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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.
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Bactérias , Óxido Nitroso , Rios , Óxido Nitroso/metabolismo , Rios/microbiologia , Rios/química , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Sedimentos Geológicos/microbiologia , Oxirredução , Filogeografia , Filogenia , MicrobiotaRESUMO
Human papillomaviruses (HPV) are small DNA viruses associated with cervical cancer, warts, and other epithelial tumors. Structural studies have shown that the HPV capsid consists of 360 copies of the major capsid protein, L1, arranged as 72 pentamers in a T=7 icosahedral lattice, coassembling with substoichiometric amounts of the minor capsid protein, L2. However, the residues involved in the coassembly of L1 and L2 remain undefined due to the lack of structure information. Here, we investigated the solvent accessibility surfaces (SASs) of the central cavity residues of the HPV16 L1 pentamer in the crystal structure because those internal exposed residues might mediate the association with L2. Twenty residues in L1 protein were selected to be analyzed, with four residues in the lumen of the L1 pentamer identified as important: F256, R315, Q317, and T340. Mutations to these four residues reduced the PsV (pseudovirus) infection capacity in 293FT cells, and mutations to R315, Q317, and T340 substantially perturb L2 from coassembling into L1 capsid. Compared with wild-type (WT) PsVs, these mutant PsVs also have a reduced ability to become internalized into host cells. Finally, we identified a stretch of negatively charged residues on L2 (amino acids [aa] 337 to 340 [EEIE]), mutations to which completely abrogate L2 assembly into L1 capsid and subsequently impair the endocytosis and infectivity of HPV16 PsVs. These findings shed light on the elusive coassembly between HPV L1 and L2. IMPORTANCE Over 200 types of HPV have been isolated, with several high-risk types correlated with the occurrence of cervical cancer. The HPV major capsid protein, L1, assembles into a T=7 icosahedral viral shell, and associates with the minor capsid protein, L2, which plays a critical role in the HPV life cycle. Despite the important role of the L2 protein, its structure and coassembly with L1 remain elusive. In this study, we analyzed the amino acid residues at the proposed interface between L1 and L2. Certain mutations at these sites decreased the amount of L2 protein assembled into the capsid, which, in turn, led to a decrease in viral infectivity. Knowledge about these residues and the coassembly of L1 and L2 could help to expand our understanding of HPV biology and aid in the development of countermeasures against a wide range of HPV types by targeting the L2 protein.
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Proteínas do Capsídeo , Papillomavirus Humano 16 , Feminino , Humanos , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidade , Infecções por Papillomavirus/virologia , Sequência de Aminoácidos/genética , Mutação , Linhagem Celular , Estrutura Terciária de Proteína/genética , Modelos MolecularesRESUMO
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.
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Compostos de Amônio , Óxido Nitroso , Óxido Nitroso/análise , Nitratos , Nitrogênio/análise , Água , SoloRESUMO
Nitrous oxide (N2O), a potent greenhouse gas, is produced in rivers through a series of microbial metabolic pathways. However, the microbial source of N2O production and the degree of N2O reduction in river systems are not well understood and quantified. This work investigated isotopic compositions (δ15N-N2O and δ18O-N2O) and N2O site preference as well as N2O-related microbial features, thereby differentiating the importance of nitrification, denitrification, and N2O reduction in controlling N2O emissions from five rivers on the eastern Qinghai-Tibet Plateau (EQTP). The average N2O concentration in overlying water (15.2 nmol L-1) was close to that in porewater (17.5 nmol L-1), suggesting that both overlying water and sediment are potentially important sources of N2O. Canonical and nitrifier denitrification dominated riverine N2O production, with contribution being approximately 90%. Nitrification is a non-negligible source of N2O production, and N2O concentration was positively correlated with nitrification genetic potential. The degree of N2O reduction ranged from 78.1 to 94.1% (averaging 90%), significantly exceeding the reported values (averaging 70%) in other freshwaters, which was attributed to the higher ratios of organic carbon to nitrogen and lower ratio of (nirS + nirK)/nosZ in EQTP rivers. This study indicates that a combination of isotopic and isotopocule values with functional microbe analysis is useful for quantifying the microbial sources of N2O in rivers, and the intense microbial reduction of N2O significantly accounts for the low N2O emissions observed in EQTP rivers, suggesting that both the production and consumption of N2O in rivers should be considered in the future.
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Desnitrificação , Rios , Tibet , Nitrificação , Óxido Nitroso/análiseRESUMO
Bacterial biodiversity is tightly correlated with ecological functions of natural systems, and bacterial rare and abundant subcommunities make distinct contributions to ecosystem functioning. However, the biogeographic pattern and elevational differentiation of sedimentary bacterial diversity have rarely been studied in cross-river systems at a continental scale. This study analyzed the biogeographic patterns and elevational differentiations of the entire, abundant, and rare bacterial (sub)communities as well as the underlying mechanisms across nine rivers that span distinct geographic regions and large elevational gradients in China. We found that bacterial rare and abundant subcommunities shared similar biogeographic patterns and both demonstrated strong distance-decay relationships, despite their distinct community compositions. However, both null model and variation partitioning analysis results showed that while environmental selection governed rare subcommunity assemblies (contribution: 51.9%), dispersal limitation (62.7%) controlled the assembly of abundant subcommunities. The disparity was associated with the broader threshold width of abundant taxa to water temperature and pH variations than rare taxa. Elevation-induced bacterial composition variations were more evident than latitude-induced ones. Some specific operational taxonomic units (OTUs), representing 16.4% of the total sequences, much preferentially and even exclusively lived in high-elevation or low-elevation habitats and demonstrated some adaptations to local conditions. Greater positive: negative link ratios in bacterial co-occurrence networks of low elevations than high elevations (P < 0.05) partly resulted from their harboring higher organic carbon: nitrogen ratios. Together, this study draws a biogeographic picture of sedimentary bacterial communities in a continental-scale riverine system and highlights the importance of incorporating elevation-associated patterns of microbial diversity into riverine microbial ecology studies. IMPORTANCE Bacterial diversity is tightly correlated with the nutrient cycling of river systems. However, previous studies on bacterial diversity are mainly constrained to one single river system, although microbial biogeography and its drivers exhibit strong spatial scale dependence. Moreover, elevational differentiations of bacterial communities across river systems have also rarely been studied. Bacterial rare and abundant subcommunities make distinct contributions to ecosystem functioning, and they share similar biogeographic patterns in some environments but not in others. Therefore, we explored the biogeography of the entire, abundant, and rare (sub)communities in nine rivers that cover a wide space range and large elevational gradient in China. Our results revealed that bacterial rare and abundant subcommunities shared similar biogeographic patterns but their assembly mechanisms were much different in these rivers. Moreover, bacterial communities showed evident differentiations between high elevations and low elevations. These findings will facilitate a better understanding of bacterial diversity features in river systems.
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Ecossistema , Rios , Bactérias/genética , Biodiversidade , China , Rios/microbiologiaRESUMO
Streams and rivers are important sources of nitrous oxide (N2 O), a powerful greenhouse gas. Estimating global riverine N2 O emissions is critical for the assessment of anthropogenic N2 O emission inventories. The indirect N2 O emission factor (EF5r ) model, one of the bottom-up approaches, adopts a fixed EF5r value to estimate riverine N2 O emissions based on IPCC methodology. However, the estimates have considerable uncertainty due to the large spatiotemporal variations in EF5r values. Factors regulating EF5r are poorly understood at the global scale. Here, we combine 4-year in situ observations across rivers of different land use types in China, with a global meta-analysis over six continents, to explore the spatiotemporal variations and controls on EF5r values. Our results show that the EF5r values in China and other regions with high N loads are lower than those for regions with lower N loads. Although the global mean EF5r value is comparable to the IPCC default value, the global EF5r values are highly skewed with large variations, indicating that adopting region-specific EF5r values rather than revising the fixed default value is more appropriate for the estimation of regional and global riverine N2 O emissions. The ratio of dissolved organic carbon to nitrate (DOC/NO3 - ) and NO3 - concentration are identified as the dominant predictors of region-specific EF5r values at both regional and global scales because stoichiometry and nutrients strictly regulate denitrification and N2 O production efficiency in rivers. A multiple linear regression model using DOC/NO3 - and NO3 - is proposed to predict region-specific EF5r values. The good fit of the model associated with easily obtained water quality variables allows its widespread application. This study fills a key knowledge gap in predicting region-specific EF5r values at the global scale and provides a pathway to estimate global riverine N2 O emissions more accurately based on IPCC methodology.
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Nitratos , Óxido Nitroso , Óxido Nitroso/análise , Nitratos/análise , Matéria Orgânica Dissolvida , Monitoramento Ambiental , RiosRESUMO
As the new coronavirus pneumonia swept the world in 2020, the demand for antibacterial products significantly increased. In this study, a soy protein isolate nano-silver hydrosol was prepared using an environmentally friendly Ag+ in situ reduction process, where the soy protein was ultrasonically blended with polyacrylic resin to obtain a polyacrylate-nano silver antibacterial wood coating. The structure of the soy protein isolate nano-silver hydrosol was assessed, and the structure and antibacterial and mechanical properties of the film were characterized. The results showed that the silver nanoparticles (AgNPs) exhibited good crystallinity and were evenly distributed in the emulsion. The composite film had good antibacterial properties against gram-negative bacteria represented by Escherichia coli and gram-positive bacteria represented by Staphylococcus aureus. With increased nano-silver content, the diameter of the inhibition zone increased from 0 to 30â¯mm, and from 18 to 50â¯mm for the two bacteria, respectively. Moreover, the elastic modulus of the film increased from 8.173 to 97.912â¯MPa, and the elongation at break decreased from 240.601 to 41.038% as the content of AgNPs changed from 0.1 to 1%, respectively. Thus, this study provides a new method for preparing waterborne polyacrylate coatings with excellent antibacterial properties.
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Anthropogenic activities can lead to the loss of soil organic carbon (SOC) or improve its storage, hence they have the potential to exacerbate or help mitigate climate change. Urban expansion results in an initial loss of soil carbon, but long-term SOC changes during urban development are poorly understood. Herein, we studied SOC changes in the suburban and urban areas of cities with high levels of urbanization based on a long-term resampling campaign in Beijing, and a compilation of SOC content data from 21 other cities with high levels of urbanization across China over the past three decades. Our results revealed that the SOC of topsoils decreased by 17.2% in the suburban areas and increased by 104.4% in the urban areas of cities with high levels of urbanization. The changes in SOC were positively correlated with the changes in vegetation coverage and productivity. Partial least square method structural equation model analyses showed that changes in vegetation could directly affect SOC changes, and the changes in vegetation coverage and productivity were induced by human activities and climate changes in Beijing. The topsoils in the urban areas of cities with high levels of urbanization can act as carbon sinks due to the increase in vegetation. This study can help improve our understanding of the role of the SOC content of cities within the global C cycle and provide suggestions for achieving the goal of carbon neutrality in China.
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Carbono , Solo , Carbono/análise , Sequestro de Carbono , China , Humanos , Solo/química , Reforma Urbana , UrbanizaçãoRESUMO
Inland waters are significant sources of nitrous oxide (N2O), a powerful greenhouse gas. However, considerable uncertainty exists in the estimates of N2O efflux from global inland waters due to a lack of direct measurements in urban inland waters, which are generally characterized by high carbon and nitrogen concentrations and low carbon-to-nitrogen ratios. Herein, we present direct measurements of N2O concentrations and fluxes in lakes and rivers of Beijing, China, during 2018-2020. N2O concentrations and fluxes in the waters of Beijing exceeded previous estimates of global rivers due to the high carbon and nutrient concentrations and high aquatic productivity. In contrast, the N2O emission factor (N2O-N/DIN, median 0.0005) was lower than global medians and the N2O yield (ΔN2O/(ΔN2O + ΔN2), average 1.6%) was higher than those typically observed in rivers and streams. The positive relationship between N2O emissions and denitrifying bacteria as well as the Michaelis-Menten relationship between N2O emissions and NO3--N concentrations suggested that bacteria control the net production of N2O in waters of Beijing with N saturation, leading to a low N2O emission factor. However, low carbon-to-nitrogen ratios are beneficial for N2O accumulation during denitrification, resulting in high N2O yields. This study demonstrates the significant N2O emissions and their distinctive patterns and controls in urban inland waters and suggests that N2O emission estimates based on nitrogen loads and simple emission factor values are not appropriate for urban inland water systems.
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Óxido Nitroso , Rios , Pequim , China , Lagos , Óxido Nitroso/análiseRESUMO
Overlying water is another potential hotspot of nitrogen removal through anammox and denitrification reactions in river systems. However, N2 production and the controlling factors have rarely been investigated in the overlying water of high-elevation rivers. This study analyzed the abundance and community of denitrifying and anammox bacteria as well as their effects on N2 production rates in the overlying water of the Yellow River source region (elevation range: 2687-4223 m). Higher suspended particle concentrations remarkably promoted functional gene abundances of both denitrifying and anammox bacteria (r > 0.9, p < 0.01). N2 production rates in overlying water samples ranged from 0.25 to 4.22 µmol N2 L-1 d-1. The overlying water was estimated to contribute to 36.8% (on average) of riverine N2 emission flux. Higher temperatures markedly accelerated N2 production rates (p = 0.051). Moreover, N2 production rates were positively related to both anammox and denitrifying bacterial abundances (p < 0.05), and such relationships were markedly affected by corresponding community compositions. The explanatory power of denitrifier abundance (R2 = 0.56) for N2 production rate variations was greatly elevated when it was integrated with community composition (R2 = 0.92). This study highlights the significance of overlying water nitrogen removal in the Yellow River source region; moreover, the effects of both microbial abundance and community composition on riverine N2 production rates should be considered in future research.
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Sedimentos Geológicos , Rios , Nitrogênio , Oxirredução , ÁguaRESUMO
Ammonia-oxidizing bacteria (AOB) and archaea (AOA) as well as comammox catalyze ammonia oxidation. The distribution and biogeography of these ammonia oxidizers might be distinctive in high-elevation rivers, which are generally characterized by low temperature and low ammonium concentration but strong solar radiation; however, these characteristics have rarely been documented. This study explored the abundance, community, and activity of ammonia oxidizers in the overlying water of five rivers in the Qinghai-Tibet Plateau (QTP). Potential nitrification rates in these rivers ranged from 5.4 to 38.4 nmol N liter-1 h-1, and they were significantly correlated with ammonium concentration rather than temperature. Comammox were found in 25 of the total 28 samples, and they outnumbered AOA in three samples. Contrary to most studied low-elevation rivers, average AOB amoA gene abundance was significantly higher than that of AOA, and AOB/AOA ratios increased with decreasing water temperature. The Simpson index of the AOA community increased with elevation (P < 0.05), and AOA and AOB communities exhibited high dissimilarities with low-elevation rivers. Cold-adapted (Nitrosospira amoA cluster 1, 33.6%) and oligotrophic (Nitrosomonas amoA cluster 6a, 31.7%) groups accounted for large proportions in the AOB community. Suspended sediment concentration exerted significant effects on ammonia oxidizer abundance (r > 0.56), and owing to their elevational variations in source and concentration, suspended sediments facilitated distance-decay patterns for AOA and AOB community similarities. This study demonstrates distinctive biogeography and distribution patterns for ammonia oxidizers in high-elevation rivers of the QTP. Extensive research should be conducted to explore the role of these microbes in the nitrogen cycle of this zone.IMPORTANCE Ammonia-oxidizing archaea (AOA) and bacteria (AOB) as well as comammox contribute to ammonia oxidation, which plays significant roles in riverine nitrogen cycle and N2O production. Source regions of numerous rivers in the world lie in high-elevation zones, but the abundance, community, and activity of ammonia oxidizers in rivers in high-elevation regions have rarely been investigated. This study revealed distinctive distribution patterns and community structures for ammonia oxidizers in five high-elevation rivers of the Qinghai-Tibet Plateau, and the individual and combined effects of low temperature, low nutrients, and strong solar radiation on ammonia oxidizers were elucidated. The findings of this study are helpful to broaden our knowledge on the biogeography and distribution pattern of ammonia oxidizers in river systems. Moreover, this study provides some implications to predict the performance of ammonia oxidizers in high-elevation rivers and its variations under global climate warming.
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Amônia/metabolismo , Archaea/classificação , Bactérias/classificação , Rios/microbiologia , Microbiologia da Água , Archaea/metabolismo , Bactérias/metabolismo , Sedimentos Geológicos/microbiologia , Oxirredução , Filogeografia , Rios/química , TibetRESUMO
Suspended sediment (SPS) is ubiquitous in rivers, and SPS with different particle sizes and compositions may affect coupled nitrification-denitrification (CND) occurring on SPS significantly. However, there is no related research report. In this work, 15N isotope tracer technique was adopted to explore the CND in systems containing SPS (8 g L-1 and 1 g L-1) collected from the Yellow River with various particle sizes, including <2, 2-20, 20-50, 50-100, and 100-200 µm. The results showed that the CND occurred on SPS and the CND rate was negatively related to particle size; both nitrification and denitrification rate constants increased with decreasing SPS particle size. For instance, SPS (8 g L-1) with a particle size below 2 µm had the highest 15N2 emission rate of 1.15 mg-N/(m3·d), which was 2.9 times that of 100-200 µm. This is because SPS with a smaller particle size had a larger specific surface area and a higher organic carbon content, which is beneficial for bacteria growth. Both the nitrifying and denitrifying bacteria population were positively correlated with CND rate (p < 0.05). Different from the 15N2 production, 15N2O emission rate did not decrease with increasing SPS particle size. For the system containing 8 g L-1 SPS, 15N2O emission rate reached the highest of 1.05 µg-N/(m3·d) in the 50-100 µm SPS system, which was 17.5 times that of 100-200 µm. Similar results could be found from the system with 1 g L-1 SPS. This is due to the fact that the oxygen concentration at the SPS-water interface increased with SPS particle size, and the oxygen conditions might be most suitable for the production of N2O in the 50-100 µm system. This study suggests that SPS size and composition play an important role in nitrogen cycle of river systems, especially for the production of N2O.
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Desnitrificação , Nitrificação , Bactérias , Nitrogênio , Óxido Nitroso , Tamanho da Partícula , RiosRESUMO
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.
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Solo , Áreas Alagadas , Carbono/análise , Salinidade , Microbiologia do Solo , Nitrogênio/análise , Fósforo/análise , Nutrientes/análiseRESUMO
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.
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Dióxido de Carbono , Sedimentos Geológicos , Gases de Efeito Estufa , Microbiota , Microplásticos , Poliésteres , Sedimentos Geológicos/microbiologia , Microbiota/efeitos dos fármacos , Microplásticos/toxicidade , Dióxido de Carbono/análise , Poliésteres/metabolismo , Altitude , Metano/metabolismo , Cloreto de Polivinila , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Óxido Nitroso/análise , Rios/microbiologia , Rios/químicaRESUMO
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.
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Processamento de Linguagem NaturalRESUMO
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.
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Anticorpos Antivirais , Anticorpos Amplamente Neutralizantes , COVID-19 , Epitopos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , SARS-CoV-2/imunologia , Humanos , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/virologia , Anticorpos Amplamente Neutralizantes/imunologia , Epitopos/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Neutralizantes/imunologia , Evasão da Resposta Imune , Vacinas contra COVID-19/imunologiaRESUMO
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.
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Chloroflexi , Microbiota , Microplásticos , Plásticos , Solo/química , Microbiologia do Solo , Poliésteres , Bactérias , PolietilenoRESUMO
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.
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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.
Assuntos
Manganês , Neoplasias , Glicoproteína da Espícula de Coronavírus , Camundongos , Humanos , Animais , Ácido Risedrônico , Durapatita , Adjuvantes Imunológicos , Vacinas de Subunidades Antigênicas , Antígenos , Adjuvantes Farmacêuticos , Imunoterapia , Anticorpos AntiviraisRESUMO
Varicella-zoster virus (VZV) is a highly infectious agent responsible for both varicella and herpes zoster disease. Despite high efficacy, there remain safety and accessibility concerns with the licensed vaccines. Here, we sought to produce a VZV gE immunogen using an E. coli expression system. We found that the soluble expression and yield of gE protein could be enhanced via C-terminal truncations to the protein, thereby facilitating a robust and scalable purification process for the purpose of vaccine manufacturing. The lead truncated gE (aa 31-358), hereafter referred to as tgE, was a homogenous monomer in solution and showed excellent antigenicity. Finally, we assessed and compared the immunogenicity of tgE with commercial vOka LAV and Shingrix vaccine. We found that aluminum-adjuvanted tgE was immunogenic as compared with vOka LAV. When adjuvanted with AS01B, a two-dose immunization of tgE showed comparable or better potency in antibody responses and cell-mediated immunity with those of the Shingrix vaccine at the same dosage, especially in terms of the proportion of IFN-γ-expressing CD4+ T cells. In conclusion, this method of E. coli-mediate tgE expression offers a cost-effective and scalable strategy to generate an ideal VZV gE immunogen for the development of both varicella and zoster vaccines.