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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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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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Procesamiento de Lenguaje NaturalRESUMEN
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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Anticuerpos Antivirales , Anticuerpos ampliamente neutralizantes , COVID-19 , Epítopos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , SARS-CoV-2/inmunología , Humanos , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/virología , Anticuerpos ampliamente neutralizantes/inmunología , Epítopos/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Anticuerpos Neutralizantes/inmunología , Evasión Inmune , Vacunas contra la COVID-19/inmunologíaRESUMEN
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 Efecto Invernadero , Microbiota , Microplásticos , Poliésteres , Sedimentos Geológicos/microbiología , Microbiota/efectos de los fármacos , Microplásticos/toxicidad , Dióxido de Carbono/análisis , Poliésteres/metabolismo , Altitud , Metano/metabolismo , Cloruro de Polivinilo , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/clasificación , Bacterias/metabolismo , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Óxido Nitroso/análisis , Ríos/microbiología , Ríos/químicaRESUMEN
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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Bacterias , Óxido Nitroso , Ríos , Óxido Nitroso/metabolismo , Ríos/microbiología , Ríos/química , Bacterias/genética , Bacterias/clasificación , Bacterias/metabolismo , Sedimentos Geológicos/microbiología , Oxidación-Reducción , Filogeografía , Filogenia , MicrobiotaRESUMEN
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 , Suelo/química , Microbiología del Suelo , Poliésteres , Bacterias , PolietilenoRESUMEN
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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Suelo , Humedales , Carbono/análisis , Salinidad , Microbiología del Suelo , Nitrógeno/análisis , Fósforo/análisis , Nutrientes/análisisRESUMEN
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.
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Manganeso , Neoplasias , Glicoproteína de la Espiga del Coronavirus , Ratones , Humanos , Animales , Ácido Risedrónico , Durapatita , Adyuvantes Inmunológicos , Vacunas de Subunidad , Antígenos , Adyuvantes Farmacéuticos , Inmunoterapia , Anticuerpos AntiviralesRESUMEN
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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Compuestos de Amonio , Óxido Nitroso , Óxido Nitroso/análisis , Nitratos , Nitrógeno/análisis , Agua , SueloRESUMEN
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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Desnitrificación , Ríos , Tibet , Nitrificación , Óxido Nitroso/análisisRESUMEN
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 de la Cápside , Papillomavirus Humano 16 , Femenino , Humanos , Proteínas de la Cápside/química , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidad , Infecciones por Papillomavirus/virología , Secuencia de Aminoácidos/genética , Mutación , Línea Celular , Estructura Terciaria de Proteína/genética , Modelos MolecularesRESUMEN
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.
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Varicela , Vacuna contra el Herpes Zóster , Herpes Zóster , Humanos , Herpesvirus Humano 3 , Escherichia coli , Linfocitos T CD4-Positivos , Herpes Zóster/prevención & control , Adyuvantes Inmunológicos , Anticuerpos AntiviralesRESUMEN
The Baculovirus Expression Vector System (BEVS), a mature foreign protein expression platform, has been available for decades, and has been effectively used in vaccine production, gene therapy, and a host of other applications. To date, eleven BEVS-derived products have been approved for use, including four human vaccines [Cervarix against cervical cancer caused by human papillomavirus (HPV), Flublok and Flublok Quadrivalent against seasonal influenza, Nuvaxovid/Covovax against COVID-19], two human therapeutics [Provenge against prostate cancer and Glybera against hereditary lipoprotein lipase deficiency (LPLD)] and five veterinary vaccines (Porcilis Pesti, BAYOVAC CSF E2, Circumvent PCV, Ingelvac CircoFLEX and Porcilis PCV). The BEVS has many advantages, including high safety, ease of operation and adaptable for serum-free culture. It also produces properly folded proteins with correct post-translational modifications, and can accommodate multi-gene- or large gene insertions. However, there remain some challenges with this system, including unstable expression and reduced levels of protein glycosylation. As the demand for biotechnology increases, there has been a concomitant effort into optimizing yield, stability and protein glycosylation through genetic engineering and the manipulation of baculovirus vector and host cells. In this review, we summarize the strategies and technological advances of BEVS in recent years and explore how this will be used to inform the further development and application of this system.
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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/análisis , Nitratos/análisis , Materia Orgánica Disuelta , Monitoreo del Ambiente , RíosRESUMEN
Precipitation can affect the residence time of nitrogen compounds, and temperature can influence nitrogen transformation in soil. Therefore, we hypothesized that climate factors can affect the emissions of N2O, an important greenhouse gas produced via nitrogen transformation, by influencing the migration and transformation of nonpoint source nitrogen in soil. To test this hypothesis and quantify the effect of climate factors on N2O emissions, the SWAT model and the modified SWAT-N2O coupler were used to study the effect of climate factors on the migration and transformation of nonpoint source nitrogen and N2O emissions in an agricultural watershed from 2009 to 2018. Temperature affected N2O emissions more significant than precipitation, and N2O emissions increased with temperature and reached a plateau when the average monthly temperature was 23.0 °C. The N2O emissions first increased rapidly with precipitation due to the increase in moisture. However, when the average monthly precipitation reached 78.8 mm, the N2O emissions began to decrease because the residence time of nitrogen compounds in soil were reduced due to fast removal via runoff, which inhibits N2O emissions. Under the context of climate change with three scenarios (RCP2.6, RCP4.5, RCP8.5), temperature would increase gradually while precipitation would not change significantly from 2021 to 2080, as a result, the changes would increase N2O emissions by 6.7%, 32.3%, and 70.7%, respectively. This study quantifies the feedback of N2O emissions to climate change in croplands, providing a scientific basis for climate change mitigation and agricultural management.
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Gases de Efecto Invernadero , Nitrógeno , Agricultura , Fertilizantes , Nitrógeno/análisis , Compuestos de Nitrógeno , Óxido Nitroso/análisis , SueloRESUMEN
Influenza A viruses pose a significant threat globally each year, underscoring the need for a vaccine- or antiviral-based broad-protection strategy. Here, we describe a chimeric monoclonal antibody, C12H5, that offers neutralization against seasonal and pandemic H1N1 viruses, and cross-protection against some H5N1 viruses. Notably, C12H5 mAb offers broad neutralizing activity against H1N1 and H5N1 viruses by controlling virus entry and egress, and offers protection against H1N1 and H5N1 viral challenge in vivo. Through structural analyses, we show that C12H5 engages hemagglutinin (HA), the major surface glycoprotein on influenza, at a distinct epitope overlapping the receptor binding site and covering the 140-loop. We identified eight highly conserved (~90%) residues that are essential for broad H1N1 recognition, with evidence of tolerance for Asp or Glu at position 190; this site is a molecular determinant for human or avian host-specific recognition and this tolerance endows C12H5 with cross-neutralization potential. Our results could benefit the development of antiviral drugs and the design of broad-protection influenza vaccines.
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Subtipo H1N1 del Virus de la Influenza A , Subtipo H5N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Infecciones por Orthomyxoviridae , Anticuerpos Monoclonales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Sitios de Unión , Anticuerpos ampliamente neutralizantes , Glicoproteínas Hemaglutininas del Virus de la Influenza , HumanosRESUMEN
Varicella-zoster virus (VZV) is the causative agent of varicella and herpes zoster (HZ) and can pose a significant challenge to human health globally. The initial VZV infection-more common in children-causes a self-limiting chicken pox. However, in later life, the latent VZV can become reactivated in these patients, causing HZ and postherpetic neuralgia (PHN), a serious and painful complication. VZV glycoprotein E (gE) has been developed into a licensed subunit vaccine against HZ (Shingrix). However, its efficacy relies on the concomitant delivery of a robust adjuvant (AS01B). Here, we sought to create a new immunogen for vaccine design by displaying the VZV-gE on the baculovirus surface (Bac-gE). Correct localization and display of gE on the engineered baculovirus was verified by flow cytometry and immune electron microscopy. We show that Bac-gE provides excellent antigenicity against VZV and induces not only stronger gE-specific CD4+ and CD8+ T cell responses but also higher levels of VZV-specific neutralizing antibodies as compared with other vaccine strategies in mice. Collectively, we show that the baculovirus display of VZV-gE confers ideal humoral and cellular immune responses required for HZ vaccine development, paving the way for a baculovirus-based vaccine design.
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Varicela , Vacuna contra el Herpes Zóster , Herpes Zóster , Animales , Baculoviridae/genética , Niño , Herpes Zóster/prevención & control , Herpesvirus Humano 3/genética , Humanos , Inmunidad Celular , RatonesRESUMEN
Stem cell differentiation is of great interest in medical research; however, specifically and effectively regulating stem cell differentiation is still a challenge. In addition to chemical factors, physical signals are an important component of the stem cell ecotone. The mechanical microenvironment of stem cells has a huge role in stem cell differentiation. Herein, we describe the knowledge accumulated to date on the mechanical environment in which stem cells exist, which consists of various factors, including the extracellular matrix and topology, substrate stiffness, shear stress, hydrostatic pressure, tension, and microgravity. We then detail the currently known signalling pathways that stem cells use to perceive the mechanical environment, including those involving nuclear factor-kB, the nicotinic acetylcholine receptor, the piezoelectric mechanosensitive ion channel, and hypoxia-inducible factor 1α. Using this information in clinical settings to treat diseases is the goal of this research, and we describe the progress that has been made. In this review, we examined the effects of mechanical factors in the stem cell growth microenvironment on stem cell differentiation, how mechanical signals are transmitted to and function within the cell, and the influence of mechanical factors on the use of stem cells in clinical applications.
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Matriz Extracelular , Células Madre , Ciclo Celular , Diferenciación Celular/fisiología , Proliferación Celular , Matriz Extracelular/fisiologíaRESUMEN
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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Ecosistema , Ríos , Bacterias/genética , Biodiversidad , China , Ríos/microbiologíaRESUMEN
Railway engineering generates large amounts of construction and demolition waste (CDW). To quantify the amount of CDW generated from railway engineering projects throughout the whole life cycle, a process-based life cycle assessment model is proposed in this paper. The life-cycle CDW is divided into four parts: CDW from off-site transportation of construction materials (OSTCM), CDW from site operation wastage of construction materials (SOWCM), discard ballast from roadbeds, stationyard, bridges and tunnels (DB), and CDW from reparation and renewal of aging components (RRAC). Yun-Gui Railway is selected as a case study to validate the developed model, and an uncertainty analysis is conducted with Oracle Crystal Ball software. The results show that between 175 and 311 million tons of CDW is generated throughout the whole life cycle of Yun-Gui Railway. DB is the largest component of the life-cycle CDW from railway engineering projects. This indicates the negative environmental impacts of railway construction can be significantly mitigated by optimizing the location of ballast disposal sites and developing suitable landfill proposals. Also, the CDW generated by wastage of construction materials during off-site construction and site operation is important in waste management in railway engineering projects, in which rubble, sand, and cement have the high potential for waste reduction. Findings from this study can contribute to the knowledge body as well as the engineering practice in green railways.