RESUMO
There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
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RNA Mensageiro/genética , RNA Viral/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Sítios de Ligação , Vacinas contra COVID-19 , Chlorocebus aethiops , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Feminino , Células HEK293 , Células HeLa , Humanos , Imunogenicidade da Vacina , Injeções Intramusculares , Macaca fascicularis , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nanopartículas/química , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Th1/imunologia , Potência de Vacina , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Células Vero , Vacinas Virais/administração & dosagem , Vacinas Virais/genéticaRESUMO
Teosinte, the wild ancestor of maize (Zea mays subsp. mays), has three times the seed protein content of most modern inbreds and hybrids, but the mechanisms that are responsible for this trait are unknown1,2. Here we use trio binning to create a contiguous haplotype DNA sequence of a teosinte (Zea mays subsp. parviglumis) and, through map-based cloning, identify a major high-protein quantitative trait locus, TEOSINTE HIGH PROTEIN 9 (THP9), on chromosome 9. THP9 encodes an asparagine synthetase 4 enzyme that is highly expressed in teosinte, but not in the B73 inbred, in which a deletion in the tenth intron of THP9-B73 causes incorrect splicing of THP9-B73 transcripts. Transgenic expression of THP9-teosinte in B73 significantly increased the seed protein content. Introgression of THP9-teosinte into modern maize inbreds and hybrids greatly enhanced the accumulation of free amino acids, especially asparagine, throughout the plant, and increased seed protein content without affecting yield. THP9-teosinte seems to increase nitrogen-use efficiency, which is important for promoting a high yield under low-nitrogen conditions.
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Nitrogênio , Zea mays , Zea mays/genética , Família , Sementes/genéticaRESUMO
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.
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Antivirais/farmacologia , Hidroxicolesteróis/farmacologia , Microcefalia/virologia , Infecção por Zika virus/complicações , Animais , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Imunofluorescência , Humanos , Macaca mulatta , Camundongos , Microscopia Confocal , Internalização do Vírus/efeitos dos fármacos , Zika virus/efeitos dos fármacos , Zika virus/fisiologiaRESUMO
Geraniol derived from essential oils of various plant species is widely used in the cosmetic and perfume industries. It is also an essential trait of the pleasant smell of rose flowers. In contrast to other monoterpenes which are produced in plastids via the methyl erythritol phosphate pathway, geraniol biosynthesis in roses relies on cytosolic NUDX1 hydrolase which dephosphorylates geranyl diphosphate (GPP). However, the metabolic origin of cytosolic GPP remains unknown. By feeding Rosa chinensis "Old Blush" flowers with pathway-specific precursors and inhibitors, combined with metabolic profiling and functional characterization of enzymes in vitro and in planta, we show that geraniol is synthesized through the cytosolic mevalonate (MVA) pathway by a bifunctional geranyl/farnesyl diphosphate synthase, RcG/FPPS1, producing both GPP and farnesyl diphosphate (FPP). The downregulation and overexpression of RcG/FPPS1 in rose petals affected not only geraniol and germacrene D emissions but also dihydro-ß-ionol, the latter due to metabolic cross talk of RcG/FPPS1-dependent isoprenoid intermediates trafficking from the cytosol to plastids. Phylogenetic analysis together with functional characterization of G/FPPS orthologs revealed that the G/FPPS activity is conserved among Rosaceae species. Site-directed mutagenesis and molecular dynamic simulations enabled to identify two conserved amino acids that evolved from ancestral FPPSs and contribute to GPP/FPP product specificity. Overall, this study elucidates the origin of the cytosolic GPP for NUDX1-dependent geraniol production, provides insights into the emergence of the RcG/FPPS1 GPPS activity from the ancestral FPPSs, and shows that RcG/FPPS1 plays a key role in the biosynthesis of volatile terpenoid compounds in rose flowers.
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Geraniltranstransferase , Rosa , Geraniltranstransferase/genética , Ácido Mevalônico/metabolismo , Rosa/metabolismo , Citosol/metabolismo , Filogenia , Terpenos/metabolismo , Flores/metabolismoRESUMO
The Zn content in cereal seeds is an important trait for crop production as well as for human health. However, little is known about how Zn is loaded to plant seeds. Here, through a genome-wide association study (GWAS), we identify the Zn-NA (nicotianamine) transporter gene ZmYSL2 that is responsible for loading Zn to maize kernels. High promoter sequence variation in ZmYSL2 most likely drives the natural variation in Zn concentrations in maize kernels. ZmYSL2 is specifically localized on the plasma membrane facing the maternal tissue of the basal endosperm transfer cell layer (BETL) and functions in loading Zn-NA into the BETL. Overexpression of ZmYSL2 increases the Zn concentration in the kernels by 31.6%, which achieves the goal of Zn biofortification of maize. These findings resolve the mystery underlying the loading of Zn into plant seeds, providing an efficient strategy for breeding or engineering maize varieties with enriched Zn nutrition.
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Estudo de Associação Genômica Ampla , Zea mays , Humanos , Zea mays/genética , Zea mays/metabolismo , Zinco/metabolismo , Melhoramento Vegetal , Sementes/genética , Proteínas de Membrana Transportadoras/genéticaRESUMO
Serine metabolic reprogramming is known to be associated with oncogenesis and tumor development. The key metabolic enzyme PSAT1 has been identified as a potential prognostic marker for various cancers, but its role in ccRCC remains unkown. In this study, we investigated expression of PSAT1 in ccRCC using the TCGA database and clinical specimens. Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT1 increased the susceptibility of sunitinib-resistant cells. Inhibition of PSAT1 increased the sensitivity of drug-resistant tumors to sunitinib in vivo. Collectively, our investigation identifies PSAT1 as an independent prognostic biomarker for advanced ccRCC patients and as a prospective therapeutic target.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Resistência a Medicamentos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Sunitinibe , Regulação para Cima/genéticaRESUMO
Diphenyl ether herbicides are extensively utilized in agricultural systems, but their residues threaten the health of sensitive rotation crops. Functional microbial strains can degrade diphenyl ether herbicides in the rhizosphere of crops, facilitating the restoration of a healthy agricultural environment. However, the interplay between microorganisms and plants in diphenyl ether herbicides degradation remains unclear. Thus, the herbicide-degrading strain Bacillus sp. Za and the sensitive crop, maize, were employed to uncover the interaction mechanism. The degradation of diphenyl ether herbicides by strain Bacillus sp. Za was promoted by root exudates. The strain induced root exudate re-secretion in diphenyl ether herbicide-polluted maize. We further showed that root exudates enhanced the rhizosphere colonization and the biofilm biomass of strain Za, augmenting its capacity to degrade diphenyl ether herbicide. Root exudates regulated gene fliZ, which is pivotal in biofilm formation. Wild-type strain Za significantly reduced herbicide toxicity to maize compared to the ZaΔfliZ mutant. Moreover, root exudates promoted strain Za growth and chemotaxis, which was related to biofilm formation. This mutualistic relationship between the microorganisms and the plants demonstrates the significance of plant-microbe interactions in shaping diphenyl ether herbicide degradation in rhizosphere soils. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 "No Rights Reserved" license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
Assuntos
Bacillus , Biofilmes , Herbicidas , Raízes de Plantas , Rizosfera , Zea mays , Zea mays/microbiologia , Bacillus/metabolismo , Bacillus/fisiologia , Herbicidas/metabolismo , Raízes de Plantas/microbiologia , Biodegradação Ambiental , Exsudatos de Plantas/metabolismo , Éteres Fenílicos/metabolismo , Poluentes do Solo/metabolismoRESUMO
Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) have attracted increasing interest in electronics due to their (semi)conducting properties. Charge-neutral 2D c-MOFs also possess persistent organic radicals that can be viewed as spin-concentrated arrays, affording new opportunities for spintronics. However, the strong π-interaction between neighboring layers of layer-stacked 2D c-MOFs annihilates active spin centers and significantly accelerates spin relaxation, severely limiting their potential as spin qubits. Herein, we report the precise tuning of the charge transport and spin dynamics in 2D c-MOFs via the control of interlayer stacking. The introduction of bulky side groups on the conjugated ligands enables a significant dislocation of the 2D c-MOFs layers from serrated stacking to staggered stacking, thereby spatially weakening the interlayer interactions. As a consequence, the electrical conductivity of 2D c-MOFs decreases by 6 orders of magnitude, while the spin density achieves more than a 30-fold increase and the spin-lattice relaxation time (T1) is increased up to â¼60 µs, hence being superior to the reference 2D c-MOFs with compact stackings whose spin relaxation is too fast to be detected. Spin dynamics results also reveal that spinless polaron pairs or bipolarons play critical roles in the charge transport of these 2D c-MOFs. Our strategy provides a bottom-up approach for enlarging spin dynamics in 2D c-MOFs, opening up pathways for developing MOF-based spintronics.
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Fat mass and obesity-associated protein (FTO) plays a crucial role in regulating the dynamic modification of N6-methyladenosine (m6A) in eukaryotic mRNA. Sensitive detection of the FTO level and efficient evaluation of the FTO demethylase activity are of great importance to early cancer diagnosis and anticancer drug discovery, which are currently challenged by limited sensitivity/precision and low throughput. Herein, a robust strategy based on the dephosphorylation switch DNAzyme-rolling circle amplification (RCA) circuit, termed DSD-RCA, is developed for highly sensitive detection of FTO and inhibitor screening. Initially, the catalytic activity of DNAzyme is silenced by engineering with an m6A modification in its catalytic core. Only in the presence of target FTO can the methyl group on DNAzyme be eliminated, resulting in the activation of the catalytic activity of DNAzyme and thus cleaving the hairpin substrate to release numerous primers. Different from the conventional methods that use the downstream cleavage primer with the original 3'-hydroxyl end directly as the RCA primer with the problem of high background signal, which should be compensated by additional separation and wash steps in heterogeneous format, our DSD-RCA assay uses the upstream cleavage primer with a 2',3'-cyclic phosphate terminus at the 3'-end serving as an intrinsically blocked 3' end. Only after a dephosphorylation reaction mediated by T4 polynucleotide kinase can the upstream cleavage primers with a resultant 3'-hydroxyl end be extended by RCA. With the high signal-to-noise ratio and homogeneous property, the proposed platform can sensitively detect FTO with a limit of detection of 31.4 pM, and the relative standard deviations (RSDs %) ranging from 0.8 to 2.0% were much lower than the heterogeneous methods. The DSD-RCA method was applied for analyzing FTO in cytoplasmic lysates from different cell lines and tissues of breast cancer patients and further used for screening FTO inhibitors without the need for separation or cleaning, providing an opportunity for achieving high throughput and demonstrating the potential applications of this strategy in disease diagnostics, drug discovery, and biological applications.
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Técnicas Biossensoriais , DNA Catalítico , Humanos , DNA Catalítico/química , Técnicas Biossensoriais/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Linhagem Celular , Polinucleotídeo 5'-Hidroxiquinase , Limite de Detecção , Dioxigenase FTO Dependente de alfa-CetoglutaratoRESUMO
Achieving accurate detection of different speciations of heavy metal ions (HMIs) in an aqueous solution is an urgent problem due to the different bioavailabilities and physiological toxicity. Herein, we nominated a novel strategy to detect HCrO4- and Cr(OH)2+ at a trace level via the electrochemical sensitive surface constructed by Co3O4-rGO modified with amino and carboxyl groups, which revealed that the interactions between distinct functional groups and different oxygen-containing groups of target ions are conducive to the susceptible and anti-interference detection. The detection sensitivities of 19.46 counts µg-1 L for HCrO4- and 13.44 counts µg-1 L for Cr(OH)2+ were obtained under optimal conditions, while the limits of detection were 0.10 and 0.12 µg L-1, respectively. Satisfactory anti-interference and actual water sample analysis results were obtained. A series of advanced optical techniques like X-ray photoelectron spectroscopy, X-ray absorption near-edge structure technology, and density functional theory calculations under an electric field demonstrated that chemical interactions between groups contribute more to the fixation of target ions than electrical attraction alone. The presence of oxygen-containing groups distinct from simple ionic forms was a critical factor in the selectivity and anti-interference detection. Furthermore, the valence cycle of Co(II)/(III) synergistically boosted the detection performance. This research provides a promising tactic from the microscopic perspective of groups' interactions to accomplish the precise speciation analysis of HMIs in the water environment.
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Solid contact (SC) calcium ion-selective electrodes (Ca2+-ISEs) have been widely applied in the analysis of water quality and body fluids by virtue of the unique advantages of easy operation and rapid response. However, the potential drift during the long-term stability test hinders their further practical applications. Designing novel redox SC layers with large capacitance and high hydrophobicity is a promising approach to stabilize the potential stability, meanwhile, exploring the transduction mechanism is also of great guiding significance for the precise design of SC layer materials. Herein, flower-like copper sulfide (CunS-50) composed of nanosheets is meticulously designed as the redox SC layer by modification with the surfactant (CTAB). The CunS-50-based Ca2+-ISE (CunS-50/Ca2+-ISE) demonstrates a near-Nernstian slope of 28.23 mV/dec for Ca2+ in a wide activity linear range of 10-7 to 10-1 M, with a low detection limit of 3.16 × 10-8 M. CunS-50/Ca2+-ISE possesses an extremely low potential drift of only 1.23 ± 0.13 µV/h in the long-term potential stability test. Notably, X-ray absorption fine-structure (XAFS) spectra and electrochemical experiments are adopted to elucidate the transduction mechanism that the lipophilic anion (TFPB-) participates in the redox reaction of CunS-50 at the solid-solid interface of ion-selective membrane (ISM) and redox inorganic SC layer (CunS-50), thereby promoting the generation of free electrons to accelerate ion-electron transduction. This work provides an in-depth comprehension of the transduction mechanism of the potentiometric response and an effective strategy for designing redox materials of ion-electron transduction triggered by lipophilic anions.
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Although utilizing nanomaterial-modified electrodes for lead ion detection has achieved great success, most of them are carried out under acidic conditions and ignore the variation of Pb(II) speciation at different pH conditions, leading to the potential inaccuracy of Pb(II) detection in a neutral natural water environment. Thus, designing a novel catalyst with high accuracy for the detection of various forms of the total amount of Pb(II) (Pb2+ and Pb(OH)+) in neutral waters is significant. Herein, Pt nanoclusters (Pt NCs) were elaborately constructed and stabilized on the Co single-atom-doped g-C3N4 with abundant N vacancies (Pt NCs/VN-C3N4), which achieved the ultrasensitive detection (102.16 µM µA-1) of Pb(II) in neutral conditions. The dynamic simulation and theoretical calculations reveal that the parallel deposition of Pb2+ and Pb(OH)+ occurs on the electrode surface modified by Pt NCs/VN-C3N4, and the current peaks of Pb(II) are cocontributed by Pb2+ and Pb(OH)+ species. An "electron inverse" phenomenon in Pt NCs/VN-C3N4 from the VN-C3N4 substrate to Pt NCs endows Pt NCs in an electron-rich state, serving as active centers to promote rapid and efficient reduction for both Pb2+ and Pb(OH)+, facilitating the accurate detection of the total amount of Pb(II) in all forms in the actual water environment.
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BACKGROUND: Ubiquitin-specific proteases family is crucial to host immunity against pathogens. However, the correlations between USP21 and immunosurveillance and immunotherapy for colorectal cancer (CRC) have not been reported. METHODS: The differential expression of USP21 between CRC tissues and normal tissues was analyzed using multiple public databases. Validation was carried out in clinical samples through qRT-PCR and IHC. The correlation between USP21 and the prognosis, as well as clinical pathological characteristics of CRC patients, was investigated. Moreover, cell models were established to assess the influence of USP21 on CRC growth and progression, employing CCK-8 assays, colony formation assays, and wound-healing assays. Subsequently, gene set variation analysis (GSVA) was used to explore the potential biological functions of USP21 in CRC. The study also examined the impact of USP21 on cytokine levels and immune cell infiltration in the tumor microenvironment (TME). Finally, the effect of USP21 on the response to immunotherapy and chemotherapy in CRC was analyzed. RESULTS: The expression of USP21 was significantly upregulated in CRC. High USP21 is correlated with poor prognosis in CRC patients and facilitates the proliferation and migration capacities of CRC cells. GSVA indicated an association between low USP21 and immune activation. Moreover, low USP21 was linked to an immune-activated TME, characterized by high immune cell infiltration. Importantly, CRC with low USP21 exhibited higher tumor mutational burden, high PD-L1 expression, and better responsiveness to immunotherapy and chemotherapeutic drugs. CONCLUSION: This study revealed the role of USP21 in TME, response to therapy, and clinical prognosis in CRC, which provided novel insights for the therapeutic application in CRC.
Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Ubiquitina Tiolesterase , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Microambiente Tumoral/imunologia , Prognóstico , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Masculino , Feminino , Proliferação de Células , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Imunoterapia/métodosRESUMO
Developing active, stable, and cost-efficient electrocatalysts to replace platinum for the alkaline hydrogen evolution reaction (HER) is highly desirable yet represents a great challenge. Here, it is reported on a facile one-pot synthesis of RuxNi layered double hydroxides (RuxNi-LDHs) that exhibit remarkable HER activity and stability after an in-situ activation treatment, surpassing most state-of-the-art Ru-based catalysts as well as commercial Ru/C and Pt/C catalysts. The structural and chemical changes triggered by in-situ activation are systematically investigated, and the results clearly show that the pristine, less-active RuxNi-LDHs are transformed into a highly active catalyst characterized by raft-like, defect-rich Ru° particles decorated on the surface of RuxNi-LDHs. Density functional theory (DFT) calculations reveal that the defective Ru sites can effectively optimize the reaction pathway and lower the free energies of the elemental steps involved, leading to enhanced intrinsic activity. This work highlights the importance of the currently understudied strategy of defect engineering in boosting the HER activity of Ru-based catalysts and offers an effective approach involving in-situ electrochemical activation for the development of high-performance alkaline HER catalysts.
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Alkali-metal doped perovskite oxides have emerged as promising materials due to their unique properties and broad applications in various fields, including photovoltaics and catalysis. Understanding the complex interplay between alkali metal doping, structural modifications, and their impact on performance remains a crucial challenge. In this study, this challenge is addressed by investigating the synthesis and properties of Rb-doped perovskite oxides. These results reveal that the doping of Rb into perovskite oxides function as a structural modifier in the as-synthesized samples and during the oxygen evolution reaction (OER) as well. Electron microscopy and first-principles calculations confirm the enrichment of Rb on the surface of the as-synthesized sample. Further investigations into the electrocatalytic reaction revealed that the Rb-doped perovskite underwent drastic restructuring with Rb leaching and formation of strontium oxide.
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The biosynthesis of specialized metabolites is strictly regulated by environmental inputs such as the day-night cycle, but the underlying mechanisms remain elusive. In Petunia hybrida cv. Mitchell flowers, the biosynthesis and emission of volatile compounds display a diurnal pattern with a peak in the evening to attract nocturnal pollinators. Using petunia flowers as a model system, we found that chromatin level regulation, especially histone acetylation, plays an essential role in mediating the day-night oscillation of the biosynthetic gene network of specialized metabolites. By performing time-course chromatin immunoprecipitation assays for histone modifications, we uncovered that a specific group of genes involved in the regulation, biosynthesis, and emission of floral volatile compounds, which displays the greatest magnitude in day-night oscillating gene expression, is associated with highly dynamic histone acetylation marks H3K9ac and H3K27ac. Specifically, the strongest oscillating genes featured a drastic removal of histone acetylation marks at night, potentially to shut down the biosynthesis of floral volatile compounds during the morning when they are not needed. Inhibiting daytime histone acetylation led to a compromised evening induction of these genes. Overall, our study suggested an active role of chromatin modification in the diurnal oscillation of specialized metabolic network.
Assuntos
Histonas , Petunia , Histonas/metabolismo , Acetilação , Redes e Vias Metabólicas , Processamento de Proteína Pós-Traducional , Cromatina/metabolismo , Flores/fisiologia , Petunia/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Nuclear-cytoplasmic trafficking is crucial for protein synthesis in eukaryotic cells due to the spatial separation of transcription and translation by the nuclear envelope. However, the mechanism underlying this process remains largely unknown in plants. In this study, we isolated a maize (Zea mays) mutant designated developmentally delayed kernel 1 (ddk1), which exhibits delayed seed development and slower filling. Ddk1 encodes a plant-specific protein known as Importin-4 ß, and its mutation results in reduced 80S monosomes and suppressed protein synthesis. Through our investigations, we found that DDK1 interacts with eIF1A proteins in vivo. However, in vitro experiments revealed that this interaction exhibits low affinity in the absence of RanGTP. Additionally, while the eIF1A protein primarily localizes to the cytoplasm in the wild-type, it remains significantly retained within the nuclei of ddk1 mutants. These observations suggest that DDK1 functions as an exportin and collaborates with RanGTP to facilitate the nuclear export of eIF1A, consequently regulating endosperm development at the translational level. Importantly, both DDK1 and eIF1A are conserved among various plant species, implying the preservation of this regulatory module across diverse plants.
Assuntos
Sementes , Zea mays , Transporte Ativo do Núcleo Celular , Zea mays/metabolismo , Sementes/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Carioferinas/genética , Carioferinas/metabolismo , Grão Comestível/metabolismoRESUMO
Core-shell hydrogel microcapsules have sparked great interest due to their unique characteristics and prospective applications in the medical, pharmaceutical, and cosmetic fields. However, complex synthetic procedures and expensive costs have limited their practical application. Herein, we designed and prepared several multichannel and multijunctional droplet microfluidic devices based on soft lithography for the effective synthesis of core-shell hydrogel microcapsules for different purposes. Additionally, two different cross-linking processes (ultraviolet (UV) exposure and interfacial polymerization) were used to synthesize different types of core-shell structured hydrogel microcapsules. Hydrogel microcapsules with gelatin methacryloyl (GelMA) as the core and polyacrylamide (PAM) as the thin shell were synthesized using UV cross-linking. Using an interfacial polymerization process, another core-shell structured microcapsule with GelMA as the core and Ca2+ cross-linked alginate with polyethylenimine (PEI) as the shell was constructed, and the core diameter and total droplet diameter were flexibly controlled by carving. Noteworthy, these hydrogel microcapsules exhibit stimuli-responsiveness and controlled release ability. Overall, a novel technique was developed to successfully synthesize various hydrogel microcapsules with core-shell microstructures. The hydrogel microcapsules possess a multilayered structure that facilitates the coassembly of cells and drugs, as well as the layered assembly of multiple drugs, to develop synergistic therapeutic regimens. These adaptable and controllable hydrogel microdroplets shall held great promise for multicell or multidrug administration as well as for high-throughput drug screening.
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Alginatos , Hidrogéis , Hidrogéis/química , Cápsulas/química , Alginatos/química , Ácido Glucurônico/química , Ácidos Hexurônicos/químicaRESUMO
Ethanethiol (EtSH), being highly toxic, flammable, and explosive, poses significant risks to human health and safety and is capable of causing fires and explosions. Room-temperature detection using chemiresistive gas sensors is essential for managing these risks. However, the gas-sensing performance of conventional metal-oxide sensing materials may be limited by their weak interaction with EtSH at room temperature. Herein, SnO2 nanoflowers assembled with non-noble Cu-site-enriched porous nanosheets were designed and prepared by an in situ self-template pyrolysis synthesis strategy to enable highly sensitive and selective room-temperature detection of EtSH. By regulating the number of non-noble Cu sites, these nanoflowers achieved efficient EtSH sensing with a Ra/Rg value of 11.0 at 50 ppb, ensuring high selectivity, reproducibility, and stability at room temperature. Moreover, a comparative analysis of the room-temperature gas-sensing performance of SnO2 nanoflowers with non-noble Fe- or Ni-site-enriched nanosheets highlights the benefits of non-noble Cu sites for EtSH detection. Density functional theory (DFT) analysis reveals that non-noble Cu sites have a unique affinity for EtSH, offering preferential binding over other gases and explaining the outstanding sensing performance of non-noble Cu-site-enriched nanosheet-assembled SnO2 nanoflowers. The structural and interface engineering of the sensing materials presented in this work provides a promising approach for offering efficient and durable gas sensors operable at room temperature.
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Polysaccharides in extracellular polymeric substances (EPS) can form a hybrid matrix network with proteins, impeding waste-activated sludge (WAS) fermentation. Amino sugars, such as N-acetyl-d-glucosamine (GlcNAc) polymers and sialic acid, are the non-negligible components in the EPS of aerobic granules or biofilm. However, the occurrence of amino sugars in WAS and their degradation remains unclear. Thus, amino sugars (â¼6.0%) in WAS were revealed, and the genera of Lactococcus and Zoogloea were identified for the first time. Chitin was used as the substrate to enrich a chitin-degrading consortium (CDC). The COD balances for methane production ranged from 83.3 and 95.1%. Chitin was gradually converted to oligosaccharides and GlcNAc after dosing with the extracellular enzyme. After doing enriched CDC in WAS, the final methane production markedly increased to 60.4 ± 0.6 mL, reflecting an increase of â¼62%. Four model substrates of amino sugars (GlcNAc and sialic acid) and polysaccharides (cellulose and dextran) could be used by CDC. Treponema (34.3%) was identified as the core bacterium via excreting chitinases (EC 3.2.1.14) and N-acetyl-glucosaminidases (EC 3.2.1.52), especially the genetic abundance of chitinases in CDC was 2.5 times higher than that of WAS. Thus, this study provides an elegant method for the utilization of amino sugar-enriched organics.