Development Of Strategies Research Articles

Enhancing electrochemical properties of PNb9O25 anodes at elevated temperature via surface modification by nitrogen-doped carbon

Improving the performance of electrode materials is a crucial step for enhancing the intrinsic safety of batteries, especially during high operating temperature and rapid charge/discharge processes. The aggravation of side reactions caused by electro-thermal behaviors especially at high operating temperature is the main factor causing the instability of surface structure. In this work, we focus on the titanium-free, coarse-grained PNb9O25 (PNO) anode and enhance its electrochemical performance at an elevated temperature of 45 °C using a nitrogen-doped carbon (N-C) surface modification strategy. The homogeneous N-C passivation layer provides favorable electronic conductivity and fast Li+ diffusion kinetics, significantly reducing chemical reactivity and improving the interfacial charge transfer capability. As a result, PNO@N-C demonstrates exceptional high-rate capacity retention (249 mAh g–1 at 0.1 A g–1 and 173 mAh g–1 at 6 A g–1 under 45 °C) and superior cycling stability, maintaining a high capacity of 147 mAh g–1 after 1000 rapid charging cycles at a current density of 4 A g–1 (∼20 C, 45 °C). This approach provides a practical strategy for further development of electrode materials for high-rate lithium-ion batteries operating at high temperatures.

Overcoming strength-ductility trade-off by hybridising different classes of titanium alloys

Two types of HYbrid Titanium Alloys (HYTAs) were created using laser powder bed fusion (LPBF): a ternary HYTA composed of α commercially pure (CP) Ti, α-β Ti-64, and β Ti-5553, and a binary HYTA made of α CP Ti and β Ti-5553. The resulting microstructures were highly heterogeneous, incorporating all possible phases and structures, which do not co-exist in traditional monolithic titanium alloys. Detailed characterisation of the intricate microstructures revealed the significant influences of several factors including the distribution of alloy particles, Marangoni convection and solute diffusion during melting, and solute microsegregation during solidification. Despite the different combinations of ingredient powders, the ternary and binary HYTAs exhibited nearly identical tensile properties, with a remarkable combination of high yield strength (1000 MPa) and enhanced ductility (uniform elongation of ∼15% and total elongation of ∼20%), surpassing various conventional titanium alloys. Both HYTAs exhibited highly heterogeneous microstructures and displayed effective coordination of major mechanisms enabling smooth transfer of deformation between regions with a wide range of hardness (4–6 GPa), leading to their exceptional performance. This outcome further demonstrates the potential of microstructure hybridisation as an innovative strategy for future alloy development.

From innovation to clinic: Emerging strategies harnessing electrically conductive polymers to enhance electrically stimulated peripheral nerve repair.

Peripheral nerve repair (PNR) is a major healthcare challenge due to the limited regenerative capacity of the nervous system, often leading to severe functional impairments. While nerve autografts are the gold standard, their implications are constrained by issues such as donor site morbidity and limited availability, necessitating innovative alternatives like nerve guidance conduits (NGCs). However, the inherently slow nerve growth rate (∼1mm/day) and prolonged neuroinflammation, delay recovery even with the use of passive (no-conductive) NGCs, resulting in muscle atrophy and loss of locomotor function. Electrical stimulation (ES) has the ability to enhance nerve regeneration rate by modulating the innate bioelectrical microenvironment of nerve tissue while simultaneously fostering a reparative environment through immunoregulation. In this context, electrically conductive polymer (ECP)-based biomaterials offer unique advantages for nerve repair combining their flexibility, akin to traditional plastics, and mixed ionic-electronic conductivity, similar to ionically conductive nerve tissue, as well as their biocompatibility and ease of fabrication. This review focuses on the progress, challenges, and emerging techniques for integrating ECP based NGCs with ES for functional nerve regeneration. It critically evaluates the various approaches using ECP based scaffolds, identifying gaps that have hindered clinical translation. Key challenges discussed include designing effective 3D NGCs with high electroactivity, optimizing ES modules, and better understanding of immunoregulation during nerve repair. The review also explores innovative strategies in material development and wireless, self-powered ES methods. Furthermore, it emphasizes the need for non-invasive ES delivery methods combined with hybrid ECP based neural scaffolds, highlighting future directions for advancing preclinical and clinical translation. Together, ECP based NGCs combined with ES represent a promising avenue for advancing PNR and improving patient outcomes.

Tarumã-do-Cerrado (Vitex cymosa Bertero ex Spreng) for Food Diversity and Nutraceutical Products

Background: Tarumã-do-Cerrado (Vitex cymosa Bertero ex Spreng, TC) is a littleexplored Brazilian native fruit. Objective: The sustainable bioprospecting of new fruits is essential to devise strategies for preventing and treating noncommunicable diseases, like obesity, and even contribute to food diversity and discovering functional ingredients. Methods: This study evaluated the proximate composition, minerals, dietary fiber, and their fractions, phenolic compounds by two types of extraction, and antioxidant activity in the TC edible part. We also determined its fatty acid profile from the seed’s crude oil. Results: TC has 100 g low-fat content (0.19 g) containing good phosphorus (91.50 mg) source and is rich in chromium (0.05 mg) and molybdenum (0.53 mg). It has a high range of dietary fiber in fresh and freeze-dried fruit (4.01 g and 26.23 g, respectively). The different extraction conditions showed medium to high content (101.58 to 598.80 µg GAE/100 g) of phenolic compounds. Antioxidant activity has been demonstrated in vitro using electron or hydrogen/proton transfer mechanisms. The crude oilseed is a source of oleic (35.91%) and linoleic acid (32.20%). Conclusion: TC provides essential nutrients, fibers, and bioactive compounds to be allied to sustainable health strategies for food diversity and nutraceutical product development.

Strategies for feature-assisted development of topology agnostic planar antennas using variable-fidelity models

Strategies for feature-assisted development of topology agnostic planar antennas using variable-fidelity models

The evaluation of DNA-linked inhibitor antibody and AlphaScreen assays for high-throughput screening of compounds targeting the cap-binding domain in influenza a polymerase.

The PB2 subunit of the influenza virus polymerase complex is essential for viral replication, primarily through a mechanism known as cap-snatching. In this process, PB2 binds to the 5' cap structure of host pre-mRNAs, enabling the viral polymerase to hijack the host transcriptional machinery. This binding facilitates the cleavage and integration of the capped RNA fragment into viral mRNA, thereby promoting efficient viral replication. Inhibiting the PB2-cap interaction is therefore crucial, as it directly disrupts the viral replication cycle. Consequently, targeting PB2 with specific inhibitors is a promising strategy for antiviral drug development against influenza. However, there are currently no available methods for the high-throughput screening of potential inhibitors. The development of new inhibitor screening methods of potential PB2 binders is the focus of this study. In this study, we present two novel methods, DIANA and AlphaScreen, for screening influenza PB2 cap-binding inhibitors and evaluate their effectiveness compared to the established differential scanning fluorimetry (DSF) technique. Using a diverse set of substrates and compounds based on the previously described PB2 binder pimodivir, we thoroughly assessed the capabilities of these new methods. Our findings demonstrate that both DIANA and AlphaScreen are highly effective for PB2 inhibitor screening, offering distinct advantages over traditional techniques such as isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR). These advantages include improved scalability, reduced sample requirements, and the capacity for label-free detection. Notably, DIANA's ability to determine Ki values from a single-well measurement significantly enhances its practicality and efficiency in inhibitor screening. This research represents a significant step forward in the development of more efficient and scalable screening strategies, helping advance efforts in the discovery of antiviral drugs against influenza.

Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in mice.

Chronic itch which is primarily associated with dermatologic, systemic, or metabolic disorders is often refractory to most current antipruritic medications, thus highlighting the need for improved therapies. Oxidative damage is a novel determinant of spinal pruriceptive sensitization and synaptic plasticity. The resolution of oxidative insult by molecular hydrogen has been manifested. Herein, we strikingly report that both hydrogen gas (2%) inhalation and hydrogen-rich saline (5mL/kg, intraperitoneal) injection prevent and alleviate persistent dermatitis-induced itch, diabetic itch and cholestatic itch. Hydrogen therapy reverses the decrease of spinal SIRT1 expression and antioxidant enzymes (SOD, GPx and CAT) activity after dermatitis, diabetes and cholestasis. Furthermore, hydrogen reduces spinal ROS generation, oxidation products (MDA, 8-OHdG and 3-NT) accumulation, β-catenin acetylation and dendritic spine density in persistent itch models. Spinal SIRT1 inhibition eliminates antipruritic and antioxidative effects of hydrogen, while SIRT1 agonism attenuates chronic itch phenotype, spinal β-catenin acetylation and mitochondrial damage. β-catenin inhibitors are effective against chronic itch via reducing β-catenin acetylation, blocking ERK phosphorylation and elevating antioxidant enzymes activity. Hydrogen treatment suppressed dermatitis and cholestasis mediated spontaneous excitatory postsynaptic currents in vitro. Additionally, hydrogen impairs cholestasis-induced the enhancement of cerebral functional connectivity between the right primary cingulate cortex and bilateral sensorimotor cortex, as well as bilateral striatum. Taken together, this study uncovers that molecular hydrogen protects against chronic pruritus and spinal pruriceptive sensitization by reducing oxidative damage via up-regulation of SIRT1-dependent β-catenin deacetylation in mice, implying a promising strategy in translational development for itch control.

Advancing sustainable energy in china:Economic and financial strategies for hydrogen and biofuel development

Advancing sustainable energy in china:Economic and financial strategies for hydrogen and biofuel development

Advances in structure-based allosteric drug design.

The identification of allosteric binding sites forms a critical connection between structural and computational biology, substantially advancing the discovery of allosteric drugs. However, the prevailing strategies for allosteric drug development predominantly rely on high-throughput screening, which suffers from high failure rates due to a limited understanding of allosteric mechanisms. This review collects insights from case studies on allosteric mechanisms, protein structure databases and computation algorithm developments, aiming to enhance our comprehension of allostery and guide more effective allosteric drug development. A crucial element in this area is the integration of structural biology with computational biology, which is vital for translating three-dimensional structural datasets into available drug discovery knowledge. These datasets and AI algorithms underpin the establishment of the allosteric binding site identification leading to structure-activity relationships (SARs) and are fueling the development of computational algorithms tailored for allosteric proteins, thereby driving forward the field of allosteric drug discovery.

High-performance PEI-based nanofiltration membrane by Mxene-regulated interfacial polymerization reaction: Design, Fabrication and Testing

Development of cost-effective materials and technologies for lithium extraction in salt-lake brines is of great importance to meeting rising lithium demands. Nanofiltration (NF) process is a feasible solution, however, it has commonly had operational problems such as low permeability. In this study, an MXene-regulated interfacial polymerization (MRIP) method was developed for fabrication of high-performance polyethyleneimine (PEI)-based polyamide (PA) NF membrane. The MXene nanosheets tiled at the water-oil interface, by which a spatio-temporal confinement effect was created; such structure could nicely regulate diffusion of monomers and precisely control PA nanofilm. The MXene-regulated membrane (PA@M) had thinner thickness, larger pore size, and better hydrophilicity. As a result, the permeance of PA@M membrane was significantly increased by more than 300%. Moreover, the membrane had outstanding cation selectivity with >98% rejection for Mg2+ and <20% rejection for Li+. Meanwhile, the selectivity factor of Li+/Mg2+ reached 31.5. Furthermore, a two-stage nanofiltration process by the membrane could reduce the Mg2+/Li+ ratio from 40 to 0.45, suggesting greater suitability of membrane for lithium extraction. The MRIP method offers a promising strategy and method for development of high-performance PA-NF membranes for resource recovery and water purification applications.

Optimizing combination targeted immunotoxin therapy: Insights from HER2 and EpCAM expression profiles.

Molecular targeted cancer therapy is a rapidly developing field, driving progress toward greater treatment efficacy. However, targeted monotherapy often fails due to the development of multidrug resistance in tumors. The combination of multiple targeted agents emerges as a possible solution to enhance treatment outcomes by activating different signaling pathways. This study systematically investigates the combined effect of targeted agents for the oncomarkers HER2 and EpCAM on cancer cells. Specifically, the study examined the impact of anti-HER2 (DARP_9.29-LoPE) and anti-EpCAM (DARP_EC1-LoPE) immunotoxins on a panel of cancer cells expressing various levels of HER2 and EpCAM. Using the Chou-Talalay combination indices, the study revealed that cells with low HER2 expression and high EpCAM expression are not optimal targets for combined HER2/EpCAM therapy. In contrast, the most effective approach involves the usage of an equimolar ratio of immunotoxins for cells exhibiting high HER2 and moderate EpCAM expression, resulting in a synergistic therapeutic effect. These findings provide significant insights into optimizing combination anti-HER2/EpCAM therapies and hold promise for the development of more effective cancer treatment strategies.

Exploring the synergistic effects of soil nutrients, rhizosphere fungi, and endophytic fungi on the shaping of root metabolites in Angelica sinensis (Oliv.) Diels.

The root of Angelica sinensis (Oliv.) Diels (Ang) is a bulk Chinese herbal medicine, and the microecological regulation is a sustainable means to enhance its quality. In this study, Angs at five bases (LZ, XZ, QS, PM, MZC) in Minxian County, Gansu Province were taken as the research objects. These bases locate in the typical spatial spans of the Ang authentic area, and are important planting bases. The Angs from production bases were systematically compared with respect to soil physicochemical properties, rhizosphere fungi, endophytic fungi, and metabolic profiles. Typically, LZ showed low levels of available nitrogen (AN), available phosphorus (AP), available potassium (AK), and soil enzyme activities, while QS had the highest AN, AP, AK, and cellulase activity. Although XZ exhibits moderate nutrient contents, its sucrase activity was highest. Based on microbiome sequencing, rhizosphere fungal communities responded these physicochemical differences, with XZ harboring more probiotics, including Tetracladium, Itersonilia, and Vishniacozyma, compared to LZ, which showed the lowest abundance of these microorganisms. Differential patterns were presented among their endophytic fungal communities. Through LC-MS detection, it was revealed that Angs in QS synthesized more short peptides, organic acids and phenylpropanoid ingredients. Upregulated metabolites with plant defense efficacy are mostly found in LZ's Angs. Whereas XZ's Angs had a moderate abundance of bioactive ingredients. Structural equation fitting further highlighted the synergistic effects of soil nutrients (AN, AP, AK) with key fungal genera (Tetracladium, Itersonilia, Paecilomyces, Aspergillus) and their potential shaping effects on amino acids, short peptides, organic acids, and phenylpropanoids such as L-phenylalanine, acetyl-L-tyrosine, Ile-His-Met-Thr, caffeic aldehyde, L-pipecolic acid, and 4-methoxycinnamic acid. This study further refined the potential action modes of these key microecological factors shaping the accumulation of main types of active ingredients. These results are expected to provide an important reference for the development of quality regulation strategies in Ang ecological cultivation.

The Neuroplastic Outcomes from Impaired Sensory Expectations (NOISE) hypothesis: How ACL dysfunction impacts sensory perception and knee stability.

The anterior cruciate ligament (ACL) is integral to maintaining knee joint stability but is susceptible to rupture during physical activity. Despite surgical restoration of passive or mechanical stability, patients struggle to regain strength and prior level of function. Recent efforts have focused on understanding how ACL-related changes in the nervous system contribute to deficits in sensorimotor control following injury and reconstruction. We hypothesize that these challenges are partially due to an increase in sensorimotor uncertainty, a state that reduces the precision of movement control. This review proposes the ACL NOISE (Neuroplastic Outcomes from Impaired Sensory Expectations) hypothesis, reframing current literature to provide a case that increased sensory noise following ACL injury and reconstruction disrupts sensory predictions, which are anticipations of immediate sensory outcomes or motor commands. This disruption in sensory predictions may contribute to altered neurophysiology, such as cross-modal brain activity, and other persistent clinical deficits. Narrative review RESULTS/FINDINGS: Following ACL injury and reconstruction, the knee and nervous system experience various neurophysiological alterations to overcome elevated sensory uncertainty and inaccurate sensory predictions, contributing to persistent motor deficits. We provide a theoretical case based on compelling evidence that suggests prolonged impairment after ACL injury may be secondary to uncertainty in knee sensory perception. Future research should consider testing the NOISE hypothesis by creating a paradigm that examines dynamic joint stability in response to unexpected perturbations. This approach would help assess motor coordination errors and drive the development of clinical strategies aimed at reducing sensory uncertainty following ACL reconstruction.

Calcium-Binding Proteins in the Autistic Brain-Potential Links to Symptom Development.

Autism spectrum disorder (ASD) is a complex challenge, influenced by genetic and environmental factors. This review focuses on the proteins calbindin (CB), calretinin (CR) and parvalbumin (PV) in the context of ASD, exploring their clinical correlations and providing a deeper understanding of the spectrum. In addition, we seek to understand the role of these proteins in GABAergic regulation and their implication in the pathophysiology of ASD. The studies reviewed revealed a significant decrease in PV+ interneurons in the prefrontal cortex of individuals with ASD compared with typical controls. This reduction is associated with local synaptic hyperconnectivity, characterized by an increase in the number of excitatory synapses and a reduction in inhibitory synapses. A correlation was also observed between the decrease in PV+ and the severity of the behavioural symptoms of ASD. The research highlights GABAergic imbalance as a crucial component in the neuropathology of ASD, highlighting the role of calcium-binding proteins, especially PV, in regulating neuronal excitability and modulating synaptic connectivity. These findings provide valuable insights for the development of new therapeutic strategies intended to modulate neuronal activity and improve the symptoms associated with ASD.

The Role of Alpha-7 Nicotinic Acetylcholine Receptors in Pain: Potential Therapeutic Implications.

Chronic pain represents a prevalent and costly medical challenge globally. Nicotinic acetylcholine receptors (nAChRs), one type of ligand-gated ion channels found extensively in both the central and peripheral nervous systems, have emerged as promising therapeutic targets for chronic pain. Although there are currently no FDA-approved analgesics specifically targeting nAChRs, accumulating preclinical and clinical evidence suggest that selective ligands for alpha 7 (α7) nAChRs show potential for treating chronic pain, boasting a reduced incidence of side effects compared with other nicotinic receptor types. The recent structural resolution of human α7 nAChRs has confirmed their negative association with heightened pain, providing a valuable foundation for the development of targeted medications. This review presents a comprehensive overview, encompassing insights into the roles of α7 nAChRs derived from structural and functional studies, recent advancements in pharmacology, and investigations into their involvement in the pathophysiology of chronic pain. Moreover, the review addresses the variability in analgesic effects based on the type of receptor agonist and highlights the current research limitations. As such, this review offers potential therapeutic approaches for the development of innovative strategies for chronic pain management.

Prevalence of Obstructive Sleep Apnea Among Veterans and Nonveterans.

Understanding disease prevalence can inform treatment and resource needs across populations. This study aimed to identify the prevalence of sleep apnea (OSA) among veterans and nonveterans. The national Comparative Health Assessment Interview Study, cross-sectional survey using probability-based sampling frames. Surveys completed by Internet or phone. 15,166 veterans (40% response rate) and 4,654 nonveterans (57% response rate). Self-report of healthcare provider-based diagnosis of OSA. Calculation of prevalence of OSA using statistical weighting to allow for direct comparison between veterans and nonveterans. Secondary analyses evaluated OSA by deployment status among veterans and compared average age of OSA diagnosis and differences in OSA prevalence among veterans and nonveterans stratified by gender, marital status, race/ethnicity, and posttraumatic stress disorder diagnosis. OSA diagnosis was more than twice as prevalent among veterans (21%, 95% CI 20%-22%) than nonveterans (9%, 95% CI 8%-10%; aOR: 2.56, 95% CI 2.22-2.95, P < .001). Deployment was associated with higher odds of OSA among veterans (aOR: 1.64, 95% CI 1.43-18.7, P < 001.) Veterans were diagnosed with OSA on average 5 years earlier than nonveterans. Veterans have a high prevalence rate of OSA, highlighting the importance of veterans' access to treatment. OSA is likely underdiagnosed in nonveterans, particularly among racial/ethnic minoritized groups. Future research should investigate disparities in access to diagnostic testing for racial/ethnic minority nonveterans and/or risk factors for OSA among racial/ethnic minority veterans. The increased odds of OSA among those with PTSD highlights in the importance of early referral for OSA testing by providers as well as development of trauma-informed strategies to promote OSA treatment adherence. Limitations include a bias toward underestimation of true disease prevalence due to self-report of diagnosis.

Trans-dimensional nanocoral gold foam interfaces affords ultrasensitive detection of influenza virus.

Development of sensitive and cost-effective strategies for detecting influenza viruses is crucial to combat the spread of infectious diseases. In this study, a novel trans-dimensional nanocoral gold foam (NCGF) was fabricated on screen-printed carbon electrodes using hydrogen template electrodeposition method. This unique structure, with interconnected large and small pores, significantly increased the specific surface area and stability of the sensor. Based on this nanostructure, the antibodies were further modified and used for influenza A viruses (IAVs) detection by enzyme-linked immunoelectrochemical method. The combination of the large specific surface area of NCGF and the catalytic reaction of alkaline phosphatase led to a dual amplification of electrochemical signals, enabling ultra-sensitive detection of IAVs. The NCGF-based biosensor demonstrated exceptional stability, sensitivity, and achieved a reliable limit of detection as low as 13.14fg/mL, which is several orders of magnitude improvement in sensitivity over conventional electrochemical immunosensor. Furthermore, 72 clinical samples were analyzed using a portable detection device that could directly read signals from a mobile phone, and the results correlated well with gold standard PCR method. Overall, this rapid, sensitive, and portable assay provides a valuable option for early viral infection diagnosis.

Fuzi decoction ameliorates intervertebral disc degeneration through ferroptosis modulation by suppressing NF-κB pathway.

Intervertebral disc degeneration (IVDD) is a complex condition that necessitates the development of novel therapeutic strategies. The objective of this study was to investigate the therapeutic potential of Fuzi decoction (FZD) in the treatment of IVDD by examining its bioactive components, target genes, molecular interactions, pathways, and therapeutic efficacy. Bioactive ingredients with an oral bioavailability (OB) of≥30% and drug likeness (DL) of≥0.18 were identified using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Target genes associated with IVDD were retrieved from various databases, and a Venn diagram was employed to determine the common targets between IVDD and FZD. Subsequent network analyses, including ingredient-target-disease networks and protein-protein interaction (PPI) networks, were constructed. Functional enrichment analyses, such as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were conducted to delineate the biological processes, pathways, and potential mechanisms. Molecular docking was utilized to validate the interactions between FZD ingredients and target genes. In vitro assays using nucleus pulposus cells (NPCs) evaluated the effects of FZD-containing serum (FCS) on extracellular matrix (ECM) degradation, ferroptosis, and NF-κB pathway modulation. Additionally, rat models were used to confirm the therapeutic effects of FZD on IVDD. FZD was found to contain 77 bioactive ingredients and 108 related targets, with 101 common targets identified between IVDD and FZD. Network analyses pinpointed key ingredients and targets, with a particular focus on PTGS2 and IL1B as central to IVDD. Enrichment analyses revealed pathways related to reactive oxygen species and NF-κB signaling. Molecular docking confirmed robust interactions between core ingredients and target proteins. Pharmacological findings were substantiated by in vitro and in vivo experiments, demonstrating that FCS alleviated IL-1β-induced ECM degradation and ferroptosis by inhibiting the NF-κB pathway in NPCs. FZD demonstrates efficacy in alleviating IVDD by regulating ECM degradation and ferroptosis through the suppression of the NF-κB signaling pathway. These findings suggest that FZD may be a promising therapeutic agent for the treatment of IVDD, offering insights into its multifaceted mechanisms and molecular interactions for potential clinical application.

Single-cell RNA sequencing reveals intrahepatic signature related to pathobiology of duck hepatitis A virus type 3 (DHAV-3) infection.

DHAV-3 is one of the main causative agents of duck viral hepatitis (DVH), an acute and highly lethal infectious disease in duck industry. However, the understanding of the pathogenesis of this virus in ducklings is limited. To dissect the molecular characteristics associated with pathobiology of ducklings to DHAV-3, we applied single-cell RNA-sequencing approach to profile the transcriptome of 1.4 million cells from 14 livers of DHAV-3 susceptible (S) and resistant (R) ducklings during viral infection and 4 uninfected healthy controls. We found that infected S ducks exhibited the activation of type I and II interferon pathways with elevated expression of interferon-stimulated genes (ISGs) compared to infected R ducks and healthy controls. DHAV-3 promoted proinflammatory phenotype and inhibited the cell apoptosis pathway of Kupffer cells of S ducks. Furthermore, we observed the elevated expression of host factor PLAC8 in S ducks and validated its ability to facilitate the infection of DHAV-3. We identified significant dysregulation of various genes in complement and coagulation cascades in hepatocytes2 exclusive to S ducks, together with over-secretion of ANGPTL4 from endothelial cells in S ducks which is confirmed to promote cellular migration, suggesting etiology of coagulopathic complications in ducks with severe DVH. Collectively, this study provides a rich resource for understanding the inflammatory immune signatures and cell communications underlying the pathogenesis of DHAV-3 infection, which may accelerate the development of better diagnostic methods and strategies for controlling this disease.

Effective analysis of thyroid toxicity and mechanisms of acetyltributyl citrate using network toxicology, molecular docking and machine learning strategies.

The growing prevalence of environmental pollutants has raised concerns about their potential role in thyroid dysfunction and related disorders. Previous research suggests that various chemicals, including plasticizers like acetyl tributyl citrate (ATBC), may adversely affect thyroid health, yet the precise mechanisms remain poorly understood. The objective of this study was to elucidate the complex effects of acetyl tributyl citrate (ATBC) on the thyroid gland and to clarify the potential molecular mechanisms by which environmental pollutants influence the disease process. Through an exhaustive exploration of databases such as ChEMBL, STITCH, and GEO, we identified a comprehensive list of 19 potential targets closely associated with ATBC and the thyroid gland. After rigorous screening using the STRING platform and Cytoscape software, we narrowed this list to 15 candidate targets, ultimately identifying five core targets: CBX5, HADHB, TRIM33, TP53, and CUL4A, utilizing three well-established machine learning methods. In-depth Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses conducted in the DAVID database revealed that the primary pathways through which ATBC affects the thyroid gland involve key signaling cascades, including the FoxO signaling pathway and metabolic pathways such as fatty acid metabolism. Furthermore, molecular docking simulations using Molecular Operating Environment software confirmed strong binding interactions between ATBC and these core targets, enhancing our understanding of their interactions. Overall, our findings provide a theoretical framework for comprehending the intricate molecular mechanisms underlying ATBC's effects on thyroid damage and pave the way for the development of preventive and therapeutic strategies against thyroid disorders caused by exposure to ATBC-containing plastics or overexposure to ATBC.