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1.
Sensors (Basel) ; 24(10)2024 May 07.
Article En | MEDLINE | ID: mdl-38793814

Machine learning and deep learning technologies are rapidly advancing the capabilities of sensing technologies, bringing about significant improvements in accuracy, sensitivity, and adaptability. These advancements are making a notable impact across a broad spectrum of fields, including industrial automation, robotics, biomedical engineering, and civil infrastructure monitoring. The core of this transformative shift lies in the integration of artificial intelligence (AI) with sensor technology, focusing on the development of efficient algorithms that drive both device performance enhancements and novel applications in various biomedical and engineering fields. This review delves into the fusion of ML/DL algorithms with sensor technologies, shedding light on their profound impact on sensor design, calibration and compensation, object recognition, and behavior prediction. Through a series of exemplary applications, the review showcases the potential of AI algorithms to significantly upgrade sensor functionalities and widen their application range. Moreover, it addresses the challenges encountered in exploiting these technologies for sensing applications and offers insights into future trends and potential advancements.

2.
Sci Adv ; 10(2): eadk0738, 2024 Jan 12.
Article En | MEDLINE | ID: mdl-38198548

The aromatic amino acids (AAAs) phenylalanine, tyrosine, and tryptophan are basic protein units and precursors of diverse specialized metabolites that are essential for plant growth. Despite their significance, the mechanisms that regulate AAA homeostasis remain elusive. Here, we identified a cytosolic aromatic aminotransferase, REVERSAL OF SAV3 PHENOTYPE 1 (VAS1), as a suppressor of arogenate dehydrogenase 2 (adh2) in Arabidopsis (Arabidopsis thaliana). Genetic and biochemical analyses determined that VAS1 uses AAAs as amino donors, leading to the formation of 3-carboxyphenylalanine and 3-carboxytyrosine. These pathways represent distinct routes for AAA metabolism that are unique to specific plant species. Furthermore, we show that VAS1 is responsible for cytosolic AAA biosynthesis, and its enzymatic activity can be inhibited by 3-carboxyphenylalanine. These findings provide valuable insights into the crucial role of VAS1 in producing 3-carboxy AAAs, notably via recycling of AAAs in the cytosol, which maintains AAA homeostasis and allows plants to effectively coordinate the complex metabolic and biosynthetic pathways of AAAs.


Arabidopsis , Transaminases , Amino Acids , Amino Acids, Aromatic , Arabidopsis/genetics , Cytosol , Homeostasis , Transaminases/genetics
3.
ACS Omega ; 8(50): 48028-48041, 2023 Dec 19.
Article En | MEDLINE | ID: mdl-38144133

Metformin (MET), commonly marketed as a hydrochloride salt (MET-HCl) for better pharmacokinetic profile over the free base, would release a high concentration of chloride ions and cause adverse gastrointestinal effects. The preparation of chloride-free MET salts could potentially circumvent this issue. In this study, seven carboxylic acids (formic acid, acetic acid, malonic acid, succinic acid, fumaric acid, cinnamic acid, and acetylsalicylic acid) were used for preparing MET carboxylate salts. When compared with MET-HCl, all MET salts/salt hydrates show lower dissolution rates in pH 6.8 phosphate buffer. However, the cinnamic acid and acetylsalicylic acid show significantly higher dissolution rates in the forms of MET salt/salt hydrate. In the permeability test, the permeability of the MET in all of the salts was not improved. However, the permeability of cinnamic acid in the MET cinnamate is reduced, and the permeability of acetylsalicylic acid in the MET acetylsalicylate is increased. Meanwhile, at a higher crystallization temperature, the acetone solvent and a hydrolyzed product of acetylsalicylic acid react with MET respectively, leading to two unexpected 1,3,5-triazine derivatives. The results of in vitro bioactivity assays indicate that one of the triazine molecules promote glucose consumption more effectively than MET-HCl, and had relatively weak lactate production ability at low concentration. This glucose metabolism regulating compound may serve as a novel lead antihyperglycemic agent for further optimization.

4.
Molecules ; 28(6)2023 Mar 12.
Article En | MEDLINE | ID: mdl-36985553

Flavonoids are a kind of secondary metabolite which widely exist in plants. They contain a lot of active hydroxyls, which can react with toxic chemicals to produce potential exposure biomarkers. In this article, the model plant Arabidopsis thaliana (L.) was exposed to the nerve agent O-Ethyl N,N-dimethyl phosphoramidocyanidate (Tabun). By comparing with the plant not exposed to Tabun, some characteristic ions were identified by quadrupole-time of flight mass spectrometry in the acetonitrile extract of the exposed leaves. These characteristic ions were selected as parent ions to produce product ion mass spectra (PIMS). Some interesting fragmentation pathways were revealed, including neutral loss of glucoside, rhamnose and ethylene. O-Ethyl N,N-dimethyl phosphoryl modified flavonoids were deduced from assignment of the PIMS. The element components and the accurate mass of the product ions from each parent ion matched well with those of the proposed fragmentation pathways. Through comparison with the PIMS of structurally closely related chemical of Isobutyl methylphosphonyl modified flavonoids, the structures and the fragmentation pathways of the O-Ethyl N,N-dimethyl phosphoryl modified flavonoids were finally confirmed. Successfully finding and identifying these three specific exposure biomarkers in plants provided a new strategy for the retrospective analysis of organophosphorus exposure and forensic analysis.


Arabidopsis , Nerve Agents , Flavonoids/chemistry , Tandem Mass Spectrometry/methods , Retrospective Studies , Chromatography, High Pressure Liquid/methods , Plants
5.
Bioorg Med Chem Lett ; 80: 129115, 2023 01 15.
Article En | MEDLINE | ID: mdl-36574853

A series of novel 2­fluoro ketolide antibiotics with 11,12­quinoylalkyl side chains derived from telithromycin and cethromycin were designed and synthesized. The corresponding targets 2a-o were tested for their in vitro activities against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed a similar antibacterial spectrum and comparable or slightly better activity to telithromycin. Among them, compounds 2g and 2k, displayed excellent activities against macrolide-sensitive and macrolide-resistant pathogens.


Ketolides , Anti-Bacterial Agents/chemistry , Macrolides , Microbial Sensitivity Tests , Quinolines
6.
J Asian Nat Prod Res ; 25(7): 697-703, 2023.
Article En | MEDLINE | ID: mdl-36409210

A total synthesis approach of CS-E oligosaccharides was established and a series of derivatives were synthesized. These oligosaccharides were evaluated for a glycosaminoglycan (GAG)-binding protein interaction against cytokines, midkine, and pleiotrophin, by surface-plasmon resonance (SPR) assay. The binding epitopes of oligosaccharides to midkine were mapped using a saturation transfer difference (STD) NMR technique. The groups on the reducing end contributed to binding affinity, and should not be ignored in biological assays. These findings contribute to the structure and activity relationship research and a foundation of understanding that will underpin potential future optimization of this class of oligosaccharides as pharmaceutical agents.


Chondroitin Sulfates , Oligosaccharides , Chondroitin Sulfates/pharmacology , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/metabolism , Midkine/metabolism , Protein Binding , Oligosaccharides/chemistry
7.
Sci Signal ; 15(765): eabo4356, 2022 12 20.
Article En | MEDLINE | ID: mdl-36538592

Histone deacetylases (HDACs) play important roles in immunity and inflammation. Through functional screening, we identified HDAC10 as an inhibitor of the type I interferon (IFN) response mediated by interferon regulatory factor 3 (IRF3). HDAC10 abundance was decreased in mouse macrophages in response to innate immune stimuli and was reduced in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) compared with that in PBMCs from healthy donors. Deficiency in HDAC10 in mouse embryonic fibroblasts and in mice promoted the expression of genes encoding type I IFNs and of IFN-stimulated genes (ISGs), leading to enhanced antiviral responses in vitro and in vivo. HDAC10 bound in a deacetylase-independent manner to IRF3 in uninfected cells to inhibit the phosphorylation of IRF3 at Ser396 by TANK-binding kinase 1 (TBK1). Upon viral infection, HDAC10 was targeted for autophagy-mediated degradation through its interaction with LC3-II. Consequently, IRF3 phosphorylation was increased, which resulted in enhanced type I IFN production and antiviral responses. Our findings identify a potential target for improving host defense responses against pathogen infection and for treating autoimmune disease.


Interferon Regulatory Factor-3 , Interferon Type I , Animals , Mice , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Leukocytes, Mononuclear/metabolism , Fibroblasts/metabolism , Immunity, Innate , Phosphorylation , Interferon Type I/metabolism , Antiviral Agents , Autophagy
8.
RSC Adv ; 12(54): 35026-35031, 2022 Dec 06.
Article En | MEDLINE | ID: mdl-36540234

As vegetation is part of our lives, plants are good candidates as indicators of toxic chemicals. Numerous components in plants may react with toxic chemicals to produce exposure biomarkers. Plant biomarkers formed by the modification of endogenous plant components by chemical warfare agents have not been reported. In this article, the model plant Arabidopsis thaliana (L.) was exposed to the nerve agent isobutyl S-2-diethylaminoethyl methylphosphonothiolate (iBuVX). Some characteristic ions were identified by liquid chromatography-high resolution mass spectrometry and their product ion mass spectra were recorded and interpreted. Some interesting fragmentation pathways were revealed including neutral loss of glucoside, rhamnose and isobutylene. Isobutyl methylphosphonyl modified flavonoids were deduced from assignment of product ions. The element components and the accurate mass of the product ions matched well with those of the proposed fragmentation pathways. The binding site of the nerve agent on flavonoids was proved to be the hydroxyl group on the benzene ring of the flavonoids by density functional theory computation and by the synthesis of the reference chemical, which was confirmed by 1H-31P HMBC NMR. The phosphonyl-modified flavonoids were evaluated for specificity in different plants. Four new flavonoid adducts as potential biomarkers were identified in the leaves of the iBuVX-exposed plant, which provided a novel strategy for the retrospective analysis of organophosphorus exposure for chemical weapon verification and forensic analysis.

9.
Front Pharmacol ; 12: 655101, 2021.
Article En | MEDLINE | ID: mdl-34305585

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that affects 1% of the population. CS-semi5 is a semisynthetic chondroitin sulfate. In this study, CS-semi5 was shown to have positive effects on a model of collagen-induced arthritis (CIA). CS-semi5 treatment had obvious effects on weight loss and paw swelling in CIA mice. Post-treatment analysis revealed that CS-semi5 alleviated three main pathologies (i.e., synovial inflammation, cartilage erosion and bone loss) in a dose-dependent manner. Further study showed that CS-semi5 could effectively reduce TNF-α and IL-1ß production in activated macrophages via the NF-κB pathway. CS-semi5 also blocked RANKL-trigged osteoclast differentiation from macrophages. Therefore, CS-semi5 may effectively ameliorate synovial inflammation, cartilage erosion and bone loss in RA through NF-κB deactivation.

10.
Future Med Chem ; 11(12): 1403-1415, 2019 06.
Article En | MEDLINE | ID: mdl-31304829

Aim: Chondroitin sulfate (CS) is a class of highly sulfated polysaccharides that possess many important biological functions. The heterogeneity of CS limits pharmacological research and leads to ambiguous mechanisms. Thus, glycomimetics are demanded as replacement of natural polysaccharides to explore important biological processes. Results & methodology: Here the preparation of CS glycodendrimers is reported as well as their use as CS mimetics to regulate the NF-κB pathway. Multivalent presentation of sugar epitopes on appropriate dendrimer scaffolds increased the suppression of the NF-κB pathway. The interaction between CS-E molecules and TNF-α was examined by nuclear magnetic resonance technology. Conclusion: Overall, the glycodendrimer reported here may be potentially employed as molecular tool to investigate the biological functions of CS.


Chondroitin Sulfates/chemical synthesis , Dendrimers/chemical synthesis , Glycosides/chemical synthesis , Animals , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/pharmacology , Dendrimers/chemistry , Dendrimers/pharmacology , Gene Expression/drug effects , Genes, Reporter , Glycosides/chemistry , Glycosides/pharmacology , Mice , Molecular Structure , NF-kappa B/genetics , RAW 264.7 Cells , Transcriptional Activation/drug effects , Tumor Necrosis Factor-alpha/genetics
11.
J Asian Nat Prod Res ; 21(5): 456-461, 2019 May.
Article En | MEDLINE | ID: mdl-29589476

A series of novel 5-O-(4',6'-O-dimodified)-mycaminose 14-membered ketolides were assessed for their in vitro antibacterial activities against a panel of sensitive and resistant pathogens. Compound 1 and compound 2, two ester analogs, showed the best antibacterial activities against several macrolide-sensitive and macrolide-resistant strains. These results indicated that introducing ester to 6-OH and a small volume ether substituent to the 4-OH of mycaminose could improve the antibacterial activities of ketolides.


Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Ketolides/chemistry , Ketolides/pharmacology , Bacteria/drug effects , Molecular Structure
12.
J Asian Nat Prod Res ; 21(7): 610-618, 2019 Jul.
Article En | MEDLINE | ID: mdl-29665718

A series of novel 4″-O-desosaminyl clarithromycin derivatives with 11, 12-arylalkyl side chains was synthesized by coupling 6-deoxy-desosamine donors (18, 19) with 4″-OH of compounds 5a-c. The activities of the target compounds were tested against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed activities against macrolide sensitive and resistant pathogens, and compounds 21d and 21e displayed significant improvement of activities against resistant pathogens.


Amino Sugars/chemistry , Anti-Bacterial Agents/chemical synthesis , Clarithromycin/analogs & derivatives , Clarithromycin/chemical synthesis , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Clarithromycin/pharmacology , Drug Resistance, Bacterial , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
13.
FEMS Microbiol Lett ; 366(1)2019 01 01.
Article En | MEDLINE | ID: mdl-30445522

Pyridine is a typical nitrogen heterocyclic and recalcitrant organic compound in coking wastewater. The pyridine-degrading bacterial strain KDPy1 was isolated from aerobic sludge in a coking wastewater treatment plant. The homology analysis based on 16S rDNA sequences suggested that KDPy1 belongs to Rhodococcus sp. The optimum temperature and pH for pyridine degradation by KDPy1 were 37°C and 7-8, respectively. The strain KDPy1 degraded 1442 mg/L of pyridine nearly 99.6% after 48 h, and the high concentration of 1442 mg/L pyridine did not show an inhibitory effect on its degradation. The degradation kinetics of pyridine were fitted with the Monod model. Furthermore, KDPy1 was capable of degrading pyridine efficiently in the synthetic wastewater containing quinoline and phenol. KDPy1 could degrade pyridine and reduce the total organic carbon in the real coking wastewater. These results showed that KDPy1 had a potential for improving the removal of pyridine from coking wastewater.


Coke/microbiology , Industrial Microbiology , Pyridines/metabolism , Rhodococcus/classification , Rhodococcus/metabolism , Wastewater/microbiology , Hydrogen-Ion Concentration , Kinetics , RNA, Ribosomal, 16S/genetics , Rhodococcus/genetics , Rhodococcus/isolation & purification , Temperature
14.
Bioorg Med Chem Lett ; 28(14): 2358-2363, 2018 08 01.
Article En | MEDLINE | ID: mdl-29937059

A series of quinoylalkyl side chains was designed and synthesized, followed by introduction into ketolides by coupling with building block 6 or 32. The corresponding targets 7a-n, 33b, and 33e were tested for their in vitro activities against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed a similar antibacterial spectrum and comparable activity to telithromycin. Among them, two C2-F ketolides, compounds 33b and 33e, displayed excellent activities against macrolide-sensitive and macrolide-resistant pathogens.


Anti-Bacterial Agents/pharmacology , Haemophilus influenzae/drug effects , Ketolides/pharmacology , Quinolines/pharmacology , Staphylococcus/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Azithromycin/pharmacology , Dose-Response Relationship, Drug , Drug Resistance, Bacterial , Ketolides/chemical synthesis , Ketolides/chemistry , Methicillin Resistance , Microbial Sensitivity Tests , Molecular Structure , Quinolines/chemistry , Structure-Activity Relationship
15.
J Org Chem ; 83(11): 5897-5908, 2018 06 01.
Article En | MEDLINE | ID: mdl-29756448

An approach was developed to synthesize chondroitin sulfate-E (CS-E) oligosaccharides by adopting a postglycosylation-transformation strategy: different from all of the traditional approaches, the characteristic groups of CS-E were introduced following the assembly of the oligosaccharides. The adjusted strategy rendered an easy chain elongation strategy. All of the elongation steps generated high yields with excellent glycosylation outcomes. An orthogonally protected disaccharide was used as the building block to provide flexibility for the group transformation and derivatization at the N-2 position of the GalNAc residue and the O-1,5 positions of the GlcA residue, thereby providing ready access for the further examination of the structure-activity relationship (SAR) of CS-E molecules.


Chondroitin Sulfates/chemical synthesis , Oligosaccharides/chemical synthesis , Carbohydrate Sequence , Disaccharides/chemistry , Glycosylation , Molecular Structure
16.
J Asian Nat Prod Res ; 19(4): 358-387, 2017 Apr.
Article En | MEDLINE | ID: mdl-28276768

Some novel josamycin derivatives bearing an arylalkyl-type side chain were designed and synthesized. By HWE or Wittig reaction, 16-aldehyde group of josamycin analogs were converted into unsaturated carbonyl compounds. They were evaluated for their in vitro antibacterial activities against a panel of respiratory pathogens. 8b and 8e exhibited comparable activities against a panel of respiratory pathogens, especially to resistant ones in the series of desmycarosyl josamycin analogs. Among of all the target molecules, 21 showed the best antibacterial activities.


Anti-Bacterial Agents , Josamycin , Ketones , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Josamycin/analogs & derivatives , Josamycin/chemical synthesis , Josamycin/chemistry , Josamycin/pharmacology , Ketones/chemical synthesis , Ketones/chemistry , Ketones/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Staphylococcus aureus/drug effects
17.
Bioorg Med Chem Lett ; 24(2): 480-4, 2014 Jan 15.
Article En | MEDLINE | ID: mdl-24374276

A series of novel 9-O-acetyl-4'-substituted 16-membered macrolides derived from josamycin has been designed and synthesized by cleavage of the mycarose of josamycin and subsequent modification of the 4'-hydroxyl group. These derivatives were evaluated for their in vitro antibacterial activities against a panel of Staphylococcus aureus and Staphylococcus epidermidis. 15 (4'-O-(3-Phenylpropanoyl)-9-O-acetyl-desmycarosyl josamycin) and 16 (4'-O-butanoyl-9-O-acetyl-desmycarosyl josamycin) exhibited comparable activities to josamycin against S. aureus (MSSA) and S. epidermidis (MSSE).


Anti-Bacterial Agents/chemical synthesis , Josamycin/chemical synthesis , Josamycin/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus epidermidis/drug effects , Anti-Bacterial Agents/pharmacology , Crystallography, X-Ray , Josamycin/analogs & derivatives , Macrolides/chemical synthesis , Macrolides/pharmacology , Microbial Sensitivity Tests/methods , Staphylococcus aureus/physiology , Staphylococcus epidermidis/physiology
18.
Bioorg Med Chem Lett ; 23(23): 6274-9, 2013 Dec 01.
Article En | MEDLINE | ID: mdl-24139585

A series of new 4″-O-desosaminyl clarithromycin derivatives were designed and synthesized. The efficient synthesis routes of 6-deoxy-desosamine donors 8 and 11 were developed and the methodology of glycosylation of clarithromycin 4″-OH with desosamine was studied. The activities of the target compounds were tested against a series of macrolide-sensitive and macrolide-resistant pathogens. Some of them showed activities against macrolide sensitive pathogens, and compounds 19 and 22 displayed significant improvement of activities against sensitive pathogens and two strains of MRSE, which verified the importance of desosamine in the interaction of macrolide and its receptor, and offered valuable information of the SAR of macrolide 4″-OH derivatives.


Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Clarithromycin/analogs & derivatives , Clarithromycin/chemical synthesis , Clarithromycin/pharmacology , Glycosylation , Macrolides/chemical synthesis , Macrolides/pharmacology , Microbial Sensitivity Tests , Structure-Activity Relationship
19.
Eur J Med Chem ; 69: 174-81, 2013 Nov.
Article En | MEDLINE | ID: mdl-24021890

A practicable method of introducing a side chain to the C-4' position of 5-O-desosamine in the 14-membered ketolides was developed. And using this method, a series of novel modified 5-O-mycaminose ketolides were synthesized. These ketolides containing 5-O-4'-carbamate mycaminose were evaluated for their in vitro antibacterial activities against some respiratory pathogens. 15b and 18e showed comparable activity to telithromycin and clarithromycin.


Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Ketolides/chemistry , Ketolides/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus epidermidis/drug effects , Anti-Bacterial Agents/chemistry , Dose-Response Relationship, Drug , Drug Resistance, Microbial/drug effects , Ketolides/chemical synthesis , Methicillin/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship
20.
J Phys Chem B ; 109(21): 10786-92, 2005 Jun 02.
Article En | MEDLINE | ID: mdl-16852311

Four donor-acceptor functionalized molecular materials with symmetrical structures have been synthesized and investigated for their use in optoelectronic applications. These pi-conjugated molecules consist of one electron-donating moiety, for instance, carbazole, triphenylamine, or phenothiazine at the center, and two acceptors at each side. Introduction of different donor moieties decreases the band gaps allowing a fine-tuning of the optical and electrical properties. These materials exhibit multifunctional properties, such as a red light-emitting behavior and a large photovoltaic effect. Red organic light-emitting diodes were fabricated in a facile nondoping configuration based on these materials. Saturated red-emission is observed with a CIE of x = 0.64 and y = 0.33, and an external quantum efficiency of 0.19%. In addition, our first observation of photovoltaic response in the pi-conjugated molecule with donor-acceptor-donor structure is reported. The organic single-component photovoltaic cells were fabricated and characterized. Their open-circuit voltage and short-circuit current density are 1.1 V and 0.07 mA cm(-2), respectively. The photovoltaic effect corresponds to the absorption characteristics of the compound and depends on the nature of the electron-donating group.

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