Search Results (297)

Legal advocacy for parents involved in the public child welfare system in the United States is typically initiated only after a child has been removed and a dependency petition has been filed. For infants, removal at or shortly after birth constitutes a profound disruption of the parent–child attachment relationship and is increasingly recognized as an adverse childhood experience. This paper focuses on a summative program evaluation of the Family Intervention Response to Stop Trauma (FIRST) Legal Clinic in Washington State, a prevention-oriented model providing free, confidential legal advocacy and peer support to pregnant and postpartum parents prior to Child Protective Services (CPS) investigation or court involvement. Administrative data from 2019 to 2025 for 1232 eligible families were utilized to examine eligibility and referral patterns, reasons for ineligibility, and case outcomes. Findings demonstrated that eligible families with known outcomes avoided dependency court involvement entirely or experienced case closure without child removal, while a smaller proportion proceeded to dependency court filings. These findings highlight the need to reduce unnecessary child welfare system entry and mitigate traumatic disruption of the parent–child attachment relationship at birth by providing legal advocacy before investigation and court involvement. Full article

The cell density effect, defined as reduced cell-specific productivity above a critical cell density, remains a major limitation in virus manufacturing processes. While medium exchange prior to infection has been reported to mitigate this effect, the role of spent medium during the early phase of infection is poorly understood. Here, we show that spent medium conditioned by high-density HEK293 cultures inhibits infection with recombinant vesicular stomatitis virus (rVSV), even when infection is performed at low cell density. The strength of inhibition increased with the density and conditioning time of the donor culture and resulted in slower replication kinetics, thereby delaying the optimal harvest time and potentially reducing overall yield. Notably, the inhibitory effect was reversible when the virus was added to cells maintained in fresh medium, indicating that inhibition is mediated by the medium rather than intrinsic changes in the cells. We excluded pH effects within 7.1–8.0, nutrient depletion, and lactate/ammonium accumulation as primary causes. Removal of cell debris and extracellular vesicles by filtration (down to 0.02 µm) and size-based retention down to 3 kDa did not restore infection, and AUC indicated no major differences in particle distributions between fresh and conditioned media. Together, our data suggest an unidentified <3 kDa inhibitor in spent medium that partially suppresses rVSV infection and slows replication kinetics. Full article

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major challenge to swine production worldwide. Current vaccines have limited efficacy against genetically diverse PRRSV strains. Therefore, strategies with alternative modes of action—such as antiviral approaches that target conserved virus–host interactions, including viral attachment and entry, rather than relying solely on adaptive immune responses—are needed. We first evaluated the in vitro effect of griffithsin (GRFT), a high-mannose-binding lectin, in the monkey kidney cell line MARC-145. Cells were pre-treated with GRFT (50–200 µg/mL) prior to PRRSV infection, after which cell morphology and viral RNA replication (measured by RT-qPCR) were assessed. Pre-treatment with 100–200 µg/mL GRFT, followed by PRRSV inoculation at a multiplicity of infection of 1 or 10, reduced viral replication in MARC145 cells in a dose-dependent manner, achieving almost 100% inhibition of ORF5 and ORF7 RNA compared with untreated controls (p < 0.0001). We next investigated the in vivo effects of intranasal GRFT administration (7.5 or 15 mg/day) in pigs (n = 56). Pigs treated with 15 mg/day GRFT exhibited significantly reduced (p < 0.05) viremia 2, 4 and 7 days post-challenge, compared with untreated, challenged, and controls (log₁₀ 8.1 ± 0.2 vs. 9.0 ± 0.25, 8.2 ± 0.1 vs. 9.1 ± 0.2, and 8.9 ± 0.2 vs. 9.3 ± 0.2, respectively), along with earlier resolution of fever and a trend toward increased average daily gain over 42 days (p < 0.1). These findings are the first report of GRFT efficacy in pigs and support its potential as an antiviral strategy against PRRSV, alongside existing interventions. Full article

RNA viruses exhibit high mutation rates, necessitating antivirals targeting conserved infection mechanisms. In this study, viral hemorrhagic septicemia virus (VHSV), a non-human pathogenic negative-sense RNA virus, was used as a surrogate model to enable high-throughput antiviral screening under reduced biosafety conditions. A recombinant VHSV expressing enhanced green fluorescent protein was used to screen 17,265 compounds, 2000 plant extracts, and 100 marine extracts. Among the candidates, the leaf extract of Phellodendron amurense Rupr. (PL extract) exhibited antiviral activity with low cytotoxicity (selectivity index ≈ 10). The extract reduced viral infectivity in a dose-dependent manner and showed cross-activity against snakehead rhabdovirus. Mechanistic analyses indicated that the PL extract acts primarily at early stages of infection. Virucidal assays demonstrated direct, time-dependent inactivation of viral particles, while pre-treatment reduced host cell susceptibility. Time-of-addition experiments confirmed that antiviral activity was restricted to early infection, suggesting interference with viral attachment or entry rather than intracellular replication. Fractionation revealed that activity was associated with the non-polar n-hexane fraction, implicating lipophilic compounds that may disrupt viral envelope integrity or membrane interactions. These findings suggest that P. amurense leaf extract is a promising candidate for broad-spectrum antivirals targeting conserved entry processes in enveloped RNA viruses. Full article

Bluetongue virus (BTV), the prototype of the genus Orbivirus, infects livestock, causing high morbidity and mortality and impacting global trade. BTV is a non-enveloped, double-capsid virus, composed of seven structural proteins and a genome of 10 double-stranded RNA segments. This manuscript highlights our group’s recent findings on the molecular and structural mechanisms underlying BTV entry and assembly during replication. Viral entry is a stepwise, pH-dependent process. The outermost protein, VP2, attaches to sialic acids and senses the acidic pH of early endosomes, triggering their dissociation. Subsequently, the second outer capsid protein, VP5, undergoes major changes in late endosomes, forming a membrane-penetrating pore that releases the transcriptionally active inner core into the host cytoplasm. Core assembly also proceeds stepwise and requires the accurate packaging of 10 positive-sense RNA segments. These segments form an RNA–RNA interaction network independent of viral proteins, beginning with the smaller segments and guiding the complete genome assortment. The small capsid protein, VP6, interacts with VP3 to facilitate RNA encapsidation. While infectious cores assemble in vitro without non-structural proteins, NS2 is essential for the in vivo formation of viral inclusion bodies via liquid–liquid phase separation, concentrating viral components and promoting genome assembly. These comprehensive characterizations of BTV provide a foundation for future control strategies against related reoviruses. Full article

CX3CR1 is a chemokine receptor expressed on respiratory epithelial and immune cells and has been identified as a host factor important for infections with respiratory syncytial virus (RSV). In this review, we discuss the roles CX3CR1 plays in the pathogenesis of RSV infections as a viral entry receptor and regulator of immune cell trafficking. The conserved CX3C motif of the RSV G glycoprotein binds to CX3CR1 to mediate viral attachment and entry into respiratory epithelial cells. Furthermore, soluble G protein (sG) can bind to CX3CR1 and competitively interfere with cell signaling induced by the chemokine CX3CL1, resulting in inhibition of immune cell recruitment to the site of infection. In addition, sG engages TLR2 on epithelial cells, activating MyD88-NF-κB signaling and priming the NLRP3 inflammasome, which enhances viral dissemination through pyroptotic cell death. CX3CR1 signaling should be viewed as one of several overlapping host factors that—along with developmental changes in interferon and STAT3 signaling, airway anatomy, inflammasome activity, and tissue-resident memory responses—contribute to differential disease outcomes of RSV infection. A more complete molecular understanding of RSV-CX3CR1 interactions and downstream host responses may enable the development of improved prevention and treatment strategies. Full article

In this work, poly(acrylic acid)-based layers were injected to form a sandwich layer between the cationic and anionic species for a compact and effective fire-retardant coating on cotton fabric using the layer-by-layer coating technique. From the SEM analysis, as the number of tri-layers increases, the attachment intensity increases, as can be seen for poly(acrylic acid) chitosan and bentonite clay PCB-5TL (the highest tri-layers), while in the case of halloysite-based coatings, as the number of tri-layers increases, instead of attachment, the agglomeration increases due to the high surface area of halloysite nanoclay tubes. FTIR and UV confirmed the finding from the new peak entry and an increase in thickness. The highest thermal residue, ~18%, was obtained for poly(acrylic acid) chitosan and halloysite nanoclay PCH-5TL with a maximum degradation peak intensity at ~389 °C. From the flammability and after-burning SEM investigation test, it was observed that the halloysite-based coating with a higher number of layers offered higher resistance against the flame spread and ignition and, thus, produced a higher amount of char. Full article

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has driven the global COVID-19 pandemic, imposing a tremendous burden on public health. As the virus continually evolves through rapid mutations, the pandemic has transitioned into a prolonged endemic phase. Despite the development of novel drugs and vaccines, clinical outcomes remain suboptimal for vulnerable populations, including the elderly and those with comorbidities or compromised immunity. Tea polyphenols, a class of structurally diverse and bioactive nutraceuticals, may modulate viral entry, replication, and host inflammatory pathways implicated in disease progression through pleiotropic effects on viral attachment, membrane fusion, intracellular replication, and proteolytic processing. Here, we provide an updated chemo-biological perspective on the antiviral and immunomodulatory mechanisms of tea polyphenols against SARS-CoV-2. Current evidence highlights their potential to serve as promising candidates for further mechanistic and translational investigation as adjunctive strategies and nutraceuticals for COVID-19 management. Importantly, no large-scale randomized controlled trials have yet demonstrated clinical benefit of tea polyphenols in COVID-19. Full article

The energy transition of small and medium-sized enterprises (SMEs) is an important element in achieving climate and energy goals, but its pace and scope remain varied. Previous studies have focused mainly on regulatory pressure, energy costs and financial barriers, while the importance of market factors has been analysed relatively rarely. The aim of this article is to assess consumer expectations perceived by enterprises as a factor that influences SMEs’ energy transition strategies. While the approach demonstrated by previous authors concentrated mostly on energy transition as a policy issue or an adjustment to legal changes, the originality and contribution of this paper lies in approaching this problem as one of a strategic adjustment to customers’ changing expectations. The study is based on a CATI survey of 417 Polish SMEs, predominantly micro- and small enterprises. The study covers the perception of customer expectations regarding energy efficiency, the use of renewable energy sources (RES) and environmental communication tools. Relationships were identified between perceived market signals and the energy-related actions of enterprises. The results indicate that SMEs perceive consumer expectations primarily as specific and quantifiable energy measures, such as reducing energy consumption and implementing renewable energy sources, while attaching less importance to formal reporting and certification tools. The energy transition is selective and incremental, focusing on solutions with low barriers to entry and short payback periods. From an energy policy perspective, the results suggest a need to design support instruments that are better aligned with how SMEs interpret market expectations. Full article

Daphnis nerii can severely damage pine forests worldwide. Daphnis nerii cypovirus-23 (DnCPV-23) is an important viral pathogen for controlling D. nerii. However, the mechanism underlying DnCPV-23 cell entry has not been elucidated. In this study, we determined that VP3 mediates the binding of DnCPV-23 to host brush border membrane vesicles. Far-Western blotting and mass spectrometry results revealed that a Manduca sexta alpha-glucosidase (MsAGL) can interact with VP3. The interaction between MsAGL and VP3 was verified by co-immunoprecipitation and glutathione S-transferase pull-down assays. Notably, MsAGL influenced DnCPV-23 entry into host cells, including attachment and the subsequent internalization of the virus. Furthermore, MsAGL inhibited DnCPV-23 infections of M. sexta cells and D. nerii larvae. In summary, we confirmed that VP3 of DnCPV-23 mediates cell entry, while also identifying MsAGL as an entry factor for DnCPV-23. The study findings provide useful insights relevant for further elucidating the cell entry mechanisms of cypoviruses. Full article

Metapneumoviruses comprise a genus of negative-sense RNA viruses that cause significant respiratory disease across human and avian hosts. Human metapneumovirus (hMPV) is a globally prevalent pathogen associated with acute lower respiratory tract infections in infants, older adults, and immunocompromised individuals. Avian metapneumovirus (aMPV) imposes substantial economic losses on the poultry industry through respiratory disease, reproductive impairment, and high mortality in the presence of secondary infections. Despite their distinctive host ranges, hMPV and aMPV share a conserved genomic architecture and encode homologous structural and non-structural proteins that mediate viral entry, replication, assembly, and evasion of host innate immunity. Comparative analysis highlights that both have deeply conserved polymerase and nucleocapsid functions, and yet have a wide range of diversity in the attachment glycoprotein (G) and small hydrophobic protein (SH), reflecting divergent evolutionary pressures in human versus avian hosts that have led to such distinctive differences. The recent emergence and detection of aMPV/A and aMPV/B across the previously aMPV-free United States beginning in late 2023, combined with rising cases globally of hMPV post-SARS-CoV-2 pandemic, underscore the continued challenges of metapneumovirus surveillance and control in humans and animals. This review aims to highlight the current knowledge on the history, molecular virology, pathogenesis, epidemiology, diagnostics, and control strategies for aMPV while drawing mechanistic parallels to hMPV. By contextualizing shared biology and structure alongside host-specific adaptations, we aim to identify key gaps that shape vaccine design, antiviral development, and future research priorities aimed at mitigating the health and economic burden posed by metapneumoviruses found in both birds and humans. Full article

Aboveground storage tanks are used to store various fluids and chemicals for many industrial purposes. According to API standard 653, the structural integrity of these tanks must be regularly assessed. The U.S. EPA requires each operator to have a Spill Prevention, Control and Countermeasure Plan (SPCC) for aboveground storage containers. The accepted practice for inspection of these tanks, particularly the tank bottoms, requires removing the tank from service, emptying the tank, and interior entry for direct inspection of the structure. The required inspection operations are hazardous due to the chemicals themselves as well as the requirement to operate within confined spaces. An inspection from outside the tank would have significant cost and time benefits and would provide a large reduction in the risks faced by inspection personnel. Guided wave (GW) testing is a promising candidate for screening of storage tank walls and bottoms from the tank exterior due to the ability of GWs to propagate over long distances from a fixed probe location. The lowest-order transverse-motion guided wave modes (e.g., torsional vibrations in pipes) are a good choice for long-range inspection because this mode is not dispersive; therefore, the wave packets do not spread out in time. A common weakness of guided wave inspection is the complexity of report generation in the presence of multiple geometry features in the structure, such as welds, welded plate corners, attachments and so on. In some cases, these features cause generation of non-relevant indications caused by mode conversion. Another significant challenge in applying GW testing is development of probes with high-enough signal amplitudes and relatively small footprints to allow them to be mounted on short tank bottom extensions. In this paper, a new generation of magnetostrictive transducers will be presented. The transducers are based on the reversed Wiedemann effect and can generate shear horizontal mode guided waves over a wide frequency range (20–150 kHz) with SNRs in excess of 50 dB. The recently developed SwRI MST 8 × 8 probe contains an array of eight pairs of individual magnetostrictive transducers (MsTs). The data acquisition hardware allows acquisition using Full Matrix Capture (FMC) and analysis software reporting of anomalies based on Total Focusing Method (TFM) image reconstruction. This novel inspection package allows generation of reports that map out corrosion locations and provide estimates of defect widths. Case studies of this technology on actual storage tank walls and bottoms will be presented together with validation of processing methods on mockups with known anomalies and geometry features. Full article

Glycan-mediated processes can be critical determinants of viral attachment and entry, yet for enveloped RNA viruses, including SARS-CoV-2, their mechanistic roles remain incompletely defined. This review synthesizes current structural and functional evidence for glycan engagement during SARS-CoV-2 attachment and entry. We describe the general viral entry pathways and their reliance on glycan recognition, followed by the interactions of the SARS-CoV-2 spike glycoprotein with host glycans, including ABO(H) blood group antigens, sialylated glycans, and endogenous lectins. Based on structural biology, glycobiology, and virology, we focus on how the spike protein exploits both glycan motifs and lectin receptors to enhance attachment, promote cellular uptake, or modulate host tropism. We contextualize these mechanisms by comparing glycan dependencies across other human viruses, including the influenza virus, HIV, and norovirus. Finally, we provide a comparative virological perspective to derive broad evolutionary insights into how enveloped viruses exploit the host glycans. Full article

Background: Human Immunodeficiency Virus type 1 (HIV-1) remains a major global health challenge. Despite advances in antiretroviral therapy, new prevention strategies are needed, particularly topical microbicides capable of blocking the earliest steps of viral entry. HIV-1 attachment relies on interactions with heparan sulfate proteoglycans on host cell surfaces; therefore, sulfated heparan-mimetic polymers have been explored as antiviral agents. In this context, sulfated chitosan microparticles are designed to mimic natural glycosaminoglycan receptors, acting as biomimetic decoys that prevent viral attachment and entry. Methods: Low-molecular-weight sulfated chitosan (LMW Chi-S) microparticles were synthesized and characterized (SEM, EDS, DLS, FTIR) following US Patent No. 11,246,839 B2. Their antiviral activity was evaluated by incubating the microparticles with high-viral-load HIV-1-positive plasma (~3.5 × 10⁶ copies/mL) to enable viral binding and removal by pull-down. The performance of the synthesized Chi-S microparticles was compared with established heparinoid controls, including soluble heparin and heparin microparticles. Results: Chi-S microparticles exhibited stronger virus-binding and neutralizing capacity than all heparinoid comparators, achieving up to 70% reduction in viral load relative to untreated HIV-1 plasma. In comparison, soluble heparin and heparin microparticles reduced viral load by approximately 53% and 60%, respectively. Subsequent evaluation across multiple tested concentrations confirmed a consistent antiviral effect, indicating that the synthesized Chi-S microparticles maintain robust virus–particle interactions throughout the concentration range examined. Conclusions: These findings demonstrate that LMW Chi-S microparticles possess potent antiviral properties and outperform classical heparinoid materials, supporting their potential application as topical microbicides targeting early HIV-1 entry mechanisms. Full article

Acinetobacter baumannii is a critical pathogen and a leading cause of hospital-acquired pneumonia, especially in immunocompromised patients. Although most research has focused on antimicrobial resistance, growing evidence shows that A. baumannii can efficiently adhere to, invade, and persist within human airway epithelial cells. Thus, the aim of this review is to summarize current knowledge on the mechanisms used by A. baumannii to establish infection, highlighting the bacterial traits responsible for attachment to airway epithelia, entry into host cells, manipulation of intracellular trafficking pathways to avoid degradation, metabolic adaptation to the host environment, and interference with immune defenses. The findings reported herein come from host–pathogen studies performed using epithelial cell lines, Galleria mellonella, and murine models, and from human primary airway cells. Despite the prominent role of the outer membrane protein OmpA, it is clear that A. baumannii pathogenicity relies on multiple, often redundant, virulence strategies to secure its intracellular niche and resist host pressures. Remarkably, strain heterogeneity in virulence traits between lab-domesticated and clinical isolates supports differential intracellular behavior and pathogenic potential. A deeper understanding of A. baumannii infection mechanisms is essential to design anti-virulence strategies that disarm this life-threatening bacterium, reduce selective pressure, limit resistance, and guide next-generation therapeutic interventions. Full article