Glycoprotein E-Displaying Nanoparticles Induce Robust Neutralizing Antibodies and T-Cell Response against Varicella Zoster Virus.

The Varicella zoster virus (VZV), responsible for both varicella (chickenpox) and herpes zoster (shingles), presents significant global health challenges. While primary VZV infection primarily affects children, leading to chickenpox, reactivation in later life can result in herpes zoster and associated post-herpetic neuralgia, among other complications. Vaccination remains the most effective strategy for VZV prevention, with current vaccines largely based on the attenuated vOka strains. Although these vaccines are generally effective, they can induce varicella-like rashes and have sparked concerns regarding cell virulence. As a safer alternative, subunit vaccines circumvent these issues. In this study, we developed a nanoparticle-based vaccine displaying the glycoprotein E (gE) on ferritin particles using the SpyCatcher/SpyTag system, termed FR-gE. This FR-gE nanoparticle antigen elicited substantial gE-specific binding and VZV-neutralizing antibody responses in BALB/c and C57BL/6 mice-responses that were up to 3.2-fold greater than those elicited by the subunit gE while formulated with FH002C, aluminum hydroxide, or a liposome-based XUA01 adjuvant. Antibody subclass analysis revealed that FR-gE produced comparable levels of IgG1 and significantly higher levels of IgG2a compared to subunit gE, indicating a Th1-biased immune response. Notably, XUA01-adjuvanted FR-gE induced a significant increase in neutralizing antibody response compared to the live attenuated varicella vaccine and recombinant vaccine, Shingrix. Furthermore, ELISPOT assays demonstrated that immunization with FR-gE/XUA01 generated IFN-γ and IL-2 levels comparable to those induced by Shingrix. These findings underscore the potential of FR-gE as a promising immunogen for the development of varicella and herpes zoster vaccines.

A cryptic site in class 5 epitope of SARS-CoV-2 RBD maintains highly conservation across natural isolates.

The emergence of SARS-CoV-2 variants raises concerns about the efficacy of existing COVID-19 vaccines and therapeutics. Previously, we identified a conserved cryptic class 5 epitope of SARS-CoV-2 receptor binding domain (RBD) by two cross-neutralizing antibodies 7D6 and 6D6. Intriguingly, this site remains resistant to substantial mutations occurred in ever-changing SARS-CoV-2 subvariants. As compared to class 3 antibody S309, 6D6 maintains broad and consistent neutralizing activities against SARS-CoV-2 variants. Furthermore, 6D6 effectively protected hamster from the virulent Beta strain. Sequence alignment of approximately 6 million documented SARS-CoV-2 isolates revealed that 6D6 epitope maintains an exceptionally high conservation rate (99.92%). Structural analysis demonstrated that all 33 mutations accumulated in XBB.1.5 since the original strain do not perturb the binding 6D6 to RBD, in line with the sequence analysis throughout the antigenicity evolution of SARS-CoV-2. These findings suggest the potential of this epitope serving as a critical determinant for vaccines and therapeutic design.

Comprehensive Overview of Broadly Neutralizing Antibodies against SARS-CoV-2 Variants.

Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about the possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories of broadly neutralizing antibodies (bnAbs) that retain prominent effectiveness against emerging variants including Omicron sub-lineages. The molecular characteristics, epitope conservation, and resistance mechanisms of these antibodies are further detailed, aiming to offer suggestion or direction for the development of therapeutic antibodies, and facilitate the design of vaccines with broad-spectrum potential.

A survey on advancements in image-text multimodal models: From general techniques to biomedical implementations.

With the significant advancements of Large Language Models (LLMs) in the field of Natural Language Processing (NLP), the development of image-text multimodal models has garnered widespread attention. Current surveys on image-text multimodal models mainly focus on representative models or application domains, but lack a review on how general technical models influence the development of domain-specific models, which is crucial for domain researchers. Based on this, this paper first reviews the technological evolution of image-text multimodal models, from early explorations of feature space to visual language encoding structures, and then to the latest large model architectures. Next, from the perspective of technological evolution, we explain how the development of general image-text multimodal technologies promotes the progress of multimodal technologies in the biomedical field, as well as the importance and complexity of specific datasets in the biomedical domain. Then, centered on the tasks of image-text multimodal models, we analyze their common components and challenges. After that, we summarize the architecture, components, and data of general image-text multimodal models, and introduce the applications and improvements of image-text multimodal models in the biomedical field. Finally, we categorize the challenges faced in the development and application of general models into external factors and intrinsic factors, further refining them into 2 external factors and 5 intrinsic factors, and propose targeted solutions, providing guidance for future research directions. For more details and data, please visit our GitHub page: https://github.com/i2vec/A-survey-on-image-text-multimodal-models.

Effects of microplastics on sedimentary greenhouse gas emissions and underlying microbiome-mediated mechanisms: A comparison of sediments from distinct altitudes.

Microplastics (MPs) are emerging contaminants in aquatic ecosystems that can profoundly affect carbon and nitrogen cycling. However, the impact mechanisms of MPs on sedimentary greenhouse gas (GHG) emissions at distinct altitudes remain poorly elucidated. Here, we investigated the effects of polyvinyl chloride (PVC) and polylactic acid (PLA) on sedimentary CO2, CH4, and N2O emissions at distinct altitudes of the Yellow River. PVC increased the relative abundance of denitrifiers (e.g., Xanthobacteriaceae, Rhodocyclaceae) to promote N2O emissions, whereas PLA reduced the abundance of AOA gene and denitrifiers (e.g., Pseudomonadaceae, Sphingomonadaceae), impeding N2O emissions. Both PVC and PLA stimulated the growth of microbes (Saprospiraceae, Aquabacterium, and Desulfuromonadia) associated with complex organics degradation, leading to increased CO2 emissions. Notably, the concurrent inhibition of PLA on mcrA and pmoA genes led to its minimal impact on CH4 emissions. High-altitude MQ sediments, characterized by abundant substrate and a higher abundance of functional genes (AOA, AOB, nirK, mcrA), demonstrated higher GHG emissions. Conversely, lower microbial diversity rendered the low-altitude LJ microbial community more susceptible to PVC, leading to a more significant promotion on GHG emissions. This study unequivocally confirms that MPs exacerbate GHG emissions via microbiome-mediated mechanisms, providing a robust theoretical foundation for microplastic control to mitigate global warming.

Biogeography and impact of nitrous oxide reducers in rivers across a broad environmental gradient on emission rates.

Microbial communities that reduce nitrous oxide (N2O) are divided into two clades, nosZI and nosZII. These clades significantly differ in their ecological niches and their implications for N2O emissions in terrestrial environments. However, our understanding of N2O reducers in aquatic systems is currently limited. This study investigated the relative abundance and diversity of nosZI- and nosZII-type N2O reducers in rivers and their impact on N2O emissions. Our findings revealed that stream sediments possess a high capacity for N2O reduction, surpassing N2O production under high N2O/NO3- ratio conditions. This study, along with others in freshwater systems, demonstrated that nosZI marginally dominates more often in rivers. While microbes containing either nosZI and nosZII were crucial in reducing N2O emissions, the net contribution of nosZII-containing microbes was more significant. This can be attributed to the nir gene co-occurring more frequently with the nosZI gene than with the nosZII gene. The diversity within each clade also played a role, with nosZII species being more likely to function as N2O sinks in streams with higher N2O concentrations. Overall, our findings provide a foundation for a better understanding of the biogeography of stream N2O reducers and their effects on N2O emissions.

Coupling and decoupling of soil carbon and nutrients cycles at different salinity levels in a mangrove wetland: Insights from CUE and enzymatic stoichiometry.

Soil carbon (C), nitrogen (N), and phosphorus (P) cycling, in conjunction with microbial metabolism, varies significantly with salinity in coastal areas. However, microbial metabolism limitation on salinity levels has received limited attention. Based on soil microbial carbon use efficiency and enzymatic stoichiometry, microbial nutrient limitation characteristics of soil microbial communities in different salinity levels (4.45 mS·cm-1 - 17.25 mS·cm-1) in a subtropical mangrove wetland were investigated. Compared to low-salinity levels, the activity of soil C-acquiring enzyme activities, enzymatic C:N ratios and enzymatic C:P ratios decreased with medium salinity levels and high salinity levels. Soil microbial metabolism was primarily constrained by C and N at different salinity levels. Boosted regression tree analysis revealed that abiotic factors had the greatest influence on C and N limitation of microbial metabolism at different salinity levels. This study underscores the significance of salinity in microbial metabolic processes and enhances our understanding of how future salinity changes induced by rising sea levels will affect soil carbon and nutrient cycling in coastal wetlands.

Microplastics alter soil structure and microbial community composition.

Microplastics (MPs), including conventional hard-to-biodegrade petroleum-based and faster biodegradable plant-based ones, impact soil structure and microbiota in turn affecting the biodiversity and functions of terrestrial ecosystems. Herein, we investigated the effects of conventional and biodegradable MPs on aggregate distribution and microbial community composition in microhabitats at the aggregate scale. Two MP types (polyethylene (PE) and polylactic acid (PLA) with increasing size (50, 150, and 300 µm)) were mixed with a silty loam soil (0-20 cm) at a ratio of 0.5 % (w/w) in a rice-wheat rotation system in a greenhouse under 25 °C for one year. The effects on aggregation, bacterial communities and their co-occurrence networks were investigated as a function of MP aggregate size. Conventional and biodegradable MPs generally had similar effects on soil aggregation and bacterial communities. They increased the proportion of microaggregates from 17 % to 32 %, while reducing the macroaggregates from 84 % to 68 %. The aggregate stability decreased from 1.4 mm to 1.0-1.1 mm independently of MP size due to the decline in the binding agents gluing soil particles (e.g., microbial byproducts and proteinaceous substances). MP type and amount strongly affected the bacterial community structure, accounting for 54 % of the variance. Due to less bioavailable organics, bacterial community composition within microaggregates was more sensitive to MPs addition compared to macroaggregates. Co-occurrence network analysis revealed that MPs exacerbated competition among bacteria and increased the complexity of bacterial networks. Such effects were stronger for PE than PLA MPs due to the higher persistence of PE in soils. Proteobacteria, Bacteroidetes, Chloroflexi, Actinobacteria, and Gemmatimonadetes were the keystone taxa in macroaggregates, while Actinobacteria and Chloroflexi were the keystone taxa in microaggregates. Proteobacteria, Actinobacteria, and Chloroflexi were the most sensitive bacteria to MPs addition. Overall, both conventional and biodegradable MPs reduced the portion of large and stable aggregates, altering bacterial community structures and keystone taxa, and consequently, the functions.

Risedronate-functionalized manganese-hydroxyapatite amorphous particles: A potent adjuvant for subunit vaccines and cancer immunotherapy.

The cGAS-STING pathway and the Mevalonate Pathway are druggable targets for vaccine adjuvant discovery. Manganese (Mn) and bisphosphonates are known to exert adjuvant effects by targeting these two pathways, respectively. This study found the synergistic potential of the two pathways in enhancing immune response. Risedronate (Ris) significantly amplified the Mn adjuvant early antibody response by 166-fold and fortified its cellular immunity. However, direct combination of Mn2+ and Ris resulted in increased adjuvant toxicity (40% mouse mortality). By the combination of doping property of hydroxyapatite (HA) and its high affinity for Ris, we designed Ris-functionalized Mn-HA micro-nanoparticles as an organic-inorganic hybrid adjuvant, named MnHARis. MnHARis alleviated adjuvant toxicity (100% vs. 60% survival rate) and exhibited good long-term stability. When formulated with the varicella-zoster virus glycoprotein E (gE) antigen, MnHARis triggered a 274.3-fold increase in IgG titers and a 61.3-fold surge in neutralization titers while maintaining a better long-term humoral immunity compared to the aluminum adjuvant. Its efficacy spanned other antigens, including ovalbumin, HPV18 VLP, and SARS-CoV-2 spike protein. Notably, the cellular immunity elicited by the group of gE + MnHARis was comparable to the renowned Shingrix®. Moreover, intratumoral co-administration with an anti-trophoblast cell surface antigen 2 nanobody revealed synergistic antitumor capabilities. These findings underscore the potential of MnHARis as a potent adjuvant for augmenting vaccine immune responses and improving cancer immunotherapy outcomes.

Nitrous Oxide (N2O) Emissions Decrease Significantly under Stronger Light Irradiance in Riverine Water Columns with Suspended Particles.

Nitrous oxide (N2O) emissions from riverine water columns with suspended particles are important for the global N2O budget. Although sunlight is known to influence the activity of nitrogen-cycling microorganisms, its specific influence on N2O emissions in river systems remains unknown. This study analyzed the influences of light irradiance on N2O emissions in simulated oxic water columns with 15N-labeling and biological molecular techniques. Our results showed that N2O emissions were inhibited by light in the ammonium system (only 15NH4+ was added) and significantly decreased with increasing light irradiance in the nitrate system (only 15NO3- was added), despite contrasting variations in N2 emissions between these two systems. Lower N2O emission rates in the nitrate system under higher light conditions resulted from higher promotion levels of N2O reduction than N2O production. Increased N2O reduction was correlated to higher organic carbon bioavailability caused by photodegradation and greater potential for complete denitrification. Lower N2O production and higher N2O reduction were responsible for the lower N2O emissions observed in the ammonium system under light conditions. Our findings highlight the importance of sunlight in regulating N2O dynamics in riverine water columns, which should be considered in developing large-scale models for N2O processing and emissions in rivers.