We prove a sharp isoperimetric inequality for the harmonic mean of the first n nonzero Neumann eigenvalues of the Witten-Laplacian on origin-symmetric Lipschitz domains in space forms, endowed with radial log-concave measures. The main novelty is that we establish the sharp harmonic mean inequality under general radial log-concave measures, without assuming the weight function to be non-increasing. This extends previous results that were restricted to specific or more restrictive weighted settings. The proof relies on a refined analysis of the first eigenfunction on geodesic balls, a monotonicity property derived from a convexity condition on the radial weight, and a matrix trace inequality.
In this paper, we investigate improvements to the Leray-Trudinger inequality. By harmonic expansion techniques and the introduction of an appropriate Trudinger type term, we establish the optimal form for the series expansion of Leray-Trudinger inequality originally obtained in [34]. Our results generalize and unify previous findings by G. Psaradakis and D. Spector [32], A. Mallick and C. Tintarev [25], G. Blasio, G. Pisante and G. Psaradakis [5] to any k is an element of N, k >= 1. Additionally, our work complements the results in [15] for series expansion of Lp-Hardy inequality in the critical case p = n. (c) 2025 Published by Elsevier Inc.
We prove a Faber-Krahn inequality for the first eigenvalue of the p-Hermite operator (the weighted p-Laplacian with Gaussian weight) on Lipschitz domains in ^n under Robin boundary conditions with positive Robin parameter. The main result states that, among all domains of given Gaussian measure, the first eigenvalue is minimized by a half-space, and equality holds only for half-spaces. This extends the classical Faber-Krahn inequalities for the p-Laplacian to the p-Hermite operator and generalizes the linear case to the full nonlinear regime p>1.
African swine fever (ASF) is a highly fatal disease caused by the African swine fever virus (ASFV). It infects domestic pigs and wild boars, causing significant economic losses worldwide. However, effective vaccines against this virus remain not be commercialized because of its large genome and high mutation frequency. Thus, antiviral therapies need to be developed urgently. Chloroquine phosphate (CQP) has been demonstrated in previous studies to exert inhibitory effects against a variety of viruses, but its inhibitory effect against the SY-1 strain of ASFV remains unclear. Therefore, we selected CQP as the research subject to investigate its anti-ASFV function. In this study, we confirmed that CQP has a significant inhibitory effect on the ASFV SY-1 strain by RT-qPCR, Western Blot, and HAD50. Transcriptome sequencing and KEGG pathway enrichment analysis showed that CQP treatment significantly affected multiple signaling pathways, including the cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, tumour necrosis factor (TNF) signaling pathway and IL-17 signaling pathway. Western Blot results further indicated that CQP can inhibit ERK phosphorylation. Treatment with the MAPK agonist C16-PAF reversed the inhibitory effect of CQP, verifying the key role of this pathway in the anti-viral mechanism of CQP. In sum, the results of this study indicate that CQP effectively inhibits ASFV replication by suppressing the MAPK-ERK signaling pathway. This study provides a theoretical basis and technical support for the development of anti-viral strategies targeting ASFV.
In this paper, we establish a comparison theorem between positive solutions of the weighted Poisson equation with nonhomogeneous Neumann boundary conditions and suitable positive solutions of its Schwarz symmetrized problem satisfying appropriate matching boundary conditions. We also prove comparison results for the weighted Poisson equation with homogeneous Neumann boundary conditions. Our main tools include weighted isoperimetric inequalities and symmetrization techniques.
This paper focuses on the constrained matrix differential Harnack inequality for a class of hypoelliptic evolution equations Lu = div(A ∇ u) + ⟨ x, B ∇ u ⟩ - ∂ _t u = 0, where A and B are N× N matrices and satisfy Hörmander’s rank condition and specific block structures. By applying the maximum principle, we get the result: for any positive solution u with u and its derivatives up to second order bounded and auxiliary solution g with |g| < u , the N× N matrix (∂ ^2/∂ x_i∂ x_jln u - ∂ ^2/∂ x_i∂ x_jlnΓ - 1/1 - h^2∂ h/∂ x_i∂ h/∂ x_j) is nonnegative definite, where Γ is the fundamental solution of the equation and h=g/u . This constrained inequality generalizes the unconstrained case and refines classical results by incorporating the gradient term of h = g/u .
African swine fever (ASF) is a highly contagious hemorrhagic disease caused by African swine fever virus (ASFV), which has inflicted devastating impacts on the global swine industry. Currently, no commercially available vaccines exist. A major obstacle in ASF research of mechanistic exploration and vaccine studies is the virus’s strict tropism for primary cells like porcine alveolar macrophages (PAMs), while exhibiting poor susceptibility to most immortalized cell lines. This study compared the replication and host response of the ASFV SY-1 strain in PAMs versus immortalized porcine macrophage cell lines (iPAMs) using qPCR, western blot, and early infection transcriptome data. Results revealed that the SY-1 strain replicates only minimally in iPAMs, with significantly lower replication capacity than in PAMs. Transcriptomic data demonstrated divergent host responses: iPAMs predominantly involved in in the regulation of lipid metabolism and response to oxidative stress, whereas PAMs preferentially activate cytokine signaling and immune responses. Furthermore, Functional validation indicated JPH4 and CYP1A1 (selected from differentially expressed genes list) as potential host factors influencing viral replication. This study delineates early host–virus dynamics in ASFV susceptible cells (PAMs) and restricted replicating cells (iPAMs), which not only provides an insight into the replication of ASFV but also improved rational design of antiviral strategies in ASF research.
This paper reviews the pivotal role of sucrose synthase (SUS) in plant development and stress responses, highlights its upstream transcriptional regulation, as well as its involvement in cellulose synthesis and starch synthesis, facilitating a deeper insight into its biological functions and molecular mechanisms. Sucrose synthase (SUS) is a key enzyme in plant sucrose metabolism, catalyzing the reversible conversion of sucrose into fructose and uridine diphosphate glucose to maintain sucrose balance between source and sink. SUS, encoded by a multigene family, is categorized into SUS I, SUS II, and SUS III types, displaying largely tissue-specific expression and differential functions among family members. It plays a regulatory role in root development, flower and fruit development, seed development, as well as fiber development and elongation. In addition, it is involved in starch biosynthesis, cellulose synthesis, sugar metabolism, and response to various abiotic stresses, including drought, heat, cold, salt, hypoxic and weak light. Here, we summarize structure characteristics, evolutionary relationships, classification, expression profiles, upstream transcriptional regulation of SUS genes, and particularly its multiple roles in plant development and stress responses, aiming to lay a theoretical foundation for further research on the biological functions and molecular regulatory mechanisms of SUS.
The H5N6 avian influenza virus, a highly pathogenic strain, poses a significant threat to poultry production and public health. The RNA-dependent RNA polymerase (comprising PB1, PB2, and PA proteins) and nucleoprotein of highly pathogenic avian influenza viruses interact with avian host proteins, influencing the efficiency of viral RNA synthesis and severity of infection. To comprehensively understand how H5N6 avian influenza virus interfaces with host cellular mechanisms during infection and replication, it is essential to identify which host proteins physically associate with viral polymerase proteins. In this study, affinity purification mass spectrometry was used to identify physical interactions between H5N6-JX polymerase proteins (PB1, PB2, PA, and nucleoprotein) and host proteins in chicken DF-1 cells. We identified 455 H5N6-chicken interacting proteins and successfully cloned 231 of these genes. Overexpression experiments revealed several host proteins involved in viral replication in DF-1 cells. Specifically, nine host genes were found to promote avian influenza virus proliferation, whereas 20 inhibited it. Furthermore, we demonstrated that avian NUP93 interacts with the viral PB1 protein, enhancing polymerase transcriptional activity and promoting viral proliferation. These findings provide a more comprehensive understanding of how host mechanisms are manipulated during H5N6 avian influenza viral infection and replication, providing insights into the mechanisms of avian influenza virus cross-species transmission.IMPORTANCEThe RNA-dependent interaction of RNA polymerase with avian host protein determines the efficiency of viral RNA synthesis and the severity of infection. However, the strain-specific interactions of the avian influenza virus (AIV) remain unclear. In this study, we identified 455 H5N6-chicken interacting proteins and successfully cloned 231 of them. Nine host genes that promote the proliferation of avian influenza virus and 20 host genes that inhibit the proliferation of avian influenza virus were identified through overexpression experiments. In addition, we demonstrated that avian NUP93 interacts with viral PB1 protein to enhance polymerase transcriptional activity and promote viral proliferation. This study contributes to a more comprehensive and detailed understanding of the molecular mechanisms of host utilization during the H5N6 highly pathogenic avian influenza virus infection and replication.
African swine fever (ASF) is an acute infectious disease that significantly threats the global pig farming industry. At present, there is no efficient vaccine or targeted therapy for this virus, primarily because of the unclear pathogenesis of ASF virus (ASFV) infection and its interactions with host responses. Here, we established an oral infection model of ASFV in Landrace pigs and identified gene expression and metabolic changes in the pig spleen following ASFV infection using transcriptomic and metabolomic analyses. After ASFV SY-1 infection, 5556 differentially expressed genes (DEGs) were identified, wherein 2577 and 2979 were upregulated and downregulated, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that these genes were dynamically enriched in various biological processes, including the innate immune response, inflammatory response, chemokine signaling, and signal transduction. Integrated transcriptome and metabolome analyses indicated that ASFV altered diverse pathways, including cysteine and methionine metabolism, cGMP-PKG signaling, choline metabolism in cancer, cholesterol metabolism, sphingolipid signaling, protein digestion and absorption, FoxO signaling, and central carbon metabolism in cancer. Additionally, we confirmed that metabolites, such as L-glutamate, glycerophosphocholine, and L-serine, significantly inhibit ASFV proliferation in vitro. This study improves our comprehension of the relationships between viruses and hosts, and it serves as a guide for identifying new inhibitors for ASFV.
Mycoplasma synoviae (MS) infection predominantly manifests as lower respiratory symptoms but also leads to reduced egg production and increased culling rates in laying hens, causing significant economic losses throughout the production cycle. Vaccination remains the most cost-effective strategy to protect layers from MS infection. Previous studies from our laboratory identified and screened immunogenic proteins of MS, culminating in the development of a subunit vaccine that provided robust protection with a two-dose immunization. Building on these findings, this study evaluated various formulations, antigen combinations, and adjuvants of MS inactivated vaccines, tailored to meet field immunization protocols and disease prevention needs. The results indicated that an inactivated vaccine combining whole-cell and subunit components of MS offered effective protection in layers during the pullet-rearing phase with a single immunization. Interestingly, vaccine-induced antibody levels did not strongly correlate with protective efficacy, underscoring the importance of host cellular immunity in combating MS infection. In conclusion, this study addresses field-relevant challenges and presents innovative strategies for MS control in laying hens, offering practical insights for improving disease control and flock management.
The adsorption of avian influenza virus (AIV) initiates the viral lifecycle, determining host tropism and pathogenicity. In addition to the classical AIV receptor, auxiliary receptors also play important roles in viral adsorption, though these remains to be fully elucidated. In this study, we identified 25 avian membrane proteins that interact with H5N6 hemagglutinin (HA), one of which, CD147, was confirmed to play a crucial role in promoting AIV adsorption and replication through overexpression and knockout experiments in DF1 and A549 cells. As a highly glycosylated transmembrane protein, CD147 was further shown to directly bind to the HA receptor-binding domain via its extracellular immunoglobulin-like domains, independently of its glycosylation, thereby mediating viral adsorption. Moreover, AIV infection upregulated the hyperglycosylated form (HG-CD147), while glycosylation inhibitors reduced viral adsorption, highlighting the role of glycosylation in modulating CD147 function. Finally, disrupting the CD147-HA interaction with soluble proteins or monoclonal antibodies inhibited viral adsorption and replication. This study identifies CD147 as an adjuvant receptor that promotes influenza virus adsorption and provides a mechanistic foundation basis for developing broad-spectrum therapeutics targeting HA-host protein interactions.
IntroductionGrassland degradation has seriously affected the ecological environment and human livelihood. To abate these, implementing effective management strategies to restore and improve the service functions and productivity of degraded grasslands is crucial.MethodsTo evaluate the influences of restoration measures combined with different grazing intensities on short-term (1 year) grassland restoration, the changes in soil physicochemical properties, as well as plant traits under restoration measures of different grazing intensities, reseeding, and fertilization, were analyzed.ResultsSoil organic carbon (SOC) increased to varying degrees, whereas available nutrients decreased under all combined restoration measures. Reseeding, alone and in combination with fertilization, substantially increased SOC, improved grassland vegetation status, and enhanced grassland productivity. The aboveground biomass of Gramineae and the total aboveground biomass increased under the combined restoration measures of transferring livestock out of the pasture 45 days in advance, reseeding, and fertilization (T4). Redundancy analysis revealed a strong correlation between grassland vegetation characteristics, SOC, and available potassium. Considering soil and vegetation factors, the short-term results suggested that the combination measures in T4had the most marked positive impact on grassland restoration.DiscussionThese findings offer valuable theoretical insights for the ecological restoration of degraded grasslands in alpine regions.
Nuclear export of the viral ribonucleoprotein (vRNP) is a critical step in the influenza A virus (IAV) life cycle and may be an effective target for the development of anti-IAV drugs. The host factor ras-related nuclear protein (RAN) is known to participate in the life cycle of several viruses, but its role in influenza virus replication remains unknown. In the present study, we aimed to determine the function of RAN in influenza virus replication using different cell lines and subtype strains. We found that RAN is essential for the nuclear export of vRNP, as it enhances the binding affinity of XPO1 toward the viral nuclear export protein NS2. Depletion of RAN constrained the vRNP complex in the nucleus and attenuated the replication of various subtypes of influenza virus. Using in silico compound screening, we identified that bepotastine could dissociate the RAN-XPO1-vRNP trimeric complex and exhibit potent antiviral activity against influenza virus both in vitro and in vivo. This study demonstrates the important role of RAN in IAV replication and suggests its potential use as an antiviral target.
To clarify the relationship between plant biomass and soil nutrients of dominant plants in desert grass-lands,this study selected five dominant plant species:Peganum harmala,Setaria viridis,Festuca sinensis,Pucci-nellia distans,and Agropyron cristatum.We measured their biomass and root-zone soil nutrients to explore bio-mass allocation and its relationship with soil nutrients.The results are as follows:(1)There were significant dif-ferences in total biomass and root-shoot ratio among the five dominant plant species(P<0.05),with Peganum har-mala having the highest total biomass and Puccinellia distans having the lowest.The perennial plants Peganum harmala,Puccinellia distans,Festuca sinensis,and Agropyron cristatum had most of their biomass allocated be-low ground,whereas the annual plant Setaria viridis had most of its biomass above ground.The order of root-shoot ratio among the five plants was as follows:Puccinellia distans>Agropyron cristatum>Festuca sinensis>Peganum harmala>Setaria viridis.(2)There were significant differences(P<0.05)in root-zone soil organic car-bon,available nitrogen,available potassium,total nitrogen,total phosphorus,total potassium,and their stoichio-metric characteristics among the five plant species.The order of soil C:N ratio among the five plants was as fol-lows:Puccinellia distans>Setaria viridis>Agropyron cristatum>Peganum harmala>Festuca sinensis.(3)Varia-tions in plant biomass,root-shoot ratio,and soil nutrients varied among the plants.The root-zone soil total potassi-um of Peganum harmala,Setaria viridis,and Festuca sinensis and the root-zone soil moisture of Puccinellia dis-tans and Agropyron cristatum exhibited weak variation,whereas the other plant characteristics,soil nutrients,and stoichiometric characteristics exhibited moderate variation.The biomass of the five dominant plant species exhib-ited a positive correlation with the root-zone soil available nitrogen and total potassium(P<0.05).The allocation of plant biomass and soil nutrient composition significantly vary among different species and life histories in the desert grassland ecosystem.In the future,it will be necessary to restore degraded desert ecosystems by applying appropriate fertilization based on the nutrient requirements of different dominant plant species.
The improper disposal of vegetable waste often leads to the risk of non-point agricultural pollution. In order to enhance our understanding of how soil quality and successive tomato production respond to the anaerobic incorporation of vegetable residues, greenhouse experiments were conducted in 2019 and 2020. The fresh tomato residues, approximately 17 tons per hectare from greenhouses, were incorporated with carefully selected decomposing agents “Yuandongli” and “Sumao” at three different levels. The results revealed a significant increase in both Soil Quality Index (SQI) and crop yield at the crop harvest stage for the tomato residues incorporation group, ranging from 7.4% to 24.50% and 2.3%–14.9%, respectively, compared to the control group. Specifically, the levels of soil organic matter (SOM), available phosphorus (AP), available potassium (AK), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) increased significantly with the anaerobic incorporation of vegetable residues by an increase of 4.5%–12.3%, 4.1%–31.0%, 2.3%–17.8%, 7.8%–29.2% and 20.0%–35.7%, respectively, compared to the control group. Additionally, enzyme activities such as soil sucrase, urease, and alkaline phosphatase were averagely enhanced by 38.9%, 28.35 and 48.6%. Moreover, the incorporation of tomato residue led to a significant decrease in both the amount of soil fungi and plant parasitic nematodes, with reductions ranging from 28.8% to 58.2% and 401.% to 85.6%, respectively, at the time of crop harvest. The direct and indirect effects of soil properties on SQI and subsequent crop yields were evaluated using a structural equation model. It was found that the contribution of soil properties, including SOM, amount of plant parasitic nematodes (APN), MBC, and AP, to driving changes in SQI accounted for 79%. Furthermore, these indexes explained 49% of the variance in crop yield. Although the type of decomposing agent had varying effects on soil properties, it had a negligible impact on SQI. Furthermore, both SQI and tomato yield did not exhibit a continuous response to the quantity of decomposing agents applied. Our findings suggest that the recommended dosages of the decomposing agent in the instructions are cost-effective and reasonable. The direct anaerobic incorporation of vegetable residues, particularly under greenhouse production conditions, could serve as an efficient and environmentally-friendly management strategy for tomato residues.
IntroductionMycoplasma synoviae (MS) is a globally important avian pathogen causing infectious synovitis and respiratory diseases in poultry, leading to significant economic losses. Despite advances in vaccine development, a commercially viable subunit vaccine against MS remains elusive.MethodsWe sequenced whole genomes of six clinical MS strains isolated from different Chinese provinces. Common genes were analyzed using Biopython software, identifying those with high copy numbers in virulent strains and shared among all strains. Vaxign2 and IEDB Antibody Epitope Prediction were used to analyze protein properties. We assessed immune protective effects of candidate proteins and developed a multivalent subunit vaccine.ResultsTen candidate vaccine proteins were initially selected. A multivalent subunit vaccine composed of MSPB, Ppht, Cfba, and EF-G displayed the best protective effect. The optimal immunization dosage was 20μg, with each protein accounting for 25%. The immune production period was determined to be 28 days post-first immunization, lasting 180 days. The immune protection rate against highly virulent strains reached 90%∼100%.DiscussionThis study provides a new approach for screening vaccine antigens and develops an effective candidate vaccine for MS prevention. The multivalent subunit vaccine shows promising results in protecting against MS infections, potentially offering a solution to reduce economic losses in the poultry industry.
In this study, our objective was to determine whether plant stoichiometry following nitrogen (N) and phosphorous (P) enrichments can enhance understanding regarding biodiversity loss processes. Thus, we conducted a field experiment involving N, P, and N + P enrichments in a sub-alpine meadow on the northeast of QinghaiTibet Plateau within the 2009-2014 period. Plant stoichiometric patterns were investigated using six exemplar species, four functional group levels, as well as the community level. The hierarchical responses of species richness, dominance, plant height, and plant ecological stoichiometry to nutrient addition were investigated. Further, step-wise regression analysis was performed and a structural equation model (SEM) was constructed to assess the linkages between ecological performances and plant stoichiometric characteristics. The model was also used to quantify the contributions of stoichiometric characteristics as drivers of changes in species richness. Our results indicated that N-only and N + P enrichments significantly reduced species richness at community-level, while enhancing grass richness and dominance. Furthermore, only the responses of the N:P ratio, P-related stoichiometry (P concentration, C:P ratios, and N:P ratio), and plant C:N:P stoichiometry to N, P, and N + P fertilizations, at community level could be mirrored at functional group and species levels. Additionally, the responses of the plant N contents and C:N ratios of different species and functional groups showed 28% similarity following nutrient addition. However, at functional group level, only 10% of these responses were similar to those observed at community level, and only in grasses and at community level did the stoichiometric responses show any convergence. We also observed that the major factors affecting ecological performance at different levels included plant N contents and C:N ratios. The species dominance of Elymus nutans (E.n) and the functional group dominance of grasses increased with increasing plant N concentration, and in terms of species richness, species, functional group, and community level stoichiometric traits could fully explain 43% of the observed species richness trend. Further, the effect of the community C:N ratio on species richness was significantly positive. Those results indicated stoichiometric responses to N and P fertilization did not entirely show scaleindependence. Moreover, in a N -limited community, plant differences with respect to nitrogen content flexibility and nitrogen use efficiency can serve as key drivers in explaining ecological performance. Community C:N ratios showed suitability for used in the prediction of species richness trends, and to clarify changes in biodiversity, it is necessary to investigate stoichiometric traits at functional group level.
The phosphorylation of three highly conserved serine residues S23, S24, and S25 (S-S-S motif) has been previously identified in NEP of influenza virus. However, it remains obscure whether and how this motif regulates the vRNPs nuclear export. Here the influenza A H5N6 viruses harboring NEP S23C, S24L, or S25L is generated, allowing to impair the phosphorylation on these sites without mutating viral NS1 protein. These mutations significantly inhibited vRNPs nuclear export are founded, decreased viral infectivity and attenuated virulence in mice. In addition, inhibition or knockout of ATM or CK2, two predicated Ser/Thr protein kinases that phosphorylate the S-S-S motif, impedes vRNP nuclear export and virus replication in cells and reduces the virulence in vivo. Moreover, treatment of NEP peptide mimics containing the S-S-S motif to competitively block NEP binding to the kinases reduces influenza virus replication in cells and mice. However, neither the inhibitors above nor the NEP peptide mimics significantly inhibit the replication of H5N6-DDD mutant, indicating phosphorylation of S-S-S motif is required for the vRNP nuclear export. This studies contribute to a better understanding of the mechanism by which NEP regulates vRNP nuclear export and provides novel insights into antiviral targets against influenza A and B viruses.
Microbiota are known to modulate the host response to influenza infection, but the mechanisms remain largely unknown. Gut metabolites are the key mediators through which gut microbes play anti-influenza effect. Transferring fecal metabolites from mice with high influenza resistance into antibiotic-treated recipient mice conferred resistance to influenza infections. By comparing the metabolites of different individuals with high or low influenza resistance, we identified and validated N-acetyl-D-glucosamine (GlcNAc) and adenosine showed strong positive correlations with influenza resistance and exerted anti-influenza effects in vivo or in vitro, respectively. Especially, GlcNAc mediated the anti-influenza effect by increasing the proportion and activity of NK cells. Several gut microbes, including Clostridium sp., Phocaeicola sartorii, and Akkermansia muciniphila, were positively correlated with influenza resistance, and can upregulate the level of GlcNAc in the mouse gut by exogenous supplementation. Subsequent studies confirmed that administering a combination of the three bacteria to mice via gavage resulted in similar modulation of NK cell responses as observed with GlcNAc. This study demonstrates that gut microbe-produced GlcNAc protects the host against influenza by regulating NK cells, facilitating the elucidation of the action mechanism of gut microbes mediating host influenza resistance.