Application and antagonistic mechanisms of atoxigenic Aspergillus strains for the management of fungal plant diseases.

This review covers, for the first time, all methods based on the use of Aspergillus strains as biocontrol agents for the management of plant diseases caused by fungi and oomycetes. Atoxigenic Aspergillus strains have been screened in a variety of hosts, such as peanuts, maize kernels, and legumes, during the preharvest and postharvest stages. These strains have been screened against a wide range of pathogens, such as Fusarium, Phytophthora, and Pythium species, suggesting a broad applicability spectrum. The highest efficacies were generally observed when using non-toxigenic Aspergillus strains for the management of mycotoxin-producing Aspergillus strains. The modes of action included the synthesis of antifungal metabolites, such as kojic acid and volatile organic compounds (VOCs), secretion of hydrolytic enzymes, competition for space and nutrients, and induction of disease resistance. Aspergillus strains degraded Sclerotinia sclerotiorum sclerotia, showing high control efficacy against this pathogen. Collectively, although two Aspergillus strains have been commercialized for aflatoxin degradation, a new application of Aspergillus strains is emerging and needs to be optimized.

Construction of recombinant Marek's disease virus co-expressing σB and σC of avian reoviruses.

Avian reoviruses (ARVs) cause viral arthritis or tenosynovitis, resulting in poor weight gain and increased feed conversion ratios in chickens. In this study, we generated three Marek's disease virus (MDV) recombinants, namely, rMDV-ARV-σB, rMDV-ARV-σC, and rMDV-ARV-σB + C, expressing ARV σB, σC, and both σB and σC, respectively. In rMDV-ARV-σB and rMDV-ARV-σC, the σB or σC gene was inserted into the US2 gene of MDV vaccine strain 814 using a fosmid-based rescue system. In rMDV-ARV-σB + C, the σB and σC genes were cloned into different expression cassettes, which were co-inserted into the US2 gene of the MDV 814 strain. In infected chicken embryo fibroblasts (CEFs), the recombinant virus rMDV-ARV-σB expressed σB, rMDV-ARV-σC expressed σC, and the rMDV-ARV-σB + C virus simultaneously expressed σB and σC. These recombinant viruses exhibited growth kinetics in CEFs similar to those of the parent MDV, and the inserted genes were stably maintained and expressed in the recombinant MDVs after 20 passages in cell cultures. These recombinant MDVs expressing σB and σC will provide potential vaccines against ARV infection in chickens.

Comprehensive analysis of the Lycopodium japonicum mitogenome reveals abundant tRNA genes and cis-spliced introns in Lycopodiaceae species.

Lycophytes and ferns represent one of the earliest-diverging lineages of vascular plants, with the Lycopodiaceae family constituting the basal clade among lycophytes. In this research, we successfully assembled and annotated the complete Lycopodium japonicum Thunb. (L. japonicum) mitochondrial genome (mitogenome) utilizing PacBio HiFi sequencing data, resulting in a single circular molecule with a size of 454,458 bp. 64 unique genes were annotated altogether, including 34 protein-coding genes, 27 tRNAs and 3 rRNAs. It also contains 32 group II introns, all of which undergo cis-splicing. We identified 195 simple sequence repeats, 1,948 dispersed repeats, and 92 tandem repeats in the L. japonicum mitogenome. Collinear analysis indicated that the mitogenomes of Lycopodiaceae are remarkably conserved compared to those of other vascular plants. We totally identified 326 RNA editing sites in 31 unique protein-coding genes with 299 sites converting cytosine to uracil and 27 sites the reverse. Notably, the L. japonicum mitogenome has small amounts foreign DNA from plastid or nuclear origin, accounting for only 2.81% of the mitogenome. The maximum likelihood phylogenetic analysis based on 23 diverse land plant mitogenomes and plastid genomes supports the basal position of lycophytes within vascular plants and they form a sister clade to all other vascular lineages, which is consistent with the PPG I classification system. As the first reported mitogenome of Lycopodioideae subfamily, this study enriches our understanding of Lycopodium mitogenomes, and sets the stage for future research on mitochondrial diversity and evolution within the lycophytes and ferns.

Recombinant Marek's disease virus type 1 provides full protection against H9N2 influenza A virus in chickens.

The H9N2 subtype of the avian influenza virus (AIV) poses a significant threat to the poultry industry and human health. Recombinant vaccines are the preferred method of controlling H9N2 AIV, and Marek's disease virus (MDV) is the ideal vector for recombinant vaccines. During this study, we constructed two recombinant MDV type 1 strains that carry the hemagglutinin (HA) gene of AIV to provide dual protection against both AIV and MDV. To assess the effects of different MDV insertion sites on the protective efficacy of H9N2 AIV, the HA gene of H9N2 AIV was inserted in UL41 and US2 of the MDV type 1 vector backbone to obtain recombinant viruses rMDV-UL41/HA and rMDV-US2/HA, respectively. An indirect immunofluorescence assay showed sustained expression of HA protein in both recombinant viruses. Additionally, the insertion of the HA gene in UL41 and US2 did not affect MDV replication in cell cultures. After immunization of specific pathogen-free chickens, although both the rMDV-UL41/HA and rMDV-US2/HA groups exhibited similar levels of hemagglutination inhibition antibody titers, only the rMDV-UL41/HA group provided complete protection against the H9N2 AIV challenge, and also offered complete protection against challenge with MDV. These results demonstrated that rMDV-UL41/HA could be used as a promising bivalent vaccine strain against both H9N2 avian influenza and Marek's disease in chickens.

Left-behind experience and mobile phone addiction among college students: A moderated mediation of social anxiety and sex.

Background: With the popularity of smartphone among Chinese college students, mobile phone addiction (MPA) is emerging a remarkable behavior problem in this population. Thus, the present study was aimed at investigating a moderated mediation model of left-behind experience (LBE) affecting MPA via social anxiety moderated by sex difference. Methods: A total of 1268 college students (Mage = 20.74, SD = 2.21) were recruited to complete self-administered questionnaires of mobile phone addiction index (MPAI) and interaction anxiousness scale (IAS). The participants also reported their sex, grade, and childhood and juvenile LBE. Results: The results indicated that LBE increased the level of MPA among college students via mediation by social anxiety. Furthermore, sex moderated the influence of social anxiety on MPA in the mediating model. Specifically, social anxiety affects male college students more strongly than female ones in terms of MPA. Conclusion: Our findings support that LBE, social anxiety, and sex difference should be critically included into consideration when performing interventions to buffer MPA among college students.

Ligilactobacillus salivarius XP132 with antibacterial and immunomodulatory activities inhibits horizontal and vertical transmission of Salmonella Pullorum in chickens.

Probiotics are increasingly recognized for their capacity to combat pathogenic bacteria. In this study, we isolated a strain of Ligilactobacillus salivarius XP132 from the gut microbiota of healthy chickens. This strain exhibited resistance to low pH and bile salts, auto-aggregation capabilities, and the ability to co-aggregate with pathogenic Salmonella. The in vitro antibacterial activity of Ligilactobacillus salivarius XP132 was tested using an Oxford cup antibacterial test, and the results showed that Ligilactobacillus salivarius XP132 exhibited broad-spectrum antibacterial activity, with especially strong antibacterial activity against Salmonella. In animal experiments with white feather broilers and specific-pathogens-free (SPF) chickens, we orally administered 1 × 109 CFU XP132 live bacteria per chicken per day, and detected the content of Salmonella in the liver, spleen, intestinal contents, and eggs of the chickens by RT-qPCR. Oral administration of Lactobacillus salivarius XP132 group significantly reduced the levels of Salmonella in chicken liver, spleen, intestinal contents and eggs, and the oral administration of Ligilactobacillus salivarius XP132 significantly inhibited the horizontal and vertical transmission of Salmonella in SPF chickens and white-feathered broilers. After oral administration of XP132, the production of chicken serum anti-infective cytokine IFN-γ was also significantly up-regulated, thereby enhancing the host's ability to resist infection. In addition, the production of various serum inflammatory cytokines, including IL-1ß, IL-6, IL-8, and TNF-α, was down-regulated, leading to significant amelioration of the inflammatory response induced by S. Pullorum in chickens. These findings suggest that Ligilactobacillus salivarius XP132 possesses potent antibacterial and immunomodulatory properties that effectively prevent both horizontal and vertical transmission of Salmonella Pullorum, highlighting its potential as a valuable tool for the prevention and control of Salmonella disease.

The Impact of Early Antibiotic Use on Clinical Outcomes of Patients Hospitalized with COVID-19: A Propensity Score-Matched Analysis.

Purpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown. Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness. Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246-4.060), p = 1.000) and ICU admission (HR=0.436(0.093-2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296-1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221-8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort. Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.

Dipicolinic acid reduces Epicoccum sorghinum symptoms on maize and inhibits tenuazonic acid biosynthesis.

BACKGROUND: Epicoccum sorghinum is a pathogenic fungus that causes leaf spot in a wide range of plants, including maize, and synthesizes the mycotoxin tenuazonic acid (TEA), which is carcinogenic. Despite the relevant economic and yield losses caused by E. sorghinum worldwide, methods for the control of this pathogen are lacking. RESULTS: In this work, the efficacy of Bacillus-produced dipicolinic acid (DPA) for control of E. sorghinum was evaluated using in vitro and in vivo assays, and compared with the efficacy of three commercial fungicides, including carbendazim, prochloraz, and thiram. DPA inhibited E. sorghinum mycelial growth, and conidia germination, and produced important alterations in E. sorghinum hyphae. Interestingly, 10 mM DPA reduced TEA biosynthesis by 86.6%. Although DPA rapidly degraded on maize leaves, 10 mM DPA showed higher preventive (67.4% lesion length inhibition) and inhibitory (89.5% lesion length inhibition) efficacies for the control of E. sorghinum on maize leaves compared to the commercial fungicides. CONCLUSIONS: Collectively, this study presents the first method for the control of E. sorghinum on maize and demonstrates that DPA application is a suitable approach to inhibit E. sorghinum symptoms in plants and TEA biosynthesis. © 2024 Society of Chemical Industry.

Germination time and in vitro gastrointestinal digestion impact on the isoflavone bioaccessibility and antioxidant capacities of soybean sprouts.

Soybeans' isoflavone content increases with germination; nevertheless, their bioaccessibility in the gastrointestinal system is limited. This study evaluated the influence of germination time (1, 3, 5, and 7 days) and in vitro gastrointestinal conditions on the isoflavone profile of soybean sprouts. The total isoflavones (4.07 mg/g) and the malonyl genistin (1.37 mg/g) had the highest contents on day 5 in the gastric phase. The highest isoflavone bioaccessibility was observed in daidzein, genistein, and glycitin. An increase in antioxidant capacity was found during germination (day 7 > day 5 > day 3); however, the same trend was not observed during in vitro digestion. In summary, the results indicate that soybean sprouts germinated for 5 days may be more beneficial for consumption since they have the highest and most readily absorbed levels of isoflavones. These data suggest that soybean sprouts may be a functional food that provides bioavailable antioxidants.

Psychometric properties of anxiety sensitivity Index-3 among Chinese college students and its preliminary application among this population experiencing campus lockdown.

PURPOSE: Anxiety sensitivity (AS) refers to fear of anxiety-related sensory arousal and has been revealed to be associated with increased psychological distress and mental problems. Although Anxiety Sensitivity Index-3 (ASI-3) has been confirmed to be effective in evaluating this construct, whether it is consistently applicable in college students is still elusive. The present study aimed to examine the psychometric properties and measurement invariance of Chinese version of ASI-3 (C-ASI-3) among college students experiencing campus lockdown due to novel coronavirus disease 2019 (COVID-19) pandemic. METHODS: A total of 1532 Chinese college students (397, 25.9% males) aged between 16 and 25 were included in this study. Confirmatory factor analysis (CFA) was used to verify the factor structure of C-ASI-3. Multi-group CFA was conducted for analysis of measurement invariance with regard to gender. McDonald's omega values were computed for examination of scale reliability. For criterion, convergent, and divergent validity, average variance extracted (AVE) values for C-ASI-3 subscales, difference between square root of AVE for each factor and inter-factor correlation, as well as pearson correlation and partial correlation between the C-ASI-3 and other three scales, including the Depression, Anxiety, and Stress Scale-21 (DASS-21), the State-Trait Anxiety Inventory (STAI), and the Fear of COVID-19 scale (FCV-19 S) were evaluated. RESULTS: The C-ASI-3 presented a three-factor scale structure with fit indices being as follows: χ2/df = 11.590, CFI = 0.938, RMSEA = 0.083, SRMR = 0.042. Strict measurement invariance was reached across gender. Regarding convergent validity, the C-ASI-3 had a high correlation with the DASS-21 (r = 0.597, p < 0.01) and the STAI (r = 0.504, p < 0.01). All AVE values for C-ASI-3 subscales were above 0.5. In terms of divergent validity, the C-ASI-3 had medium correlation with the FCV-19 S (r = 0.360, p < 0.01). Square of root of AVE for each factor was higher that inter-factor correlation. McDonald's omega values of the three dimensions ranged from 0.898 ~ 0.958. CONCLUSION: The C-ASI-3 has acceptable psychometric properties among college students. College students with different gender have consistent understanding on the scale construct.

Occurrence and management of the emerging pathogen Epicoccum sorghinum.

Epicoccum sorghinum is a notorious fungal pathogen that causes leaf spot symptoms on a wide range of plants, leading to devastating losses in crop production and quality. Here, all reports regarding the occurrence and management of E. sorghinum are covered for the first time. E. sorghinum has been detected in tropical and subtropical climate areas during the rainy season, mainly from March to August, since 2016. Although E. sorghinum shows broad host spectrum, the disease incidence is especially notorious in cereal crops and ornamental plants, suggesting that these plants are especially susceptible. Control methods based on synthetic fungicides, plant extracts, and microbial biocontrol agents have been reported. However, most agents were applied using only in vitro conditions, restricting the information about their actual applicability in field conditions. Additionally, E. sorghinum can colonize cereal grains and synthesize the carcinogenic mycotoxin tenuazonic acid, posing an enormous hazard for human health. Furthermore, although E. sorghinum is an emerging pathogen that is currently causing yield penalties in important crops, there is lack of information about its pathogenic mechanisms and virulence factors, and there is currently no commercial antifungal agent to manage E. sorghinum. Collectively, it is imperative to conduct in vivo studies to determine the efficacy of antifungal agents and the most effective methods of application in order to develop suitable management strategies against E. sorghinum.

Nanostructures and multi-scale aggregation of high ion exchange capacity short-side-chain perfluorosulfonic acid dispersion.

Short-side-chain perfluorosulfonic acid (SSC-PFSA) ionomers with high ion-exchange-capacity are promising candidates for high-temperature proton exchange membranes (PEMs) and catalyst layer (CL) binders. The solution-casting method determines the importance of SSC-PFSA dispersion characteristics in shaping the morphology of PEMs and CLs. Therefore, a thorough understanding of the chain behavior of SSC-PFSA in dispersions is essential for fabricating high-quality PEMs and CLs. In this study, we have employed multiple characterization techniques, including dynamic light scatting (DLS), small-angle X-ray scattering (SAXS), and cryo-transmission electron microscope (Cryo-TEM), to fully study the chain aggregation behaviors of SSC-PFSA in water-ethanol solvents and elucidate the concentration-dependent self-assembly process. In dilute dispersions (2 mg/mL), SSC-PFSA assembles into mono-disperse rod-like aggregates, featuring a twisted fluorocarbon backbone that forms a hydrophobic stem, and the sulfonic acid side chains extending outward to suit the hydrophilic environment. As the concentration increases, the radius of rod particles increases from 1.47 to 1.81 nm, and the mono-disperse rod particles first form a "end-to-end" configuration that doubles length (10 mg/mL), and then transform into a swollen network structure in semi-dilute dispersion (20 mg/mL). This work provides a well-established structure model for SSC-PFSA dispersions, which is the key nanostructure to be inherited by PEMs.

The effect of emotion regulation strategies on nomophobia in college students: The masking role of resilience.

College students have a high prevalence of nomophobia. However, research on the effects of emotion regulation and resilience on nomophobia in China is lacking. This research investigated how cognitive reappraisal and expressive suppression strategies directly and indirectly affect nomophobia through resilience. Therefore, from March to May 2023, 756 university student volunteers (21.4 % men) were selected from a university in northeastern China for a questionnaire survey. Our findings suggest that college students' resilience has a masking effect on the relationship between cognitive reappraisal and nomophobia and can attenuate the negative effect of the frequency of using cognitive reappraisal strategies on nomophobia. The frequency of expressive suppression strategies directly and positively affected nomophobia. Early psychological interventions targeting resilience might be potentially effective in alleviating nomophobia among college students.

Loop PDE of viral capsid protein is involved in immune escape of the emerging novel variant infectious bursal disease virus.

Infectious bursa disease (IBD) is an acute, highly contactable, lethal, immunosuppressive infectious disease caused by the Infectious bursa disease virus (IBDV). Currently, the emerged novel variant IBDV (nVarIBDV) and the sustainedly prevalent very virulent IBDV (vvIBDV) are the two most prevalent strains of IBDV in China. The antigenic properties of the two prevalent strains differed significantly, which led to the escape of nVarIBDV from the immune protection provided by the existing vvIBDV vaccine. However, the molecular basis of the nVarIBDV immune escape remains unclear. In this study, we demonstrated, for the first time, that residues 252, 254, and 256 in the PDE of VP2 are involved in the immune escape of the emerging nVarIBDV. Firstly, the IFA-mediated antigen-antibody affinity assay showed that PBC and PDE of VP2 could affect the affinity of vvIBDV antiserum to VP2, of which PDE was more significant. The key amino acids of PDE influencing the antigen-antibody affinity were also identified, with G254N being the most significant, followed by V252I and I256V. Then the mutated virus with point or combined mutations was rescued by reverse genetics. it was further demonstrated that mutations of V252I, G254N, and I256V in PDE could individually or collaboratively reduce antigen-antibody affinity and interfere with antiserum neutralization, with G254N being the most significant. This study revealed the reasons for the widespread prevalence of nVarIBDV in immunized chicken flocks and provided innovative ideas for designing novel vaccines that match the antigen of the epidemic strain.

Biocontrol Methods for the Management of Sclerotinia sclerotiorum in Legumes: A Review.

Sclerotinia sclerotiorum is an economically damaging fungal pathogen that causes Sclerotinia stem rot in legumes, producing enormous yield losses. This pathogen is difficult to control due to its wide host spectrum and ability to produce sclerotia, which are resistant bodies that can remain active for long periods under harsh environmental conditions. Here, the biocontrol methods for the management of S. sclerotiorum in legumes are reviewed. Bacillus strains, which synthesized lipopeptides and volatile organic compounds, showed high efficacies in soybean plants, whereas the highest efficacies for the control of the pathogen in alfalfa and common bean were observed when using Coniothyrium minitans and Streptomyces spp., respectively. The biocontrol efficacies in fields were under 65%, highlighting the lack of strategies to achieve a complete control. Overall, although most studies involved extensive screenings using different biocontrol agent concentrations and application conditions, there is a lack of knowledge regarding the specific antifungal mechanisms, which limits the optimization of the reported methods.

OASL suppresses infectious bursal disease virus replication by targeting VP2 for degrading through the autophagy pathway.

Infectious bursal disease (IBD) is an acute and fatal immunosuppressive disease caused by infectious bursal disease virus (IBDV). As an obligate intracellular parasite, IBDV infection is strictly regulated by host factors. Knowledge on the antiviral activity and possible mechanism of host factors might provide the theoretical basis for the prevention and control of IBD. In this study, RNA-sequencing results indicated that many host factors were induced by IBDV infection, among which the expression levels of OASL (2´,5´-oligadenylate synthetase-like protein) was significantly upregulated. OASL overexpression significantly inhibited IBDV replication, whereas OASL knockdown promoted IBDV replication. Interestingly, the antiviral ability of OASL was independent of its canonical enzymatic activity, i.e., OASL targeted viral protein VP2 for degradation, depending on the autophagy receptor p62/SQSTM1 in the autophagy pathway. Additionally, the 316 lysine (K) of VP2 was the key site for autophagy degradation, and its replacement with arginine disrupted VP2 degradation induced by OASL and enhanced IBDV replication. Importantly, our results for the first time indicate a unique and potent defense mechanism of OASL against double-stranded RNA virus by interaction with viral proteins, which leads to their degradation. IMPORTANCE: OASL (2´,5´-oligadenylate synthetase-like protein) exhibits broad-spectrum antiviral effects against single-stranded RNA viruses in mammals, potentially serving as a promising target for novel antiviral strategies. However, its role in inhibiting the replication of double-stranded RNA viruses (dsRNA viruses), such as infectious bursal disease virus (IBDV), in avian species remains unclear. Our findings indicated a unique and potent defense mechanism of OASL against dsRNA viruses. It has been previously shown in mammals that OASL inhibits virus replication through increasing interferon production. The groundbreaking aspect of our study is the finding that OASL has the ability to interact with IBDV viral protein VP2 and target it for degradation and thus exerts its antiviral effect. Our results reveal the interaction between avian natural antiviral immune response and IBDV infection. Our study not only enhances our understanding of bird defenses against viral infections but can also inform strategies for poultry disease management.

The first reported pulmonary nocardiosis caused by Nocardia gipuzkoensis resisted to trimethoprim/sulfamethoxazol (TMP-SMZ) in an immunocompetent patient.

OBJECTIVES: Nocardia gipuzkoensis was first described as a novel and distinct species in 2020 by Imen Nouioui and pulmonary nocardiosis associated with N. gipuzkoensis was once reported in two bronchiectasis patients. Noteworthy, both reported N. gipuzkoensis cases showed sensitivity to trimethoprim/sulfamethoxazol (TMP-SMZ), which are usually recommended for empirical therapy. METHODS: We reported the third case of N. gipuzkoensis infection in a 16-year-old girl with chief complaints of cough and persistent chest and back pain. No underlying immuno-suppressive conditions and glucocorticoid use was revealed. Patchy lesions next to the spine and located in the posterior basal segment of the lower lobes of the left lung were seen in thorax computed tomography (CT), but no pathogenic bacteria were detected according to routine laboratory testings. RESULTS: Metagenomic next-generation sequencing (mNGS) combined with whole-genome sequencing (WGS) was used to classified our isolate from bronchoalveolar lavage fluid (BALF) as N. gipuzkoensis. It is worth mentioning that drug susceptibility testing of our isolate showed resistance to TMP-SMZ, which was never reported before. The patient improved remarkably both clinically and radiographically according to the treatment with imipenem-cilastatin infusion alone. CONCLUSION: mNGS and WGS showed excellent performance in identifying the Nocardia genus to the species level and improving the detection rate of N. gipuzkoensis ignored by traditional culture. Different from previously reported cases, the N. gipuzkoensis infection case showed resistance to TMP-SMZ, which is an unprecedented finding and a crucial addition to our understanding of the antibacterial spectrum of N. gipuzkoensis. The successful treatment with imipenem-cilastatin infusion alone in this case is a testament to the importance of precise identification and tailored antibiotic therapy.

N123I mutation in the ALV-J receptor-binding domain region enhances viral replication ability by increasing the binding affinity with chNHE1.

The subgroup J avian leukosis virus (ALV-J), a retrovirus, uses its gp85 protein to bind to the receptor, the chicken sodium hydrogen exchanger isoform 1 (chNHE1), facilitating viral invasion. ALV-J is the main epidemic subgroup and shows noteworthy mutations within the receptor-binding domain (RBD) region of gp85, especially in ALV-J layer strains in China. However, the implications of these mutations on viral replication and transmission remain elusive. In this study, the ALV-J layer strain JL08CH3-1 exhibited a more robust replication ability than the prototype strain HPRS103, which is related to variations in the gp85 protein. Notably, the gp85 of JL08CH3-1 demonstrated a heightened binding capacity to chNHE1 compared to HPRS103-gp85 binding. Furthermore, we showed that the specific N123I mutation within gp85 contributed to the enhanced binding capacity of the gp85 protein to chNHE1. Structural analysis indicated that the N123I mutation primarily enhanced the stability of gp85, expanded the interaction interface, and increased the number of hydrogen bonds at the interaction interface to increase the binding capacity between gp85 and chNHE1. We found that the N123I mutation not only improved the viral replication ability of ALV-J but also promoted viral shedding in vivo. These comprehensive data underscore the notion that the N123I mutation increases receptor binding and intensifies viral replication.

G-site residue S67 is involved in the fungicide-degrading activity of a tau class glutathione S-transferase from Carica papaya.

Thiram is a toxic fungicide extensively used for the management of pathogens in fruits. Although it is known that thiram degrades in plant tissues, the key enzymes involved in this process remain unexplored. In this study, we report that a tau class glutathione S-transferase (GST) from Carica papaya can degrade thiram. This enzyme was easily obtained by heterologous expression in Escherichia coli, showed low promiscuity toward other thiuram disulfides, and catalyzed thiram degradation under physiological reaction conditions. Site-directed mutagenesis indicated that G-site residue S67 shows a key influence for the enzymatic activity toward thiram, while mutation of residue S13, which reduced the GSH oxidase activity, did not significantly affect the thiram-degrading activity. The formation of dimethyl dithiocarbamate, which was subsequently converted into carbon disulfide, and dimethyl dithiocarbamoylsulfenic acid as the thiram degradation products suggested that thiram undergoes an alkaline hydrolysis that involves the rupture of the disulfide bond. Application of the GST selective inhibitor 4-chloro-7-nitro-2,1,3-benzoxadiazole reduced papaya peel thiram-degrading activity by 95%, indicating that this is the main degradation route of thiram in papaya. GST from Carica papaya also catalyzed the degradation of the fungicides chlorothalonil and thiabendazole, with residue S67 showing again a key influence for the enzymatic activity. These results fill an important knowledge gap in understanding the catalytic promiscuity of plant GSTs and reveal new insights into the fate and degradation products of thiram in fruits.

Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent manner.

Viruses have evolved intricate mechanisms to evade host antiviral responses and exploit cellular resources by manipulating the expression profile of host genes. During infection, viruses encode proteins with shutoff activity to globally inhibit host protein synthesis, which is an effective strategy for immune evasion. In this study, compelling evidence shows that infectious bursal disease virus (IBDV) infection triggers the suppression of host protein synthesis. Furthermore, using both in vitro and in vivo viral infection models, we have identified that IBDV specifically impedes the transcription of host genes via the shutoff activity of viral VP5, simultaneously conferring advantages to IBDV infection in these circumstances. The proposed mechanism suggests that VP5 competitively binds to RanBP1, disrupting the RanGDP/GTP gradient. This disruption interferes with cellular nucleocytoplasmic transport, impairing the nuclear import of proteins bearing nuclear localization signals. The nuclear transport of pivotal transcriptional regulatory factors, such as p65 and IFN regulatory factor 7, is also compromised, leading to the inhibition of pro-inflammatory cytokines and interferon expression. This newly discovered strategy employed by IBDV enables them to manipulate host gene expression, providing novel insights into how viruses evade host immune responses and establish infections.IMPORTANCEViruses manipulate host processes at various levels to regulate or evade both innate and adaptive immune responses, promoting self-survival and efficient transmission. The "host shutoff," a global suppression of host gene expression mediated by various viruses, is considered a critical mechanism for evading immunity. In this study, we have validated the presence of host shutoff during infectious bursal disease virus (IBDV) infection and additionally uncovered that the viral protein VP5 plays a pivotal role in inhibiting the overall synthesis of host proteins, including cytokines, through a transcription-dependent pathway. VP5 competitively binds with RanBP1, leading to disruption of the Ran protein cycle and consequently interfering with nucleocytoplasmic transport, which ultimately results in the suppression of host gene transcription. These findings unveil a novel strategy employed by IBDV to evade host innate immunity and rapidly establish infection. This study also suggests a novel supplement to understanding the pathway through which viruses inhibit host protein synthesis.