Search Results (297)

Transmissible viral proventriculitis (TVP) is an emerging disease in chickens, linked to chicken proventricular necrosis virus (CPNV), a recently identified birnavirus. Here, we provide the first molecular confirmation of TVP in Bangladesh from a coloured meat-type parent stock (PS) flock, while documenting a contemporaneous white layer flock with consistent clinical signs and characteristic gross lesions. Affected birds exhibited growth retardation, diarrhoea, and increased mortality, alongside hallmark gross changes in proventricular enlargement and wall thickening. From the meat-type PS, proventricular samples were collected for histopathology and molecular diagnostics. Histological analysis revealed severe glandular epithelial damage, necrosis, mononuclear infiltration, epithelial hyperplasia, and metaplasia. Using RT-PCR on nucleic acid extracted from FTA card samples, CPNV was detected. In addition, infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), and avian reovirus (ARV) nucleic acids were also identified. The amplified CPNV VP1 fragment was sequenced, and phylogenetic analysis placed the Bangladeshi strain within clades of previously reported CPNV isolates. This study represents the first molecularly confirmed report of CPNV associated with TVP in Bangladesh, highlighting the need for active surveillance in commercial and breeder poultry flocks to understand the virus’s epidemiology and support the development of control strategies. Full article

This study aimed to establish an indirect ELISA for detecting the avian reovirus (ARV) epidemic strain xj-1.1 by using the purified recombinant protein pET-σC as the coating antigen. To optimize assay performance, key parameters were systematically evaluated, including antigen-coating concentration, serum dilution, blocking reagent and duration, serum incubation time, and the dilution and reaction time of the HRP-conjugated secondary antibody. The optimized conditions identified were a coating antigen dilution of 1:100, serum dilution of 1:1600, coating at 37 °C for 1 h followed by overnight incubation at 4 °C, and blocking with 5% skim milk for 2 h. The optimal serum incubation time was 1.5 h, with the secondary antibody diluted 1:1000 and incubated for 2 h, followed by a 20-min color development step. The cut-off value for distinguishing positive and negative samples was determined to be 0.121. Validation of the assay demonstrated favorable specificity, sensitivity, and repeatability, indicating that the developed indirect ELISA provides a reliable method for detecting ARV xj-1.1 infection. Full article

Background: Prostate cancer remains a leading cause of male cancer-related mortality, largely driven by the dysregulated activation of the androgen receptor (AR) signaling pathway. The emergence of resistance, particularly in castration-resistant prostate cancer (CRPC), necessitates the discovery of innovative therapeutic approaches. This systematic review aims to consolidate contemporary evidence regarding natural products as bioactive alternatives capable of targeting the AR signaling axis. Methods: Adhering to PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, and ScienceDirect databases. The review identified and qualitatively analyzed 15 original research studies that investigated the efficacy and mechanisms of various natural compounds in modulating AR signaling. Results: The analysis reveals that natural products deactivate the AR signaling axis through diverse mechanisms. Neoisoliquiritin and α-terthienyl were found to suppress AR expression, activity, and nuclear translocation. Notably, α-mangostin facilitates the degradation of the AR-V7 splice variant, a key driver of treatment resistance. Manzamine A inhibits AR biosynthesis by targeting the transcription factor E2F8. Furthermore, alternative pathways are modulated through 5-α-reductase inhibition (Annona muricata compounds) and the activation of the non-classical membrane receptor ZIP9 by (-)-epicatechin to induce apoptosis. Conclusions: The emergence of resistance, particularly in castration-resistant prostate cancer (CRPC), necessitates the exploration of innovative therapeutic approaches. This systematic review consolidates contemporary evidence regarding natural products as potential bioactive alternatives for modulating the androgen receptor (AR) signaling axis. Rather than providing a definitive clinical roadmap, this work establishes a preclinical framework for identifying substances that may deactivate the receptor, break down its resistant forms, or prevent nuclear translocation. Full article

Infectious bursal disease virus (IBDV) and avian reovirus (ARV) are major immunosuppressive pathogens controlled through the widespread use of live attenuated vaccines. Concerns persist regarding potential immune interference when these vaccines are co-administered, though comprehensive in vivo data are lacking. Here, we reported the immunogenicity and protective efficacy of a live IBDV vaccine (W2512G-61) and a live ARV vaccine (ZJS) administered simultaneously or sequentially at 3-, 5-, and 7-day intervals in specific-pathogen-free (SPF) chickens. The IBDV live vaccine elicits strong, interval-independent humoral immunity and conferred 100% protection, demonstrating no compromise from ARV co-administration. Conversely, ARV-specific immunity was severely impaired by close temporal vaccination. ARV protection rates fell from 86.7% (ARV-only) to 46.7% with simultaneous administration and from 93.3% to 66.7% with a 3-day interval. Extending the interval to five or seven days eliminated this interference, restoring ARV antibody titers and protection to levels equivalent to ARV-only control vaccinated groups. This study provides the first definitive evidence of asymmetric immune interference between live IBDV and ARV vaccines. The results establish a minimum safe interval of five days to prevent interference and ensure robust ARV vaccine efficacy. These findings offer critical, evidence-based guidance for optimizing vaccination schedules to improve disease control in commercial poultry production. Full article

Avian reovirus (ARV) infections pose a significant and evolving threat to China’s poultry industry, the world’s largest. Diverse farming systems—ranging from modern intensive operations to traditional waterfowl-poultry polyculture—foster a unique ecological niche for ARV, defined by complex serotypic and genotypic diversity, marked regional variations, potential interspecies transmission between chickens and waterfowl, and recurrent co-infections. Collectively, these factors undermine the efficacy of conventional diagnostic approaches. This review systematically outlines the current epidemic landscape of ARV in China, highlighting the molecular characteristics of prevailing strains (particularly those from waterfowl) and their roles in diagnostic evasion. We critically assess the performance and limitations of existing diagnostic techniques (virus isolation, ELISA, PCR/qPCR) within the Chinese epidemiological setting. Furthermore, we discuss innovative technologies—including multiplex qPCR, CRISPR-Cas systems, and next-generation sequencing (NGS)—that offer potential for developing next-generation diagnostics tailored to China’s specific challenges. Finally, we propose future directions, with an emphasis on standardization, data sharing, and interdisciplinary collaboration to bridge the gap between cutting-edge innovation and on-farm application for precise ARV control. Full article

Underwater vehicles performing sampling tasks often encounter significant buoyancy variations due to payload adjustments and environmental changes, which severely challenge the stability and accuracy of controllers. To address this issue, this paper proposes a hybrid control framework that integrates Proximal Policy Optimization (PPO) with adaptive PID tuning. The framework employs PPO to dynamically adjust PID parameters online while incorporating output saturation, stepwise quantization, and dead zone filtering to ensure control safety and actuator longevity. A dual-error state representation—combining instantaneous error and its derivative—along with actuator command buffering is introduced to compensate for system lag and inertia. Comparative simulations and experimental tests demonstrate that the proposed method achieves faster convergence, lower steady-state error, and smoother control signals compared to both conventional PID and pure PPO-based control. The framework is validated through pool tests and field trials, confirming its robustness under realistic hydrodynamic disturbances. This work provides a practical and safe solution for adaptive depth control of sampling-capable AUVs operating in dynamic underwater environments. Full article

Background/Objectives: Insulin resistance and ambulatory blood pressure monitoring (ABPM) abnormalities represent distinct but interrelated pathways contributing to cardiovascular risk. The triglyceride–glucose (TyG) index reflects metabolic burden, whereas arterial load—captured through arterial stiffness, blood pressure variability, and morning surge—reflects hemodynamic instability. Whether the coexistence of these domains identifies a particularly high-risk ambulatory phenotype remains unclear. To evaluate the independent and combined effects of metabolic burden (TyG) and arterial load on circadian blood pressure pattern and short-term systolic blood pressure variability. Methods: This retrospective cross-sectional study included 294 adults who underwent 24 h ABPM. Arterial load was defined using three ABPM-derived indices (high AASI, high SBP-ARV, high morning surge). High metabolic burden was defined as TyG in the upper quartile. The “double-high” phenotype was classified as high TyG plus high arterial load. Primary and secondary outcomes were non-dipping pattern and high SBP variability. Multivariable logistic regression and Firth penalized models were used to assess independent associations. Predictive performance was evaluated using ROC analysis. Results: The double-high phenotype (n = 15) demonstrated significantly higher nighttime SBP, reduced nocturnal dipping, and markedly elevated BP variability. It was the strongest independent predictor of non-dipping (adjusted OR = 42.0; Firth OR = 11.73; both p < 0.001) and high SBP variability (adjusted OR = 41.7; Firth OR = 26.29; both p < 0.001). Arterial load substantially improved model discrimination (AUC = 0.819 for non-dipping; 0.979 for SBP variability), whereas adding TyG to arterial load produced minimal incremental benefit. Conclusions: The coexistence of elevated TyG and increased arterial load defines a distinct hemodynamic endotype characterized by severe circadian blood pressure disruption and exaggerated short-term variability. While arterial load emerged as the principal determinant of adverse ambulatory blood pressure phenotypes, TyG alone demonstrated limited discriminative capacity. These findings suggest that TyG primarily acts as a metabolic modifier, amplifying adverse ambulatory blood pressure phenotypes predominantly in the presence of underlying arterial instability rather than serving as an independent discriminator. Integrating metabolic and hemodynamic domains may therefore improve risk stratification and help identify a small but clinically meaningful subgroup of patients with extreme ambulatory blood pressure dysregulation. Full article

The Hedgehog (Hh) signaling pathway regulates key cellular processes, such as proliferation, differentiation, and morphogenesis. Although its canonical activation involves ligand binding to PTCH1, which activates Smoothened (SMO), noncanonical features of the pathway significantly contribute to cancer progression, particularly in prostate cancer (PCa). GLI3, a central transcription factor in the Hh pathway, can act as a repressor or activator depending on posttranslational modifications. In androgen-deprived PCa, GLI3 plays a critical role in driving castration-resistant phenotypes by interacting with the androgen receptor (AR), particularly the AR-V7 variant. This interaction enhances tumor survival and growth even under androgen deprivation therapy (ADT). Aberrant GLI3 activity is further driven by mutations in upstream regulators such as SPOP and MED12, which contribute to the progression of both prostate and other malignancies. Preclinical studies have shown promise in reducing tumor cell proliferation and migration, and in inducing apoptosis, by pharmacologically inhibiting the GLI3 pathway with SMO antagonists or GSK3β inhibitors. Recent evidence also highlights reciprocal interactions between Sonic Hedgehog (Shh) signaling and the AR that sustain tumor growth under ADT. GLI3 engagement with AR reinforces AR-dependent transcription, supporting tumor progression through noncanonical pathways. These findings suggest that targeting GLI3, particularly in combination with AR inhibition, could effectively overcome castration resistance and improve outcomes in patients with castration-resistant prostate cancer (CRPC). This review explores the role of GLI3 in both canonical and noncanonical Hh signaling, its potential as a therapeutic target, and future directions for overcoming resistance in Hh-driven cancers. Full article

Due to their therapeutic potential and effects on cells, exosomes derived from bovine colostrum (BCE) and milk (BME) are molecules that have been at the center of recent studies. Their properties include the ability to cross biological barriers, their natural biocompatibility, and their structure, which enable them to act as stable nanocarriers. Exosomes derived from milk and colostrum stand out in cancer prevention and treatment due to these properties. BMEs can be enriched with bioactive peptides, lipids, and nucleic acids. The targeted drug delivery capacity of BMEs can be made more efficient through these enrichment processes. For example, BME enriched with an iRGD peptide and developed using hypoxia-sensitive lipids selectively transported drugs and reduced the survival rate of triple-negative breast cancer (TNBC) cells. ARV-825-CME formulations increased antitumor activity in some cancer types. The anticancer effects of exosomes are supported by these examples. In addition to their anticancer activities, exosomes also exhibit effects that maintain immune balance. BME and BCE can regulate inflammatory responses with their miRNA and protein loads. These effects of BMEs have been demonstrated in studies on colon, breast, liver, and lung cancers. The findings support the safety and scalability of these effects. However, significant challenges remain in terms of their large-scale isolation, load heterogeneity, and regulatory standardization. Consequently, BMEs represent a new generation of biogenic nanoplatforms at the intersection of nutrition, immunology, and oncology, paving the way for innovative therapeutic approaches. Full article

Radiotherapy is an effective treatment for cancer; however, radioresistant cancer cells result in recurrence. Therefore, elucidating the mechanisms of radioresistance is urgently needed. Super-enhancers (SEs) are clusters of enhancers occupied by a high density of master transcription factors, mediators, and bromodomain protein BRD4. Recently, we reported that ΔNp63, an oncogenic transcription factor, promotes radioresistance in human head and neck squamous cell carcinoma (HNSCC) cells. As ΔNp63 establishes SEs in HNSCC cells, SEs may be involved in radioresistance. Here, we investigated the role of the SE component BRD4 in the radiation responses of HNSCC cells using a BRD4 degrader ARV-771 or BRD4 knockdown. First, Western blotting confirmed that ARV-771 decreased BRD4 protein expression. ARV-771 treatment resulted in reduced cell proliferation and enhanced apoptosis in irradiated HNSCC cells. Moreover, colony formation assays revealed that both ARV-771 and BRD4 knockdown enhanced the radiosensitivity of HNSCC cells, suggesting BRD4 contributes to the radioresistance of HNSCC cells. Furthermore, fluorescence immunostaining revealed distinct localization patterns of γH2AX, a marker of DNA double-strand breaks, compared with BRD4 and ΔNp63 in irradiated cells. Notably, ARV-771 and BRD4 knockdown decreased ΔNp63 and BRD4 protein expression, whereas ΔNp63 knockdown had minimal impact on BRD4 expression. Taken together, these findings suggest that BRD4-dependent maintenance of ΔNp63 expression may contribute, at least in part, to the regulation of radioresistance in HNSCC cells. Full article

Background/Objective: The poultry industry requires extensive vaccination of chickens against IBV in an effort to prevent the disease in animals and significant economic losses. Current vaccination strategies often lack effectiveness, and the continual emergence of new IBV variants makes disease control increasingly challenging. We have developed an inactivated vaccine for poultry containing nine different antigens (Nobilis Multriva), including two IBDV strains, two ARV strains, one NDV strain, one AMPV strain, one EDSV strain and two IBV strains: M41 (genotype GI-1) and 4–91 (genotype GI-13). In this study, the IB efficacy of this novel inactivated vaccine was investigated against homologous and heterologous IBV strains. Methods: Inactivated IBV vaccine containing the M41 and 4–91 strains (Nobilis Multriva) was administered intramuscularly, either alone or following vaccine priming, in SPF and commercial chickens. Birds were challenged with homologous and heterologous IBV strains at defined ages (peak of lay, mid-lay and end of lay). Vaccine efficacy was evaluated through serological assays, clinical observations, and monitoring of egg production post-challenge. Results: This vaccine provided excellent broad protection against different IBV strains circulating in different parts of the world, including IBV M41, 4–91, QX, Q1 and Var2. Furthermore, the vaccine provided long-lasting IBV serological response against IB M41 and IB 4–91 until at least 96 weeks of age in SPF and commercial layers and breeder birds. This vaccine will allow farmers to reduce the number of vaccination moments, thereby minimizing stress to the birds, while also decreasing labor demands and the risk of human error, ultimately contributing to lower overall vaccination costs. Conclusions: Given its demonstrated broad cross-protection and sustained serological responses, this nine-valent inactivated vaccine (Nobilis Multriva) represents a key component of an effective vaccination regimen for controlling IBV infections in the poultry industry. Full article

Background/Objectives: Tuberculosis (TB) remains the leading cause of death from a single infectious agent worldwide. In line with the World Health Organization’s (WHO) goal to end TB by 2035, the rapid development and clinical implementation of new, effective vaccines is urgently needed. To support global TB control efforts, we developed a novel candidate subunit multistage vaccine. Methods: This vaccine incorporates multiple Mycobacterium tuberculosis antigens expressed during both dormant and active stages of infection, fused into a single recombinant protein (ESAT6-CFP10-Ag85A-Rv2660c-Rv1813c). The antigen was encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles along with the pattern recognition receptor (PRR) agonists monophosphoryl lipid A (MPLA) and muramyl dipeptide (MDP), which function as adjuvants. Results: Using a mixed intramuscular/nasal prime-boost regimen, the vaccine elicited a mixed Th1/Th17 cell-mediated immune response, as well as a robust humoral response characterized by sustained systemic IgG (lasting at least one year) and prominent local secretory IgA. The vaccine demonstrated protective efficacy as a prophylactic booster following BCG priming in both murine and guinea pig models and was also effective in a therapeutic setting in a murine infection model. Conclusions: The results of this study provide empirical evidence that multistage tuberculosis vaccines represent a promising strategy for achieving global TB control. Full article

Prostate cancer remains a leading cause of cancer-related mortality and castration-resistant prostate cancer (CRPC) is a critical therapeutic challenge. This review establishes a conceptual framework analyzing ferroptosis vulnerability through two principles: “robustness through redundancy” in defense systems and the “evolutionary arms race” between androgen receptor (AR) signaling and oxidative resistance. We traced the evolutionary trajectory of hormone-sensitive diseases, where the AR coordinates ferroptosis defenses via SLC7A11, MBOAT2, and PEX10 regulation through progressive adaptations: AR-V7 splice variants that maintain defense independently of androgens, AR amplification conferring hypersensitivity, and AR-independent JMJD6-ATF4 bypass in SPOP-mutated tumors. This transforms ferroptosis from a static vulnerability to a stage-specific strategy. Novel approaches include menadione-based VPS34 targeting, which induces triaptosis through an oxidative endosomal catastrophe. We categorized the rational combinations mechanistically as vertical inhibition (multi-step targeting of single pathways), horizontal inhibition (synthetic lethality across parallel defenses), and vulnerability induction (creating exploitable dependencies). Ferroptosis-induced immunogenic cell death enables synergy with checkpoint inhibitors, potentially transforming immunologically “cold” prostate tumors. This review establishes ferroptosis targeting as a precision medicine paradigm exploiting the tension between the oxidative requirements of cancer cells and their evolved, yet architecturally vulnerable, defense systems, providing a framework for stage-specific, biomarker-guided interventions. Full article

In 2016, the South African government approved free oral PrEP distribution among high-risk groups like female sex workers (FSWs) to reduce new HIV infections. Despite the availability, unique barriers exist that challenge PrEP persistence, including limited knowledge, side effects, stigma, and mobility that hinder adherence. As such, engaging FSWs in the design of an FSW-led intervention program is crucial to promote PrEP uptake, adherence, and retention. Processes of an intervention mapping approach were applied to design and develop the program in KwaZulu-Natal, South Africa. A needs analysis was completed through existing literature and through engagements with FSWs, FSW peer educators, and a healthcare provider. The working group, comprising eight FSW peer educators and a researcher, co-created the intervention following a six-step mapping process. A total of six meetings took place, during which intervention determinants, change objectives, theory-based methods, and the intervention program were discussed and formulated, as well as implementing partners and the evaluation plan identified. The program focuses on the development of agency, self-efficacy, and hope among FSWs and aims to destigmatize PrEP through positive messaging, equipping FSWs with the ability to differentiate PrEP from ARVs given to people living with HIV. Through role-playing, participants will practice discussing PrEP with their intimate partners and friends, receive suggestions on managing pill supply and side effects, and be equipped to become PrEP ambassadors. The introduction of PrEP as a pill for high-risk groups can be stigmatizing. Therefore, it is crucial to involve marginalized groups in the design and implementation of their interventions to foster acceptance and develop a sense of ownership, ensuring the programs’ sustainability. Full article

This study presents an integrated micro-system solution to address the challenges of gait instability in patients with impaired hip motor function. We developed a novel wearable hip exoskeleton, where a flexible support unit and a parallel drive mechanism achieve self-alignment with the biological hip joint to minimize parasitic forces. The system is driven by an active brain–computer interface (BCI) that synergizes an augmented reality visual stimulation (AR-VS) paradigm for enhanced motor intent recognition with a high-performance decoding algorithm, all implemented on a real-time embedded processor. This integration of micro-sensors, control algorithms, and actuation enables the establishment of a gait phase-dependent hybrid controller that optimizes assistance. Online experiments demonstrated that the system assisted subjects in completing 10 gait cycles with an average task time of 37.94 s, a correlated instantaneous rate of 0.0428, and an effective output ratio of 82.17%. Compared to traditional models, the system achieved an 18.64% reduction in task time, a 28.31% decrease in instantaneous rate, and a 7.36% improvement in output ratio. This work demonstrates a significant advancement in intelligent micro-system platforms for human-centric rehabilitation robotics. Full article