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1.
Cell ; 186(9): 2002-2017.e21, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-37080201

RESUMO

Paired mapping of single-cell gene expression and electrophysiology is essential to understand gene-to-function relationships in electrogenic tissues. Here, we developed in situ electro-sequencing (electro-seq) that combines flexible bioelectronics with in situ RNA sequencing to stably map millisecond-timescale electrical activity and profile single-cell gene expression from the same cells across intact biological networks, including cardiac and neural patches. When applied to human-induced pluripotent stem-cell-derived cardiomyocyte patches, in situ electro-seq enabled multimodal in situ analysis of cardiomyocyte electrophysiology and gene expression at the cellular level, jointly defining cell states and developmental trajectories. Using machine-learning-based cross-modal analysis, in situ electro-seq identified gene-to-electrophysiology relationships throughout cardiomyocyte development and accurately reconstructed the evolution of gene expression profiles based on long-term stable electrical measurements. In situ electro-seq could be applicable to create spatiotemporal multimodal maps in electrogenic tissues, potentiating the discovery of cell types and gene programs responsible for electrophysiological function and dysfunction.


Assuntos
Eletrônica , Análise de Sequência de RNA , Humanos , Diferenciação Celular , Células-Tronco Pluripotentes Induzidas/fisiologia , Miócitos Cardíacos/metabolismo , Análise de Célula Única , Transcriptoma , Eletrônica/métodos
2.
PLoS Genet ; 18(4): e1010137, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35421082

RESUMO

Viral infections can alter host transcriptomes by manipulating host splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative splicing (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and transcriptomic sequencing data to study AS changes in COVID-19 patients. We discovered that RNA splicing is among the major down-regulated proteomic signatures in COVID-19 patients. The transcriptome analysis showed that SARS-CoV-2 infection induces widespread dysregulation of transcript usage and expression, affecting blood coagulation, neutrophil activation, and cytokine production. Notably, CD74 and LRRFIP1 had increased skipping of an exon in COVID-19 patients that disrupts a functional domain, which correlated with reduced antiviral immunity. Furthermore, the dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity. In summary, our data highlight that a better understanding of the AS landscape may aid in COVID-19 diagnosis and therapy.


Assuntos
COVID-19 , Processamento Alternativo/genética , COVID-19/genética , Teste para COVID-19 , Humanos , Proteômica , SARS-CoV-2/genética , Transcriptoma
3.
Chem Soc Rev ; 53(19): 9560-9581, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39171573

RESUMO

Chiral amine scaffolds are among the most important building blocks in natural products, drug molecules, and functional materials, which have prompted chemists to focus more on their synthesis. Among the accomplishments in chiral amine synthesis, transition-metal-catalyzed enantioselective C-N cross-coupling is considered one of the most efficient protocols. This approach combines traditional C(sp2)-N cross-coupling methods (such as the Buchwald-Hartwig reaction Ullmann-type reaction, and Chan-Evans-Lam reaction), aryliodonium salt chemistry and radical chemistry, providing an attractive pathway to a wide range of structurally diverse chiral amines with high enantioselectivity. This review summarizes the established protocols and offers a comprehensive outlook on the promising enantioselective C-N cross-coupling reaction.

4.
J Neurosci ; 43(16): 2907-2920, 2023 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-36868854

RESUMO

General anesthesia shares many similarities with natural sleep in behavior and electroencephalogram (EEG) patterns. The latest evidence suggests that general anesthesia and sleep-wake behavior may share overlapping neural substrates. The GABAergic neurons in the basal forebrain (BF) have recently been demonstrated to play a key role in controlling wakefulness. It was hypothesized that BF GABAergic neurons may participate in the regulation of general anesthesia. Here, using in vivo fiber photometry, we found that the activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia, having obviously decreased during the induction of anesthesia and being gradually restored during the emergence from anesthesia, in Vgat-Cre mice of both sexes. Activation of BF GABAergic neurons with chemogenetic and optogenetic approaches decreased sensitivity to isoflurane, delayed induction, and accelerated emergence from isoflurane anesthesia. Optogenetic activation of BF GABAergic neurons decreased EEG δ power and the burst suppression ratio (BSR) during 0.8% and 1.4% isoflurane anesthesia, respectively. Similar to the effects of activating BF GABAergic cell bodies, photostimulation of BF GABAergic terminals in the thalamic reticular nucleus (TRN) also strongly promoted cortical activation and behavioral emergence from isoflurane anesthesia. Collectively, these results showed that the GABAergic BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthesia via the GABAergic BF-TRN pathway. Our findings may provide a new target for attenuating the depth of anesthesia and accelerating emergence from general anesthesia.SIGNIFICANCE STATEMENT The basal forebrain (BF) is a key brain region controlling sleep-wake behavior. Activation of GABAergic neurons in the BF potently promotes behavioral arousal and cortical activity. Recently, many sleep-wake-related brain structures have been reported to participate in the regulation of general anesthesia. However, it is still unclear what role BF GABAergic neurons play in general anesthesia. In this study, we aim to reveal the role of BF GABAergic neurons in behavioral and cortical emergence from isoflurane anesthesia and elucidate the underlying neural pathways. Understanding the specific role of BF GABAergic neurons in isoflurane anesthesia would improve our understanding of the mechanisms of general anesthesia and may provide a new strategy for accelerating emergence from general anesthesia.


Assuntos
Prosencéfalo Basal , Isoflurano , Masculino , Feminino , Camundongos , Animais , Isoflurano/farmacologia , Prosencéfalo Basal/fisiologia , Neurônios GABAérgicos/fisiologia , Sono/fisiologia , Eletroencefalografia , Anestesia Geral
5.
J Hepatol ; 80(1): 41-52, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37858684

RESUMO

BACKGROUND & AIMS: HBsAg loss is only observed in a small proportion of patients with chronic hepatitis B (CHB) who undergo interferon treatment. Investigating the host factors crucial for functional cure of CHB can aid in identifying individuals who would benefit from peginterferon-α (Peg-IFNα) therapy. METHODS: We conducted a genome-wide association study (GWAS) by enrolling 48 patients with CHB who achieved HBsAg loss after Peg-IFNα treatment and 47 patients who didn't. In the validation stage, we included 224 patients, of whom 90 had achieved HBsAg loss, to validate the identified significant single nucleotide polymorphisms. To verify the functional involvement of the candidate genes identified, we performed a series of in vitro and in vivo experiments. RESULTS: GWAS results indicated a significant association between the rs7519753 C allele and serum HBsAg loss in patients with CHB after Peg-IFNα treatment (p = 4.85 × 10-8, odds ratio = 14.47). This association was also observed in two independent validation cohorts. Expression quantitative trait locus analysis revealed higher hepatic TP53BP2 expression in individuals carrying the rs7519753 C allele (p = 2.90 × 10-6). RNA-sequencing of liver biopsies from patients with CHB after Peg-IFNα treatment revealed that hepatic TP53BP2 levels were significantly higher in the HBsAg loss group compared to the HBsAg persistence group (p = 0.035). In vitro and in vivo experiments demonstrated that loss of TP53BP2 decreased interferon-stimulated gene levels and the anti-HBV effect of IFN-α. Mechanistically, TP53BP2 was found to downregulate SOCS2, thereby facilitating JAK/STAT signaling. CONCLUSION: The rs7519753 C allele is associated with elevated hepatic TP53BP2 expression and an increased probability of serum HBsAg loss post-Peg-IFNα treatment in patients with CHB. TP53BP2 enhances the response of the hepatocyte to IFN-α by suppressing SOCS2 expression. IMPACT AND IMPLICATIONS: Chronic hepatitis B (CHB) remains a global public health issue. Although current antiviral therapies are more effective in halting disease progression, only a few patients achieve functional cure for hepatitis B with HBsAg loss, highlighting the urgent need for a cure for CHB. This study revealed that the rs7519753 C allele, which is associated with high expression of hepatic TP53BP2, significantly increases the likelihood of serum HBsAg loss in patients with CHB undergoing Peg-IFNα treatment. This finding not only provides a promising predictor for HBsAg loss but identifies a potential therapeutic target for Peg-IFNα treatment. We believe our results are of great interest to a wide range of stakeholders based on their potential clinical implications.


Assuntos
Antivirais , Hepatite B Crônica , Humanos , Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/genética , Estudo de Associação Genômica Ampla , Quimioterapia Combinada , Interferon-alfa/farmacologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Antígenos E da Hepatite B , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , DNA Viral/genética , Proteínas Reguladoras de Apoptose
6.
BMC Plant Biol ; 24(1): 366, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711037

RESUMO

BACKGROUND: Nitrogen (N) is essential for plant growth and development. In Lithocarpus polystachyus Rehd., a species known for its medicinal and food value, phlorizin is the major bioactive compound with pharmacological activity. Research has revealed a positive correlation between plant nitrogen (N) content and phlorizin synthesis in this species. However, no study has analyzed the effect of N fertilization on phlorizin content and elucidated the molecular mechanisms underlying phlorizin synthesis in L. polystachyus. RESULTS: A comparison of the L. polystachyus plants grown without (0 mg/plant) and with N fertilization (25, 75, 125, 175, 225, and 275 mg/plant) revealed that 75 mg N/plant fertilization resulted in the greatest seedling height, ground diameter, crown width, and total phlorizin content. Subsequent analysis of the leaves using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detected 150 metabolites, including 42 flavonoids, that were differentially accumulated between the plants grown without and with 75 mg/plant N fertilization. Transcriptomic analysis of the L. polystachyus plants via RNA sequencing revealed 162 genes involved in flavonoid biosynthesis, among which 53 significantly differed between the N-treated and untreated plants. Fertilization (75 mg N/plant) specifically upregulated the expression of the genes phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL), and phlorizin synthase (PGT1) but downregulated the expression of trans-cinnamate 4-monooxygenase (C4H), shikimate O-hydroxycinnamoyltransferase (HCT), and chalcone isomerase (CHI), which are related to phlorizin synthesis. Finally, an integrated analysis of the transcriptome and metabolome revealed that the increase in phlorizin after N fertilization was consistent with the upregulation of phlorizin biosynthetic genes. Quantitative real-time PCR (qRT‒PCR) was used to validate the RNA sequencing data. Thus, our results indicated that N fertilization increased phlorizin metabolism in L. polystachyus by regulating the expression levels of the PAL, PGT1, 5-O-(4-coumaroyl)-D-quinate 3'-monooxygenase (C3'H), C4H, and HCT genes. CONCLUSIONS: Our results demonstrated that the addition of 75 mg/plant N to L. polystachyus significantly promoted the accumulation of flavonoids, including phlorizin, and the expression of flavonoid synthesis-related genes. Under these conditions, the genes PAL, 4CL, and PGT1 were positively correlated with phlorizin accumulation, while C4H, CHI, and HCT were negatively correlated with phlorizin accumulation. Therefore, we speculate that PAL, 4CL, and PGT1 participate in the phlorizin pathway under an optimal N environment, regulating phlorizin biosynthesis. These findings provide a basis for improving plant bioactive constituents and serve as a reference for further pharmacological studies.


Assuntos
Fertilizantes , Metaboloma , Nitrogênio , Florizina , Transcriptoma , Nitrogênio/metabolismo , Metaboloma/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Perfilação da Expressão Gênica , Espectrometria de Massas em Tandem , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
7.
Acc Chem Res ; 56(18): 2537-2554, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37694726

RESUMO

ConspectusAtropisomers bearing a rotation-restricted axis are common structural units in natural products, chiral ligands, and drugs; thus, the prevalence of asymmetric synthesis has increased in recent decades. Research into atropisomers featuring an N-containing axis (N-X atropisomers) remains in its infancy compared with the well-developed C-C atropisomer analogue. Notably, N-X atropisomers could offer divergent scaffolds, which are extremely important in bioactive molecules. The asymmetric synthesis of N-X atropisomers is recognized as both appealing and challenging. Recently, we devoted our efforts to the catalytic asymmetric synthesis of N-X atropisomers, benzimidazole-aryl N-C atropisomers, indole-aryl N-C atropisomers, hydrogen-bond-assisted N-C atropisomers, pyrrole-pyrrole N-N atropisomers, pyrrole-indole N-N atropisomers, and indole-indole N-N atropisomers. To obtain the N-C atropisomers, an asymmetric Buchwald-Hartwig reaction of amidines or enamines was employed. Using a Pd(OAc)2/(S)-BINAP or Pd(OAc)2/(S)-Xyl-BINAP catalyst system, benzimidazole-aryl N-C atropisomers and indole-aryl N-C atropisomers were readily obtained. To address the issue of the reduced stability of the diarylamine axis, a six-membered intramolecular N-H-O hydrogen bond was introduced into the N-C atropisomer scaffold. A tandem N-arylation/oxidation process was used for the chiral phosphoric acid (CPA)-catalyzed asymmetric synthesis of N-aryl quinone atropisomers. For N-N atropisomers, a copper-mediated asymmetric Friedel-Crafts alkylation/arylation reaction was developed. The desymmetrization process was completed successfully via a Cu(OTf)2/chiral bisoxazoline or (CuOTf)·Tol/bis(phosphine) dioxide system, thereby achieving the first catalytic asymmetric synthesis of N/N bipyrrole atropisomers. Asymmetric Buchwald-Hartwig amination of enamines was utilized to provide N-N bisindole atropisomers with excellent stereogenic control. This was the first asymmetric synthesis of N-N atropisomers featuring a bisindole structural scaffold using the de novo indole construction strategy. The asymmetric N-N heterobiaryl atropisomer synthesis was substantially facilitated using palladium-catalyzed transient directing group (TDG)-mediated C-H functionalization. Atropisomeric alkenylation, allylation, or alkynylation was accomplished using the Pd(OAc)2/l-tert-leucine system. Herein, we summarize our work on the palladium-, copper-, and CPA-catalyzed asymmetric syntheses of N-C and N-N atropisomers. Furthermore, the application of our work in the synthesis of bioactive molecule analogues and axially chiral ligands is demonstrated. Subsequently, the stability of the chiral N-containing axis is briefly discussed in terms of single crystals and obtained rotational barriers. Finally, an outlook on the asymmetric N-X atropisomer synthesis is provided.

8.
Acc Chem Res ; 56(2): 95-105, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36594628

RESUMO

Nanothermometry is increasingly demanded in frontier research in physics, chemistry, materials science and engineering, and biomedicine. An ideal thermometer should have features of reliable temperature interpretation, high sensitivity, fast response, minimum disturbance of the target's temperature, applicability in a variety of environments, and a large working temperature range. For applications in nanosystems, high spatial resolution is also desirable. Such requirements impose great challenges in nanothermometry since the shrinking of the sensor volume usually leads to a reduction in sensitivity.Diamond with nitrogen-vacancy (NV) centers provides opportunities for nanothermometry. NV center spins have sharp resonances due to their superb coherence. NV centers are multimodal sensors. They can directly sense magnetic fields, electric fields, temperature, pressure, and nuclear spins and, through proper transduction, measure other quantities such as the pH and deformation. In particular, their spin resonance frequencies vary with temperature, making them a promising thermometer. The high thermal conductivity, high hardness, chemical stability, and biocompatibility of diamond enable reliable and fast temperature sensing in complex environments ranging from erosive liquids to live systems. Chemical processing of diamond surfaces allows various functionalities such as targeting. The small size and the targeting capability of nanodiamonds then enable site-specific temperature sensing with nanoscale spatial resolution. However, the sensitivity of NV-based nanothermometry is yet to meet the requirement of practical systems with a large gap of a few orders of magnitude. On the other hand, although NV-based quantum sensing works well from 0.3 to 600 K, extending the sensing scheme to high temperature remains challenging due to uncertainty in identifying the exact physical limits and possible solution at elevated temperatures.This Account focuses on our efforts to enhance the temperature sensitivity and widen the working temperature range of diamond-based nanothermometry. We start with explaining the working principle and features of NV-based thermometry with examples of applications. Then a transducer-based concept is introduced with practical schemes to improve the sensitivity of the nanodiamond thermometer. Specifically, we show that the temperature signal can be transduced and amplified by adopting hybrid structures of nanodiamond and magnetic nanoparticles, which results in a record temperature sensitivity of 76 µK/√Hz. We also demonstrate quantum sensing with NV at high temperatures of up to 1000 K by adopting a pulsed heating-cooling scheme to carry out the spin polarization and readout at room temperature and the spin manipulation (sensing) at high temperatures. Finally, unsolved problems and future endeavors of diamond nanothermometry are discussed.


Assuntos
Diamante , Nanodiamantes , Nanodiamantes/química , Temperatura , Nitrogênio/química
9.
Phys Rev Lett ; 132(20): 200802, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38829065

RESUMO

Correlations of fluctuations are essential to understanding many-body systems and key information for advancing quantum technologies. To fully describe the dynamics of a physical system, all time-ordered correlations (TOCs), i.e., the dynamics-complete set of correlations are needed. The current measurement techniques can only access a limited set of TOCs, and there has been no systematic and feasible solution for extracting the dynamic-complete set of correlations hitherto. Here we propose a platform-universal protocol to selectively detect arbitrary types of TOCs via quantum channels. In our method, the quantum channels are synthesized with various controls, and engineer the evolution of a sensor-target system along a specific path that corresponds to a desired correlation. Using nuclear magnetic resonance, we experimentally demonstrate this protocol by detecting a specific type of fourth-order TOC that has never been accessed previously. We also show that the knowledge of the TOCs can be used to significantly improve the precision of quantum optimal control. Our method provides a new toolbox for characterizing the quantum many-body states and quantum noise, and hence for advancing the fields of quantum sensing and quantum computing.

10.
Chemistry ; 30(2): e202303165, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-37850396

RESUMO

Atropisomers have emerged as important structural scaffolds in natural products, drug design, and asymmetric synthesis. Recently, N-N biaryl atropisomers have drawn increasing interest due to their unique structure and relatively stable axes. However, its asymmetric synthesis remains scarce compared to its well-developed C-C biaryl analogs. In this concept, we summarize the asymmetric synthesis of N-N biaryl atropisomers including N-N pyrrole-pyrrole, N-N pyrrole-indole, N-N indole-indole, and N-N indole-carbazole, during which a series synthetic strategies are highlighted. Also, a synthetic evolution is briefly reviewed and an outlook of N-N biaryl atropisomers synthesis is offered.

11.
Exp Eye Res ; 241: 109851, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38453039

RESUMO

The accumulation of oleic acid (OA) in the meibum from patients with meibomian gland dysfunction (MGD) suggests that it may contribute to meibomian gland (MG) functional disorder, as it is a potent stimulator of acne-related lipogenesis and inflammation in sebaceous gland. Therefore, we investigate whether OA induces lipogenesis and inflammasome activation in organotypic cultured mouse MG and human meibomian gland epithelial cells (HMGECs). Organotypic cultured mouse MG and HMGECs were exposed to OA or combinations with specific AMPK agonists 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Lipogenic status, ductal keratinization, squamous metaplasia, NLRP3/ASC/Caspase-1 inflammasome activation, proinflammatory cytokine IL-1ß production, and AMPK pathway phosphorylation in MG were subsequently examined by lipid staining, immunofluorescence staining, immunohistochemical staining, ELISA assay, and Western blot analyses. We found that OA significantly induced lipid accumulation, ductal keratinization, and squamous metaplasia in organotypic cultured MG, as evidenced by increased lipids deposition within acini and duct, upregulated expression of lipogenic proteins (SREBP-1 and HMGCR), and elevation of K10/Sprr1b. Additionally, OA induced NLRP3/ASC/Caspase-1 inflammasome activation, cleavage of Caspase-1, and production of downstream proinflammatory cytokine IL-1ß. The findings of lipogenesis and NLRP3-related proinflammatory response in OA-stimulated HMGECs were consistent with those in organotypic cultured MG. OA exposure downregulated phospho-AMPK in two models, while AICAR treatment alleviated lipogenesis by improving AMPK/ACC phosphorylation and SREBP-1/HMGCR expression. Furthermore, AMPK amelioration inhibited activation of the NLRP3/ASC/Caspase-1 axis and secretion of IL-1ß, thereby relieving the OA-induced proinflammatory response. These results demonstrated that OA induced lipogenic disorder and NLRP3 inflammasome activation in organotypic cultured mouse MG and HMGECs by suppressing the AMPK signaling pathway, indicating OA may play an etiological role in MGD.


Assuntos
Carcinoma de Células Escamosas , Inflamassomos , Humanos , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Ácido Oleico/farmacologia , Ácido Oleico/metabolismo , Glândulas Tarsais/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Lipogênese , Células Epiteliais/metabolismo , Caspase 1/metabolismo , Citocinas/metabolismo , Metaplasia/metabolismo , Carcinoma de Células Escamosas/metabolismo , Interleucina-1beta/metabolismo
12.
Biotechnol Bioeng ; 121(5): 1674-1687, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38372655

RESUMO

Hollow fiber filter fouling is a common issue plaguing perfusion production process for biologics therapeutics, but the nature of filter foulant has been elusive. Here we studied cell culture materials especially Chinese hamster ovary (CHO) cell-derived extracellular vesicles in perfusion process to determine their role in filter fouling. We found that the decrease of CHO-derived small extracellular vesicles (sEVs) with 50-200 nm in diameter in perfusion permeates always preceded the increase in transmembrane pressure (TMP) and subsequent decrease in product sieving, suggesting that sEVs might have been retained inside filters and contributed to filter fouling. Using scanning electron microscopy and helium ion microscopy, we found sEV-like structures in pores and on foulant patches of hollow fiber tangential flow filtration filter (HF-TFF) membranes. We also observed that the Day 28 TMP of perfusion culture correlated positively with the percentage of foulant patch areas. In addition, energy dispersive X-ray spectroscopy-based elemental mapping microscopy and spectroscopy analysis suggests that foulant patches had enriched cellular materials but not antifoam. Fluorescent staining results further indicate that these cellular materials could be DNA, proteins, and even adherent CHO cells. Lastly, in a small-scale HF-TFF model, addition of CHO-specific sEVs in CHO culture simulated filter fouling behaviors in a concentration-dependent manner. Based on these results, we proposed a mechanism of HF-TFF fouling, in which filter pore constriction by CHO sEVs is followed by cake formation of cellular materials on filter membrane.


Assuntos
Anticorpos Monoclonais , Filtração , Cricetinae , Animais , Cricetulus , Células CHO , Perfusão , Filtração/métodos , Reatores Biológicos , Membranas Artificiais
13.
Langmuir ; 40(40): 20906-20917, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39323030

RESUMO

In this work, a smart self-healing coating with long-term anticorrosion ability was developed based on multiresponsive polyaniline (PANI) porous microspheres. The polyaniline porous microspheres loaded with corrosion inhibitor (benzotriazole, BTA) was prepared by the emulsion template method and photopolymerization. The BTA loaded in the polyaniline microspheres acted as a corrosion inhibitor, while the polyaniline in the shell performed the multiple functions of corrosion inhibition, pH-responsive and photoresponsive release, and photothermal conversion. Owing to the inherent corrosion-inhibiting nature of BTA and PANI, the BTA-loaded polyaniline microsphere could endow coating with dual anticorrosive properties. The coating with polyaniline microspheres did not show any corrosion product after 700 h of salt spray testing, while obvious pitting corrosion could be observed for the blank coating after 100 h of the salt spray test. Thanks to the photothermal properties of PANI, the composite coating exhibited self-healing behavior under NIR light irradiation. The coating with 10 wt % polyaniline microspheres could achieve rapid closure and recover its barrier properties within 5 s of NIR irradiation. And the release of BTA could form a passivation film on scratches to further repair coating defects. The on-command responsive release, high healing efficiency, and excellent anticorrosion properties of this dual self-healing anticorrosion coating provide perspectives on extending the service life of metals.

14.
Langmuir ; 40(35): 18652-18660, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39158702

RESUMO

Incorporating unmodified silica nanoparticles onto polymer latexes to fabricate aqueous polymer dispersions without relying on electrostatic attraction during the Pickering emulsion polymerization process still faces challenges. For negatively charged silica nanoparticles to successfully adsorb onto polymer latexes, particularly in an anionic initiator emulsion polymerization system, they have remained elusive without the use of auxiliary monomers and cationic initiators. This study investigates various experimental parameters, such as emulsion polymerization temperature, monomer solubility, salt concentration, and cation type, to elucidate the factors influencing the adsorption of unmodified silica nanoparticles in Pickering emulsion polymerization. While poly(methyl methacrylate) (PMMA)/SiO2 hybrid latexes can be obtained under pH conditions of 5-6 and at temperatures of 65 °C or below, the loading rate of silica nanoparticles decreases as the reaction temperature increases, resulting in bare PMMA latexes without silica nanoparticle adsorption at temperatures exceeding 70 °C. Introducing styrene (St) into the monomer mixture with methyl methacrylate in a ratio of up to 10 wt % leads to a gradual decrease in silica nanoparticle loading rate, from 27.3 to 8.2 wt %, attributed to the low solubility of St in water. Furthermore, the presence of sodium ions (Na+) is found to be crucial for silica nanoparticle adsorption onto PMMA latexes, as the sodium ions have a stabilizing effect on both the silica nanoparticles and the silica nanoparticle-armored latexes. These findings highlight the complex nature of Pickering emulsion polymerization in the presence of unmodified silica nanoparticles, demonstrating that the loading rate of silica nanoparticles onto polymer latexes is influenced by various factors. These insights pave the way for developing aqueous polymer dispersions with high silica nanoparticle loading rates onto polymer latexes, which is a desirable trait in the coating industry.

15.
Org Biomol Chem ; 22(30): 6189-6197, 2024 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-39027944

RESUMO

A series of chromone-deferiprone hybrids were designed, synthesized, and evaluated as inhibitors of human monoamine oxidase B (hMAO-B) with iron-chelating activity for the treatment of Alzheimer's disease (AD). The majority exhibited moderate inhibitory activity towards hMAO-B and potent iron-chelating properties. Particularly, compound 25c demonstrated remarkable selectivity against hMAO-B with an IC50 value of 1.58 µM and potent iron-chelating ability (pFe3+ = 18.79) comparable to that of deferiprone (pFe3+ = 17.90). Molecular modeling and kinetic studies showed that 25c functions as a non-competitive hMAO-B inhibitor. According to the predicted results, compound 25c can penetrate the blood-brain barrier (BBB). Additionally, it has been proved to display significant antioxidant activity and the ability to inhibit neuronal ferroptosis. More importantly, compound 25c reduced the cognitive impairment induced by scopolamine and showed significant non-toxicity in short-term toxicity assays. In summary, compound 25c was identified as a potential anti-AD agent with hMAO-B inhibitory, iron-chelating and anti-ferroptosis activities.


Assuntos
Doença de Alzheimer , Cromonas , Deferiprona , Quelantes de Ferro , Inibidores da Monoaminoxidase , Monoaminoxidase , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/síntese química , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Quelantes de Ferro/farmacologia , Quelantes de Ferro/química , Quelantes de Ferro/síntese química , Deferiprona/farmacologia , Deferiprona/química , Monoaminoxidase/metabolismo , Humanos , Cromonas/química , Cromonas/farmacologia , Cromonas/síntese química , Relação Estrutura-Atividade , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/síntese química , Ferroptose/efeitos dos fármacos , Estrutura Molecular , Simulação de Acoplamento Molecular , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Relação Dose-Resposta a Droga
16.
Mycorrhiza ; 34(4): 283-292, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38918244

RESUMO

Mycoheterotrophic plants (MHPs) rely on their mycorrhizal fungus for carbon and nutrient supply, thus a shift in mycobionts may play a crucial role in speciation. This study aims to explore the mycorrhizal diversity of two closely related and sympatric fully MHPs, Monotropastrum humile var. humile (Mhh) and M. humile var. glaberrimum (Mhg), and determine their mycorrhizal associations. A total of 1,108,710 and 1,119,071 ectomycorrhizal fungal reads were obtained from 31 Mhh and 31 Mhg, and these were finally assigned to 227 and 202 operational taxonomic units, respectively. Results show that sympatric Mhh and Mhg are predominantly associated with different fungal genera in Russulaceae. Mhh is consistently associated with members of Russula, whereas Mhg is associated with members of Lactarius. Associating with different mycobionts and limited sharing of fungal partners might reduce the competition and contribute to their coexistence. The ectomycorrhizal fungal communities are significantly different among the five forests in both Mhh and Mhg. The distinct mycorrhizal specificity between Mhh and Mhg suggests the possibility of different mycobionts triggered ecological speciation between sympatric species.


Assuntos
Biodiversidade , Micorrizas , Micorrizas/fisiologia , Micorrizas/classificação , Micorrizas/genética , Simpatria , Asteraceae/microbiologia , Filogenia , Microbiologia do Solo
17.
Phytother Res ; 38(7): 3782-3800, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38839050

RESUMO

Pediatric intestinal development is immature, vulnerable to external influences and produce a variety of intestinal diseases. At present, breakthroughs have been made in the treatment of pediatric intestinal diseases, but there are still many challenges, such as toxic side effects, drug resistance, and the lack of more effective treatments and specific drugs. In recent years, dietary polyphenols derived from plants have become a research hotspot in the treatment of pediatric intestinal diseases due to their outstanding pharmacological activities such, as anti-inflammatory, antibacterial, antioxidant and regulation of intestinal flora. This article reviewed the mechanism of action and clinical evidence of dietary polyphenols in the treatment of pediatric intestinal diseases, and discussed the influence of physiological characteristics of children on the efficacy of polyphenols, and finally prospected the new dosage forms of polyphenols in pediatrics.


Assuntos
Enteropatias , Polifenóis , Humanos , Polifenóis/farmacologia , Criança , Enteropatias/tratamento farmacológico , Enteropatias/dietoterapia , Enteropatias/prevenção & controle , Antioxidantes/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Dieta
18.
Arch Pharm (Weinheim) ; 357(3): e2300524, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38036297

RESUMO

In the literature, daidzein has been reported to exhibit cardiovascular protective effects and hypoglycemic activity in mice. We sought to design and synthesize a novel compound, SJ-6, an analog of daidzein, with improved hypoglycemic properties. Although SJ-6 demonstrated favorable hypoglycemic effects, its pharmacokinetic limitations prompted us to design and synthesize prodrugs of SJ-6. We conducted a comprehensive evaluation of the prodrugs, including in vitro and in vivo studies, such as cytotoxicity, absorption, distribution, metabolism, excretion, and toxicity (ADMET) simulation analysis, in vitro blood-brain barrier (BBB) permeability evaluation, compound effect on insulin resistance, oral glucose tolerance test (OGTT), in vivo plasma concentration testing, acute toxicity test in rats, and long-term gavage administration experiment. Furthermore, we examined the antidiabetic nephropathy activity of our lead compound, compound 10, which demonstrated superior efficacy compared with the positive control drug, metformin hydrochloride. Our findings suggest that compound 10 represents a promising lead compound for the prevention and treatment of diabetic nephropathy.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Pró-Fármacos , Animais , Camundongos , Ratos , Nefropatias Diabéticas/tratamento farmacológico , Relação Estrutura-Atividade , Hipoglicemiantes/farmacologia , Barreira Hematoencefálica
19.
Angew Chem Int Ed Engl ; 63(8): e202319289, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38185722

RESUMO

Inherent chirality is used to describe chiral cyclic molecules devoid of central, axial, planar, or helical chirality and has tremendous applications in chiral recognition and enantioselective synthesis. Catalytic and divergent syntheses of inherently chiral molecules have attracted increasing interest from chemists. Herein, we report the enantioselective synthesis of inherently chiral tribenzocycloheptene derivatives via chiral phosphoric acid (CPA)-catalyzed condensation of cyclic ketones and hydroxylamines. This chemistry paves the way to accessing the less stable derivatives of 7-membered rings with inherent chirality. A series of chiral tribenzocycloheptene oxime ethers was synthesized in good yields (up to 97 %) with excellent enantioselectivities (up to 99 % ee).

20.
Angew Chem Int Ed Engl ; 63(39): e202407752, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-38844430

RESUMO

Inherently chiral calix[4]arenes are an excellent structural scaffold for enantioselective synthesis, chiral recognition, sensing, and circularly polarized luminescence. However, their catalytic enantioselective synthesis remains challenging. Herein, we report an efficient synthesis of inherently chiral calix[4]arene derivatives via cascade enantioselective cyclization and oxidation reactions. The three-component reaction features a broad substrate scope (33 examples), high efficiency (up to 90 % yield), and excellent enantioselectivity (>95 % ee on average). The potential applications of calix[4]arene derivatives are highlighted by their synthetic transformation and a detailed investigation of their photophysical and chiroptical properties.

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