HSP70 positively regulates translation by interacting with the IRES and stabilizes the viral structural proteins VP1 and VP3 to facilitate duck hepatitis A virus type 1 replication.

The maintenance of viral protein homeostasis depends on the interaction between host cell proteins and viral proteins. As a molecular chaperone, heat shock protein 70 (HSP70) has been shown to play an important role in viral infection. Our results showed that HSP70 can affect translation, replication, assembly, and release during the life cycle of duck hepatitis A virus type 1 (DHAV-1). We demonstrated that HSP70 can regulate viral translation by interacting with the DHAV-1 internal ribosome entry site (IRES). In addition, HSP70 interacts with the viral capsid proteins VP1 and VP3 and promotes their stability by inhibiting proteasomal degradation, thereby facilitating the assembly of DHAV-1 virions. This study demonstrates the specific role of HSP70 in regulating DHAV-1 replication, which are helpful for understanding the pathogenesis of DHAV-1 infection and provide additional information about the role of HSP70 in infection by different kinds of picornaviruses, as well as the interaction between picornaviruses and host cells.

Unique solvation structure induced by anionic Cl in aqueous zinc ion batteries.

Aqueous zinc ion batteries (AZIBs) have garnered significant attention in large-scale static energy storage battery systems due to their low cost, high safety and environmental friendliness. However, it has some inherent problems during operation, such as the occurrence of side reactions (hydrogen evolution reaction, HER) and anode corrosion, formation of by-products and growth of metal dendrites. To analyze the mechanism of generation from aspect of the electrolyte solvation structure and make cell efficiency further improvements based on it, so we use DFT calculations to find the most stable solvation structure in AZIBs with ZnCl2 as the electrolyte and analyze it. We define the relative concentration Cr, and calculate different groups metal cation cluster structures such as [Zn(H2O)n]2+, [ZnCl(H2O)n]+, [ZnCl2(H2O)n] and [ZnCl3(H2O)n]- that exist at different Cr. We discuss the effect of different clusters formed due to the Cr variations on the battery performance in terms of three aspects: the structural conformation, the cluster characteristics (including the hydrogen bonding network, bond lengths, bond angles, as well as the electrostatic potential ESP) and the cluster performance (including the adsorption energy Ea, binding energy Eb, and desolvation energy Edes). The results shows that the electrolyte metal cation Zn2+ can be coordinated with up to six H2O molecules in first shell, and this metal cation solvation structure contributes to the occurrence and formation of side reactions and by-products, which reduces the battery efficiency. Increasing the electrolyte anion Cl- concentration by appropriately increasing the Cr helps to desolvate the metal cation cluster structure, which greatly improves the battery efficiency and suppresses the side reactions and by-products. Yet the improvement effect was not obviously further improved by further increasing the Cl- concentration.

E-M349E and NS2A/2B-P1(T) are compensatory mutations of rDTMUV-NS2AB-P1P1'(AA), which regain virus proliferation by enhancing the virus package and restoring NS2A/2B cleavage.

Duck Tembusu virus (DTMUV) belongs to the Flaviviridae family and mainly infects ducks. The genome of DTMUV is translated into a polyprotein, which is further cleaved into several protein by viral NS2B3 protease and host proteases. Crucially, the cleavage of the NS2A/2B precursor during this process is essential for the formation of replication complexes and viral packaging. Previous research has demonstrated that alanine mutations in NS2A/2B (P1P1' (AA)) result in an attenuated strain (rDTMUV-NS2A/2B-P1P1' (AA)) by disrupting NS2A/2B cleavage. In this study, we investigate the effects of the P1P1' (AA) mutation on the viral life cycle and explore compensatory mutations in rDTMUV-NS2A/2B-P1P1' (AA). Infected ducklings exhibit similar body weight gain and viral tissue loads to DTMUV-WT. Compensatory mutations E-M349E and P1(T) emerge, restoring proliferation levels to those of rDTMUV-WT. Specifically, E-M349E enhances viral packaging, while P1(T) reinstates NS2A/2B proteolysis in vitro. Thus, our findings reveal novel compensatory sites capable of restoring the attenuated DTMUV during polyprotein cleavage and packaging.

Functions of tensile and compressive strain on electronic and optical properties of B-doped monolayer arsenene.

CONTEXT: The structurals stability, electronic structure, density of states (DOS), and optical properties of B-doped arsenene under biaxial tensile and compressive strains were investigated using density functional theory (DFT) calculations. The doping system was found to exhibit good stability. The introduction of B atom transformed the originally indirect band gap of arsenene into a direct band gap. Under compressive strain, the band gap remained direct, gradually decreasing in value. In contrast, under tensile strain, the direct band gap occurred a transition into an indirect band gap, of which value initially increasing and then decreasing with an increasing strain. The static dielectric constant was increased under both compressive and tensile strains, but compressive strain had a stronger effect. Compressive strain led to an increase in the imaginary peak of the dielectric function, while tensile strain resulted in a decrease. Moreover, as compressive strain increased, the absorption and loss function peak initially blue-shifted and then red-shifted, while tensile strain caused a gradual red-shift of the absorption peak. METHOD: All DFT calculations were performed using Quantum Espresso software; the structures were optimized using generalized gradient approximation (GGA-PBE), and electronic structure and optical properties are performed using Heyd-Sceria-Ernzerhof (HSE06). The cut-off energy was set as 70 Ry, the Monkhorst-Pack grid was set to 10 × 10 × 1, the atomic convergence criterion was set as 1.0 × 10-6 Ry, and the convergence criterion of interatomic force was set as 1.0 × 10-4 Ry/Bohr.

JWA binding to NCOA4 alleviates degeneration in dopaminergic neurons through suppression of ferritinophagy in Parkinson's disease.

Parkinson's disease (PD) poses a significant challenge in neurodegenerative disorders, characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). The intricate mechanisms orchestrating DA neurodegeneration in PD are not fully understood, necessitating the exploration of innovative therapeutic approaches. Recent studies have implicated ferroptosis as a major contributor to the loss of DA neurons, revealing a complex interplay between iron accumulation and neurodegeneration. However, the sophisticated nature of this process challenges the conventional belief that mere iron removal could effectively prevent DA neuronal ferroptosis. Here, we report JWA, alternatively referred to as ARL6IP5, as a negative regulator of ferroptosis, capable of ameliorating DA neuronal loss in the context of PD. In this study, synchronized expression patterns of JWA and tyrosine hydroxylase (TH) in PD patients and mice were observed, underscoring the importance of JWA for DA neuronal survival. Screening of ferroptosis-related genes unraveled the engagement of iron metabolism in the JWA-dependent inhibition of DA neuronal ferroptosis. Genetic manipulation of JWA provided compelling evidence linking its neuroprotective effects to the attenuation of NCOA4-mediated ferritinophagy. Molecular docking, co-immunoprecipitation, and immunofluorescence studies confirmed that JWA mitigated DA neuronal ferroptosis by occupying the ferritin binding site of NCOA4. Moreover, the JWA-activating compound, JAC4, demonstrated promising neuroprotective effects in cellular and animal PD models by elevating JWA expression, offering a potential avenue for neuroprotection in PD. Collectively, our work establishes JWA as a novel regulator of ferritinophagy, presenting a promising therapeutic target for addressing DA neuronal ferroptosis in PD.

2D Exfoliation Chemistry Towards Covalent Pseudo-Layered Phosphate Framework Derived by Radical/Strain-Synergistical Process.

2D compounds exfoliated from weakly bonded bulk materials with van der Waals (vdW) interaction are easily accessible. However, the strong internal ionic/covalent bonding of most inorganic crystal frameworks greatly hinders 2D material exfoliation. Herein, we first proposed a radical/strain-synergistic strategy to exfoliate non-vdW interacting pseudo-layered phosphate framework. Specifically, hydroxyl radicals (•OH) distort the covalent bond irreversibly, meanwhile, H2O molecules as solvents, further accelerating interlayered ionic bond breakage but mechanical expansion. The innovative 2D laminar NASICON-type Na3V2(PO4)2O2F crystal, exfoliated by •OH/H2O synergistic strategy, exhibits enhanced sodium-ion storage capacity, high-rate performance (85.7 mA h g-1 at 20 C), cyclic life (2300 cycles), and ion migration rates, compared with the bulk framework. Importantly, this chemical/physical dual driving technique realized the effective exfoliation for strongly coupled pseudo-layered frameworks, which accelerates 2D functional material development.

Dynamic monitoring soft tissue healing via visualized Gd-crosslinked double network MRI microspheres.

By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K2 (SL)6 K2 (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.

Integrative and conjugative elements of Pasteurella multocida: Prevalence and signatures in population evolution.

Pasteurella multocida (P. multocida) is a bacterial pathogen responsible for a range of infections in humans and various animal hosts, causing significant economic losses in farming. Integrative and conjugative elements (ICEs) are important horizontal gene transfer elements, potentially enabling host bacteria to enhance adaptability by acquiring multiple functional genes. However, the understanding of ICEs in P. multocida and their impact on the transmission of this pathogen remains limited. In this study, 42 poultry-sourced P. multocida genomes obtained by high-throughput sequencing together with 393 publicly available P. multocida genomes were used to analyse the horizontal transfer of ICEs. Eighty-two ICEs were identified in P. multocida, including SXT/R391 and Tn916 subtypes, as well as three subtypes of ICEHin1056 family, with the latter being widely prevalent in P. multocida and carrying multiple resistance genes. The correlations between insertion sequences and resistant genes in ICEs were also identified, and some ICEs introduced the carbapenem gene blaOXA-2 and the bleomycin gene bleO to P. multocida. Phylogenetic and collinearity analyses of these bioinformatics found that ICEs in P. multocida were transmitted vertically and horizontally and have evolved with host specialization. These findings provide insight into the transmission and evolution mode of ICEs in P. multocida and highlight the importance of understanding these elements for controlling the spread of antibiotic resistance.

Effects of esketamine and fluoxetine on depression-like behaviors in chronic variable stress: a role of plasma inflammatory factors.

Mounting evidence has identified the rapid and sustained antidepressive and anxiolytic-like effects of esketamine. However, the underlying mechanism of this no-monoamine target rapid-onset antidepressant is still underexplored. Immune-inflammatory pathways and cell-mediated immune activation, mainly including inflammatory cytokines in plasma, play a pivotal role in the pathogenesis of major depressive disorder and are also a potential therapeutic target for MDD. The current study was designed to clarify the role of esketamine on the expression of plasma cytokines in a depressive-like model introduced by chronic variable stress (CVS). In this study, a 21-day consecutive CVS protocol was applied to produce depressive- and anxiety-like behaviors. After the single dose or 7-day repeated administration of esketamine or fluoxetine, the depressive- and anxiety-like behaviors and the expression of inflammatory cytokines in plasma were examined. Both a single dose of esketamine and 7-days repeated fluoxetine administration elicited anti-depressive and anxiolytic effects in mice exposed to CVS. Additionally, CVS produced significant changes in the plasma inflammatory factors, notably increasing the expression of IL-1ß, IL-6, IL-8, IL-17A, TNFα, IL-4, IL-9, IL-24, IL-37, IFN-ß, and CXCL12, while reducing IL-10 and IL-33. With the administration of esketamine and fluoxetine, CVS-produced inflammatory disturbances were partially normalized. Together, our findings provide a novel insight that acute esketamine treatment could rescue CVS-produced depressive-like and anxiety-like behaviors in mice by normalizing the expression of inflammatory cytokines; this effect was similar to the repeated administration of fluoxetine. These results contributed to the understating of rapid anti-depressant effects elicited by esketamine.

Multiple functions of the nonstructural protein 3D in picornavirus infection.

3D polymerase, also known as RNA-dependent RNA polymerase, is encoded by all known picornaviruses, and their structures are highly conserved. In the process of picornavirus replication, 3D polymerase facilitates the assembly of replication complexes and directly catalyzes the synthesis of viral RNA. The nuclear localization signal carried by picornavirus 3D polymerase, combined with its ability to interact with other viral proteins, viral RNA and cellular proteins, indicate that its noncatalytic role is equally important in viral infections. Recent studies have shown that 3D polymerase has multiple effects on host cell biological functions, including inducing cell cycle arrest, regulating host cell translation, inducing autophagy, evading immune responses, and triggering inflammasome formation. Thus, 3D polymerase would be a very valuable target for the development of antiviral therapies. This review summarizes current studies on the structure of 3D polymerase and its regulation of host cell responses, thereby improving the understanding of picornavirus-mediated pathogenesis caused by 3D polymerase.

Iron efflux by IetA enhances ß-lactam aztreonam resistance and is linked to oxidative stress through cellular respiration in Riemerella anatipestifer.

BACKGROUND: Riemerella anatipestifer encodes an iron acquisition system, but whether it encodes the iron efflux pump and its role in antibiotic resistance are largely unknown. OBJECTIVES: To screen and identify an iron efflux gene in R. anatipestifer and determine whether and how the iron efflux gene is involved in antibiotic resistance. METHODS: In this study, gene knockout, streptonigrin susceptibility assay and inductively coupled plasma mass spectrometry were used to screen for the iron efflux gene ietA. The MIC measurements, scanning electron microscopy and reactive oxygen species (ROS) detection were used to verify the role of IetA in aztreonam resistance and its mechanism. Mortality and colonization assay were used to investigate the role of IetA in virulence. RESULTS: The deletion mutant ΔietA showed heightened susceptibility to streptonigrin, and prominent intracellular iron accumulation was observed in ΔfurΔietA under excess iron conditions. Additionally, ΔietA exhibited increased sensitivity to H2O2-produced oxidative stress. Under aerobic conditions with abundant iron, ΔietA displayed increased susceptibility to the ß-lactam antibiotic aztreonam due to heightened ROS production. However, the killing efficacy of aztreonam was diminished in both WT and ΔietA under anaerobic or iron restriction conditions. Further experiments demonstrated that the efficiency of aztreonam against ΔietA was dependent on respiratory complexes Ⅰ and Ⅱ. Finally, in a duckling model, ΔietA had reduced virulence compared with the WT. CONCLUSION: Iron efflux is critical to alleviate oxidative stress damage and ß-lactam aztreonam killing in R. anatipestifer, which is linked by cellular respiration.

The topological model of NS4B and its TMD3 in duck TMUV proliferation.

Duck Tembusu virus (DTMUV) belongs to the Flaviviridae family and mainly infects ducks. Duck Tembusu virus genome encodes one polyprotein that undergoes cleavage to produce 10 proteins. Among these, NS4B, the largest transmembrane protein, plays a crucial role in the viral life cycle. In this study, we investigated the localization of NS4B and found that it is located in the endoplasmic reticulum, where it co-localizes with DTMUV dsRNA. Subsequently, we confirmed 5 different transmembrane domains of NS4B and discovered that only its transmembrane domain 3 (TMD3) can traverse ER membrane. Then mutations were introduced in the conserved amino acids of NS4B TMD3 of DTMUV replicon and infectious clone. The results showed that V111G, V117G, and I118G mutations enhanced viral RNA replication, while Q104A, T106A, A113L, M116A, H120A, Y121A, and A122G mutations reduced viral replication. Recombinant viruses with these mutations were rescued and studied in BHK21 cells. The findings demonstrated that A113L and H120A mutations led to higher viral titers than the wild-type strain, while Q104A, T106A, V111G, V117G, and Y121A mutations attenuated viral proliferation. Additionally, H120A, M116A, and A122G mutations enhanced viral proliferation. Furthermore, Q104A, T106A, V111G, M116A, V117G, Y121A, and A122G mutants showed reduced viral virulence to 10-d duck embryos. Animal experiments further indicated that all mutation viruses resulted in lower genome copy numbers in the spleen compared to the WT group 5 days postinfection. Our data provide insights into the topological model of DTMUV NS4B, highlighting the essential role of NS4B TMD3 in viral replication and proliferation.

Three-dimensional texture analyses of multi-quantitative relaxation time maps for evaluating cartilage repair with the treatment of allogeneic human adipose-derived mesenchymal progenitor cells.

BACKGROUND: To explore the ability of three-dimensional texture analyses based on gray-level run-length matrix (GLRLM) for examining the spatial distribution of pixel values on magnetic resonance imaging (MRI) relaxation time maps and detecting the compositional variation of cartilage repair following treatment with allogeneic human adipose-derived mesenchymal progenitor cells (haMPCs). METHODS: Participants with knee osteoarthritis were randomly divided into three groups with intra-articular haMPCs injections: low-, medium-, and high-dose groups. We analyzed five GLRLM parameters in the T1rho, T2 and T2star maps, including run length non-uniformity (RLNonUni), gray-level non-uniformity (GLevNonU), long run emphasis (LngREmph), short run emphasis (ShrtREmp), and fraction of images in runs. We used the relative D values (the ratio of difference values to baseline) as the objective to avoid errors caused by individual differences. We calculated the two-tailed Pearson's linear correlation coefficient (r) to investigate the correlations of the texture parameters with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. RESULTS: Compared with the base time, significant reduction of WOMAC score was observed in both high and medium doses groups at terminal time, indicating relief of pain symptoms in high and medium groups with the treatment of allogeneic haMPCs. Significant differences were observed in the GLRLM parameters of cartilage MR relaxation time maps in different doses groups. In both T1rho and T2 relaxation time maps, the high-dose group showed significant increases in relative D values of RLNonUni, GLevNonU, LngREmph and ShrtREmp, which indicated significant changes in the uniformity of relaxation time maps. For T2star map, GLRLM parameters such as GLevNonU and ShrtREmp, especially LngREmph, showed significant increases in relative D values in high-dose group. Among all GLRLM features, LngREmph of three relaxation time maps had performed excellent linear correlations with WOMAC scores. CONCLUSIONS: Texture analysis of the cartilage may allow the detection of compositional variation in cartilage repair with the treatment of allogeneic haMPCs. This technique displays potential applications in understanding the mechanism of stem cell repair of the cartilage and assessing the treatment response.

Theoretical study on the role of magnesium chloride complexes induced by different magnesium-to-chlorine ratios in magnesium-sulfur batteries.

In magnesium-sulfur batteries, electrolyte exploration is vital for developing high-energy-density, safe, and reliable batteries. This study focused on cyclic THF and chain DME, representative solvents in ether electrolytes. MgCl2, an ideal anionic salt, forms mono-nuclear (MgCl2(DME)2), bi-nuclear ([Mg2(µ-Cl)2(DME)4]2+), and tri-nuclear ([Mg3(µ-Cl)4(DME)5]2+) complexes in DME. With increasing salt concentration, these complexes sequentially form. Under lower salt concentrations, THF and MgCl2 form mono-nuclear complexes ([MgCl2(THF)4]) and continue to form bi-nuclear complexes ([Mg2(µ-Cl)3(THF)6]+). However, at higher salt concentrations, bi-nuclear complexes ([Mg2(µ-Cl)3(THF)6]+) directly form in THF. Comparing HOMO-LUMO values, [Mg(DME)3]2+ is easily oxidized. Energy gaps decrease with Cl- ion addition, enhancing solution conductivity. Ratios of Mg2+ and Cl- in S-reduction complexes differ, suggesting DME is better at a low Mg/Cl ratio, and THF at a high Mg/Cl ratio. This study contributes to understanding complexes and enhancing Mg-S battery performance.

Porous and graphitic carbon nanosheets with controllable structure for zinc-ion hybrid capacitor.

The imbalances of storage capacity and reaction kinetics between carbonaceous cathodes and zinc (Zn) anodes restrict the widespread application of Zn-ion hybrid capacitor (ZIHC). Structure optimization is a promising strategy for carbon materials to achieve sufficient Zn2+ storage sites and satisfied ion-electron kinetics. Herein, porous graphitic carbon nanosheets (PGCN) were simply synthesized using a K3[Fe(C2O4)3]- and urea-assisted foaming strategy with polyvinylpyrrolidone as carbon precursor, followed by activation and graphitization. Sufficient pores with well-matched pore sizes (0.80-1.94 nm) distributed across the carbon nanosheets can effectively shorten mass-transfer distance, promoting accessibility to active sites. A partially graphitic carbon structure with high graphitization degree can accelerate electron transfer. Furthermore, high nitrogen doping (7.2 at.%) provides additional Zn2+ storage sites to increase storage capacity. Consequently, a PGCN-based ZIHC has an exceptional specific capacity of 181 mAh g-1 at 0.5 A g-1, superb energy density of 145 Wh kg-1, and excellent cycling ability without capacity decay over 10,000 cycles. In addition, the flexible solid-state device assembled with PGCN exhibits excellent electrochemical performances even when bent at various angles. This study proposes a straightforward and economical strategy to construct porous graphitic carbon nanosheets with enhanced storage capacity and fast reaction kinetics for the high performance of ZIHC.

Jiangu formula: A novel osteoclast-osteoblast coupling agent for effective osteoporosis treatment.

BACKGROUND: The discovering of an osteoclast (OC) coupling active agent, capable of suppressing OC-mediated bone resorption while concurrently stimulating osteoblast (OB)-mediated bone formation, presents a promising strategy to overcome limitations associated with existing antiresorptive agents. However, there is a lack of research on active OC coupling agents. PURPOSE: This study aims to investigate the potential of Jiangu Formula (JGF) in inhibiting OCs while maintaining the OCOB coupling function. METHODS: The anti-osteoporosis efficacy of JGF was evaluated in osteoporosis models induced by ovariectomy in C57BL/6 mouse and SD rats. The effect of JGF on OCs was evaluated by detecting its capacity to inhibit OC differentiation and bone resorption in an in vitro osteoclastogenesis model induced by RANKL. The OCOB coupling activity of JGF was evaluated by measuring the secretion levels of OC-derived coupling factors, OB differentiation activity of MC3T3-E1 interfered with conditioned medium, and the effect of JGF on OC inhibition and OB differentiation in a C3H10T1/2-RAW264.7 co-culture system. The mechanism of JGF was studied by network pharmacology and validated using western blot, immunofluorescence (IF), and ELISA. Following that, the active ingredients of JGF were explored through a chemotype-assembly approach, activity evaluation, and LC-MS/MS analysis. RESULTS: JGF inhibited bone resorption in murine osteoporosis without compromising the OCOB coupling effect on bone formation. In vitro assays showed that JGF preserved the coupling effect of OC on OB differentiation by maintaining the secretion of OC-derived coupling factors. Network analysis predicted STAT3 as a key regulation point for JGF to exert anti-osteoporosis effect. Further validation assays confirmed that JGF upregulated p-STAT3(Ser727) and its regulatory factors IL-2 in RANKL-induced RAW264.7 cells. Moreover, 23 components in JGF with anti-OC activity identified by chemotype-assembly approach and verification experiments. Notably, six compounds, including ophiopogonin D, ginsenoside Re, ginsenoside Rf, ginsenoside Rg3, ginsenoside Ro, and ononin were identified as OC-coupling compounds. CONCLUSION: This study first reported JGF as an agent that suppresses bone loss without affecting bone formation. The potential coupling mechanism of JGF involves the upregulation of STAT3 by its regulators IL-2. Additionally, the chemotype-assembly approach elucidated the activity compounds present in JGF, offering a novel strategy for developing an anti-resorption agent that preserves bone formation.

Molecular characterization of a virulent goose astrovirus genotype-2 with high mortality in vitro and in vivo.

Goose astrovirus (GAstV) is a newly identified viral pathogen threatening waterfowl, exhibiting a high prevalence across various regions in China. Notably, the Guanghan District of Deyang City, situated in Sichuan Province, has faced a outbreak of GAstV, resulting in significant mortality among goslings due to the induction of gout-like symptoms. In our research, we successfully isolated a GAstV strain known as GAstV SCG3. This strain exhibits efficient replication capabilities, proving virulent in goslings and goose embryos. Our study delved into the characteristics of GAstV SCG3 both in vitro and in vivo. Additionally, we examined tissue phagocytosis and the distribution of GAstV SCG3 in deceased goslings using H&E staining and IHC techniques. According to the classification established by the ICTV, GAstV SCG3 falls under the category of GAstV genotype-2. Notably, it demonstrates the highest homology with the published AHAU5 sequences, reaching an impressive 98%. Furthermore, our findings revealed that GAstV SCG3 exhibits efficient proliferation exclusively in goose embryos and in LMH cells, while not manifesting in seven other types of avian and mammalian cells. Significantly, the mortality of GAstV on goslings and goose embryos are 93.1 and 80%, respectively. Moreover, the viral load in the livers of infected goslings surpasses that in the kidneys when compared with the attenuated strain GAstV SCG2. The mortality of GAstV is usually between 20% and 50%, our study marks the first report of a virulent GAstV strain with such a high mortality.

Intraoperative application of intelligent, responsive, self-assembling hydrogel rectifies oxygen and energy metabolism in traumatically injured brain.

In managing severe traumatic brain injury (TBI), emergency surgery involving the removal of damaged brain tissue and intracerebral hemorrhage is a priority. Secondary brain injury caused by oxidative stress and energy metabolic disorders, triggered by both primary mechanical brain damage and surgical insult, is also a determining factor in the prognosis of TBI. Unfortunately, the effectiveness of traditional postoperative intravenous neuroprotective agents therapy is often limited by the lack of targeting, timeliness, and side effects when neuroprotective agents systemically delivered. Here, we have developed injectable, intelligent, self-assembling hydrogels (P-RT/2DG) that can achieve precise treatment through intraoperative application to the target area. P-RT/2DG hydrogels were prepared by integrating a reactive oxygen species (ROS)-responsive thioketal linker (RT) into polyethylene glycol. By scavenging ROS and releasing 2-deoxyglucose (2DG) during degradation, these hydrogels functioned both in antioxidation and energy metabolism to inhibit the vicious cycle of post-TBI ROS-lactate which provoked secondary injury. In vitro and in vivo tests confirmed the absence of systemic side effects and the neuroprotective function of P-RT/2DG hydrogels in reducing edema, nerve cell apoptosis, neuroinflammation, and maintaining the blood-brain barrier. Our study thus provides a potential treatment strategy with novel hydrogels in TBI.

Oxidative Modification, Structural Conformation, and Gel Properties of Pork Paste Protein Mediated by Oxygen Concentration in Modified Atmosphere Packaging.

The objective of this study was to investigate the effect of pork oxidation through modified atmosphere packaging (MAP) on gel characteristics of myofibrillar proteins (MP) during the heat-induced gelation process. The pork longissimus thoracis (LT) was treated by MAP at varying oxygen concentrations (0, 20, 40, 60, and 80% O2) with a 5-day storage at 4 °C for the detection of MP oxidation and gel properties. The findings showed the rise of O2 concentration resulted in a significant increase of carbonyl content, disulfide bond, and particle size, and a decrease of sulfhydryl content and MP solubility (p < 0.05). The gel textural properties and water retention ability were significantly improved in MAP treatments of 0-60% O2 (p < 0.05), but deteriorated at 80% O2 level. As the concentration of O2 increased, there was a marked decrease in the α-helix content within the gel, accompanied by a simultaneous increase in ß-sheet content (p < 0.05). Additionally, a judicious oxidation treatment (60% O2 in MAP) proved beneficial for crafting dense and uniform gel networks. Our data suggest that the oxidation treatment of pork mediated by O2 concentration in MAP is capable of reinforcing protein hydrophobic interaction and disulfide bond formation, thus contributing to the construction of superior gel structures and properties.