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PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves a wide range of use cases. In the past two years, a number of changes were made to PubChem. Data from more than 120 data sources was added to PubChem. Some major highlights include: the integration of Google Patents data into PubChem, which greatly expanded the coverage of the PubChem Patent data collection; the creation of the Cell Line and Taxonomy data collections, which provide quick and easy access to chemical information for a given cell line and taxon, respectively; and the update of the bioassay data model. In addition, new functionalities were added to the PubChem programmatic access protocols, PUG-REST and PUG-View, including support for target-centric data download for a given protein, gene, pathway, cell line, and taxon and the addition of the 'standardize' option to PUG-REST, which returns the standardized form of an input chemical structure. A significant update was also made to PubChemRDF. The present paper provides an overview of these changes.
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Bases de Dados de Compostos Químicos , Descoberta de Drogas , Descoberta de Drogas/métodos , Bioensaio , Proteínas , QuimioinformáticaRESUMO
Studying glycans and their functions in the body aids in the understanding of disease mechanisms and developing new treatments. This necessitates resources that provide comprehensive glycan data integrated with relevant information from other scientific fields such as genomics, genetics, proteomics, metabolomics, and chemistry. The present paper describes two resources at the U.S. National Center for Biotechnology Information (NCBI), the NCBI Glycans and PubChem, which provide glycan-related information useful for the glycoscience research community. The NCBI Glycans ( https://www.ncbi.nlm.nih.gov/glycans/ ) is a dedicated website for glycobiology data content at NCBI and provides quick access to glycan-related information scattered across multiple NCBI databases as well as other information resources external to NCBI. Importantly, the NCBI Glycans hosts the official web page for the symbol nomenclature for glycans (SNFG), which is the standard graphical representation of glycan structures recommended for scientific publication. On the other hand, PubChem ( https://pubchem.ncbi.nlm.nih.gov ) is a research-focused, large-scale public chemical database, containing a substantial number of glycan-containing records and is integrated with important glycoscience resources like GlyTouCan, GlyCosmos, and GlyGen. PubChem organizes glycan-related information within multiple data collections (i.e., Substance, Compound, Protein, Gene, Pathway, and Taxonomy) and provides various tools and services that allow users to access them both interactively through a web browser and programmatically through a REST-ful interface, including PUG-View. The NCBI Glycans and PubChem highlight glycan-related data and improve their accessibility, helping scientists exploit these data in their research.
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The atomic precision of ultrasmall metal nanoclusters has opened the door to elucidating the structural evolution principles of metal nanomaterials at the molecular level. Here, we report a novel set of super-atomic Ag clusters, including [Ag19(TBBT)16(DPPP)4]+ (Ag19), [Ag22(DMAT)8(DPPM)4Cl8]2+ (Ag22), Ag26(SPh3,5-CF3)15(DPPF)4Cl5 (Ag26), and [Ag30(DMAT)12(DPPP)4Cl8]2+ (Ag30). The core structures of these clusters correspond to one decahedral Ag7, perpendicular bi-decahedrons, three-dimensional penta-decahedrons, and hexa-decahedrons, respectively. The Ag atoms in AgS2 blocks show a strong correlation with the decahedral cores: the five equatorial Ag atoms in the decahedral Ag7 core of Ag19 all adopt the AgS2 coordination, while the Ag atoms in AgS2 blocks of Ag22, Ag26, and Ag30 unexceptionally constitute additional decahedral structures with the core Ag atoms. Specifically, two and four core Ag atoms of Ag26 and Ag30 clusters occupy positions that highly resemble that of Ag (in AgS2 motifs) of Ag22. The strong structural correlation demonstrates the motif-to-core evolution of the surface Ag (on AgS2) to build extra-decahedral blocks. Density functional theory calculations indicate that the 2e, 4e, 6e, and 8e clusters (from Ag19 to Ag30) adopt 1S2, 1S21P2, 1S21P4, and 1S21P6 electron configurations, all of which feature excellent super-atomic characters.
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PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves the scientific community as well as the general public, with millions of unique users per month. In the past two years, PubChem made substantial improvements. Data from more than 100 new data sources were added to PubChem, including chemical-literature links from Thieme Chemistry, chemical and physical property links from SpringerMaterials, and patent links from the World Intellectual Properties Organization (WIPO). PubChem's homepage and individual record pages were updated to help users find desired information faster. This update involved a data model change for the data objects used by these pages as well as by programmatic users. Several new services were introduced, including the PubChem Periodic Table and Element pages, Pathway pages, and Knowledge panels. Additionally, in response to the coronavirus disease 2019 (COVID-19) outbreak, PubChem created a special data collection that contains PubChem data related to COVID-19 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
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COVID-19/prevenção & controle , Bases de Dados de Compostos Químicos , Armazenamento e Recuperação da Informação/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , Interface Usuário-Computador , COVID-19/epidemiologia , COVID-19/virologia , Descoberta de Drogas/estatística & dados numéricos , Epidemias , Humanos , Armazenamento e Recuperação da Informação/métodos , Internet , Saúde Pública/estatística & dados numéricos , SARS-CoV-2/fisiologia , SoftwareRESUMO
Apolygus lucorum (Hemiptera, Insecta), cosmopolitan true bug, is a major pest of the Chinese jujube (Ziziphus jujuba). To propose control measures of A. lucorum, we investigated the molecular mechanisms of resistance in two varieties of jujube (wild jujube and winter jujube) with different sensitivities to this pest. We monitored changes of two species of jujube in the transcriptome, jasmonic acid (JA) and salicylic acid (SA) content, and the expression of genes involved in signaling pathways. The preference of A. lucorum for jujube with exogenous SA and methyl jasmonate (MeJA) were also examined. The results showed that wild jujube leaves infested by A. lucorum showed stronger resistance and non-selectivity to A. lucorum than winter jujube. By comparing data from the A. lucorum infested plants with the control, A total of 438 and 796 differentially expressed genes (DEGs) were found in winter and wild jujube leaves, respectively. GO analysis revealed that biological process termed "plant-pathogen interactions", "plant hormone transduction" and "phenylpropanoid biosynthesis". Most of DEGs enriched in JA pathways were upregulated, while most DEGs of SA pathways were downregulated. A. lucorum increased the JA content but decreased the SA content in jujube. Consistently, the JA and SA contents in winter jujube were lower than those in wild jujube leaves. The key genes ZjFAD3, ZjLOX, ZjAOS, ZjAOC3 and ZjAOC4 involved in JA synthesis of jujube leaves were significantly up-regulated after A. lucorum infestation, especially the expression and up-regulation ratio of ZjFAD3, ZjLOX and ZjAOS in wild jujube were significantly higher than those in winter jujube. MeJA-treated jujube showed an obvious repellent effect on A. lucorum. Based on these findings, we conclude that A. lucorum infestation of jujube induced the JA pathway and suppressed the SA pathway. In jujube leaves the ZjFAD3, ZjLOX and ZjAOS played important roles in increasing of JA content in jujube leaves. Thus, JA played an important role in repelling and resisting against A. lucorum in jujube.
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Heterópteros , Ziziphus , Animais , Ziziphus/metabolismo , Transdução de Sinais , Insetos , Ácido Salicílico/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
BACKGROUND: A variety of cis-acting RNA elements with structures in the 5'- or 3'-untranslated region (UTR) of viral genomes play key roles in viral translation. Cherry virus A (CVA) is a member of the genus Capillovirus in the family Betaflexiviridae. It has a positive single-stranded RNA genome of ~ 7400 nucleotides (nt). The length of the CVA 5'-UTR is ~ 100 nt; however, the function of this long UTR has not yet been reported. METHODS: Molecular and phylogenetic analyses were performed on 75 CVA sequences, which could be divided into four groups, and the RNA secondary structure was predicted in four CVA 5'-UTR types. These four CVA 5'-UTR types were then inserted upstream of the firefly luciferase reporter gene FLuc (FLuc), and in vitro translation of the corresponding transcripts was evaluated using wheat germ extract (WGE). Then, in-line structure probing was performed to reveal the conserved RNA structures in CVA-5'UTR. RESULTS: The four CVA 5'-UTR types appeared to have a conserved RNA structure, and the FLuc construct containing these four CVA 5'-UTR types increased the translation of FLuc by 2-3 folds, suggesting weak translation enhancement activity. Mutations in CVA 5'-UTR suppressed translation, suggesting that the conserved RNA structure was important for function. CONCLUSION: The conserved RNA secondary structure was identified by structural evolution analysis of different CVA isolates and was found to regulate translation.
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Flexiviridae , RNA Viral , Regiões 3' não Traduzidas , Regiões 5' não Traduzidas , Flexiviridae/genética , Filogenia , RNA Viral/química , RNA Viral/genéticaRESUMO
PubChem (https://pubchem.ncbi.nlm.nih.gov) is a key chemical information resource for the biomedical research community. Substantial improvements were made in the past few years. New data content was added, including spectral information, scientific articles mentioning chemicals, and information for food and agricultural chemicals. PubChem released new web interfaces, such as PubChem Target View page, Sources page, Bioactivity dyad pages and Patent View page. PubChem also released a major update to PubChem Widgets and introduced a new programmatic access interface, called PUG-View. This paper describes these new developments in PubChem.
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Biologia Computacional/métodos , Bases de Dados de Compostos Químicos , Preparações Farmacêuticas/química , Bibliotecas de Moléculas Pequenas/química , Animais , Bioensaio/métodos , Descoberta de Drogas/métodos , Ensaios de Triagem em Larga Escala/métodos , Humanos , Armazenamento e Recuperação da Informação/métodos , Internet , Estrutura Molecular , Patentes como Assunto , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Virus disease is one of the main diseases in grapevine, and there has been no report on Plum bark necrosis and stem pitting-associated virus infecting grapevine in China. OBJECTIVE: The leaf samples of grapevine cultivar 'Cabernet Gernischt' were collected from Shandong province, which the leaves suffered from viral-like symptoms with spotting and crinkle. METHODS: Small RNA-seq combined with reverse transcription PCR (RT-PCR) were performed to detect the potential viruses in these field samples. Phylogenetic tree was constructed using the neighbor joining method in MEGA 5.1 CONCLUSIONS: This is the first report of PBNSPaV infecting grapevine in China, contributing to a better understanding of the epidemiology and host range distribution of this pathogen.
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Closteroviridae/genética , Especificidade de Hospedeiro , Doenças das Plantas/virologia , Folhas de Planta/virologia , Prunus domestica/virologia , Vitis/virologia , China , Closteroviridae/classificação , Closteroviridae/patogenicidade , Genoma Viral , Filogenia , Casca de Planta/virologia , RNA Viral/genéticaRESUMO
BACKGROUND: Rice black-streaked dwarf virus (RBSDV) and Southern rice black-streaked dwarf virus (SRBSDV) seriously interfered in the production of rice and maize in China. These two viruses are members of the genus Fijivirus in the family Reoviridae and can cause similar dwarf symptoms in rice. Although some studies have reported the phylogenetic analysis on RBSDV or SRBSDV, the evolutionary relationship between these viruses is scarce. METHODS: In this study, we analyzed the evolutionary relationships between RBSDV and SRBSDV based on the data from the analysis of codon usage, RNA recombination and phylogenetic relationship, selection pressure and genetic characteristics of the bicistronic RNAs (S5, S7 and S9). RESULTS: RBSDV and SRBSDV showed similar patterns of codon preference: open reading frames (ORFs) in S7 and S5 had with higher and lower codon usage bias, respectively. Some isolates from RBSDV and SRBSDV formed a clade in the phylogenetic tree of S7 and S9. In addition, some recombination events in S9 occurred between RBSDV and SRBSDV. CONCLUSIONS: Our results suggest close evolutionary relationships between RBSDV and SRBSDV. Selection pressure, gene flow, and neutrality tests also supported the evolutionary relationships.
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Evolução Molecular , Vírus de Plantas/genética , RNA Viral/genética , Reoviridae/genética , China , Fluxo Gênico , Fases de Leitura Aberta , Oryza/virologia , Doenças das Plantas/virologia , RNA/genética , RNA Mensageiro , Seleção Genética , Zea mays/virologiaRESUMO
Chromatin remodeling is essential for gene expression regulation in plant development and response to stresses. Brahma (BRM) is a conserved ATPase in the SWI/SNF chromatin remodeling complex and is involved in various biological processes in plant cells, but the regulation mechanism on BRM protein remains unclear. Here, we report that BRM interacts with AtMMS21, a SUMO ligase in Arabidopsis (Arabidopsis thaliana). The interaction was confirmed in different approaches in vivo and in vitro. The mutants of BRM and AtMMS21 displayed a similar defect in root development. In the mms21-1 mutant, the protein level of BRM-GFP was significantly lower than that in wild type, but the RNA level of BRM did not change. Biochemical evidence indicated that BRM was modified by SUMO3, and the reaction was enhanced by AtMMS21. Furthermore, overexpression of wild-type AtMMS21 but not the mutated AtMMS21 without SUMO ligase activity was able to recover the stability of BRM in mms21-1 Overexpression of BRM in mms21-1 partially rescued the developmental defect of roots. Taken together, these results supported that AtMMS21 regulates the protein stability of BRM in root development.
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Adenosina Trifosfatases/genética , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Ligases/genética , Raízes de Plantas/genética , Adenosina Trifosfatases/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Montagem e Desmontagem da Cromatina/genética , Immunoblotting , Ligases/metabolismo , Microscopia Confocal , Modelos Genéticos , Mutação , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Ligação Proteica , Estabilidade Proteica , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Abiotic stresses often disrupt protein folding and induce endoplasmic reticulum (ER) stress. There is a sophisticated ER quality control (ERQC) system to mitigate the effects of malfunctioning proteins and maintain ER homeostasis. The accumulation of misfolded proteins in the ER activates the unfolded protein response (UPR) to enhance ER protein folding and the degradation of misfolded proteins mediate by ER-associated degradation (ERAD). That ERQC reduces abiotic stress damage has been well studied in mammals and yeast. However, in plants, both ERAD and UPR have been studied separately and found to be critical for plant abiotic stress tolerance. In this study, we discovered that UPR-associated transcription factors AtbZIP17, AtbZIP28 and AtbZIP60 responded to tunicamycin (TM) and NaCl induced ER stress and subsequently enhanced Arabidopsis thaliana abiotic stress tolerance. They regulated the expression level of ER chaperones and the HRD1-complex components. Moreover, overexpression of AtbZIP17, AtbZIP28 and AtbZIP60 could restore stress tolerance via ERAD in the HRD1-complex mutant hrd3a-2, which suggested that UPR and ERAD have an interactive mechanism in Arabidopsis.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Degradação Associada com o Retículo Endoplasmático/fisiologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/genética , Estresse do Retículo Endoplasmático/fisiologia , Degradação Associada com o Retículo Endoplasmático/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Resposta a Proteínas não Dobradas/genética , Resposta a Proteínas não Dobradas/fisiologiaRESUMO
Marker-free transgenic plants can be developed through transposon-mediated transgene reintegration, which allows intact transgene insertion with defined boundaries and requires only a few primary transformants. In this study, we improved the selection strategy and validated that the maize (Zea mays) Activator/Dissociation (Ds) transposable element can be routinely used to generate marker-free transgenic plants. A Ds-based gene of interest was linked to green fluorescent protein in transfer DNA (T-DNA), and a green fluorescent protein-aided counterselection against T-DNA was used together with polymerase chain reaction (PCR)-based positive selection for the gene of interest to screen marker-free progeny. To test the efficacy of this strategy, we cloned the Bacillus thuringiensis (Bt) δ-endotoxin gene into the Ds elements and transformed transposon vectors into rice (Oryza sativa) cultivars via Agrobacterium tumefaciens. PCR assays of the transposon empty donor site exhibited transposition in somatic cells in 60.5% to 100% of the rice transformants. Marker-free (T-DNA-free) transgenic rice plants derived from unlinked germinal transposition were obtained from the T1 generation of 26.1% of the primary transformants. Individual marker-free transgenic rice lines were subjected to thermal asymmetric interlaced-PCR to determine Ds(Bt) reintegration positions, reverse transcription-PCR and enzyme-linked immunosorbent assay to detect Bt expression levels, and bioassays to confirm resistance against the striped stem borer Chilo suppressalis. Overall, we efficiently generated marker-free transgenic plants with optimized transgene insertion and expression. The transposon-mediated marker-free platform established in this study can be used in rice and possibly in other important crops.
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Elementos de DNA Transponíveis/genética , Oryza/genética , Plantas Geneticamente Modificadas/genética , Animais , Bacillus thuringiensis/genética , DNA Bacteriano/genética , DNA de Plantas/genética , Resistência à Doença/genética , Marcadores Genéticos/genética , Vetores Genéticos/genética , Proteínas de Fluorescência Verde/genética , Lepidópteros , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transformação Genética/genética , Transgenes/genéticaRESUMO
Plants modify their growth and development to protect themselves from detrimental conditions by triggering a variety of signaling pathways, including the activation of the ubiquitin-mediated protein degradation pathway. Endoplasmic reticulum (ER)-associated protein degradation (ERAD) is an important aspect of the ubiquitin-proteasome system, but only a few of the active ERAD components have been reported in plants. Here, we report that the Arabidopsis thaliana ubiquitin-conjugating enzyme, UBC32, a stress-induced functional ubiquitin conjugation enzyme (E2) localized to the ER membrane, connects the ERAD process and brassinosteroid (BR)-mediated growth promotion and salt stress tolerance. In vivo data showed that UBC32 was a functional ERAD component that affected the stability of a known ERAD substrate, the barley (Hordeum vulgare) powdery mildew O (MLO) mutant MLO-12. UBC32 mutation caused the accumulation of bri1-5 and bri1-9, the mutant forms of the BR receptor, BRI1, and these mutant forms subsequently activated BR signal transduction. Further genetic and physiological data supported the contention that UBC32 plays a role in the BR-mediated salt stress response and that BR signaling is necessary for the plant to tolerate salt. Our data indicates a possible mechanism by which an ERAD component regulates the growth and stress response of plants.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Brassinosteroides/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Immunoblotting , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Cloreto de Sódio/farmacologia , Enzimas de Conjugação de Ubiquitina/genéticaRESUMO
Protein ubiquitination requires the concerted action of three enzymes: ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin ligase (E3). These ubiquitination enzymes belong to an abundant protein family that is encoded in all eukaryotic genomes. Describing their biochemical characteristics is an important part of their functional analysis. It has been recognized that various E2/E3 specificities exist, and that detection of E3 ubiquitination activity in vitro may depend on the recruitment of E2s. Here, we describe the development of an in vitro ubiquitination system based on proteins encoded by genes from Arabidopsis. It includes most varieties of Arabidopsis E2 proteins, which are tested with several RING-finger type E3 ligases. This system permits determination of E3 activity in combination with most of the E2 sub-groups that have been identified in the Arabidopsis genome. At the same time, E2/E3 specificities have also been explored. The components used in this system are all from plants, particularly Arabidopsis, making it very suitable for ubiquitination assays of plant proteins. Some E2 proteins that are not easily expressed in Escherichia coli were transiently expressed and purified from plants before use in ubiquitination assays. This system is also adaptable to proteins of species other than plants. In this system, we also analyzed two mutated forms of ubiquitin, K48R and K63R, to detect various types of ubiquitin conjugation.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Genes de Plantas , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitinação , Sequência de Aminoácidos , Arabidopsis/enzimologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Sequência Conservada , Ativação Enzimática , Estabilidade Enzimática , Escherichia coli/genética , Escherichia coli/metabolismo , Mutação Puntual , Estrutura Terciária de Proteína , Especificidade por Substrato , Enzimas de Conjugação de Ubiquitina/genéticaRESUMO
Fluoroglycofen and acetochlor are two different herbicides used in vineyards to eradicate weeds. This present study first characterized the effects of these chemicals on phenotype of grape leaves. Results showed that acetochlor caused the middle- and upper-node grape leaves become yellow at 60th day after treatment, while fluoroglycofen caused the ones became dark green. Then the effects of fluoroglycofen on photosynthetic pigments and chloroplast ultrastructure were characterized. Results showed that fluoroglycofen increased the chlorophyll and carotenoid contents by different extent in different node leaves, while it did not affect the net photosynthesis rate significantly. Chloroplast ultrastructure analysis showed that the gap between thylakoids layers in few chloroplasts of middle-node leaves increased, which was also observed in ones of upper-node leaves; the number and size of chloroplast increased. Analysis on the deformed leaves of grapevines treated with 375 g ai ha(-1) fluoroglycofen showed that the starch grain per cell was much more and larger than that in the same size control leaves; the dark green and yellow parts had more or fewer chloroplast than the control, respectively, but both with more grana per chloroplast and less layers per granum. Chloroplasts went larger and round. Taken together, these results suggested that fluoroglycofen caused the grape leaves become dark green, which might be associated with the changes of chloroplast; the growth inhibition in the second year might be due to accumulation of starch.
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Herbicidas/toxicidade , Hidrocarbonetos Halogenados/toxicidade , Nitrobenzoatos/toxicidade , Folhas de Planta/efeitos dos fármacos , Toluidinas/toxicidade , Vitis/efeitos dos fármacos , Dióxido de Carbono/metabolismo , Carotenoides/metabolismo , Clorofila/metabolismo , Cloroplastos/efeitos dos fármacos , Cloroplastos/ultraestrutura , Microscopia Eletrônica de Transmissão , Fenótipo , Fotossíntese/efeitos dos fármacos , Folhas de Planta/metabolismo , Folhas de Planta/ultraestrutura , Vitis/metabolismo , Vitis/ultraestruturaRESUMO
PubChem ( https://pubchem.ncbi.nlm.nih.gov ) is a public chemical information resource containing more than 100 million unique chemical structures. One of the most requested tasks in PubChem and other chemical databases is to search chemicals by name (also commonly called a "chemical synonym"). PubChem performs this task by looking up chemical synonym-structure associations provided by individual depositors to PubChem. In addition, these synonyms are used for many purposes, including creating links between chemicals and PubMed articles (using Medical Subject Headings (MeSH) terms). However, these depositor-provided name-structure associations are subject to substantial discrepancies within and between depositors, making it difficult to unambiguously map a chemical name to a specific chemical structure. The present paper describes PubChem's crowdsourcing-based synonym filtering strategy, which resolves inter- and intra-depositor discrepancies in synonym-structure associations as well as in the chemical-MeSH associations. The PubChem synonym filtering process was developed based on the analysis of four crowd-voting strategies, which differ in the consistency threshold value employed (60% vs 70%) and how to resolve intra-depositor discrepancies (a single vote vs. multiple votes per depositor) prior to inter-depositor crowd-voting. The agreement of voting was determined at six levels of chemical equivalency, which considers varying isotopic composition, stereochemistry, and connectivity of chemical structures and their primary components. While all four strategies showed comparable results, Strategy I (one vote per depositor with a 60% consistency threshold) resulted in the most synonyms assigned to a single chemical structure as well as the most synonym-structure associations disambiguated at the six chemical equivalency contexts. Based on the results of this study, Strategy I was implemented in PubChem's filtering process that cleans up synonym-structure associations as well as chemical-MeSH associations. This consistency-based filtering process is designed to look for a consensus in name-structure associations but cannot attest to their correctness. As a result, it can fail to recognize correct name-structure associations (or incorrect ones), for example, when a synonym is provided by only one depositor or when many contributors are incorrect. However, this filtering process is an important starting point for quality control in name-structure associations in large chemical databases like PubChem.
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In industrial process monitoring, it is always a challenging and practical problem to analyze the causes of the system fault by isolating true fault variables from vast amounts of process data. However, the phenomenon of smearing effect occurs by using the traditional contribution analysis-based isolation methods since the defined isolation indices of different variables affect each other. In this paper, a new fault isolation method is proposed based on local outlier factor and improved k-nearest neighbor rule aiming to improve the isolation accuracy. Firstly, the nearest neighbors of each sample are obtained along the direction of a specific variable. Based on the nearest neighbors, the outlier-degree value of the variable is calculated and regarded as the contribution of the variable. Then, the contribution of the variable in all samples are obtained in the same way, among which the maximum one is selected as the isolation threshold value of this variable. During the online monitoring, the contribution of the variable in the newly collected sample is calculated in real time. Once the contribution is greater than the threshold, the variable is judged to be the dominant factor causing the system fault. Two cases on numerical example and Tennessee Eastman process are conducted to evaluate the effectiveness of the proposed method.
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The atomic precision of sub-nanometer-sized metal nanoclusters makes it possible to elucidate the kinetics of metal nanomaterials from the molecular level. Herein, the size reduction of an atomically precise [Au23(CHT)16]- (HCHT = cyclohexanethiol) cluster upon ligand exchange with HSAdm (1-adamantanethiol) has been reported. During the 16 h conversion of [Au23(CHT)16]- to Au16(SR)12, the neutral 6e Au21(SR)15, and its 1e-reduction state, i.e. the 5e, cationic radical, [Au21(SR)15]+, are active intermediates to account for the formation of thermodynamically stable Au16 products. The combination of spectroscopic monitoring (with UV-vis and ESI-MS) and DFT calculations indicates the preferential size-reduction on the corner Au atoms on the core surface and the terminal Au atoms on longer AunSn+1 staples. This study provides a reassessment on the electronic state of the Au21 structure and highlights the single electron transfer processes in cluster systems and thus the importance of the EPR analysis on the mechanistic issues.
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Following the national dynamic zero-COVID strategy adjustment, the utilization of broad-spectrum nasal neutralizing antibodies may offer an alternative approach to controlling the outbreak of Omicron variants between late 2022 and early 2023 in China. This study involved an investigator-initiated trial (IIT) to assess the pharmacokinetic, safety and efficacy of the F61 nasal spray. A total of 2,008 participants were randomly assigned to receive F61 nasal spray (24 mg/0.8 mL/dose) or normal saline (0.8 mL/dose) and 1336 completed the follow-up in the IIT. Minimal absorption of F61 antibody into the bloodstream was detected in individuals receiving F61 nasal spray for seven consecutive days. No treatment-emergent adverse reactions of grade 3 severity or higher were reported. In the one-dose cohort, the 7-day cumulative SARS-CoV-2 infection rate was 79.0% in the F61 group and 82.6% in the placebo group, whereas, in the multiple-dose (once daily for 7 consecutive days) cohort, the rates were 6.55% in the F61 group and 23.83% in the placebo group. The laboratory-confirmed efficacy of F61 was 3.78% (-3.74%-10.75%) in the one-dose cohort and 72.19% (57.33%-81.87%) in the multiple-dose cohort. In the real-world study, 60,225 volunteers in four different regions were administered the F61 nasal spray based on the subject's wishes, over 90% efficacy rate was observed against different Omicron variants. The F61 nasal spray, with its favourable safety profile, could be a promising prophylactic monoclonal antibody against SARS-CoV-2 VOCs.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Sprays Nasais , Pandemias , China , Anticorpos Monoclonais , Anticorpos Amplamente Neutralizantes , Anticorpos Neutralizantes , Anticorpos AntiviraisRESUMO
Brassinosteroids (BRs) are a class of steroid hormones with great potential for use in crop improvement. De-repression is usually one of the key events in hormone signaling. However, how the stability of GSK2, the central negative regulator of BR signaling in rice (Oryza sativa), is regulated by BRs remains elusive. Here, we identify the U-box ubiquitin ligase TUD1 as a GSK2-interacting protein by yeast two-hybrid screening. We show that TUD1 is able to directly interact with GSK2 and ubiquitinate the protein. Phenotypes of the tud1 mutant are highly similar to those of plants with constitutively activated GSK2. Consistent with this finding, GSK2 protein accumulates in the tud1 mutant compared with the wild type. In addition, inhibition of BR synthesis promotes GSK2 accumulation and suppresses TUD1 stability. By contrast, BRs can induce GSK2 degradation but promote TUD1 accumulation. Furthermore, the GSK2 degradation process is largely impaired in tud1 in response to BR. In conclusion, our study demonstrates the role of TUD1 in BR-induced GSK2 degradation, thereby advancing our understanding of a critical step in the BR signaling pathway of rice.