Bordetella pertussis, a Gram-negative bacteria. Pertussis is a relatively contagious infectious disease in people of all ages, mainly affecting newborns and infants under 2 months of age. Pertussis is undergoing a resurgence despite decades of high rates of vaccination. To better cope with the challenge of pertussis resurgence, we evaluated its possible causes and potential countermeasures in the narrative review. Expanded vaccination coverage, optimized vaccination strategies, and the development of a new pertussis vaccine may contribute to the control of pertussis.Pertussis (whooping cough) is a respiratory disease caused primarily by  Bordetella pertussis (B. pertussis) was the most important pathogen that caused pertussis. It is a small, non-motile, strictly aerobic, Gram-negative bacillus that colonizes the respiratory tract of humans, causing respiratory disease. In the 1950s, Pearl Kendrick, Grace Eldering, and Loney Gordon developed an efficient whole-cell Pertussis (wP) that was used in a Diphtheria, Tetanus, and whole-cell Pertussis (DTwP) combined vaccine. The emergence of DTwP and its sequential use in some developed countries have substantially reduced the incidence of pertussis [B. pertussis is prone to adverse reactions. Therefore, vaccination coverage rates fell in many countries in the 1970s [B. pertussis, prevented pertussis with an efficiency similar to that of DTwP. Following successful clinical trials in the 1990s, the wP in many countries has been replaced by the safer acellular pertussis (aP) for pertussis vaccination [B. pertussis in aP include fimbrial proteins 2 and 3 (Fim2/3), filamentous hemagglutinin (FHA), pertussis toxin (PT), and pertactin (PRN) [B. pertussis and is expressed on the bacterial surface to promote bacterial binding to host cells [Pertussis (whooping cough) is called ‘cough for 100 days’ in folk medicine and is an acute respiratory infectious disease [ertussis . Howeverhe 1970s ,4. Sciencination ,7,8. Thest cells . FHA resst cells . PT is tst cells ,14. The st cells . The glost cells . Still, st cells . This phst cells . UnderstB. pertussis due to the respiratory tissue-resident memory T cells (TRM cells) induced by wP [B. pertussis was lower than that induced by natural infection and DTwP vaccination. The Pertussis resurgence is also associated with the low mucosal immune response induced by aP and the coverage of the vaccine. A study assessing pertussis vaccination and anti-pertussis herd immunity levels in the target vaccination population in 2019 found that low percentages of vaccination coverage and low anti-pertussis herd immunity levels in the target vaccination population were two of the factors explaining pertussis resurgence and persistence worldwide [B. pertussis presents antigenic drift under immune selection pressure after vaccination. The ongoing genetic shift and gene loss of B. pertussis affected the protection efficacies of the existing vaccines [B. pertussis [B. pertussis in nasopharyngeal specimens and thus help improve the diagnostic level [Pertussis resurgence might be attributed to the lower efficacy of the DTaP compared to the DTwP . Serum aed by wP . Thus, Dorldwide . In 2019orldwide . Anti-peorldwide . Vaccineorldwide ,29. Currvaccines , such asvaccines ,32. The vaccines ,34,35,36vaccines ,38. Withertussis ,40. In pertussis . Public ic level . TraditiB. pertussis infection in infants and young children, preventing approximately 70–90% of potential cases of pertussis disease and up to 90.5% of pertussis disease-related hospitalizations among infants under 3 months old [The vaccination policies should be optimized by establishing pertussis monitoring protocols, strengthening the pertussis monitoring, improving the detection level, understanding the actual incidence of pertussis, and then establishing prevention and control strategies according to its incidence and epidemic characteristics. Prenatal vaccination of pregnant women in the third trimester of pregnancy allows pregnant women to produce high levels of antibodies before delivery. These antibodies are transmitted to the fetus through the placenta. Then, infants are born with a high antibody titer to defend against pertussis infection . DTaP vanths old ,48. In 2nths old . Benefitnths old . Boosternths old ,52. Manynths old . Around nths old . Accordinths old . Becausenths old ,57. TherB. pertussis from the respiratory tract [B. pertussis infection by activating neutrophils [B. pertussis infection [Optimizing immunization policies, which only reduce pertussis incidence by increasing vaccine coverage, cannot significantly enhance the efficacy and duration of immune protection provided by the vaccine. Therefore, novel pertussis vaccines are urgently needed to address this challenge. Innate immune mechanisms by dendritic cells, macrophages, neutrophils, natural killer cells, and antimicrobial peptides contribute to the control of pertussis infection. However, complete bacterial clearance requires cellular-mediated immunity mediated by Th1 and Th17 cells . IFN-γ sry tract . Th17 cetrophils . The weanfection . The typnfection . TherefoB. pertussis using genetic engineering (by mutating the 9th residue arginine of the subunit to lysine and the 129th residue glutamic acid to glycine) to prepare pertussis strains with enzymatically inactive SA subunit reduced the complexity of traditional chemical detoxification processes and helped achieve more sustained immune protection [The use of the previously used pertussis vaccine, wP, has been almost eliminated because of more adverse reactions, including endotoxins such as lipo-oligosaccharide (LOS), which, although contributing considerably to the reactogenicity and efficacy of pertussis vaccines, are highly inflammatory. Chemical elimination of LOS significantly reduced the wP-induced endotoxin content (by 20%) and endotoxin-related toxicity (by up to 97%) without compromising the integrity, potency (antibody and T-cell response), and stability of wP . The SA otection .B. pertussis, which is required for infection and is an effective immunogen and protective antigen. The addition of the C terminal toxin repeat domain (RTX) antigen of ACT to aP at the appropriate dose enhanced the protection of immunized mice against the B. pertussis challenge [Δ), in combination with antigenic components of the pertussis vaccine, enhanced serum IgG antibody responses, induced NO and IFN-γ production in peritoneal macrophages and spleen cells. The increased immune response provided protection against the B. pertussis challenge [B. pertussis infection, may be involved in iron acquisition during host colonization, and is a highly antigenic protein. In a previous study, immunization of mice with recombinant AfuA-induced opsonophagocytic antibodies was found to protect the mice against pertussis [B. pertussis and positively regulated by iron starvation. Immunization of mice with recombinant IRP1–3 produced a strong antibody response that recognized native proteins on the bacterial surface, thus promoting effective phagocytosis of bacteria by human polymorphonuclear neutrophils (PMNs), which is a key protective approach against this pathogen. Thus, IRP1–3 exhibited a protective effect against B. pertussis infection in the mouse model [B. pertussis I and Saadet strains [Currently, the safety of aP is satisfactory, but the spectrum, depth, and persistence of aP-induced immune protection are poor. The addition of more antigenic components can effectively increase the immune protection provided by the existing aP. Adenylate cyclase toxin  is the main virulence factor of hallenge ,66. Adenhallenge . AfuA  was the most abundant, surface-exposed protein. A mice model proved that antibodies to BipA were found to efficiently opsonize bacteria [B. pertussis [B. pertussis biofilms. The antibodies induced by B. pertussis biofilms can effectively block the transmission and respiratory infection of B. pertussis. The immunization of mice with a combination of rBamB-rLptD and DTaP in the biofilm components induced IFN-γ and IL-17a locally in the spleen and lymph nodes. It provoked IgG2a antibody responses, exhibited better protection efficacy against B. pertussis than DTaP alone, and was well tolerated [Bacterial biofilm (BF) refers to a large number of bacterial aggregation membrane-like substances wrapping themselves. It is formed by bacteria adhering to the contact surface, secreting polysaccharide matrix, fibrin, lipid proteins, etc. The formation of biofilms might enhance the virulence of cination . In a prbacteria . In anotertussis . Extraceolerated . DTaP haB. pertussis-specific splenic Th1 and Th17 memory responses, as well as CD4+ TRM cells producing IL-17 and IFN-γ in the lungs induced by pertussis-OMV, play an important role in maintaining immune persistence [+ TRM cell responses [Outer membrane vesicles (OMVs) are secreted by bacteria into the external environment and are composed of several substances, such as outer membrane proteins, lipopolysaccharides (LPSs), and nucleic acids. OMVs have been used in two meningitis vaccines, which demonstrated the feasibility of OMVs as components of bacterial vaccines . A totalsistence . Parenteesponses . Vaccinaesponses ,85.B. pertussis infection because of the lack of Th1 cellular immunity [B. pertussis infection than equivalent aP prepared with aluminum adjuvant [B. pertussis (LP1569), synergistically induced the production of IFN-β, IL-12, and IL-23, as well as the maturation of DCs. Parenteral immunization of mice with LP-GMP combined with aP promoted Th1 and Th17 responses and protected the mice against B. pertussis lung infection. Moreover, intranasal immunization induced B. pertussis-specific Th17 responses and respiratory CD4+ TRM cell responses secreting IL–17 and provided a high degree of protection against intranasal colonization and lung infection for at least 10 months [B. pertussis-specific Th1 and Th17 responses and serum IgG2a/b antibodies and enhanced the protective efficacy of the aP against pertussis aerosol challenge [Lipopolysaccharide (LPS), a bacterial cell wall component of the wP, activates innate immune cells through toll-like receptor 4 (TLR4) and has good immunoreactivity . As a puimmunity . Some noimmunity . Only a immunity . Compareadjuvant . LP-GMP 0 months . The aP 0 months . The sma0 months . The aP hallenge . Similarhallenge . Adsorpthallenge . CpG adjhallenge ,97,98,99B. pertussis [In addition to TLR agonist adjuvants, other novel adjuvants have also been investigated in pertussis vaccines. Layered dihydroxide (LDH) is an efficient adjuvant platform that has been demonstrated to induce effective and persistent immune responses. Mg/Al-LDH, as a nanoadjuvant, significantly improved pertussis humoral immune responses . Poly [dertussis .B. pertussis-specific mucosal secretory IgA responses, whereas the Tdap group in this trail did not induce consistent mucosal secretory IgA responses. BPZE1 was well tolerated, with mild reactogenicity and no serious adverse events related to the vaccination [B. pertussis gene that encodes for skin necrosis toxin and replacement of the A mpG gene of pertussis by the A mpG gene of Escherichia coli, thus greatly reducing tracheal cytotoxin production. Studies have shown that the BPZE1 vaccine induced CD4+ CD69+ CD103+ TRM cells in the nasal mucosa of mice. These cells, in turn, produced high levels of IL-17 and considerable levels of IFN-γ. IL-17-dependent and SIgA-mediated protect the nasal and lung tissues of the mice from B. pertussis infection [B. pertussis [In order to induce protective systemic and mucosal immunity, vaccine candidates for live attenuated vaccines have been developed, including attenuated vaccine BPZE1, which has been assessed in several clinical trials ,103,104.cination . GamLPV,cination . BPZE1 wnfection ,108. BPZnfection . Ciaran nfection . These pnfection . TLR4-deertussis . At the ertussis .B. pertussis induced the production of anti-PT IgG antibodies. pcDNA/S1 showed significant protection against intracerebral challenge with lethal doses of B. pertussis [B. pertussis infection in the mice lungs [B. pertussis [Despite limited studies on nucleic acid vaccines for pertussis, some promising experimental results remain. Immunization of mice with plasmid DNA expressing the SA subunit of PT (PTS1) (pcDNA/S1) of ertussis . Other sce lungs . DNA vacce lungs . Furtherertussis . The furertussis .Δ, etc.) as well as OMV pertussis vaccines have the potential to be used in combination with tetanus and diphtheria vaccines, turning them into the novel pertussis–diphtheria–tetanus combined vaccines [Factors contributing to pertussis resurgence include the low immune potency of existing aP adjuvants, the regression of immunity in previously vaccinated individuals, the emergence of non-vaccine-type strains, and the mutation of new strains allowing them to escape the selection pressure of vaccines ,120. Incvaccines ,67,73,81vaccines ,123.The safety and social benefits of pertussis vaccines with new adjuvants for children and adults require careful consideration. Introducing new adjuvants to aP vaccines requires consideration of both the protective efficacy of the vaccines and extensive preclinical and clinical research. The impact of the new adjuvant on the immunogenicity of co-administered antigens such as diphtheria and tetanus components in the short or long term is still uncertain. Studies on TLR agonist-adjuvanted aP showed that TLR agonists alone induced better aP protection to a limited extent. A combination of several adjuvants was often required to stimulate strong antibody-based and cellular immune protection against each component of pertussis. The combination vaccines need to be used in early infancy, which introduces challenges regarding the safety of the novel adjuvanted pertussis–diphtheria–tetanus combination vaccines. Among the clinical trials on novel pertussis vaccines (excluding existing marketed aP vaccine manufacturing practices) , the cliCurrently, several attenuated pertussis vaccines are clinically available, including attenuated BPZE1 vaccines, which have been assessed through several clinical studies with ideal results. However, the BPZE1 vaccines need to be administered intranasally; therefore, they cannot be combined with existing diphtheria and tetanus vaccines to prepare a combined vaccine. Considering that the participants of the clinical studies on the existing BPZE1 vaccines comprise individuals aged 6–50 years , these vaccines can be used as a booster immunization and for “cocoon strategy” to promote early Th2 responses induced by DTaP vaccination to shift to more protective Th1/Th17 and mucosal responses ,124. How


Pasteurella multocida is a pathogen that seriously harms the cattle breeding industry. In this study, the clinical signs, bacterial load and proteomics of infected yaks were studied by infecting yaks with wild-type (WT) (P0901) and OmpH-deficient strains (ΔOmpH) of Pasteurella multocida. We found that compared with the mutant strain, the titer of wild-type strains was significantly higher in tissues. Additionally, compared with other organs, the bacteria titer was significantly higher in the spleen. Compared with the WT P0910 strain, the mutant strain generated milder pathological changes in the tissues of yak. Proteomics analysis revealed that 57 of the 773 proteins expressed in Pasteurella multocida were significantly differentially expressed between the ΔOmpH and P0910 groups. It was also found that P0910 and ΔOmpH in Pasteurella multocida infection activated the expression of ropE, HSPBP1, FERH, ATP10A, ABCA13, RRP7A, IL-10, IFN-γ, IL-17A, EGFR and dnaJ. Overall, deletion of the OmpH gene weakened the virulence but maintained the immunogenicity of Pasteurella multocida in yak. The findings of this study provide a strong foundation for the pathogenesis of Pasteurella multocida and the management of related septicemia in yaks.OmpH is among the most important virulence factors of Pasteurella multocida, which mediates septicemia in yaks (Bos grunniens I) after infection with the bacteria. In the present study, yaks were infected with wild-type (WT) (P0910) and OmpH-deficient (ΔOmpH) P. multocida strains. The mutant strain was generated through the reverse genetic operation system of pathogens and proteomics technology. The live-cell bacterial count and clinical manifestations of P. multocida infection in Qinghai yak tissues  were analyzed. The expression of differential proteins in the yak spleen under different treatments was analyzed using the marker-free method. We found that compared with the mutant strain, the titer of wild-type strains was significantly higher in tissues. Additionally, compared with other organs, the bacteria titer was significantly higher in the spleen. Compared with the WT p0910 strain, the mutant strain generated milder pathological changes in the tissues of yak. Proteomics analysis revealed that 57 of the 773 proteins expressed in P. multocida were significantly differentially expressed between the ΔOmpH and P0910 groups. Of the 57, 14 were over-expressed, whereas 43 were under-expressed. The differentially expressed proteins in the ΔompH group regulated the ABC transporter (ATP-powered translocation of many substrates across membranes) system, the two-component system, RNA degradation, RNA transcription, glycolysis/gluconeogenesis, biosynthesis of ubiquinone and other terpenoid-quinones, oxidative phosphorylation (citrate cycle) as well as fructose and mannose metabolism. The relationship among 54 significantly regulated proteins was analyzed using STRING. We found that WT P0910 and ΔOmpH of P. multocida infection activated the expression of ropE, HSPBP1, FERH, ATP10A, ABCA13, RRP7A, IL-10, IFN-γ, IL-17A, EGFR, and dnaJ. Overall, deletion of the OmpH gene weakened the virulence but maintained the immunogenicity of P. multocida in yak. The findings of this study provide a strong foundation for the pathogenesis of P. multocida and the management of related septicemia in yaks. Bos grunniens) is the main bovine on the Tibetan plateau and thrives well at an altitude above 3000 m. Yak is a versatile and hardy animal that thrives in very harsh environments [Pasteurella multocida (P. multocida), characterized by high fever, pneumonia, occasional acute gastroenteritis, and internal organ bleeding. It is among the most important diseases affecting Qinghai yak production [P. multocida poses a substantial public health risk. However, the genetic blueprint and the virulence and immune response mechanism against P. multocida in yak are unclear.Yak , among the most important outer membrane proteins of P. multocida, plays a key role in the pathogenicity and invasiveness of the bacteria [OmpH gene Pasteurella multicida of poultry origin is a 1062 bp fragment and displays 99.9% homology with the cp39 gene that codes for the capsule protein [OmpH gene deletion significantly reduces the resistance of the mutant bacteria to phagocytosis. Compared with the live attenuated bacteria, inactivated P. multocida display stronger immunogenicity and adhesion to the HeLa cells. The 39 kDa protein encoded by the OmpH gene is related to the pathogenicity of P. multocida. Interestingly, the 39 kDa protein in the P. multocida capsule is present in the inactivated but not live bacteria. The OmpH mutant provides 100% protection (against P. multocide) in poultry [P. multocida in Qinghai yaks might be related to hypoxia [ protein . Howeverue cells . Apart fbacteria . The Omp protein ,9. OmpH  poultry . Previou hypoxia .Pasteurella multocida has been detected in tissues, secretions, and excreta of livestock and poultry. The bacteria have also been detected in the tonsils and upper respiratory tract of healthy livestock and poultry [Pasteurella multocida infection mainly occurs via the digestive and respiratory routes, and transmission through animal bites, damaged skin, mucous membrane, insect vectors, contaminated equipment, drinking water, and feeds has also been reported [OmpH participates in the adhesion, invasion, pathogenesis, and virulence of P. multocida in yak is unclear. We explored this phenomenon in the present study. The effect of OmpH deletion on the immunogenicity of P. multocida was also explored. Reverse genetic operation systems of pathogens and proteomics technology have become powerful tools for assessing the effect of specific genes deletion on the virulence and pathogenicity of pathogenic organisms. Herein, Qinghai yaks were infected with wild-type strain (P0910) and OmpH-deficient strains (ΔOmpH). The corresponding viable bacteria count in tissues of this animal  was then quantified. The subsequent clinical manifestations in these organs and the immune response to these pathogens in the yak spleen were examined using label-free mass spectrometry. Herein, we explored the effect of OmpH gene deletion on the virulence and immunogenicity of P. multocida in yak. The findings of this study provide a solid background on the infection, pathogenicity, immunogenicity, as well as control and management of P. multocida infection, improving yak production. poultry . Pasteurreported ,14. WhetThe protocol for the animal experiments was approved by the Animal Care Committee of Qinghai University, China. Slaughtering of the animals was performed in accordance with the National Administration of Cattle Slaughtering and Quarantine guidelines .This research was conducted at Haibei Tibetan Autonomous Prefecture (HTAP), Qinghai Province, China. The region is located at more than 3000 m above sea level, northeastern of Qinghai–Tibetan Plateau. A total of 15 Qinghai yak calves  were used in this study and were fed through grazing on natural pastures.P. multocida P0910 strain used in this study was isolated from dead yaks in Qilian County, Qinghai Province. Pasteurella multocida was cultured in Trypticase Soy Broth (TSB) at 37 °C under constant shaking and the concentration of the bacterial solution was determined by plate counting. E. coli DH5α competent cells were purchased from Sangon . E. coli DH5α recombinant strains were screened on plates of Luria–Bertani (LB) medium supplemented with 100 μg/mL ampicillin. The pEX18AP plasmid was obtained from Dr Qingmin Wu, China Agricultural University.The OmpH gene downstream was amplified by Wu2011 and Wu2012. The upper and lower arm fragments were ligated by overlapping PCR and inserted into the EcoR I and BamH I sites of pEX18AP using the In-Fusion®HD Cloning Kit  to generate the recombinant plasmid pEX18AP-OMPH. The recombinant plasmid pEX18AP-OMPH was transformed into E. coli DH5α and positive samples were screened using LB agar with resistance. The pEX18AP-OMPH plasmid was transferred into P0910 receptor cells by electroporation, and the ΔOmpH mutant was screened on TSB ager with 100 μg/mL ampicillin and verified by PCR.Primers used in mutant strain construction are listed in 6 CFU/mL). Another six yaks in group B received a subcutaneous injection of ΔOmpH . Three yaks in the check group (Group C) received a subcutaneous injection of sterilized normal saline. After P0910 and ΔOmpH were adjusted to 2.0 × 106 CFU/mL, 1 mL of different bacterial solution was injected subcutaneously into different groups of yaks. Yaks in each group were raised separately. The morbidity and mortality in each group were observed every day. The thymus, lung, spleen, lymph node, liver, kidney, and heart tissues from the animals were collected at 24 and 48 h. The yaks that did not die at 24 and 48 h were dissected and the pathological changes were observed.The calves were randomly divided into three groups. Six yak calves in group A received a subcutaneous injection of P0910  of the tissue samples using the micro-inoculation colony counting method, each sample was repeated 3 times.FERH, HSPBP1, ABCA13 ATP10A RRP7A, IL-10, IFN-γ and dnaJ). All the primers were synthesized and provided by Sangon   phosphate-buffered saline solution. Proteomics analysis was performed at Novogene . The experiments were performed indecently three times. Proteins in the spleen were extracted using lysis buffer. The proteins (250 μg of each sample) were digested using the FASP procedure . The amo, China) .http://www.genome.jp/kegg/mapper.html (accessed on 15 November 2021). Significantly regulated pathways were identified using the Fisher’s exact test with statistical significance set at p < 0.05. The protein–protein interactions (PPIs) were predicted using the STRING program (http://string-db.org/ (accessed on 15 November 2021)). Bioinformatics analyses were performed as previously described by Jia . Functiop < 0.05.Continuous normally distributed data were expressed as the mean ± standard deviation (SD). Differences between groups were analyzed using the Duncan’s post hoc test. Statistical significance was set at OmpH gene in P. multocida, we constructed OmpH deletion strain (ΔOmpH) of P. multocida P0910. PCR results showed that the upstream and downstream homologous arms (362 bp and 462 bp) of the OmpH gene were amplified , but there was no interaction between the two factors (p > 0.05). Additionally, the viable count was significantly high in group A (P0910), relative to group B (ΔOmpH) (p < 0.05). Just like pathogenicity, infection time greatly influenced the number of viable bacterial count (p < 0.05), but there was no significant interaction between organs and infection time and the number of viable bacterial count (p > 0.05). Compared with other organs, the viable bacterial count was significantly higher in the spleen (p < 0.05) because the spleen is probably the main target organ for the bacteria  in tissues and organs strongly depended on the infection time and strains . Additionally, compared with the P0910 group, 439 and 334 proteins were over and under-expressed, respectively, in the ΔOmpH infection group. Among them, 57 were significantly differently expressed, in which 14 were significantly over-expressed, whereas 43 proteins were significantly under-expressed , molecular function (MF), and biological process (BP) regulated by the significantly regulated proteins between the P0910 and ΔOmpH groups were evaluated using Gene Ontology (GO) analysis a. The maKEGG pathway enrichment analysis revealed that 20 major pathways were regulated by the 57 differentially expressed proteins between the P0910 and ΔOmpH groups b. The moFurther analyses of the 57 differently expressed proteins between the ΔOmpH and the P0910 groups revealed that coding  and immune response-related proteins  formed a complex and intricate protein interaction network c.FERH, HSPBP1, ABCA13 ATP10A RRP7A, IL-10, IFN-γ and dnaJ). We found that the gene expression of FERH, HSPBP1, and ABCA13 genes was significantly higher in the ΔOmpH group, relative to the P0910 group (p < 0.05), but there was no significant difference in the expression of ATP10A between the two groups. However, the expressions of RRP7A, IL-10, IFN-γ, and dnaJ were (significantly high) higher in the P0910 than in the ΔOmpH group (p < 0.05). Overall, qPCR and the label-free analysis revealed comparable findings regarding the selected differentially expressed proteins  and respiratory tract of some healthy livestock and poultry. Upon entry into the body, P. multocida evades phagocytosis of macrophages to colonize the lungs [P. multocida wild-type strain by macrophages. This implies that inhibition of OmpH activity promotes the phagocytic activity of macrophages against the p0910 wild-type strain. ultocida . It medithe host . Recent nfection . The pat capsule ,22. Non- capsule . It has and mice . This ishe lungs . Macrophhe lungs . Intereshe lungs . They foPasteurella multocida is an economically important pathogen of animals. Proteomics analyses revealed had been a key method to clarify the pathogenesis of Pasteurellosis [P. multocida, and the pathogenic mechanism of P. multocida and the immunoprotection of OmpH gene deletion mutation strains were analyzed. The yak spleen proteome with treatment by P0910 and ΔompH of P. multocida were screened and analyzed by label-free mass spectrometry. Results showed that of the 773 proteins (expressed in wild-type P0910 P. multocida), 57 were significantly differentially expressed in ΔOmpH mutant strains. Of the 57, 14 were over-expressed, whereas 43 of them were under-expressed in the ΔOmpH strain. The differentially expressed proteins in ΔOmpH strain regulated ABC transportation, two-component system, RNA degradation, RNA polymerase, glycolysis/gluconeogenesis, ubiquinone and other terpenoid-quinone biosynthesis, the citrate cycle (TCA cycle) as well as fructose and mannose metabolism. The expression of ABC transporters, the activities of the two-component system, RNA degradation, and RNA transcription were significantly high in the ΔOmpH group. In contrast, glycolysis/gluconeogenesis, biosynthesis of ubiquinone, and other terpenoid-quinones, the citrate cycle (TCA cycle), and fructose and mannose metabolism were significantly low in the ΔOmpH group. STRING further revealed a complex and intricate connection among 54 of the 57 differently expressed proteins. Injection of wild-type P0910 and ΔOmpH mutant P. multocida strains activated the activities of ropE, HSPBP1, FERH, ATP10A, ABCA13, RRP7A, IL-10, IFN-γ, IL-17A, EGFR, and dnaJ. Thus, these proteins are potential markers for hemorrhagic sepsis in Qinghai yak following P. multocida and could also explain the molecular mechanism underlying the pathogenesis of P. multocida.rellosis . FurtherPasteurella multocida infection disrupts pathways that participate in the expression of several key proteins , and immune response-related  as well as Fructos fructose e and mannose metabolism) pathways [P. multocida and participates in maintaining bacterial growth and survival in adverse environments. Heat shock proteins (HSPs) are highly conserved in eukaryotes and prokaryotes and are essential for the survival of organisms [Edwardsiella tarda [P. multocida.pathways ,28. PPI pathways ,30. RpoEpathways . Additiorganisms . DNA J ila tarda . Mucosalla tarda . ATP10A la tarda . Abca13 OmpH gene disrupts the normal expression of specific proteins in P. multocida. Additionally, infection with OmpH mutant P. multocida disrupts the expression of several proteins in the yak spleen tissue, affecting immune response against the bacteria. OmpH gene deletion influences the pathogenesis of P. multocida in Qinghai yak, including the associated hemorrhagic sepsis. These findings deepen our understanding of the pathogenesis and control of P. multocida in Qinghai yak.Deletion of the


Asthma is a heterogeneous and often difficult to treat condition that results in a disproportionate cost to healthcare systems. Children with severe asthma are at increased risk for adverse outcomes including medication-related side effects, life-threatening exacerbations, and impaired quality of life. An important therapeutic focus is to achieve disease control, which is supposed to involve a personalized approach to treatment of asthma of any severity. Asthma is a multifactorial disease with a significant genetic determinant, however, the inheritance of asthma has not been fully elucidated. Polymorphic genes of inflammatory mediators, including cytokines, play an important role in developing various disease forms. In the current study, large-scale original data on the prevalence of cytokine gene genotypes  among Russian children with asthma in Krasnoyarsk region have been obtained. Genotyping was carried out using real-time PCR. We identified markers predisposing to the development of different variants of the course of childhood asthma: the CT genotype and T allele of IL4 rs2243250 are associated with asthma (p < 0.05), especially in mild asthma and in controlled asthma. The TT genotype and allele T of IL13 rs1800925 are associated with severe and uncontrolled asthma (p < 0.05). The AA genotype of IL17A rs2275913, the TT genotype of IFNG rs2069705 and allelic A variants of TNFA rs1800629 are associated with mild asthma, and the TT genotype of IFNG rs2069705 is additionally associated with controlled asthma. The results obtained will supplement information on the prevalence of polymorphic variants of the cytokine genes in the Russian population and in asthma patients with different disease courses, which is likely to be used in order to shape a plan for Public Health Authority to prevent the development of severe uncontrolled asthma and to optimize personalized therapy. Asthma is one of the most common diseases of the lowerrespiratory tract; it is a heterogeneous disease characterizedby airway inflammation and hyperactivity. Asthma most oftenbegins in early childhood, has a variable course and an unstablephenotype progressing over time . Itsignificantly limits and worsens the quality of human life incase of uncontrolled and severe disease. According to WHOestimates, asthma annually leads to the loss of 26.2 millionin the world as measured by DALYs ,which is 1 % of the total global burden of disease . Today,asthma is a global health problem of great socio-economicimportance, i. e. about 339 million people worldwide sufferfrom asthma. The increase in the prevalence and incidence ofasthma worldwide is influenced by both genetic backgroundand a large number of environmental factors included in the“modern lifestyle” concept. Moreover, asthma prevalence, severity,and mortality vary greatly by ethno-geographic origin.Based on expert estimates, the number of asthma patientsin Russia exceeds official figures, i. e. according to their calculations,5.9 million instead of 1.3 million people suffer fromasthma in our country. In addition, according to the reporteddata, since asthma is a disabling and dangerous disease,about 41 % of asthma patients receive a disability pension.The prevalence of the disease among adults is 6–7 %, amongchildren and adolescents it is 8–10 %, exceeding the incidencerate of cardiovascular disease, breast cancer and HIVinfection . According to 2020 data,more than 42.5 thousand asthma individuals were recorded inKrasnoyarsk region, including both adults and children. Theprevalence among adolescents has been noted to be steadilyincreasingThere are a number of asthma phenotypes and endotypes.Asthma classification is to group patients based on observablecombinations of clinical, biological and physiologicalcharacteristics into so-called phenotypes. Simply stated, phenotypesare defined as “observable characteristics resultingfrom a combination of hereditary and environmental influences”. It is important to emphasize that thephenotype of asthma can change over time, which is causedby environmental factors, allergens, seasonal changes, respiratoryinfections, iGCS  therapy,etc. Asthma is known to be classified according to the GlobalInitiative for Asthma (GINA) and both severity and level ofcontrol as well.Asthma severity is associated with the intensity of the pathologicalprocess and it is possible to correctly determine itsdegree before treatment, since there is a decrease in symptomswith effective therapy. According to the recommendations ofthe GINA working group, the asthma severity can be distinguishedas: intermittent, persistent-mild, persistent-moderate,and persistent-severe. Level of disease control is the degreeto which symptoms and functional limitations are controlled,as well as the minimization of risks of asthma exacerbation,and the prevention of deterioration in lung function with medicaltreatment. Whatever the disease severity, the goal forpatients is to have well-controlled asthma. According to thedegree of control, it is classified into controlled and uncontrolledasthmaAn important characteristic of asthma is the multifactorialnature of the disease, with the pathogenesis of developmentcombining both genetic and environmental factors. Extrinsicfactors are sure to be numerous and responsible for the activationof asthma manifestation or cause its exacerbation.The internal characteristics of the individual are of greatestimportance. Intrinsic  factors include genetic predisposition,gender and ethnic origin. The important role ofheredity in asthma occurrence has been confirmed by family,twin, and genetic epidemiological studies .The genetic component of the disease is provided by thecombined action of various groups of genes. The same asthmaphenotype in different individuals may result from the“breakdown” of various genes; the disease development mightresult from a mutation of several genes at once in every singleindividual. In addition, not only the possibility of developingthe disease, but also its severity, response to therapy, etc. aredetermined by hereditary factorsAirway inflammation underlying asthma is also causedby the so-called cytokine network, which is a self-regulatingsystem; when its functionality is impaired, an excess or insufficientproduction of various cytokines takes place, which turnsout to result in the development of pathological processes.More than 50 cytokines are known to be involved in the immunepathogenesis of this disease, and the role of each of thosehas not been fully elucidated. Significantly higher levels ofcytokines such as GM-CSF, IL-4, IL-5, IL-10, IL-12, IL-13,IL-17A, IL-8, IL-18, TNF-α can be detected in serum.Gene polymorphism is known to cause differences in theexpression and level of protein production. Currently, a hugenumber of polymorphic regions have been identified in thegenes of a number of cytokines and their receptors. Despitethe progress made in the study of the immune-pathogenesisof asthma, there has been no agreement of opinion on thepathogenetic role of polymorphic variants for cytokine genesrelated to asthma development as well as its phenotypes,which is to be further studied. In addition, there have beensome contradictions in the study results for different populationsworldwide, as the frequency distribution of polymorphicvariants of genes, including cytokine ones, has unique featuresdepending on ethno-geographic characteristics . Therefore, a comparative analysis of genetic parametersin a single population in order to identify risk factors forasthma phenotype development is to be relevant.Thus, asthma is the subject of research aimed at studyingthe disease process, the role of various mediators (includingcytokines), treatment approaches, and the role of the geneticdeterminant as well.The aim of the study was to identify markers for the developmentof various asthma phenotypes in Russian children ofKrasnoyarsk region.Asthma patients (n = 317) and healthy children (controlgroup) (n = 229) matched by sex, age and ethnicity were theobject of the study. Criteria for patients to be involved in thestudy were the following: an established diagnosis of bronchialasthma; age from 8 to 18 years; more than one-year ofasthma experience; both parents of the child being Russians.There are some criteria for exclusion from the study such asconcomitant decompensated diseases as well as for inclusionin the control group: the absence of allergic pathologies andbronchopulmonary diseases; age from 6 to 18 years; bothparents of the child being Russians.Depending on the severity of the disease, determined inaccordance with the recommendations of the GINA workinggroup , the following groups were distinguished: intermittent,persistent-mild, persistent-moderate, and persistent-severe.In the course of the study, we grouped patients accordingto the following severity levels: intermittent asthma andpersistent-mild asthma into the “mild” asthma group (n = 131),persistent-moderate and persistent-severe into the “severe”asthma group (n = 186) due to the small number of patients insome groups. Depending on the level of disease control, basedon the results of the asthma control test in children , the following groups were distinguished:controlled asthma (n = 171) – 20 or more points, and uncontrolledasthma – less than 19 points (n = 146).The work was performed in accordance with the principlesstated in the Declaration of Helsinki on research in humansand animals. The studies were approved at a meeting of thelocal ethical committee of Scientific Research Institute of MedicalProblems of the North . The examination protocol for patients andhealthy children (control group) met ethical standards and wasapproved by the Biomedical Ethics Committee of ScientificResearch Institute of Medical Problems of the North. Theright to conduct an examination was legally secured by theinformed written consent of the parentDNA extraction from blood was carried out using theDIAtom™ DNA Prep100 reagent kit . Genotypingwas conducted by the real-time PCR method usingspecific oligonucleotide primers and fluorescently labeledprobes according to the manufacturer’s protocol  and the Rotor-Gene Q 6 plex instrument.Comparison of allele and genotype frequencies betweengroups was performed using an online calculator https://medstatistic.ru/. The χ2 test was used to assess the association ofa trait-genotype with the disease in groups of sick and almosthealthy children. The threshold significance level was takenequal to 0.05. The odds ratio (OR) was used with a 95 %confidence interval (CI) for an assessment of the degree ofassociation of genetic markers with traits.In order to identify genetic markers of asthma, a comparativeanalysis of the frequency of single nucleotide polymorphisms(SNPs) between patients and children in the control group wasmade. Comparative analysis of allele and genotype frequenciesbetween the cohort of asthma patients and controls revealedstatistically significant differences in the SNPs distribution inthe promoter regions of IL4 rs2243250 and IL13 rs1800925(Table 1).The prevalence of the IL4 rs2243250 T allele in the group ofasthma patients relative to the control group was shown , with the frequency of the heterozygousCT genotype of IL4 rs2243250 being also statisticallysignificantly higher in asthma patients compared to the controlgroup (p = 0.006). The frequencies of the TT genotype andT allele of IL13 rs1800925 are significantly higher in the groupof patients relative to the control group ( p <0.05).A comparison of the genotype and allele frequencies in thegroup of asthma patients depending on the severity and levelof asthma control was made (Tables 2 and 3) to study in detailthe association of allelic variants of cytokine genes with thecharacteristics of asthma developmentAs a result of analysis of the IL4 rs2243250 and IL13rs1800925 distribution depending on the severity of asthma,a high frequency of both the CT genotypes of IL4 rs2243250and TT genotypes of IL13 rs1800925 in the group with severeasthma relative to the control group was noted, and for theСТ genotype of IL4 rs2243250, in the group of children withmild asthma ( p <0.05). Analysis of the allele frequencies ofthese polymorphic gene variants revealed significant differencesin the rare T allele frequency of IL4 rs2243250 and IL13rs1800925 in children with mild and severe asthma (in thecase of rs1800925) compared with healthy children ( p < 0.05).When comparing the frequency of IL17A rs2275913,IFNG rs2069705 and TNFA rs1800629 genotypes and alleles,AA homozygotes of rs2275913 ( p = 0.01), TT of rs2069705( p = 0.03) and allelic A variant of TNFA rs1800629 wereshown to be significantly more common in the group of childrenwith mild asthma relative to the control group.As a result of the analysis of the IL4 rs2243250 and IL13rs1800925 distribution depending on the level of asthma control,it was demonstrated that the CT of IL4 rs2243250 andTT of IL13 rs1800925 genotypes are more common in the uncontrolledasthma group compared to the controls ( p < 0.05).The CT genotype of IL4 rs2243250 is also significantly morecommon in controlled asthma patients than in controls. Allelefrequency analysis revealed the differences in the frequency ofthe rare T allele of IL13 rs1800925 between groups of childrenwith both controlled and uncontrolled asthma, and healthychildren as well ( p < 0.05). When comparing the frequencyof the IFNG rs2069705 genotypes, the homozygous TT wasshown to be significantly higher in the controlled asthma groupcompared to the control group ( p < 0.05).Since the inflammatory response regulation for asthma hasbeen carried out using mediators/cytokines, the mechanismsof violation of their functionality have to be studied. The levelof cytokine concentration in blood serum is affected by geneticpolymorphism of the cytokine network, which turns out tohave an effect on the asthma progression type. By 2022, about1500 genes have been studied for asthma, including cytokinesand their receptors (according to Phenopedia). The influence ofvarious genes on the formation of a genetic predisposition toasthma should be noted to be significantly different in variouspopulations, i. e. has some ethnogeographic features. Hence,there are some conflicting data in the studies on the role ofgenetic factors in the asthma pathogenesis. As a result of the1000 Genomes project (http://www.1000genomes.org), dataon a number of SNPs in genes, including those in promoter,exons, and intron regions have been obtained. However, thereare few functional polymorphic variants (affecting the proteinfunctions or structure) with their contribution to the pathologyof asthma being ambiguous.In our study the SNP allele and genotype frequencies of keycytokines produced by different types of the immune systemcells that mediate inflammatory reactions in diseases amongRussian children in Krasnoyarsk region were studied. Wefound significant differences in the frequency of polymorphicdistribution of cytokine genes between asthma patients and thecontrol group, allowing us to identify genetic markers that aresuggestive risk factors for developing asthma, i. e. the heterozygousCT genotype and the T allele of IL4 rs2243250, thehomozygous TT variant and the T allele of IL13 rs1800925.As mentioned above, the disease course prediction, effectivenessof treatment, controlled course, prevention of the severeasthma development, as well as providing personalizedtherapy and asthma prophylaxis are of the greatest importance.In order to find genetic markers of different types of asthma,we analyzed the SNPs distribution of cytokine genes in patientswith different severity and control of the disease. TheCT genotype and the T allele of IL4 rs2243250 was foundto be associated with mild asthma, the CT genotype of IL4rs2243250 was also associated with severe asthma; moreover,the TT genotype of IL13 rs1800925 was associated with severeasthma, and the T allele of IL13 rs1800925 – with both mildand severe asthma. Genetic markers predisposing to differentforms of asthma depending on the control were also identified,i. e. both the CT genotype of IL4 rs2243250 and the T alleleof IL13 rs1800925 were associated with both controlled anduncontrolled asthma, with the TT genotype of IL13 rs1800925being associated with with uncontrolled one.The IL4 and IL13 genes are located in one cluster of chromosome5q31.1 and encode cytokines that play a key role inthe asthma pathogenesis, namely, IL-4 and IL-13 promoteairway eosinophilia, mucus hyperproduction, bronchial hyperreactivity,and IgE synthesis . The SNP(rs2243250) in the IL4 promoter is associated with increasedexpression and production of IL-4, and SNP IL13 rs1800925enhances the expression of IL-13 in Th2 cells. Аsthmapatients with an elevated IgE level were reported to have ahomozygous genotype for the rare allele T of IL4 rs2243250.Our data obtained as a result of analysis of the frequency distributionof genotypes and alleles rs2243250 and rs1800925in Krasnoyarsk children are consistent with the study resultsof other scientists.It was previously determined that the CT genotype of IL4rs2243250 predominates in the group of Russian children withatopic asthma, and Arab asthma patients having this genotypewere also found to have the highest incidence of eczema comparedto the patients with the TT genotype . In the asthma children group,an increased incidence rate of the TC and TT genotypes ofthe IL4 (C-590T) polymorphism (rs2243250) compared tohealthy ones was shown . W. Nie etal., in the meta-analysis including 40 studies, concluded thatthe CT vs. CC was significantly associated with an increasedrisk of developing asthma. In addition, when analyzed byethnicity, significant associations were found in Asians andCaucasians, but not in African Americans .However, some studies obtained different results, for instance,the analysis of genotypes associated with asthma for C-589T ofthe IL4 gene did not reveal statistically significant differencesbetween the control group and the group of asthma patients,which might be due to the small number of studied samples. And in a meta-analysis carried out byChinese scientists, a rare allele was said to be a weak risk factorfor asthma development in Caucasians .Z. Liu et al. (2014) have shown that the CT and TT genotypesof IL13 rs1800925 were more common in the group ofasthma patients. Scientists from Malaysia have found out thatthe percentage of the minor T allele in asthma patients wasabove the frequency of the same allele in the control, being arisk factor for the development of this pathology . However, the study results on a populationof children in Costa Rica have demonstrated that the T allelers1800925 led to the progression of asthma only in childrentaking corticosteroids and was not associated with the risk ofdeveloping the disease .As a result of meta-analysis, the mutation rs1800925 wasassociated with an increased risk of developing asthma onlyin the Caucasian population, and not associated with a predispositionto asthma in Asians .There are also controversial data, which are likely to berelated to the small number of studied samples, in particular,an analysis of the distribution of alleles and genotypes ofIL13 rs1800925 did not reveal statistically significant differencesbetween the control and the group of asthma patients.However, there was a tendency to increase the proportion ofallele C in the group of asthma patients .Nevertheless, polymorphic variants of the TNFA, IL4, and IL13cytokine genes have been shown to contribute to the formationof a genetic predisposition to asthma in the Republic ofBashkortostan .While working, we have also found that the AA genotypeof IL17A rs2275913, the TT genotype of IFNG rs2069705,and the A allele of TNFA rs1800629 were associated withmild asthma, and the TT genotype of IFNG rs2069705 – withcontrolled asthma.The literature available on the association of IL17Ars2275913, localized in the promoter region, with the expressionlevel and cytokine activity of IL-17A are very inconsistent.Thus, an association between the SNP and susceptibilityto asthma in children has been noted, i. e. the GG genotypepatients have mild to moderate asthma and low levels ofIL-17A . The A allele of rs2275913 hasbeen reported to increase the activity of the IL17A promoterand upregulate its transcription, leading to increased airwayinflammation . However, another studyfailed to find an association between IL17A rs2275913 andasthma risk , while J. Chen et al. havedemonstrated that the level of IL-17A expression in peripheralblood mononuclear cells was not affected by rs2275913 . One of the ethnicity-specific analysis showedthat the G allele of IL17A rs2275913 was a protective factorof the asthma in Asians, with no association being found inAfricans .It is known that one of the key Th1-cytokines is IFN-γ, involvedin the many features regulation of asthma pathogenesis,including suppression of the of Th2 profile cytokine release,inhibition of the recruitment of effector cells to the site ofinflammation, apoptosis induction of T-cells, eosinophils, etc. Nevertheless, there have currently been a limited number ofstudies investigating the role of polymorphic sites in the IFNGin the pathogenesis of asthma. The G-238A mutation in theTNFA gene has been shown to reduce the risk for developingasthma, whereas the SNP G-308A (rs1800629) was associatedwith the development of asthma and an increase in TNF-αproduction . The A allele of rs1800629has also been shown to be associated with increased TNFAtranscription compared to the G allele, with its frequencyvarying significantly between ethnic groups and being rarein Japanese (less than 3 %) .Tomsk scientists, who have been studying pathogeneticsof asthma for many years, found an association of thepolymorphic variant of the TNFA gene (rs1800629) with thedevelopment of asthma, namely, the AA genotype was moreoften indicated in the group of patients compared to the control. According to a series of studyresults, an analysis depending on ethnodemographic datais necessary. Only in this case, the obtained markers of thediseases can be used as prognostic ones.Some researchers have distinguished not only geneticmarkers of the risk of developing a disease or its forms, butalso some protective markers. The CC genotypes of IL4rs2243250, IL6 rs1800795, IL13 rs1800925, as well as theGG genotype of TNFA rs1800629 were shown in our study tobe protective against the development of mild asthma. It wasalso determined that the CC genotypes of IL4 rs2243250, IL6rs1800795, IL13 rs1800925 and the allelic variant T of IL12Brs3212220 can be considered to be potentially protective forthe development of uncontrolled asthma.Thus, the obtained data on the prevalence of genetic variantsindicate that functional SNPs in cytokine genes are associatedwith asthma and various disease courses not only in adults, butalso in children. However, it is evident that the results do notalways agree with each other; this is due to several reasons,namely, the ethnicity of the population, the study sample size,the presence of concomitant diseases, etc. In addition, differencesbetween children and adults can be caused by eitherthe presence or absence, as well as the different duration ofexposure of asthma patients to some environmental risk factors,including contact allergens and irritants, air pollution,smoking and occupational exposure.An important aspect of medical practice is to achievedisease control, which is supposed to involve a personalizedapproach to treatment for asthma of any severity. It shouldbe taken into account that children with severe asthma are atincreased risk for adverse outcomes, including drug-relatedside effects, life-threatening exacerbations, and poor quality oflife. As a result, the study of the distribution of allelic variantsof cytokine genes in asthma among patients of different ages,representatives of different populations needs to be continuedin order to find risk factors for different types of asthma. Theobtained results will update with the data on the polymorphicdistribution of cytokine genes in the Russian population andin asthma patients with different disease courses. This is mostlikely to be ultimately used for practical healthcare authoritiesto develop measures both in order to prevent severe uncontrolledasthma and to optimize personalized therapy.The authors declare no conflict of interest.Chen J., Deng Y., Zhao J., Luo Z., Peng W., Yang J., Ren L., Wang L.,Fu Z., Yang X., Liu E. The polymorphism of IL-17 G-152A wasassociated with childhood asthma and bacterial colonization of thehypopharynxin bronchiolitis. J. Clin. Immunol. 2010;30(4):539-545. 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Med. 2017;5(9):691-706. DOI 10.1016/S2213-2600(17)30293-X.Hancox R.J., Cowan D.C., Aldridge R.E., Cowan J.O., Palmay R., WilliamsonA., Town G.I., Taylor D.R. Asthma phenotypes: Consistencyof classification using induced sputum. Respirology. 2012;17(3):461-466. DOI 10.1111/J.1440-1843.2011.02113.X.Hijazi Z., Haider M.Z. Interleukin-4 gene promoter polymorphism[C590T] and asthma in Kuwaiti Arabs. Int. Arch. Allergy Immunol.2000;122(3):190-194. DOI 10.1159/000024396. DOI 10.1165/AJRCMB.25.3.4483.Hunninghake G.M., Soto-Quirós M.E., Avila L., Su J., Murphy A.,Demeo D.L., Ly N.P., Liang C., Sylvia J.S., Klanderman B.J.,Lange C., Raby B.A., Silverman E.K., Celedón J.C. Polymorphismsin IL13, total IgE, eosinophilia, and asthma exacerbations in childhood.J. Allergy Clin. Immunol. 2007;120(1):84-90. 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P ≤ 0.001) and TC levels  and increased HDL levels . In the weighted mean difference analysis, vitamin D significantly decreased only TG levels . The present study supports that vitamin D supplementation could be considered a beneficial adjuvant therapy in managing lipid profile levels, especially in individuals with vitamin D deficiency.According to published meta-analyses, vitamin D exerts different beneficial effects in preventing and controlling risk factors associated with noncommunicable chronic diseases; however, the results are still conflicting. The purpose of this umbrella meta-analysis was to investigate the effect of vitamin D supplementation on low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol (TC), and triglyceride (TG) as components of the lipid profile. PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews were systematically searched for meta-analyses of randomized controlled trials. The umbrella meta-analysis followed the PRISMA guidelines. The random-effects model was employed to estimate the overall effect size (ES). Overall, 25 meta-analyses were included. In the standardized mean difference analysis, vitamin D significantly decreased TG (ES: −0.15; 95% CI: −0.23, −0.08; This systematic review was registered in PROSPERO as CRD42022306334. Various studies have reported that vitamin D may improve lipid profiles; however, some reported different results. This study, which is the first and the most comprehensive review in this regard, revealed that vitamin D may exert beneficial effects on lipid profiles.Globally, cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality, with atherosclerosis playing a crucial role in its development . AtherosIn addition to LDL cholesterol, the first lipoprotein of interest, triglyceride (TG), HDL cholesterol, and total cholesterol (TC) play a significant role in CVD, with HDL cholesterol having a potential preventive role and the other lipid profile components having a negative effect . Here, “Vitamin D is a unique nutrient because it can be obtained either through endogenous synthesis or through diet. Vitamin D, within cells, regulates the transcription of a large and diverse number of genes by binding to its nuclear receptor, the vitamin D receptor (VDR). Through this mechanism, vitamin D not only maintains calcium and phosphate homeostasis and bone mineralization but also regulates cellular growth, differentiation, and immune function, among other vital functions. It may also play a plausible role in cancer, CVD, diabetes, and other diseases .In observational and interventional studies, inadequate vitamin D levels were associated with unfavorable serum lipid profiles, whereas adequate vitamin D levels were associated with favorable lipid profiles . A PolisThese findings should be interpreted with caution, considering the number of studies, the heterogeneity of interventions and outcomes, and the methodological quality of the studies. Therefore, given the global prevalence of vitamin D deficiency and the purported beneficial effects of vitamin D on lipid profile, our designed umbrella review of meta-analyses of RCTs aims to evaluate the effects of vitamin D supplements on the lipid profile  in adults and appraise the existing evidence to inform clinical practice, as well as to highlight additional areas for future research.The protocol of the present study was registered in the PROSPERO database (CRD42022306334). In addition, the present umbrella meta-analysis was reported according to the PRISMA guidelines .The present umbrella meta-analysis of RCTs was conducted to determine the effect of vitamin D supplementation on the lipid profile. The primary outcomes were TG, TC, LDL cholesterol, and HDL cholesterol levels. There were no additional secondary outcomes.Supplementary Information.We comprehensively searched PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews with the assistance of a librarian experienced in systematic reviews to retrieve relevant meta-analyses. We also searched PROSPERO for related reviews. The references of retrieved articles and existing reviews were manually checked for additional resources. The primary search was conducted from database inception until February 2022, and on September 2022, an additional search was performed to update and locate any potential new studies. Based on the relevant keywords ((“Vitamin D”) AND (TG OR TC OR LDL-c OR HDL-c) AND ), a structured search strategy was determined. The search strategy is detailed in Only meta-analyses of RCTs investigating the effect of vitamin D supplementation on TG, TC, LDL cholesterol, and HDL cholesterol levels in adult male and female subjects aged 18 and older were included in this study. The PICO  framework is shown in We excluded any other type of study than meta-analyses of RCTs. We also excluded those studies that lacked relevant data. Studies that investigated the effect of vitamin D on children were excluded. Moreover, meta-analyses evaluating the effect of vitamin D in combination with cosupplements were excluded. However, meta-analyses that did not intend to evaluate a combination of vitamin D with cosupplements but have included one or 2 such studies were included. Studies with vitamin D supplementation in fortified foods, as the amount of vitamin cannot be defined accurately, were excluded.Two independent reviewers  screened all retrieved articles through titles and abstracts. If there was any uncertainty regarding whether a study should be excluded, the study was advanced to the full-text screen to reduce the likelihood of being erroneously excluded. Two reviewers obtained the full text of potentially relevant papers for an independent analysis. A third party (AO) reconciled any disagreements. Articles excluded in the full-text screening phase were reported with respective reasons. We completed a PRISMA flowchart to summarize this process, and a PRISMA checklist is also appended.Included studies underwent a standardized data extraction process employing a preformatted spreadsheet by one of the authors (NR). A second reviewer (MZ) verified the extracted data to reduce reviewer errors and bias. In the case of missing data from reports, we attempted to contact the study authors to get the necessary information. Where an included study had more than 2 comparisons, only the ones that met the eligibility criteria were considered. The following details were extracted: first author, year of publication, study design, type of study, sample size, length of follow-up, type and dosage of vitamin D supplements, age, sex, and effect size (ES) and their corresponding confidence intervals (CIs) for TG, TC, LDL cholesterol, and HDL cholesterol.Two review authors  independently assessed the quality of meta-analyses according to the AMSTAR 2 tool . This toP < 0.10 in conjunction with the I2 measure to evaluate statistical heterogeneity [2 test assesses the percentage of total variation across studies due to heterogeneity rather than chance [P value < 0.05 was considered a significant level.The reported ESs and CIs were used to estimate the overall ES. We pooled estimates of treatment effects where possible, using standard statistical techniques. The random-effects model was applied to conduct statistical analysis using the restricted maximum likelihood method. Due to the natural differences between standardized mean difference (SMD) and weighted mean difference (WMD), the analysis was performed for each separately. We used the chi-squared test with a significance level of ogeneity . The I2 n chance . Values n chance . We explReporting bias arises when the nature and direction of results influence the dissemination of research findings. Publication bias is one of several possible causes of small-study effects, which tends to estimate the effect of an intervention to be more beneficial in smaller studies.We used funnel plots to assess small-study effects visually , along wThe flow diagram of the literature search process is summarized in The characteristics of the included studies are presented in The results of the quality assessment of meta-analyses according to the AMSTAR2 questionnaire are summarized in P ≤ 0.001)   A. There = 0.483) A. Subgro= 0.483) . Further= 0.483) .FIGURE 2P = 0.386 and P = 0.304, respectively). However, publication bias was observed by visually examining the funnel plot. Therefore, trim-and-fill analysis was performed with 2 imputed studies, but the results did not change   B.P = 0.003)   A. There = 0.003) A. The nu= 0.003) . In addi= 0.003) .FIGURE 3P = 0.224 and P = 0.474, respectively). A visual inspection of the funnel plot also revealed publication bias. Thus, trim-and-fill analysis was conducted with 2 imputed studies, with no change in the result   B.P ≤ 0.001)   . There w= 0.719) . Accordi= 0.719) . Moreove= 0.719) .FIGURE 4Sensitivity analysis showed that no single study likely affected the overall ES. Due to the small number of included studies for this outcome, neither Begg’s nor Egger’s tests were conducted. In addition, the funnel plot was not conducted for the same reason.P = 0.066)   A. Signif≤ 0.001) A. Study ≤ 0.001) . In addi≤ 0.001) .FIGURE 5P = 0.843 and P= 0.940, respectively). In addition, the asymmetric distribution of studies was not observed by visual inspection of the funnel plot    A. There = 0.015) A. Sex, a= 0.015) . Moreove= 0.015) .FIGURE 6P = 1.000 and P = 0.972, respectively). Moreover, an examination of the funnel plot revealed an asymmetric distribution. Consequently, trim-and-fill analysis was carried out on 11 studies (2 imputed studies). Even after trim-and-fill analysis, the corrected ES for publication bias exhibited no significant effect   B.2= 75.5%, p ≤ 0.001)  in the pooled results of 16 meta-analyses with 17 ESs, based on the WMD A. There ≤ 0.001) . Age, su≤ 0.001) . In addi≤ 0.001) .FIGURE 7P = 1.000 and P = 0.807, respectively). In addition, a visual examination of the funnel plot revealed asymmetric distribution. Consequently, trim-and-fill analysis was conducted on 18 studies (1 imputed study). After correcting for publication bias, the results still remained nonsignificant   B.P = 0.025)   A. There = 0.360) A. Subgro= 0.360) . Moreove= 0.360) .FIGURE 8P = 0.675 and P = 0.582, respectively). In addition, publication bias was identified through a visual examination of the funnel plot. In light of this, a trim-and-fill analysis was conducted with 2 imputed studies, and the results remained statistically significant after adjusting for publication bias   B.P = 0.453)   A. Howeve≤ 0.001) A. Follow≤ 0.001) . Moreove≤ 0.001) .FIGURE 9P = 0.444 and P = 0.281, respectively). Moreover, publication bias was identified by visual examination of the funnel plot. Therefore, trim-and-fill analysis was performed with no imputed studies, and even after correcting for publication bias, the results remained nonsignificant   B.Contradictory findings have been reported regarding the effect of vitamin D on the lipid profile, an important factor in various diseases. Therefore, the present study was conducted to investigate this topic in greater depth and detail. The findings of this umbrella meta-analysis support the theory that vitamin D supplementation benefits the lipid profile and is advantageous as a dietary intervention in managing dyslipidemia. According to this study, vitamin D significantly decreased TG levels while having no significant effect on LDL cholesterol levels. In addition, the effects of vitamin D on HDL cholesterol and TC levels produced contradictory findings. Subgroup analyses suggested that doses ≥ 4000 IU/d and duration of intervention ≤12 wk may be key variables.The current investigation indicated that vitamin D significantly decreased TG levels according to WMD and SMD analyses. In subgroup analysis, the WMD and SMD analyses yielded comparable results, such as a significant drop in TG levels in participants ≤50 y old following vitamin D supplementation. Nevertheless, there were some differences. In the SMD analysis, vitamin D supplementation significantly decreased TG levels in studies involving both sexes and both subcategories of vitamin D dose and duration, with >4000 IU/d supplementation dose and ≤14 wk intervention having a more robust effect. In the WMD analysis, vitamin D supplementation decreased TG levels significantly only in females and those receiving supplementation for >14 wk. Two studies by Bjelakovic et al.  and AlAnRegarding TC, the levels of this lipid profile component decreased significantly following vitamin D supplementation according to SMD but not WMD analysis. However, in the WMD analysis, after excluding the articles that were performed on individuals with liver and renal disease, results changed, and a significant reduction in TC levels was reported. This may be due to the role of these organs in activating vitamin D in the body, and a disorder in these organs may reduce the effectiveness of vitamin D supplementation in correcting vitamin D deficiency and restoring proper function. The studies in the WMD analysis exhibited a high degree of heterogeneity. One of the potential causes of this heterogeneity might be due to the study by AlAnouti et al. , which rThe current umbrella review reported that vitamin D did not significantly affect LDL cholesterol levels in both SMD and WMD analyses. In the SMD analysis, an interesting result was reported. In a meta-analysis by Manousopoulou et al. , vitaminThe WMD analysis also yielded comparable results. According to the meta-analysis conducted by Wang et al. , vitaminThe results varied regarding the effect of vitamin D supplementation on HDL cholesterol levels. Based on SMD analysis, vitamin D supplementation resulted in a significant increase in HDL cholesterol levels, in contrast to the WMD analysis. Notably, 2 studies conducted by Jafari et al.  and Liu 1) By promoting calcium absorption, vitamin D may inhibit the absorption of fatty acids. Comparable interactions between calcium and bile acids strengthen this effect. The interaction between calcium and bile acids may reduce the quantity of bile acid available to facilitate fat absorption in the intestinal tract [2) Vitamin D might improve the lipid profile by reducing insulin resistance [3) By increasing peroxisome proliferator-activated receptor (PPAR)-γ expression, which increases insulin synthesis and release, and possibly by promoting insulin receptor expression or suppressing proinflammatory cytokines, vitamin D may reduce insulin resistance, thereby affecting the lipid profile [4) By increasing PPAR-α expression, vitamin D may significantly impact lipid profile metabolism [5) Vitamin D may increase lipoprotein lipase activity and gene expression in muscles and adipose tissue, thereby enhancing the clearance of lipoprotein particles from circulation and altering the lipid profile to reduce atherosclerosis. The most noticeable effect of lipoprotein lipase (LPL) is a reduction in serum TGs and an increase in serum HDL [6) Elevated parathyroid hormone (PTH) concentrations can reduce plasma post-heparin lipolytic activity; thus, the suppressive effect of vitamin D on serum PTH concentrations may reduce serum TGs via increased peripheral removal [7) Vitamin D may regulate macrophage function on reverse cholesterol transport and large HDL particles; in this case, serum TG levels might decrease [8) Insulin-induced gene-2 (Insig-2) inhibits cholesterol synthesis by downregulating sterol regulatory-element binding protein-2 activation and 3-hydroxy-3-methylglutaryl-coenzyme A reductase expression. Vitamin D can affect this pathway via its effect on the transcriptional activity of VDR and Insig-2 expression [9) According to an experimental study, vitamin D may reduce TG deposition in differentiated adipocytes, increase fatty acid β-oxidation, and decrease de novo fatty acid synthesis [10) Vitamin D may affect the lipid profile by modifying Apo B100 (the major component of LDL cholesterol) and Apo A1 levels (the major component of HDL cholesterol). However, studies have reported inconsistent results [The following mechanisms may explain how vitamin D affects lipid profile levels: al tract . 2) Vitasistance . 3) By i profile . 4) By itabolism . 5) Vitaerum HDL . 6) Elev removal . 7) Vitadecrease . 8) Insupression . 9) Accoynthesis . 10) Vit results ,72. A me results .. Basically, meta-analyses cannot pool RCTs with cosupplements with the ones without. However, in some meta-analyses, this criterion was not considered in their study selection, and at least one RCT with cosupplement was included. Therefore, our subgroup analyses attempted to adjust this issue to some extent. However, there were some limitations. Included studies should have considered the initial 25(OH)D and lipid profile levels, whether there are within the normal range or not, which most did not. Furthermore, some studies did not consider topics such as altitude, race, body fat, and BMI, which can affect the relationship between vitamin D and lipid profile. Therefore, we could not evaluate these variables and determine their effects. The meta-analyses included RCTs comparing calcitriol, ergocalciferol, cholecalciferol, and alfacalcidol to placebo or no treatment, with some studies not even reporting the type of vitamin D supplement. Therefore, despite our best efforts and as per the protocol, we could not separate the effects of the various vitamin D supplements.The present study is the first umbrella meta-analysis investigating the impact of vitamin D supplementation on lipid profile. In all variables, no small-study effect was observed. Furthermore, in case of publication bias, the significant or nonsignificant results of none of the lipid profiles changed after correction by trim-and-fill. The quality of studies was checked using the AMSTAR2 toolThis umbrella meta-analysis reported that vitamin D might decrease TG levels. It may also decrease TC levels in individuals who were supplemented with a dose of >4000 IU/d or for ≤14 wk. Moreover, after statistical analyses, it can be suggested that vitamin D might decrease LDL cholesterol levels. Regarding HDL cholesterol, we could not make a clear conclusion. However, due to the high heterogeneity of some of our results and the poor quality of the included meta-analyses, results should be interpreted with caution. In addition, although the results are statistically significant, the clinical significance may not be considerable. The present study supports that vitamin D supplementation could be considered a beneficial adjuvant therapy in managing lipid profile levels, especially in individuals with vitamin D deficiency.The authors’ responsibilities were as follows—NR: conceived the study, developed the criteria, conducted the systematic search, screened articles, extracted data, and drafted and revised the manuscript; MZ: performed analysis, conducted the systematic search, screened articles, extracted data, assisted in study design, and revised the manuscript; PJ: assisted in the study design and revised the manuscript; AO conceived the study, developed the criteria, provided content expertise, and revised the manuscript; and all authors: read and approved the final version.The authors report no conflicts of interest.The authors reported no funding received for this study.Data described in the manuscript, code book, and analytic code will be made available upon request pending.


Brassica juncea (L.) Czern. & Coss. (Indian mustard) is an economically important edible oil crop. Over the years, plant breeders have developed many elite varieties of B. juncea with better yield traits, but research work on the introgression of stress resilience traits has largely been lagging due to scarcity of resistant donors. Crop wild relatives (CWRs) are the weedy relatives of domesticated plant species which are left unutilized in their natural habitat due to the presence of certain undesirable alleles which hamper their yield potential, and thus, their further domestication. CWRs of B. juncea namely include Sinapis alba L. (White mustard), B. tournefortii Gouan. (African mustard), B. fruticulosa Cirillo (Twiggy turnip), Camelina sativa L. (Gold-of-pleasure), Diplotaxis tenuisiliqua Delile , D. erucoides L. , D. muralis L. , Crambe abyssinica R.E.Fr. (Abyssinian mustard), Erucastrum gallicum Willd. (Common dogmustard), E. cardaminoides Webb ex Christ (Dogmustard), Capsella bursa-pastoris L. (Shepherds purse), Lepidium sativum L. (Garden Cress) etc. These CWRs have withstood several regimes of biotic and abiotic stresses over the past thousands of years which led them to accumulate many useful alleles contributing in resistance against various environmental stresses. Thus, CWRs could serve as resourceful gene pools for introgression of stress resilience traits into Indian mustard. This review summarizes research work on the introgression of resistance against Sclerotinia stem rot (caused by Sclerotinia sclerotiorum), Alternaria blight (caused by Alternaria brassicae), white rust (caused by Albugo candida), aphid attack, drought and high temperature from CWRs into B. juncea. However, various pre- and post-fertilization barriers due to different ploidy levels are major stumbling blocks in the success of such programmes, therefore, we also insightfully discuss how the advances made in -omics technology could be helpful in assisting various breeding programmes aiming at improvisation of stress resilience traits in B. juncea. Brassica juncea (L.) Czern & Coss.] is an economically important, edible oilseed crop of Brassicaceae family belonging to the rapeseed-mustard (RM) group. B. juncea is cultivated in India, China, Bangladesh, Pakistan, Australia, Canada and some European countries  and abiotic factors   . While, d frost) . It has d frost) . Throughstresses . Among din India . HoweverB. juncea majorly include Sinapis alba L. (White mustard), B. tournefortii Gouan. (African mustard), B. fruticulosa Cirillo (Twiggy turnip), Camelina sativa L. (Gold-of-pleasure), Diplotaxis tenuisiliqua Delile , D. erucoides L. , D. muralis L. , Crambe abyssinica R.E.Fr. (Abyssinian mustard), Erucastrum gallicum Willd. (Common dogmustard), E. cardaminoides Webb ex Christ (Dog mustard), Capsella bursa-pastoris L. (Shepherds purse), Lepidium sativum L. (Garden Cress) etc.  are the weedy, wild relatives of domesticated plants, which usually occur and are maintained mostly in their centers of origin . CWRs hass) etc. . Over thenalties . In the Alternaria leaf spot and white rust are major diseases caused by fungal pathogens which may amount to more than 90% yield losses in this oilseed crop  has become a very serious disease of mustard. This necrotrophic fungus causes yield losses ranging from 5-100% in mustard production  remained stable throughout consecutive generations and displayed significant resistance against SSR  were achieved by association mapping. Selected ILs showed high levels of resistance against SSR (B. juncea-B. fruticulosa helped in studying marker trait associations (MTA’s) and reported 49 significant SNPs corresponding to different loci on different chromosomes  and national disease nurseries (NDN) levels under the All India Crop Improvement Programme on Rapeseed-Mustard (AICRP-RM) has led to the identification of more than twenty five white rust resistance (WRR) donors among B. juncea germplasm which are being registered at ICAR-NBPGR, New Delhi , as a bridge to transfer resistant traits from B. fruticulosa to B. juncea  and non-natural host cowpea aphid (A. craccivora) has highlighted the mechanistic differences of defense response activation in B. juncea by both species  and late (flowering and seed ripening stage) stages, resulting in economic losses to mustard production . When exposed to heat stress, B. tournefortii (Rawa) showed maximum percent increase in germination (38.46%). This study highlights heat tolerance capacities of B. tournefortii (Rawa) during early stages of growth, i.e. germination  system is often relied upon for successful F1 seed production in Brassicaceae  with B. juncea  + B. juncea , carrying mitochondria and chloroplasts from M. arvensis, to B. juncea (D. erucoides × B. campestris) × B. juncea and (D. berthautii × B. campestris) × B. juncea. These were backcrossed with B. juncea   nucleus into the cytoplasm of B. fruticulosa. Complete and stable male sterility was observed in the B. juncea genotypes which developed rudimentary anthers with sterile pollen grains and no observed changes in other vegetative parts  . Completsativus) . This syoleracea . Wild reoleracea . Among tticulosa . This have parts . Successenotypes . The CMSB. juncea. However, genetic bottlenecks have always been an issue . While, others deployed protoplast fusion and embryo rescue for development of inter-generic hybrids of B. juncea and CWRs with improved stress resistance. For the stabilization of newly introduced traits many generations of recurrent parent back-crossing and open-pollination is further required in these hybrids. Therefore, in every generation, it becomes a herculean task to screen the desired hybrid plants expressing the trait of interest by crop genotyping and phenotyping.Due to reduced stringency for the selection of yield-related traits, CWRs of B. juncea CWRs. While, use of transcriptomics would enhance our knowledge on differential regulation of various genes under stress, further genomics studies would be helpful in functional characterization of these genes, followed by their targeted transfer into elite high yielding varieties of B. juncea using biotechnological tools. Further, whole genome sequencing of CWRs and pangenomics would increase our understanding of how genotypic and phenotypic diversity was shaped during domestication/selection processes from CWRs to B. juncea. This would also be helpful in solving the challenges related to breeding and conservation of genetic resources. The whole genome sequencing of CWRs would pave the way for identification of the genes governing resistance to a particular trait and thus suitable molecular markers/candidate-gene specific markers may be deployed for selection of the desired plants, ensuring the trait introgression.In the past few years, the advances made in omics technologies have discovered novel information on the molecular regulators of biotic and abiotic stress tolerance in different crop plants. These -omics advances have yet not been fully utilized for mining of genes and molecular regulators of stress tolerance in SV: Conceptualization, Resources, Writing – review & editing, Writing – original draft. ND: Writing – original draft, Writing – review & editing. KS: Writing – review & editing. NP: Writing – review & editing. LS: Writing – review & editing. DS: Writing – review & editing. DR: Writing – review & editing. KT: Writing – review & editing. DV: Writing – review & editing. AT: Writing – review & editing, Conceptualization, Resources, Writing – original draft.


Engelhardia are important components of subtropical and tropical forests in South-eastern Asia with great ecological and economic values. However, phylogenetic relationships within Engelhardioideae (Juglandaceae) remains obscure. In this study, we report the first complete chloroplast genome sequences of Engelhardia sensu stricto, Engelhardia hainanensis Chen, a rare species endemic in southern China. Its complete chloroplast genome is 161,574 bp in length, with a typical quadripartite structure that includes a large single-copy region of 91,158 bp, a small single-copy region of 18,790 bp, and its GC content is 35.8%. A total of 128 genes were identified, including 83 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Furthermore, a phylogenetic tree of Juglandaceae was constructed based the complete chloroplast genome sequence, which strongly support the three-subfamily classification system in Juglandaceae, and E. hainanensis was resolved sister to two Alfaropsis species. This study provides valuable genomic information for the species identification and phylogenetic study of Juglandaceae.Trees of  Engelhardia Leschenault ex Blume is a deciduous, semievergreen or evergreen tree group of Juglandaceae which distributes in South-Eastern Asia from eastern Pakistan to New Guinea  which contains ca. five species, and a monotypic genus Alfaropsis Iljinsk. which contains only Alfaropsis roxburghiana  Iljinsk. . Leaves were dried with silica gel in the field. Once completely dried, the leaf tissues were stored at −20 °C freezer until further use. Voucher specimen (collector and collection number: Xian-Yun Mu (xymu85@bjfu.edu.cn) and MU4973) is deposited at the herbarium of Beijing Forestry University (www.bjfu.edu.cn).The fresh leaves of Genomic DNA were extracted from the above leaf tissues using the DNAsecure Plant Kit , and sequenced by next-generation sequencing method on Illumina Hiseq X Ten platform. In total of 4.1 Gb of 150-bp clean reads were generated for chloroplast genome assembly.A. roxburghiana . All sequences were aligned using MAFFT  , and its schematic circular map was showed in E. hainanensis, including 83 protein-coding genes (77 unique genes), 37 tRNA genes (29 unique genes), and 8 rRNA genes (4 unique genes). Among them, there were 12 protein-coding genes  and 6 tRNA genes  with introns. The trans-splicing gene rps12 had three unique exons .The complete chloroplast genome of Castanea mollissima Blume . A large sampling scheme covering more species is needed for further clarification of phylogenetic relationships intra subfamily Engelhardioideae.Phylogenetic relationships intra Juglandoideae are frequently investigated (Zhang et al. me Blume  (Fagacear Walter  (BetulacLoureiro  (MyricacLoureiro . This isLoureiro . FurtherEngelhardia s.s., E. hainanensis. The assembly circular plastome was 16,534 bp in length. The phylogenetic analysis results strongly supported the three-subfamily classification system in Juglandaceae, and E. hainanensis was a resolved sister to two Alfaropsis species. The plastome sequence of E. hainanensis presented here provides valuable genomic information for further species identification and phylogenetic study of Juglandaceae.We reported the first complete chloroplast genome sequences of Click here for additional data file.Click here for additional data file.Click here for additional data file.