Effect of plant-soil system on the restoration of community stability after wildfire in the northeast margin of Qinghai-Tibet plateau.

Wildfires, as an environmental filter, are pivotal ecological disturbances that reshape plant communities and soil dynamics, playing a crucial role in regulating biogeographic patterns and ecosystem services. In this study, we aim to explore the effects of wildfires on forest ecosystems, specifically focusing on the plant-soil feedback mechanisms within the northeastern margin of the Qinghai-Tibet Plateau (QTP). Utilizing Partial Least Squares Path Modeling (PLS-PM), we investigated the interrelationships among soil physicochemical properties, enzyme activities, species diversity, and community stability at varying post-fire recovery stages (5, 15, and 23 years). Results indicated that in the early recovery stages, rapid changes in soil properties such as decreased pH (p < 0.001) and increased nutrient availability facilitate the emergence of early successional species with high resource utilization traits. As the ecosystem evolved toward a climax community, the soil and vegetation exhibit increased stability. Furthermore, soil enzyme activities displayed dynamic patterns that corresponded with changes in soil nutrient content, directly influencing the regeneration and diversity of plant communities. Importantly, our study documented a transition in the influence of soil properties on community stability from direct positive effects in initial recovery phases to negative impacts in later stages, while indirect benefits accrue through increased species diversity and enzyme activity. Vegetation composition and structure changed dynamically with recovery time during community succession. Plant nutrient absorption and accumulation affected nutrient dynamics in the soil, influencing plant regeneration, distribution, and diversity. Our results underscore the complex interactions between soil and vegetation that drive the recovery dynamics post-wildfire, highlighting the resilience of forest ecosystems to fire disturbances. This study contributes to the understanding of post-fire recovery processes and offers valuable insights for the management and restoration of fire-affected forest ecosystems.

Overexpression of TNFSF11 reduces GPX4 levels and increases sensitivity to ferroptosis inducers in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD), the most common and lethal subtype of lung cancer, continues to be a major health concern worldwide. Despite advances in targeted and immune therapies, only a minority of patients derive substantial benefits. As a result, the urgent need for novel therapeutic strategies to improve lung cancer treatment outcomes remains undiminished. METHODS: In our study, we employed the TIMER database to scrutinize TNFSF11 expression across various cancer types. We further examined the differential expression of TNFSF11 in normal and tumor tissues utilizing the TCGA-LUAD dataset and tissue microarray, and probed the associations between TNFSF11 expression and clinicopathological parameters within the TCGA-LUAD dataset. We used the GSE31210 dataset for external validation. To identify genes strongly linked to TNFSF11, we engaged LinkedOmics and conducted a KEGG pathway enrichment analysis using the WEB-based Gene SeT AnaLysis Toolkit. Moreover, we investigated the function of TNFSF11 through gene knockdown or overexpression approaches and explore its function in tumor cells. The therapeutic impact of ferroptosis inducers in tumors overexpressing TNFSF11 were also investigated through in vivo and in vitro experiments. Through these extensive analyses, we shed light on the potential role of TNFSF11 in lung adenocarcinoma, underscoring potential therapeutic targets for this malignancy. RESULTS: This research uncovers the overexpression of TNFSF11 in LUAD patients and its inverse correlation with peroxisome-related enzymes. By utilizing gene knockdown or overexpression assays, we found that TNFSF11 was negatively associated with GPX4. Furthermore, cells with TNFSF11 overexpression were relatively more sensitive to the ferroptosis inducers. CONCLUSIONS: Our research has provided valuable insights into the role of TNFSF11, revealing its negative regulation of GPX4, which could be influential in crafting therapeutic strategies. These findings set the stage for further exploration into the mechanisms underpinning the relationship between TNFSF11 and GPX4, potentially opening up new avenues for precision medicine in the treatment of LUAD.

YBX1 as a prognostic biomarker and potential therapeutic target in hepatocellular carcinoma: A comprehensive investigation through bioinformatics analysis and in vitro study.

BACKGROUNDS: Y-box binding protein 1 (YBX1) is a DNA/RNA binding protein known to contribute to the progression of various malignancies, however, a comprehensive pan-cancer analysis to investigate YBX1 across a broad spectrum of cancer types has not yet been conducted. METHODS: We utilized the TIMER database for a comprehensive pan-cancer analysis and assessed YBX-1 expression via the TCGA and GEO databases. The relationship between YBX-1 expression and tumor-infiltrating cells was examined using TIMER and the R programming language. To evaluate the prognostic value of YBX1, we performed Kaplan-Meier plots and Cox regression analyses. Through LinkedOmics, we identified genes significantly correlated with YBX-1. The WEB-based Gene SeT AnaLysis Toolkit was used for KEGG pathway enrichment analysis. Additionally, using shRNA-mediated knockdown, we explored the potential role of YBX1 in tumor cell biology. RESULTS: Our study identifies pronounced overexpression of YBX-1 across multiple cancer types, correlating with adverse outcomes, notably in liver hepatocellular carcinoma (LIHC). A distinct association between elevated YBX-1 expression and heightened immune cell infiltration suggests YBX-1's potential role in reshaping the tumor microenvironment. Intriguingly, our KEGG pathway analysis indicated a tight nexus between YBX-1 expression and lipid metabolism. Moreover, the suppression of YBX-1 via shRNA revealed diminished cellular proliferation and marked reductions in crucial molecules steering the fatty acid synthesis pathway, implicating YBX-1's potential regulatory role in lipid metabolism within LIHC. CONCLUSIONS: YBX-1 serves as a favorable prognostic indicator in various cancers, particularly in liver hepatocellular carcinoma. Targeting YBX1 in HCC offers potential therapeutic strategies. This work paves the way for fresh insights into targeted therapeutic approaches for cancers, especially benefiting liver hepatocellular carcinoma patients.

Measurement of Soot Concentration in Burner Diffusion Flames through Emission Spectroscopy with Particle Swarm Optimization.

Measuring soot concentration in a burner flame is essential for an in-depth understanding of the formation mechanism and to abate its generation. This paper presents an improved emission spectroscopy (ES) method that uses an adaptive particle swarm optimization (APSO) algorithm for measuring the concentration of soot in methane burner flames. Experimental tests were conducted on a laboratory-scale facility under a methane flowrate ranging between 0.6 and 0.9 L/min. A comparison analysis of the soot concentration measured by the ES method, the improved emission spectroscopy (IES) method, and the thermocouple particle density (TPD) method (as a reference) was conducted. The ES method obtained a maximum absolute deviation of 0.84 ppm from the average soot concentration at the three measurement points compared to the TPD method, while that of the IES was only 0.09 ppm. The experimental results demonstrate that the proposed IES method can obtain a more accurate soot concentration of diffusion flames.

Defects-Induced Single-Atom Anchoring on Metal-Organic Frameworks for High-Efficiency Photocatalytic Nitrogen Reduction.

Aiming to improve the photocatalytic activity in N2 fixation to produce ammonia, herein, we proposed a photochemical strategy to fabricate defects, and further deposition of Ru single atoms onto UiO-66 (Zr) framework. Electron-metal-support interactions (EMSI) were built between Ru single atoms and the support via a covalently bonding. EMSI were capable of accelerating charge transfer between Ru SAs and UiO-66, which was favorable for highly-efficiently photocatalytic activity. The photocatalytic production rate of ammonia improved from 4.57 µmol g-1 h-1 to 16.28 µmol g-1 h-1 with the fabrication of defects onto UiO-66, and further to 53.28 µmol g-1 h-1 with Ru-single atoms loading. From the DFT results, it was found that d-orbital electrons of Ru were donated to N2 π✶-antibonding orbital, facilitating the activation of the N≡N triple bond. A distal reaction pathway was probably occurred for the photocatalytic N2 reduction to ammonia on Ru1 /d-UiO-66 (single Ru sites decorated onto the nodes of defective UiO-66), and the first step of hydrogenation of N2 was the reaction determination step. This work shed a light on improving the photocatalytic activity via feasibly anchoring single atoms on MOF, and provided more evidences to understand the reaction mechanism in photocatalytic reduction of N2 .

Phylogenetic Partitioning of Gansu Flora: Unveiling the Core Transitional Zone of Chinese Flora.

Floristic regions, conventionally established using species distribution patterns, have often overlooked the phylogenetic relationships among taxa. However, how phylogenetic relationships influence the historical interconnections within and among biogeographic regions remains inadequately understood. In this research, we compiled distribution data for seed plants in Gansu, a region of significant biogeographic diversity located in northwestern China.We proposed a novel framework for floristic regions within Gansu, integrating distribution data and phylogenetic relationships of genera-level native seed plants, aiming to explore the relationship between phylogenetic relatedness, taxonomic composition, and regional phylogenetic delineation. We found that (1) phylogenetic relatedness was strongly correlated with the taxonomic composition among floras in Gansu. (2) The southeastern Gansu region showed the lowest level of spatial turnover in both phylogenetic relationships and the taxonomic composition of floristic assemblages across the Gansu region. (3) Null model analyses indicated nonrandom phylogenetic structure across the region, where most areas showed higher phylogenetic turnover than expected given the underlying taxonomic composition between sites. (4) Our results demonstrated a consistent pattern across various regionalization schemes and highlighted the preference for employing the phylogenetic dissimilarity approach in biogeographical regionalization investigations. (5) Employing the phylogenetic dissimilarity approach, we identified nine distinct floristic regions in Gansu that are categorized into two broader geographical units, namely the northwest and southeast. (6) Based on the phylogenetic graphic regions of China across this area.

Differences in particulate matter retention and leaf microstructures of 10 plants in different urban environments in Lanzhou City.

Particulate matter (PM) is a major primary environmental air pollutant and poses a threat to human health. Differences in the environment and leaf microstructures of plants will result in varying abilities to retain PM, but the effects of changes in these factors on PM retention are not yet well understood. This study selected 10 plant species in four urban areas (sports field, park, residential green space, and greenway) as the study objects. The amount of retained PM by the different species was measured, and the leaf microstructures were observed. It was found that the environment significantly affected both PM retention and leaf microstructure. The ranking of PM retention in the 10 species in four areas was greenway > residential green space > park > sports field. The ranking of average stomatal width and length was park > sports field > residential green space > greenway, while that of average stomatal density was greenway > residential green space > park > sports field. Different environments affected the length and density of trichomes in the leaves. These changes represented the adaptation of plant species to the growth environment. The stomata and grooves of the leaf surface significantly affected the ability of plants to retain PM. The amount of PM retained by different species varied. In all four urban areas, Prunus × cistena N. E. Hansen ex Koehne (purple leaf sand cherry), Prunus cerasifera Ehrhart f. atropurpurea (Jacq.) Rehd. (cherry plum), Buxus sinica var. parvifolia M. Cheng (common boxwood), and Ligustrum × vicaryi Rehder (golden privet) showed strong PM retention. The results of this study will provide information for planners and urban managers for the selection of plant species.

Association between geriatric nutritional risk index and pathological phenotypes of IgA nephropathy.

Background: IgA nephropathy (IgAN) is an immune disease related to oxidative stress and inflammation. It is the most common type of glomerulonephritis in the world and is the cause of chronic kidney disease and end-stage renal disease (ESRD). The Geriatric Nutritional Risk Index (GNRI) is a practical and uncomplicated method to assess the risk of morbidity and mortality, but its ability to assess IgAN is still unclear. Here, we evaluated the association between the GNRI and clinical and histologic findings of IgAN. Methods: In a cross-sectional study, we included 348 biopsy-verified IgAN patients. The Oxford classification was used to analyze the pathological characteristics of the included patients. Based on previous studies, the participants were divided into two groups using a cutoff value of 92. Differences in clinicopathological indices between the two groups were compared. The correlation between the GNRI and the indicators was evaluated by using a bivariate correlation analysis. A binary logistic regression analysis was conducted to determine the factors associated with the crescent lesions in IgAN. Results: In this study, 138 out of 348 patients (39.7%) had low GNRI scores (GNRI < 92). Patients in the low GNRI group tended to have a significantly lower body mass index; lower hemoglobin, serum albumin, serum IgG, and serum C3 levels; and higher 24-h proteinuria. The proportions of females, Oxford M1 and Oxford C1/2 were higher in the low GNRI group. The GNRI was positively correlated with body mass index (r = 0.57, P < 0.001), hemoglobin (r = 0.35, P < 0.001), serum albumin (r = 0.83, P < 0.001), serum IgG (r = 0.32, P < 0.001), and serum C3 (r = 0.26, P < 0.001) and negatively correlated with 24-h proteinuria (r = -0.36, P < 0.001) and the proportion of crescents (r = -0.24, P < 0.001). The GNRI scores and serum IgG levels were considered independent factors influencing the crescent lesions in IgAN. Conclusions: The GNRI can reflect the severity of clinical and histologic phenotypes in IgAN patients. Lower GNRI and serum IgG levels may suggest an increased risk of crescent lesions and are potential markers for disease monitoring in IgAN.

Recent review of BixMOy (M=V, Mo, W) for photocatalytic CO2 reduction into solar fuels.

The utilization of solar energy for CO2 conversion not only enables a green and low-carbon recycling of CO2 with renewable energy, but also solves ecological problems. BixMOy (M = V, Mo, W) materials have typical layered structures and unique electronic properties that provide suitable band gaps and potential to meet the basic conditions for CO2 reduction. However, pristine BixMOy faces with problems such as small specific surface area, insufficient active sites, low charge carriers' separation and utilization efficiency. This review comprehensively described the basic principles and reaction pathways of photocatalytic CO2 reduction, and further presented the research progress of BixMOy catalysts in CO2 conversion reactions. In this perspective, we further focus on the design concepts and modification strategies to improve the photocatalytic CO2 reduction activity of BixMOy, such as morphology control, constructing surface vacancies and heterojunction fabrication. Finally, based on representative researches, the present review will be expected to provide updated information and insights for developing advanced BixMOy materials to further improve CO2 reduction activity and selectivity.

A novel bismuth hydroxide (Bi(OH)3) semiconductor with highly-efficient photocatalytic activity.

Herein, a novel Bi(OH)3 photocatalyst was successfully synthesized. Benefiting from the suitable band positions, abundant alkaline groups and oxygen vacancies, the as-prepared semiconductor exhibits efficient activity in both photocatalytic CO2 reduction with a CO production rate of 36 µmol g-1 h-1 and phenol decomposition with a 92.7% degradation rate in 180 min.

Serum homocysteine is associated with tubular interstitial lesions at the early stage of IgA nephropathy.

BACKGROUND: The association between homocysteine (Hcy) and IgA nephropathy (IgAN) is not well understood. We aimed to investigate the relationship between Hcy and clinicopathologic features in IgAN patients. METHODS: A total of 337 IgAN patients and 150 sex- and age- matched healthy controls were enrolled in this single-center retrospective study. According to Hcy ≤ 10 µmol/L or > 10 µmol/L, patients were divided into low and high Hcy groups. Multivariate logistic regression was performed to explore the risk factors for elevated Hcy. RESULTS: Serum Hcy was higher in IgAN patients than in healthy controls [11.6 (9.1,15.3) vs. 8.8 (7.5,10.6) µmol/L, P < 0.001], unanimously in the subgroup of 156 patients with a normal estimated glomerular filtration rate (eGFR) (≥ 90 ml/min/1.73 m2) [9.9 (7.6,12.4) vs. 8.8 (7.5,10.6) µmol/L, P < 0.001]. Compared to the low Hcy group, serum creatinine (Scr), blood urine nitrogen (BUN), uric acid (UA), endocapillary hypercellularity (E) and tubular atrophy/interstitial fibrosis lesion (T) were higher in the high Hcy group. Hcy levels were positively correlated with Scr, BUN, UA, 24-h urine protein, and E and T lesions, but negatively correlated with eGFR and superoxide dismutase (SOD). In the subgroup with normal eGFR, patients with higher Hcy were persistent with higher Scr, BUN and T lesions. A multivariate logistic regression model showed that the risk of elevated Hcy in patients with pathological T increased by 2.87-fold. T lesions could better predict high Hcy, with an odds ratio (OR) of 14.20 in the subgroup with normal eGFR. CONCLUSIONS: Pathologic T was an independent risk factor associated with elevated Hcy, especially at the early stage of IgAN.

A stepwise docking molecular dynamics approach for simulating antibody recognition with substantial conformational changes.

Conformational changes or rearrangements are common events during inter-biomolecular recognition. Tracking these changes are essential for exploring the allosteric mechanism and it is usually achieved by molecular dynamics simulation in silico. We previously identified a broad-neutralizing antibody against H5 influenza virus, 13D4, and solved the crystal structures of the free 13D4 Fab and its complex with hemagglutinin (HA). Structural comparison of the unbound and bound 13D4 Fabs showed that the heavy chain complementarity-determining region 3 (HCDR3) undergoes a substantial conformational rearrangement when it recognizes the receptor-binding site (RBS). Here, we used molecular dynamics (MD) to simulate the conformational changes that occur during antibody recognition. We showed that neither conventional MD nor steered MD could recapitulate the loop fitting of the RBS structure contour. Consequently, to simulate these challenging conformational changes, we engaged a stepwise docking MD method that allowed for the gradual docking of the ligand to receptor. This new method recapitulates the bound shape of the HCDR3 and provides the best approximation of the shape rendered by the co-crystal structure, with an RMSD of 0.926 Å. This strategy affords a flexible MD approach for simulating complicated conformational changes that occur during molecular recognition, and helps to provide an understanding of the involved allosteric mechanism.

Recent Advances of Photocatalytic Application in Water Treatment: A Review.

Photocatalysis holds great promise as an efficient and sustainable oxidation technology for application in wastewater treatment. Rapid progress developing novel materials has propelled photocatalysis to the forefront of sustainable wastewater treatments. This review presents the latest progress on applications of photocatalytic wastewater treatment. Our focus is on strategies for improving performance. Challenges and outlooks in this promising field are also discussed. We hope this review will help researchers design low-cost and high-efficiency photocatalysts for water treatment.

New insight into reactive oxidation species (ROS) for bismuth-based photocatalysis in phenol removal.

Bismuth-based semiconductors (BBS) are a group of promising candidates applied to visible light-induced photocatalysis. With deep positions of valence bands (2.34-4.04 eV), BBS exhibited excellent activity in oxidation processes. Fundamental studies on the reactive oxidation species primarily focused on TiO2 under ultraviolet, and it was recognized that OH radicals were effective reactive oxidative species in photocatalytic oxidation processes. This verdict may not be applicable for all other photocatalytic systems. In this study, the reactive oxidation species for BBS in the photocatalytic decomposition of phenol were explored. BBS were prepared with Hierarchical structures and high crystallinity. It was found that OH radicals and superoxide radicals were negligibly produced in most BBS photocatalytic systems. Instead, separated holes on the valence band may directly react with adsorbed species including organics, and acted as the primary ROS. One of the possible explanations of this phenomenon may be due to the shorter lifetime of photogenerated charge carriers on most BBS (212.3-415.7 ms) compared to that of TiO2 (1193.8 ms). Photocatalytic reaction pathways of degradation of phenol were also different between BBS and TiO2, which were proposed. This work shed light on the significance of addressing and clarifying the reactive oxidation species in BBS photocatalysis.

Removal of SO2 and NOx from flue gas using mud-phosphorus slurry.

In this study, the mud-phosphorus slurry was used to simultaneously remove SO2 and NOx. The technology proposed new avenues for the purification and utilization of remove SO2 and NOx in flue gas. The effects of reaction temperature, solid-liquid ratio, and oxygen content on the efficiency of desulfurization and denitrification were studied experimentally. Results show that the parameters were solid-liquid ratio of 5.0 g/40 mL, T = 60 °C, φ (O2) = 20%, Q = 300 mL/min under the best experimental conditions. The maximum amount of ozone generated was 563.8 mg/m3. The reaction time with desulfurization rate ≥ 99% was 340 min; the reaction time with denitrification rate ≥ 99% was 160 min. Response surface analysis method was used to perform a three-factor three-level response surface experiment. Results show that the oxygen content had a highly significant effect on the desulfurization and denitrification efficiency, and the relationship between the desulfurization and denitrification efficiency was oxygen content > mud-phosphorus slurry liquid-solid ratio > reaction temperature. The process is simple, the solid waste is used to treat the flue gas, and the removal effect is good, which is convenient for popularization.

Ryanodine receptor-targeting small molecule fluorescent probes enables non-isotopic labeling and efficient drug screening for green insecticides.

Ryanodine receptors (RyRs) are calcium release channels located on endoplasmic reticulum (ER) membrane, which play important role in excitation-contraction coupling in muscular response. Flubendiamide represents a novel chemical family of green insecticides which selectively activate invertebrate RyR by interacting with the receptor distinct from the ryanodine binding site and has almost no effect on mammalian ryanodine receptors. Traditional methods to screen RyR modulators involve either radio-labeled RyR substrates or calcium signal-based indirect approaches. However, there is lack of RyR-directed non-isotope molecular tools for RyR agonists/antagonists screening and bioimaging. Here we developed a series of fluorescent probes based on the pharmacophore of flubendiamide with the aims to elucidate the mechanism of diamide insecticides and screen novel RyR-targeting insecticides. These probes revealed the specific RyR staining and in vivo RyR targeting properties in diamondback moth RyR transfected Sf9 cells (Sf9-RyR) and RyR enriched insect tissues. The designed fluorescent probes could induce an effective calcium release from ER membrane of Sf9-RyR cells and also showed competitive RyR binding effect with flubendiamide in cell-based fluorometric assay. Having the non-isotope RyR recognition probes will not only accelerate the screening process of new green agrochemicals but also enables deciphering molecular mechanisms of the high selectivity and the drug resistance associated with the diamides.

Photocatalytic oxidation of methanol to formaldehyde on bismuth-based semiconductors.

Methanol is widely applied in photocatalysis as a scavenger of holes, and is also studied as a model system for heterogeneous photocatalysis for the production of formaldehyde. Compared to commercial processes for formaldehyde production via thermal catalytic methanol oxidation, photocatalytic oxidation of methanol to formaldehyde may be more promising when considering the following aspects: 1) lower reaction temperature and pressure (generally operated at room temperature and ambient pressure); 2) lower cost of the energy source (such as solar light) and 3) easy-to-design reactive system. Photocatalytic methanol oxidation was carried out using four different bismuth-based semiconductors (BBS), Bi2WO6, Bi2MoO6, BiOBr and BiVO4, under varying system temperature (5-50 °C), bubbling speed (0.1-1.0 LPM), catalyst dosage (0.2-2.0 g/L), and initial methanol concentration (12.5-250 mM). It was found that the formaldehyde formation rate for all photocatalysts increased as a function of each of these system parameters. Of these four BBS, it was found that Bi2WO6 had the highest formaldehyde formation rate (0.081 mM/h). This work provides a new approach to produce formaldehyde using photocatalysis, and future work has also been proposed.

HIV-1 Membrane-Proximal External Region Fused to Diphtheria Toxin Domain-A Elicits 4E10-Like Antibodies in Mice.

The production of broadly neutralizing antibodies (bNAbs) is a major goal in the development of an HIV-1 vaccine. The membrane-proximal external region (MPER) of gp41, which plays a critical role in the virus membrane fusion process, is highly conserved and targeted by bNAbs 2F5, 4E10, and 10E8. As such, MPER could be a promising epitope for vaccine design. In this study, diphtheria toxin domain A (CRM197, amino acids 1-191) was used as a scaffold to display the 2F5 and 4E10 epitopes of MPER, named CRM197-A-2F5 and CRM197-A-4E10. Modest neutralizing activities were detected against HIV-1 clade B and D viruses in the sera from mice immunized with CRM197-A-4E10. Monoclonal antibodies raised from CRM197-A-4E10 could neutralize several HIV-1 strains, and epitope-mapping analysis indicated that some antibodies recognized the same amino acids as 4E10. Collectively, we show that 4E10-like antibodies can be induced by displaying MPER epitopes using an appropriate scaffold. These results provide insights for HIV-1 MPER-based immunogens design.

Bioengineered Nanocage from HBc Protein for Combination Cancer Immunotherapy.

Protein nanocages are promising multifunctional platforms for nanomedicine owing to the ability to decorate their surfaces with multiple functionalities through genetic and/or chemical modification to achieve desired properties for therapeutic and diagnostic purposes. Here, we describe a model antigen (OVA peptide) that was conjugated to the surface of a naturally occurring hepatitis B core protein nanocage (HBc NC) by genetic modification. The engineered OVA-HBc nanocages (OVA-HBc NCs), displaying high density repetitive array of epitopes in a limited space by self-assembling into symmetrical structure, not only can induce bone marrow derived dendritic cells (BMDC) maturation effectively but also can be enriched in the draining lymph nodes. Naïve C57BL/6 mice immunized with OVA-HBc NCs are able to generate significant and specific cytotoxic T lymphocyte (CTL) responses. Moreover, OVA-HBc NCs as a robust nanovaccine can trigger preventive antitumor immunity and significantly delay tumor growth. When combined with a low-dose chemotherapy drug (paclitaxel), OVA-HBc NCs could specifically inhibit progression of an established tumor. Our findings support HBc-based nanocages with modularity and scalability as an attractive nanoplatform for combination cancer immunotherapy.

An IgM antibody targeting the receptor binding site of influenza B blocks viral infection with great breadth and potency.

Broadly neutralizing antibodies (bnAbs) targeting the receptor binding site (RBS) of hemagglutinin (HA) have potential for developing into powerful anti-influenza agents. Several previously reported influenza B bnAbs are nevertheless unable to neutralize a portion of influenza B virus variants. HA-specific bnAbs with hemagglutination inhibition (HI) activity may possess the ability to block virus entry directly. Polymeric IgM antibodies are expected to more effectively inhibit virus attachment and entry into target cells due to their higher avidity and/or steric hindrance. We therefore hypothesized that certain RBS-targeted IgM antibodies with strong cross-lineage HI activity might display broader and more potent antiviral activity against rapidly evolving influenza B viruses. Methods: In this study, we generated IgM and IgG bnAbs targeting the RBS of influenza B virus using the murine hybridoma technique. IgM and IgG versions of the same antibodies were then developed by isotype switching and characterized in subsequent in vitro and in vivo experiments. Results: Two IgM and two IgG bnAbs against influenza B virus HA were identified. Of these, one IgM subtype antibody, C7G6-IgM, showed strong HI and neutralization activities against all 20 representative influenza B strains tested, with higher potency and broader breadth of anti-influenza activity in vitro than the IgG subtype variant of itself, or other previously-reported influenza B bnAbs. Furthermore, C7G6-IgM conferred excellent cross-protection against distinct lineages of influenza B viruses in mice and ferrets, performing better than the anti-influenza drug oseltamivir, and showed an additive antiviral effect when administered in combination with oseltamivir. Mechanistically, C7G6-IgM potently inhibits infection with influenza B virus strains from different lineages by blocking viral entry. Conclusion: In summary, our study highlights the potential of IgM subtype antibodies in combatting pathogenic microbes. Moreover, C7G6-IgM is a promising candidate for the development of prophylactics or therapeutics against influenza B infection.