Search Results (27,368)

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens affecting the global swine industry. This review summarizes current knowledge of PRRSV-induced suppression of adaptive immune responses, with particular emphasis on impaired T cell activity, dysregulated B cell responses, delayed and insufficient neutralizing antibody production, and viral strategies that limit effective immune clearance. In addition, recent advances and limitations in vaccine development and antiviral strategies are presented. By integrating insights from viral pathogenesis and host immune responses, this review provides a comprehensive perspective on current challenges and emerging strategies for effective PRRSV control. Full article

Classical liquid chromatography–tandem mass spectrometry (LC-MS/MS) remains a cornerstone of proteomics, but deep profiling of complex biofluids is constrained by the extreme dynamic range of protein abundance and low sample throughput. Emerging high-multiplex platforms address these limitations through distinct high-throughput configurations, including antibody-based proximity assays, modified aptamers, nanoparticle-assisted mass spectrometry, and digital single-molecule immunoassays. Despite their discovery potential, these technologies operate within alternative bottom-up or affinity-based frameworks, meaning that they are not interchangeable. Quantitative measurements of nominally identical proteins frequently show poor to moderate cross-platform agreement, reflecting fundamental differences in chemistry, epitope accessibility, matrix susceptibility, genetic variants, and peptide-level protein inference. Crucially, because these platforms generally yield aggregate quantitative readouts, they typically average across the proteoform spectrum, limiting their ability to differentiate whether an abundance shift is driven by specific splice variants, localized post-translational modifications, or a uniform increase in the protein’s overall concentration. This review provides a balanced, decision-oriented comparison of the Olink Proximity Extension Assay, SomaLogic SomaScan, Seer Proteograph and Quanterix Simoa, delineating their operational utility alongside their respective technical limitations. We propose a practical framework to guide platform selection based on the specific biological question, cohort size, and required structural resolution, while evaluating strategies to enhance cross-platform reproducibility via standardized reference matrices, structure-informed interpretation, and multi-tiered validation workflows. Full article

Background: The continuous emergence of antigenically distinct SARS-CoV-2 variants of concern (VOCs) necessitates the development of versatile and effective vaccine platforms capable of inducing broad and sustained immunity. Methods: We designed a chimeric trivalent recombinant protein, TriRBD, incorporating the receptor-binding domains (RBDs) of the Delta, Omicron BA.1, and XBB.1 subvariants. To enhance delivery efficiency and immunogenicity, TriRBD was formulated into a dissolving hyaluronic-acid-based microneedle array patch (MAP) using the droplet extension (DEN) technique. We investigated the synergistic effects of two squalene-based oil-in-water (O/W) emulsions, SqTS (Squalene/Tween-80/Span-85) and SqT (Squalene/Tween-80), as adjuvants within the MAP after gamma-irradiation sterilization, alongside safety evaluations via rabbit skin tests. Results: The SqTS-adjuvanted MAP formulation was found to be non-irritating. Immunogenicity studies in BALB/c mice revealed that MAP-delivered TriRBD elicited significantly higher and more durable IgG endpoint titers (EPT) compared to intramuscular injection, with robust antibody levels sustained for up to 52 weeks. Notably, the irradiated SqT-adjuvanted MAP group exhibited a highly balanced Th2/Th1 immune response (IgG1/IgG2a ratio), while the irradiated SqTS-adjuvanted MAP group shifted toward a Th2-preferred against TriRBD. Although the EPT against the Omicron BA.1 variant was relatively lower, the irradiated MAP-SqT-TriRBD group elicited significantly both of IgG1 and IgG2a, resulting in a balanced and broadened antibody repertoire. Conclusions: These findings demonstrate that combining a trivalent RBD antigen with a SqT-adjuvanted MAP platform provides a potent, safe, and thermostable strategy for broad-spectrum protection against evolving SARS-CoV-2 variants and future pandemic threats. Full article

Insulin resistance (IR) is a multifactorial metabolic condition that can precede type 2 diabetes, motivating integrated monitoring of complementary biomarkers associated with glucose–insulin homeostasis and adipose tissue dysfunction. Here, we present a hybrid multi-biorecognition laser-scribed graphene (LSG) electrochemical platform with four independently functionalized working electrodes for detecting glucose, insulin, adiponectin, and leptin. The platform combines glucose oxidase-mediated enzymatic sensing, a methylene-blue-labeled insulin aptamer, and antibody-based recognition for adiponectin and leptin. Each sensing channel showed concentration-dependent electrochemical responses in PBS and analyte-spiked 10% human serum. The glucose sensor retained comparable sensitivity in PBS and serum, while the insulin aptasensor and the adiponectin and leptin immunosensors remained responsive in the diluted biological matrix. A preliminary mixed-analyte study further showed that all four channels remained responsive in a common four-biomarker sample. Importantly, the four-analyte panel combines glucose and insulin, used in HOMA-IR, with adiponectin and leptin, which form the adiponectin-to-leptin ratio, demonstrating thcombines high surface area, good electrical conductivitye feasibility of integrating complementary biomarkers and distinct biosensing approaches side by side within a single multiplexed electrochemical platform, with potential for future application in early-stage insulin resistance assessment. Full article

Today, pharmaceutical sciences rely on a wide range of innovative therapeutics of varying sizes: nanoparticles, proteins, antibodies, and nanocarriers for drug delivery. Measuring their size is one of the crucial parameters in their characterization, to ensure drug safety, stability, and effectiveness. Over the past two decades, Taylor Dispersion Analysis has emerged as an important sizing method. Its scope of application is perfectly suited to the sizes of these therapeutics. By design, it can be coupled with a wide range of detectors, and extensive research has been conducted in this field. In this review, we will present an overview of the studies conducted, and discuss how the application drives the choice of one detector or another (size measurement, aggregation studies, interaction studies, and other analyses, performed in both simple biological buffers and in more complex media, particularly serum) and makes Taylor Dispersion Analysis a highly versatile tool. Full article

Dengue virus (DENV) causes the most prevalent arboviral infection worldwide. Although classically regarded as an acute illness, growing evidence describes Post-Dengue Syndrome (PDS) as a chronic entity affecting a subset of patients, with pooled estimates placing post-infectious fatigue at 20.0% (95% CI 10–36) and no standardized case definition yet available. This narrative review analyzes its pathophysiology: the cytokine storm, antibody-dependent enhancement, and NS1-triggered molecular mimicry, together with the cells that execute them—dendritic cells, mononuclear phagocytes, NK cells, platelets, and complement on the innate side, and plasmablast expansion, follicular helper T cell activation, defective regulatory control, and PD-L1/PD-1-mediated exhaustion on the adaptive side. Almost all of these immunological mechanisms have been characterized during acute infection; few studies have sampled the same patients during convalescence, and even fewer have compared those who developed persistent symptoms with those who recovered. They are therefore established features of acute dengue and, at present, hypotheses about PDS rather than demonstrated features. Genetic susceptibility is examined through polymorphisms of HLA, FcγRIIa, Toll-like receptor, and cytokine genes. Multisystemic manifestations are described—persistent fatigue, fibromyalgia-like myalgia and arthralgia, alopecia, brain fog, and mood disturbance—alongside neurological complications, categorized into direct neuroinvasion and post-infectious immune-mediated damage such as Guillain–Barré syndrome and encephalomyelitis. Recent population-based data linking dengue to acute neurological events and to later cognitive decline are examined critically, as is the unsettled question of whether post-dengue neuroinflammation amounts to neurodegeneration. Finally, the authors address the influence of age and sex and outline therapeutic and research priorities, offering an immunoclinical perspective for the multidisciplinary management of these patients. Full article

In the broiler production industry, antibiotics such as florfenicol are widely used. Although these antibiotics exert therapeutic effects against bacterial diseases, they can induce a series of physiological alterations in broilers under certain exposure scenarios. This study aimed to investigate the effects of chicory aqueous extract (CAE) on broiler growth performance, immune function, and intestinal health, and to compare the impacts of CAE and florfenicol exposure on the physiological status of broilers. A total of 200 one-day-old broilers were randomly divided into five groups (5 replicates per group): the blank control group (NC) drank tap water freely, the florfenicol group (FFC) was given 0.15 g/L of florfenicol solution in the drinking water, the CAE groups were given 1.25 g/L (LCAE), 2.5 g/L (MCAE), and 5 g/L (HCAE) of CAE in the drinking water, respectively. The experimental period was 42 days. The results showed that the addition of CAE to drinking water could significantly improve the growth performance of broilers, specifically manifested as increased body weight and a significantly decreased feed-to-gain ratio (F/G) (p < 0.05). Regarding immune function, CAE enhanced immune capacity by increasing immune organ indices, serum antibody titers, and serum levels of immunoglobulin A (IgA) and immunoglobulin G (IgG) (p < 0.05). In terms of intestinal function, CAE significantly increased villus height (VH) and villus-crypt ratio (V/C), elevated activities of digestive enzymes including chymotrypsin, α-amylase, and lipase, and raised both secretory immunoglobulin A (sIgA) content and Occludin mRNA relative expression levels (p < 0.05), thereby improving intestinal digestion and absorption. Additionally, CAE enhanced serum superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) content (p < 0.05), effectively enhancing the antioxidant capacity of broilers. Notably, compared with the NC group and all CAE-treated groups, broilers in the FFC group exhibited significantly reduced growth performance, suppressed immune function, and evident damage to intestinal tissue structure and physiological functions. Comprehensive analysis indicates that CAE can effectively promote broiler growth and development, enhance immune status and intestinal digestive-absorptive function, and enrich gut bacteria such as Lactobacillus and Bifidobacterium, thus optimizing intestinal microbiota composition. Among the gradient doses tested in this study, the 2.5 g/L dose of CAE demonstrated the best overall effect, suggesting that CAE may exert beneficial physiological effects under the present experimental conditions, and further investigations are needed to assess its practical application potential. Full article

Background/Objectives. VHHs (Nanobodies^®) are camelid single-domain antibody fragments with broad applicability in central nervous system (CNS) research, including blood–brain barrier transport, modulation of pathological proteins and molecular detection. However, few VHHs have been developed for cell-type-specific targeting within the brain. Astrocytes play essential roles in CNS homeostasis and contribute to many neurological disorders, making them an appealing target for diagnostic and therapeutic approaches. Here, we report the development and validation of the first VHHs directed against the astrocyte-enriched glutamate transporters GLT-1 and GLAST-1. Methods. VHHs were generated from a camelid immune library using phage display. Target specificity and affinity were evaluated in cells overexpressing the mouse and human transporters, as well as in iPSC-derived astrocytes. Target engagement and astrocyte specificity was further assessed ex vivo on brain sections using immunohistochemistry and in dissociated mouse brain cell suspensions by flow cytometry. VHH in vivo binding was evaluated by stereotactic injections within the brain striatum. Results. One anti-GLT-1 VHH and four anti-GLAST-1 VHHs demonstrated high specificity and apparent nanomolar affinity when binding tocells overexpressing the mouse transporters. The anti-GLT-1 VHH was additionally cross-reactive with the human ortholog, as demonstrated in overexpressing cells and iPSC-derived astrocytes. All VHHs showed target engagement on mouse brain sections and astrocyte specificity in dissociated mouse brain cell suspensions. VHH direct brain delivery resulted in localized transporter-specific signal around the injection site, whereas the non-binding isotype control VHH produced no detectable signal. Conclusions. Here we present the first set of VHHs capable of selectively recognizing astrocyte-enriched glutamate transporters GLT-1 and GLAST-1 in vitro, ex vivo, and in vivo. These VHHs constitute promising tools for astrocyte detection in research applications and the cross-reactive anti-GLT-1 lead might hold potential for future diagnostic or therapeutic strategies, including cell-targeted payload delivery. Full article

Background: Several B-cell maturation antigen (BCMA)-directed therapy (BDT) modalities have been approved by the US Food and Drug Administration (FDA) for relapsed-refractory multiple myeloma (RRMM). Ideal sequencing of these therapies remains unknown. Methods: We report one of the largest multicenter retrospective patient cohorts in this real-world analysis of patients receiving a BDT in both BDT-naïve and exposed settings at major academic centers. Results: In the BDT-naïve setting, which included 276 patients, 169 (61%) received chimeric antigen receptor T-cell therapy (CAR-T), whereas 107 (39%) received bispecific antibodies (BsAbs). Median progression-free survival (PFS) in the BDT-naïve setting was significantly longer with CAR-T than with BsAbs (16.1 vs. 13.5 months, p = 0.007) with a higher overall response rate (ORR) (87 vs. 68%). Multivariable Cox regression analysis revealed that receiving CAR-T (hazard ratio [HR] = 0.41), cytokine release syndrome (CRS) of any grade (HR = 0.50), achieving a best response of ≥very good partial response (VGPR) (HR = 0.12), and high-risk cytogenetic abnormalities (HRCA) (HR = 2.29) were all significant prognostic indicators of PFS. Similarly, HRCA (HR = 2.32), CRS (HR = 0.36), and a best response of ≥VGPR (HR = 0.16) were all independent prognostic factors of overall survival (OS). Of the 80 patients who received prior BDT, 22 received CAR-T (28%) and 58 (72%) received BsAbs. The median PFS was 6.3 months in the CAR-T group, with 64% ORR, vs. 4.4 months in the BsAb group, with 53% ORR (PFS HR, 0.93). Only the best response, ≥VGPR (HR = 0.20), achieved significance in the multivariable model. Conclusions: CAR-T led to more durable responses in the BDT-naïve setting than BsAbs. Responses to either modality were weaker in the BDT-exposed setting. These results highlight the importance of sequencing BDT in RRMM. Full article

Background: Breast cancer is the most common malignancy among women. The HER2-low subgroup represents one of its prevalent subtypes; however, due to its unique characteristics, it presents challenges in diagnosis and treatment, complicating clinical management. This narrative review aims to synthesize evidence regarding the epidemiology, diagnosis, treatment, and prognosis of this subgroup. Methods: In this narrative review, following a search of PubMed, Web of Science, Scopus, and Google Scholar databases and the evaluation of 91 studies, findings were synthesized qualitatively and descriptively. Additionally, cohort studies, systematic reviews, and meta-analyses were utilized to explore associations and summarize prognostic trends. Results: The prevalence of HER2-low varied between 30% and 65% across different populations, with most studies reporting an association with hormone receptor (HR)-positive status and age over 50 years. Diagnostic challenges primarily stemmed from poor inter-pathologist agreement and laboratory variability. However, emerging technologies such as artificial intelligence (AI) and radiomics have shown promising results in diagnosis. Therapeutically, trastuzumab deruxtecan (T-DXd) demonstrated efficacy with response rates ranging from 21% to 62%; nevertheless, cross-resistance to antibody–drug conjugates (ADCs) and high drug costs remain significant barriers. Patient prognosis and survival, beyond HER2 status, depended on factors such as HR status, Ki-67 index, lymph node involvement, and treatment response. Conclusions: HER2-low tumors constitute a distinct, highly prevalent subgroup with specific clinical features, necessitating differentiated diagnostic and therapeutic approaches. Despite the efficacy of T-DXd, obstacles such as intragroup heterogeneity, treatment resistance, high costs, and the lack of standardized diagnostic criteria persist. Therefore, attention to molecular profiling, standardization of diagnostic methods, and the development of cost-effective strategies are essential for equitable access to treatment. Full article

Oncolytic viruses (OVs) can selectively lyse tumor cells and remodel the immunosuppressive tumor microenvironment. However, monotherapy is limited by low response rates, systemic delivery barriers and antiviral-mediated viral clearance. Combinatorial strategies with immune-checkpoint inhibitors, CAR-T cells, cancer vaccines, microbiota intervention, chemotherapy and radiotherapy produce potent synergistic antitumor effects. Herein, we review the spatiotemporal-dependent synergistic mechanisms by which OVs convert “cold” tumors into immunologically “hot” lesions, alongside recent pre-clinical and clinical progress of various combination regimens. We further discuss major bottlenecks including unstable efficacy, cumulative toxicity and translational obstacles. Several promising biomarkers, such as baseline TME immunophenotypes, dynamic neutralizing-antibody kinetics, STING-IFN signaling and gut microbiota, support individualized OV-based therapy. Finally, we outline near-term sequential-optimization strategies and long-term directions centered on intelligently engineered OVs and multi-modal combinatorial platforms, offering guidance for future rational design of oncolytic viro-immunotherapy. Full article

The purpose of this review article is to discuss the current treatment modalities and ongoing clinical trials regarding cardiac amyloidosis (CA), specifically transthyretin cardiac amyloidosis (ATTR-CA). Amyloidosis refers to the extracellular deposition of insoluble amyloid fibrillar proteins. When these proteins are deposited in the heart’s myocardium, it is referred to as cardiac amyloidosis. CA can be divided into two main groups: light chain cardiac amyloidosis (AL-CA) and transthyretin cardiac amyloidosis (ATTR-CA), which can be further subdivided into wild-type transthyretin amyloidosis (ATTRwt) and hereditary transthyretin amyloidosis (ATTRv). ATTR-CA is an increasingly recognized cause of heart failure in the setting of progressive restrictive cardiomyopathy, particularly among older adults, males, and individuals of African descent, with remarkable advances in the therapeutic landscape. TTR stabilizers, including Tafamidis (approved in 2019) and Acoramidis (approved in 2024), have demonstrated significant reductions in mortality and cardiovascular hospitalizations. Gene silencing therapies, including Vutrisiran (approved in 2025), represent a new drug group that targets TTR production at the RNA level. Meanwhile, CRISPR-based gene editing with nexiguran ziclumeran (nex-z or NTLA-2001) and amyloid-depleting monoclonal antibodies offer the prospect of one-time curative treatments and active fibril clearance, respectively. However, despite these advances, substantial knowledge gaps persist: no head-to-head trials have compared stabilizers to silencers, optimal combination therapy regimens remain undefined, and the role of conventional guideline-directed medical therapy in ATTR-CA has only been supported by observational data. Full article

Development of therapies and pharmacological management of central nervous system diseases is significantly hampered by the presence of the highly selective blood–brain barrier (BBB). Receptor-mediated transcytosis (RMT) has proven to be a robust mechanism for delivering a wide variety of therapeutic modalities across the BBB. The present study describes the use of a neurotensin-based pharmacodynamic model to evaluate the brain penetrating capacity of FC5, a well-characterized RMT shuttle. Here we produce fusion molecules of FC5 with human Fc and neurotensin and show that intact but not C-terminally clipped neurotensin proteins containing either FC5 (FC5Fc-neurotensin) or a non-BBB-crossing control (A20.1Fc-neurotensin) retain the ability to activate neurotensin receptor type 1. In in vivo studies, intravenous administration of FC5Fc-neurotensin, but not neurotensin alone or A20.1Fc-neurotensin, induced a drop in the core body temperature in both rats and mice. We further extended these findings to non-human primates, demonstrating the ability of FC5 to cross the BBB in this species. Collectively, our results further support the potential of FC5 in delivering payloads across the BBB. The neurotensin model of hypothermia is also validated as a pharmacodynamic approach for assessing brain delivery, albeit with some necessary considerations into the molecular characterization of fusion constructs before in vivo evaluation. Full article

Background/Objectives: Lyssaviruses pose a persistent global public health threat, underscoring the need for broad-spectrum neutralizing antibodies to improve rabies post-exposure prophylaxis (PEP). The humanized monoclonal antibody cocktail SYN023 is approved for PEP in China and under active global regulatory review. This study aimed to validate pseudovirus-based neutralization assays, verify SYN023 epitope prediction accuracy, and systematically characterize its pan-lyssavirus neutralizing activity. Methods: Assay validation was performed by directly comparing neutralization titers obtained with authentic rabies virus (RABV) and pseudotyped virus. Epitope analysis was performed, followed by in vivo evaluation in a canine PEP challenge model. The pseudovirus-based neutralization assay was used to assess SYN023 broad-spectrum activity across diverse lyssaviruses. Results: Neutralization titers from authentic and pseudotyped viruses showed high concordance (R² = 0.8341, p < 0.0001), supporting the pseudovirus system as a reliable surrogate assay. Epitope analysis confirmed that SYN023’s epitope is fully conserved in the highly virulent New York City (NYC) RABV strain. In canine PEP challenge studies using the NYC strain, SYN023 conferred strong protection at 0.1–0.5 mg/kg. SYN023 exhibited potent neutralizing activity against phylogenetically diverse non-rabies lyssaviruses, including Mokola virus (MOKV; EC₅₀ = 14.74 µg/mL), whereas three clinically validated reference antibodies failed to neutralize MOKV even at concentrations up to 1000 µg/mL. Conclusions: This study demonstrates that the pseudovirus-based neutralization assay is a reliable surrogate assay. It also confirms the functional accuracy of the epitope mapping strategy and demonstrates the broad neutralization spectrum of SYN023 against a diverse panel of lyssaviruses. Full article

Mycoplasma bovis (M. bovis)-positive clinical Bovine Respiratory Disease (BRD) seriously threatens the survival and growth of calves. Against the global backdrop of escalating antimicrobial resistance, effective vaccines represent a promising strategy for the prevention and control of M. bovis-positive clinical BRD. This study aimed to characterize the epidemiological features of BRD on a large-scale dairy farm in Yancheng, Jiangsu Province, and to assess the efficacy of an inactivated M. bovis strain HM vaccine using a randomized, double-blind, controlled field trial conducted during the high-incidence season. In total, 200 healthy 3–4-week-old Holstein calves seronegative for M. bovis-specific antibodies were randomly allocated to either a vaccine group or a control group. Calves in the vaccine group received two intramuscular vaccine doses on day 0 and day 14, while control calves received an equal volume of placebo at identical time points. The entire trial spanned 194 days. A comprehensive assessment was carried out, including vaccine tolerability, growth performance, serum antibody and cytokine profiles, BRD incidence, infection rates of common pathogens, and vaccine protective efficacy. The results showed that the farm-level annual BRD incidence was 9.27%, consistent with typical temporal–spatial-herd distribution patterns. Calves exhibited good tolerability after vaccination, and the vaccine had no adverse effect on body-weight gain. Importantly, vaccination markedly elevated serum specific antibody levels, seropositivity rates, and concentrations of inflammatory cytokines including IL-4, IL-6, and IL-10 (p < 0.05). Moreover, vaccination reduced the risk of M. bovis-positive clinical BRD by 61% and decreased infection risks for several respiratory pathogens. Collectively, this inactivated vaccine demonstrated satisfactory tolerability and protective effects, providing critical technical evidence for the prevention and control of M. bovis-positive clinical BRD in dairy farms. Full article