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1.
Nat Commun ; 14(1): 138, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627283

RESUMO

ß-Nucleosides and their analogs are dominant clinically-used antiviral and antitumor drugs. α-Nucleosides, the anomers of ß-nucleosides, exist in nature and have significant potential as drugs or drug carriers. Currently, the most widely used methods for synthesizing ß- and α-nucleosides are via N-glycosylation and pentose aminooxazoline, respectively. However, the stereoselectivities of both methods highly depend on the assisting group at the C2' position. Herein, we report an additive-controlled stereodivergent iodocyclization method for the selective synthesis of α- or ß-nucleosides. The stereoselectivity at the anomeric carbon is controlled by the additive (NaI for ß-nucleosides; PPh3S for α-nucleosides). A series of ß- and α-nucleosides are prepared in high yields (up to 95%) and stereoselectivities (ß:α up to 66:1, α:ß up to 70:1). Notably, the introduced iodine at the C2' position of the nucleoside is readily functionalized, leading to multiple structurally diverse nucleoside analogs, including stavudine, an FDA-approved anti-HIV agent, and molnupiravir, an FDA-approved anti-SARS-CoV-2 agent.


Assuntos
Fármacos Anti-HIV , COVID-19 , Humanos , Nucleosídeos , Estereoisomerismo , Antivirais/farmacologia
2.
Comput Intell Neurosci ; 2022: 6822467, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845901

RESUMO

Since China's reform and opening up, the social economy has achieved rapid development, followed by a sharp increase in carbon dioxide (CO2) emissions. Therefore, at the 75th United Nations General Assembly, China proposed to achieve carbon peaking by 2030 and carbon neutrality by 2060. The research work on advance forecasting of CO2 emissions is essential to achieve the above-mentioned carbon peaking and carbon neutrality goals in China. In order to achieve accurate prediction of CO2 emissions, this study establishes a hybrid intelligent algorithm model suitable for CO2 emissions prediction based on China's CO2 emissions and related socioeconomic indicator data from 1971 to 2017. The hyperparameters of Least Squares Support Vector Regression (LSSVR) are optimized by the Adaptive Artificial Bee Colony (AABC) algorithm to build a high-performance hybrid intelligence model. The research results show that the hybrid intelligent algorithm model designed in this paper has stronger robustness and accuracy with relative error almost within ±5% in the advance prediction of CO2 emissions. The modeling scheme proposed in this study can not only provide strong support for the Chinese government and industry departments to formulate policies related to the carbon peaking and carbon neutrality goals, but also can be extended to the research of other socioeconomic-related issues.


Assuntos
Inteligência Artificial , Dióxido de Carbono , Dióxido de Carbono/análise , China , Indústrias
3.
Plant J ; 109(3): 598-614, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34775642

RESUMO

Pollen tube integrity, growth and guidance are crucial factors in plant sexual reproduction. Members of the plant Skewed5 (SKU5) Similar (SKS) family show strong similarity to multicopper oxidases (MCOs), but they lack conserved histidines in MCO active sites. The functions of most SKS family members are unknown. Here, we show that Arabidopsis pollen-expressed SKS11 and SKS12 play important roles in pollen tube integrity, growth and guidance. The sks11sks12 mutant exhibited significantly reduced male fertility. Most of the pollen from sks11sks12 plants burst when germinated, and the pollen tubes grew slowly and exhibited defective growth along the funiculus and micropyle. SKS11-GFP and SKS12-mCherry were detected at the cell wall in pollen tubes. The contents of several cell wall polysaccharides and arabinogalactans were decreased in the pollen tube cell walls of sks11sks12 plants. Staining with a reactive oxygen species (ROS)-sensitive dye and use of the H2 O2 sensor HyPer revealed that the ROS content in the pollen tubes of sks11sks12 plants was remarkably reduced. SKS11444His-Ala , in which the last conserved histidine was mutated, could restore the mutant phenotypes of sks11sks12. Thus, SKS11/12 are required for pollen tube integrity, growth and guidance possibly by regulating the ROS level and cell wall polysaccharide deposition or remodeling in pollen tubes.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Glicoproteínas de Membrana/metabolismo , Tubo Polínico/efeitos dos fármacos , Tubo Polínico/crescimento & desenvolvimento , Tubo Polínico/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Fenótipo
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