Search Results (2,923)

Vaccination remains one of the most effective strategies for preventing infectious diseases. Yet, the success of modern vaccines increasingly depends on the rational design of adjuvants that enhance and shape immune responses. In this review, we examine current and emerging adjuvant strategies for viral vaccines across the human lifespan. Traditional adjuvants, particularly aluminum salts, have long served as the foundation of vaccine formulations. Still, their limitations have driven the exploration of novel platforms, including emulsions, nucleic acid-based adjuvants, and advanced particulate delivery platforms with intrinsic immunostimulatory properties. These newer approaches act through diverse mechanisms, such as activating innate immune pathways via pattern recognition receptors (PRRs) and stimulating antigen-presenting cells (APCs), thereby improving both humoral and cellular immunity. Recent advances in molecular biology, nanotechnology, and systems vaccinology have deepened mechanistic understanding and enabled more precise modulation of immune responses. However, significant challenges remain, including incomplete knowledge of adjuvant mechanisms, limited diversity among licensed adjuvants, safety concerns, and inconsistent efficacy across age groups. In particular, immune immaturity in infants and immunosenescence in older adults highlight the need for age-specific adjuvant strategies. The review identifies critical gaps in comparative studies, long-term safety data, and the development of adjuvants capable of inducing broad and durable immunity. Further, this article integrates licensed and emerging viral vaccine adjuvants through a lifespan framework. Addressing these limitations through interdisciplinary research and precision-based approaches will be essential for advancing next-generation vaccines and improving global preparedness for emerging infectious diseases. Full article

Background/Objectives: Kangaroo Mother Care (KMC) has been proposed as a protective intervention that may modulate the epigenetic regulation of stress-related genes, such as SLC6A4, which encodes the serotonin transporter. Few studies have explored this association in humans. This study aimed to evaluate whether KMC affects the methylation status of SLC6A4 in preterm newborns. Methods: This longitudinal observational study included preterm infants with birth weight ≤ 1800 g and gestational age between 25 and 34 weeks. Blood samples were collected at birth, Neonatal Intensive Care Unit discharge, and hospital discharge. Methylation levels at 13 CpG sites within the SLC6A4 promoter region were quantified by bisulfite conversion and pyrosequencing. Methylation dynamics were analyzed using linear mixed-effects models adjusted for clinical covariates. Results: 75 preterm infants were analyzed (51 KMC; 24 non-KMC). Methylation levels ranged from 0.78% to 10.76% across all CpG sites and remained stable over time. At hospital discharge, the KMC group exhibited lower methylation at CpG6 than the non-KMC group (median = 0.96% vs. 1.21%, p = 0.021), but this difference was not statistically significant after correction for multiple testing. No significant differences were observed at other sites or in longitudinal methylation trajectories between groups. Conclusions: KMC was not associated with major longitudinal changes in SLC6A4 methylation during the neonatal period. The nominal difference at CpG6 should be interpreted as exploratory and warrants further investigation. Larger, multicenter studies with long-term follow-up are needed to clarify the epigenetic mechanisms linking early caregiving experiences with stress regulation and neurodevelopmental outcomes in preterm infants. Full article

Background: Long-read, single-CpG-resolution sequencing is redefining the information-to-depth ratio in epigenomics. While conventional methylome analysis often requires high coverage, we propose a scalable pipeline designed to extract high-density regulatory logic from shallow sequencing data. Methods: By utilizing the progenitor-like HepaRG cell line as a model for liver plasticity, we validated this framework across two divergent developmental trajectories: hepatic maturation and sphere-induced retrodifferentiation. Our technical approach combines CpG-centric enrichment and regional methylation aggregation to reconstruct regulatory landscapes from sparse data. Using long-read Nanopore sequencing, we mapped the dynamics of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Results: Our pipeline revealed that these trajectories are not inverse processes but engage distinct epigenetic strategies. Hepatic maturation is characterized by the accumulation of 5hmC that partially targets repressive heterochromatin (H3K9me3, H4K20me3) and pioneer factors such as FOXA2. In contrast, retrodifferentiation increases 5mC, potentially silencing adult regulators such as HNF1A via Polycomb-associated networks. In addition, aggregation-based analysis can distinguish widespread focal perturbations from a restricted subset of transcription factors that translate epigenetic changes into regional accessibility. Conclusions: This study provides a scalable computational framework for investigating cellular fate transitions, proving that high-value epigenetic insights are attainable even at reduced sequencing depths. Full article

This study investigates the effects of high-volume calcined phosphogypsum (CPG) on the workability, mechanical properties, and frost resistance of phosphogypsum slag cement concrete (PSCC). CPG was used as a sulfate activator to prepare PSCC mixtures with CPG contents ranging from 40% to 70%. The slump, flexural and compressive strengths, water absorption, relative dynamic modulus of elasticity, and mass loss rate after freeze–thaw cycles were evaluated. The results show that the slump of fresh concrete decreases from 275 mm to 35 mm as the CPG content increases from 40% to 70%. The compressive strength decreases with increasing CPG content; however, the 90-day compressive strength still ranges from 39.9 MPa to 56.4 MPa. Even at high CPG contents, the concrete maintains moderate to relatively high strength levels. At a CPG content of 40%, the water absorption rate is 5.9%, meeting the requirement of the Chinese standard JC/T 899-2016. Freeze–thaw cycle tests indicate that a higher CPG content results in a higher mass loss rate. Nevertheless, all mixtures comply with the Chinese standard JC/T 899-2016, which limits the mass loss rate to no more than 3.0% after 50 freeze–thaw cycles for curbstones. The relative dynamic modulus of elasticity shows a trend of decreasing, then increasing, with increasing CPG content. Full article

Selecting appropriate tree species is crucial for mitigating soil acidification and restoring biogeochemical cycles in subtropical acid rain regions. The objective of this study was to elucidate the influence of species selection on litter nutrient dynamics and its implications for soil carbon (C) and nitrogen (N) cycling. To achieve this, three forest types were examined at the Tieshanping Forest Farm (Chongqing, China). Twelve plots were established, including pure stands of Pinus massoniana Lamb. or Cinnamomum camphora (Linn) Presl, and mixed stands of these species. Litterfall was collected monthly (December 2020–November 2021) to determine pH, C, N, phosphorus, potassium, lignin, and cellulose contents, alongside potential nutrient returns and stoichiometric ratios. Results indicated that while total annual litterfall production did not differ significantly among the forest types, their seasonal dynamics varied distinctly, with C. camphora and P. massoniana peaking in spring and summer, respectively. Furthermore, C. camphora stands exhibited significantly higher annual P and K returns. Conversely, P. massoniana litter was characterized by the highest C:P ratio and mean annual lignin content (344.78 mg g⁻¹), indicating lower decomposability that may restrict organic C turnover and N release. Consequently, the nutrient-rich and readily decomposable litter of C. camphora is more effective than P. massoniana at alleviating soil acidification and facilitating healthier C and N cycling. These findings highlight the critical role of aboveground litter quality in driving belowground soil C and N dynamics, providing a vital scientific basis for species selection during ecological restoration in acid rain-affected areas. Full article

The information available on cervical myelopathies (CMs) and cervical pain (CP) in non-chondrodystrophic breeds remains limited compared to chondrodystrophic breeds. The expression of CP in CMs may depend on lesion type, severity and onset of clinical signs. This retrospective single-centre study reviewed the medical records of 112 purebred non-chondrodystrophic dogs referred for neurological evaluation, in which C1-T2 lesions were subsequently confirmed by magnetic resonance imaging (MRI). Clinical onset was categorised as acute (≤7 days) or chronic (>7 days). Neurological grade was classified into four neurological groups (G1–G4). CP was graded using a study-specific, non-validated five-point ordinal clinical scale. Multifactorial analysis of variance (ANOVA), odds ratios with 95% confidence intervals, and multivariable binomial logistic regression were performed. ANOVA showed significant effects of group (p < 0.0001), disease category (p < 0.05), and clinical onset (p < 0.02) on CP scores. Post-hoc comparison showed significantly lower CP scores in chronic onset than in acute onset (p < 0.0001). Acute onset was associated with CP in G2 (OR = 71.0; p < 0.0002) and remained associated with CP after adjustment for groups (adjusted OR = 4.42; 95% CI: 1.28–15.28; p = 0.019). These findings suggest that clinical onset may contribute to CP expression in non-chondrodystrophic dogs with CMs. Acute onset, particularly in ambulatory myelopathic patients, appears more frequently associated with CP. However, due to the retrospective design, the heterogeneous diagnostic composition, and the study-specific nature of the CP score, these associations should be interpreted cautiously. Full article

The glyoxalase pathway detoxifies reactive dicarbonyls generated during hyperglycemia, but the role of its epigenetic regulation in renal dysfunction and inflammatory dysregulation in older adults remains unclear. We investigated CpG-specific DNA methylation within the glyoxal detoxification pathway, focusing on the GLO1 gene, and examined associations with glycemic status, renal function, and systemic inflammation in hospitalized older adults. We identified a single CpG site within the GLO1 gene (cg26053840) significantly associated with fasting glycemia, suggesting that methylation levels at this locus reflects metabolic stress. Higher methylation at cg26053840 was also associated with impaired renal function, including increased serum creatinine and reduced estimated glomerular filtration rate. Additionally, GLO1 methylation correlated with multiple inflammatory indices, including C-reactive protein, erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio, and the CRP-to-albumin ratio. Associations with circulating cytokines and immune activation markers such as IL-6, IL-17A, GDF-15, CXCL9, CD163, and soluble RAGE further indicated broader immune–metabolic dysregulation. In silico analyses revealed a significant inverse correlation between cg26053840 methylation and GLO1 mRNA expression in the Broad Institute GDAC Firehose dataset. Genomic annotation further identified putative CEBPD and MYF6 transcription factor binding sites in proximity to the CpG site, suggesting a potential regulatory context. These findings support a model in which glycemic dysregulation increases methylglyoxal production, while reduced renal clearance enhances dicarbonyl stress, potentially driving epigenetic modulation of GLO1. These findings suggest the presence of a metabolic–epigenetic–inflammatory axis, although longitudinal and mechanistic studies are required to determine whether it contributes to organ dysfunction and vulnerability in hospitalized older adults. Full article

Background: The relationship between neonatal DNA methylation (DNAm) and childhood atopy, particularly its temporal dynamics, remains inadequately characterized. Establishing this will provide insights into the epigenetic mechanisms underlying atopy development. Methods: Skin prick tests (SPT) for 11 common allergens were performed in the Isle of Wight third-generation birth cohort (IOWF2) at ages 1, 3, and 6 years. Atopy was defined as a positive response to one or more allergens on SPT. DNAm at birth at 294,265 CpGs from umbilical cords (n = 192) or Guthrie cards (n = 107) was screened (through R package ttscreening) for potential association with atopy. Pathway enrichment analysis of screened CpGs was performed using the missMethyl package in R. Associations between CpGs that passed screening and atopy status were assessed via logistic regressions with repeated measures, adjusting for age, sex, and birth weight. Age-specific associations were examined via DNAm × age interactions. CpGs showing age-specific association were further tested in the parental cohort (IOWBC (F1); n = 717). Multiple testing was controlled using FDR-adjusted p-values at 0.05. Results: In total, 601 CpGs passed screening. Pathway enrichment analysis identified enrichment of the cell activation pathway (GO:0001775; FDR-adjusted p-value = 0.017). DNAm at 502 CpGs in F2 showed age-specific associations with atopy. Among these, 102 CpGs showed consistent directions in F1, and 14 were statistically significant (p-value < 0.05). Except for cg01519508 (FOXF1), DNAm–atopy associations weakened over time at the remaining 13 CpGs. Conclusions: At certain CpGs, DNAm at birth is associated with childhood atopy in an age-dependent manner, and for CpGs showing association at an earlier age, such associations weaken at later ages. Full article

Feline leishmaniosis (FeL) caused by Leishmania infantum is increasingly recognized in endemic areas, but the inflammatory profile during infection remains poorly defined. This case–control study evaluated the acute phase proteins (APPs) serum amyloid A (SAA), haptoglobin (Hp), and ceruloplasmin (Cp) in cats with anti-L. infantum antibodies and/or DNA and compared them with healthy negative controls. A total of 125 cats were enrolled, including 62 cats positive by IFAT and/or qPCR and 63 healthy controls. Total protein, albumin, albumin-to-globulin ratio (A/G), and serum protein electrophoresis were also assessed, and correlations with APPs were investigated in positive cats. Compared with controls, L. infantum-positive cats had significantly higher Hp and Cp concentrations, whereas SAA did not differ significantly. They also showed higher total protein, beta2- and gamma-globulin concentrations and lower albumin and A/G ratio. SAA and Hp were negatively correlated with albumin, whereas Cp was positively correlated with total protein and beta-globulin fractions. No significant correlations were found between APPs and IFAT antibody titer. In exploratory analyses, IFAT seropositivity (cut-off ≥ 1:80) was associated with higher Hp, whereas qPCR positivity was associated with higher SAA and Cp concentrations; however, these results should be interpreted cautiously because qPCR-positive cats were few. These findings indicate a measurable inflammatory and dysproteinemic profile in cats with laboratory evidence of L. infantum exposure and/or infection, but do not establish APPs as disease-specific diagnostic markers. However, diagnostic heterogeneity, limited qPCR testing, lack of standardized clinical staging, and possible confounding diseases limit causal and clinical interpretation. Full article

Over the past decade, changes in consumer dietary habits have driven an increasing demand for protein-enriched confectionery products. Consequently, research has increasingly focused on the utilization of alternative protein origins, including Acheta domesticus. This research paper aims to characterize Acheta domesticus protein powder (CP) in terms of its functional properties and chemical composition. In addition, the amino acid profile was determined using HPLC, while antioxidant capacity was evaluated by spectrophotometric methods (including the ABTS assay). Edibility was further assessed in proteins, both in their native form and after incorporation into cocoa cream products, using an in vitro digestion model. The results indicated that methionine was the most abundant essential amino acid in CP (17.71 mg/100 g protein), while glycine was the predominant non-essential amino acid (42.38 mg/100 g protein). CP also demonstrated high solubility (80.00%) and notable water- and oil-binding capacities (90.26% and 94.87%, respectively). However, its emulsifying properties were limited, as emulsifying stability was maintained for only 26 min. In contrast, digestibility results indicated strong protein hydrolysis in both native and cocoa cream samples enriched with CP in different concentrations (10, 12.5 and 15%), hereafter designated as CPC10, CPC12.5, and CPC15. The degree of hydrolysis was higher after the digestion process, with 39.11% for the control and 47.14%, 48.62% and 50.05% for the fortified samples—CPC10, CPC12.5 and CPC15, respectively. The ABTS assay further confirmed the increase in antioxidant activity after digestion. The ABTS values of the digested fortified samples ranged from 20.91% for CPC10 to 40.45% for CPC15, suggesting the release of bioactive peptides during gastrointestinal digestion. Overall, the findings highlight CP as a promising protein source for the fortification of cocoa cream products, which are naturally low in protein content. Full article

This study examined the effects of dietary crude protein (CP) level and starch: fat ratio (SFR) on glucose and lipid metabolism in geese. A total of 360 male Jiangnan White geese were allocated to a 3 × 2 factorial arrangement with two CP levels (14.5% and 16.5%) and three SFRs (SFR_20:1, SFR_11:1, and SFR_5:1) from 28 to 63 days of age. Under the low-protein condition, Both the SFR_11:1 and SFR_5:1 group enhanced body weight of geese at 63 d, but SFR _5:1 increased subcutaneous and abdominal fat deposition. Dietary SFR changed liver cholesterol metabolism and glycogen content, while CP levels mainly affected the activity of enzymes related to liver glucose and lipid metabolism: 14.5% CP increased AMPK and ACC activity, but decreased FAS, CS and G6PC activity. Both CP level and SFR altered muscle fatty acid composition, but the effect of SFR was usually more significant. An SFR of 11:1 was beneficial for improving the muscle fatty acid profile. Gene expression analysis further revealed that low protein compensatorily regulated liver energy metabolism, while excessive fat in low SFR diets led to lipid metabolism disorders. In conclusion, optimizing the energy structure of low-protein diets, especially by maintaining a medium SFR (11:1), could improve glucose and lipid metabolism in geese while increasing body weight. Full article

Restoration of degraded shrublands is a major challenge for combating desertification in arid and semi-arid regions. Caragana korshinskii Kom., a dominant sand-fixing shrub widely planted in northern China, often shows growth decline and structural degradation as stand age increases. Stubble management is widely used to rejuvenate degraded shrublands; however, its influence on nutrient cycling and carbon-nitrogen-phosphorus (C-N-P) stoichiometric coupling within the leaf-soil system remains unclear. Here, we conducted a two-factor field experiment in a 30-year-old degraded C. korshinskii plantation in the Kubuqi Desert, northern China, manipulating stubble height and stubble density. Moderate stubble height (10 cm) significantly increased leaf N concentration (27.37 g kg⁻¹) and improved soil C and N availability, whereas higher stubble height (20 cm) led to elevated leaf N:P ratios (24.2), indicating stronger phosphorus limitation. In addition, all stubble density treatments significantly reduced leaf C:N, C:P, and N:P ratios. Among them, the two stubbled after one retained exhibited the most pronounced effect, with C:N and C:P decreasing to 14 and 273, respectively, and N:P to 20, suggesting an improved nutrient balance and allocation efficiency. Multivariate analyses showed that lower stubble heights combined with alternate-plant stubble patterns (H2D1 and H2D2) enhanced leaf-soil nutrient coupling and promoted coordinated recovery of C-N-P stoichiometry during regeneration. Overall, stubble management regulates shrub rejuvenation mainly by modifying leaf-soil nutrient coupling rather than single-element responses. It is recommended that, in the management of degraded C. korshinskii shrublands, a stubble height of approximately 10 cm combined with staggered cutting (alternate-plant or every two plants) be prioritized as an optimized management regime. Full article

Glatiramer acetate (GA) is a first-line disease-modifying therapy for multiple sclerosis (MS) with well-established moderate efficacy and high safety, yet its mechanisms of action remain incompletely understood. DNA methylation plays a significant role in MS development and is modulated by various environmental factors, including therapeutic drugs. In this pilot study, we report the first prospective analysis of genome-wide DNA methylation changes in peripheral blood mononuclear cells (PBMCs) from four female relapsing-remitting MS patients before GA initiation and after approximately four and eight months of therapy. We identified 365 loci that are characterized by differential methylation, distinguishing post-treatment time points from baseline, with significant enrichment in CpG islands, shores, and promoter regions. Two distinct temporal patterns emerged: (1) non-monotonic DNA methylation changes peaking at four months and associated with response to foreign antigenic stimuli, and monotonic changes progressively increasing by eight months and related to mTOR-associated pathways relevant to chronic inflammation and neurodegeneration. Integration of DNA methylation and transcriptomic data revealed significant methylation-expression correlations for eight genes, including HLA-DMA, PDE4A, and SMOX—genes with established roles in MS-associated antigen presentation, immunoregulation, and neuroinflammation. Cell composition of PBMCs remained stable throughout treatment. In general, GA therapy for MS appears to induce dynamic, locus-specific DNA methylation changes in PBMCs, with distinct temporal patterns suggesting a biphasic response of the immune system. However, given that none of the individual DMPs reached genome-wide significance, the results presented in this pilot study strongly require validation in larger independent cohorts. Nevertheless, we believe that our findings provide insights into the immunomodulatory effects of GA and lay the foundation for future hypothesis-driven studies to develop epigenetic biomarkers for therapeutic monitoring and generic GA product assessment. Full article

Glyphosate [N-(phosphonomethyl)glycine] is the most widely used herbicide worldwide, and its environmental persistence has prompted increasing interest in microbial processes that may contribute to its dissipation. This study evaluated a collection of 15 soil-derived actinobacterial strains for plant growth-promoting traits, extracellular enzymatic activities, glyphosate tolerance, and glyphosate removal under nutrient-sufficient and phosphate-starved conditions. Herbicide tolerance evaluated on agar plates was widespread across the collection, with all strains sustaining growth at 10 and 50 g L⁻¹ of glyphosate. Under nutrient-sufficient conditions glyphosate removal remained limited, with maximum values of 16.15 ± 2.08% (Streptomyces sp. Con7.16) and 15.34 ± 2.89% (Streptomyces sp. Z38). In contrast, prior phosphate starvation markedly enhanced removal efficiency, reaching 42.21 ± 3.59% in Streptomyces sp. Z38 and 39.46 ± 1.94% in Streptomyces sp. Con7.16. Transmission electron microscopy coupled with X-ray microanalysis in the selected Streptomyces sp. Z38 revealed starvation-associated depletion of intracellular polyphosphate granules, followed by partial replenishment when glyphosate was supplied as the sole phosphorus source, consistent with indirect evidence of glyphosate-derived phosphorus acquisition. Genome mining of Streptomyces sp. Z38 identified candidate genes potentially consistent with a non-canonical, C-P lyase-independent phosphonate utilization route; however, these assignments are based exclusively on bioinformatic evidence and require experimental validation. Collectively, these findings indicate that phosphate limitation enhances glyphosate removal in the selected actinobacteria, and the physiological and genomic data are consistent with a starvation-triggered shift toward alternative phosphorus scavenging strategies. Because this strain is intended for future phytoremediation applications in glyphosate-contaminated agricultural soils, elucidating the underlying phosphorus dynamics is essential for anticipating its functional behavior and environmental relevance. Full article

DNA methylation is one of the most important epigenetic mechanisms regulating gene expression. DNA methyltransferases (DNMTs) are key players in these processes, regulating dynamic DNA methylation patterns in embryonic and adult cells. Therefore, dysfunction of DNMTs can lead to serious diseases and cancer due to distortions in gene methylation, including that of tumor suppressor genes. Due to the reversibility of DNA methylation, DNMTs are considered an important epigenetic target for drug development. This narrative review summarizes knowledge about DNMTs, including structural features and biological functions, and describes the development of DNMT inhibitors as therapeutics, from the earliest developments to the most modern and promising ones. Full article