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Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution.

Glioma progression is a complex process controlled by molecular factors that coordinate the crosstalk between tumor cells and components of the tumor microenvironment (TME). Among these, immune cells play a critical role in cancer survival and progression. The complex interplay between cancer cells and the immune TME influences the outcome of immunotherapy and other anti-cancer therapies. Here, we present an updated view of the pro- and anti-tumor activities of the main myeloid and lymphocyte cell populations in the glioma TME. We review the underlying mechanisms involved in crosstalk between cancer cells and immune cells that enable gliomas to evade the immune system and co-opt these cells for tumor growth. Lastly, we discuss the current and experimental therapeutic options being developed to revert the immunosuppressive activity of the glioma TME. Knowledge of the complex interplay that elapses between tumor and immune cells may help develop new combination treatments able to overcome tumor immune evasion mechanisms and enhance response to immunotherapies.

BACKGROUND: Dexamethasone is routinely administered to horses but its effect on the antibody response to a commercial EIV/EHV vaccine is unclear. HYPOTHESIS: Horses receiving dexamethasone will have lower postvaccination antibody levels against EIV and EHV-1 than vaccinated controls. ANIMALS: Fifty-five healthy adult research horses. METHODS: Randomized cohort study. Control (no vaccine, group 1), vaccination only (EIV/EHV-1/EHV-4, Prestige 2, Merck Animal Health, group 2), vaccination and concurrent single intravenous dose of dexamethasone (approximately .05 mg/kg, group 3), vaccination and 3 intravenous doses of dexamethasone at 24 hours intervals (group 4). Serum SAA levels were measured on day 1 and day 3. Antibody levels against EIV (hemagglutination inhibition assay, Kentucky 2014 antigen) and EHV-1 (multiplex ELISA targeting total IgG and IgG 4/7) were measured on day 1 and day 30. RESULTS: Significantly increased mean antibody titers after vaccination were only noted against EIV and only after the vaccination alone (n = 14, prevaccine mean [prvm] 166.9, SD 259.6, 95% CI 16.95-316.8; postvaccine mean [povm] 249.1, SD 257.2, 95% confidence interval [CI] 100.6-397.6, P = .02) and the single dose dexamethasone (n = 14, prvm 93.14, SD 72.2, CI 51.45-134.8; povm 185.1, SD 118, CI 116.7-253.6, P = .01), but not after multiple doses of dexamethasone (n = 14, prvm 194.3, SD 258.3, CI 45.16-343.4; povm 240.0, SD 235.7, CI 103.9-376.1, P > .05). CONCLUSION: The effect of dexamethasone on the postvaccine antibody response varies depending on the dosing frequency and the antigen-specific antibody type.

Background and Aim Methods Results Conclusions Ulcerative colitis (UC) is a chronic inflammatory disease driven by immune dysregulation. PANoptosis, a novel form of programmed cell death, has been implicated in inflammatory diseases, but its specific role in UC remains unclear. This study aimed to identify PANoptosis‐related genes (PRGs) that may contribute to immune dysregulation in UC.Using bioinformatics analysis of the GEO databases, we identified seven hub PRGs. Based on these genes, we developed a predictive model to differentiate UC patients from healthy controls, and evaluated its diagnostic performance using ROC curve analysis. We further conducted functional enrichment, GSVA, and immune infiltration analyses. Immunohistochemistry (IHC) was used to validate the expression of hub genes in UC patients.The prediction model, based on the seven hub genes, exhibited diagnostic ability in discriminating UC patients from controls. Furthermore, these hub PRGs were found to be associated with immune cells, including dendritic cells, NK cells, macrophages, regulatory T cells (Tregs), and CD8+ T cells. They were also linked to key signaling pathways implicated in UC pathogenesis, such as IFNγ, TNFα, IL6‐and JAK‐STAT3, as well as hypoxia and apoptosis. Immunohistochemistry analysis validated the expression levels of hub PRGs in UC patients using paraffin sections of intestinal biopsy specimens.This study identified PANoptosis‐related genes with potential diagnostic value for UC and suggest that PANoptosis may contribute to the pathogenesis of UC by regulating specific immune cells and interacting with key signaling pathways. This highlights the potential importance of PANoptosis‐related genes as therapeutic targets in UC management. [ABSTRACT FROM AUTHOR]

Background: Cancer cells induce neutrophil extracellular traps (NETs) to promote tumor progression and metastasis. However, only a few studies have focused on the role of NETs in Neuroblastoma (NB). Methods: First, based on the expression of NET-related genes, consensus clustering analysis was conducted to cluster NB samples into different subtypes. Differential analysis was performed to identify DEGs between subtypes. Functional items and related pathways of DEGs were identified using enrichment analysis. Univariate Cox analysis and the LASSO algorithm were used to identify biomarkers for prognosis. Furthermore, independent prognostic analysis was performed. Immune infiltration analysis was performed to identify differential immune cells. Finally, the verification of prognostic model genes were taken by the immunohistochemical staining and quantitative real-time PCR. Results: Consensus clustering analysis demonstrated that NB samples were clustered into two subtypes. There were 125 DEGs between the two subtypes of NB. Moreover, the enrichment analysis results showed that the DEGs were mainly associated with 'external side of plasma membrane,' 'immune receptor activity' 'regulation of leukocyte migration' GO items. There were also several GO items related to neutrophils, such as regulation of neutrophil migration and differentiation. KEGG pathways revealed that the DEGs were correlated with in immunity-related activities, including 'Complement and coagulation cascades,' 'Neutrophil extracellular trap formation, 'T cell receptor signaling pathway,' 'PD-L1 expression and PD-1 checkpoint pathway in cancer' and so on. A total of five biomarkers,[Selenoprotein P1 (SEPP1), Fibrinogen-like protein 2 (FGL2), NK cell lectin-like receptor K1 (KLRK1), ATP-binding cassette transporters 6(ABCA6) and Galectins(GAL)], were screened, and a risk model based on the biomarkers was created. Furthermore, a nomogram for forecasting the survival rates of patients with NB was established based on the risk score, age at diagnosis, and MYCN status. Eight differential immune cells (CD8 + T cells, resting mast cells, etc.) were acquired between the two risk subgroups. The expression levels of five prognostic model genes at the protein and mRNA were verified and all results were consistent with the results of our bioinformatics analysis. Conclusion: We initially found that five NET-related genes were significantly differentially expressed in NETs-associated molecular isoforms and two Netrg molecular isoforms were found to be associated with poorer prognosis. This stratification might provide insight into the prediction of prognosis and ideal immunotherapy strategies for patients with NB. However, we also noted that the formation of NETs is a complex biological process involving the regulation of multiple cytokines and cellular interactions. Therefore, the exact roles of these genes and their specific mechanisms in the formation of NETs and the development of NB still need to be further investigated. [ABSTRACT FROM AUTHOR]

Stressful life events and glucocorticoid (stress) hormones appear to increase the risk of Alzheimer's disease and hasten its progression, but the reasons for this remain unclear. One potential explanation is that when amyloid β (Aβ) pathology is accumulating in the preclinical disease stage, glucocorticoid receptor signalling during stressful events exacerbates cellular dysfunction caused by Aβ. Alternatively, Aβ may disrupt glucocorticoid receptor signalling. To explore these possibilities, we investigated whether the synthetic glucocorticoid dexamethasone and Aβ have overlapping effects on the cellular proteome and whether Aβ influences canonical glucocorticoid receptor function. Human olfactory neurosphere‐derived (ONS) cells, collected from the olfactory mucosa of six adult donors, were treated with soluble Aβ40 or Aβ42 followed by dexamethasone. Proteins were quantified by mass spectrometry. After 32 h treatment, Aβ40 and Aβ42 both induced profound changes in innate immunity‐related proteins. After 72 h, Aβ42 formed widespread aggregates and induced few proteomic changes, whereas Aβ40 remained soluble and altered expression of mitochondrial and innate immunity‐related proteins. ONS cells revealed overlapping impacts of Aβ40 and dexamethasone, with 23 proteins altered by both treatments. For 16 proteins (including eight mitochondrial proteins) dexamethasone counteracted the effects of Aβ40. For example, caspase 4 and methylmalonate‐semialdehyde dehydrogenase were increased by Aβ40 and decreased by dexamethasone. Consistent with this finding, Aβ40 increased, but dexamethasone decreased, ONS cell proliferation. For seven proteins, including superoxide dismutase [Mn] mitochondrial, dexamethasone exacerbated the effects of Aβ40. For some proteins, including complement C3, the effects of dexamethasone differed depending on whether Aβ40 was present or absent. Neither Aβ species influenced glucocorticoid receptor nuclear translocation. Overall, this study revealed that glucocorticoid receptor signalling modifies the intracellular effects of Aß40, counteracting some effects and exacerbating others. It suggests that cellular mechanisms through which glucocorticoid receptor signalling influences Alzheimer's disease risk/progression are complex and determined by the balance of beneficial and detrimental glucocorticoid effects. [ABSTRACT FROM AUTHOR]

Obesity is a prevalent metabolic disease that reduces bacterial diversity, colonizes the epidermis with lipophilic bacteria, and increases intestinal pro-inflammatory species, all of which lead to impaired epithelial barriers. Adipose tissue secretes immunomodulatory molecules, such as adipokines, leptin, and adiponectin, which alters the morphology of adipocytes and macrophages as well as modulates T cell differentiation and peripheral Th2-dominated immune responses. Atopic dermatitis (AD) and obesity have similar pathological manifestations, including inflammation as well as insulin and leptin resistance. This review examines the major mechanisms between obesity and AD, which focus on the effect on skin and gut microbiota, immune responses mediated by the toll like receptor (TLR) signaling pathway, and changes in cytokine levels (TNF-a, IL-6, IL-4, and IL13). Moreover, we describe the potential effects of adipokines on AD and finally mechanisms by which PPAR-γ suppresses and regulates type 2 immunity. [ABSTRACT FROM AUTHOR]

Ulcerative Colitis (UC) is an inflammatory disorder characterized by chronic intestinal inflammation and immune dysregulation. Despite a clear association between cellular senescence and chronic inflammation and immune dysregulation, the mechanisms underlying cellular senescence in UC remain unclear. We screened differentially expressed genes (DEGs) associated with cellular senescence in multiple UC datasets, performed immune infiltration analysis, and constructed clinical diagnostic models. Additionally, we investigated the relationship between key genes related to cellular senescence and disease remission in UC patients undergoing biologic therapy, validating their expression in a single-cell dataset. We identified six DEGs associated with cellular senescence (TWIST1, IGFBP5, MME, IFNG, ME1, FOS). Immune infiltration results indicated strong correlations of four of these genes with immune cells and pathways. Through WGCNA, GO, and KEGG analyses, we found that gene modules strongly associated with the expression of hub genes in cellular senescence were enriched in inflammation-related pathways. In the single-cell dataset, the expression of these six key genes exhibited similarities with Immune infiltration results. Additionally, we constructed a nomogram using these six genes for diagnosing UC, demonstrating good diagnostic capability and clinical efficacy. Kaplan–Meier survival analysis revealed a significant association between changes in the expression levels of these cell genes and disease remission in UC patients undergoing biologic therapy. This study utilizes bioinformatic analysis and machine learning to identify and analyze features associated with cellular senescence in multiple UC datasets. It provides insights into the role of cellular senescence in the premature onset of intestinal aging in UC and offers new perspectives for exploring novel therapeutic targets. [ABSTRACT FROM AUTHOR]

The Athens Canadian Random Bred (ACRB) heritage broiler breed, which has not been selectively bred since the 1950s, is a point of comparison to the modern-day broiler and could highlight potential genetic-derived differences in immune responses. To observe the modern and heritage birds' immune responses in action, the innate immune ligand CpG oligonucleotides were administered at multiple time points through the birds' lives from the day after hatch to day 35 post-hatch. This study allowed for the observation of changes in metabolic and immune signaling in response to repeated injections of a known Toll-like receptor (TLR) ligand, CpG. Jejunum and cecal tonsil samples at multiple time points during grow out were collected and used for kinome array analysis to measure kinase activity in immunometabolic signaling pathways in the gut tissue. In addition cytokine gene expression was measured in these tissues. The modern birds' response to the treatment was more innate and showed evidence of metabolic energy shift. The heritage birds' response to the treatment was adaptive, with metabolic changes indicative of a well-regulated response. Overall, the results from this study suggest that modern broiler chickens do not adequately balance resources between growth and immune responses during an immune challenge, and this deficit is most evident around the 2-week post-hatch time point. This is a critical time for these birds, as their muscle deposition continues to accelerate, and they are vulnerable to disease challenges. Ideally, future work can clarify the reason for this response discrepancy in the modern broiler and therapeutic interventions to rescue this phenotype could be elucidated. [ABSTRACT FROM AUTHOR]

Galectin-9 (gal-9) is a protein that belongs to the galectin family. Gal-9 is expressed in cells of the innate and adaptive immune system, including lymphocytes, dendritic cells, giant salivary cells, eosinophils and T cells, etc. In different immune cells, the role of gal-9 is different. Gal-9 can induce the proliferation and activation of immune cells, and also promote the apoptosis of immune cells. This effect of gal-9 affects the occurrence and development of a variety of immune-related diseases, such as the invasion of pathogenic microorganisms, immune escape of tumor cells, and inflammatory response. Thus, understanding the biological roles of gal-9 in innate and adaptive immunity may be essential for autoimmune diseases treatment and diagnosis to improve patient quality of life. In this review, we aim to summarize current research on the regulatory roles of gal-9 in human immune system and potential inducers and inhibitors of gal-9, which may provide new strategies for immune diseases therapies. [ABSTRACT FROM AUTHOR]

As a biologically essential transition metal, copper is widely involved in various enzymatic reactions and crucial biological processes in the body. It plays an increasingly important role in maintaining normal cellular metabolism and supporting the growth and development of the human body. As a trace element, copper maintains the dynamic balance of its concentration in body fluids through active homeostatic mechanisms. Both excess and deficiency of copper ions can impair cell function, ultimately leading to cell damage and death. Cuproptosis is a novel form of cell death where copper ions cause cell death by directly binding to the lipoylated components of the citric acid cycle (CAC) in mitochondrial respiration and interfering with the levels of iron-sulfur cluster (Fe-S cluster) proteins, ultimately causing protein toxic stress. Its primary characteristics are Cu2+ concentration dependence and high expression in mitochondrial respiratory cells. Recent research has revealed that, compared to other forms of programmed cell death such as apoptosis, necrosis, and autophagy, cuproptosis has unique morphological and biochemical features. Cuproptosis is associated with the occurrence and development of various diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases. This article focuses on a review of the relevance of cuproptosis in gastric cancer (GC). [ABSTRACT FROM AUTHOR]

AbstractThis study aimed to identify important clotting associated genes (CRGs) associated with septic shock in children and explore possible important mechanisms of the disease. Five hub genes with diagnostic performance were identified using GEO database and data from literature. These hub genes have strong correlation with immune cells. ceRNA network was constructed to explore potential pathogenic mechanisms. Ten candidate small molecule compounds were identified. In summary, the hub genes may play an important role in the immunity and disease development of septic shock, providing new ideas and strategies for future diagnosis and mechanism evaluation of children with septic shock. [ABSTRACT FROM AUTHOR]

Systemic immune, inflammatory, and nutritional indices are prognostic across multiple tumor sites. Comprehensive analysis of these markers in patients with locally advanced cervical cancer (LACC) treated with definitive (chemo)radiotherapy [(C)RT] is limited and may assist with future prognostication. For this retrospective cohort study, patients with LACC treated with definitive (C)RT were identified from a comprehensive cancer center's clinicopathological database. Pre-treatment indices were derived including systemic immune-inflammation index (SII), platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), albumin to alkaline phosphatase ratio (AAPR) and prognostic nutritional index (PNI). Univariate analysis was performed for PFS and OS. ROC curves were analyzed to determine optimal cut points. PFS and OS were assessed by the Kaplan-Meier method and Log-Rank test. Multivariate analysis was performed using Cox regression. 196 patients were identified: median follow-up 7 years (IQR 2–11). Higher SII (≤700 vs >700; p = 0.01), higher PLR (≤ 250 vs >250; p < 0.001) and higher NLR (≤ 5 vs >5; p = 0.003) were associated with worse PFS. Higher SII (≤700 vs >700: p = 0.02), higher PLR (≤ 250 vs >250: p < 0.001) and higher NLR (≤ 5 vs >5; p = 0.01) were associated with worse OS. On multivariate analysis, SII, NLR and PLR were independently associated with PFS. SII and PLR were independently associated with OS. SII and PLR were independently associated with PFS and OS in patients with LACC treated with definitive (C)RT. NLR was independently associated with PFS. High inflammatory state is associated with shorter survival suggesting this as a target for interventions if validated in future studies. • First comprehensive analysis of immune, inflammatory, and nutritional indices in cervical cancer patients treated with (C)RT. • Systemic immune-inflammation index (SII) and platelet lymphocyte ratio (PLR) are independently associated with OS and PFS. • Neutrophil lymphocyte ratio is independently associated with PFS. [ABSTRACT FROM AUTHOR]

The channels commonly responsible for maintaining cell resting membrane potentials are referred to as K2P (two-P-domain K+ subunit) channels. These K+ ion channels generally remain open but can be modulated by their local environment. These channels are classified based on pharmacology, pH sensitivity, mechanical stretch, and ionic permeability. Little is known about the physiological nature of these K2P channels in invertebrates. Acidic conditions depolarize neurons and muscle fibers, which may be caused by K2P channels given that one subtype can be blocked by acidic conditions. Doxapram is used clinically as a respiratory aid known to block acid-sensitive K2P channels; thus, the effects of doxapram on the muscle fibers and synaptic transmission in larval Drosophila and crawfish were monitored. A dose-dependent response was observed via depolarization of the larval Drosophila muscle and an increase in evoked synaptic transmission, but doxapram blocked the production of action potentials in the crawfish motor neuron and had a minor effect on the resting membrane potential of the crawfish muscle. This indicates that the nerve and muscle tissues in larval Drosophila and crawfish likely express different K2P channel subtypes. Since these organisms serve as physiological models for neurobiology and physiology, it would be of interest to further investigate what types of K2P channel are expressed in these tissues. (212 words) [ABSTRACT FROM AUTHOR]

This study evaluated the effect of feeding colostrum obtained from an intramammary administration (IA) of LPS from Escherichia coli (O55:B5) to dairy goats at parturition, on goat kid performance, biochemical parameters (i.e., calcium, lactate dehydrogenase, glucose, total proteins, albumin, and urea) and immune status (i.e., IgG and IgM) during the first month of life. At birth, goat kids were weighted (d 0) and immediately allocated into either the LPS group (n = 15) or the control (CON) group (n = 21) based on the experimental group of the dam. At parturition, 20 multiparous dairy goats were allocated in 1 of the 2 experimental groups (LPS vs. CON). The LPS group received an IA of saline solution (2 mL) containing 50 µg of LPS in each half udder whereas goats in the CON group received an IA of saline solution (2 mL) without LPS. Goat kids were bottle-fed dam colostrum equivalent to 10% of the birth BW divided in 2 meals (i.e., at 3 and 12 h relative to birth), and then fed twice daily with milk replacer ad libitum. Individual milk intake (MI) and BW were recorded on d 7, 15, 21 and 30 of life. Blood samples were collected on d 0, 1, 2, 4, 7, 15, 21 and 30 after birth. Data were analyzed using the MIXED procedure of SAS (9.4; SAS Institute Inc.). The model included IA, time (T), and their interaction (IA × T) as fixed effects, and sex and litter size as random effects. Both groups showed similar MI, except on d 7 relative to birth as the LPS group showed higher MI than the CON group (910.5 ± 69.77 and 683.9 ± 59.64 mL, respectively; mean ± SEM). No differences in BW or rectal temperature were observed between groups, neither in plasma IgG nor IgM concentrations. Despite the IA did not affect calcium, glucose, LDH, total protein, and albumin concentrations an interaction between the IA and T was observed for urea concentration, showing the LPS group higher urea concentrations than the CON group on d 0 (20.1 ± 1.34 and 20.0 ± 1.25 mg/dL, respectively). In conclusion, feeding colostrum from goats that received an IA of LPS at parturition does not affect goat kid performance, plasma immunoglobulin concentrations and serum metabolites during the first month of life. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of 1800 MHz continuous wave (CW) and global system for mobile communications (GSM) modulated radiofrequency electromagnetic field (RFEMF) exposures on signal transduction (ST) protein and cytokine expression in differentiated human-derived monocytic THP-1 cells. Materials and methods: THP-1 cells were differentiated into adherent macrophage-like cells using phorbol 12-myristate 13-acetate (PMA). Following differentiation, cells were exposed to 1800 MHz CW or GSM modulated RFEMF for 0.5, 4, or 24 h at a specific absorption rate (SAR) of 0 (sham) or 2.0 W/kg. Concurrent positive controls (lipopolysaccharide for cytokines; anisomycin for ST proteins) and negative controls were included in each experiment. The expression levels of cytokines (GM-CSF, IFN-γ, IL-1β, IL-6, IL-10, TNF-α) from culture media and phosphorylated and total ST proteins (CREB, JNK, NF-κB, p38, ERK1/2, Akt, p70S6k, STAT3, STAT5) from cell lysates were assessed using Milliplex magnetic bead array panels. Results: No consistent effect of RFEMF exposure was observed in differentiated THP-1 cells. A statistically significant effect of overall exposure condition was observed for IL-6 with GSM modulation (P = 0.042), but no difference between RFEMF and sham for any exposure condition remained following adjustment for multiple comparisons (P ≥ 0.128). No statistically significant effect of exposure condition was detected for any other cytokine evaluated with either of the RFEMF modulations (P ≥ 0.078). There were no statistically significant changes in expression levels for any of the ST proteins under any studied exposure condition (P ≥ 0.320). Conclusions: In this study, no evidence of changes were observed in differentiated human derived THP-1 cells following exposure of up to 24 h to 1800 MHz RFEMF at SARs of 0 and 2.0 W/kg on the expression of ST proteins or cytokines. [ABSTRACT FROM AUTHOR]

Liver cancer, one of the most common malignant tumors, has seriously threatened people's physical and mental health. The paper was conducted to investigate the functions of two different anesthesia methods on Tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and T lymphocyte subsets in patients undergoing liver cancer resection, and to explore the liver function impact of patients undergoing liver cancer surgery. 80 liver cancer patients were split into propofol intravenous anesthesia group and sevoflurane inhalation anesthesia group. The patient's operation-related indicators and changes in TNF-α, CRP and T lymphocyte subsets before anesthesia, after anesthesia, 1 day after anesthesia, and 3 days after anesthesia were calculated. The levels of TNF-α and CRP in the two groups after operation were clearly higher than those before anesthesia, but there was no obvious difference between the two groups. After operation, the TNF-α of the propofol intravenous anesthesia group was lower than the sevoflurane inhalation anesthesia group. The CD3+, CD4+ and CD4+/CD8+ levels in both groups recovered to the pre-anaesthesia level 3 days after the operation. The levels of ALT, AST, ALB and TBIL returned to normal at d4 in both propofol intravenous anesthesia and sevoflurane inhalation anesthesia groups. Compared with evoflurane inhalation anesthesia for patients with liver cancer, intravenous anesthesia with propofol can reduce the body's inflammatory response to a certain extent, has weak inhibitory effect on T lymphocyte immune function, and a smaller effect on liver function. [ABSTRACT FROM AUTHOR]

Introduction: The immune system's defense against pathogens involves innate and adaptive responses, crucial in maintaining overall health. Immunosuppressed states render individuals more susceptible to potential diseases, indicating the need for effective strategies to bolster immune functions. Objectives: Although the immunostimulatory effects of various probiotics have been studied, the specific effects and molecular mechanisms of Lactococcus lactis OTG1204 (OTG1204) remain unknown. In this study, the aim was to investigate the molecular mechanisms of OTG1204 in RAW 264.7 macrophages, the key effector cells of the innate immune system involved in host defense and inflammatory responses. Additionally, in this study, the effects of OTG1204 on cyclophosphamide (CTX)-induced immunosuppression states were investigated, thereby demonstrating its potential as an immune stimulant. Methods: To assess the macrophage activation ability and underlying mechanisms of OTG1204, RAW 264.7 cells were utilized with transfection, enzyme-linked immunosorbent assay, and quantitative real-time PCR analyses. Furthermore, to evaluate the immunostimulatory effects under immunosuppressed conditions, CTX-induced immunosuppression mice model was employed, and analyses were performed using hematoxylin and eosin staining, flow cytometry, and microbiota examination. Results: OTG1204 activated RAW 264.7 macrophages, leading to increased production of nitric oxide, prostaglandin E2, and cytokines. This immune activation was mediated through the upregulation of toll-like receptor 2, which subsequently activated the nuclear factor-κB (NF-kB) and mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) pathways, thereby stimulating the immune response. In CTX-treated mice, OTG1204 recovered body weight, spleen, and mesenteric lymph node indices, and natural killer cell activity. It re-established populations of innate and adaptive immune cells and activated T cells to secrete cytokines. We also examined the gut barrier integrity and microbiota composition to assess OTG1204's impact on intestinal health, as these factors play a significant role in immune enhancement. OTG1204 enhanced gut barrier integrity by upregulating mucin 2 and tight junction proteins and modulated the gut microbiota by restoring the Firmicutes/Bacteroidetes balance and reducing the abundance of Actinobacteria and Tenericutes. Conclusion: These results suggest that OTG1204 may serve as an effective probiotic for immune enhancement and gut health management by targeting the NF-κB and MAPK/AP-1 pathways, with minimal side effects. [ABSTRACT FROM AUTHOR]

Background: This study reports the 2-year outcomes and biomarker analysis results of patients with locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma who received neoadjuvant chemotherapy and immunotherapy in a phase II WuhanUHGI001 trial. Methods: Eligible patients with cT3/4aN+M0 locally advanced G/GEJ adenocarcinoma were screened, enrolled, and treated with 3 cycles of neoadjuvant tislelizumab and SOX followed by D2 gastrectomy and another 5 cycles of postoperative adjuvant SOX. The primary endpoint was major pathological response. Results: Of the 49 included patients, 24 (49.0%) achieved major pathological response and 13 (26.5%) achieved pathological complete response. During a median follow-up of 26.8 months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 69.4% and 81.2%, respectively. Grade 3–4 adverse events occurred in six patients (12.2%) during the neoadjuvant period, eight patients (17.0%) during the postoperative period, and seven patients (15.2%) during the adjuvant period. Biomarker analysis revealed that the pathological complete response showed no association with 2-year PFS and OS. Major pathological response showed a potentially strong association with improved 2-year PFS and OS rates. In addition, preoperative circulating tumor cells combined with pathological responses are helpful in prognosis assessment. In addition, our results showed that T downstaging, lymphocyte-to-monocyte ratio, and CD3+ T cells were independent factors that affect PFS. The signet ring cell component (SRCC), T downstaging, and neutrophil-to-lymphocyte ratio were independent factors affecting OS. Prognostic nomograms of PFS and OS constructed based on the multivariate Cox regression results demonstrated suitable calibration and discrimination ability. Conclusions: Neoadjuvant tislelizumab plus SOX exhibits promising efficacy and acceptable toxicity in patients with locally advanced G/GEJ adenocarcinoma. In addition, our study established a prognostic risk signature and nomograms based on clinicopathological characteristics, which can accurately predict patient outcomes and aid in personalized treatment planning. [ABSTRACT FROM AUTHOR]

Immunity is a critical self-defense mechanism of the human body, wherein immune cells and immune molecules play a crucial role. Extracellular vesicles (EVs), derived from immune cells or other cells, play a significant role in tumors, autoimmune diseases and other immune-related disorders by serving as carriers and facilitating intercellular communication through the transfer of cargoes. Numerous studies have revealed that EVs can exacerbate disease development by modulating immune responses. Therefore, this paper focuses on the effects of EVs on the number, activity and function of different types of immune cells and the release of immune molecules (such as cytokines, antigens, antibodies, etc) in various diseases, as well as the roles of EVs associated with different types of immune cells in various diseases. We aim to provide a comprehensive review of the negative effects that EVs play in the immune system to provide more ideas and strategies for the management of clinical immune diseases. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a highly heterogeneous hematological malignancy that is currently incurable. Individualized therapeutic approaches based on accurate risk assessment are essential for improving the prognosis of MM patients. Nevertheless, current prognostic models for MM exhibit certain limitations and prognosis heterogeneity still an unresolved issue. Recent studies have highlighted the pivotal involvement of mitochondrial autophagy in the development and drug sensitivity of MM. This study seeks to conduct an integrative analysis of the prognostic significance and immune microenvironment of mitophagy-related signature in MM, with the aim of constructing a novel predictive risk model. GSE4581 and GSE47552 datasets were acquired from the Gene Expression Omnibus database. MM-differentially expressed genes (DEGs) were identified by limma between MM samples and normal samples in GSE47552. Mitophagy key module genes were obtained by weighted gene co-expression network analysis in the Cancer Genome Atlas (TCGA)-MM dataset. Mitophagy DEGs were identified by the overlap genes between MM-DEGs and mitophagy key module genes. Prognostic genes were selected through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, and a risk model was subsequently constructed based on these prognostic genes. Subsequently, the MM samples were stratified into high- and low-risk groups based on their median risk scores. The validity of the risk model was further evaluated using the GSE4581 dataset. Moreover, a nomogram was developed using the independent prognostic factors identified from the risk score and various clinical indicators. Additionally, analyses were conducted on immune infiltration, immune scores, immune checkpoint, and chemotherapy drug sensitivity. The 17 mitophagy DEGs were obtained by intersection of 803 MM-DEGs and 1084 mitophagy key module genes. Five prognostic genes (CDC6, PRIM1, SNRPB, TOP2A, and ZNF486) were selected via LASSO and univariate cox regression analyses. The predictive performance of the risk model, which was constructed based on the five prognostic genes, demonstrated favorable results in both TCGA-MM and GSE4581 datasets as indicated by the receiver operating characteristic (ROC) curves. In addition, calibration curve, ROC curve, and decision curve analysis curve corroborated that the nomogram exhibited superior predictive accuracy for MM. Furthermore, immune analysis results indicated a significant difference in stromal scores of two risk groups categorized on median risk scores. And four immune checkpoints (CD274, CTLA4, LAG3, and PDCD1LG2) showed significant differences in different risk groups. The analysis of chemotherapy drug sensitivity revealed that etoposide and doxorubicin, which target TOP2A, exhibited superior treatment outcomes in the high-risk group. A novel prognostic model for MM was developed and validated, demonstrating significant potential in predicting patient outcomes and providing valuable guidance for personalized immunotherapy counseling. [ABSTRACT FROM AUTHOR]

Background: Mongolian cattle are local breeds in northern China with excellent adaptability to harsh environmental conditions. Adipose tissues play essential roles in tolerance to cold and disease, but the associated cellular and molecular mechanisms are unclear. Methods: Single-nucleus RNA sequencing (snRNA-seq) was performed on the adipose tissues from the subcutaneous (SAT), greater omentum (OAT) and perirenal (PAT) of 3 healthy cattle. The adipogenic trajectory was analyzed, and the functional roles of gene of interest were verified in vitro. Results: There were different cell subpopulations in adipose tissues. The lipid-deposition adipocytes identified by the PTGER3 marker exhibited outstanding characteristics in SAT. In PAT and OAT, aldosterone was expressed to provide clues for the differential brown adipocytes. Among the DEGs by comparing OAT with SAT and PAT with OAT, C3 was significantly expressed in most of the cell populations in SAT. G0S2, LIPE, LPIN1, PTGER3 and RGCC took part in the adipogenic trajectory from preadipocyte commitment to mature adipocytes. S100A4 expression affected Ca2+ signaling and the expression of UCP1 ~ 3, FABP4 and PTGER3. Conclusion: The cell heterogeneity and genes expressed in adipose tissues of Mongolian cattle not only determine the endocrine and energy storage, but contribute to adapt to cold and disease resistance. [ABSTRACT FROM AUTHOR]

Septic patients with T2DM were prone to prolonged recovery and unfavorable prognoses. Thus, this study aimed to pinpoint potential genes related to sepsis with T2DM and develop a predictive model for the disease. The candidate genes were screened using protein–protein interaction networks (PPI) and machine learning algorithms. The nomogram and receiver operating characteristic curve were developed to assess the diagnostic efficiency of the biomarkers. The relationship between sepsis and immune cells was analyzed using the CIBERSORT algorithm. The biomarkers were validated by qPCR and western blotting in basic experiments, and differences in organ damage in mice were studied. Three genes (MMP8, CD177, and S100A12) were identified using PPI and machine learning algorithms, demonstrating strong predictive capabilities. These biomarkers presented significant differences in gene expression patterns between diseased and healthy conditions. Additionally, the expression levels of biomarkers in mouse models and blood samples were consistent with the findings of the bioinformatics analysis. The study elucidated the common molecular mechanisms associated with the pathogenesis of T2DM and sepsis and developed a gene signature‐based prediction model for sepsis. These findings provide new targets for the diagnosis and intervention of sepsis complicated with T2DM. [ABSTRACT FROM AUTHOR]

Gremlin 1 (GREM1) can regulate the development of many cancers. However, a few studies have revealed the role of GREM1 in bladder cancer (BC). To evaluate the expression and potential function of GREM1 in bladder cancer, we used R version 3.6.3 and related packages to analyze the data from common databases. Samples from our institution were assessed by immunohistochemical staining (IHC), which was approved by the Institutional Ethics Committee (K20220830). GREM1 was highly expressed in BC tissues according to the TCGA and IHC data. Data from TCGA, GSE31684, GSE32894, and IHC showed that GREM1 has significant prognostic value for BC patients. GREM1 is involved in immune and metabolism-related pathways. According to the TIDE algorithm, 61.0% of patients with low GREM1 expression responded well to immunotherapy, compared to only 13.3% in the high GREM1 expression group. High GREM1 expression was associated with sensitivity to cisplatin, docetaxel, gemcitabine, and vinblastine. Thus, GREM1 can predict prognosis and responses to immunotherapy and chemotherapy in BC patients, making it a potential biomarker and therapeutic target. [ABSTRACT FROM AUTHOR]

The impact of selection on host immune function genes has been widely documented. However, it remains essentially unknown how mutation influences the quantitative immune traits that selection acts on. Applying a classical mutation accumulation (MA) experimental design in Drosophila serrata , we found the mutational variation in susceptibility (median time of death, LT50) to Drosophila C virus (DCV) was of similar magnitude to that reported for intrinsic survival traits. Mean LT50 did not change as mutations accumulated, suggesting no directional bias in mutational effects. Maintenance of genetic variance in immune function is hypothesized to be influenced by pleiotropic effects on immunity and other traits that contribute to fitness. To investigate this, we assayed female reproductive output for a subset of MA lines with relatively long or short survival times under DCV infection. Longer survival time tended to be associated with lower reproductive output, suggesting that mutations affecting susceptibility to DCV had pleiotropic effects on investment in reproductive fitness. Further studies are needed to uncover the general patterns of mutational effect on immune responses and other fitness traits, and to determine how selection might typically act on new mutations via their direct and pleiotropic effects. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to combine proteomics and metabolomics to evaluate the immune system of short‐track speed skaters (STSS) before and after a training course. Our research focused on changes in urinary proteins and metabolites that have the potential to serve as indicators for training load. Methods: Urine samples were collected from 21 elite STSS (13 male and 8 female) of the China National Team before and immediately after one training course. First‐beat sports sensor was used to monitor the training load. Proteomic detection was performed using a Thermo UltiMate 3000 ultra high performence chromatography nano liquid chromatograph and an Orbitrap Exploris 480 mass spectrometer. MSstats (R package) was used for the statistical evaluation of significant differences in proteins from the samples. Two filtration criteria (fold change [FC] > 2 and p < 0.05) were used to identify the differential expressed proteins. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis for differential proteins was performed to identify the pathways involved. Nontargeted metabolomic detection was performed using ultra performance liquid chromatography tandem mass spectrometry (UPLC‐MS/MS_) with an ACQUITY 2D UPLC plus Q Exactive (QE) hybrid Quadrupole‐Orbitrap mass spectrometer. Differential metabolites were identified using non‐parametric statistical methods (Wilcox's rank test). Two filtration criteria (FC > 1.2 and p < 0.05) were used to identify differential metabolites. Combined analysis of proteomic and metabolomics were performed on the "Wu Kong" platform. Correlation analysis was performed using Spearman's rank correlation coefficient. Results: (1) The most upregulated proteins were immune‐related proteins, including complement proteins (C9, C4–B, and C9) and immunoglobulins (IgA, IgM, and IgG). The most downregulated proteins were osteopontin (OPN) and CD44 in urine. The correlation analysis showed that the content of OPN and CD44 (the receptor for OPN) in urine were significantly negatively correlated with the upregulated immune‐related proteins. The content of OPN and CD44 is sex‐dependent and negatively correlated with the training load. (2) The most upregulated metabolites included lactate, cortisol, inosine, glutamine, argininosuccinate (the precursor for arginine synthesis), 3‐methyl‐2‐oxobutyrate (the catabolite of valine), 3‐methyl‐2‐oxovalerate (the catabolite of isoleucine), and 4‐methyl‐2‐oxopentanoate (the catabolite of leucine), which is sex‐dependent and negatively correlated with OPN and CD44. (3) The joint analysis revealed five main related pathways, including the immune and innate immune systems. The enriched immune‐related proteins included complements, immunoglobulins, and protein catabolism‐related proteins. The enriched immune‐related metabolites included cAMP, N‐acetylgalactosamine, and glutamate. (4) There is a significant negative correlation between the content of OPN and CD44 in urine and the training load. Conclusion: One training course can lead to the activation of the immune system and a sex‐dependent decrease in the content of OPN and CD44. Training load has a significant and negative correlation with the content of OPN and CD44, suggesting that OPN and CD44 could be potential indicators for training load. [ABSTRACT FROM AUTHOR]

Objectives: CD8+ T cells play a critical role in the immune dysfunction associated with liver cirrhosis. CD38+HLA‐DR+CD8+ T cells, or bystander‐activated CD8+ T cells, are involved in tissue injury but their specific contribution to liver cirrhosis remains unclear. This study sought to identify the mechanism for CD38+HLA‐DR+CD8+ T cell‐mediated pathogenesis during liver cirrhosis. Methods: The immunophenotype, antigen specificity, cytokine secretion and cytotoxicity‐related indicators of CD38+HLA‐DR+CD8+ T cells were determined using flow cytometry. The functional properties of these cells were assessed using transcriptome analysis. CD38+HLA‐DR+CD8+ T‐cell killing was detected using cytotoxicity and antibody‐blocking assays. Results: The proportion of CD38+HLA‐DR+CD8+ T cells was significantly elevated in liver cirrhosis patients and correlated with tissue damage. Transcriptome analysis revealed that these cells had innate‐like functional characteristics. This CD8+ T‐cell population primarily consisted of effector memory T cells and produced a high level of cytotoxicity‐related cytokines, granzyme B and perforin. IL‐15 promoted CD38+HLA‐DR+CD8+ T‐cell activation and proliferation, inducing significant TCR‐independent cytotoxicity mediated through NKG2D. Conclusions: CD38+HLA‐DR+CD8+ T cells correlated with cirrhosis‐related liver injury and contributed to liver damage by signalling through NKG2D in a TCR‐independent manner. [ABSTRACT FROM AUTHOR]

Due to prolong domestication, silkworm develops less immunity and less adaptability for which they are often attacked by different agents and is vulnerable to various pathogens resulting in disease that causes loss of almost 20% of the total cocoon production every year. Any abnormal condition of a part, organ or system of an organism from various causes such as infection inflammation environmental factors or genetic defect and characterized by an identifiable group of signs symptoms or both. Diseases of silkworm are big challenge to the rearers. Grasserie, Muscardine, Pebrine, Flacherie, and Cytoplasmic polymerasic are the major diseases observed in cocoon culture. caused by Nucleopolyhedrosis Virus (BmNPV). Generally, bivoltine silkworms are more susceptible to diseases as compared to multivoltine silkworm breed. The factors responsible for disease incidence are higher pathogen load, wider fluctuation of temperature between day and night, higher humidity in the later stage of rearing and poor quality of mulberry leaves available for rearing in North West Indian condition. The most popular methods of disease control in silkworm are prophylactic. There is no race of B. mori, totally resistant or immune to diseases and pests. Hence, proper disinfection is required to kill all the pathogens present in the rearing environment and to eliminate risk of disease transmission as "Prevention is better than cure" is best in silkworm rearing. The present study deals with pathogen and pathogenesis of silkworm along with their prevention and control measures. [ABSTRACT FROM AUTHOR]

Objectives: To compare the clinicopathological, molecular, and immune features of conventional and high‐grade transformation (HGT) secretory carcinoma (SC) in salivary glands. Materials and Methods: The clinicopathological data of 88 cases including 74 conventional SCs and 14 SCs with HGT were reviewed. Targeted next‐generation sequencing was performed in 11 SCs with HGT and 7 conventional SCs. The level of PD‐L1 and CD8+ TILs was determined by immunohistochemistry. Results: Compared with the conventional group, the rates of nodal metastasis, local recurrence, distant metastasis and mortality were significantly higher in the HGT cohort. Mutations of ARID1A/B, KMT2A, HOXD13, NRG1 and ETV6 genes were identified in HGT SCs. A recurrent E307G mutation in GATA6 gene was also observed in two cases. Two deceased HGT patients with distant metastasis harboured NOTCH3 mutations. ETV6‐RET translocation was prone to occur in the HGT SCs. Additionally, PD‐L1 expression was low, and CD8+ TILs were sparse in most HGT cases. Conclusion: Our findings reveal novel gene alterations involved in the progression of HGT in SCs. Most HGT SCs patients cannot benefit from PD‐L1 blocking and may be approached with a distinct treatment strategy including the lymph node dissection and application of molecular target drugs in precision oncology. [ABSTRACT FROM AUTHOR]

OBJECTIVE To develop an accessible ruminant immune challenge model for rapid in vivo assessments of feed additives. ANIMALS 60 hair-breed ram lambs. METHODS Sheep were randomly assigned to 1 of 4 treatments: treatment 1, not immunosuppressed, control fed (n = 12); treatment 2, immunosuppressed, supplemented with a yeast and botanical extract (n = 18); treatment 3, immunosuppressed, supplemented with a blend of natural aluminosilicates and yeast components (n = 18); and treatment 4, immunosuppressed, control fed (n = 12). Twice-daily injections of dexamethasone (Dex; 0.1 mg/kg bodyweight, SC) were used to induce immunosuppression throughout the study (from September 25, 2020, to November 2, 2020). All sheep were immunized with keyhole limpet hemocyanin (KLH) on days 0 and 14 and injected with heataggregated KLH, ID, to induce a skin induration on day 15. Measurements included body weight (BW), average daily gain (ADG), CBC, and skin induration diameter. RESULTS Dex treatment resulted in reduced BW and ADG that was not mitigated by either feed additive. Dex reduced lymphocyte percentage, RBC count, hemoglobin, hematocrit, and skin induration diameter and increased concentrations of granulocytes and granulocyte percentage. Effects on hematocrit, hemoglobin, RBC, and skin induration diameter were mitigated with the addition of feed additives. CLINICAL RELEVANCE The described model is a tool to evaluate the ability of feed additives to mitigate the immunosuppressive effects of Dex. [ABSTRACT FROM AUTHOR]

Background: The most common progressive form of non-alcoholic fatty liver disease (NAFLD) is non-alcoholic steatohepatitis (NASH), which is characterized by the development of cirrhosis, and requires liver transplantation. We screened for the differentially expressed necroptosis-related genes in NASH in this study, and analyzed immune infiltration through microarray and bioinformatics analysis to identify potential biomarkers, and explore the molecular mechanisms involved in NASH. Methods: The GSE24807 microarray dataset of NASH patients and healthy controls was downloaded, and we identified the differentially expressed genes (DEGs). Necroptosis-related differential genes (NRDEGs) were extracted from these DEGs, and functionally annotated by enrichment analyses. The core genes were obtained by constructing gene co-expression networks using weighted gene co-expression network analysis (WGCNA). Finally, the transcription factor (TF) regulatory network and the mRNA-miRNA network were constructed, and the infiltrating immune cell populations were analyzed with CIBERSORT. Results: We identified six necroptosis-related genes (CASP1, GLUL, PYCARD, IL33, SHARPIN, and IRF9), and they are potential diagnostic biomarkers for NASH. In particular, PYCARD is a potential biomarker for NAFLD progression. Analyses of immune infiltration showed that M2 macrophages, γδ T cells, and T follicular helper cells were associated with the immune microenvironment of NASH, which is possibly regulated by CASP1, IL33, and IRF9. Conclusions: We identified six necroptosis-related genes in NASH, which are also potential diagnostic biomarkers. Our study provides new insights into the molecular mechanisms and immune microenvironment of NASH. [ABSTRACT FROM AUTHOR]

Carp is a key aquaculture species worldwide. The intensification of carp farming, aimed at meeting the high demand for protein sources for human consumption, has resulted in adverse effects such as poor water quality, increased stress, and disease outbreaks. While antibiotics have been utilized to mitigate these issues, their use poses risks to both public health and the environment. As a result, alternative and more sustainable practices have been adopted to manage the health of farmed carp, including the use of probiotics, prebiotics, phytobiotics, and vaccines to prevent disease outbreaks. Phytobiotics, being both cost-effective and abundant, have gained widespread acceptance. They offer various benefits in carp farming, such as improved growth performance, enhanced immune system, increased antioxidant capacity, stress alleviation from abiotic factors, and enhanced disease resistance. Currently, a focal point of research involves employing molecular approaches to assess the impacts of phytobiotics in aquatic animals. Gene expression, the process by which genetic information encoded is translated into function, along with transcription profiling, serves as a crucial tool for detecting changes in gene expression within cells. These changes provide valuable insights into the growth rate, immune system, and flesh quality of aquatic animals. This review delves into the positive impacts of phytobiotics on immune responses, growth, antioxidant capabilities, and flesh quality, all discerned through gene expression changes in carp species. Furthermore, this paper explores existing research gaps and outlines future prospects for the utilization of phytobiotics in aquaculture. [ABSTRACT FROM AUTHOR]

Our previous studies have found that functional changes in the hippocampal circuit from dentate gyrus (DG) to cornu ammonis 3 and 1 (CA3, CA1) are highly associated with schizophrenia (SZ). However, no studies have explored the genetic expression across the three and two human hippocampal subfields (DG-CA3-CA1 and CA3-CA1) between subjects with SZ and healthy controls (CT). We matched cohorts between CT (n = 13) and SZ (n = 13). Among SZ, 6 subjects were on antipsychotics (AP) while 7 were off AP. We combined RNA-seq data from all three and two hippocampal subfields and performed differentially expressed gene analyses across DG-CA3-CA1 and CA3-CA1 affected by either SZ or AP. We found that differentially expressed genes (DEGs) from effects of SZ and AP across DG-CA3-CA1 and CA3-CA1 were highly associated with gene ontology terms related to hormonal and immune signaling, cellular mitosis and apoptosis, ion and amino acid transports, and protein modification and degradation. Additionally, we found that multiple genes related to solute-carrier family and immune signaling were significantly upregulated across DG-CA3-CA1 and CA3-CA1 in patients with SZ relative to CT, and AP consistently and robustly repressed the expression of these upregulated genes in the DG-CA3-CA1 and CA3-CA1 from subjects with SZ. Together, these data suggest that the upregulated solute-carrier family genes in the hippocampus might have important roles in the pathophysiology of SZ, and that AP may reduce the symptoms of psychosis in SZ via rescuing the solute-carrier gene expression. [ABSTRACT FROM AUTHOR]

As a kind of green and high quality feed, fermented feed has the activity of promoting growth and improving immunity in aquaculture. The aim of this study was to develop a new liquid fermented feed for the culture of sea cucumber Apostichopus japonicus and evaluate its nutritional value and function. After the commercial feed of the sea cucumber was fermented by Corynebacterium glutamicum, the contents of crude protein, free amino acids, palmitoleic acid, linoleic acid, arachidonic acid, and the total content of polyunsaturated fatty acids were significantly increased. By feeding the fermented food, the weight gain rate, special growth rate and feed conversion rate of the sea cucumber were significantly increased, and the mortality rate was significantly reduced in the challenge test. The cellulase activity in the gut of the sea cucumber fed with the fermented feed was significantly increased, while the activities of alkaline phosphatase, acid phosphatase, total nitric oxide synthase, catalase, and lysozyme in the coelomic fluid were significantly increased. The fermented feed changed the gut microbiota of the sea cucumber and significantly reduced the relative abundance of Vibrio, which was the main pathogen causing skin ulcer syndrome. Transcriptome analysis revealed 4492 differentially expressed genes that can be enriched in biological processes such as immune system processes and immune responses, and affect the growth performance and immune regulation of the sea cucumber through metabolic pathways such as ribosomal biogenesis. Further gene expression analysis showed that the upregulation of genes such as NFκBI, TLR, TLR3, TRAF6, MyD88, and p38 activated the TLR signaling pathway and enhances the immune response of the sea cucumber. Therefore, C. glutamicum fermented feed can promote the growth of the sea cucumber, enhance non-specific immunity, and resist pathogen infection, making it a highly promising feed for application. [ABSTRACT FROM AUTHOR]

Immune system dysfunction and blood-brain barrier (BBB) impairment are implicated in multiple sclerosis (MS) risk and severity. However, the causal relationships and potential therapeutic targets remain unclear. Leveraging the MRC IEU OpenGWAS data infrastructure, we extracted 1254 peripheral immune systems and 792 BBB biomarkers as genetic instruments for exposure. MS risk data from the International Multiple Sclerosis Genetics Consortium (IMSGC) (47,429 MS cases, 68,374 controls) served as one outcome, replicated in FinnGen (1048 cases, 217,141 controls) and the UK Biobank (1679 cases, 461,254 controls). Genetic associations with MS severity derived from IMSGC and MultipleMS Consortium GWAS data (12,584 cases). Two-sample, bidirectional, and protein drug-target MR analyses were conducted, along with interaction analysis of identified proteins and druggability assessment. Causal relationships between 45 immunological markers, 15 BBB markers, and MS risk were strongly supported. In peripheral immunity, the causal associations with MS are predominantly concentrated in CD4+ T cells and CD8+ T cells. Notably, anti-Epstein-Barr virus nuclear antigen (EBNA) IgG levels exhibited the most significant causal effect on MS risk (OR = 225.62, P = 5.63E-208), replicated in the MS severity (OR = 1.11, P = 0.04). Weak causal evidence was found between 62 immunological markers, 35 BBB markers, and MS severity. Reverse MR analysis suggested potential causal effects of MS risk on 8 markers. Drug-targeted MR analysis indicated potential therapeutic benefits in reducing MS risk for CD40 (OR = 0.71, P = 7.24E-13, PPH4 = 97.6 %), AHSG (OR = 0.88, P = 2.91E-05, PPH4 = 94.4 %), and FCRL3 (Sun BB et al.: OR = 0.83, P = 8.93E-09, PPH4 = 94.2 %, Suhre K et al.: OR = 0.88, P = 5.20E-08, PPH4 = 99.2 %). This study provides evidence supporting the causal effects of immune system and BBB dysfunction on MS risk and severity. It emphasizes the significant role of anti-EBNA IgG levels, CD4+ T cells, and CD8+ T cells in MS, and delineates the potential therapeutic benefits of targeting three proteins associated with MS risk: CD40, AHSG, and FCRL3. • Genetic evidence supports the causal effects of immune system and BBB dysfunction on MS risk and severity. • Anti-EBNA IgG levels, CD4+ T cells, and CD8+ T cells play significant roles in MS. • Targeting CD40, AHSG, and FCRL3 shows potential therapeutic benefits. [ABSTRACT FROM AUTHOR]

Background: A novel valuable prognostic model has been developed on the basis of immune-related genes (IRGs), which could be used to estimate overall survival (OS) in ovarian cancer (OC) patients in The Cancer Genome Atlas (TCGA) dataset and the International Cancer Genome Consortium (ICGC) dataset. Methods: This prognostic model was engineered by employing LASSO regression in training cohort (TCGA dataset). The corresponding growth predictive values of this model for individualized survival was evaluated using survival analysis, receiver operating characteristic curve (ROC curve), and risk curve analysis. Combined with clinical characteristics, a model risk score nomogram for OS was well built. Thereafter, depended on the model risk score, patients were divided into high and low risk subgroups. The survival difference between these subgroups was measured using Kaplan-Meier survival method. In addition, correlations containing pathway enrichment, treatment, immune cell infiltration and the prognostic model were also analyzed. We established the ovarian cancer cell line W038 for this study and identified the performances of GBP1P1 knockdown on a series of activities including cellular proliferation, apoptosis, migration, and invasion of W038 cells in vitro. Results: We constructed a 25-genes prognostic model (TNFAIP8L3, PI3, TMEM181, GBP1P1 (LOC400759), STX18, KIF26B, MRPS11, CACNA1C, PACSIN3, GMPR, MANF, PYGB, SNRPA1, ST7L, ZBP1, BMPR1B-DT, STAC2, LINC02585, LYPD6, NSG1, ACOT13, FAM120B, LEFTY1, SULT1A2, FZD3). The areas under the curves (AUC) of 1, 2 and 3 years were 0.806, 0.773 and 0.762, in the TCGA cohort, respectively. Besides, the effectiveness of the model was verified using ICGC testing data. Univariate and multivariate Cox regression analysis exposes the risk score as an independent prognosis predictor for OS both in the TCGA and ICGC cohort. In summary, we utilized comprehensive bioinformatics analysis to build an effective prognostic gene model for OC patients. These bioinformatic results suggested that GBP1P1 could act as a novel biomarker for OC. GBP1P1 knockdown substantially inhibited the proliferation, migration, and invasion of W038 cells in vitro, and increased the percentage of apoptotic W038 cells. Conclusions: The analyses of genetic status of patients with 25-genes model might improve the ability to predict the prognosis of patients with OC and help to select patients suit able to therapies. Immune-related gene GBP1P1 might serve as prognostic biomarker for OC. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a prevalent psychiatric condition often accompanied by severe impairments in cognitive and functional capacities. This research was conducted to identify RNA modification-related gene signatures and associated functional pathways in MDD. Differentially expressed RNA modification-related genes in MDD were first identified. And a random forest model was developed and distinct RNA modification patterns were discerned based on signature genes. Then, comprehensive analyses of RNA modification-associated genes in MDD were performed, including functional analyses and immune cell infiltration. The study identified 29 differentially expressed RNA modification-related genes in MDD and two distinct RNA modification patterns. TRMT112, MBD3, NUDT21, and IGF2BP1 of the risk signature were detected. Functional analyses confirmed the involvement of RNA modification in pathways like phosphatidylinositol 3-kinase signaling and nucleotide oligomerization domain (NOD)-like receptor signaling in MDD. NUDT21 displayed a strong positive correlation with type 2 T helper cells, while IGF2BP1 negatively correlated with activated CD8 T cells, central memory CD4 T cells, and natural killer T cells. In summary, further research into the roles of NUDT21 and IGF2BP1 would be valuable for understanding MDD prognosis. The identified RNA modification-related gene signatures and pathways provide insights into MDD molecular etiology and potential diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Background: The metabolism of abnormal bile acids (BAs) is implicated in the initiation and development of gastrointestinal (GI) cancer. However, there was a lack of research on the molecular mechanisms of BAs metabolism in GI. Methods: Genes involved in BAs metabolism were excavated from public databases of The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, and Molecular Signatures Database (MSigDB). ConsensusClusterPlus was used to classify molecular subtypes for GI. To develop a RiskScore model for predicting GI prognosis, univariate Cox analysis was performed on the genes in protein–protein interaction (PPI) network, followed by using Lasso regression and stepwise regression to refine the model and to determine the key prognostic genes. Tumor immune microenvironment in GI patients from different risk groups was assessed using the ESTIMATE algorithm and enrichment analysis. Reverse transcription–quantitative real‐time PCR (RT‐qPCR), Transwell assay, and wound healing assay were carried out to validate the expression and functions of the model genes. Results: This study defined three molecular subtypes (C1, C2, and C3). Specifically, C1 had the best prognosis, while C3 had the worst prognosis with high immune checkpoint gene expression levels and TIDE scores. We selected nine key genes (AXIN2, ATOH1, CHST13, PNMA2, GYG2, MAGEA3, SNCG, HEYL, and RASSF10) that significantly affected the prognosis of GI and used them to develop a RiskScore model accordingly. Combining the verification results from a nomogram, the prediction of the model was proven to be accurate. The high RiskScore group was significantly enriched in tumor and immune‐related pathways. Compared with normal gastric mucosal epithelial cells, the mRNA levels of the nine genes were differential in the gastric cancer cells. Inhibition of PNMA2 suppressed migration and invasion of the cancer cells. Conclusion: We distinguished three GI molecular subtypes with different prognosis based on the genes related to BAs metabolism and developed a RiskScore model, contributing to the diagnosis and treatment of patients with GI. [ABSTRACT FROM AUTHOR]

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Wounds are the common fates in various microbial infections and physical damages including accidents, surgery, and burns. In response, a healthy body with a potent immune system heals that particular site within optimal time by following the coagulation, inflammation, proliferation, and remodeling phenomenon. However, certain malfunctions in the body due to various diseases particularly diabetes and other physiological factors like age, stress, etc., prolong the process of wound healing through various mechanisms including the Akt, Polyol, and Hexosamine pathways. The current review thoroughly explains the wound types, normal wound healing mechanisms, and the immune system's role. Moreover, the mechanistic role of diabetes is also elaborated comprehensively. Comparative analysis of the molecular events during different wound healing phases in healthy and diabetic/stressed/aged individuals. [ABSTRACT FROM AUTHOR]

Background. Emerging research has identified ferroptosis as a novel form of programmed cell death, and Arachidonic acid 15-lipoxygenase-1 (ALOX15) stands out as a pivotal gene in mediating this process. Nonetheless, the role of ALOX15 in human tumors remains elusive. Methods. We utilized TIMER 2.0 to investigate the differential expression profiles of ALOX15 between pan-cancer and normal tissues. Further data from the TCGA, GEPIA, UALCAN, HPA, and CPTAC databases were analyzed to verify the levels of mRNA, protein expression, and promoter methylation across various cancer types. The survival prognosis, clinical features, and genetic alterations of ALOX15 were also evaluated. GO/KEGG enrichment analyses and single-cell transcriptome sequencing were employed for functional enrichment analysis. The gene mutation of ALOX15 and its prognostic value were analyzed using the cBioPortal platform. Finally, the relationship between ALOX15 and immune cell infiltration, Immune Checkpoints (ICKs), genomic instability, and drug sensitivity was further explored using GSCA. Results. Our findings revealed that the transcription and protein expression of ALOX15 were significantly reduced in HNSC, LUAD, LUSC, SKCM, KICH, and THCA, while they were up-regulated in ESCA, LIHC, PRAD, and UCEC. Notably, the expression of ALOX15 had prognostic value for certain cancers, including LUAD, LUSC, LIHC, KIRC, HNSC, THCA, and LGG. Additionally, ALOX15 expression was markedly correlated with clinical characteristics, immune cell infiltration, ICKs, genomic instability, and antitumor drug sensitivity in various tumors. Gene mutations of ALOX15 and their prognostic value were discovered in pan-cancers. Furthermore, GO/KEGG analysis and single-cell transcriptome sequencing indicated that ALOX15 was significantly associated with cancer-related pathways. Conclusion. Our comprehensive pan-cancer analysis shed light on the role and significance of ALOX15, suggesting its potential as a prognostic and immunotherapeutic marker for pan-cancer. These findings may provide new directions and evidence for cancer therapeutics. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is a global malignancy characterized by metastatic invasiveness and recurrence. Long non-coding RNAs (lncRNAs) and Telomeres are closely connected with several cancers, but their potential as practical prognostic markers in OC is less well-defined. Methods: Relevant mRNA and clinical data for OC were sourced from The Cancer Genome Atlas (TCGA) database. The telomere-related lncRNAs (TRLs) prognostic model was established by univariate/LASSO/multivariate regression analyses. The effectiveness of the TRLs model was evaluated and measured via the nomogram. Additionally, immune infiltration, tumor mutational load (TMB), and drug sensitivity were evaluated. We validated the expression levels of prognostic genes. Subsequently, PTPRD-AS1 knockdown was utilized to perform the CCK8 assay, colony formation assay, transwell assay, and wound healing assay of CAOV3 cells. Results: A six-TRLs prognostic model (PTPRD-AS1, SPAG5-AS1, CHRM3-AS2, AC074286.1, FAM27E3, and AC018647.3) was established, which can effectively predict patient survival rates and was successfully validated using external datasets. According to the nomogram, the model could effectively predict prognosis. Furthermore, we detected the levels of regulatory T cells and M2 macrophages were comparatively higher in the high-risk TRLs group, but the levels of activated CD8 T cells and monocytes were the opposite. Finally, the low-risk group was more sensitive to anti-cancer drugs. The mRNA levels of PTPRD-AS1, SPAG5-AS1, FAM27E3, and AC018647.3 were significantly over-expressed in OC cell lines (SKOV3, A2780, CAOV3) in comparison to normal IOSE-80 cells. AC074286.1 were over-expressed in A2780 and CAOV3 cells and CHRM3-AS2 only in A2780 cells. PTPRD-AS1 knockdown decreased the proliferation, cloning, and migration of CAOV3 cells. Conclusion: Our study identified potential biomarkers for the six-TRLs model related to the prognosis of OC. [ABSTRACT FROM AUTHOR]

Background: Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown. Methods: Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations. The association between UBE2D2 and immunotherapy response was assessed by gene set enrichment analysis, tumor microenvironment, immune gene co-expression and drug half maximal inhibitory concentration (IC50) analysis. Results: The mRNA and protein levels of UBE2D2 were markedly elevated in most cancer types, and UBE2D2 exhibited prognostic significance in liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), uveal melanomas (UVM), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and kidney renal papillary cell carcinoma (KIRP). UBE2D2 expression was correlated with clinical features, tumor mutation burden, microsatellite instability, and anti-tumor drug resistance in several tumor types. Gene enrichment analysis showed that UBE2D2 was significantly associated with immune-related pathways. The expression level of UBE2D2 was correlated with immune cell infiltration, including CD4 + T cells、Macrophages M2、CD8 + T cells in pan-cancer. PDCD1, CD274 and CTLA4 expression levels were positively correlated with UBE2D2 level in multiple cancers. Conclusions: We comprehensively investigated the potential value of UBE2D2 as a prognostic and immunotherapeutic predictor for pan-cancer, providing a novel insight for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Sea buckthorn pomace is an industrial by-product, rich in a variety of functional compounds, but it has not been effectively used yet. This experiment was conducted to evaluate the effects of sea buckthorn pomace (SBP) supplementary levels on production performance and serum metabolizes in weaned piglets. A total of 40 28-day-old weaned piglets (Duroc × Landrace × Yorkshire; half female and half castrated male) with 10 ± 0.30 kg of IBW were randomly assigned to 4 group (1 female and 1 castrated male/pen and 5 replicates/group). Piglets were consumed a basal diet, or the basal diet supplemented with 0.5%, 1.0%, and 2.0% SBP for 30 d, respectively. The results showed that the ADG, ADFI, and FBW were greater (p < 0.05), whereas the FCR was lesser (p < 0.05) in 2.0% and 1.0% SBP group than in 0% SBP group. The concentration of C3 was greater (p < 0.05) in 2.0% SBP group than in another group. The concentrations of IgM and IgG were greater (p < 0.05) when SBP supplemented than 0% SBP group. The concentration of IgA was greater (p < 0.05) in 2.0% SBP group than in 0% SBP and 0.5% SBP group. The concentration of T-AOC, activities of CAT and GSH-Px were greater (p < 0.05) when SBP supplemented than 0% SBP group. The activity of SOD and concentration of MDA were lesser (p < 0.05) in 2.0% and 1.0% SBP group than in 0% SBP group. It concluded that SBP could improve production, immune function, and antioxidant status on weaned piglets, and the appropriate level of SBP supplementation would be from 1.0% to 2.0%. [ABSTRACT FROM AUTHOR]

Contents of antinuclear antibodies (ANA), rheumatoid factor (RF), tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) were measured in serum from 20 dogs with immune-mediated fever. Seven out of 20 patients were ANA positive, 1 out of 20 was positive to antibodies against extractable nuclear antigens (ENA), 1 out of 20 was positive to antibodies against deoxynucleoproteins (DNP), 2 out of 13 were RF positive and none out of 20 patients had antibodies against native DNA in the serum. TNF-α was not detected in any serum of 15 dogs with immune-mediated fever, while 10 out of 13 presented with elevated IL-6. The results varied between patients, but the IL-6 level was high in most of them. This indicate a role for IL-6 in the pathogenesis of immune-mediated fever in most cases. [ABSTRACT FROM AUTHOR]

Normal veins could develop to varicose vein (VV) by some risk factors, and might further progress to shallow vein thrombosis (SVT). However, the molecular mechanism of key genes associated with the progression and regression of VV are still not thorough enough. In this study, the healthy control (HC), VV, and SVT vascular samples were collected for transcriptome sequencing. The differentially expressed genes (DEGs) were screened by "DESeq2", including DEGs1 (HC vs. VV), DEGs2 (HC vs. SVT) and DEGs3 (VV vs. SVT). And their functional enrichment analyses were conducted by "ClusterProfiler". The receiver operating characteristic (ROC) curve was used to obtain the key genes (KGs) of the pathogenesis of VV and SVT. The qRT-PCR assay was performed to validate the expressions of KGs. Immune cell infiltration analyses were conducted based on ssGSEA method. The competitive endogenous RNAs (ceRNAs) regulatory network was constructed. The target drugs of KGs were predicted using DrugBank database. The biofunctions of DACT3 were further investigated through a series of experiments in vitro. All of these DEGs were associated with inflammation and immunity related functions. Immune cell infiltration was significantly different between VV and SVT. Six key genes including PLP2, DACT3, LRRC25, PILRA, MSX1 and APOD that were associated with the progression and regression of VV were screened. The expression of LRRC25 and PILRA was significantly negatively associated with central memory T cell, and significantly positively associated with B cell. Besides, XIST was the critical regulator of multiple KGs. Cimetidine was potential drug for VV and SVT therapy. Overexpression of DACT3 significantly inhibited the proliferation and migration of vascular smooth muscle cells (VSMCs), and affected their cell cycle and phenotypic transition. This study identified six key genes associated with the progression and regression of VV. Among them, DACT3 was proved to hinder VV progression. These findings may help to deepen understanding its underlying mechanisms. [ABSTRACT FROM AUTHOR]

The dependence of tumor cells on glycolysis provides essential energy and raw materials for their survival and growth. Recent research findings have indicated that long chain non-coding RNAs (LncRNAs) have a key regulatory function in the tumor glycolytic pathway and offer new opportunities for cancer therapy. LncRNAs are analogous to a regulatory key during glycolysis. In this paper, we review the mechanisms of LncRNA in the tumor glycolytic pathway and their potential therapeutic strategies, including current alterations in cancer-related energy metabolism with lncRNA mediating the expression of key enzymes, lactate production and transport, and the mechanism of interaction with transcription factors, miRNAs, and other molecules. Studies targeting LncRNAregulated tumor glycolytic pathways also offer the possibility of developing new therapeutic strategies. By regulating LncRNA expression, the metabolic pathways of tumor cells can be interfered with to inhibit tumor growth and metastasis, thus affecting the immune and drug resistance mechanisms of tumor cells. In addition, lncRNAs have the capacity to function as molecular markers and target therapies, thereby contributing novel strategies and approaches to the field of personalized cancer therapy and prognosis evaluation. In conclusion, LncRNA, as key molecules regulating the tumor glycolysis pathway, reveals a new mechanism of abnormal metabolism in cancer cells. Future research will more thoroughly investigate the specific mechanisms of LncRNA glycolysis regulation and develop corresponding therapeutic strategies, thereby fostering new optimism for the realization of precision medicine. [ABSTRACT FROM AUTHOR]

Hibernation, an evolved survival trait among animals, enables them to endure frigid temperatures and food scarcity during the winter months, and it is a widespread phenomenon observed in mammals. The gut microbiota, a crucial component of animal nutrition and health, exhibits particularly dynamic interactions in hibernating mammals. This manuscript comprehensively evaluates the impacts of fasting, hypothermia, and hypometabolism on the gut microbiota of hibernating mammals. It suggests that alterations in the gut microbiota may contribute significantly to the maintenance of energy metabolism and intestinal immune function during hibernation, mediated by their metabolites. By delving into these intricacies, we can gain a deeper understanding of how hibernating mammals adapt to their environments and the consequences of dietary modifications on the symbiotic relationship between the gut microbiota and the host. Additionally, this knowledge can inform our comprehension of the protective mechanisms underlying long-term fasting in non-hibernating species, including humans, providing valuable insights into nutritional strategies and health maintenance. [ABSTRACT FROM AUTHOR]

Background: COVID-19 vaccines are crucial for reducing the threat and burden of the pandemic on global public health, yet the epigenetic, especially RNA editing in response to the vaccines remains unelucidated. Results: Our current study performed an epitranscriptomic analysis of RNA-Seq data of 260 blood samples from 102 healthy and SARS-CoV-2 naïve individuals receiving different doses of the COVID-19 vaccine and revealed dynamic, transcriptome-wide adenosine to inosine (A-to-I) RNA editing changes in response to COVID-19 vaccines (RNA editing in response to COVID-19 vaccines). 5592 differential RNA editing (DRE) sites in 1820 genes were identified, with most of them showing up-regulated RNA editing and correlated with increased expression of edited genes. These deferentially edited genes were primarily involved in immune- and virus-related gene functions and pathways. Differential ADAR expression probably contributed to RNA editing in response to COVID-19 vaccines. One of the most significant DRE in RNA editing in response to COVID-19 vaccines was in apolipoprotein L6 (APOL6) 3' UTR, which positively correlated with its up-regulated expression. In addition, recoded key antiviral and immune-related proteins such as IFI30 and GBP1 recoded by missense editing was observed as an essential component of RNA editing in response to COVID-19 vaccines. Furthermore, both RNA editing in response to COVID-19 vaccines and its functions dynamically depended on the number of vaccine doses. Conclusion: Our results thus underscored the potential impact of blood RNA editing in response to COVID-19 vaccines on the host's molecular immune system. [ABSTRACT FROM AUTHOR]

Simple Summary: Plant extracts have emerged as a viable alternative to antibiotics in livestock production, contributing to the sustainable development of modern animal husbandry. Among these extracts, tea polyphenols, derived from tea leaves as polyhydroxyphenolic compounds, exhibit diverse bioactive properties. This study aimed to assess the impact of tea polyphenols on serum parameters, rumen microbiota, rumen metabolism, and liver metabolism in Hu sheep. The results indicated that dietary supplementation with tea polyphenols did not significantly affect the serum physiological indices of the sheep but enhanced serum immunity and antioxidant levels. Moreover, Firmicutes dominated the network map of the top 80 abundant microorganisms at the genus level, identifying 13 biomarkers at the genus level. Furthermore, tea polyphenols have been found to modulate both rumen and liver metabolism, particularly in relation to energy and lipid metabolism. Furthermore, strong correlations were observed between liver and rumen metabolites, particularly between rumen succinic acid and liver alanyl−serine and methylmalonic acid. This establishes a theoretical basis for tea polyphenol applications and suggests directions for optimizing future additive dosages. This study investigated the impact of tea polyphenols on serum indices, rumen microorganisms, rumen metabolism, and liver metabolism in Hu sheep. Sixty healthy lambs, aged three months and with similar average weights, were chosen and randomly assigned to control (CON), TP400, TP800, and TP1200 groups, each consisting of fifteen lambs. The control group received a basal diet, while the experimental groups were provided with basal diet supplemented with 400 mg/kg, 800 mg/kg, and 1200 mg/kg of tea polyphenols, respectively. Compared with the CON group, the addition of tea polyphenols to the diet significantly increased serum IgA, GSH−Px, and TSOD. In addition, tea polyphenols were able to increase rumen pH but had no significant effect on the rumen NH3−N, VFA molar content, and the microbial top 10 phylum and genus levels. Moreover, Firmicutes predominated in the network map of the top 80 abundant microorganisms at the genus level, identifying 13 biomarkers at the genus level. In addition, strong correlations were observed between liver and rumen metabolites, particularly between rumen succinic acid and liver alanyl−serine and methylmalonic acid. Furthermore, tea polyphenol additions changed the enrichment of liver and rumen metabolites in the top five KEGG metabolic pathways, but 400−1200 mg/kg additions had no negative impact on the liver and rumen. In summary, TP significantly influences rumen and liver metabolites in Hu sheep, enhancing lamb immunity and antioxidant capacity, with 400 mg/kg being the most effective dosage. [ABSTRACT FROM AUTHOR]