Search Results (311)

Background/Objectives: Adjuvants, added to vaccines to enhance immune responses, are central to shaping the magnitude and durability of immunity, yet their precise mechanisms remain incompletely defined. This study evaluated how diverse adjuvant combinations influence HPV vaccine immunogenicity in non-human primates, with a particular focus on impacts on hematopoietic biology—megakaryocytes and platelets—and broader innate and adaptive pathways. Methods: Eight adjuvanted formulations, each incorporating distinct immunomodulatory components and delivery platforms, were compared against an alum-only control in non-human primates. Longitudinal antibody titers (HPV16-specific) were measured up to 54 weeks, and blood transcriptomes were profiled at Day 1 and Day 7 after both prime and boost doses to assess pathway-level enrichment and gene-expression patterns. Results: Several adjuvant combinations significantly increased antibody titers at 54 weeks compared with alum alone. Formulations containing cationic lipid or monophosphoryl lipid A (MPL) were associated with enhanced antibody responses. Early upregulation of immune-related genes across innate and adaptive pathways was also observed, with some combinations (e.g., inclusion of QS21 or ISCOMs) showing similar trends. Distinct group- and time-dependent transcriptional signatures were observed, with higher-responding formulations exhibiting stronger enrichment in pathogen-influenced signaling and cellular/humoral immune programs. Conclusions: Adjuvant selection and formulation strategy substantially modulate vaccine immunogenicity and early transcriptional programs, including innate, adaptive, and hematopoietic pathways. While individual adjuvants differentially regulate immune and platelet-associated genes, common pathway-level patterns emerge across formulations. These findings suggest candidate mechanisms for prolonged vaccine efficacy and provide actionable insights to guide rational adjuvant design for sustained immune protection. Full article

Aim of the study: To investigate the detection rate of respiratory viruses identified by multiplex real-time PCR (MPL real-time PCR) in respiratory specimens collected from hospitalized patients with acute lower respiratory tract infections (LRTI) over a five-year period (2020–2024), and to emphasize the importance of MPL real-time PCR testing in identifying respiratory viruses responsible for severe lower respiratory tract infections requiring hospitalization. Subjects and Methods: This cross-sectional retrospective study analyzed 15,936 respiratory specimens collected from hospitalized patients between 2020 and 2024. Seventeen respiratory viruses were detected using MPL real-time PCR. Statistical comparisons were performed using the chi-square test. Results and Discussion: The overall respiratory virus detection rate was 31.88% and was significantly higher in children than in adults (52.98% vs. 18.10%). The most frequently detected viruses were rhinovirus, influenza A, respiratory syncytial virus, and parainfluenza virus type 3, while influenza A and SARS-CoV-2 predominated in adults. During the peak of the COVID-19 pandemic in 2021, SARS-CoV-2 accounted for 78.92% of detected viruses, accompanied by marked suppression of other respiratory pathogens. Measles virus re-emerged in 2024, predominantly affecting children (17.65%). Most Respiratory virus-positive cases (82.8%) involved single-agent infections. Conclusions: Hospitalized acute LRTI cases often lack distinctive clinical signs to identify viral pathogens. MPL real-time PCR provides simultaneous multi-virus detection, enabling accurate etiological diagnosis and strengthening hospital-based viral surveillance, particularly in resource-limited settings. Full article

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases originating from hematopoietic stem cell transformation, characterized by the clonal proliferation of hematopoietic progenitors. A specific subset includes myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions, particularly involving PDGFR A or B, which are sensitive to TK inhibitor treatment. We report a case of a 21-year-old patient with a myeloproliferative/myelodysplastic neoplasm, presenting with hyperleukocytosis, anemia, thrombocytopenia, and elevated LDH. The peripheral blood smear showed hypogranular neutrophils, eosinophils, basophils, and myeloid precursors. The absence of BCR::ABL1 and mutations in JAK2, CALR, and MPL excluded common MPNs. Cytogenetic analysis revealed a rearrangement between chromosomes 5 and 14. FISH analysis confirmed an inverted insertion from chromosome 5 to chromosome 14, involving the PDGFRB gene. WGS and RNAseq identified a fusion between PDGFRB and CCDC88C, causing the constitutive activation of PDGFRB. The fusion gene was confirmed by sequencing. This allowed for targeted therapy with a tyrosine kinase inhibitor (TKI), leading to molecular remission monitored by RT-qPCR. This case highlights how a multidisciplinary approach can identify atypical transcripts in MPN, guiding targeted therapy with TK inhibitors, thus resulting in effective treatment and molecular remission. Full article

Varicella-zoster virus (VZV) is a human neurotropic herpesvirus. The primary infection with VZV causes chickenpox and establishes latency in sensory and dorsal root ganglia. Viral reactivation leads to herpes zoster (HZ), which is accompanied by complications such as postherpetic neuralgia (PHN), causing a significant disease burden. At present, vaccination is the most effective preventive measure. We developed a recombinant zoster vaccine, gE/BFA01, which comprises truncated VZV glycoprotein E and the liposome-based adjuvant BFA01 (containing MPL and QS-21). In this study, we evaluated the recombinant zoster vaccine’s immunogenicity in a live attenuated VZV-primed C57BL/6N mouse model and explored the mechanism of action of the BFA01 adjuvant. The results indicate that the gE/BFA01 vaccine induces superior antibody responses and stronger cellular immune responses compared with gE with aluminum hydroxide. Furthermore, gE/BFA01 showed comparable immunogenicity to the licensed vaccine Shingrix. Mechanistic investigations revealed that the BFA01 adjuvant can enhance the recruitment of innate immune cells at the injection site, increase the expression of DCs surface maturation markers, and activate multiple inflammatory signaling pathways in lymph nodes. Collectively, these findings indicate that gE/BFA01 can induce potent humoral and cellular responses, supporting its further development as a high-efficiency vaccine candidate. Full article

Primary myelofibrosis (PMF) is a Philadelphia chromosome (Ph)-negative myeloproliferative neoplasm (MPN) that features clonal proliferation of atypical megakaryocytes and myeloid cells, fibrosis of the bone marrow, extramedullary hematopoiesis, and increased risk of leukemic transformation to acute myeloid leukemia (AML). With the widespread application of molecular studies, especially next generation sequencing (NGS), significant advances have reshaped our understanding of the molecular pathogenesis of PMF and the prognostic relevance of specific gene mutations. In this review, we summarize its clinicopathologic features, genetic and molecular findings, updated diagnostic criteria, and differential diagnosis. These updates have been incorporated into the 5th edition of the World Health Organization classification of Hematolymphoid Tumors (WHO-5th) and the 2022 International Consensus Classification (ICC), thereby improving diagnostic accuracy and risk stratification, both of which are essential for tailoring treatment strategies and enhancing patient outcomes. Full article

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders characterized by the abnormal proliferation of myeloid cells. In addition to the main driver mutations in JAK2, MPL, and CALR, the transcription factor nuclear factor erythroid 2 (NFE2) has emerged as a key contributor to MPN pathophysiology. NFE2 expression is elevated in the majority of MPN patients, and augmented NFE2 activity in hematopoietic stem cells is sufficient to induce an MPN phenotype with spontaneous leukemic transformation in murine models. Moreover, NFE2 mutations, found in a subset of MPN patients, augment NFE2 activity and are associated with a markedly increased risk of progression to acute myeloid leukemia (AML). However, the molecular mechanism by which NFE2 mutations cause leukemogenesis is not understood. Here, we demonstrate that the E3 ubiquitin ligase ITCH mediates proteasomal degradation of wild-type (wt) NFE2 in HEK-293T cells. A gain-of-function truncation mutant, NFE2-226aa, retains the capacity to interact with ITCH but is no longer degraded. Rather, NFE2-226aa protects wt NFE2 from ITCH-dependent degradation, resulting in enhanced NFE2 activity. Full article

The PBLH affects the intensity of the surface turbulence and the state of pollutant dispersion. Current research on PBLH characteristics and their relationship with pollution in coastal megacities remains insufficient. Moreover, existing studies rarely evaluate the consistency of various boundary layer solution methods, making it difficult to identify deviations in single methods. So, we conducted enhanced observation experiments in Shenzhen, a megacity in China, between March and July 2023. The characteristics of the PBLH was analyzed by five months of observations from Micro-Pulse Lidar (MPL) and Microwave Radiometer (MWR). Five retrieval methods (Parcel, GRA, STD, WCT, and Theta) were applied for comparative assessment. The results shows that all methods captured similar diurnal patterns. During daytime, the PBLH ranged from 512 to 1345 m, with Theta yielding the highest and STD the lowest average values. At night, PBLH decreased overall, and method-dependent differences persisted. Under different pollution levels, this study also discussion the properties of PBLH using MPL and microwave radiometer. And aerosol optical depth (AOD) and PBLH showed a strong negative correlation, indicating aerosol-induced suppression of boundary layer growth. The study of boundary layer characteristics in coastal megacities can provide reference for atmospheric physics research in economically developed coastal areas. Full article

Platelet shortage poses a significant barrier to research and transfusion therapies because native megakaryocytes (MKs) are scarce in blood. To overcome this limitation, pluripotent stem cell–derived MKs (PSC-MKs) offer a standardized, donor-independent platform for research and therapeutic development, including disease modeling and ex vivo platelet production. Here, we report a chemically defined, feeder-free protocol to generate MKs from human pluripotent stem cells (hPSCs). The protocol combines the small molecule MPL agonist Butyzamide, macrophage colony-stimulating factor (M-CSF), and three-dimensional (3D) suspension culture, achieving high efficiency and reproducibility. Butyzamide replaced recombinant thrombopoietin (TPO), yielding comparable CD41⁺/CD42b⁺ populations and enhanced polyploidization. M-CSF accelerated nuclear lobulation and induced 4N MKs, while 3D culture increased yield, cell size, and substrate detachment. Multiple independent assays confirmed mature MK hallmarks, multi-nuclei, demarcation membranes, granules, and elevated mitochondrial respiration. Single-cell RNA sequencing outlined a continuous trajectory from early progenitors to functionally specialized MK subsets. This platform enables reliable MK supply for mechanistic studies and in vitro platelet production, advancing both basic research and therapeutic development. Full article

Urban residents’ transportation modes play a pivotal role in shaping transportation planning and policies for sustainable cities. Mining refined transportation modes from mobile phone location (MPL) data is a key spatiotemporal big data application for sustainable city planning and traffic management. However, key challenges persist: low recognition accuracy due to insufficient consideration of travel features of transportation modes, the positioning uncertainty of MPL data, and ineffective evaluation due to lacking validation datasets. To address these limitations, we propose an analytical framework for transportation mode recognition. First, precise moving segments are constructed through road network matching and linear interpolation, resolving the positioning uncertainty issues of MPL data. Then, we propose a comprehensive feature parameter system for transportation mode recognition and construct a transportation mode recognition model based on eXtreme Gradient Boosting (XGBoost). Finally, using synchronously collected GPS data and travel logs, we validated the framework’s recognition results, demonstrating its ability to improve the accuracy of transportation mode recognition. Full article

Background/Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease, in which multiple genetic and environmental factors may contribute. This study aimed to identify potential genetic determinants in patients with CTEPH and to compare their occurrence to a control group, which included patients with pulmonary embolism who had not developed CTEPH. Methods: Tier 1 and 2 genes related to coagulation, fibrinolysis and platelet disorders—as recommended by the International Society on Thrombosis and Haemostasis—and genes associated with vascular conditions were analyzed in n = 15 patients with CTEPH and n = 17 controls using next-generation sequencing. Non-synonymous, rare variants were collected and interpreted. Results: As expected, no single gene or variant was consistently present among CTEPH patients. Instead, individuals carried different mutations and combinations of variants. We identified several variants that were not found in the control group. Candidate variants were detected in F12, F13A1, F13B, F5, KNG1, SERPIND1, THBD, ADAMTS13, VWF, STIM1, ETV6, THPO, MPL, SERPINA1, ENG, RASA1, ACVRL1, GDF2, NFE2, SOX17 and RNF213. We did not detect exclusive variants in FGA, CPB2, and BMPR2 although they were suggested as candidates in previous studies. Elevated factor VIII and von Willebrand factor in CTEPH could not be explained by mutations in VWF and F8. Conclusions: Our study supports the hypothesis of heterogeneous genetic background in CTEPH, involving multiple pathways such as coagulation, altered fibrinolysis and impaired angiogenesis. These results provide a basis for more detailed investigations into specific genes and variants potentially associated with CTEPH in larger cohorts. Full article

Most reinforcement learning (RL) methods for portfolio optimization remain limited to single markets and a single algorithmic paradigm, which restricts their adaptability to regime shifts and heterogeneous conditions. This paper introduces a generalized version of the Modular Portfolio Learning System (MPLS), extending beyond its initial PPO backbone to integrate four RL algorithms: Proximal Policy Optimization (PPO), Deep Q-Network (DQN), Deep Deterministic Policy Gradient (DDPG), and Soft Actor-Critic (SAC). Building on its modular design, MPLS leverages specialized components for sentiment analysis, volatility forecasting, and structural dependency modeling, whose signals are fused within an attention-based decision framework. Unlike prior approaches, MPLS is evaluated independently on three major equity indices (S&P 500, DAX 30, and FTSE 100) across diverse regimes including stable, crisis, recovery, and sideways phases. Experimental results show that MPLS consistently achieved higher Sharpe ratios—typically +40–70% over Minimum Variance Portfolio (MVP) and Risk Parity (RP)—while limiting drawdowns and Conditional Value-at-Risk (CVaR) during stress periods such as the COVID-19 crash. Turnover levels remained moderate, confirming cost-awareness. Ablation and variance analyses highlight the distinct contribution of each module and the robustness of the framework. Overall, MPLS represents a modular, resilient, and practically relevant framework for risk-aware portfolio optimization. Full article

The article introduces the Guarantee-Based Bandwidth Traffic Engineering Queue (GB(Bw)-TEQ) and Guarantee-Based Utilization Traffic Engineering Queue (GB(U)-TEQ) models for queue management on router interfaces. These models implement the principles of Traffic Engineering Queues and support both DiffServ and IntServ. Their novelty lies in the ability to provide guarantees either for the bandwidth allocated to a class queue or for its utilization coefficient. Such guarantees stabilize and control the average queue length, positively affecting key Quality of Service (QoS) indicators, particularly average delay and packet loss probability. The unreserved portion of the interface bandwidth is allocated among queues in proportion to their classes. Therefore, the higher-priority queues have lower utilization, while lower-priority queues operate with higher utilization, which is consistent with DiffServ principles. The models are formulated as a mixed-integer linear programming problem with an optimality criterion and a system of constraints. Computational experiments confirmed the operability and efficiency of GB(Bw)-TEQ and GB(U)-TEQ compared to the known analogue CB-TEQ model, which does not provide service-level guarantees. The results demonstrate that the proposed models achieve the stated guarantees and enable differentiated service without blocking the lowest-class queues. These solutions can be applied to automate queue management in IP/MPLS switches and routers as well as in software-defined networks. Full article

This study evaluated whether the combined Lactiplantibacillus plantarum CRL1506 and MPL16 nasal priming more effectively modulated the Toll-like receptor (TLR)-3- and respiratory syncytial virus (RSV)-mediated respiratory immune responses in mice than single strains. The interaction of single and combined strains with porcine alveolar macrophages (AMs) and porcine respiratory epithelial cells (PBE cells) in the context of TLR3 activation and porcine reproductive and respiratory syndrome virus (PRRSV) was also evaluated. The in vivo studies in mice revealed that the CRL1506 + MPL16 combination was more effective than the individual strains at reducing RSV replication, protecting the lung from TLR3-mediated inflammatory injury and modulating innate antiviral responses, particularly in AMs. In vitro, lactobacilli treatment also increased the resistance of porcine AMs to PRRSV infection. Notably, the CRL1506 + MPL16 combination was not more effective than the single strains in modulating AMs antiviral immunity. Complementary assays in PBE cells revealed that L. plantarum CRL1506 induced higher production of IFN-λ than the MPL16 strain in response to TLR3 activation. Thus, the superior in vivo protection against RSV seen with the L. plantarum CRL1506–MPL16 combination likely reflects complementary actions of lactobacilli: MPL16 would efficiently modulate AMs, whereas CRL1506 would be more effective to target respiratory epithelial cells driving greater IFN-λ production that further boosts AM antiviral activity. The results from the animal models of this work furnish the scientific basis for proposing future human trials to assess the efficacy of the CRL1506 + MPL16 combination in improving respiratory antiviral immunity. Full article

Microplastic (MPL) and nanoplastic (NPL) contamination in soils is widespread, impacting soil invertebrates, microbial communities, and soil–plant systems. Here, we compiled the information from 100 research articles from 2018 onwards to enhance and synthesize the status quo of MPLs’ and NPLs’ impacts on such groups. The effects of these pollutants depend on multiple factors, including polymer composition, size, shape, concentration, and aging processes. Research on soil invertebrates has focused on earthworms and some studies on nematodes and collembolans, but studies are still limited to other groups, such as mites, millipedes, and insect larvae. Beyond soil invertebrates, plastics are also altering microbial communities at the soil–plastic interface, fostering the development of specialized microbial assemblages and shifting microbial functions in ways that remain poorly understood. Research has largely centered on bacterial interactions with MPLs, leaving understudied fungi, protists, and other soil microorganisms. Furthermore, MPLs and NPLs also interact with terrestrial plants, and their harmful effects, such as adsorption, uptake, translocation, and pathogen vectors, raise public awareness. Given the complexity of these interactions, well-replicated experiments and community- and ecosystem-level studies employing objective-driven technologies can provide insights into how MPLs and NPLs influence microbial and faunal diversity, functional traits, and soil ecosystem stability. Full article

Myeloproliferative neoplasms (MPNs) encompass three principal subtypes: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These hematologic malignancies originate from clonal hematopoietic stem cells (HSCs) and exhibit pathological overproduction of myeloid lineage cells. Recent advances in molecular diagnostics, particularly the precise detection of core driver mutations (JAK2 V617F, CALR, and MPL) and non-driver mutations (ASXL1, TET2, SRSF2), has refined diagnostic precision and risk stratification. A variety of prognostic models for MPNs provide guidance for treatment. Treatment methods mainly include bloodletting therapy, low-dose aspirin anticoagulant therapy, cytoreductive therapy, and allogeneic hematopoietic stem cell transplantation (HSCT). JAK inhibitors (such as ruxolitinib) remain the basic therapeutic drugs. However, emerging strategies targeting epigenetic dysregulation and the interaction in the immune microenvironment (such as interferon-α) show promise in reducing drug resistance. New methods, including combination therapy (combination of JAK inhibitors and BCL-XL inhibitors) and mutation-independent immunotherapy, are under investigation. This review summarizes the latest advancements in the diagnosis and treatment of MPNs, highlighting the importance of molecular mechanisms in guiding therapeutic approaches and the potential for precision medicine in the future. Full article