aspects of protective host immunity. However, since recombinant antigens do not elicit a wide spectrum of protective immune responses as living or attenuated parasite vaccines, there are some limitations associated with using a single recombinant cidiosis .E. acervulina protein elicited significant protective immunity against E. acervulina challenge infection. The 3-1E cDNA vaccine significantly reduced fecal oocyst shedding, and the efficacy of the vaccine was enhanced when the 3-1E cDNA vaccine was co-administered with an IFN-γ- or IL-2-expressing plasmid [E. acervulina infection showed an improved serum antibody response and higher levels of protection based on growth performance and parasite fecundity [E. tenella also induced protective immunity against coccidiosis based on reduced oocyst shedding and improved growth performance following E. tenella infection [E. maxima which is involved in apoptotic cell death, cell cycle control, and mitogenic signal transduction was evaluated [E. maxima in the pVAX1 vector reduced jejunum lesions and body weight loss following challenge infection with E. maxima. Furthermore, chickens vaccinated with Em14-3-3 showed higher percentages of circulating CD4+ lymphocytes with enhanced IFN-γ and TGF-β production compared to control chickens immunized with PBS alone. Zhang et al. [E. tenella and chicken IL-2 gene in pVAX1, elicited a significant level of protection against E. tenella infection, as indicated by a higher survival rate, greater average body weight gain, and a lower gut lesion score in vaccinated chickens. In addition, intramuscular delivery was the most efficient route for inducing a protective immune response, and two injections with 80 µg of each DNA were highly effective in terms of protection against coccidiosis challenge infection. Chickens vaccinated with a DNA vaccine of E. tenella surface antigen 4 (EtSAG4) exhibited higher levels of secretory IgY antibodies, a greater IL-17 and IFN-γ cytokine response, and better clinical performance in terms of body weight, oocyst output, and gut lesion scores compared to the non-immunized control [The principle of a DNA vaccine is to use a plasmid vector to transfer genes, since DNA must enter the cell in order to express the antigen it carries . Lilleho plasmid . Embryo ecundity . In anotnfection . The potvaluated . The immg et al.  investig control . Eimeria vaccine. Using a novel adjuvant delivery system, QCDC, Lee et al. [Eimeria. In other vaccine trials, Montanide IMS or an ISA series of adjuvants that comprise a mixture of a defined, enriched light mineral oil enhanced the immunogenicity of recombinant vaccines and elicited desired immune responses [E. tenella infection. Chickens co-immunized with profilin and ginsenoside extract showed greater antibody production, reduced gut lesions, and lowered oocyst fecundity compared to the chickens immunized with profilin only. Although many recombinant vaccines against coccidiosis have been reported, their effectiveness has not been comparable to live and attenuated vaccines in terms of the level of protection. Therefore, there is a timely need to evaluate various adjuvants and antigen delivery systems to maximize the efficacy of recombinant vaccines . Min et e et al.  demonstresponses ,122,132.esponses  evaluateSalmonella strains and pVAX1), a yeast vector (Saccharomyces cerevisiae), or bacterial vectors (pMV361 and pET32a) were evaluated in combination with immunogenic Eimeria antigens [Saccharomyces cerevisiae vector induced a higher level of protection with increased weight gain and reduced cecal pathology and fecal oocyst shedding compared with non-immunized chickens [E. maxima 14-3-3 antigen in pVAX1 and pET32a (+) delivery vectors induced significant protective response in E. maxima-infected chickens, including reduced oocyst production, lower jejunum lesions, and lower body weight loss, and better immune responses as indicated by higher percentages of CD4+ cells and enhanced serum antibody titers [The efficacy of recombinant vaccines can be improved by optimizing the antigen presentation system and using an antigen delivery system that induces a broader protective immune response . Variousantigens ,144,145.y titers .Salmonella enterica serovar Typhi (S. Typhi) or S. Typhimurium, have been successfully used to deliver heterologous antigens from various pathogens [Salmonella enteritidis (S. enteritidis) to deliver E. maxima TRAP family protein (EmTFP250) to demonstrate its vaccine efficacy against coccidiosis as measured by improved weight gain and reduced mortality. Wang et al. [E. tenella infection as measured by reduced cecal lesions and oocyst output.Attenuated strains of athogens  to stimuathogens . Shivaraathogens  used Salg et al.  used theEimeria parasites as vectors carrying other antigens has also been explored [Eimeria parasite delivery system due to its strict host specificity, safety, and large genome size [E. tenella oocysts as vaccine vectors to express the E. maxima antigens EmAMA1 and EmIMP1. The oral immunization of chickens with E. tenella vector carrying a Campylobacter jejuni antigen, CjaA, induced approximately 90% immune protection against Campylobacter jejuni infection compared with non-immunized or wild-type E. tenella-immunized chickens [E. tenella oocysts expressing two different viral antigens from infectious bursal disease virus (IBDV) and infectious laryngotracheitis virus (ILTV) elicited a serum antibody response [The possibility of using explored ,130,148.ome size ,150. Tanome size  and Pastome size  demonstrresponse .E. maxima gametocyte antigen (Gam82) which was expressed in tobacco leaves and showed its protective effects in terms of body weight gain and parasite fecundity.Studies utilizing plant-derived vectors have also been reported . Plant-bIn addition to vaccine development, various antibiotic alternative strategies, including hyperimmune egg yolk antibodies, phytochemicals, probiotics, prebiotics, and host defense peptides, have been successfully developed to mitigate coccidiosis . In addiMost of these have high potential because they reduce the pathogenic load, mitigate gut damage, and enhance local immunity in the intestines of poultry . In addiPassive immunization with pathogen-specific IgY antibodies is an effective prevention and treatment strategy which is effective as a potential antibiotic alternative for the treatment and prevention of various human and animal diseases . IgY antPassive immunization utilizing pathogen-specific egg yolk antibodies (IgY) is attracting increasing interest as an alternative strategy to AGPs to improve growth and feed efficiency in poultry ,164,165.®) protected chickens from a subsequent challenge of E. acervulina. Chickens fed diets supplemented with 10% or 20% Supracox® showed greater weight gain and lower oocyst production than chickens fed the basal diet. For chickens fed lower levels of Supracox® , fecal oocyst shedding was markedly reduced, but no effect on body weight gain in E. acervulina infection was observed. A similar effect was observed in E. maxima- and E. tenella-infected chickens with less body weight loss, alleviated intestinal lesions, and fecal oocyst production when compared to chickens fed a basal diet [Eimeria spp. . In another study, Xu et al. [Eimeria spp.  and observed its protective effect in E. tenella-infected chickens. Chickens fed diets supplemented with hyperimmune IgY showed greater body weight gain, reduced mortality, mitigated cecal lesion scores, and lower oocyst output compared with chickens fed a basal diet. The use of IgY antibodies in passive immunization offers several advantages in that it is environmentally friendly, nontoxic, and reduces the numbers of animals required for antibody production. The successful application of IgY in disease treatment and prevention of enteric pathogen infections in poultry and humans has already been achieved, but a novel delivery system will enhance its field application.Lee et al.  reportedsal diet . In bothu et al.  utilizedProbiotics are live microbial feed supplements which beneficially affect the host animal by improving its intestinal microbial balance. Prebiotics, by contrast, are non-digestible feed ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the gut ,170,171.In humans and animals, gut microflora is an important component of a primary line of defense. In poultry, probiotic supplementation of the intestinal microflora has been shown to positively regulate the microbiota in the intestine and inhibit the proliferation of pathogen colonies . TherefoLactobacillus-based probiotics in stimulating local immunity against coccidiosis. Lee et al. [bacillus-based direct-fed microbials  reduced the clinical signs and increased immunity in E. maxima-challenged chickens. In a study using a commercial product, Pediococcus, and Saccharomyces-based probiotics (MitoMax®), 1.0% or 0.1% MitoMax-supplemented diets decreased oocyst shedding in E. acervuline- or E. tenella-infected chickens. In addition, a 0.1% MitoMax-supplemented diet increased the serum levels of Eimeria-specific antibodies [Bacillus subtilis 1781 or 747 supplementation on E. maxima-infected chickens was investigated [B. subtilis 1781 or 747 showed improved growth performance to a level comparable to that induced by antibiotics (virginiamycin or BMD) without E. maxima infection. Post E. maxima infection, diet supplementation with B. subtilis 747 enhanced intestinal immunity and epithelial barrier integrity. With the development of “omics” technologies related to the investigation of gut health, the term “postbiotics” was coined and defined as a novel class of feed additives that are generally produced by beneficial gut microbes and which exert a positive influence on host health. In a recent in vivo feeding trial, the dietary feeding of Bacillus subtilis 1781 strain induced an alteration of chicken gut metabolites which was associated with the growth- and immune-promoting effects of B. subtilis probiotics [Dalloul et al. ,174 conde et al.  reportedtibodies . In a restigated . Chickenobiotics . InteresPrebiotics are non-digestible oligosaccharides and potential modulators of intestinal microflora that promote the growth of probiotics and their activities in the gut . ArabinoEimeria infection in poultry have been reported [E. acervulina lesions in chickens orally infected with three Eimeria spp. mixtures  at subclinical doses  [Eimeria spp. infection. In a subsequent study, the efficacy of an in ovo-delivered commercial prebiotic, Bi2tos , was examined [Eimeria. Prebiotics and probiotics have many antibacterial mechanisms in common. Accordingly, the use of prebiotics is emerging as a new approach to control coccidiosis.In some studies, the inhibitory effects of prebiotics against reported ,182,183.examined . In in oHost defense peptides (HDPs) are important effector molecules of the innate immune system; they are present in several organisms and play a significant role in the first line of host defense . They arEimeria parasites. Chicken NK-lysin-2 (cNK-2) is a natural lytic peptide that has been reported to have effective cytotoxicity against apicomplexan parasites such as Eimeria, by disrupting the sporozoite membrane [Eimeria spp. both in vitro and in vivo [+ and CD8+ intestinal IELs post infection with E. acervulina, E. maxima, and E. tenella. Subsequently, Lee et al. [E. tenella and E. acervulina. In addition, the disruption of the outer plasma membrane and loss of intracellular contents of E. tenella sporozoites were detected by transmission electron microscopy. The in vivo administration of the cNK-2 peptide demonstrated a novel anti-parasiticidal activity, measured by increased body weight gain and reduced fecal oocyst shedding. Antimicrobial peptides (AMPs) are another effective alternative to antibiotics since they have broad spectrum of bactericidal activity and selectivity. Cationic antimicrobial peptides are highly conserved in all organisms and are effective against many bacteria, including multidrug-resistant strains. AMPs act by disrupting the bacterial membrane based on their cationic nature . The immmembrane . cNK-2,  in vivo . Hong et in vivo  reportede et al.  investigBacillus spores to the intestine where Eimeria parasites interact with the host’s gut epithelial cells has been reported [B. subtilis that carries the cNK-2 peptide was orally given to young broiler chickens, following which they were challenged with viable E. acervulina oocysts. The results showed that B. subtilis-cNK-2 treatment is a promising and effective alternative strategy to replace antibiotics against coccidiosis based on its ability to reduce parasite survival, reduce coccidiosis-induced body weight loss, and decrease gut damage based on the enhanced expression of proteins associated with gut integrity and intestinal health. Su et al. [Eimeria spp. challenge. Overall, the AvBD response to an Eimeria challenge was inconsistent, whereas the expression of LEAP2 was continuously downregulated in the duodenum, jejunum, ileum, and ceca of chickens infected with E. acervulina, E. maxima, or E. tenella. This result suggests that LEAP2 is closely involved in the control of Eimeria infection. In a sustainable delivery system, AMPs not only promote host local immunity but also reduce parasite growth and promote a healthy gut microbial community. Moreover, effective industry-friendly delivery strategies for antibiotic alternatives will reduce the cost of labor and increase the effectiveness of antibiotic-free animal production. Recently, an oral delivery strategy using reported . A stablu et al.  profiledE. maxima-infected chickens, measured by lower oocyst shedding and the mitigation of lesions [The use of organic acids has resulted in considerable achievements in poultry and swine production. Dietary supplementation of acetic acid in broiler chickens was shown to improve growth performance (weight gain and feed consumption ratio) and pathological parameters  . Butyric lesions . The mec lesions . However lesions . No orgaE. acervulina and E. maxima were found to decrease the transcript levels of digestive enzymes and nutrient transporters [Lactobacillus, Ruminococcaceae, and Akkermansia, and decreased Bacteroides, which is responsible for poor feed efficiency in chickens [Bacillus spp. In chickens infected with a six-fold concentration of coccidial vaccine, an enzyme blend  in combination with three strains of Bacillus spp. reduced the inflammatory response and maintained a performance similar to that of unchallenged chickens [Coccidiosis infection noticeably increases the maintenance energy requirement of the host . In addisporters ,197. A fsporters ,198. Diechickens . Furtherchickens .Beyond the above-mentioned feed additives, new technologies are being applied to identify novel feed additives that trigger natural, physiological mechanisms in animals to cope with enteric infections, including quorum sensing, bacteriophages, and small molecular weights chemicals.Antibiotic alternatives represent a major unmet need for the livestock sector. However, the factors predicting their success or failure are complex. A framework for the evaluation of alternative candidates that may empower federal agencies, philanthropic organizations, and other key stakeholders to prioritize investments in antibiotic alternatives consistently and transparently was proposed in a recent workshop . This frEimeria parasites. Due to the complexity of host-parasite immunobiology, developing novel strategies for the effective prevention of coccidiosis will require a systematic, detailed analysis of host–parasite interactions at the molecular and cellular levels. Furthermore, a better understanding of the role of gut microbiota in the development and functioning of GALT, the interaction of the gut immune system with gut microbiota, and new concepts on gut–brain interaction is needed. Using optimal combinations of various alternatives coupled with good management and husbandry practices will be the key to maximizing performance and maintaining animal productivity while we move forward with the ultimate goal of reducing the use of antibiotics in the animal agriculture industry.Chicken is one of the most commonly available meat protein sources, and its demand is steadily increasing globally. The decline in the use of AGPs and the lack of discovery of new antimicrobials provide impetus to find alternatives to antibiotics. The recombinant vaccine strategy is one of the logical antibiotic-independent alternatives that has engendered much interest from the pharmaceutical industry ever since the technological advancement in genetic engineering was achieved. However, it has been difficult to find the nature of immunogenic parasite antigens, that elicit a wide spectrum of host protective immune responses, which is comparable to those induced by live parasites. Furthermore, the high-level production of these recombinant proteins is cost-prohibitive and there is a lack of appropriate delivery systems for recombinant proteins to ensure sustainable large flock field vaccination due to the high levels of mutability of


Helicobacter pylori species (NHPS) are newly emerging bacteria that naturally inhabit birds and mammals apart from humans and rarely cause diseases in humans. In recent years, a rise in the number of cases associated with NHPS infections in humans has been observed. Among them, infections with Helicobacter (H.) canis are sporadic and challenging to recognise clinically. To date, ten cases of H. canis infections in mainly immunocompromised humans have been reported in the literature. Transmission pathway is most likely zoonotic via the faecal-oral route during close contacts with dogs and cats or may result from a contaminated sheep milk intake. No clear guidelines for successful antibiotic regimen are known. Important additional risk factor for infection might be biologic agents and Janus kinase inhibitors (JAKi) used in the treatment of rheumatoid arthritis (RA) and other conditions. Herein we present the first case of H. canis bacteraemia in a RA patient treated with novel JAKi tofacitinib.Non-H. canis bacteraemia with underlying multilevel degenerative lumbar spinal stenosis. Identification of H. canis was performed by MALDI-TOF MS and 16 S rRNA gene sequence analysis of isolate from subcultured positive aerobic blood culture bottles. Antimicrobial susceptibility testing showed low minimum inhibitory concentrations to amoxicillin-clavulanate, cefotaxime, ceftriaxone, meropenem, and gentamicin. She was treated with combined antibiotic regimen  for 14 days, which resulted in total remission of the infection.A 65-year-old female patient with RA and rituximab-induced hypogammaglobulinemia treated with tofacitinib, methotrexate, and methylprednisolone came to a planned visit in our outpatient rheumatology clinic. She presented with a history of back pain that significantly worsened 2 days before visit. She had numbness and tingling sensation in both legs and muscle weakness. Neurological examination was within a normal range. The patient was afebrile, had no chills, and was haemodynamically stable. She was in close contact with her pet dogs. Laboratory examination showed increased markers of inflammation. She was found to have H. canis infection risk in patients with recent pet exposure and predisposing factors such as immunodeficiency disorders or diseases that demand immunosuppressive drug therapy. A minimum of two weeks of antibiotic therapy is suggested.Clinicians should recognise  Helicobacter (H.) pylori and non-Helicobacter pylori species (NHPS). H. pylori infects up to 50% of the human population and has been associated with peptic ulcers, chronic gastritis, and gastric cancer in humans [Helicobacter species are newly emerging Gram-negative spiral bacteria with unclear epidemiology and zoonotic transmission pathway . To daten humans . Contrarn humans . They han humans –4. In ren humans , 3, 4.Helicobacter canis is a member of the NHPS that inhabits lower intestinal as well as hepatobiliary tract of dogs and cats [Helicobacter canis, clinical case, infection) in April 2020, ten clinical cases of H. canis infection associated with human diseases have been described [H. canis [H. canis is most likely zoonotic via the faecal-oral route during close contacts with dogs and cats or may result from a contaminated sheep milk intake [H. canis bacteraemia in patients with primary immunodeficiency diseases  [H. canis bacteraemia in patients treated with immunosuppressive drugs [and cats . Accordiand cats  search  , 13. Anove drugs , 14. TabH. canis infection and that interfere with host immune system are biologic agents and Janus kinase inhibitors (JAKi) used in the treatment of rheumatoid arthritis (RA) and other conditions [One class of drugs that could represent a risk factor for nditions . Kourbetnditions . HoweverOne of the common biologic agents used for RA management is rituximab (RTX), a B-cell depleting drug . A commoOn the other hand, JAKi  are novel drugs that reversibly inhibit JAK and interfere with cytokine function and signal transduction to the nucleus via the JAK/STAT pathway . CompareH. canis in a female RA patient treated with tofacitinib and secondary rituximab-induced IgM/IgG hypogammaglobulinemia who was in close contact with her pet dogs. To the best of our knowledge, H. canis infection in a patient treated with tofacitinib has not been described before.Herein we present a case of bacteraemia caused by A 65-year patient with seropositive RA and arterial hypertension came to a planned visit in our outpatient rheumatology clinic. She was diagnosed with RA in 1996 based on the American Rheumatism Association revised criteria for RA classification . During 9/L; reference value 4.00–10.00 × 109/L), mild neutrophilia , mild anaemia , increased C-reactive protein , increased sedimentation rate , and negative procalcitonin . She was admitted to the hospital because of a suspected spondylodiscitis. Immunosuppressive therapy was discontinued. As the patient was afebrile, had no chills, no left shift leukocytosis, negative procalcitonin and there was a possibility that increased markers of inflammation reflected the baseline disease (RA), no empirical antibiotic therapy was initiated.In the outpatient clinic, the patient presented with a history of back pain that significantly worsened 2 days before visit with severe pain radiating to both legs, numbness and tingling sensation in both legs, and muscle weakness. She was unstable while walking. Neurological examination was within a normal range. The patient was afebrile, had no chills, and was haemodynamically stable. Laboratory examination showed normal blood leukocyte count  degenerative lumbar spinal stenosis . The same day, blood samples were collected for culture. Blood was drawn in 4 blood culture bottles . After 5 days of incubation , both aerobic bottles flagged positive. Gram stain showed the presence of Gram-negative spiral rods Fig. . As it whttps://www.cdc.gov/microbenet/index.html).Additionally, 16 S rRNA sequence analysis of isolate was performed. DNA from pure culture was extracted with Chelex 100 Resin (BioRad). Amplification of the full  16 S rRNA gene was performed as described previously by Bianciotto et al. . AmplifiH. canis previously obtained with MALDI-TOF MS. Antimicrobial susceptibility testing, performed with gradient E-test MIC method (ETEST - BioMerieux), showed low minimum inhibitory concentrations (MICs) to amoxicillin-clavulanate, cefotaxime, ceftriaxone, meropenem, and gentamicin .On the 9th day, after  reports , 13. FivBorrelia burgdorferi, Leptospira spp., and stool culture  were negative.In between, due to anaemia and increased markers of inflammation, other foci of inflammation or malignancy were investigated . HoweverHelicobacter species at discharge.Before discharge, blood samples for control blood cultures were collected. All were sterile. Furthermore, primary sterile samples were tested for 16 S rRNA gene sequencing. All samples were negative for 16 S rRNA gene of H. canis and RA treated with tofacitinib in combination therapy. Infection occurred 8 months after treatment initiation. According to previous case reports , 4.1% risk for herpes zoster, and 0.6% risk for opportunistic infections excluding TBC . The risH. canis case reports might be challenging and easily overlooked laboratory recognition. H. canis can grow in standard aerobic blood cultures, however, in general, micro-aerophilic atmosphere conditions (37 or 42 °C) are needed for growth [Another factor contributing to a low number of r growth . Furtherr growth . Until rr growth , 13, 27.H. canis bacteraemia are available. Previous case reports described different treatment regimens. Some patients were treated with amoxicillin-clavulanate [in vitro antimicrobial susceptibility testing are presented. Like our results, Leeman et al. found susceptibility of H. canis to amoxicillin, amoxicillin-clavulanate, ceftriaxone, piperacillin-tazobactam, imipenem, metronidazole, and clindamycin [H. canis infections cannot be made. However, this is the fifth case where either a third-generation cephalosporin or doxycycline was used and resulted in complete remission of H. canis infection [Currently, no recommendations for treatment of vulanate  or ceftrvulanate , whereasvulanate  or a comvulanate . A minimndamycin . Other sndamycin . Clear rnfection , 13, 14.H. canis infections are rare and difficult to diagnose. Clinicians should recognise risk for infection in patients with recent exposure to dogs, cats or sheep while not improving with standard therapy. Risk further increases with underlying comorbidities, especially, autoimmune diseases, immunodeficiency disorders, or use of immunosuppressive agents. A minimum of 2 weeks of therapy is suggested [In conclusion, uggested .


New imaging approaches question a long-standing model for how the eyes of fruit flies acquire their geometric patterning. Related research article Gallagher KD, Mani M, Carthew RW. 2022. Emergence of a geometric pattern of cell fates from tissue-scale mechanics in the Drosophila eye. eLife11:e72806. doi: 10.7554/eLife.72806.Drosophila, with clusters of photoreceptor neurons regularly distributed amongst epithelial support cells. Each cluster will go on to form one facet in the compound adult eye  for an organism to develop (A few recent studies focusing on the later stages of eye development in  develop . These f


Streptococcus equi subsp. zooepidemicus (S. equi subsp. zooepidemicus), which carries the Lancefield group C antigen, is an uncommon human pathogen. It is considered an opportunistic commensal of the equine upper respiratory tract and causes invasive infections in immunocompromised hosts, following close contact to infected horses. Meningitis caused by S. equi subsp. zooepidemicus is a rare infectious disease with high rates of complications. We present the case of a 56-year-old female with acutely altered mental status following three days of fever and vomiting. For several months, she was taking care of horses. The most relevant preexisting illnesses were chronic hepatitis C infection and traumatic paraplegia due to spinal cord injury 30 years ago. Laboratory evaluation on admission revealed leukocytosis, hyponatremia, and elevated C-reactive protein. Cerebral CT scan showed diffuse cerebral edema. Whereas cerebrospinal fluid real-time PCR assay for common pathogens was negative, cultures showed S. equi subsp. zooepidemicus. She recovered fully after intravenous administration of ceftriaxone for four weeks. This is one of only few reported cases of S. equi subsp. zooepidemicus meningitis and the first case in chronic hepatitis C infection. Our case supports the necessity for extended microbiological examination especially in immunocompromised patients if PCR examination for common pathogens is negative. Streptococcus equi subsp. zooepidemicus (S. equi subsp. zooepidemicus) belongs to a group of beta-hemolytic streptococci with Lancefield group C antigen, whereas S. dysgalactiae subsp. dysgalactiae, S. dysgalactiae subsp. equisimilis, S. equi subsp. equi, S. anginosus, S. constellatus subsp. pharyngis, and S. phocae may contain the C antigen as well [S. equi subsp. equi, S. equi subsp. zooepidemicus is a typically opportunistic pathogen in horses and causes severe diseases such as pneumonia, arthritis, and wound infection [S. equi subsp. zooepidemicus infections are rare but capable to induce a variety of clinical symptoms including sinusitis, endocarditis, septic arthritis, osteomyelitis, pericarditis, and streptococcal toxic shock syndrome [S. equi subsp. zooepidemicus in a patient with chronic hepatitis C. This has previously not been recognized as an infectious agent in this context. as well . In contnfection . In humasyndrome . Howeversyndrome , 4. We rμl. CSF real-time PCR assay for common CSF pathogens  was negative. Blood cultures taken on admission were negative. CSF cultures confirmed β-hemolytic, gram-positive streptococci (S. equi subsp. zooepidemicus by mass spectrometry due to MALDI-TOF MS (Bruker®) using the MBT IVD Library 9.0 giving a score value of 2.49. In addition, the cerebrospinal fluid was examined by a commercial PCR targeting the 16S ribosomal DNA . DNA was extracted by MolYsis™ complete kit (Molzym). Both kits were used according to the manufacturer's instructions. The PCR product of 430 base pairs was sequenced and used for Blast® search in GenBank® . The sequence obtained from the CSF was identical to S. equi, but subspecies could not be identified by this molecular tool.A 56-year-old Caucasian female presented with a 3-day history of fever, vomiting for 2 days, and altered sensorium since the morning of presentation to our emergency department. On examination, the weight was 52 kg and the height was 168 cm. She suffered from complete paraplegia due to spinal cord injury 30 years ago with absence of motor and sensory function below Th1 and from chronic hepatitis C infection. She was drowsy but arousable. At the time of admission, body temperature was 101.8 F, with otherwise normal vital signs. Except for preexisting paraplegia, there were no further symptoms or signs of neurological deficit, in particular, no nuchal rigidity. Laboratory chemistry revealed normal hepatic and altered inflammatory parameters , as well as reduced levels of natrium (131 mmol/l). Initial computed tomography scan of the brain showed diffuse cerebral edema . The patptococci  which weS. equi subsp. zooepidemicus isolates were tested susceptible for ceftriaxone as well as for penicillin and ampicillin. Resistance determination was carried out according to the current EUCAST Standard Version 11.0 of 2021 using agar diffusion methods. Searching for a possible path of infection, a small chronic wound on the left leg was observed. However, multiple cultures of the skin lesions were tested negative. The patient confirmed close contact to horses before onset of symptoms and recovered completely after a two-week course of ceftriaxone.The S. equi subsp. zooepidemicus is known to be pathogenic especially in horses and considered as an opportunistic commensal of the upper respiratory tract. In humans, contact with infected horses or dogs or ingestion of unpasteurized cheese or milk from infected cows has reported prerequisites for infection with S. equi subsp. zooepidemicus [Streptococcus equi” in combination with “meningitis” evaluated 32 cases of reported meningitis with S. equi subsp. zooepidemicus [idemicus . In our idemicus . Classicidemicus . As in oS. equi subsp. zooepidemicus meningitis may be higher as expected. Most of the regularly used real-time PCR tests for common CSF pathogens do not include the detection of S. equi subsp. zooepidemicus. These streptococci usually respond to treatment with β-lactam antibiotics, which are recommended and used for therapy of unclear pathogens [Moreover, the real incidence of athogens .S. equi subsp. zooepidemicus [S. equi subsp. zooepidemicus bacteremia, our patient did not develop liver cirrhosis [Immunosuppression may be a risk factor for infection with idemicus , 4. Our irrhosis . Howeverirrhosis , 8.S. equi subsp. zooepidemicus meningitis, and hearing loss is a frequent complication (19%). Only 38% of patients recover completely; the majority of recovered patients received extended therapy with penicillins or third-generation cephalosporins [Fortunately, our patient recovered completely following a two-week administration of intravenous ceftriaxone. Remarkably, there is a crude mortality rate of 24% in patients with ication 1%. Only 3In particular, in cases of unclear pathogens in sepsis and/or meningitis, multiple cultures of relevant samples for microbiological diagnostic before antibiotic treatment are highly important.


RAD), belongs to the MYB gene family and regulates a variety of functions including floral dorsoventral asymmetry in Antirrhinum majus and development of fruit proteins in Solanum lycopersicum. RAD genes contain an SNF2_N superfamily domain. Here, we comprehensively identified 68 RAD genes from six different species including Arabidopsis and five species of cotton.RADIALIS . Next, GhRAD genes were regulated by phytohormonal stresses . Moreover, Ghi-miRN1496, Ghi-miR1440, Ghi-miR2111b, Ghi-miR2950a, Ghi-miR390a, Ghi-miR390b and Ghi-miR7495 were the miRNAs targeting most of GhRAD genes.Phylogenetic analysis classified RAD genes are evolutionary conserved and might be involved in different developmental processes and hormonal stress response. Data presented in our study could be used as the basis for future studies of RAD genes in cotton.Our study revealed that The online version contains supplementary material available at 10.1186/s12864-021-08248-z. MYB gene family members mainly regulate apoptosis, cell differentiation and proliferation. A- MYB, B- MYB and C-MYB are three groups of MYB gene family ..GGPPS . He. HeGossyRAD genes from Arabidopsis and five Gossypium species. Interestingly, the number of GhRAD genes was higher as compared to GaRAD and GrRAD genes, possibly because G. hirsutum is an allotetraploid crop resulting from hybridization of A and D genome progenitors. In upland cotton, both At and Dt sub-genome donors are orthologous relatives, leading to the GhRAD gene duplication [GhRAD genes, the numbers of GhRAD genes were equal to the total number of GaRAD and GrRAD genes. Phylogenetic analysis naturally classified RAD genes into five clades from RAD-a to RAD-e with 24 genes in RAD-a clade and two genes in RAD-e clade. Most of the RAD genes from diploids and allotetraploids were distributed closely in the phylogenetic tree, indicating that tetraploid cotton was produced after the hybridization of A and D genomes progenitors. From the phylogenetic tree we observed that RAD-a, RAD-b and RAD-d clades were ancient groups containing RAD genes from all selected plant species. Whereas, RAD-e clade might be more advanced containing RAD genes from only two selected plant species including G. hirsutum and G. raimondii, however, RAD-c clade lacks the genes from Arabidopsis.In this study, we identified lication . BecauseG. hirsutum, G. raimondii and Arabidopsis also supported these findings as the results of sequence logos showed significantly conserved pattern of amino acid across N and C terminals. Each conserved amino acid showed similar positions in three different species.Analysis of sequence logos of cis-acting elements in promoter regions are specific and consistent, for example, cis-acting elements of AuxRE were generally present in auxin-induced promoters regions [cis-acting elements, I-box, G-box, and GT1-motif were generally present in the light-induced promoters [cis-acting elements were found in drought-induced promoters [cis-acting elements were present in GhRAD genes promotors. Previous studies have shown that phytohormones maintain the integrity of plant cell walls. MeJA mediates gene expression in responses to plant injury [cis-acting elements help plants to respond quickly to stress and improve plant resistance to environmental stresses by activating different stress related genes. GhRAD promoter regions contain different cis-acting elements related to phyto- hormones, plant growth and development, seed specific regulation, meristem and endosperm expression and cell cycle regulation. In the present study, we found the uneven distribution of GhRADs on the chromosomes of At and Dt sub-genome. Uneven distribution of GhRAD genes indicated that during evolution and hybridization, these genes might have experienced gene duplication.Interaction between transcription factors and promoter binding sites is important for gene regulation at the transcriptional level and transcriptional regulation is mainly responsible for regulation of gene expression. Different external signals activated inducible promoters and  regions , similarromoters –45. Likeromoters . In our t injury . Auxin rt injury . In strat injury . Stress GhRADs intron length might play major roles. It has been reported that gene structure is associated with the evolution of different plant species [RAD genes showed that most of the RAD genes were greatly conserved during evolution. As RAD genes introns were not lost during evolution and at the early expansion stages of evolution, these genes diverged, whereas, over evolutionary time, other genes lost their introns [GhRAD genes was conserved indicating that the proteins with similar kind of motif distribution pattern might have some specific functions in cotton growth and development.Gene structure is important to predict gene evolution . Here, w species . The evo introns , indicat introns . Gene fa introns  while geRAD genes in different plant species but no research has been conducted to find the functional mechanisms of RAD genes in cotton. As our results indicated that promotor of GhRADs contain elements related to phytohormones, plant growth and development, seed specific regulation, meristem and endosperm expression and cell cycle regulation, so to check the potential regulatory functions of GhRADs during cotton growth and development, we evaluated the transcript patterns of 17 GhRAD genes using qRT-PCR. Results indicated that many GhRAD genes showed high expression in roots. However, GhRAD2, GhRAD3, GhRAD4 and GhRAD11 showed significantly high expression in flower tissues. Results indicated that GhRAD genes might be playing a positive role in root and flower development. All GhRAD genes showed poor expression in fiber development stages except GhRAD11 had relatively high expression at 20 DPA fiber.In the recent years, different researches have been done to identify the function of GhRADs for three different phytohormones indicated that GhRAD genes can be regulated by the exposure of phytohormones such as BL, IAA and JA. GhRAD1 and GhRAD2 showed upregulated expression for observed phytohormones, suggesting that these genes may have a positive role in phytohormones signaling.Different research studies indicated that phytohormones respond positively to abiotic stress response . Auxin rGhRAD genes targeted by various miRNA. Precisely, Ghi-miRN1496, Ghi-miR1440, Ghi-miR2111b, Ghi-miR2950a, Ghi-miR390a, Ghi-miR390b and Ghi-miR7495 were the miRNAs targeting most of GhRAD genes. Our results will lay the foundation for future research about biological functions of GhRAD miRNAs and also their target sites in G. hirsutum.Previous studies reported that miRNAs have significant functions in plant growth and development, regulation of cell growth and different metabolism associated with cotton fiber development and also respond to different environmental stresses including cold, heat and drought . In the Ka/Ks ratios of GhRADs and GbRADs. Genes with Ka/Ks = 1.0 are considered as pseudogenes as a result of neutral selection, Ka/Ks less than1.0 demonstrates the tendency of duplicated genes for purifying selection, while Ka/Ks ratios greater than 1.0 exhibits positive selection of accelerated evolution. Ka/Ks values of most GhRAD and GbRAD were less than 1 indicating that during the long-term evolutionary process, RAD gene family experienced purifying selection pressure.Next we calculated the RAD genes. Phylogenetic analysis divided RAD genes into five clades on the basis of sequence homology. Sequence logos, exon-intron structure, protein motifs and conserved domain analysis indicated that GhRAD genes were highly conserved during evolution with the uneven distribution on the chromosomes. Collinearity and selection pressure analysis indicated the expansion of RAD gene family in G. hirsutum and G. barbadense with purifying selection pressure. Promoter cis-acting elements analysis indicated the presence of several plant growth and stress related regulatory elements. Tissue specific expression pattern analysis of GhRAD genes indicated that some GhRAD genes showed significantly high expression in roots and flowers, except GhRAD11 had maximum expression at 20 DPA fiber. Further, GhRADs showed regulatory response under three phytohormonal stresses indicating candidate genetic material for cotton breeding against different stresses.In the present study, we conducted a comprehensive genome wide analysis to identify phylogenetic relationship, sequence conservation and biological functions of G. hirsutum, G. raimondii, G. arboreum, G. barbadense and G. herbaceum) were acquired from the Cotton FGD (https://cottonfgd.org/) [Arabidopsis protein sequences of RAD genes were acquired from Arabidopsis Information Resource, version 10 (TAIR 10) (http://www.arabidopsis.org). The AtRAD genes were used as queries to identify the RAD genes in other plant species. SMART (http://smart.embl-heidelberg.de/) and Interproscan 63.0 (http://www.ebi.ac.uk/InterProScan/) were used to confirm RAD protein sequences [http://pfam.janelia.org/) and hidden Markov model (HMM) was used to identify the conserved domain of RADs [RAD genes, ExPASy-ProtParam tool (http://us.expasy.org/tools/protparam.html) was used. Subcellular localization was predicted by CELLO v2.5 server [The database of cotton species including (gd.org/) . The Araequences . Further of RADs . Moreove5 server .RAD gene family, Clustal W was used for multiple sequence alignment [Arabidopsis, G. hirsutum and G. raimondii were aligned with Clustal W [For phylogenetic analysis of lignment  with thelignment  with 100lustal W  and protlustal W .GhRADs was determined by cotton genome annotation data (ftp://ftp.bioinfo.wsu.edu/species/Gossypium hirsutum/NAU-NBI_G) and extracted gff3-files was used in MapInspect software (https://mapinspect.software.informer.com/) to map genes to their corresponding chromosomes. For gene structure analysis of GhRADs, Gene Structure Display Server 2.0 (GSDS) was used (http://gsds.cbi.pku.edu.cn/index.php) [http://meme-suite.org) [GhRAD gene family and finally motifs were displayed by TBtools [Chromosomal position of dex.php) . Online ite.org)  was used TBtools .cis-acting element, 2-kb upstream promotor regions were downloaded from Cotton FGD website [http://www.bork.embl.de/pal2nal/). Finally, Ka and Ks values were calculated with the help of the CODEML program using the PAML package. For expression pattern analysis of GhRADs, RNA seq data (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482290/) was used and heatmap was generated by using TBtools [For analysis of promotor  website  and subj website . During  website , 76 and  website . Non-syn TBtools .http://bioinformatics.cau.edu.cn/PMRD/) [www.mirbase.org/) [http://www.ncbi.nlm.nih.gov/nucest) were used to obtain MicroRNA sequences of G. hirsutum. Predictions of miRNA target sites were done with the help of psRNATarget server (http://plantgrn.noble.org/psRNATarget/home) as described previously [Plant MicroRNA database (n/PMRD/) , miRBasese.org/)  and the eviously .GhHis3 (GenBank accession no. AF024716) was used as internal control. PCR reaction was done in three replications. Results of qRT-PCR were calculated as described previously [In this research, the CRI24 variety was used for gene expression analysis. Total RNA was extracted by collecting cotton samples from the field. For tissue specific expression pattern analysis, plant samples such as root, stem, leaf, flower and 0, 5, 1 and 20 DPA fiber were used. Similarly, for hormonal stresses, cotton seedlings were subjected to JA, BL and IAA treatment for 1, 3, 6 and 12 h. RNA extraction was done with the help of RNAprep Pure Plant Kit , after that cDNA was synthesized by using the Prime-Script®RT reagent kit . Green qPCR SuperMix was used to conduct qRT-PCR assay and eviously . PrimersAdditional file 1 : Figure S1. Phylogenetic relationship between G. hirsutum and Arabidopsis. Phylogenetic tree was constructed using RAD protein sequences by iTOL software.Additional file 2 : Figure S2. Gene structure of GhRAD genes. Yellow boxes represent exons while black lines indicate introns.Additional file 3 : Figure S3. Conserved domain analysis of GhRAD proteins. Each domain was represented in different colors and their names were mentioned with color boxes.Additional file 4 : Figure S4. Protein motif analysis of GhRAD proteins. Each motif was indicated with different color and phylogenetic analysis grouped GhRAD proteins according to the protein motif distribution pattern.Additional file 5 : Figure S5. Chromosomal distribution of GhRAD genes. MapInspect software (https://mapinspect.software.Informer.com/) was used to map genes to their corresponding chromosomes.Additional file 6 : Figure S6. RNA-seq data analysis of 17 GhRAD genes in root, stem, leaf, torus, petal, stamen, pistil, calycle, − 3, − 1, 0, 1, 3, 5, 10, 20, 25 and 35 DPA ovules and 5, 10, 20 and 25 DPA fiber.Additional file 7 : Table S1.RAD5/RAD16-like Gene Family members.Additional file 8 : Table S2. Biophysical properties of the GhRAD genes.Additional file 9 : Table S3. Orthologous.paralogous gene pairs and Ks/Ks values of GhRAD gene family members.Additional file 10 : Table S4. Orthologous.paralogous gene pairs and Ks/Ks values of GbRAD gene family members.Additional file 11 : Table S5. MicroRNA (miRNA) target sites of GhRAD genes.Additional file 12 : Table S6.GhRAD genes primers for qRT-PCR.Additional file 13 : Table S7. Proposed name of RAD gene family members.


Pseudomonas cannabina pv. alisalensis and P. syringae pv. maculicola cause bacterial leaf blight and bacterial leaf spot of crucifers (Brassicaceae). Both pathogens are threats to the cultivation of cruciferous crops. Here, we sequenced two strains of each pathogen, which will contribute to the development of countermeasures for the above diseases. Pseudomonas cannabina pv. alisalensis and Pseudomonas syringae pv. maculicola cause bacterial leaf blight and bacterial leaf spot of crucifers (Brassicaceae). Both pathogens are threats to the cultivation of cruciferous crops. Here, we sequenced two strains of each pathogen, which will contribute to the development of countermeasures for the above diseases. Pseudomonas cannabina pv. alisalensis and Pseudomonas syringae pv. maculicola cause bacterial leaf blight in crucifers and bacterial leaf spot of crucifers, respectively  and the draft genome sequences of P. cannabina pv. alisalensis MAFF 106156 (Chinese cabbage isolate) and P. syringae pv. maculicola SUPP 2206 (turnip isolate).ectively . Both paectively . It is iThe MAFF strains were deposited in the NARO Genebank, and the SUPP strain was maintained in the Shizuoka University Plant Pathology Culture Collection. Information about all the strains used in this study  is described in our previous paper . Each stde novo following a hybrid Nanopore DNBseq approach using Unicycler v0.4.7 . For long-read sequencing, a ligation sequencing kit was used  without DNA shearing; sequencing was conducted using a GridION X5 system (ONT) on an R9.4.1 flow cell (FLO-MIN106). Long-read sequence data were base called using Guppy v4.0.11+f1071ce   for MAFFde novo using SOAPdenovo v1.05  using the HiSeq 4000 platform . Short-read sequencing (2 × 100-bp paired-end format) was carried out as described in our previous report , yieldinvo v1.05  and annoGenomic information is listed in P. cannabina pv. alisalensis MAFF 301419  and P. syringae pv. maculicola MAFF 302723 , as well as the draft genome sequences of P. cannabina pv. alisalensis MAFF 106156 (accession no. JAEVFO000000000) and Pseudomonas syringae pv. maculicola SUPP 2206 (accession no. JAEVFP000000000), have been deposited in GenBank. The raw sequencing reads were deposited under the SRA accession no. SRR13295144 and SRR13295143 for MAFF 301419, SRR13295147 and SRR13295146 for MAFF 302723, SRR13295759 for MAFF 106156, and SRR13295745 for SUPP 2206.The complete genome sequences of


Acinetobacter baumannii. We sought to characterize potential interactions between rifabutin and colistin, the last-resort drug for carbapenem-resistant infections. Rifabutin and colistin were synergistic in vitro and in vivo, and low-dose colistin significantly suppressed emergence of resistance to rifabutin. Thus, this combination is a promising therapeutic option for highly resistant A. baumannii infections.Recently, we reported rifabutin hyperactivity against  Acinetobacter baumannii. We sought to characterize potential interactions between rifabutin and colistin, the last-resort drug for carbapenem-resistant infections. Rifabutin and colistin were synergistic in vitro and in vivo, and low-dose colistin significantly suppressed emergence of resistance to rifabutin. Thus, this combination is a promising therapeutic option for highly resistant A. baumannii infections.Recently, we reported rifabutin hyperactivity against  Acinetobacter baumannii poses a significant problem for health care and has been identified by the World Health Organization (WHO) and the Centers for Disease Control (CDC) as a priority pathogen for which new antibiotics are needed . We found that rifabutin (RBT) possesses previously unrecognized hyperactivity (MIC < 0.05 mg/liter) against A. baumannii but only in physiological media and not in rich media  (Carbapenem-resistant e needed –3. We rech media . Additioin (RIF) .A. baumannii infections, but it did not significantly improve mortality  for treatment of extremely drug-resistant ortality . Since RA. baumannii were tested for susceptibility toward RBT, RIF, and COL in Mueller-Hinton II Broth (MHII) and RPMI with serum. The 10 selected isolates comprised a panel with different susceptibilities against RBT and COL, including antibiotic-sensitive, single-antibiotic-resistant, and double-antibiotic-resistant  with COL in vitro . HoweverA. baumannii (P < 0.05) (One of the concerns with using rifamycins as monotherapy is that bacteria may rapidly acquire resistance. We sought to determine whether the addition of COL could suppress the emergence of RBT resistance in aumannii . By plat < 0.05) .To allow for the accumulation of low-resistance-conferring mutations, we also conducted low inoculum serial passage of bacteria by serially passaging 20 times in sub-MIC conditions in MHII and RPMI without serum . Antibioin vivo. As suggested by prior results  and with RBT monotherapy  (P = 0.05)  plates supplemented with 8 mg/liter RBT  and E. I= 0.026) . There w = 0.05) .A. baumannii because RBT, and not RIF, is able to rapidly traffic through the bacterial FhuE protein (We and others have recently described that RBT is hyperactive against  protein , 6. Furt protein , 7, 8. TA. baumannii infections. Importantly, a subtherapeutic dose of COL, which likely would result in diminished toxicity compared to that of standard dosing, was able to reduce the emergence of resistance to RBT during treatment of A. baumannii bacteremia in mice. These results indicate the promise of a low-dose COL + RBT combination regimen in the treatment of such infections.In summary, combination RBT + COL is a promising strategy to improve survival and reduce the emergence of resistance to RBT during treatment of


This study analyzed response inhibition, cognitive flexibility and working memory in three groups of patients diagnosed with obsessive-compulsive disorder, social anxiety disorder and generalized anxiety disorder, considering some variables that may influence results . Neuropsychological measures were completed using a computerized Wisconsin card sorting test, Stroop color word test, go/no-go task, digits and Corsi. Significant differences were obtained among groups in cognitive flexibility and working memory variables. The obsessive-compulsive disorder (OCD) group showed the worst results. The social anxiety disorder group obtained greater effect sizes in visuospatial memory. However, significant differences between groups in visuospatial memory were no longer present when nonverbal reasoning was controlled. Comorbidity influenced interference in the OCD and generalized anxiety disorder (GAD) groups. In addition, the executive functions were differently influenced by the level of obsessions and anxiety, and the use of pharmacotherapy. Study limitations include a non-random selection of participants, modest sample size and design type . The OCD group showed the worst results in flexibility cognitive and verbal working memory. Comorbidity, use of pharmacotherapy and level anxiety and obsessions were variables influencing the performance of executive functions. In the latest edition of the Statistical Manual of Mental Disorders , obsessiEF (executive function) can be considered as a set of high-level mechanisms whose purpose is the regulation of cognitive, motor and psychophysiological responses to achieve an objective . ResponsRI integrates all neural circuits responsible for intentional and voluntary control that prevent interference of non-relevant information with ongoing responses or response patterns. This system can suppress information that was needed in the past but is no longer needed today . RI is nResults obtained by some studies that analyzed EF in OCD, SAD and GAD are not conclusive. Along with OCD, the most researched anxiety disorders regarding EF are GAD, posttraumatic stress disorder (PTSD) and SAD . OCD andIn the successful review carried out by O’Toole and Pedersen , a totalOn the other hand, research developed by Fuji et al.  concludeThe most recent studies about SAD also present inconsistent data and results. Heeren et al.  in a stuNeuropsychological studies comparing executive functions among groups diagnosed with OCD, SAD and/or GAD are less frequent than those comparing a single type of disorder to HC. Cohen et al.  observedSome authors highlight limitations affecting the interpretation of study results. Some studies use self-report measures rather than clinical interviews; others have not evaluated anxiety and depression with quantitatively validated measurement instruments; not all studies controlled for modulatory variables; some variables could influence results—OCD subtypes, use of pharmacotherapy, age and sex, duration of disorder, age of onset and comorbidity—all of which should be controlled in each study. The use of non-standardized neuropsychological tests prevents a comparison of results and replication. The application of dimensional measures versus a categorical approach may result in the generation of analogous groups, hindering a comparison of results ,30,31,32Aims were as follows: (1) To analyze RI, CF and WM differences among clinical groups. (1.1.) To study if EF performance can be influenced by nonverbal reasoning. (1.2) To analyze if there are differences in EF among clinical groups. (1.3) To assess the relationship between EF and obsessions, worry and social anxiety.There were 89 participants between 17 and 61 years of age , diagnosed with OCD, GAD and SAD [Inclusion criteria were as follows: (i) diagnosis of OCD, GAD and SAD , (ii) OCThe study met ethical standards of the Declaration of Helsinki and has been approved by the Ethics Committee of the University of Murcia (Spain). All families provided written informed consent.After providing written consent, participants engaged in an individual diagnostic interview based on DSM-5 criteria, conducted by three clinical psychologists. An assessment was provided in two 60-min sessions by three experienced clinical psychologists who were trained by the fourth author for two sessions of one hour each. The test presentation order was the same for all participants. Participation in this study was voluntary and participants could discontinue at any given time.α = 0.87–90) and good convergent validity (r = 0.74 to r = 0.47). A total average greater than or equal to 16 is considered of clinical significance. In this study, Cronbach’s alpha in the OCD group was 0.86.Yale Brown Obsessive-Compulsive Scale (Y-BOCS) . Comprisα = 0.96).Penn State Worry Questionnaire (PSWQ) . A 16-itLiebowitz Social Anxiety Scale (LSAS) . A 24-itBeck-II Depression Inventory (BDI) . A 21-itBeck Anxiety Inventory (BAI) . A 21-itWisconsin card sorting test (WCST) . AssesseStroop color word test (SCWT) . Assesser = 0.87).Go/no-go task ,41 EvaluDigits span test (WAIS-IV) . This teCorsi block task (WMS-III) . EvaluatReynolds intellectual screening test (RIST) . It has Reliability indexes of neuropsychological measures were carried out on all persons who participated in the study.Firstly, Chi-square and one-factor ANOVA were used to examine potential group differences in clinical and demographic variables. Subsequently, ANOVA analysis (Brown–Forsythe) and post-hoc comparisons (Tukey or Games–Howell) of EF were then carried out. A covariance analysis was performed when there were significant differences among groups in some variables considered influential in their performance. Independent samples tests  were performed within each clinical group, taking into account the comorbidity, educational level and use of pharmacotherapy. The Pearson correlation was used to analyze the relationship between variables. Cohen’s d were calculated to estimate the magnitude of between-groups differences. All participants were included in the analyses. SPSS Statistic 22.00  was used for statistical analysis.p = 0.001), comorbidity p < 0.001), psychiatric treatment (p < 0.001) or type of pharmacotherapy (p < 0.001). Differences were seen in the categories variable (p = 0.003). See Groups were not equivalent in years of disorder duration (p = 0.002), perseverative responses (p = 0.007), perseverative errors (p = 0.003), non-perseverative errors of WSCT (p = 0.023), errors of omission of Go/No-Go (p = 0.036), with the GAD group obtaining the best scores. The highest effect size (ES) was in total errors and perseverative errors.Comparisons between the OCD and GAD groups reached statistical significance in the following variables: total errors (p = 0.036), non-perseverative errors (p = 0.021), digits span backward (p = 0.038), Corsi span forward (p = 0.001), Corsi span backward span (p < 0.01), total Corsi (p = 0.001), with the SAD group obtaining the best scores. The highest ES was in perseverative errors, non-perseverative errors and Corsi .Comparisons between the OCD and SAD groups reached statistical significance in the following variables: perseverative errors (p = 0.000), digits span backward (p = 0.010), Corsi span forward (p = 0.001), Corsi span backward (p = 0.010) and total Corsi (p = 0.036). The SAD group obtained the best scores. The GAD group achieved better results in errors of omission, and the SAD group presented greater effect sizes in digit span backward and Corsi. Comparisons between the GAD and SAD groups reached statistical significance only in the following variables: errors of omission (p = 0.026), being the differences between SAD and GAD (p = 0.007).Since the variable  obtained statistically significant differences among groups, an analysis of covariance was carried out see . This vap > 0.05). In total Corsi, only mean differences between the GAD and SAD groups (p = 0.007) were maintained, with the latter group achieving best results. Comparison between OCD and SAD did not achieve significant differences (p = 0.071).On the other hand, significant differences between groups no longer exist when controlling nonverbal reasoning in Corsi SPAN backward (p = 0.025), Stroop interference (p = 0.023), digit span backward (p = 0.022), total digit (p = 0.008) and total Corsi (p = 0.015), with higher performance in patients with no comorbidity. Pharmacotherapy type influenced the Corsi backward score (p < 0.01). Patients who were taking antipsychotics presented the worst scores.The OCD group presented significant differences regarding comorbidity in errors of commission (p = 0.034), Stroop interference (p = 0.049) and digit span forward (p = 0.023), with higher performance in patients who only presented GAD. The use of pharmacotherapy influenced variables: number of categories completed (p = 0.017), total errors (p = 0.045), non-perseverative errors (p = 0.001), errors of omission (p = 0.005), errors of commission (p = 0.041), Corsi span backward (p > 0.05) and total Corsi (p > 0.05). Participants not taking medication performed better.GAD participants suffering from other comorbid disorders presented significant differences in number of errors (p = 0.014), total errors (p < 0.001), perseverative response (p < 0.001), non-perseverative errors (p = 0.004), perseverative errors (p < 0.001), Corsi span backward (p = 0.022) and total Corsi (p = 0.001) with higher performance in patients not taking medication.No differences were found in the SAD group regarding comorbidity. The use of pharmacotherapy influenced in the number of categories completed  the higher the score in obsessions the higher number of errors.The OCD group only presented significant relationships between scores in OCI-R and errors of commission , Interference Stroop , Total Digit  and Corsi Span backward  with Worry a variable that negatively influenced results.The GAD group achieved significant correlations between the scores of the Penn State Worry Questionnaire and Stroop colors , perseverative responses , perseverative errors , non-perseverative errors , Digit Span forward , Digit Span backward , Digit Span increasing , Total Digit , Corsi Span backward  and Total Corsi . Therefore, the higher the average in Social performance, the worse the results.The SAD group presented significant relationships between scores in Social performance and total errors , total errors , perseverative responses , perseverative errors , non-perseverative errors , digit span forward , digit span backward , digit span increasing , total digit , and total Corsi . Therefore, the higher the score in social interaction the worse the performance.Social interaction reached significant relationships with total categories . The factors most closely related to OCD dysfunctions that WCST assesses are the number of categories completed and perseverative errors . No diffThe relationship of RI with anxiety disorders is unclear. On the one hand, some studies relate it only to disorders sharing transdiagnostic characteristics with OCD, such as Tourette’s disorder and trichotillomania , but notOur study provides empirical evidence of statistically significant differences among the three groups of disorders in errors of omission. In particular, the ES between OCD and SAD was small but high between SAD-GAD and moderate–high between GAD-OCD. These data indicate that OCD and SAD present a processing speed slower than GAD. Contrary to our hypothesis, we found no differences among groups in cognitive RI (Stroop interference) and motor RI . In future studies, the relationship between the different components of the variables analyzed should be analyzed with a larger sample size in order to see what kind of interactions arise between them. . CognitiThe main conclusions have been that the OCD group showed worse results in cognitive flexibility and working memory than the GAD and SAD groups. The SAD group presented better results in visuospatial working memory than the OCD and GAD groups. Comorbidity affected performance in cognitive and verbal RI in the OCD and GAD groups. The use of medication influenced visuospatial WM in all clinical groups. Furthermore, CF in the. SAD group and RI in the GAD group were affected by this variable. Finally, executive functions were differently influenced by the level of obsessions and anxiety.