Search Results (1,328)

The gut microbiota of macaques, highly homologous to humans in biological characteristics and metabolic functions, serves as an ideal model for studying the mechanisms of human intestinal diseases and therapeutic approaches. A comprehensive characterization of the macaque gut microbiota provides unique insights into human health and disease. This study employs metagenomic sequencing to assess the gut microbiota of wild M. mulatta brevicaudus across various ages, sexes, and physiological states. The results revealed that the dominant bacterial species in various age groups included Segatella copri and Bifidobacterium adolescentis. The predominant bacterial species in various sexes included Alistipes senegalensis and Parabacteroides (specifically Parabacteroides merdae, Parabacteroides johnsonii, and Parabacteroides sp. CT06). The dominant species during lactation and non-lactation periods were identified as Alistipes indistinctus and Capnocytophaga haemolytica. Functional analysis revealed significant enrichment in pathways such as global and overview maps, carbohydrate metabolism and amino acid metabolism. This study enhances our understanding of how age, sex, and physiological states shape the gut microbiota in M. mulatta brevicaudus, offering a foundation for future research on (1) host–microbiome interactions in primate evolution, and (2) translational applications in human health, such as microbiome-based therapies for metabolic or immune-related disorders. Full article

The intelligent upgrade of heating systems faces the challenge of accurately identifying high-dimensional pipe-network resistance coefficients; difficulties in accomplishing this can lead to hydraulic imbalance and redundant energy consumption. To address the limitations of traditional Differential Evolution (DE) algorithms under high-dimensional operating conditions, this paper proposes an Improved Differential Evolution Algorithm (SDEIA) incorporating chaotic mapping, adaptive mutation and crossover strategies, and an immune mechanism. Furthermore, a multi-constrained identification model is constructed based on Kirchhoff’s laws. Validation with actual engineering data demonstrates that the proposed method achieves a lower average relative error in resistance coefficients and exhibits a more concentrated error distribution. SDEIA provides a high-precision tool for multi-heat-source networking and dynamic regulation in heating systems, facilitating low-carbon and intelligent upgrades. Full article

Protein-losing nephropathy (PLN) involves a heterogeneous group of pathologies leading to selective glomerular damage and development of renal disease. ICGN, the main cause of PLN, requires immunosuppressive treatment. However, the scientific evidence in veterinary medicine on immunosuppressive therapeutic schemes in this condition is limited. The aim of this study is to describe the clinical and paraclinical evolution of five dogs with PLN, presumably associated with ICGN, treated with chlorambucil as immunosuppressive monotherapy. Suspected IGCN was established by the presence of a urine protein–creatinine ratio (UPC) ≥ 3 without response to standard therapy, hypoalbuminemia < 2, or progressive azotemia. Patients were treated with a dosage range of chlorambucil from 0.16 to 0.4 mg/kg (mean 0.25 mg/kg) every 24 h as the sole immunosuppressant. In the end, 4/5 patients showed significant clinical improvement, 3/3 had resolution of the nephrotic syndrome, 5/5 had a sustained decrease in UPC values during follow-up and no relevant adverse effects were observed. In this report, chlorambucil proved to be a well-tolerated and potentially effective monotherapy for immune-mediated PLN in dogs. Full article

The 13th International Foamy Virus (FV) Conference was held from 8 to 10 November 2023 at the BioParque/Zoological Garden in Rio de Janeiro, Brazil. This was the first conference on spumaretroviruses to be held in the Southern Hemisphere and in the unique environment of the rainforest. New developments and current perspectives in FV research were presented. Highlights of the conference included the structural biology of the envelope protein (Env) and insights into its function and evolution, epidemiologic identification of Amazonian indigenous people with a high prevalence of simian FV (SFV) infections, investigations of virus biology and genomics using synthetic FV DNAs, studies of humoral immune response, and development and applications of SFV vectors. The last day of the meeting was a special tour of the Centro de Primatologia do Rio de Janeiro, located northeast of Rio de Janeiro amidst the protected rainforest, where New World primate hosts of spumaretroviruses are rescued and studied. Our report summarizes the meeting highlights and outcomes for future discussions. Full article

Chronic inflammatory response syndrome (CIRS) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are debilitating multisystem illnesses that share overlapping symptoms and molecular patterns, including immune dysregulation, mitochondrial impairment, and vascular dysfunction. This review provides a chronological synthesis of biomarker development in CIRS, tracing its evolution from early functional tests such as visual contrast sensitivity (VCS) to advanced transcriptomic profiling. Drawing on peer-reviewed studies spanning two decades, we examine the layered integration of neuroendocrine, immunologic, metabolic, and genomic markers that collectively support a multisystem model of innate immune activation specific to environmentally acquired illness. Particular focus is given to the Gene Expression: Inflammation Explained (GENIE) platform’s use of transcriptomics to classify disease stages and distinguish CIRS from other fatiguing conditions. While ME/CFS research continues to explore overlapping pathophysiologic features, it has yet to establish a unified diagnostic model with validated biomarkers or exposure-linked mechanisms. As a result, many patients labeled with ME/CFS may, in fact, represent unrecognized CIRS cases. This review underscores the importance of structured biomarker timelines in improving differential diagnosis and guiding treatment in complex chronic illness and highlights the reproducibility of the CIRS framework in contrast to the diagnostic ambiguity surrounding ME/CFS. Full article

Aging in sexually reproducing organisms is shaped by the declining force of natural selection after reproduction begins. In Drosophila melanogaster, experimental evolution shows that altering the age of reproduction shifts the timing of aging. Using the Drosophila experimental evolution population (DEEP) resource, which includes long- and short- lived populations evolved under distinct reproductive schedules, we investigated how immune defense against Beauveria bassiana changes with age and evolved lifespan. We tested survival post-infection at multiple ages and examined genomic differentiation for immune-related genes. Both population types showed age-related declines in immune defense. Long-lived populations consistently exhibited age-specific defense when both long- and short-lived populations were tested. Genomic comparisons revealed thousands of differentiated loci, yet no enrichment for canonical immune genes or overlap with gene sets from studies of direct selection for immunity. These results suggest that enhanced immune defense can evolve alongside extended lifespan, likely via general physiological robustness rather than traditional immune pathways. A more detailed analysis may reveal that selection for lifespan favors tolerance-based mechanisms that reduce infection damage without triggering immune activation, in contrast to direct selection for resistance. Our findings demonstrate the utility of experimentally evolved populations for dissecting the genetic architecture of aging and immune defense to inform strategies to mitigate age-related costs associated with immune activation. Full article

Projections indicate that the global urban population is anticipated to reach 67.2% by 2050, accompanied by a threefold increase in urban built-up areas worldwide. Urbanization has profoundly transformed Earth’s natural environment, notably characterized by the drastic reduction and fragmentation of wildlife habitats. These changes contribute to local species extinction, leading to biodiversity loss and profoundly impacting ecological processes and regional sustainable development. However, within urban settings, certain ‘generalist’ species demonstrate survival capabilities contingent upon phenotypic plasticity. The co-evolution of gut microbiota with their hosts emerges as a key driver of this phenotypic plasticity. The presence of diverse gut microbiota constitutes a crucial adaptive mechanism essential for enabling hosts to adjust to rapid environmental shifts. This review comprehensively explores amniote gut microbial changes in the context of urbanization, examining potential drivers of these changes (including diet and environmental pollutants) and their potential consequences for host health (such as physiology, metabolism, immune function, and susceptibility to infectious and non-infectious diseases). Ultimately, the implications of the gut microbiome are highlighted for elucidating key issues in ecology and evolution. This understanding is expected to enhance our comprehension of species adaptation in the Anthropocene. Full article

The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 variants. This review aimed to evaluate the factors influencing the immunogenicity and effectiveness of COVID-19 vaccines to inform future vaccine advancement strategies. A narrative review with systematic approach was conducted following PRISMA guidelines for narrative review. Literature was sourced from databases including PubMed, Embase, and Web of Science for studies published between December 2019 and May 2025. Encompassed studies assessed vaccine efficacy, immunogenicity, and safety across various populations and vaccine platforms. Data were collected qualitatively, with quantitative data from reviews highlighted where available. We have uncovered a decline in vaccine efficacy over time and weakened protection against novel variants such as Delta and Omicron. Booster doses, specifically heterologous regimens, improved immunogenicity and increased protection. Vaccine-induced neutralizing antibody titers have been found to correlate with clinical protection, although the long-term correlates of immunity remain poorly defined. The induction of IgG4 antibodies after repeated mRNA vaccinations raised concerns about potential modulation of the immune response. COVID-19 vaccines have contributed significantly to pandemic control; however, their efficacy is limited by the evolution of the virus and declining immunity. Forthcoming vaccine strategies should focus on broad-spectrum, variant-adapted formulations and defining robust comparisons of protection. Recognizing the immunological basis of vaccine response, including the role of specific antibody subclasses, is fundamental for optimizing long-term protection. Full article

Background: Parvovirus B19 (B19V) can cause severe relapsing episodes of pure red cell aplasia in immunocompromised individuals, which are commonly treated with intravenous immunoglobulins (IVIGs). Few data are available on B19V intra-host evolution and the role of humoral immune selection. Here, we report the dynamics of genomic mutations and subsequent protein changes during relapsing infection. Methods: Longitudinal plasma samples from immunocompromised patients with relapsing B19V infection in the period 2011–2019 were analyzed using whole-genome sequencing to evaluate intra-host evolution. The impact of mutations on the 3D viral protein structure was predicted by deep neural network modeling. Results: Of the three immunocompromised patients with relapsing infections for 3 to 9 months, one patient developed two consecutive nonsynonymous mutations in the VP1/2 region: T372S/T145S and Q422L/Q195L. The first mutation was detected in multiple B19V IgG-seropositive follow-up samples and resolved after IgG seroreversion. Computational prediction of the VP1 3D structure of this mutant showed a conformational change in the proximity of the antibody binding domain. No conformational changes were predicted for the other mutations detected. Discussion: Analysis of relapsing B19V infections showed mutational changes occurring over time. Resulting amino acid changes were predicted to lead to a conformational capsid protein change in an IgG-seropositive patient. The impact of humoral response and IVIG treatment on B19V infections should be further investigated to understand viral evolution and potential immune escape. Full article

The rapid evolution of SARS-CoV-2 has underscored the need for a detailed understanding of antibody binding mechanisms to combat immune evasion by emerging variants. In this study, we investigated the interactions between Class I neutralizing antibodies—BD55-1205, BD-604, OMI-42, P5S-1H1, and P5S-2B10—and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein using multiscale modeling, which combined molecular simulations with the ensemble-based mutational scanning of the binding interfaces and binding free energy computations. A central theme emerging from this work is that the unique binding strength and resilience to immune escape of the BD55-1205 antibody are determined by leveraging a broad epitope footprint and distributed hotspot architecture, additionally supported by backbone-mediated specific interactions, which are less sensitive to amino acid substitutions and together enable exceptional tolerance to mutational escape. In contrast, BD-604 and OMI-42 exhibit localized binding modes with strong dependence on side-chain interactions, rendering them particularly vulnerable to escape mutations at K417N, L455M, F456L and A475V. Similarly, P5S-1H1 and P5S-2B10 display intermediate behavior—effective in some contexts but increasingly susceptible to antigenic drift due to narrower epitope coverage and concentrated hotspots. Our computational predictions show strong agreement with experimental deep mutational scanning data, validating the accuracy of the models and reinforcing the value of binding hotspot mapping in predicting antibody vulnerability. This work highlights that neutralization breadth and durability are not solely dictated by epitope location, but also by how binding energy is distributed across the interface. The results provide atomistic insight into mechanisms driving resilience to immune escape for broadly neutralizing antibodies targeting the ACE2 binding interface—which stems from cumulative effects of structural diversity in binding contacts, redundancy in interaction patterns and reduced vulnerability to mutation-prone positions. Full article

The rapid evolution of pathogens and the limited genetic diversity of hosts are two major factors contributing to the plant pathogenic phenomenon known as the loss of disease resistance in maize (Zea mays L.). It has emerged as a significant biological stressor threatening the global food supplies and security. Based on previous cross-species homologous gene screening assays conducted in the laboratory, this study identified the maize disease-resistance candidate gene ZmNLR-7 to investigate the maize immune regulation mechanism against Bipolaris maydis. Subcellular localization assays confirmed that the ZmNLR-7 protein is localized in the plasma membrane and nucleus, and phylogenetic analysis revealed that it contains a conserved NB-ARC domain. Analysis of tissue expression patterns revealed that ZmNLR-7 was expressed in all maize tissues, with the highest expression level (5.11 times) exhibited in the leaves, and that its transcription level peaked at 11.92 times 48 h post Bipolaris maydis infection. Upon inoculating the ZmNLR-7 EMS mutants with Bipolaris maydis, the disease index was increased to 33.89 and 43.33, respectively, and the lesion expansion rate was higher than that in the wild type, indicating enhanced susceptibility to southern corn leaf blight. Physiological index measurements revealed a disturbance of ROS metabolism in ZmNLR-7 EMS mutants, with SOD activity decreased by approximately 30% and 55%, and POD activity decreased by 18% and 22%. Moreover, H₂O₂ content decreased, while lipid peroxide MDA accumulation increased. Transcriptomic analysis revealed a significant inhibition of the expression of the key genes NPR1 and ACS6 in the SA/ET signaling pathway and a decrease in the expression of disease-related genes ERF1 and PR1. This study established a new paradigm for the study of NLR protein-mediated plant immune mechanisms and provided target genes for molecular breeding of disease resistance in maize. Overall, these findings provide the first evidence that ZmNLR-7 confers resistance to southern corn leaf blight in maize by synergistically regulating ROS homeostasis, SA/ET signal transduction, and downstream defense gene expression networks. Full article

Background/Objectives: The ongoing evolution of SARS-CoV-2 has highlighted the limitations of parenteral vaccines in preventing viral transmission, largely due to their failure to elicit robust mucosal immunity. Methods: Here, we evaluated an intranasal (IN) vaccine formulation consisting of recombinant receptor-binding domain (RBD) adsorbed onto human probiotic Bacillus subtilis DG101 spores. Results: In BALB/c mice, IN spore-RBD immunization induced strong systemic and mucosal humoral responses, including elevated specific IgG, IgM, and IgA levels in serum, bronchoalveolar lavage fluid (BALF), nasal-associated lymphoid tissue (NALT), and saliva. It further promoted mucosal B cell and T cell memory, along with a Th1/Tc1-skewed T cell response, characterized by increased IFN-γ-expressing CD4⁺ and CD8⁺ T cells in the lungs. Conclusions: All in all, these findings highlight the potential of intranasal vaccines adjuvanted with probiotic B. subtilis spores in inducing sterilizing immunity and limiting SARS-CoV-2 transmission. Full article

Mycobacterium tuberculosis—an acid-fast staining bacterium—is a serious global health challenge that can have both short-term and long-term complications. Although the immune response helps trap the infection, it can also cause necrosis and calcification, leading to lung tissue damage. Calcification is a known outcome of chronic granuloma evolution in TB. Multiple pathways contribute to fibrosis and calcification; some examples are IL-1β, TGF-β, and TNF-α. Current antifibrotic drugs, such as nintedanib and pirfenidone, are effective but may increase the risk of latent tuberculosis reactivation in certain patients. Experimental therapies such as artemisinin derivatives have shown promise in preclinical TB fibrosis models, while cell-based therapies like bone marrow-derived mononuclear cells are also under early investigation for dual antifibrotic and immunomodulatory effects. This literature review will explore recent studies on the pathogenesis of M. tuberculosis, the mechanisms underlying calcification in granuloma formation, and subsequent complications of the disease process. Full article

The emergence of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus closely related to SARS-CoV and officially known as Betacoronavirus pandemicum precipitated a substantial surge in vaccine development that culminated during the global COVID-19 pandemic. At present, there are dozens of vaccines for the prevention of SARS-CoV-2 being utilized across the globe. However, only 10 of these vaccines have been authorized by the World Health Organization (WHO). These include mRNA-based, viral vector, subunit and whole-virion inactivated vaccines. At the current end of the pandemic, there has been a decline in the global vaccination rate, both for the general population and for those most at risk of severe illness from the virus. This suggests that the effectiveness of the vaccines may be waning. The decline occurs alongside a decrease in testing and sequencing for SARS-CoV-2. Furthermore, the process of tracking viruses becomes increasingly complex, thereby providing a selective advantage for SARS-CoV-2 and allowing it to evolve stealthily. In this review, we provide a comprehensive overview of viral evolution and vaccine development. We also discuss ways to overcome viral variability and test universal vaccines for all SARS-CoV-2 variants. Full article

Innate immune cells appear to have an important implication in the resolution and/or the aggravation of the COVID-19 pathogenesis after infection with SARS-CoV-2. To better appreciate the role of these cells during COVID-19, changes in blood eosinophil, the neutrophil and monocyte count, and levels of surface protein markers have been reported. However, analyses at several timepoints of multiple surface markers on granulocytes and monocytes over a period of one month after a SARS-CoV-2 infection are missing. Therefore, in this study, we performed blood eosinophil, neutrophil, and monocyte phenotyping using a list of surface proteins and flow cytometry during a period of 30 days after the hospitalization of patients with severe SARS-CoV-2 infections. Blood cell counts were reported at seven different timepoints over the 30-day period as well as measures of multiple mediators in serum using a targeted multiplex assay approach. Our results indicate a 95% drop in the blood eosinophil count by D1, with eosinophils displaying a phenotype defined as CD69/CD63/CD125^high and CCR3/CD44^low during the early phases of hospitalization. Conversely, by D7 the neutrophil count increased significantly and displayed an immature, activated, and immunosuppressive phenotype (i.e., 3% of CD10/CD16^low and CD10^lowCD177^high, 6.7% of CD11b^highCD62L^low, and 1.6% of CD16^highCD62L^low), corroborated by enhanced serum proteins that are markers of neutrophil activation. Finally, our results suggest a rapid recruitment of non-classical monocytes leaving CD163/CD64^high and CD32^low monocytes in circulation during the very early phase. In conclusion, our study reveals potential very early roles for eosinophils and monocytes in the pathogenesis of COVID-19 with a likely reprogramming of eosinophils in the bone marrow. The exact roles of the pro-inflammatory neutrophils and the functions of the eosinophils and the monocytes, as well as these innate immune cell types, interplays need to be further investigated. Full article