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喫煙による肺胞マクロファージ（AM）への影響と喫煙中止後の回復機構について，マウスに10日間喫煙させ，喫煙中止後の影響を検討した。AM の細胞数は，喫煙により有意に増加したが，喫煙中止後8週目で減少し，非喫煙群と同程度の回復が認められた。細胞形態は，喫煙により細胞の肥大化や空胞形成などの内部構造の複雑化が認められたが，8週目で回復した。超微形態構造は，喫煙により偽足の消失と細胞内に封入体が観察され，8週目でも封入体が残存し，回復は認められなかった。細胞内自家蛍光は，喫煙により増強したが，4週目，8週目で徐々に回復傾向が認められた。CD11c表面抗原発現は，喫煙による影響は認められなかった。TNF-α mRNA 発現は，喫煙により有意に減少し，その後4週目，8週目でも回復は認められなかった。活性酸素（H2O2）産生は，喫煙により有意に増加し，4週目，8週目でも回復は認められなかった。DNA 損傷は，喫煙により有意に増加しDNA 損傷が引き起こされたが，中止後4週目，8週目で回復した。CAT mRNA 発現は，喫煙により有意に増加し，その後4週目，8週目で回復した。CD206 陽性細胞比率は，喫煙により有意に低下し，回復は認められなかった。AM の細胞数と細胞形態は，喫煙中止後8週目で回復が認められたが，免疫機能は抑制され，回復は認められなかった。その抑制機構の要因として，過剰な活性酸素産生による可能性が考えられた。喫煙中止によりAM の細胞数，細胞形態は回復したが，免疫機能の回復は認められなかった。またM1，M2 型AM の機能は，喫煙中止により回復は認められなかった。喫煙によるAM への影響が長期間持続し免疫機能が回復されないことが，喫煙関連肺疾患の発症に関与している可能性が示唆される。

We aimed to assess the effects of serratus anterior plane block (SAPB) and thoracic paravertebral nerve block (TPVB) on analgesia, immune function and serum tumor markers in patients after thoracoscopic radical resection of lung cancer. A total of 132 patients enrolled from February 2019 to November 2020 were prospectively selected and randomly divided into 3 groups (n=44). Control group received general anesthesia. After induction of general anesthesia, TPVB or SAPB group was given TPVB or SAPB. Their clinical data, operation conditions, Visual Analogue Scale (VAS) score, immune function, serum tumor markers and adverse reactions were compared. TPVB and SAPB groups had lower dosage of sufentanil during operation, later time of first pressing patient-controlled intravenous analgesia (PCA) pump after operation and smaller number of pressing PCA pump within 48 h after operation than those of control group (P0.05). SAPB and TPVB can markedly improve postoperative analgesic effect, enhance immune function and decrease serum tumor marker levels in patients receiving thoracoscopic radical resection of lung cancer, without increasing adverse reactions. However, TPVB may puncture the pleura.

The present research examined the efficacy of dietary interventions in mitigating the incidence and intensity of Acute Otitis Media (AOM) through a randomised controlled trial involving 200 AOM patients. The study involved the random allocation of participants into two groups: an intervention group that received dietary recommendations and supplements aimed at enhancing immune function and reducing inflammation, and a control group that received standard care. Over a period of two years, information pertaining to the incidence, severity, nutrient utilisation, and unfavourable outcomes of acute otitis media (AOM) was gathered. The group that received the intervention exhibited a noteworthy reduction in both the frequency and intensity of acute otitis media (AOM) in comparison to the group that did not receive the intervention. The findings of the regression analysis indicate that there exists a negative correlation between the severity of acute otitis media (AOM) and the intake of certain nutrients, namely vitamins A, C, D, E, zinc, and omega-3 fatty acids. The intervention exhibited efficacy across diverse age cohorts and was well-received by the study participants. The results indicate that dietary interventions that prioritise nutrients with immune-boosting properties have the potential to mitigate the frequency and severity of acute otitis media (AOM). The integration of dietary counselling within the management strategies for acute otitis media (AOM) may yield advantageous outcomes. Additional investigation is required to enhance the precision of nutritional recommendations and authenticate these discoveries across a range of demographics.

Immunosenescence is the adverse change in the human immune function during aging, leaving older people more prone to an increased risk of infections and morbidity. Acute upper respiratory tract infections (URTIs) are very common among older people, often resulting in continued morbidity and mortality. Therefore, approaches, such as consuming probiotics, that shorten the duration or even reduce the incidence of URTIs in older people are being studied. The aim of this study was to determine the effects of a multi-strain probiotic OMNi-BiOTiC® Active, which contains 11 live probiotic strains, on the incidence, duration, and severity of URTIs in older people. In this randomized double-blinded placebo-controlled study, 95 participants, with an average age of 70.9 years in the probiotic group and 69.6 years in the placebo group, were randomly allocated to two groups: 1010 cfu per day of the multi-strain probiotic intervention OMNi-BiOTiC® Active (49) or placebo (46). The incidence of URTIs in older people after 12 weeks supplementation with OMNi-BiOTiC® showed no statistically significant difference between the two groups (p = 0.5244). However, the duration of the URTI infections was statistically significantly different between the groups (p = 0.011). The participants that consumed the probiotic had an average duration of illness of 3.1 ± 1.6 days, whilst participants that received the placebo had symptoms for an average of 6.0 ± 3.8 days (p = 0.011). Statistically significant differences in lymphocyte counts in both groups after supplementation (p = 0.035 for the probiotic group and p = 0.029 for the placebo group) and between both groups were found (p = 0.009). Statistically significant differences in eosinophil (p = 0.002) and basophil counts (p = 0.001) in the probiotic groups before and after supplementation with probiotics were also found. Supplementation with the multi-strain probiotic OMNi-BiOTiC® Active may benefit older people with URTIs. Larger randomised controlled clinical trials are warranted. Clinical Trial Registration; identifier NCT05879393.

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease in ruminants, a chronic enteritis which results in emaciation and eventual loss of the animal. Recent advances in metagenomics have allowed a more in-depth study of complex microbiomes, including that of gastrointestinal tracts, and have the potential to provide insights into consequences of the exposure of an animal to MAP or other pathogens. This study aimed to investigate taxonomic diversity and compositional changes of the faecal microbiome of cattle experimentally challenged with MAP compared to an unexposed control group. Faecal swab samples were collected from a total of 55 animals [exposed group (n = 35) and a control group (n = 20)], across three time points (months 3, 6 and 9 post-inoculation). The composition and functional potential of the faecal microbiota differed across time and between the groups (p < 0.05), with the primary differences, from both a taxonomic and functional perspective, occurring at 3 months post inoculation. These included significant differences in the relative abundance of the genera Methanobrevibacter and Bifidobacterium and also of 11 other species (4 at a higher relative abundance in the exposed group and 7 at a higher relative abundance in the control group). Correlations were made between microbiome data and immunopathology measurements and it was noted that changes in the microbial composition correlated with miRNA-155, miR-146b and IFN-ɣ. In summary, this study illustrates the impact of exposure to MAP on the ruminant faecal microbiome with a number of species that may have relevance in veterinary medicine for tracking exposure to MAP.

AIM:To observe the curative effect of take oral and cold-wet compress on eyes with Tiaoti Tuomin Decoction and the changes of immunologic function in patients with allergic conjunctivitis. METHODS:Totally 160 patients 320 eyes with allergic conjunctivitis were randomly divided into observation group and control group. The 80 patients(160 eyes)in the observation group were treated with Tiaoti Tuomin Decoction take oral and cold-wet compress on eyes. The 80 patients(160 eyes)in the control group were treated with 0.05% Azelastine Hydrochloride Eye Drops. After 14d of continuous treatment, the symptom and sign scores, quality of life questionnaire scores of allergic conjunctivitis, and the levels of serum immunoglobulin IgG, IgA, IgE of the two groups were compared and analyzed.RESULTS:After treatment, the scores of symptom and sign, quality of life questionnaire of allergic conjunctivitis in both groups were better than those before treatment(P0.05), the level of serum immunoglobulin IgE in the observation group were significantly improved than before treatment(P

Obesity prevention is stated as a simple objective in the public health guidelines of most countries: avoid adult weight gain. However, the success of the global population in accomplishing this goal is limited as reflected in the persisting pandemic of overweight and obesity. While many intervention strategies have been proposed, most are directed at mitigating the consequences of obesity. Efforts intended to prevent unintentional weight gain and associated adiposity are termed anti-obesogenic. Herein, evidence is presented that a neglected category of foods, pulses, i.e., grain legumes, have anti-obesogenic activity. Using a preclinical mouse model of obesity, a dose–response study design in animals of both biological sexes, and cooked, freeze-dried, and milled common bean as a representative pulse, data are presented showing that the rate of body weight gain is slowed, and fat accumulation is suppressed when 70% of the dietary protein is provided from common bean. These anti-obesogenic effects are reduced at lower amounts of common bean (17.5% or 35%). The anti-obesogenic responsiveness is greater in female than in male mice. RNA sequence analysis indicates that the sex-related differences extend to gene expression patterns, particularly those related to immune regulation within adipose tissue. In addition, our findings indicate the potential value of a precision nutrition approach for human intervention studies that identify “pulse anti-obesogenic responders”. A precision approach may reduce the concentration of pulses required in the diet for benefits, but candidate biomarkers of responsivity to pulse consumption remain to be determined.

Elderly often show reduced immune functioning and can develop chronic low-grade inflammation. Why some elderly are more prone to become frail is unknown. We investigated whether frailty is associated with altered cytokine signaling through the JAK-STAT pathway in leukocytes of 34 individuals aged 65-74 years. In addition, we investigated how this relation is affected by chronic low-grade inflammation during the previous 20 years. Cytokine signaling was quantified by measuring intracellular STAT1, STAT3, and STAT5 phosphorylation in monocytes, B cells, CD4+ T cells and CD8+ T cells upon stimulation with IL-2, IL-6, IL-10, IFNα and IFNγ, using phospho-flow cytometry. Presence of chronic low-grade inflammation was investigated by evaluating 18 different plasma inflammatory markers that had been measured repeatedly in the same individuals over the previous 20 years. Frailty was assessed as a score on a frailty index.

This study investigated the effect of resveratrol on the immune and inflammatory responses and the mRNA levels of splenic toll-like receptor (TLR)-4 signaling pathway-related genes of broilers under heat stress (HS). One hundred and sixty-two birds were allocated to three groups, each with 6 replicates, for 21 continuous days. The three treatments were as follows: the control group (22 ± 1 °C), the HS (33 ± 1 °C for 10 h d-1 and 22 ± 1 °C for the remaining time) group and the HS + resveratrol (400 mg kg-1) group. At the end of the trial, one bird per replicate close to the average body weight (BW) was selected, exsanguinated, and slaughtered. Compared with the control group, the HS treatment decreased (p

Laron syndrome (LS) is a rare genetic disorder characterized by low levels of insulin-like growth factor 1 (IGF1) and high levels of growth hormone (GH) due to mutations in the growth hormone receptor gene (GHR). A GHR-knockout (GHR-KO) pig was developed as a model for LS, which displays many of the same features as humans with LS-like transient juvenile hypoglycemia. This study aimed to investigate the effects of impaired GHR signaling on immune functions and immunometabolism in GHR-KO pigs. GHR are located on various cell types of the immune system. Therefore, we investigated lymphocyte subsets, proliferative and respiratory capacity of peripheral blood mononuclear cells (PBMCs), proteome profiles of CD4− and CD4+ lymphocytes and IFN-α serum levels between wild-type (WT) controls and GHR-KO pigs, which revealed significant differences in the relative proportion of the CD4+CD8α− subpopulation and in IFN-α levels. We detected no significant difference in the respiratory capacity and the capacity for polyclonal stimulation in PBMCs between the two groups. But proteome analysis of CD4+ and CD4− lymphocyte populations revealed multiple significant protein abundance differences between GHR-KO and WT pigs, involving pathways related to amino acid metabolism, beta-oxidation of fatty acids, insulin secretion signaling, and oxidative phosphorylation. This study highlights the potential use of GHR-KO pigs as a model for studying the effects of impaired GHR signaling on immune functions.

Background Per- and polyfluoroalkyl substances (PFAS) are of public health concern, because of their ubiquitous and extremely persistent occurrence, and depending on their structure, their bio-accumulative, mobile and toxic properties. Human health effects associated with exposure to PFAS include adverse effects on the immune system. In 2020, EFSA (the European Food Safety Authority) defined adverse effects on the immune system as the most critical effect for human health risk assessment, based on reduced antibody responses to childhood vaccines and similar effects observed in experimental animal studies. Likewise, the U.S. EPA (Environmental Protection Agency) considers PFAS-induced immunotoxicity, especially in children, as the critical effect for risk assessment. However, the mechanisms by which antibody concentrations are impacted are not completely understood. Furthermore, other targets of the immune system functions have been reported in the literature. Objective The aim of this review is to explore PFAS-associated immune-related effects. This includes, relevant mechanisms that may underlie the observed effects on the immune system, immunosuppression as well as immunoenhancement, such as i) modulation of cell signalling and nuclear receptors, such as NF-κB and PPARs; ii) alteration of calcium signalling and homoeostasis in immune cells; iii) modulation of immune cell populations; iv) oxidative stress and v) impact on fatty acid metabolism & secondary effects on the immune system. Methods A literature research was conducted using three databases (Web of Science, PubMed, and Scopus), which were searched in July 2021 for relevant studies published in the time frame from 2018 to 2021. In total, 487 publications were identified as potentially eligible and following expert-based judgement, articles relevant for mechanisms of PFAS induced immunotoxicity are discussed. Conclusions Taken together, we show that there is substantial evidence from both in vitro and in vivo experimental as well as epidemiological studies, supporting that various PFAS, not only PFOA and PFOS, affect multiple aspects of the immune system. Timing of exposure is critical, because the developing immune system is especially vulnerable to toxic insults, resulting in a higher risk of particularly adverse immune effects but also other organs later in life.

Poultry is frequently contaminated by Salmonella, a pathogen leading to human health concern worldwide. This study aimed to evaluate the effect of Bacillus subtilis (BS)strain 048 (BS048) on the activation, phagocytosis, sterilization, cytokine secretion, and nitrogen oxide synthesis of HD11 chicken macrophages subjected to Salmonella enteritidis challenge, using lipopolysaccharide treatment as a negative control. The results showed: (1) BS048 had no significant effect on extracellular lactate dehydrogenase activity (p>0.05), while lipopolysaccharide treatment significantly increased extracellular lactate dehydrogenase activity (p

The present study investigated the effects of methionine (Met) on growth, immune function, and antioxidant capacity in partridge shank broilers, which were treated with either an anticoccidial drug or a coccidia vaccine. Chickens were fed five graded levels of Met (0.33%, 0.39%, 0.45%, 0.51%, or 0.57%) for 21 days in combination with the drug or vaccine. The results revealed that an optimal level of Met supplementation (1) increased ADFI (average daily feed intake), ADG (average daily gain), and F/G values (feed-to-gain ratio), indicating improved production; (2) increased OPG levels (oocysts per gram feces), intestinal lesion scores, bursa of Fabricius and thymus indexes, and sIgA content; (3) improved GSH-Px activities, and increased content levels of T-protein, albumin, and urea nitrogen. In addition, birds in the anticoccidial drug group had higher final weights, higher ADFI and ADG values, as well as lower F/G values, compared with birds in the vaccine group, indicating that coccidia vaccine reduces the performance of broilers. In conclusion, we found that an optimal level of dietary Met improved the production of partridge shank broilers, and this result might be related to immune function and antioxidant capacity. Optimal levels of digestible Met in terms of production performance (ADG and F/G) and immune function (sIgA in ileum mucosa) in partridge shank broilers (1–21 days) were found to be 0.418, 0.451, and 0.451 of diet, respectively, when birds were given anticoccidial drug treatment, with corresponding figures of 0.444, 0.455, and 0.452% when the coccidia vaccine was administered.

Background Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has a further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. Methods/design We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11–19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMCLBM) Z-score at 48 weeks, measured by dual-energy X-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip strength at 48 and 96 weeks and TBLH-BMCLBMZ-scores at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. Discussion This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual in childhood is critical for optimising adolescent and early adult bone health and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. Trial registration Pan African Clinical Trials Registry PACTR20200989766029. Registered on 3 September 2020

In systematically considering the advantages and disadvantages of complementarity in high or low milk feeding, novel milk feeding schemes involving altering the volume of supplied milk in different stages of the pre-weaning period but maintaining the total milk feeding volume were tested. Twenty-seven newborn male Holstein calves were selected and randomly assigned to 3 treatments. Calves in the control (CON) group were fed 7 L of milk daily from 4 to 66 d of age. Calves in the low-high (LH) group were fed 6 L of milk daily at the beginning, and then the daily feeding volume was later increased to 7 to 8 L of milk, which served as the early-period low-volume feeding group. The calves in the high-low (HL) group were fed 7 to 8 L daily at the beginning, and then the daily feeding volume was decreased to 6 L of milk, which served as the early-period high-volume feeding group. Then all calves were fed 3 L of milk daily from 67 to 70 d of age, weaned at 70 d of age, and then fed starter feed to 100 d of age. All calves had access to the starter feed from 15 to 100 d of age. The diarrheal condition of calves was recorded daily and the growth performance including the starter feed intake and body weight of calves was recorded at 70 and 100 d of age. Then, five 100-d-old calves from each treatment were sampled for measurement of plasma indices, ruminal morphology, and volatile fatty acids. When compared with the CON and LH groups, calves in the HL group exhibited a significantly increased body weight and lower diarrhoeal rate. When compared with the CON group, calves in the HL group exhibited a significantly increased average daily feed intake, ruminal epithelium papillae length, total volatile fatty acids, and percentages of propionate and butyrate. Moreover, the significantly increased plasma immunoglobulin G (IgG) content and a trend of decreased tumor necrosis factor-α (TNF-α) content (P = 0.083) were also identified in the HL group when compared with the CON group. Overall, the early-period high-volume feeding for calves produced greater body weight gain and a lower incidence of diarrhea.

Light at night is a pervasive problem in our society; over 80% of the world’s population experiences significant light pollution. Exacerbating this issue is the reality that artificially lit outdoor areas are growing by 2.2% per year and continuously lit areas brighten by 2.2% each year due to the rapid growths in population and urbanization. Furthermore, the increase in the prevalence of night shift work and smart device usage contributes to the inescapable nature of artificial light at night (ALAN). Although previously assumed to be innocuous, ALAN has deleterious effects on the circadian system and circadian-regulated physiology, particularly immune function. Due to the relevance of ALAN to the general population, it is important to understand its roles in disrupting immune function. This review presents a synopsis of the effects of ALAN on circadian clocks and immune function. We delineate the role of ALAN in altering clock gene expression and suppressing melatonin. We review the effects of light at night on inflammation and the innate and adaptive immune systems in various species to demonstrate the wide range of ALAN consequences. Finally, we propose future directions to provide further clarity and expansion of the field.

Objective To investigate the inhibitory effect of cordycepin on immune function injury in lung cancer rats after radiation therapy through JAK2/STAT3 signaling pathway. Methods Fifty rats were used to establish tumor-bearing model and other 10 rats were taken as normal group. After successful modeling, the rats were randomly divided into model group, radiotherapy group, cordycepin group, agonist group and agonist+cordycepin group (10 rats in each group). We compared tumor weight, tumor volume, tumor inhibition rate, IL-6, TNF-α, spleen index and thymus index, the number of T lymphocyte subsets, JAK2, p-JAK2, STAT3 and p-STAT3 protein expression levels among all groups. Results Compared with normal group, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 in model group were increased, while spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05). Compared with model group, tumor weight, tumor volume, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased in radiotherapy group, while IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were increased (P < 0.05). Compared with radiotherapy group, tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were decreased in cordycepin group, while tumor inhibition rate, spleen index thymus index, CD4+ and CD4+/CD8+ were increased; tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 protein expression were increased in agonist group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05). Compared with agonist+cordycepin group, tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were decreased in cordycepin group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were increased; tumor weight, tumor volume, IL-6, TNF-α, CD8+, p-JAK2 and p-STAT3 were increased in agonist group, while tumor inhibition rate, spleen index, thymus index, CD4+ and CD4+/CD8+ were decreased (P < 0.05). Conclusion Cordycepin can effectively inhibit the immune function injury in lung cancer rats after radiation therapy, and may play a regulatory role by inhibiting the JAK2/STAT3 signal pathway.

BACKGROUND At present, colorectal cancer is routinely treated with adjuvant radiotherapy and chemotherapy postoperatively. The adverse effects (AEs) of chemotherapy usually interrupt the treatment of chemotherapy. Traditional Chinese medicine (TCM) has demonstrated great potential in improving patients' clinical symptoms, regulating the immune function, improving the life quality, and reducing the AEs of chemotherapy. AIM To observe the clinical efficacy of Yiqi Jianpi anti-cancer prescription combined with chemotherapy in patients with colorectal cancer after operation. METHODS Data from patients diagnosed with colorectal cancer between January 2019 and February 2021 were collected from Liaoning Cancer Hospital and Institute and the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine. Patients receiving the chemotherapy regimen of capecitabine plus oxaliplatin (CAPOX) after radical resection of colorectal cancer were prospectively collected and randomly divided into an experimental group and a control group. The experimental group was given Yiqi Jianpi anti-cancer prescription combined with the CAPOX regimen, while the control group was given the CAPOX regimen alone. After six cycles of chemotherapy, the scores of TCM symptoms, Karnofsky performance scale (KPS) score, levels of T-cell subsets, and AEs after chemotherapy of the two groups were compared. RESULTS A total of 70 patients were randomly divided into either an experimental group (n = 35, no dropout) or a control group (n = 33, with 2 dropouts). Compared with the control group, the experimental group improved significantly (P < 0.05) in scores of TCM symptoms, KPS score, levels of T-cell subsets, and AEs of chemotherapy. CONCLUSION Yiqi Jianpi anti-cancer prescription can effectively improve spleen deficiency, regulate the immune function, and alleviate the AEs of chemotherapy, so as to improve the life quality of patients with good therapeutic effects and application prospect in clinical practice.

Seasonal variation in immune function can be attributed to life history trade-offs, and to variation in environmental conditions. However, because phenological stages and environmental conditions co-vary in temperate and arctic zones, their separate contributions have not been determined. We compared immune function and body mass of incubating (female only), chick-feeding (female and male), and non-breeding (female and male) red-capped larksCalandrella cinereabreeding year-round in three tropical equatorial (Kenya) environments with distinct climates. We measured four immune indices: haptoglobin, nitric oxide, agglutination, and lysis. To confirm that variation in immune function between breeding (i.e., incubating or chick-feeding) and non-breeding was not confounded by environmental conditions, we tested if rainfall, average minimum temperature (Tmin), and average maximum temperature (Tmax) differed during sampling times among the three breeding statuses per location.TminandTmaxdiffered between chick-feeding and non-breeding, suggesting that birds utilized environmental conditions differently in different locations for reproduction. Immune indices did not differ between incubating, chick-feeding and non-breeding birds in all three locations. There were two exceptions: nitric oxide was higher during incubation in cool and wet South Kinangop, and it was higher during chick-feeding in the cool and dry North Kinangop compared to non-breeding birds in these locations. For nitric oxide, agglutination, and lysis, we found among-location differences within breeding stage. In equatorial tropical birds, variation in immune function seems to be better explained by among-location climate-induced environmental conditions than by breeding status. Our findings raise questions about how within-location environmental variation relates to and affects immune function.

Exposure to perfluorinated alkylate substances (PFAS) is associated with harmful effects on human health, including developmental immunotoxicity. This outcome was chosen as the critical effect by the European Food Safety Authority (EFSA), which calculated a new joint reference dose for four PFAS using a Benchmark Dose (BMD) analysis of a study of 1-year old children. However, the U.S. Environmental Protection Agency (EPA) recently proposed much lower exposure limits.MethodsWe explored the BMD methodology for summary and individual data and compared the results with and without grouping for two data sets available. We compared the performance of different dose-response models including a hockey-stick model and a piecewise linear model. We considered different ways of testing the assumption of equal weight-based toxicity of the four PFAS and evaluated more flexible models with exposure indices allowing for differences in toxicity.ResultsResults relying on full and decile-based data were in good accordance. However, BMD results for the larger study were lower than observed by EFSA for the smaller study. EFSA derived a lower confidence limit for the BMD of 17.5 ng/mL for the sum of serum-PFAS concentration, while similar calculations in the larger cohort yielded values of about 1.5 ng/mL. As the assumption of equal weight-based toxicity of the four PFAS seems questionable, we confirmed dose-dependencies that allowed potency differences between PFAS. We also found that models linear in the parameters for the BMD analysis showed superior coverage probabilities. In particular, we found the piecewise linear model to be useful for Benchmark analysis.ConclusionsBoth data sets considered could be analyzed on a decile basis without important bias or loss of power. The larger study showed substantially lower BMD results, both for individual PFAS and for joint exposures. Overall, EFSA’s proposed tolerable exposure limit appears too high, while the EPA proposal is in better accordance with the results. BackgroundExposure to perfluorinated alkylate substances (PFAS) is associated with harmful effects on human health, including developmental immunotoxicity. This outcome was chosen as the critical effect by the European Food Safety Authority (EFSA), which calculated a new joint reference dose for four PFAS using a Benchmark Dose (BMD) analysis of a study of 1-year old children. However, the U.S. Environmental Protection Agency (EPA) recently proposed much lower exposure limits.MethodsWe explored the BMD methodology for summary and individual data and compared the results with and without grouping for two data sets available. We compared the performance of different dose-response models including a hockey-stick model and a piecewise linear model. We considered different ways of testing the assumption of equal weight-based toxicity of the four PFAS and evaluated more flexible models with exposure indices allowing for differences in toxicity.ResultsResults relying on full and decile-based data were in good accordance. However, BMD results for the larger study were lower than observed by EFSA for the smaller study. EFSA derived a lower confidence limit for the BMD of 17.5 ng/mL for the sum of serum-PFAS concentration, while similar calculations in the larger cohort yielded values of about 1.5 ng/mL. As the assumption of equal weight-based toxicity of the four PFAS seems questionable, we confirmed dose-dependencies that allowed potency differences between PFAS. We also found that models linear in the parameters for the BMD analysis showed superior coverage probabilities. In particular, we found the piecewise linear model to be useful for Benchmark analysis.ConclusionsBoth data sets considered could be analyzed on a decile basis without important bias or loss of power. The larger study showed substantially lower BMD results, both for individual PFAS and for joint exposures. Overall, EFSA's proposed tolerable exposure limit appears too high, while the EPA proposal is in better accordance with the results.

Aquaculture is the fastest growing agricultural sector in the world, and the annual aquaculture production reached 82 million tonnes in 2018. Fish feed is the most expensive component of aquaculture. The partial replacement of commercial fish feed with biofloc was evaluated as a dietary ingredient in feed for barramundi (Lates calcarifer), a high-value carnivorous fish. Biofloc was produced from the effluent of a recirculating aquaculture system under microaerophilic conditions, as part of its water treatment process, which was based on nutrient assimilation by microbial biomass. The biofloc was harvested and used in fish feed. The experimental feed was prepared by replacing 20% (w/w) of commercial barramundi feed with dry biofloc powder. Six 100 l plastic tanks were stocked with barramundi (average weight 27 ± 0.9 g) at a density of 20 kg/m3. The fish in three tanks were fed a commercial feed and the others with the experimental diet for 8 weeks, at 2% bodyweight per day. The fish were weighed weekly. At the end of the trial, the proximate body compositions and immune functions of the fish were analyzed. Fifteen fish from each treatment were challenged with Vibrio harveyi to examine their disease resistance. Weight gain was 14% higher (p < 0.05) in the control group compared to biofloc -fed group, but fish fed biofloc showed significantly higher survival rates after bacterial challenge (89% survival) compared to control (58% survival, p = 0.01). Sera of the biofloc -fed fish had higher levels of lysozyme and myeloperoxidase activity (p < 0.001). Similarly, the expression of immune-related genes in the kidneys was significantly higher in the biofloc -fed fish than in the control (p < 0.05). These results, together with an economic evaluation, demonstrate the potential practical application of biofloc as a feed ingredient in barramundi aquaculture. Further optimization of this practice is required.

To investigate developmental changes in immunity and different responses to weaning stress of piglets from different breeds during suckling and weaning periods, a total of 30 litters of Taoyuan black (TB) piglets, Xiangcun black (XB) piglets, and Duroc (DR) piglets (ten litters per breed) were selected at 1, 10, 21, and 24 days of age, respectively. The results showed that the liver index of TB piglets was higher at 10 days of age than that of the other days of age and breeds. Regardless of the days of age, TB and XB piglets had a higher plasma IgA level and lower ileal IgM level than in the DR piglets, and XB piglets had a lower plasma IgG level than the other breeds. TB and XB piglets had a higher IL-6 level and lower IL-17 level in plasma at 24 days of age than DR piglets, regardless of the days of age. The ileal levels of IL-2, IL-10, IFN-γ, and TNF-α were lower in the TB and XB piglets at 24 days of age than in the DR piglets. The ileal expression levels of IRAK1, CD14, MyD88, and NF-κB were down-regulated in the TB and XB piglets at 24 days of age compared to those in the DR piglets. These findings suggest that there were differences in the development of immune function among different pig breeds. Moreover, TB and XB piglets presented stronger resistance to weaning stress than the DR piglets, which may be related to the immune regulation mediated by the MyD88/NF-κB signaling pathway.

Background Elderly often show reduced immune functioning and can develop chronic low-grade inflammation. Why some elderly are more prone to become frail is unknown. We investigated whether frailty is associated with altered cytokine signaling through the JAK-STAT pathway in leukocytes of 34 individuals aged 65–74 years. In addition, we investigated how this relation is affected by chronic low-grade inflammation during the previous 20 years. Cytokine signaling was quantified by measuring intracellular STAT1, STAT3, and STAT5 phosphorylation in monocytes, B cells, CD4+ T cells and CD8+ T cells upon stimulation with IL-2, IL-6, IL-10, IFNα and IFNγ, using phospho-flow cytometry. Presence of chronic low-grade inflammation was investigated by evaluating 18 different plasma inflammatory markers that had been measured repeatedly in the same individuals over the previous 20 years. Frailty was assessed as a score on a frailty index. Results We found that lower cytokine-induced pSTAT responsiveness in the various cell subsets was seen with higher frailty scores in both men and women, indicative of dysfunctional pSTAT responses in frailer individuals. Associations differed between men and women, with frailer women showing lower pSTAT1 responses in monocytes and frailer men showing lower pSTAT5 responses in CD4+ and CD8+ T cells. Notably, lower IL-10-induced pSTAT3 responses in men were related to both higher frailty scores and higher CRP levels over the past 20 years. This might indicate poor resolution of low-grade inflammation due to defective regulatory pSTAT signaling in older men. Conclusions Our results emphasize the importance of preserved JAK-STAT pathway signaling in healthy aging and reveal cellular pSTAT levels as a candidate biomarker of frailty.

De-Song Shen,1 Chang Yan,1 Yu Liang,1 Kai-Hua Chen,1 Xiao-Dong Zhu1,2 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of ChinaCorrespondence: Xiao-Dong Zhu Tel +86 771 533 1466Email zhuxdonggxmu@126.comPurpose: We set out to explore the prognostic value of circulating lymphocyte subsets in patients with nasopharyngeal carcinoma (NPC) before treatment and to investigate changes in lymphocyte subsets resulting from chemoradiotherapy.Patients and Methods: This retrospective study included 677 patients with non-metastatic NPC. The cutoff value of lymphocyte subsets was determined by the receiver operating characteristic curve (ROC), and the prognostic significance of lymphocyte subsets was evaluated by the Log rank test and Cox proportional hazards model. The endpoints were overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). Differences in lymphocyte subsets before and after chemoradiotherapy were analyzed by Wilcoxon signed rank test.Results: NPC patients with high levels of CD19+ B cells (> 9.55%) had better 5-year OS (90.4% VS 76.8%, P < 0.001), 5-year PFS (85.3% VS 71.6%, P < 0.001) and 5-year DMFS (94% VS 86.8%, P = 0.002) than patients with low levels of CD19+ B cells. Patients with high levels of CD4+ T cells (> 37.05%) had better 5-year PFS (83% VS 74.2%, P = 0.015) and better 5-year DMFS (95.8% VS 86.7%, P < 0.001) than those with low levels of CD4+ T cells. Multivariate analyses indicated that CD19+ B cell was an independent prognostic factor for OS, PFS and DMFS in NPC. And CD4+ T cell was an independent prognostic factor for PFS and DMFS. Within 1 month after chemoradiotherapy, the percentages of CD4+ T cells, CD19+ B cells, and the CD4/CD8 ratio decreased significantly, while the percentages of CD8+ T cells increased significantly.Conclusion: NPC patients with low levels of CD19+ B cells or CD4+ T cells before treatment have a poor prognosis. In addition, chemoradiotherapy may reduce the body’s immune function in NPC patients.Keywords: nasopharyngeal carcinoma, lymphocyte subsets, prognosis, chemoradiotherapy, immune function

Ci Dian Dan Zeng, Yi Xin Tong, Ai Tang Xiao, Chun Gao, Sheng Zhang Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Chun Gao; Sheng Zhang Email gaochun75@hotmail.com; aloof3737@126.comBackground: Immune function influenced patients’ recovery from major abdominal surgery. The aim of this study is to explore the clinical feasibility of peripheral lymphocyte absolute counts for predicting short-term surgical outcomes in gastric cancer patients after laparoscopic D2 gastrectomy.Methods: This is a prospective cohort study from a single tertiary referral hospital. Patients diagnosed with gastric cancer who met the inclusion criteria were included in this study. We collected the demographic and clinicopathological characteristics of included patients. We monitored perioperative dynamics of absolute counts of peripheral lymphocyte subsets. Predictive factors for length of postoperative hospital stay and complications were investigated in univariate and multivariate analyses.Results: A total of 137 gastric cancer patients were included. Decreased preoperative absolute counts of peripheral lymphocyte subsets were correlated with advanced clinical stage. In multivariate analysis, independent predictive factors for prolonged hospital stay were age (p=0.04), decreased preoperative B cell counts (p=0.05), decreased preoperative NK cell counts (p=0.05) and complications (p< 0.01). For postoperative complication, independent predictive factors were age (p=0.02), operation time (p=0.05), lymphocyte to C-reactive protein ratio (p=0.01) and decreased preoperative B cell counts (p=0.01).Conclusion: Our findings for the first time revealed that absolute counts of peripheral lymphocyte subsets are independent predictive factors for surgical outcomes in gastric cancer patients after D2 gastrectomy. We suggested that patients with impaired immune state should receive both preoperative immune modulator and nutritional support.Keywords: gastric cancer, absolute counts of peripheral lymphocyte subsets, immune function, surgical outcome, inflammatory cytokines

Background: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has gradually become a global public health crisis. Some patients who have recovered from COVID-19 subsequently tested positive again for SARS-CoV-2 after discharge (retesting-positive, RTP). However, the underlying mechanism is unknown. Methods: Here, 30 RTP patients, 20 convalescent patients, and 20 healthy controls were enrolled for analysis of the immunological characteristics of their peripheral blood mononuclear cells (PBMCs). Furthermore, we sought to comprehensively characterize the transcriptional changes in the three groups by transcriptome sequencing. Findings: It was found that the absolute numbers of CD4+ T cells, CD8+ T cells, and NK cells were not decreased remarkably, while the expression of activation markers on these cells was significantly decreased in RTP patients. Furthermore, the percentage of granzyme B-producing T cells was also decreased in RTP patients compared with that in convalescent patients. Moreover, the high expression of inhibitor of differentiation-1 (ID1) and the low expression of IFITM10 may be associated with the insufficient activation of immune cells and RTP occurrence. Interpretation: Our findings provide insights into the impaired immune function and pathogenesis of RTP occurrence in COVID-19, which may contribute to the development of immunotherapy for RTP patients. Funding Statement: This work was supported by China National Center for Biotechnology Development (2020YFC0843800 and 2020YFC0846800), Ministry of Science and Technology of China (2020TFC0844100), and China Postdoctoral Science Foundation (2020T130112ZX). Declaration of Interests: The authors declare no potential conflict of interest. Ethics Approval Statement: The studies were approved by the Ethics Committee of the First Affiliated Hospital of the University of Science & Technology of China (2020-XG(H)-005) and Peking University First Hospital (2020-Research-112) for Emerging Infectious Diseases. Experiments were conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki, the Principles of Good Clinical Practice, and the guidelines of China’s regulatory requirements.

Ci Dian Dan Zeng, Yi Xin Tong, Ai Tang Xiao, Chun Gao, Sheng Zhang Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Chun Gao; Sheng Zhang Email gaochun75@hotmail.com; aloof3737@126.comBackground: Immune function influenced patients’ recovery from major abdominal surgery. The aim of this study is to explore the clinical feasibility of peripheral lymphocyte absolute counts for predicting short-term surgical outcomes in gastric cancer patients after laparoscopic D2 gastrectomy.Methods: This is a prospective cohort study from a single tertiary referral hospital. Patients diagnosed with gastric cancer who met the inclusion criteria were included in this study. We collected the demographic and clinicopathological characteristics of included patients. We monitored perioperative dynamics of absolute counts of peripheral lymphocyte subsets. Predictive factors for length of postoperative hospital stay and complications were investigated in univariate and multivariate analyses.Results: A total of 137 gastric cancer patients were included. Decreased preoperative absolute counts of peripheral lymphocyte subsets were correlated with advanced clinical stage. In multivariate analysis, independent predictive factors for prolonged hospital stay were age (p=0.04), decreased preoperative B cell counts (p=0.05), decreased preoperative NK cell counts (p=0.05) and complications (p< 0.01). For postoperative complication, independent predictive factors were age (p=0.02), operation time (p=0.05), lymphocyte to C-reactive protein ratio (p=0.01) and decreased preoperative B cell counts (p=0.01).Conclusion: Our findings for the first time revealed that absolute counts of peripheral lymphocyte subsets are independent predictive factors for surgical outcomes in gastric cancer patients after D2 gastrectomy. We suggested that patients with impaired immune state should receive both preoperative immune modulator and nutritional support.Keywords: gastric cancer, absolute counts of peripheral lymphocyte subsets, immune function, surgical outcome, inflammatory cytokines

Background To evaluate the immune function of gastric cancer patients after single-incision laparoscopic distal gastrectomy (SIDG) or multiport laparoscopic distal gastrectomy (MLDG) guided by enhanced recovery after surgery (ERAS). Methods A retrospective cohort study was performed on 120 patients who underwent laparoscopic distal gastrectomy for gastric cancer. The patients were divided into two groups according to operation method: group A (MLDG) and group B (SIDG), both guided by ERAS concept. The indicators reflecting immune function and inflammation, such as CD3+, CD4+, CD8+ and NK cell count, CD4+/CD8+ cell ratios, IgA, IgM and IgG levels, C-reactive protein (CRP), total lymphocyte count (TLC) and neutrophil-to-lymphocyte ratio (NLR) were tested 3 days and 7 days after surgery. Results The skin incision length of patients in group B was significantly shorter than that in group A, but the operation time was significantly longer in group B than that in group A (P P P > 0.05). On the 7th day after surgery, the immune indexes of both groups recovered somewhat, approaching the preoperative level (P > 0.05). Inflammation indexes increased 3 days after surgery and decreased 7 days after surgery in both groups, among them the CRP level in group A was higher than that in group B (P Conclusion Compared with MLDG guided by ERAS, SIDG under the guidance of the ERAS concept has better cosmetic effect and similar effect on immune function of gastric cancer patients.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, poses a significant threat to public health worldwide, and diabetes is considered a risk factor for the rapid progression and poor prognosis of COVID-19. Limited immune function is a clinical feature of COVID-19 patients, and diabetes patients have defects in innate and adaptive immune functions, which may be an important reason for the rapid progression and poor prognosis of COVID-19 in patients with diabetes. We review the possible multiple effects of immune impairment in diabetic patients on the immune responses to COVID-19 to provide guidance for the diagnosis and treatment of diabetic patients with COVID-19.

Due to a swift and continuous growth of the insect rearing industry during the last two decades, there is a need for a better understanding of insect diseases (caused by insect pathogens). In the insect production sector, insect diseases are a bottleneck for every type and scale of rearing system with different degrees of technology investment (i.e. semi-open rearing, closed rearing, industrial production, small-scale farming). In this paper, we provide an overview of insect pathogens that are causing disease in the most common insect species reared or collected for use in food and feed. We also include a few examples of diseases of insect species, which are not (yet) reported to be used as food or feed; those examples may increase our understanding of insect diseases in general and for the development of disease prevention and control measures. We pay special attention to the effect of selected biotic and abiotic factors as potential triggers of insect diseases. We discuss the effect of such factors in combination with other production variables on disease development and insect immunocompetence. Additionally, we touch upon prevention and control measures that have been carried out and suggested up to now for insect production systems. Finally, we point towards possible future research directions with possibilities to enhance the resilience of insect production to insect disease outbreaks.

Background Grass carp (Ctenopharyngodon idella) is one of the most widely cultivated fishes in China. High stocking density can reportedly affect fish growth and immunity. Herein we performed PacBio long-read single-molecule real-time (SMRT) sequencing and Illumina RNA sequencing to evaluate the effects of high stocking density on grass carp transcriptome. Results SMRT sequencing led to the identification of 33,773 genes (14,946 known and 18,827 new genes). From the structure analysis, 8,009 genes were detected with alternative splicing events, 10,219 genes showed alternative polyadenylation sites and 15,521 long noncoding RNAs. Further, 1,235, 962, and 213 differentially expressed genes (DEGs) were identified in the intestine, muscle, and brain tissues, respectively. We performed functional enrichment analyses of DEGs, and they were identified to be significantly enriched in nutrient metabolism and immune function. The expression levels of several genes encoding apolipoproteins and activities of enzymes involved in carbohydrate enzymolysis were found to be upregulated in the high stocking density group, indicating that lipid metabolism and carbohydrate decomposition were accelerated. Besides, four isoforms of grass carp major histocompatibility complex class II antigen alpha and beta chains in the aforementioned three tissue was showed at least a 4-fold decrease. Conclusions The results suggesting that fish farmed at high stocking densities face issues associated with the metabolism and immune system. To conclude, our results emphasize the importance of maintaining reasonable density in grass carp aquaculture.

Parasites can play an important role in host sexual selection. According to the ‘Hamilton & Zuk hypothesis’, females acquire benefits from choosing parasite-free or parasite-resistant males based on their secondary sexual traits (e.g. colourful plumage) as indicators of heritable parasite resistance. However, females may also gain benefits by avoiding sexually transmitted parasites or acquiring more parental care, higher quality sperm and nuptial gifts provided by uninfected males. Here we tested how the presence of the Ophryocystis elektroscirrha-like parasite (OE-like) affected longevity, reproduction and mating frequency in the moth Helicoverpa armigera. We found that OE-like infection affected the sexes differently: the life span of uninfected males was reduced when paired with infected females, while these females had higher reproductive output than when paired with infected males. These results suggest some form of terminal investment by infected males. When we assessed the effect of OE-like infections on female calling behaviour and sex pheromone signal, we found that the OE-like parasite did not affect the female's pheromone signal in quality or quantity, but it did reduce her reproductive output, suggesting that infected females reallocate resources to maintain an attractive sex pheromone signal. In mate choice experiments, when females were the choosing sex, infected females mated significantly more often with uninfected than with infected males. Since these females produced approximately 12% more offspring, and uninfected females did not prefer uninfected or infected males, these results indicate female choice for uninfected males. Unexpectedly, when we compared the calling behaviour of the two females that were caged together, we found that infected females called significantly earlier than uninfected females, while this was not the case when females were housed alone. Thus, OE-like infection affects reproductive strategies in both males and females, but in different ways, which suggests sex-specific parasite-mediated selection.

Tannins were traditionally considered as anti-nutritional factors in poultry production. Recent studies found that the addition of hydrolyzed gallotannin (HGT) could improve animal health; however, the proper dosage of HGT in chickens’ diet is still unknown. Hence, our study aims to recommend its optimal dose by exploring the effects of HGT from Chinese gallnuts on the growth performance, immune function, and antioxidant capacity of yellow-feather broilers. A total of 288 male yellow-feather broilers (34.10 ± 0.08 g) were randomly allocated to four diet treatments, the basal diet with 0 (CON), 150, 300, and 450 mg/kg HGT for 63 days, respectively, with six replications per treatment and 12 birds per replication. The growth performance, slaughter performance, immune organ index, liver antioxidant-related indicators, and serum immune-related factors were evaluated. Results show that HGT supplementation did not influence the growth performance of broilers, but the diets supplemented with 300 and 450 mg/kg HGT increased the semi-eviscerated rate. Furthermore, HGT increased the content of liver T-AOC and the ratio of GSH/GSSG, which can protect against oxidative damage of birds. Additionally, supplementing HGT raised the contents of serum IL-10, IL-4, IL-6, IgA, and IgM. In conclusion, diet supplemented with 450 mg/kg HGT may be the optimal to the health of yellow-feather broilers on the whole.

1. Differences in hatching dates can shape intraspecific interactions through size-mediated priority effects (SMPE), a phenomenon where bigger, early hatched individuals gain advantage over smaller, late hatched ones. While SMPE may be important for population dynamics, to what extent and how these are affected by key environmental factors such as warming and predation risk imposed by top predators remains unclear.2. In a laboratory experiment, we studied effects of warming (low and high temperature) and predation risk (presence and absence of predator cues of perch) on SMPE in life history and physiological traits in the cannibalistic damselfly Ischnura elegans. We induced SMPE by manipulating hatching dates, thereby creating four groups: non-mixed phenology early (E) and late (L) hatchers, and mixed phenology early (E+L) and late (L+E) hatchers. 3. We found strong SMPE for survival and emergence success, with the highest values in E+L larvae and the lowest values in L+E larvae. Neither temperature nor predator cues affected SMPE for these two life history traits. The other life history traits (development rate and mass at emergence) did not show SMPE, but were affected by temperature and predator cues.4. SMPE was found for protein content, but only in the high temperature treatment. The other physiological traits (immune function measured as phenoloxidase activity and fat content) showed fixed expressions across treatments, indicating decoupling between physiology and life history. 5. The results underline that SMPEs are trait-dependent, and only weakly affected by temperature and predation risk.

Dairy cows undergo dynamic physiological changes from late gestation to early lactation, including metabolic changes and immune dysfunction. The aim of this study was to investigate the relationship between immune function and metabolic changes in peripartum dairy cows. Fifteen healthy Holstein dairy cows were enrolled 14 days prior to parturition, and plasma was collected on day −7, 0, 7, and 21 relative to calving. Plasma non-esterified fatty acids (NEFAs), glucose, β-hydroxybutyric acid (BHBA), immunoglobulin G (IgG), tumor necrosis factor alpha (TNF-α), and interleukin-2 levels were measured, and metabolic profiles were determined using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry. The data were analyzed using Tukey–Kramer adjustment for multiple comparisons, and multivariate and univariate statistical analyses were performed to screen for differential metabolites. The results showed that the concentrations of NEFAs, glucose, BHBA, and TNF-α in the plasma significantly increased and concentrations of IgG and interleukin-2 in plasma significantly decreased from −7 d to the calving day (p < 0.05). Additionally, the concentrations of glucose, IgG, and TNF-α significantly decreased from 0 to +7 d, and concentrations of NEFAs decreased significantly from +7 to +21 d (p < 0.05). The following six primary metabolic pathways were identified in all time point comparisons, and L-glutamate, linoleic acid, taurine, and L-tryptophan were involved in these major metabolic pathways. Correlation and pathway analyses indicated that a negative energy balance during the transition period adversely affects immune responses in cows, and L-tryptophan exerts immunomodulatory effects through the Trp-Kyn pathway, resulting in depletion of Trp and elevation of Kyn.

Occupational factors can have numerous impacts on wellbeing and mental health, from under- or over-employment, to shift work, and commuting time. However, the neural mechanisms by which such occupational factors influence subjective wellbeing, and engender vulnerability to mental health symptoms, are not comprehensively understood. This project aims to characterize the neurophysiological processes through which occupational factors affect our health and wellbeing in an analysis of data from the UK Biobank: a large-scale epidemiological study of 500,000 individuals, ~40,000 of whom have completed an MRI session at the time of writing. We intend to successively update our preregistration documentation as we proceed through the analysis. This document forms the second document in this series. Analysis workflows, together with time-stamped logs detailing data access events, if available, will be linked to subsequent preregistration documentation.

Traditional Chinese medicine has attracted the attention of researchers worldwide according to its positive impact on human and animal health, as well as its potential in immune regulation, prevention and treatment of various diseases (Dhama et al., 2018). Its main active components are polysaccharides, organic acid glycosides and flavonoids. According to existing literature, polysaccharides have great potential in enhancing cellular immunity, promoting antibody production and promoting cytokine secretion (Qiu et al., 2007). Astragalus membranaceus (AM) is a plant in the Leguminosae family that has long been utilized as a well-known traditional Chinese medicine and functional food (Jia et al., 2012). Astragalus Polysaccharide (APS) is the most abundant compound extracted from Astragali Radix, the dry root of Astragalus membranaceus. Although a growing body of research has reported APS as a potentially effective immune enhancer for poultry, results have been varying. The main obstacle to reaching a comprehensive conclusion is that there are variances in the preparation process, feeding method, and levels of feeding of APS among different studies (Farag & Alagawany, 2019). Overall, the use and effectiveness of APS in poultry appear to be quite complex. To our knowledge, no published research has systematically investigated all studies using APS. To gain a better understanding of the effectiveness of using APS in enhancing immune function, it is necessary to systematically evaluate the use of APS in poultry and compare its effectiveness as an immune enhancer in different situations.

In insects, proteins and carbohydrates are the most important macronutrients, because they are necessary for survival, development and reproduction. Different studies have tested the effect of the proportion of proteins and carbohydrates (p:c) in the diet, on lifespan, immune response and reproduction. In most, it has been found that a diet low in protein and rich in carbohydrates increases lifespan, however with the opposite diet there is a better performance in the immune response, while in reproduction the effect varies depending on the sex. Nonetheless, these patterns have not been quantitatively examined. We will test for the influence of a number of variables (moderators) that could modulate the use of the p:c ratio in the diet. Among these moderators are the individual's stage, sex, the stress they face (if any) and the type of metamorphosis they experience. By performing analyses, we will determine whether the above moderators differently affect the use of the p:c ratio on lifespan, immune response and reproduction.

The effects of glutamine (Gln) on immunity and intestinal barrier gene expression levels in broilers challenged with Salmonella Enteritidis were evaluated. A total of 400 1-day-old broilers were randomly assigned to four groups, 10 repetition treatments per group with 10 broiler chickens for a 21-day feeding trial. The groups were the normal control group (CON, no infected group, fed with a basal diet); the S. Enteritidis-infected control group (SCC, infected with 2.0 × 104 CFU/mL of S. Enteritidis, fed a basal diet); and the Gln 1 and 2 groups, who were challenged with S. Enteritidis and fed a basal diet plus Gln at 0.5% and 1.0%, respectively. The results show that S. Enteritidis had adverse effects on the average daily feed intake, average daily gain, and the feed conversion ratio of infected broilers compared with those of CON broilers on d 7 (p < 0.05); decreased serum immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) concentrations, and intestinal mucosa Bcl-2 mRNA expression levels (p < 0.05); increased the Lysozyme (LZM, only serum), NO, inducible NO synthase (iNOS) (except at 4 d), and total nitric oxide synthase (TNOS) (except at 4 d) activities in serum and the intestinal mucosa; and increased intestinal mucosa polymeric immunoglobulin receptor (pIgR) (except at 21 d), Avian beta-defensin 5 (AvBD5), AvBD14, Bax, and Bak mRNA expression levels during the experimental period (p < 0.05). Supplementation with Gln improved growth performance; increased serum IgA, IgG, and IgM concentrations and intestinal mucosa Bcl-2 mRNA expression levels (p < 0.05); decreased the LZM (only serum), NO, iNOS (except at 4 d), and TNOS (except at 4 d) activities in serum and the intestinal mucosa; and decreased intestinal mucosa pIgR (except at 21 d), AvBD5, AvBD14, Bax, and Bak mRNA expression levels during the experimental period (p < 0.05). These results suggest that Gln might lessen the inflammatory reaction of the small intestine and enlarge the small bowel mucosa immune and barrier function in broiler chickens challenged with S. Enteritidis.

As growth-promoting feed additives, compound acidifiers (CAs) have been widely reported in many farmed fish species, whereas there is little information on the application of CAs in the eel diet. The present trial was conducted to evaluate the supplementation effects of CAs on growth performance, serum biochemical parameters, and body composition of the juvenile American eel (Anguilla rostrata). The CAs supplementation levels in the diet of American eel were 0, 2.0, 3.0, 4.0, and 5.0 g/kg, respectively. The trial lasted for 12 weeks. The most beneficial effects of CAs on promoting growth performance, decreasing levels of serum lipid, modifying parameters of the liver function and immune function in the serum, and increasing the utilization of calcium and phosphorus in the diet were observed in the fish fed with 4.0 g/kg CAs. Dietary CAs supplementation had no significant effects on the body composition of whole fish, whereas 5.0 g/kg of dietary CAs supplementation exerted negative effects on growth performance, serum biochemical parameters, and utilization of calcium and phosphorus. The recommended level of CAs in the diet was 3.5–3.7 g/kg to achieve the optimal weight gain and feed conversion ratio for the juvenile American eel.

Macrophages are innate immune cells which have an unparalleled diversity of functions in health and disease, fueled by their remarkable ability to change their phenotype in response to diverse environmental stimuli. Critical to macrophage function is their ability to control their cellular metabolism, which not only provides energy for the cell but also unique fuels required for specific macrophage functions. Here we examine the roles of lipid and glucose metabolism in the control of macrophage function, particularly as it pertains to their response to inflammation and oxidative stress. In the first part of this dissertation, we interrogate the role of acetyl-CoA carboxylase (ACC), the committed step of fatty acid biosynthesis, in macrophage acute and chronic inflammation. We find that loss of ACC impairs the acute inflammatory response but is dispensable for the chronic inflammation observed in metabolic syndrome. In the second part of this dissertation, we attempt to understand how macrophages regulate their metabolism in order to limit the oxidative stress of heme degradation and uncover a necessity of glucose shuttling through the pentose phosphate pathway for macrophage heme clearance. We then examine how macrophage metabolism regulates heme-induced inflammation and oxidative stress in the context of Sickle Cell Disease. In summary, this work uncovers as-yet unappreciated roles for control of glucose and lipid metabolism in control of macrophage inflammatory and antioxidant function, reinforcing the importance of macrophage metabolism in the pathophysiology of diverse diseases and identifying novel targets for therapeutic treatment of pathological inflammation.

Elderly often show reduced immune functioning and can develop chronic low-grade inflammation. Why some elderly are more prone to become frail is unknown. We investigated whether frailty is associated with altered cytokine signaling through the JAK-STAT pathway in leukocytes of 34 individuals aged 65-74 years. In addition, we investigated how this relation is affected by chronic low-grade inflammation during the previous 20 years. Cytokine signaling was quantified by measuring intracellular STAT1, STAT3, and STAT5 phosphorylation in monocytes, B cells, CD4+ T cells and CD8+ T cells upon stimulation with IL-2, IL-6, IL-10, IFNα and IFNγ, using phospho-flow cytometry. Presence of chronic low-grade inflammation was investigated by evaluating 18 different plasma inflammatory markers that had been measured repeatedly in the same individuals over the previous 20 years. Frailty was assessed as a score on a frailty index.

A novel polysaccharide was extracted from Sipunculus nudus (SNP). The molecular weight (MW) of SNP was determined to be 9223 Da by high‐performance gel permeation chromatography analyses, and the structure of the SNP repeat units was determined to be →3,4‐β‐D‐GlcpNAC (1→ and →4) ‐α‐D‐Glcp (1→ in the ratio of 15:1; →2) ‐α ‐D‐Galp ‐ (1→ as a side chain; and β‐D‐Galp‐(1→ and α‐ D‐Glcp ‐ (1→ as end groups by GC‐MS analysis and NMR assays. The effect of SNP on hepatoma HepG2‐bearing mice was analysed to verify its potential in the clinical treatment of liver cancer. A total of 90 male athymic nu/nu mice were divided into therapeutic and preventive groups and fed with different amounts of SNP. The antitumour effect of SNP on HepG2‐bearing mice and mechanism of such were studied by analysing the tumour size, spleen index, thymus index, immune factors in the blood, tumour apoptosis factors, etc. The results suggest that SNP not only increased the index of immune organs in the body, but also enhanced the secretion of immune factors, including interleukin‐2, interferon gamma and tumour necrosis factor‐alpha in the serum. SNP induced the apoptosis of tumour cells via the mitochondrial apoptosis pathway, which upregulated caspase‐3, caspase‐8, caspase‐9 and BCL2‐associated X, but downregulated B‐cell lymphoma‐2 and vascular endothelial growth factor protein expression. In conclusion, SNP inhibited tumour growth by enhancing immune function and inducing tumour cell apoptosis in HepG2‐bearing mice. Therefore, SNP may be further investigated as a promising candidate for future antitumour drugs.

ispartof: OIKOS vol:130 issue:9 pages:1535-1547 status: published

Background and Objectives: The aim of this research was to evaluate the effectiveness of acceptance and commitment based therapy on immune function, quality of life and physical symptoms in patients with irritable bowel syndrome. Material and Methods: This research was an experimental with pre-test, post-test and 90 days later follow-up with the control group. The research sample were selected as available and included 30 patients with irritable bowel syndrome. Using available sampling method with the consent of the patients, They randomly sampled into two groups of 15 experimental and control, using availa be sampling method with the consent of the patients. The experimental group received acceptance and commitment group therapy for 8 sessions, while the control group did not receive any intervention. Both groups were assessed before and after the intervention and in the follow-up stage using quality of life questionnaires, irritable bowel syndrome evaluation questionnaire (Rome IV) and fecal calprotectin test for immune function. Data analysis was performed first by repeated measures analysis of variance and then by repeated measures analysis of variance by considering the protein variable in the pre-test stage as a covariate variable. Results: In the repeated measures method, the results showed that the effect of time on all three variables of safety function (F = 8.597, P = 0.001), physical condition (F = 63.95, P = 0.0001) and quality of life (F = 65.93, P = 0.0001) is significant. In the method of repeated measures with covariate, the effect of time on the safety performance variable is not significant (F = 0.217, P = 0.645) and it is significant in the variables of physical condition (F = 11.302, P = 0.0001) and quality of life (F = 13.154, P = 0.0001). The results of intergroup test also indicated the significance of the effect of treatment (control and experiment) in all three variables studied in both methods. Conclusion: The findings of the research showed that acceptance and commitment therapy can play an effective role in reducing physical symptoms and improving patients' immune function and improving their quality of life. Therefore, this treatment is recommended as an adjunctive therapy in patients with irritable bowel syndrome.

Dietary fiber has high functional value in relation to gut flora. We searched for a high-lysine mutant of the most popular rice cultivar in Japan, 'Koshihikari', as a route to a higher dietary fiber content like a success case in new barley cultivar, 'Beau-fiber'. We found several promising high-lysine mutants with high dietary fiber content. One of these, 'WFE5', has three times the dietary fiber content in white rice. Two rounds of backcrossing to Koshihikari produced a near-isogenic line with a high fiber content. The line's agronomic traits were close to those of Koshihikari except for yield and eating quality. As these two traits are critical, we discuss how to improve them.

This dissertation was primarily focused on the immune response, inflammatory response and molecular mechanisms in the skin, head kidney and spleen of grown-up grass carp (Ctenopharyngodon idella). Six iso-nitrogen diets differing in lysine concentrations (5.6, 8.5, 11.6, 14.4, 17.5 and 20.7 g/kg) were fed to 540 grass carp (164.85 ± 0.79 g) for 60 d. After that, grass carp were challenged by Aeromonas hydrophila for 6 d. This study revealed that lysine deficiency (1) suppressed the growth performance of the fish and decreased their ability to resist skin lesion morbidity, (2) impaired the immune organ's immune response by decreasing the gene expressions of mucin, liver-expressed antimicrobial peptide (LEAP)-2B, β-defensin-1 and LEAP-2A and the production of antibacterial compounds of grown-up grass carp, and (3) aggravated the inflammatory response of immune organs in the fish by increasing the gene expressions of pro-inflammatory cytokines (interferon γ2 [IFN-γ2], tumor necrosis factor α [TNF-α], interleukin [IL]-15, IL-17D, IL-12p40, IL-6 and IL-8) and down-regulating anti-inflammatory cytokines (IL-11, transforming growth factor β1 [TGF-β1], IL-10 and IL-4/13A), which were tightly correlated with signal transducer and activator of transcription (STAT)1 and STAT3 signaling pathway, respectively. The different phenomenon in the skin, spleen and head kidney of fish may be correlated with the difference in gene subtype. In addition, using quadratic regression analysis of percent weight gain (PWG), skin lesion morbidity, and the lysozyme activities in the spleen and head kidney, the dietary lysine requirements for grown-up grass carp were estimated to be 13.58, 13.51, 14.56 and 14.18 g/kg, respectively.

Introduction There is a balance between oxidative stress, antioxidant capacity and immune response. Their roles in physiological and behavioural mechanisms are important for the maintenance of the organism’s internal equilibrium. This study aimed to evaluate the antioxidant effects of the exogenous alga Spirulina platensis (Arthrospira platensis) in a stress-induced rat model, and to describe its possible mechanism of action. Material and Methods Thirty-six adult male Sprague Dawley rats were separated into four groups: control (C), stress (S), S. platensis (Sp), and S. platensis + stress (SpS). The rats in groups Sp and SpS were fed with 1,500 mg/kg b.w./day Spirulina platensis for 28 days. All rats were exposed to prolonged light phase conditions (18 h light : 6 h dark) for 14 days. The SpS and S groups were exposed to stress by being kept isolated and in a crowded environment. Blood samples were obtained by puncturing the heart on the 28th day. The effect of stress on serum corticosterone, oxidative stress markers (TOS, TAC, PON1, OSI) and immunological parameters (IL-2, IL-4, IFN-ɣ) were tested. Also, the brain, heart, intestines (duodenum, ileum, and colon), kidney, liver, spleen, and stomach of the rats were weighed. Results Serum corticosterone levels were higher in the S group than in the C group, and significantly lower in the SpS group than in the S group. Mean total antioxidant capacity were lower in the S group than in the C group, and Spirulina reversed this change. Although not significantly different, IL-2 was lower in the S group than in the C group. However, in the SpS group, IL-2 increased due to Spirulina platensis mitigating effects of stress. Conclusion Male rats fed a diet with Spirulina platensis could experience significantly milder physiological changes during stress, although stress patterns may be different. Exogenous antioxidant supplements merit further investigation in animals and humans where the endogenous defence mechanism against stress may not be sufficient.

Wushen (WS) is a mixed food containing 55 natural products that is beneficial to human health. This study aimed to reveal the preventive effect of WS on aging via a combined analysis of gut microbiome and metabolome. Senescence-accelerated mouse prone 8 (SAMP8) mice were used as aging model and senescence-accelerated mouse resistant 1 (SAMR1) mice as control. The mice were fed four diet types; control diet (for SAMR1 mice), standard diet (for SAMP8 mice, as SD group), WS diet, and fecal microbiota transplantation (FMT; transplanted from aging-WS mice). Our results showed that the weight, food intake, neurological function, and general physical conditions significantly improved in WS-fed mice compared to those fed with SD. The CA1 hippocampal region in WS-fed aged mice showed fewer shriveled neurons and increased neuronal layers compared to that of the SD group. WS-fed mice showed a decrease in malondialdehyde and an increase in superoxide dismutase levels in the brain; additionally, IL-6 and TNF-α levels significantly decreased, whereas IL-2 levels and the proportion of lymphocytes, CD3+CD8+ T, and CD4+IFNγ+T cells increased in WS-fed mice. After fed with WS, the abundance of Ruminococcus and Butyrivibrio markedly increased, whereas Lachnoclostridium and Ruminiclostridium significantly decreased in the aging mice. In addition, 887 differentially expressed metabolites were identified in fecal samples, among these, Butyrivibrio was positively correlated with D-glucuronic acid and Ruminococcus was positively associated with 5-acetamidovalerate. These findings provide mechanistic insight into the impact of WS on aging, and WS may be a valuable diet for preventing aging.