Search Results (1,074)

Avian orthoavulavirus 1 (AOaV-1), commonly known as Newcastle disease virus (NDV), despite widespread vaccination, remains a significant threat to domestic chickens (Gallus gallus domesticus). Currently available live-attenuated NDV vaccines are derived from genotypes I and II lentogenic strains, whereas genetically divergent velogenic strains predominantly caused recent NDV outbreaks. This study examined the extent of genotypic divergence between NDV vaccine strains and field strains using phylogenetic and multivariate analyses of two major antigenic and virulence-associated genes: fusion (F) and haemagglutinin-neuraminidase (HN). A total of 121 full-length NDV-F and 81 NDV-HN gene sequences, representing reported NDV genotypes, were downloaded from GenBank and analysed using maximum-likelihood (ML) phylogenetic trees and principal coordinates analysis (PCoA). The phylogeny revealed genotype-specific clustering for both genes, consistent with current NDV classification. NDV vaccine strains belonging to genotypes I and II formed distinct clades, segregated from the majority of NDV field strains, including velogenic or virulent NDV genotypes. The principal coordinates analysis of both genes further confirmed the phylogenetic clustering of NDV genotypes, indicating increased genomic heterogeneity. These findings suggest genetic segregation of divergent velogenic or virulent genotypes from lentogenic NDV vaccines, requiring biological experiments for determining their efficacy against field strains. This study highlights the importance of molecular surveillance of NDV to monitor its genomic diversity, which is crucial for developing strategies to combat NDV outbreaks in domestic chickens. This study provides an updated, NDV-glycoprotein-gene-based comparative analysis across reported NDV genotypes using phylogenetic and multivariate approaches. Full article

Neurodegenerative diseases arise when normally functional aggregation-prone proteins transition into stable cross-β amyloid fibrils. Although these fibrils share a conserved architecture, the pathways that lead to fibrillation vary across proteins and cellular environments. Liquid–liquid phase separation is now recognized as a central organizer of intracellular biochemistry that modulates protein aggregation. Physiological condensation can buffer aggregation by maintaining macromolecular solubility and providing partner interactions that compete against pathological protein–protein interactions. However, condensates can transform and age into gel-like states that can favor the emergence of β-rich oligomers and solid-state fibrils. Across six disease-linked proteins that include Tau, ⍺-synuclein, amyloid-β, TDP-43, FUS, and hnRNPA1, we compare how sequence-encoded interaction motifs, cellular cofactors, and interfacial microenvironments shape the balance between physiological condensates and pathological amyloids. Here, we highlight the unifying drivers of aggregation and intervention points that preserve native function while limiting toxic amyloid formation. Full article

Neurodegenerative diseases feature diverse pathological protein aggregates, including Lewy bodies in Alzheimer’s disease (AD) and skein-like filaments in amyotrophic lateral sclerosis (ALS). The physical mechanisms underlying this morphological diversity remain unclear. Here, we demonstrate that aggregation of the prion-like domain of hnRNPA1 (A1PrD), implicated in AD and ALS, is driven by solution composition and phase transition dynamics. Utilizing 3D timelapse and fluorescence lifetime imaging microscopy, we show that solution conditions modulate phase separation, gelation, and fibrillation, resulting in distinct structures such as fibril, gel, and starburst morphologies. Homotypic and heterotypic interactions between A1PrD and RNA were observed to shift the balance between pathological and physiological condensates. Importantly, amyloid-rich starbursts displayed prion-like infection capabilities toward amyloid-poor condensates. Our findings highlight how the interplay between solution composition and kinetic balances of liquid-liquid phase separation, gelation, and fibrillation shapes the diverse pathological aggregate morphologies characteristic of neurodegenerative diseases. Full article

To achieve precise control over droplet size and generation frequency in the granulation process of HNS-IV, this study introduces a novel droplet granulation strategy that utilizes pulsed air-jet shearing technology. This approach enables independent and precise regulation of droplet injection frequency (fg) and volume (V) through systematic adjustments of air pressure (P), frequency (fp), duty cycle (η), and liquid flow rate (Q). By controlling the suspension flow rate (Q), we successfully achieved primary particle size control, obtaining median particle sizes (D50) of 375.84 μm, 444.45 μm, and 504.22 μm in ascending order. Furthermore, we systematically investigated the influence of calcium alginate (CA) concentration on both the sphericity of the resultant particles and the thermal decomposition characteristics of HNS microspheres. Our findings demonstrate that while increased CA content enhances particle sphericity, it simultaneously affects the thermal decomposition behavior of the microspheres. The proposed pulsed air-jet shearing method offers significant advantages by significantly reducing the accumulation of volatile organic solvents typical of liquid–liquid biphasic systems. Furthermore, the residual non-toxic aqueous solutions can be easily managed, establishing a greener, safer, and highly controllable approach for HNS-IV granulation. This methodology presents a valuable reference for achieving precise and controllable granulation of various energetic materials. Full article

Mobile Wireless Sensor Networks (MWSNs) enhance traditional wireless sensor networks by allowing sensor nodes to move, resulting in continuously changing network topologies. Although this mobility enables advanced applications such as disaster response, intelligent transportation systems, and mission-critical monitoring, it poses major challenges for secure and scalable key management in large-scale deployments. Most existing key management and key pre-distribution schemes are tailored to static or lightly mobile networks and therefore suffer from limited scalability, excessive memory consumption, inefficient key utilization, and increased vulnerability to node capture when applied to highly mobile environments. This paper proposes a mobility-aware, zone-based key management scheme that integrates an enhanced composite key distribution mechanism with dynamic key refinement. The network is partitioned into logical zones, each maintaining an independent key pool to confine security breaches and improve scalability. To adapt to mobility-induced topology changes, sensor nodes continuously refine their key rings by preserving only the cryptographic keys associated with persistent neighbor relationships. This selective retention strategy significantly reduces storage overhead while strengthening resilience against key compromise and unauthorized access. Comprehensive analytical modeling and performance evaluations demonstrate that the proposed scheme achieves higher secure connectivity, stronger resistance to node capture attacks, and improved scalability compared to existing approaches, particularly in dense and highly mobile MWSN scenarios. Full article

Objective: Emphysema is an important chronic obstructive pulmonary disease (COPD) phenotype characterized by the destruction of air spaces distal to the terminal bronchiole. Aiming to detect potential emphysema biomarkers and to assess the systemic effects of emphysema in blood plasma, we conducted a small cross-sectional shotgun proteomics study. Methods: This study included N = 40 participants divided into four subgroups (N = 10 per group): patients with emphysema and COPD (CE), patients with COPD but without emphysema (CN), healthy smokers (HS) and healthy never-smokers (HN). The participants were sampled non-probabilistically to be similar in terms of age, sex and comorbidities. Participants’ blood plasma was analyzed using liquid chromatography–mass spectrometry. Bioinformatic analysis included detection of differentially expressed proteins (DEPs) and overrepresentation analysis (ORA). Results: Across all groups, a total of 994 proteins were identified, with NADP-dependent malic enzyme (NADP-ME; encoded by ME1) being the only DEP in the CE vs. CN contrast. Proteins such as BMP1, ADAMTSL-2, -4 and IGFBP4, -5, 6 were identified to be upregulated in CE vs. HN. Fibulin-1, -3 and several immunoglobulin components were identified to be downregulated in the CE vs. HN contrast. ORA revealed several enriched processes, including serine-type endopeptidase activity, insulin-like growth factor I and II binding, and signaling receptor binding. Conclusion: We propose NADP-ME, an important enzyme of intermediary metabolism and redox homeostasis, as a potential biomarker candidate of emphysema. Notably, NADP-ME is also implicated in anoikis resistance. Additionally, changes in the expression levels of BMP1, ADAMTSL-2 and -4, and fibulin suggest potential major systemic effects of extracellular matrix perturbation. As all data was derived from LC-MS analysis, these findings need to be further evaluated with complementary methods. Full article

Phascolosoma esculenta is an economic species endemic in China and a highly prized delicacy along the country’s southeastern coast. This study focused on five P. esculenta populations and investigated their genetic diversity, population structure, and historical population dynamics. These populations were sampled from five locations, namely Beihai (BH) and Fangchenggang (FCG), in Guangxi; Putian, in Fujian (FJ); Danzhou, in Hainan (HN); and Zhanjiang (ZJ), in Guangdong. Genomic data were obtained through restriction site-associated DNA sequencing (RAD-seq) of 100 individuals. After quality filtering, a panel of 158,264 high-quality single nucleotide polymorphism (SNP) markers was established for subsequent analysis. The results revealed that the observed heterozygosity (Ho = 0.1872–0.2065) was lower than the expected heterozygosity (He = 0.2304–0.2382), with inbreeding coefficients (Fis) ranging from 0.1114 to 0.1592, indicating heterozygote deficiency and moderate inbreeding. Genetic diversity was moderate across all populations, as reflected in the values I (0.5220–0.5530), π (0.2415–0.2478), and PIC (0.1914–0.1982). Low genetic differentiation was observed among populations (Fst: 0.0339–0.0509) accompanied by high gene flow (Nm = 4.6658–7.1192), suggesting ongoing genetic exchange between populations. Analysis of Molecular Variance (AMOVA) indicated that most genetic variation occurred within populations. Genetic distance and genetic similarity ranged from 0.0345 to 0.0522 and 0.9491 to 0.9661, respectively, with no significant isolation by distance (Mantel test, R = 0.0793, p = 0.4307). Analysis of the species’ historical population dynamics suggests that P. esculenta may have experienced a substantial population contraction beginning approximately 300 years ago. Overall, the five populations exhibit moderate genetic diversity, though signs of inbreeding and recent population decline may indicate early stages of germplasm degradation. These findings provide important insights for the conservation and sustainable aquaculture of this species. Full article

H-NS (histone-like nucleoid-structuring protein) is a global regulator affecting diverse bacterial processes. This study aimed to elucidate the regulatory role of H-NS in the virulence of Klebsiella pneumoniae (K. pneumoniae), particularly in relation to capsule synthesis and anchoring. A clinically isolated ST11-KL64 strain of K. pneumoniae FK6741 with low virulence was used. The role of H-NS was evaluated using colony morphology, the string test, viscosity measurement, capsule quantification, transmission electron microscopy, growth curve, biofilm assay, a mouse infection model, transcriptomic analysis, and RT-qPCR. Deletion of hns converted FK6741 into a hypermucoid phenotype in the positive string test; capsule quantification and transmission electron microscopy (TEM) showed increased polysaccharide chains but a reduced and tightly bound capsule. The mutant was initially found to grow slowly but formed stronger biofilms. In vivo, it displayed reduced virulence but induced stronger inflammation. Molecular assays revealed upregulation of capsule synthesis genes (galF, wzi, wcaJ, and wzc) and downregulation of wabG, which is involved in capsule anchoring. H-NS represses capsule synthesis genes, limiting capsule formation in K. pneumoniae. In contrast, loss of H-NS downregulates wabG, a key gene involved in GalA-mediated capsule anchoring, resulting in unstable surface attachment and loss of capsular polysaccharides. Consequently, these unanchored polysaccharides fail to confer effective protection, resulting in reduced bacterial virulence. Full article

Background/Objectives: Tissue-agnostic therapy has transformed oncology by enabling treatment selection based on molecular alterations rather than tumor origin. Since 2017, nine U.S. Food and Drug Administration approvals across six biomarker classes have defined this paradigm. Thoracic and head and neck (H&N) cancers have been underrepresented in the registrational evidence supporting these approvals. This review systematically evaluated biomarker representation, histologic distribution, and clinical applicability of tissue-agnostic therapies in thoracic and H&N malignancies. Methods: A narrative systematic review was conducted using PubMed, ClinicalTrials.gov, and regulatory documents for all tissue-agnostic approvals between January 2017 and October 2025. Data were extracted from pivotal trials, including total enrollment, objective response rate (ORR), histologic distribution, and thoracic/H&N representation. Emerging biomarkers and resistance mechanisms were assessed from phase I–III studies and basket trials. Results: Nine tissue-agnostic approvals encompassing six biomarkers were identified: MSI-H/dMMR, TMB-High, NTRK, RET, BRAF V600E, and HER2 (IHC 3+). Across pivotal datasets (3800 patients), thoracic and H&N cancers accounted for fewer than 8% (n = 290) of enrolled patients. Thoracic representation was dominated by non-small-cell lung cancer (NSCLC) in RET, NTRK, and HER2 programs (150 patients, 4%), while small-cell lung, mesothelioma, and thymic carcinomas contributed <1% combined. H&N cancers comprised 140 patients (3–4%), primarily secretory salivary carcinoma in NTRK trials (n = 12–20), thyroid carcinoma in BRAF (n = 36) and RET (n = 45) programs, and rare HER2-positive salivary duct carcinomas. Conventional HNSCC and sinonasal cancers were limited to 1–2 cases per trial. Only two of nine trials (22%) reported prespecified CNS endpoints, and RNA-based fusion testing was employed in <40%, underscoring diagnostic variability and limited applicability. Conclusions: Although tissue-agnostic therapy has expanded the reach of precision oncology, thoracic and H&N cancers remain underrepresented in registrational evidence. Most approvals rely on single-arm basket studies with small, heterogeneous subsets that preclude histology-specific conclusions. Future research should prioritize histology-enriched trial designs, standardized molecular diagnostics, and real-world validation to establish reliable, equitable standards of care for these underrepresented malignancies. Full article

Prostate cancer frequently progresses to lethal, drug-resistant castration-resistant prostate cancer (CRPC), where conventional therapies often fail due to intrinsic and acquired resistance mechanisms. This resistance creates a critical therapeutic impasse, leaving patients with limited options and poor prognoses. Immunotherapy has emerged as a promising strategy to harness the immune system against these treatment-refractory tumors, offering a potential avenue to overcome the immunosuppressive barriers that underlie CRPC drug resistance. This review synthesizes findings from a structured search of PubMed, Web of Science, and Embase (2020–2025), revealing significant clinical progress: 4 vaccine trials, 5 immune checkpoint inhibitor trials, 18 combination therapy trials (≥2 agents), and 6 targeted drug trials have been conducted. Preliminary efficacy was observed in novel approaches like bispecific antibodies (e.g., Xaluritamig achieving 59% PSA50 response), PSMA-CAR-T (P-PSMA-101), and oncolytic viruses (Ad5 PSA/MUC-1/brachyury). Basic research identified four targeted resistance mechanisms (e.g., AR-LLT1, Pygo2, and HnRNP L) and one nanoparticle-mediated triple-combination therapy (CM-AMS@AD NPs integrating photothermal, chemotherapy, and immunotherapy), which enhanced cytotoxic T-cell infiltration and suppressed CRPC growth preclinically. These collective findings suggest the potential of immunotherapy for CRPC in overcoming resistance barriers and improving patient outcomes, with bispecific T cell engagers (Xaluritamig, 59% PSA50) and PSMA-directed CAR-T therapy (P-PSMA-101, >50% PSA reduction) emerging as the most promising near-term candidates and biomarker-stratified combinations (nivolumab plus rucaparib, 84.6% PSA50, in HRR-deficient patients) illustrating the transformative power of precision patient selection; however, these findings require validation in larger, biomarker-stratified trials before definitive conclusions can be drawn. Translating this potential into clinical reality requires optimized patient selection through predictive biomarkers and rigorously validated Phase III trials to confirm durable clinical responses and long-term survival benefits. Full article

Carbon dioxide (CO₂) emissions resulting from natural gas flaring are significant contributors to atmospheric greenhouse gases, posing a substantial risk to the Earth’s climate by exacerbating global warming. As a response, both the oil industry and government authorities are actively exploring cost-effective strategies to address this issue through carbon capture, utilization, and storage (CCUS), as well as reducing natural gas flaring and CO₂ leaks in the oil fields to mitigate the adverse consequences of greenhouse gas emissions. This study presents a numerical investigation of CO₂ utilization for enhanced oil recovery (EOR) and associated CO₂ retention in unconventional reservoirs, using the Bakken Formation as a representative case. A compositional reservoir model is developed to simulate CO₂ Huff-n-Puff (HnP) processes in a fractured horizontal well. The model incorporates dual-porosity and dual-permeability formulations, fluid–rock interactions, and an equation-of-state-based compositional framework to capture multiphase flow behavior. Key operational parameters, including reservoir pressure, injection rate, injection duration, and CO₂ molecular diffusion, are systematically evaluated to assess their impact on oil recovery and CO₂ retention. The results show that lower bottom-hole pressures enhance oil recovery through increased drawdown, while operating pressures near the minimum miscibility pressure (MMP) improve CO₂ solubility and overall retention. Extended injection durations and higher diffusion coefficients increase CO₂ dissolution in the oil phase but exhibit diminishing marginal benefits beyond an optimal injection time. The study quantifies residual and solubility trapping mechanisms during the operational timeframe of CO₂-EOR and provides mechanistic insights into optimizing CO₂-HnP performance in tight formations. The proposed framework establishes a technical basis for integrating CO₂-EOR with emission mitigation strategies in unconventional reservoirs. Full article

Background: Obstructive sleep apnea (OSA) is a highly prevalent and heterogeneous disorder associated with substantial cardiometabolic morbidity. Although continuous positive airway pressure (CPAP) remains first-line therapy, long-term effectiveness is frequently limited by suboptimal adherence. Advances in airway devices, surgical techniques, neuromodulation, and pharmacologic therapies have expanded the therapeutic landscape and created opportunities for individualized, mechanism-based treatment. Methods: We conducted a selective, narrative review with structured quantitative synthesis of randomized controlled trials, comparative cohorts, long-term follow-up studies, registries, and mechanistic investigations addressing OSA therapies beyond CPAP. Evidence spanning oral appliances, upper-airway and skeletal surgery, hypoglossal nerve stimulation, neuromuscular electrical stimulation, positional therapy, and pharmacologic interventions targeting metabolic and non-anatomical endotypes was integrated. Outcomes of interest included apnea–hypopnea index (AHI), oxygenation, blood pressure, patient-reported symptoms, durability, safety, and real-world adherence. Results: Mandibular advancement devices (MADs) consistently reduced AHI relative to placebo and produced symptom relief comparable to CPAP in mild-to-moderate OSA, largely due to superior adherence. Palatal surgery yielded meaningful short-term improvement in selected patients but demonstrated limited long-term durability. In contrast, maxillomandibular advancement (MMA) achieved the largest and most durable reductions in OSA severity, with efficacy comparable to CPAP and superior to other surgical modalities in appropriate skeletal phenotypes. Hypoglossal nerve stimulation (HNS) produced substantial, durable improvements in AHI and symptoms with high adherence, supported by randomized trials, long-term follow-up, and real-world registry data; newer bilateral and proximal stimulation systems may further broaden candidacy. Neuromuscular electrical stimulation and positional therapy provided modest, phenotype-dependent benefits, primarily as adjunctive or early-stage interventions. A major advance is the emergence of metabolic and endotype-targeted pharmacotherapy: longitudinal data demonstrate a dose-dependent relationship between weight change and OSA progression or regression, while randomized trials show that GLP-1-based therapies—particularly dual GLP-1/GIP agonism with tirzepatide—produce large, clinically meaningful reductions in AHI and cardiometabolic risk in obesity-associated OSA. Additional pharmacologic strategies targeting ventilatory loop gain and arousal threshold further support an endotype-driven treatment paradigm. Conclusions: Contemporary OSA management is shifting from a CPAP-centric model toward a precision-guided, multimodal framework that aligns therapy with dominant anatomic and physiological contributors to airway collapse. Integrating metabolic, neuromodulatory, and structural interventions—often in combination—offers the potential for durable disease control and improved patient-centered outcomes. Future priorities include head-to-head and combination trials, long-term cardiovascular outcomes, cost-effectiveness analyses, and pragmatic tools to operationalize personalized OSA therapy in routine clinical practice. Full article

Background/Objectives: Primary ciliary dyskinesia (PCD) is a rare inherited disorder caused by dysfunction of motile cilia, leading to chronic respiratory disease. Diagnosis is challenging due to heterogeneous and non-specific clinical manifestations and the absence of a single definitive diagnostic test. Current diagnostic strategies rely on a combination of functional, ultrastructural, and genetic analyses. The objective of this study was to evaluate whether ciliary beat frequency (CBF), combined with ciliary beat pattern (CBP) assessment using digital high-speed video microscopy (DHSV), could serve as an effective first-line screening tool to identify patients requiring further diagnostic investigations. Methods: This single-center retrospective study included 65 patients (52 children and 13 adults) with clinical suspicion of PCD. Ciliary beat analysis was performed on nasal or bronchial samples using DHSV and Sisson–Ammons Video Analysis software. CBF and CBP were assessed and compared between patients with confirmed PCD and those in whom PCD was excluded based on transmission electron microscopy (TEM) and/or molecular genetic analysis. Results: Fifteen patients were diagnosed with PCD. Mean CBF was significantly lower in the PCD group compared with the non-PCD group (3.3 Hz vs. 8.1 Hz; p < 0.001). A CBF cut-off value of 5.25 Hz yielded a sensitivity of 78.6% and a specificity of 95.7%. Three patients with PCD had CBF values above this threshold; however, two of them exhibited abnormal CBP. Sample type, patient age, and the presence of airway pathogens did not significantly influence CBF measurements. Conclusions: CBF and CBP analysis using DHSV represents a useful first-line screening tool within a multifaceted diagnostic approach for PCD, allowing rapid identification of patients who should undergo further confirmatory testing. Full article

Background: Hearing loss is one of the most common yet often overlooked sensory deficits worldwide, with consequences extending well beyond auditory function. Mounting evidence highlights the complex interrelationships among hearing loss, cognitive decline, and psychosocial well-being. Neural mechanisms underlying this association include increased cognitive load, cortical reorganisation, and social isolation, which mediate the impact of auditory deprivation on the brain and mental health. Furthermore, hearing impairment is consistently associated with a higher risk of depression and anxiety, particularly when the duration of untreated deafness is prolonged. Methods: This narrative review summarises recent longitudinal and neuroimaging studies investigating the effects of hearing loss and the timing of intervention with hearing aids. The review focuses on evidence addressing cognitive, psychological, and neural outcomes in relation to early versus delayed amplification. Results: Across multiple studies, early adoption of hearing aids within a limited timeframe after diagnosis is linked to better cognitive performance, lower depressive symptom scores, and more preserved neural network integrity. Experimental evidence supports the existence of sensitive periods for auditory intervention, during which brain plasticity allows for optimal reorganisation and recovery of function. Conversely, delayed amplification may lead to irreversible cortical changes and persistent psychosocial distress. Despite this, several barriers—healthcare accessibility, patient attitudes, and economic constraints—continue to delay timely intervention. Conclusions: Early identification and management of hearing loss are critical to preserve cognitive and emotional health. An integrated approach addressing both hearing and cognitive well-being, supported by patient education and personalised care strategies, may maximise the benefits of amplification and improve overall quality of life. Full article

Unfavorable terrain conditions and intensive emissions have led to a deteriorating trend of ozone (O₃) pollution in the Fenwei Plain (FWP), which has attracted increasing attention. However, the lack of observations and Volatile Organic Compound (VOC) component observation data has seriously constrained an in-depth understanding of the formation mechanisms of O₃ pollution. The multi-source observations conducted in this study provides first-hand evidence for characterizing the evolution of O₃ pollution in the FWP. O₃ lidar vertical profiles reported high-concentration layers exceeding 130 µg/m³, O₃ vertical flux high-concentration layers exceeding −50 µg/(m²⋅s), confirming downward transport to the surface. The VOCs components were dominated by Oxygenated Volatile Organic Compounds (OVOCs) (>300 ppbv) and alkanes (>20 ppbv). O₃ source apportionment technology analysis indicated transport from the Henan (HN) and Hubei (HB) contributed 24.99% and 40.02% of surface O₃ enhancement. Interestingly, a close linkage between O₃ precursor sensitivity (OPS) variations and contribution from potential source regions was noticed. Large contributions from HN and HB drove the OPS toward a VOC-limited regime, with a concurrent drop in the HCHO/NO₂ indicator to 1.73. Our results underscore the great importance of the impacts of regional transport on OPS from different source areas when formulating strategies for regional joint prevention and control. Full article