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1.
bioRxiv ; 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39463981

RESUMO

This study demonstrates a silicon nanopillar metasurface coupled with localized surface plasmon resonance (LSPR) mediated by the presence of cephalexin antibiotics in solution for biosensing applications. A facile fabrication process was developed to create the metasurface on silicon wafers with a unique resonance signature. The resulting metasurface consists of periodic nanopillars approximately 180 nm in diameter, 210 nm deep, and with a controlled edge-to-edge separation of 200 nm. These dimensions were chosen based on a finite element method simulation that was used to investigate the ideal parameters to produce the desired resonance effect in the metasurface reflection spectra. Optimization of the nanopillar surface properties and the sidewall angle allowed for replication of the simulations. This metasurface was coupled with BSA-coated gold nanospheres (BSANS) to mediate the redshift of peak resonance wavelength values, occurring only in the presence of the antibiotic linker. The device fabricated herein exhibits a significant 22 nm wavelength shift resulting from changes to the local refractive index in the presence of the BSANS-antibiotic coupling. Further enhancement of the binding events is promoted by the LSPR hot spots formed between the nanoparticles and the metasurface allowing for sensitive and real-time detection.

2.
Free Radic Biol Med ; 224: 770-784, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39313014

RESUMO

Gaudichaudione H (GH) is a natural small molecular compound isolated from Garcinia oligantha Merr. (Clusiaceae). Being an uncommon rare caged polyprenylated xanthone, the potential pharmacological functions of GH remain to be fully elucidated currently. In this study, we primarily focused on identifying potential bioavailable targets and elucidating related therapeutic actions. Herein, the network pharmacology analysis, metabolomics analysis and genome-wide mRNA transcription assay were performed firstly to predict the major pharmacological action and potential targets of GH. To confirm the hypothesis, gene knockout model was created using CRISPR/Cas9 method. The pharmacological action of GH was evaluated in vitro and in vivo. Firstly, our results of network pharmacology analysis and omics assay indicated that GH significantly activated NRF2 signaling pathway, and the function could be associated with liver disease treatment. Then, the pharmacological action of GH was evaluated in vitro and in vivo. The treatment with GH significantly increased the protein levels of NRF2 and promoted the transcription of NRF2 downstream genes. Further analysis suggested that GH regulated NRF2 through an autophagy-mediated non-canonical mechanism. Additionally, the administration of GH effectively protected the liver from carbon tetrachloride (CCl4)-induced liver fibrosis and inflammation, which depended on the activation of NRF2 in hepatic stellate cells and inflammatory cells respectively. Collectively, our findings underscore the potential therapeutic effect of GH on alleviating hepatic fibrosis and inflammation through the augmentation of NRF2 signaling pathway, providing a promising avenue for the treatment of liver fibrosis and inflammation in clinical settings.

3.
Physiol Plant ; 176(5): e14508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39295090

RESUMO

Camptotheca acuminata Decne., a significant natural source of the anticancer drug camptothecin (CPT), synthesizes CPT through the monoterpene indole alkaloid (MIA) pathway. In this study, we used single-cell RNA sequencing (scRNA-seq) to generate datasets encompassing over 60,000 cells from C. acuminata shoot apexes and leaves. After cell clustering and annotation, we identified five major cell types in shoot apexes and four in leaves. Analysis of MIA pathway gene expression revealed that most of them exhibited heightened expression in proliferating cells (PCs) and vascular cells (VCs). In contrast to MIA biosynthesis in Catharanthus roseus, CPT biosynthesis in C. acuminata did not exhibit multicellular compartmentalization. Some putative genes encoding enzymes and transcription factors (TFs) related to the biosynthesis of CPT and its derivatives were identified through co-expression analysis. These include 19 cytochrome P450 genes, 8 O-methyltransferase (OMT) genes, and 62 TFs. Additionally, these pathway genes exhibited dynamic expression patterns during VC and EC development. Furthermore, by integrating gene and transposable element (TE) expression data, we constructed novel single-cell transcriptome atlases for C. acuminata. This approach significantly facilitated the identification of rare cell types, including peripheral zone cells (PZs). Some TE families displayed cell type specific, tissue specific, or developmental stage-specific expression patterns, suggesting crucial roles for these TEs in cell differentiation and development. Overall, this study not only provides novel insights into CPT biosynthesis and spatial-temporal TE expression characteristics in C. acuminata, but also serves as a valuable resource for further comprehensive investigations into the development and physiology of this species.


Assuntos
Camptotheca , Camptotecina , Regulação da Expressão Gênica de Plantas , Folhas de Planta , Brotos de Planta , Camptotheca/genética , Camptotheca/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Brotos de Planta/genética , Brotos de Planta/metabolismo , Elementos de DNA Transponíveis/genética , Análise de Sequência de RNA , Análise de Célula Única/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Análise da Expressão Gênica de Célula Única
4.
Environ Manage ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39349642

RESUMO

Machine learning (ML) techniques have been researched and used in various environmental monitoring applications. Few studies have reported the long-term evaluation of such applications. Discussions regarding the risks and regulatory frameworks of ML applications in environmental monitoring have been rare. We monitored the performance of six predictive models developed using ML and statistical methods for 28 months. The six models used to predict NOx emissions were developed using six different algorithms. The model developed with a moderate complexity algorithm, adaptive boosting, had the best performance in long-term monitoring, with a root mean square error (RMSE) of 0.48 kg/hr in the 28-month monitoring period, and passed two of the three relative accuracy test audits. High complexity models based on gradient boosting and neural network algorithms had the best training performance, with a minimum RMSE of 0.23 kg/hr and 0.26 kg/hr, but also had the worst RMSE scores, of 0.51 kg/hr and 0.57 kg/hr, during the monitoring period. In addition, all six models failed all three relative accuracy test audits. The following problems were observed: (1) Complex ML models tended to have overfitting problems, thus indicating the importance of the trade-off between model accuracy and complexity. (2) Model input sensor drift or out of high-frequency ranges from the training data resulted in inaccurate predictions or an accuracy lower than the minimum allowed by regulators. (3) Existing regulatory frameworks must be modernized to keep pace with current machine learning practices. Some statistical tests are unsuitable for applications developed by using ML methods.

5.
J Phys Chem Lett ; 15(34): 8628-8635, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39150409

RESUMO

Polycrystalline lithium manganese oxide (LMO) is known to suffer from severe surface structure degradation and electrochemical polarization due to its mixed crystal plane orientations. A hexagonal prism single-crystal LMO (LMOS-HP), engineered through the SrO-induced preferential growth effect, features the most stable {111} top surfaces and the fastest Li+ diffusion {110} side surfaces, effectively addressing these challenges. Consequently, LMOS-HP exhibits superior electrochemical capability, with only 0.021% capacity fading per cycle after 500 cycles and achieves a discharge capacity of 81.9 mAh g-1 at 20C. This innovative design offers a promising approach for tuning surface crystal orientation to improve performance.

6.
Eur J Med Chem ; 277: 116735, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39098131

RESUMO

The molecular generation models based on protein structures represent a cutting-edge research direction in artificial intelligence-assisted drug discovery. This article aims to comprehensively summarize the research methods and developments by analyzing a series of novel molecular generation models predicated on protein structures. Initially, we categorize the molecular generation models based on protein structures and highlight the architectural frameworks utilized in these models. Subsequently, we detail the design and implementation of protein structure-based molecular generation models by introducing different specific examples. Lastly, we outline the current opportunities and challenges encountered in this field, intending to offer guidance and a referential framework for developing and studying new models in related fields in the future.


Assuntos
Inteligência Artificial , Modelos Moleculares , Proteínas , Proteínas/química , Conformação Proteica , Descoberta de Drogas , Humanos
7.
Angew Chem Int Ed Engl ; 63(44): e202411503, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-38985723

RESUMO

Anisotropy is crucial for birefringence (Δn) in optical materials, but optimizing it remains a formidable challenge (Δn >0.3). Supramolecular frameworks incorporating π-conjugated components are promising for achieving enhanced birefringence because of their structural diversity and inherent anisotropy. Herein, we first synthesized (C6H6NO2)+Cl- (NAC) and then constructed a halogen-bonded supramolecular framework I+(C6H4NO2)- (INA) by halogen aliovalent substitution of Cl- with I+. The organic moieties are protonated and deprotonated nicotinic acid (NA), respectively. The antiparallel arrangement of birefringent-active units in NAC and INA leads to significant differences in the bonding characteristics between the interlayer and intralayer domains. Moreover, the [O⋅⋅⋅I+⋅⋅⋅N] halogen bond in 1D [I+(C6H4NO2)-] chain exhibits stronger interactions and stricter directionality, resulting in a more pronounced in-plane anisotropy between the intrachain and interchain directions. Consequently, INA exhibits exceptional birefringent performance, with a value of 0.778 at 550 nm, twice that of NAC (0.363 at 550 nm). This value significantly exceeds those of commercial birefringent crystals, such as CaCO3 (0.172 at 546 nm), and is the highest reported value among ultraviolet birefringent crystals. This work presents a novel design strategy that employs halogen bonds as connection sites and modes for birefringent-active units, opening new avenues for developing high-performance birefringent crystals.

8.
Mikrochim Acta ; 191(8): 466, 2024 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-39017814

RESUMO

The CRISPR/Cas13 nucleases have been widely documented for nucleic acid detection. Understanding the intricacies of CRISPR/Cas13's reaction components is pivotal for harnessing its full potential for biosensing applications. Herein, we report on the influence of CRISPR/Cas13a reaction components on its trans-cleavage activity and the development of an on-chip total internal reflection fluorescence microscopy (TIRFM)-powered RNA sensing system. We used SARS-CoV-2 synthetic RNA and pseudovirus as a model system. Our results show that optimizing Mg2+ concentration, reporter length, and crRNA combination significantly improves the detection sensitivity. Under optimized conditions, we detected 100 fM unamplified SARS-CoV-2 synthetic RNA using a microtiter plate reader. To further improve sensitivity and provide a new amplification-free RNA sensing toolbox, we developed a TIRFM-based amplification-free RNA sensing system. We were able to detect RNA down to 100 aM. Furthermore, the TIRM-based detection system developed in this study is 1000-fold more sensitive than the off-coverslip assay. The possible clinical applicability of the system was demonstrated by detecting SARS-CoV-2 pseudovirus RNA. Our proposed sensing system has the potential to detect any target RNA with slight modifications to the existing setup, providing a universal RNA detection platform.


Assuntos
Sistemas CRISPR-Cas , RNA Viral , SARS-CoV-2 , SARS-CoV-2/genética , RNA Viral/análise , RNA Viral/genética , Humanos , COVID-19/diagnóstico , COVID-19/virologia , Técnicas Biossensoriais/métodos , Proteínas Associadas a CRISPR , Microscopia de Fluorescência , Dispositivos Lab-On-A-Chip , Limite de Detecção , Magnésio/química , Teste de Ácido Nucleico para COVID-19/métodos
9.
bioRxiv ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38915492

RESUMO

A. Numerous studies have been trying to create nanomaterials based antimicrobial surfaces to combat the growing bacterial infection problems. Mechanical durability has become one of the major challenges to applying those surfaces in real life. In this study, we demonstrate the Durable Antimicrobial Microstructures Surface (DAMS) consisting of DLP 3D printed microstructures and zinc oxide (ZnO) nanoflowers. The microstructures serve as a protection armor for the nanoflowers during abrasion. The antimicrobial ability was tested by immersing in 2E8 CFU/mL Escherichia coli ( E. coli ) suspension and then evaluated using electron microscopy. Compared to the bare control, our results show that the DAMS reduces bacterial coverage by more than 90% after 12 hrs of incubation and approximately 50% after 48 hrs of incubation before abrasion. Importantly, bacterial coverage is reduced by approximately 50% after 2 min of abrasion with a tribometer, and DAMS remains effective even after 6 min of abrasion. These findings highlight the potential of DAMS as an affordable, scalable, and durable antimicrobial surface for various biomedical applications.

10.
Dalton Trans ; 53(25): 10536-10543, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38842192

RESUMO

Herein, the first F-containing iodate-phosphate, namely Ba2Ga2F6(IO3)(PO4), was prepared via a hydrothermal reaction, in which HPF6 (70 wt% solution in water) was used as the source of both fluoride and phosphate anions for the first time. Ba2Ga2F6(IO3)(PO4) features an unprecedented 1D [Ga2F6(IO3)(PO4)]4- helix chain, composed of a 1D Ga(1)(IO3)O4F chain via the bridging of 0D Ga(2)(PO4)F5. The UV-Vis spectrum shows that Ba2Ga2F6(IO3)(PO4) has a wide bandgap with a short-UV absorption edge (4.35 eV; 253 nm). Birefringence measurement under a polarizing microscope shows that Ba2Ga2F6(IO3)(PO4) displays a moderate birefringence of 0.072@550 nm, which is consistent with the value (0.070@550 nm) obtained by DFT calculations, indicating that Ba2Ga2F6(IO3)(PO4) has potential applications as a short-UV birefringent material. This study highlights the crucial role played by the incorporation of specific functional groups into compounds, shedding light on their contribution to promising inorganic functional materials.

11.
Medicine (Baltimore) ; 103(23): e38339, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847666

RESUMO

In this study, we developed a method for determining cotinine and 3-hydroxycotinine in human serum and established a methodology for an in-depth study of tobacco exposure and health. After the proteins in the human serum samples were precipitated with acetonitrile, they were separated on a ZORBAX SB-Phenyl column with a mobile phase of methanol encompassing 0.3% formic acid-water encompassing 0.15% formic acid. The measurement was performed on an API5500 triple quadrupole mass spectrometer in the multiple reaction monitoring mode. Cotinine, 3-hydroxycotinine, and cotinine-d3 isotope internal standards were held for 2.56 minutes, 1.58 minutes, and 2.56 minutes, respectively. In serum, the linear range was 0.05 to 500 ng·mL-1 for cotinine and 0.50 to 1250 ng·mL-1 for 3-hydroxycotinine. The lower limit of quantification (LLOQ) was 0.05 ng·mL-1 and 0.5 ng·mL-1 for cotinine and 3-hydroxycotinine, respectively. The intra-day and inter-day relative standard deviations were <11%, and the relative errors were within ±â€…7%. Moreover, the mean extraction recoveries of cotinine and 3-hydroxycotinine were 98.54% and 100.24%, respectively. This method is suitable for the rapid determination of cotinine and 3-hydroxycotinine in human serum because of its rapidity, sensitivity, strong specificity, and high reproducibility. The detection of cotinine levels in human serum allows for the identification of the cutoff value, providing a basis for differentiation between smoking and nonsmoking populations.


Assuntos
Cotinina , Espectrometria de Massas em Tandem , Humanos , Cotinina/sangue , Cotinina/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Reprodutibilidade dos Testes , Limite de Detecção
12.
Life Sci ; : 122861, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925222

RESUMO

SARS-CoV-2 is a highly contagious pathogen that predominantly caused the COVID-19 pandemic. The persistent effects of COVID-19 are defined as an inflammatory or host response to the virus that begins four weeks after initial infection and persists for an undetermined length of time. Chronic effects are more harmful than acute ones thus, this review explored the long-term effects of the virus on various human organs, including the pulmonary, cardiovascular, and neurological, reproductive, gastrointestinal, musculoskeletal, endocrine, and lymphoid systems and found that SARS-CoV-2 adversely affects these organs of older adults. Regarding diagnosis, the RT-PCR is a gold standard method of diagnosing COVID-19; however, it requires specialized equipment and personnel for performing assays and a long time for results production. Therefore, to overcome these limitations, artificial intelligence employed in imaging and microfluidics technologies is the most promising in diagnosing COVID-19. Pharmacological and non-pharmacological strategies are the most effective treatment for reducing the persistent impacts of COVID-19 by providing immunity to post-COVID-19 patients by reducing cytokine release syndrome, improving the T cell response, and increasing the circulation of activated natural killer and CD8 T cells in blood and tissues, which ultimately reduces fever, nausea, fatigue, and muscle weakness and pain. Vaccines such as inactivated viral, live attenuated viral, protein subunit, viral vectored, mRNA, DNA, or nanoparticle vaccines significantly reduce the adverse long-term virus effects in post-COVID-19 patients; however, no vaccine was reported to provide lifetime protection against COVID-19; consequently, protective measures such as physical separation, mask use, and hand cleansing are promising strategies. This review provides a comprehensive knowledge of the persistent effects of COVID-19 on people of varying ages, as well as diagnosis, treatment, vaccination, and future preventative measures against the spread of SARS-CoV-2.

13.
Adv Sci (Weinh) ; 11(31): e2304687, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38889331

RESUMO

The microenvironment mediated by the microglia (MG) M1/M2 phenotypic switch plays a decisive role in the neuronal fate and cognitive function of Alzheimer's disease (AD). However, the impact of metabolic reprogramming on microglial polarization and its underlying mechanism remains elusive. This study reveals that cordycepin improved cognitive function and memory in APP/PS1 mice, as well as attenuated neuronal damage by triggering MG-M2 polarization and metabolic reprogramming characterized by increased OXPHOS and glycolysis, rather than directly protecting neurons. Simultaneously, cordycepin partially alleviates mitochondrial damage in microglia induced by inhibitors of OXPHOS and glycolysis, further promoting MG-M2 transformation and increasing neuronal survival. Through confirmation of cordycepin distribution in the microglial mitochondria via mitochondrial isolation followed by HPLC-MS/MS techniques, HKII and PDK2 are further identified as potential targets of cordycepin. By investigating the effects of HKII and PDK2 inhibitors, the mechanism through which cordycepin targeted HKII to elevate ECAR levels in the glycolysis pathway while targeting PDK2 to enhance OCR levels in PDH-mediated OXPHOS pathway, thereby inducing MG-M2 polarization, promoting neuronal survival and exerting an anti-AD role is elucidated.


Assuntos
Desoxiadenosinas , Modelos Animais de Doenças , Microglia , Mitocôndrias , Animais , Microglia/metabolismo , Microglia/efeitos dos fármacos , Desoxiadenosinas/farmacologia , Desoxiadenosinas/metabolismo , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Hexoquinase/metabolismo , Hexoquinase/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Glicólise/efeitos dos fármacos , Reprogramação Metabólica
14.
Lab Chip ; 24(14): 3490-3497, 2024 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-38920004

RESUMO

Point-of-care (POC) diagnostics have emerged as a crucial technology for emerging pathogen detections to enable rapid and on-site detection of infectious diseases. However, current POC devices often suffer from limited sensitivity with poor reliability to provide quantitative readouts. In this paper, we present a self-powered digital loop-mediated isothermal amplification (dLAMP) microfluidic chip (SP-dChip) for the rapid and quantitative detection of nucleic acids. The SP-dChip utilizes a vacuum lung design to passively digitize samples into individual nanoliter wells for high-throughput analysis. The superior digitization scheme is further combined with reverse transcription loop-mediated isothermal amplification (RT-LAMP) to demonstrate dLAMP detection of Zika virus (ZIKV). Firstly, the LAMP assay is loaded into the chip and passively digitized into individual wells. Mineral oil is then pipetted through the chip to differentiate each well as an individual reactor. The chip did not require any external pumping or power input for rapid and reliable results to detect ZIKA RNA as low as 100 copies per µL within one hour. As such, this SP-dChip offers a new class of solutions for truly affordable, portable, and quantitative POC detections for emerging viruses.


Assuntos
Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Técnicas de Amplificação de Ácido Nucleico , Zika virus , Técnicas de Amplificação de Ácido Nucleico/instrumentação , Técnicas de Amplificação de Ácido Nucleico/métodos , Zika virus/isolamento & purificação , Zika virus/genética , Técnicas Analíticas Microfluídicas/instrumentação , Desenho de Equipamento , Humanos , Técnicas de Diagnóstico Molecular/instrumentação , Técnicas de Diagnóstico Molecular/métodos , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia , Sistemas Automatizados de Assistência Junto ao Leito , RNA Viral/análise , RNA Viral/genética
15.
Nano Lett ; 24(20): 6061-6068, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38728017

RESUMO

van der Waals (vdW) superlattices, comprising different 2D materials aligned alternately by weak interlayer interactions, offer versatile structures for the fabrication of novel semiconductor devices. Despite their potential, the precise control of optoelectronic properties with interlayer interactions remains challenging. Here, we investigate the discrepancies between the SnS/TiS2 superlattice (SnTiS3) and its subsystems by comprehensive characterization and DFT calculations. The disappearance of certain Raman modes suggests that the interactions alter the SnS subsystem structure. Specifically, such structural changes transform the band structure from indirect to direct band gap, causing a strong PL emission (∼2.18 eV) in SnTiS3. In addition, the modulation of the optoelectronic properties ultimately leads to the unique phenomenon of thermally activated photoluminescence. This phenomenon is attributed to the inhibition of charge transfer induced by tunable intralayer strains. Our findings extend the understanding of the mechanism of interlayer interactions in van der Waals superlattices and provide insights into the design of high-temperature optoelectronic devices.

16.
Bioorg Chem ; 147: 107420, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38718461

RESUMO

Phytochemical analysis of Chloranthus henryi var. hupehensis roots led to the identification of a new eudesmane sesquiterpenoid dimer, 18 new sesquiterpenoids, and three known sesquiterpenoids. Among the isolates, 1 was a rare sesquiterpenoid dimer that is assembled by a unique oxygen bridge (C11-O-C8') of two highly rearranged eudesmane-type sesquiterpenes with the undescribed C16 carbon framework. (+)-2 and (-)-2 were a pair of new skeleton dinorsesquiterpenoids with a remarkable 6/6/5 tricyclic ring framework including one γ-lactone ring and the bicyclo[3.3.1]nonane core. Their structures were elucidated using spectroscopic data, single-crystal X-ray diffraction analysis, and quantum chemical computations. In the LPS-induced BV-2 microglial cell model, 17 suppressed IL-1ß and TNF-α expression with EC50 values of 6.81 and 2.76 µM, respectively, indicating its excellent efficacy in inhibiting inflammatory factors production in a dose dependent manner and without cytotoxicity. In subsequent mechanism studies, compounds 3, 16, and 17 could reduce IL-1ß and TNF-α production by inhibiting IKBα/p65 pathway activation.


Assuntos
Relação Dose-Resposta a Droga , Raízes de Plantas , Sesquiterpenos , Transdução de Sinais , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Raízes de Plantas/química , Transdução de Sinais/efeitos dos fármacos , Estrutura Molecular , Camundongos , Animais , Relação Estrutura-Atividade , Fator de Transcrição RelA/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Descoberta de Drogas , Inibidor de NF-kappaB alfa/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação
17.
Front Plant Sci ; 15: 1394587, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779067

RESUMO

Gynostemma pentaphyllum (Thunb.) Makino is an important producer of dammarene-type triterpenoid saponins. These saponins (gypenosides) exhibit diverse pharmacological benefits such as anticancer, antidiabetic, and immunomodulatory effects, and have major potential in the pharmaceutical and health care industries. Here, we employed single-cell RNA sequencing (scRNA-seq) to profile the transcriptomes of more than 50,000 cells derived from G. pentaphyllum shoot apexes and leaves. Following cell clustering and annotation, we identified five major cell types in shoot apexes and four in leaves. Each cell type displayed substantial transcriptomic heterogeneity both within and between tissues. Examining gene expression patterns across various cell types revealed that gypenoside biosynthesis predominantly occurred in mesophyll cells, with heightened activity observed in shoot apexes compared to leaves. Furthermore, we explored the impact of transposable elements (TEs) on G. pentaphyllum transcriptomic landscapes. Our findings the highlighted the unbalanced expression of certain TE families across different cell types in shoot apexes and leaves, marking the first investigation of TE expression at the single-cell level in plants. Additionally, we observed dynamic expression of genes involved in gypenoside biosynthesis and specific TE families during epidermal and vascular cell development. The involvement of TE expression in regulating cell differentiation and gypenoside biosynthesis warrant further exploration. Overall, this study not only provides new insights into the spatiotemporal organization of gypenoside biosynthesis and TE activity in G. pentaphyllum shoot apexes and leaves but also offers valuable cellular and genetic resources for a deeper understanding of developmental and physiological processes at single-cell resolution in this species.

18.
iScience ; 27(6): 109824, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38779484

RESUMO

Hydrodesulfurization (HDS) is a commonly used route for producing clean fuels in modern refinery. Herein, ammonium/amine-intercalated MoS2 catalysts with various content of 1T phase and S vacancies have been successfully synthesized. Along with the increment of 1T phase and S vacancies of MoS2, the initial reaction rate of the HDS of dibenzothiophene (DBT) can be improved from 0.09 to 0.55 µmol·gcat-1·s-1, accounting for a remarkable activity compared to the-state-of-the-art catalysts. In a combinatory study via the activity evaluation and catalysts characterization, we found that the intercalation species of MoS2 played a key role in generating more 1T phase and S vacancies through the 'intercalation-deintercalation' processes, and the hydrogenation and desulfurization of HDS can be significantly promoted by 1T phase and S vacancies on MoS2, respectively. This study provides a practically meaningful guidance for developing more advanced HDS catalysts by the intercalated MoS2-derived materials with an in-depth understanding of structure-function relationships.

19.
J Med Chem ; 67(10): 7911-7920, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38709774

RESUMO

Using copper-ionophores to translocate extracellular copper into mitochondria is a clinically validated anticancer strategy that has been identified as a new type of regulated cell death termed "cuproptosis." This study reports a mitochondria-targeting Cu(I) complex, Cu(I)Br(PPh3)3 (CBP), consisting of a cuprous ion coordinated by three triphenylphosphine moieties and a Br atom. CBP exhibited antitumor and antimetastatic efficacy in vitro and in vivo by specifically targeting mitochondria instigating mitochondrial dysfunction. The cytotoxicity of CBP could only be reversed by a copper chelator rather than inhibitors of the known cell death, indicating copper-dependent cytotoxicity. Furthermore, CBP induced the oligomerization of lipoylated proteins and the loss of Fe-S cluster proteins, consistent with characteristic features of cuproptosis. Additionally, CBP induced remarkable intracellular generation of reactive oxygen species (ROS) through a Fenton-like reaction, indicating a complex antitumor mechanism. This is a proof-of-concept study exploiting the antitumor activity and mechanism of the Cu(I)-based mitochondria-targeting therapy.


Assuntos
Antineoplásicos , Complexos de Coordenação , Cobre , Mitocôndrias , Espécies Reativas de Oxigênio , Cobre/química , Cobre/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Animais , Espécies Reativas de Oxigênio/metabolismo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Camundongos , Linhagem Celular Tumoral
20.
Eur J Microbiol Immunol (Bp) ; 14(3): 243-260, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-38801662

RESUMO

Serious risks to human health are posed by acute campylobacteriosis, an enteritis syndrome caused by oral infection with the food-borne bacterial enteropathogen Campylobacter jejuni. Since the risk for developing post-infectious autoimmune complications is intertwined with the severity of enteritis, the search of disease-mitigating compounds is highly demanded. Given that benzoic acid is an organic acid with well-studied health-promoting including anti-inflammatory effects we tested in our present study whether the compound might be a therapeutic option to alleviate acute murine campylobacteriosis. Therefore, microbiota-depleted IL-10-/- mice were perorally infected with C. jejuni and received benzoic acid through the drinking water from day 2 until day 6 post-infection. The results revealed that benzoic acid treatment did not affect C. jejuni colonization in the gastrointestinal tract, but alleviated clinical signs of acute campylobacteriosis, particularly diarrheal and wasting symptoms. In addition, benzoic acid mitigated apoptotic cell responses in the colonic epithelia and led to reduced pro-inflammatory immune reactions in intestinal, extra-intestinal, and systemic compartments tested on day 6 post-infection. Hence, our preclinical placebo-controlled intervention trial revealed that benzoic acid constitutes a promising therapeutic option for treating acute campylobacteriosis in an antibiotic-independent fashion and in consequence, also for reducing the risk of post-infectious autoimmune diseases.

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