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Objective To investigate the association between the systemic immunity‐inflammation index (SII) and fatigue, cancer, and cancer‐related fatigue (CRF) populations. Methods The National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 provided data for this retrospective cross‐sectional study. By dividing the platelet count by the neutrophil count and the lymphocyte count, SII was calculated. Participants were categorized into four groups: normal, fatigue, cancer, and cancer‐related fatigue (CRF), with the normal group serving as the reference. Binary logistic regression was applied to assess the correlations. The dose–response relationship between SII and outcomes in the four groups was evaluated using restricted cubic splines. Use threshold effect analysis to determine the optimal SII value for each of the three groups. Stratified and subgroup analyses were performed based on sociodemographic factors and confounders, with specific attention to fatigue severity levels (mild, moderate, severe) in the fatigue and CRF groups. Results Data analysis included a total of 32,491 participants, including 14,846 in the normal group, 14,581 in the fatigue group, 1520 in the cancer group, and 1544 in the CRF group. The results of binary logistic regression showed that SII was positively correlated with the fatigue group (1.43[1.33, 1.55]), cancer group (1.67 [1.43, 1.95]) and CRF group (1.93 [1.66, 2.25]). Restricted cubic spline analysis revealed a linear relationship between SII and outcomes. The threshold values (k) for each of these groups were identified as 464.78 × 103 cells/μL, 448.97 × 103 cells/μL, and 454.65 × 103 cells/μL, respectively. Stratified analysis indicates that most groups exhibit significant differences. The subgroup analysis indicated that fatigue severity increased with higher SII levels, with the CRF group exhibiting the highest rate of severe fatigue (171% increase). Conclusion SII is positively correlated with fatigue, cancer, and CRF in a linear way. Higher SII values are associated with greater fatigue, particularly in the CRF population.

Infectious diseases and infections remain a leading cause of death in low-income countries and a major risk to vulnerable groups, such as infants and the elderly. The immune system plays a crucial role in the susceptibility, persistence, and clearance of these infections. With 70–80% of immune cells being present in the gut, there is an intricate interplay between the intestinal microbiota, the intestinal epithelial layer, and the local mucosal immune system. In addition to the local mucosal immune responses in the gut, it is increasingly recognized that the gut microbiome also affects systemic immunity. Clinicians are more and more using the increased knowledge about these complex interactions between the immune system, the gut microbiome, and human pathogens. The now well-recognized impact of nutrition on the composition of the gut microbiota and the immune system elucidates the role nutrition can play in improving health. This review describes the mechanisms involved in maintaining the intricate balance between the microbiota, gut health, the local immune response, and systemic immunity, linking this to infectious diseases throughout life, and highlights the impact of nutrition in infectious disease prevention and treatment.

The systemic immunity-inflammation index (SII) is a novel inflammatory marker, and aberrant blood lipid levels are linked to inflammation. This study aimed to look at the probable link between SII and hyperlipidemia. The current cross-sectional investigation was carried out among people with complete SII and hyperlipidemia data from the 2015–2020 National Health and Nutrition Examination Survey (NHANES). SII was computed by dividing the platelet count × the neutrophil count/the lymphocyte count. The National Cholesterol Education Program standards were used to define hyperlipidemia. The nonlinear association between SII and hyperlipidemia was described using fitted smoothing curves and threshold effect analyses. A total of 6117 US adults were included in our study. A substantial positive correlation between SII and hyperlipidemia was found [1.03 (1.01, 1.05)] in a multivariate linear regression analysis. Age, sex, body mass index, smoking status, hypertension, and diabetes were not significantly correlated with this positive connection, according to subgroup analysis and interaction testing (p for interaction > 0.05). Additionally, we discovered a non-linear association between SII and hyperlipidemia with an inflection point of 479.15 using a two-segment linear regression model. Our findings suggest a significant association between SII levels and hyperlipidemia. More large-scale prospective studies are needed to investigate the role of SII in hyperlipidemia.

Immunological mechanisms have come into the focus of current translational stroke research, and the modulation of neuroinflammatory pathways has been identified as a promising therapeutic approach to protect the ischemic brain. However, stroke not only induces a local neuroinflammatory response but also has a profound impact on systemic immunity. In this review, we will summarize the consequences of ischemic stroke on systemic immunity at all stages of the disease, from onset to long‐term outcome, and discuss underlying mechanisms of systemic brain‐immune communication. Furthermore, since stroke commonly occurs in patients with multiple comorbidities, we will also overview the current understanding of the potential role of systemic immunity in common stroke‐related comorbidities, such as cardiac dysfunction, atherosclerosis, diabetes, and infections. Finally, we will highlight how targeting systemic immunity after stroke could improve long‐term outcomes and alleviate comorbidities of stroke patients. Graphical Abstract This Review discusses the impact of ischemic stroke on systemic immunity, its interaction with common comorbidities, and the underlying mechanisms of systemic brain‐immune communication.

Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little validation has been done in vivo. We utilized CRISPR gene editing to delete most known immune-inducible AMPs of Drosophila, namely: 4 Attacins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking these ten AMP genes, we characterize the in vivo function of individual and groups of AMPs against diverse bacterial and fungal pathogens. We found that Drosophila AMPs act primarily against Gram-negative bacteria and fungi, contributing either additively or synergistically. We also describe remarkable specificity wherein certain AMPs contribute the bulk of microbicidal activity against specific pathogens, providing functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting. All animals – from humans to mice, jellyfish to fruit flies – are armed with an immune system to defend against infections. The immune system’s first line of defence often involves a group of short proteins called antimicrobial peptides. These proteins are found anywhere that germs and microbes come into contact with the body, including the skin, eyes and lungs. In many cases, it is unclear how individual antimicrobial peptides work. For example, which germs are they most effective against? Do they work alone, or in a mixture of other antimicrobial peptides? To learn more about a protein, scientists can often delete the gene that encodes it and observe what happens. Antimicrobial peptides, however, are small proteins encoded by a large number of very short genes, which makes them difficult to target with most genetic tools. Fortunately, gene editing via the CRISPR/Cas9 system can overcome many of the limitations of more traditional methods; this allowed Hanson et al. to systematically remove the antimicrobial peptide genes from fruit flies to explore how these proteins work. In the experiments, ten antimicrobial peptide genes known from fruit flies were removed, and the flies were then infected with a variety of bacteria and fungi. Hanson et al. found that the antimicrobial peptides were effective against many bacteria, but unexpectedly they were far more important for controlling one general kind of bacterial infection, but not another kind. Further experiments showed that some of these proteins work alone, targeting only a particular species of microbe. This finding suggested that animals might fight infections by very specific bacteria with a very specific antimicrobial peptide rather than with a mixture. By understanding how antimicrobial peptides work in more detail, scientists can learn what types of microbes they are most effective against. In the future, this information may eventually lead to the development of new types of antibiotics and better management of diseases that affect important insects, like bumblebees.

Hand-foot-and-mouth disease (HFMD) is an infectious disease of children caused by more than 20 types of enteroviruses, with most cases recovering spontaneously within approximately one week. Severe HFMD in individual children develops rapidly, leading to death, and is associated with other complications such as viral myocarditis and type I diabetes mellitus. The approval and marketing of three inactivated EV-A71 vaccines in China in 2016 have provided a powerful tool to curb the HFMD epidemic but are limited in cross-protecting against other HFMD-associated enteroviruses. This review focuses on the epidemiological analysis of HFMD-associated enteroviruses since the inactivated EV-A71 vaccine has been marketed, collates the progress in the development of multivalent enteroviruses vaccines in different technical routes reported in recent studies, and discusses issues that need to be investigated for safe and effective HFMD multivalent vaccines.

Hypertension is a disease closely related to inflammation, and the systemic immunity-inflammation index (SII) is a new and easily detectable inflammatory marker. We aimed to investigate the association between SII and hypertension risk in a adult population in the US. We utilized data from the National Health and Nutrition Examination Survey spanning from 1999 to 2018, incorporating comprehensive information from adults reporting hypertension. This included details on blood pressure monitoring, complete blood cell counts, and standard biochemical results. The SII was computed as the platelet count multiplied by the neutrophil count divided by the lymphocyte count. We employed a weighted multivariate logistic regression model to examine the correlation between SII and hypertension. Subgroup analyses were conducted to explore potential influencing factors. Furthermore, smooth curve fitting and two-piecewise logistic regression analysis were employed to describe non-linear relationships and identify inflection points. This population-based study involved 44,070 adults aged 20–85 years. Following Ln-transformation of the SII, multivariable logistic regression revealed that, in a fully adjusted model, participants in the highest quartile of Ln(SII) had a 12% increased risk of hypertension compared to those in the lowest quartile, which was statistically significant (OR:1.12; 95% CI 1.01, 1.24; P  < 0.001), with a P for trend = 0.019. Subgroup analysis indicated no significant interactions between Ln(SII) and specific subgroups except for the body mass index subgroup (all P for interaction > 0.05). Additionally, the association between Ln(SII) and hypertension displayed a U-shaped curve, with an inflection point at 5.89 (1000 cells/μl). Based on this research result, we found a U-shaped correlation between elevated SII levels and hypertension risk in American adults, with a inflection point of 5.89 (1000 cells)/μl). To validate these findings, larger scale prospective surveys are needed to support the results of this study and investigate potential mechanisms.

There is a compelling link between severe brain trauma and immunosuppression in patients with traumatic brain injury (TBI). Although acute changes in the systemic immune compartment have been linked to outcome severity, the long-term consequences of TBI on systemic immune function are unknown. Here, adult male C57Bl/6 mice underwent moderate-level controlled cortical impact (CCI) or sham surgery, and systemic immune function was evaluated at 1, 3, 7, 14, and 60 days post-injury. Bone marrow, blood, thymus, and spleen were examined by flow cytometry to assess changes in immune composition, reactive oxygen species (ROS) production, phagocytic activity, and cytokine production. Bone marrow derived macrophages (BMDMs) from sham and 60-day CCI mice were cultured for immune challenge studies using lipopolysaccharide (LPS) and interleukin-4 (IL-4) models. Acutely, TBI caused robust bone marrow activation and neutrophilia. Neutrophils and monocytes exhibited impairments in respiratory burst, cytokine production, and phagocytosis; in contrast, ROS levels and pro-inflammatory cytokine production were chronically elevated at 60 days post-injury. Cultures of BMDMs from chronic CCI mice demonstrated defects in LPS- and IL-4-induced polarization when compared with stimulated BMDMs from sham mice. TBI also caused thymic involution, inverted CD4:CD8 ratios, chronic T lymphopenia, greater memory conversion, increased T cell activation, impaired interferon γ induction, and chronically elevated Th1 cytokine and ROS production. Collectively, our in-depth phenotypic and functional analyses demonstrate that TBI induces widespread suppression of innate and adaptive immune responses after TBI. Moreover, at chronic time points, TBI mice exhibit hallmarks of accelerated immune aging, displaying chronic deficits in systemic immune function.

Mucosal vaccines offer the advantage of inducing immunity at pathogen entry sites; however, concerns about safety and limited efficacy have hindered the widespread use of viral-vectored intranasal vaccines. Nexavant (NVT), a well-defined TLR3 agonist, was investigated as a non-viral mucosal adjuvant. NVT was formulated with commercial subunit and polysaccharide–protein conjugate antigens and administered intranasally to mice. NVT-adjuvanted vaccines elicited robust mucosal IgA and systemic IgG responses, enhanced antigen-specific CD4 + T cell activation, and conferred strong protection against high-dose influenza virus challenge. Antigen-specific mucosal IgA was detected not only in nasal washes but also in distal mucosal sites such as saliva, vaginal washes, and feces, indicating broad mucosal immune crosstalk. These immune responses were abolished in IFNAR1 - / - mice, demonstrating a critical role for type I interferon signaling in NVT’s mechanism of action. The adjuvant was effective across diverse antigen types and demonstrated a favorable safety profile. These findings support NVT as a promising mucosal adjuvant platform for next-generation intranasal vaccines.

Background The systemic immunity-inflammation index(SII) is a new indicator of composite inflammatory response. Inflammatory response is an important pathological process in stroke. Therefore, this study sought to investigate the association between SII and stroke. Methods We collected data on participants with SII and stroke from the 2015–2020 cycle of National Health and Nutrition Examination Survey (NHANES) for the cross-sectional investigation. Multivariate linear regression models were used to test the association between SII and stroke. Fitted smoothing curves and threshold effect analysis were applied to describe the nonlinear relationship. Results A total of 13,287 participants were included in our study, including 611 (4.598%) participants with stroke. In a multivariate linear regression analysis, we found a significant positive association between SII and stroke, and the odds ratio (OR) [95% CI] of SII associating with prevalence of stroke was [1.02 (1.01, 1.04)] (P < 0.01). In subgroup analysis and interaction experiments, we found that this positive relationship was not significantly correlated among different population settings such as age, gender, race, education level, smoking status, high blood pressure, diabetes and coronary heart disease (P for trend > 0.05). Moreover, we found an nonlinear relationship between SII and stroke with an inflection point of 740 (1,000 cells /µl) by using a two-segment linear regression model. Conclusions This study implies that increased SII levels are linked to stroke. To confirm our findings, more large-scale prospective investigations are needed.