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1.
Environ Toxicol ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563506

RESUMO

Excessive exposure to manganese (Mn) through drinking water and food during pregnancy significantly heightens the likelihood of neurodevelopmental damage in offspring. Multiple studies have indicated that melatonin (Mel) may help to relieve neurodevelopmental disorders caused by Mn, but potential mechanisms underlying this effect require further exploration. Here, we utilized primary neural stem cells (NSCs) as a model to elucidate the molecular mechanism underlying the protective function of Mel on Mn-induced cell proliferation dysfunction and cycle arrest. Our results showed that Mn disrupted the cell cycle in NSCs by suppressing positive regulatory proteins (CDK2, Cyclin A, Cyclin D1, and E2F1) and enhancing negative ones (p27KIP1 and p57KIP2), leading to cell proliferation dysfunction. Mel inhibited the Mn-dependent changes to these proteins and the cell cycle through nuclear receptor-related protein 1 (Nurr1), thus alleviating the proliferation dysfunction. Knockdown of Nurr1 using lentivirus-expressed shRNA in NSCs resulted in a diminished protective effect of Mel. We concluded that Mel mitigated Mn-induced proliferation dysfunction and cycle arrest in NSCs through Nurr1.

2.
Bioorg Chem ; 147: 107387, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38643561

RESUMO

Histamine 4 receptor (H4R), the most recently identified subtype of histamine receptor, primarily induces inflammatory reactions upon activation. Several H4R antagonists have been developed for the treatment of inflammatory bowel disease (IBD) and atopic dermatitis (AD), but their use has been limited by adverse side effects, such as a short half-life and toxicity. Natural products, as an important source of anti-inflammatory agents, offer minimal side effects and reduced toxicity. This work aimed to identify novel H4R antagonists from natural products. An H4R target-pathway model deconvoluted downstream Gi and MAPK signaling pathways was established utilizing cellular label-free integrative pharmacology (CLIP), on which 148 natural products were screened. Cryptotanshinone was identified as selective H4R antagonist, with an IC50 value of 11.68 ± 1.30 µM, which was verified with Fluorescence Imaging Plate Reader (FLIPR) and Cellular Thermal Shift (CTS) assays. The kinetic binding profile revealed the noncompetitive antagonistic property of cryptotanshinone. Two allosteric binding sites of H4R were predicted using SiteMap, Fpocket and CavityPlus. Subsequent molecular docking and dynamics simulation indicated that cryptotanshinone interacts with H4R at a pocket formed by the outward interfaces between TM3/4/5, potentially representing a new allosteric binding site for H4R. Overall, this study introduced cryptotanshinone as a novel H4R antagonist, offering promise as a new hit for drug design of H4R antagonist. Additionally, this study provided a novel screening model for the discovery of H4R antagonists.

3.
BMC Pediatr ; 24(1): 222, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561702

RESUMO

BACKGROUND AND OBJECTIVES: To investigate the relationship between body mass index (BMI) and blood biochemical indicators in early adolescence, and to provide ideas for early prevention of diseases and explore possible disease-related predictors. METHODS: 3125 participants aged 10 ∼ 14 years were selected from China from the survey of "China Nutrition and Health Surveillance ( 2016 ∼ 2017 ) ". Employing advanced statistical methods, including generalized linear models, heatmaps, hierarchical clustering, and generalized additive models, the study delved into the associations between BMI and various biochemical indicators. RESULTS: In early adolescence, indicators including systolic pressure, diastolic pressure, weight, height, BMI, hemoglobin, blood uric acid, serum creatinine, albumin, vitamin A presented increasing trends with the increase of age ( P < 0.05 ), whereas LDL-C, vitamin D, and ferritin showed decreasing trends with the increase of age ( P < 0.05 ). The increase in hemoglobin and blood uric acid levels with age was more pronounced in males compared to females ( P < 0.05 ). BMI was positively correlated with blood glucose, hemoglobin, triglyceride, LDL-C, blood uric acid, serum creatinine, ferritin, transferrin receptor, hs-CRP, total protein, vitamin A ( P < 0.05 ). There was a significant BMI × age interaction in the correlation analysis with LDL-C, transferrin receptor, serum creatinine, and hs-CRP ( P < 0.05 ). BMI was a risk factor for hypertension, hypertriglyceridemia, low high density lipoprotein cholesterolemia, and metabolic syndrome in all age groups ( OR > 1, P < 0.05 ). CONCLUSIONS: High BMI was a risk factor for hypertension, hypertriglyceridemia, low high density lipoprotein cholesterolemia, and MetS in early adolescents. With the focus on energy intake beginning in early adolescence, the maintenance of a healthy weight warrants greater attention.


Assuntos
Hipertensão , Hipertrigliceridemia , Masculino , Feminino , Humanos , Adolescente , Índice de Massa Corporal , Proteína C-Reativa/análise , LDL-Colesterol , Ácido Úrico , Creatinina , Vitamina A , Hipertensão/epidemiologia , Lipoproteínas HDL , Hemoglobinas/análise , Ferritinas , Receptores da Transferrina
5.
Heliyon ; 10(7): e29035, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38633658

RESUMO

Traditional apple-picking robots are unable to detect apples in real-time in complex environments. In order to improve detection efficiency, a fast CenterNet apple recognition method for multiple apple targets in dense scenes is proposed. This method can quickly and accurately identify multiple apple targets in dense scenes. The backbone network mainly consists of resnet-44 fully convolutional network, region of interest network (RPN), and region of interest (ROI). The experimental results show that the improved YoloV5 network model has a higher recognition accuracy of 94.1% and 95.8% for apple in the night environment, which improves the recognition accuracy of the occluded features and the features in the dark light, and the model is more robust in the actual data set.

6.
Chem Sci ; 15(15): 5642-5652, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38638228

RESUMO

Passivation treatment is an effective method to suppress various defects in perovskite solar cells (PSCs), such as cation vacancies, under-coordinated Pb2+ or I-, and Pb-I antisite defects. A thorough understanding of the diversified impacts of different defect passivation methods (DPMs) on the device performance will be beneficial for making wise DPM choices. Herein, we choose a hydrophobic Lewis acid tris(pentafluorophenyl)borane (BCF), which can dissolve in both the perovskite precursor and anti-solvent, as the passivation additive. BCF treatment can immobilize organic cations via forming hydrogen bonds. Three kinds of DPMs based on BCF are applied to modify perovskite films in this work. It is found that the best DPM with BCF dissolved in anti-solvent can not only passivate multiple defects in perovskite, but also inhibit δ phase perovskite and improve the stability of devices. Meanwhile, DPM with BCF dissolved in both the perovskite precursor and anti-solvent can cause cracks and voids in perovskite films and deteriorate device performance, which should be avoided in practical applications. As a result, PSCs based on optimal DPMs of BCF present an increased efficiency of 22.86% with negligible hysteresis as well as improved overall stability. This work indicates that the selection and optimization of DPMs have an equally important influence on the photovoltaic performance of PSCs as the selection of passivation additives.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38586878

RESUMO

Muscular fatty infiltration is a common issue after rotator cuff tears (RCT) which impairs shoulder function. Females suffer higher prevalence and more severe degree of muscular fatty infiltration after RCT when compared to males, with the underlying mechanisms remaining unclear. Fibro/adipogenic progenitors (FAPs) are the primary source of muscular fatty infiltration following RCT. Our findings disclose that gender-specific disparities in muscular fatty infiltration are linked to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Furthermore, metformin could enhance mTOR/ULK1 mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Together, our study reveals that gender differences in muscular fatty infiltration arise from distinct autophagic activities. Metformin could be a promising non-invasive intervention to ameliorate muscular fatty infiltration of RCT.

8.
Sci Rep ; 14(1): 7052, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528006

RESUMO

Cobalt is a critical resource in industrial economies for the manufacture of electric-vehicle batteries, alloys, magnets, and catalysts, but has acute supply-chain risks and poses a threat to the environment. Large-scale sequestration of cobalt in low-cost materials under mild conditions opens a path to cobalt recycling, recovery and environmental clean-up. We describe such sequestration of cobalt by a widely available commercial calcium silicate material containing the mineral xonotlite. Xonotlite rapidly and spontaneously takes up 40 percent of its weight of cobalt under ambient conditions of temperature and pressure and reduces dissolved cobalt concentrations to low parts per million. A new Sharp Front experimental design is used to obtain kinetic and chemical information. Sequestration occurs by a coupled dissolution-precipitation replacement mechanism. The cobalt silicate reaction product is largely amorphous but has phyllosilicate features.

9.
Mater Today Bio ; 25: 101017, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38495914

RESUMO

The limited osteointegration often leads to the failure of implant, which can be improved by fixing bioactive molecules onto the surface, such as arginyl-glycyl-aspartic acid (RGD): a cell adhesion motif. Metal-Phenolic Networks (MPNs) have garnered increasing attention from different disciplines in recent years due to their simple and rapid process for depositing on various substrates or particles with different shapes. However, the lack of cellular binding sites on MPNs greatly blocks its application in tissue engineering. In this study, we present a facile and efficient approach for producing PC/Fe@c(RGDfc) composite coatings through the conjugation of c(RGDfc) peptides onto the surface of PC/Fe-MPNs utilizing thiol-click reaction. By combined various techniques (ellipsometry, X-ray photoelectron spectroscopy, Liquid Chromatography-Mass Spectrometry, water contact angle, scanning electronic microscopy, atomic force microscopy) the physicochemical properties (composition, coating mechanism and process, modulus and hydrophilicity) of PC/Fe@c(RGDfc) surface were characterized in detail. In addition, the PC/Fe@c(RGDfc) coating exhibits the remarkable ability to positively modulate cellular attachment, proliferation, migration and promoted bone-implant integration in vivo, maintaining the inherent features of MPNs: anti-inflammatory, anti-oxidative properties, as well as multiple substrate deposition. This work contributes to engineering MPNs-based coatings with bioactive molecules by a facile and efficient thiol-click reaction, as an innovative perspective for future development of surface modification of implant materials.

11.
Virulence ; 15(1): 2333237, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38528779

RESUMO

Infectious bursal disease virus (IBDV) causes immunosuppression and high mortality in young chickens. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are important regulators during viral infection. However, detailed the regulatory mechanisms of lncRNA-miRNA-mRNA have not yet been described in IBDV infection. Here, we analysed the role of lncRNA53557/gga-miR-3530-5p/STAT1 axis in very virulent IBDV (vvIBDV) infection. Evidently upregulated expression of lncRNA53557 was observed in bursa of Fabricius and DT40 cells. Meanwhile, overexpression of lncRNA53557 promoted STAT1 expression and inhibited vvIBDV replication and vice versa, indicating that the upregulation of lncRNA53557 was part of the host antiviral defence. The subcellular fractionation assay confirmed that lncRNA53557 can be localized in the cytoplasm. Further, dual-luciferase reporter, RNA pulldown, FISH and RT-qPCR assays revealed that lncRNA53557 were directly bound to gga-miR-3530-5p and had a negative regulatory relationship between them. Subsequent mechanistic analysis showed that lncRNA53557 acted as a competing endogenous RNA (ceRNA) of gga-miR-3530-5p to relieve the repressive effect of gga-miR-3530-5p on its target STAT1, as well as Mx1, OASL, and ISG15, thereby suppressing vvIBDV replication. The study reveals that a network of enriched lncRNAs and lncRNA-associated ceRNA is involved in the regulation of IBDV infection, offering new insight into the mechanisms underlying IBDV-host interaction.


Assuntos
MicroRNAs , RNA Longo não Codificante , Animais , Galinhas , RNA Longo não Codificante/genética , Linhagem Celular , MicroRNAs/genética , MicroRNAs/metabolismo
12.
J Reprod Immunol ; 163: 104212, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38432052

RESUMO

Interferon-τ (IFN-τ) participates in the establishment of endometrial receptivity in ruminants. However, the precise mechanisms by which IFN-τ establishes bovine endometrial receptivity remain largely unknown. Interferon regulatory factor 1 (IRF1) is a classical interferon-stimulated gene (ISG) induced by type I interferon, including IFN-τ. Leukemia inhibitory factor receptor (LIFR) is a transmembrane receptor for leukemia inhibitory factor (LIF), which is a key factor in regulating embryo implantation in mammals. This study aimed to investigate the roles of IRF1 and LIFR in the regulation of bovine endometrial receptivity by IFN-τ. In vivo, we found IRF1 and LIFR were upregulated in the bovine endometrial luminal epithelium on Day 18 of pregnancy compared to Day 18 of the estrous cycle. In vitro, IFN-τ could upregulate IRF1, LIFR, and endometrial receptivity markers (LIF, HOXA10, ITGAV, and ITGB3) expression, downregulate E-cadherin expression and reduce the quantity of microvilli of bovine endometrial epithelial cells (bEECs). Overexpression of IRF1 had similar effects to IFN-τ on endometrial receptivity, and interference of LIFR could block these effects, suggesting the positive effects of IRF1 on endometrial receptivity were mediated by LIFR. Dual luciferase reporter assay verified that IRF1 could transactivate LIFR transcription by binding to its promoter. In conclusion, IFN-τ can induce IRF1 expression in bovine endometrial epithelial cells, and IRF1 upregulates LIFR expression by binding to LIFR promoter, contributing to the enhancement of bovine endometrial receptivity.

13.
J Ethnopharmacol ; 328: 118068, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38513777

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Prostatitis and benign prostatic hyperplasia (BPH) are inflammations of the prostate gland, which surrounds the urethra in males. Jinqiancao granules are a traditional Chinese medicine used to treat kidney stones and this medicine consists of four herbs: Desmodium styracifolium (Osbeck) Merr., Pyrrosia calvata (Baker) Ching, Plantago asiatica L. and stigma of Zea mays L. AIM OF THE STUDY: We hypothesized that Jinqiancao granules could be a potential therapy for prostatitis and BPH, and this work aimed to elucidate active compounds in Jinqiancao granules and their target mechanisms for the potential treatment of the two diseases. MATERIALS AND METHODS: Jinqiancao granules were commercially available and purchased. Database-driven data mining and networking were utilized to establish a general correlation between Jinqiancao granules and the two diseases above. Ultra-performance liquid chromatography-mass spectrometry was used for compound separation and characterization. The characterized compounds were evaluated on four G-protein coupled receptors (GPCRs: GPR35, muscarinic acetylcholine receptor M3, alpha-1A adrenergic receptor α1A and cannabinoid receptor CB2). A dynamic mass redistribution technique was applied to evaluate compounds on four GPCRs. Nitric acid (NO) inhibition was tested on the macrophage cell line RAW264.7. Molecular docking was conducted on GPR35-active compounds and GPR35 crystal structure. Statistical analysis using GEO datasets was conducted. RESULTS: Seventy compounds were isolated and twelve showed GPCR activity. Three compounds showed potent GPR35 agonistic activity (EC50 < 10 µM) and the GPR35 agonism action of PAL-21 (Scutellarein) was reported for the first time. Docking results revealed that the GPR35-targeting compounds interacted at the key residues for the agonist-initiated activation of GPR35. Five compounds showed weak antagonistic activity on M3, which was confirmed to be a disease target by statistical analysis. Seventeen compounds showed NO inhibitory activity. Several compounds showed multi-target properties. An experiment-based network reflected a pharmacological relationship between Jinqiancao granules and the two diseases. CONCLUSIONS: This study identified active compounds in Jinqiancao granules that have synergistic mechanisms, contributing to anti-inflammatory effects. The findings provide scientific evidence for the potential use of Jinqiancao granules as a treatment for prostatitis and BPH.


Assuntos
Hiperplasia Prostática , Prostatite , Masculino , Humanos , Prostatite/tratamento farmacológico , Prostatite/metabolismo , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Simulação de Acoplamento Molecular , Próstata , Receptores Acoplados a Proteínas G/metabolismo
14.
J Stroke Cerebrovasc Dis ; 33(6): 107687, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38521147

RESUMO

OBJECTIVE: Recent research indicates that autophagy is essential for the rupture of intracranial aneurysm (IA). This study aimed to examine and validate potential autophagy-related genes (ARGs) in cases of IA using bioinformatics analysis. METHODS: Two expression profiles (GSE54083 and GSE75436) were obtained from the Gene Expression Omnibus database. Differentially expressed ARGs (DEARGs) in cases of IA were screened using GSE75436, and enrichment analysis and Protein-Protein Interaction (PPI) networks were used to identify the hub genes and related pathways. Furthermore, a novel predictive diagnostic signature for IA based on the hub genes was constructed. The area under the Receiver Operating Characteristic curve (AUC) was used to evaluate the signature performance in GSE75436. RESULTS: In total, 75 co-expressed DEARGs were identified in the GSE75436 and GSE54083 dataset (28 upregulated and 47 downregulated genes). Enrichment analysis of DEARGs revealed several enriched terms associated with proteoglycans in cancer and human immunodeficiency virus 1 infection. PPI analysis revealed interactions between these genes. Hub DEARGs included insulin-like growth factor 1, clusters of differentiation 4, cysteine-aspartic acid protease 8, Bcl-2-like protein 11, mouse double mutant 2 homolog, toll-like receptor 4, growth factor receptor-bound protein 2, Jun proto-oncogene, AP-1 transcription factor subunit, hypoxia inducible factor 1 alpha, and erythroblastic oncogene B-2. Notably, the signature showed good performance in distinguishing IA (AUC = 0.87). The sig calibration curves showed good calibration. CONCLUSION: Bioinformatic analysis identified 75 potential DEARGs in cases of IA. This study revealed that IA is affected by autophagy, which could explain the pathogenesis of IA and aid in its diagnosis and treatment. However, future research with experimental validation is necessary to identify potential DEARGs in cases of IA.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124181, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38527410

RESUMO

Distinct diagnosis between Lung cancer (LC) and gastric cancer (GC) according to the same biomarkers (e.g. aldehydes) in exhaled breath based on surface-enhanced Raman spectroscopy (SERS) remains a challenge in current studies. Here, an accurate diagnosis of LC and GC is demonstrated, using artificial intelligence technologies (AI) based on SERS spectrum of exhaled breath in plasmonic metal organic frameworks nanoparticle (PMN) film. In the PMN film with optimal structure parameters, 1780 SERS spectra are collected, in which 940 spectra come from healthy people (n = 49), another 440 come from LC patients (n = 22) and the rest 400 come from GC patients (n = 8). The SERS spectra are trained through artificial neural network (ANN) model with the deep learning (DL) algorithm, and the result exhibits a good identification accuracy of LC and GC with an accuracy over 89 %. Furthermore, combined with information of SERS peaks, the data mining in ANN model is successfully employed to explore the subtle compositional difference in exhaled breath from healthy people (H) and L/GC patients. This work achieves excellent noninvasive diagnosis of multiple cancer diseases in breath analysis and provides a new avenue to explore the feature of disease based on SERS spectrum.


Assuntos
Neoplasias Pulmonares , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Inteligência Artificial , Neoplasias Pulmonares/diagnóstico , Análise Espectral Raman , Testes Respiratórios/métodos , Pulmão
16.
BMC Oral Health ; 24(1): 375, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519926

RESUMO

BACKGROUND: While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear. METHODS: This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk. RESULTS: MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167-1.721, p < 0.001) and the risk of OCC. Furthermore, two inflammatory cytokines significantly influenced by OLP, IL-13 (OR = 1.088, 95% CI: 1.007-1.175, P = 0.032) and IL-9 (OR = 1.085, 95% CI: 1.005-1.171, P = 0.037), were identified. Subsequent analysis revealed a significant causal association only between IL-13 (OR = 1.408, 95% CI: 1.147-1.727, P = 0.001) and higher OCC risk, establishing it as a potential mediator. Further, MVMR analysis indicated that IL-13 (OR = 1.437, 95% CI = 1.139-1.815, P = 0.002) mediated the relationship between OLP and OCC, accounting for 8.13% of the mediation. CONCLUSION: This study not only elucidates the potential causal relationship between OLP and the risk of OCC but also highlights the pivotal mediating role of IL-13 in this association.


Assuntos
Líquen Plano Bucal , Neoplasias Bucais , Humanos , Citocinas , Interleucina-13/genética , Líquen Plano Bucal/genética , Análise da Randomização Mendeliana , Neoplasias Bucais/genética , Estudo de Associação Genômica Ampla
17.
J Trace Elem Med Biol ; 84: 127438, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38520795

RESUMO

BACKGROUND: Occupation, environmental heavy metal exposure, and renal function impairment are closely related. The relationship between mixed metal exposure and chronic renal injury is inadequately described, and the interaction between each metal is poorly explored. OBJECTIVE: This cross-sectional study assessed mixed heavy metal exposure in the general population and their relationship with early renal impairment, as well as possible interactions between metals. METHODS: The study was conducted in two communities in Taiyuan City in northern China. Multiple linear regression, weighted quantile sum (WQS) and bayesian kernel machine regression (BKMR) regression were used to explore the relationship of mixed heavy metal exposure with indicators of early kidney injury (N-acetyl-ß-D- glucosidase (UNAG), urinary albumin (UALB)). Meanwhile, BKMR was used to explore the possible interactions between mixed heavy metal and indicators of early kidney injury. RESULTS: Based on the WQS regression results, we observed adjusted WQS coefficient ß (ß-WQS) of 0.711 (95% CI: 0.543, 0.879). Notably, this change was primarily driven by As (35.6%) and Cd (22.5%). In the UALB model, the adjusted ß-WQS was 0.657 (95% CI: 0.567, 0.747), with Ni (30.5%), Mn (22.1%), Cd (21.2%), and As (18.6%) exhibiting higher weights in the overall effect. The BKMR results showed a negative interaction between As and other metals in the UNAG and UALB models, a positive interaction between Mn and Ni and other metals. No significant pairwise interaction was observed in the association of metals with indicators of early kidney injury. CONCLUSION: Through multiple linear regression, WQS regression, and BKMR analyses, we found that exposure to mixed heavy metals such as Cd, Cr, Pb, Mn, As, Co and Ni was positively correlated with UNAG and UALB. Moreover, there are complex interactions between two or more heavy metals in more than one direction.

18.
Bioorg Chem ; 145: 107252, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437763

RESUMO

Isoquinoline alkaloids are an important class of natural products that are abundant in the plant kingdom and exhibit a wide range of structural diversity and biological activities. With the deepening of research in recent years, more and more isoquinoline alkaloids have been isolated and identified and proved to contain a variety of biological activities and pharmacological effects. In this review, we introduce the research progress of isoquinoline alkaloids from 2019 to 2022, mainly in the part of biological activities, including antitumor, antimicrobial, antidiabetic, antiviral, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, analgesic, and other activities. This study provides a clear direction for the rational development and utilization of isoquinoline alkaloids, suggesting that these alkaloids have great potential in the field of drug research.


Assuntos
Alcaloides , Anti-Infecciosos , Alcaloides/química , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Isoquinolinas/farmacologia , Isoquinolinas/química
19.
Appl Microbiol Biotechnol ; 108(1): 248, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430229

RESUMO

Porcine epidemic diarrhea (PED) caused by porcine epidemic diarrhea virus (PEDV), is an acute and highly infectious disease, resulting in substantial economic losses in the pig industry. Given that PEDV primarily infects the mucosal surfaces of the intestinal tract, it is crucial to improve the mucosal immunity to prevent viral invasion. Lactic acid bacteria (LAB) oral vaccines offer unique advantages and potential applications in combatting mucosal infectious diseases, making them an ideal approach for controlling PED outbreaks. However, traditional LAB oral vaccines use plasmids for exogenous protein expression and antibiotic genes as selection markers. Antibiotic genes can be diffused through transposition, transfer, or homologous recombination, resulting in the generation of drug-resistant strains. To overcome these issues, genome-editing technology has been developed to achieve gene expression in LAB genomes. In this study, we used the CRISPR-NCas9 system to integrate the PEDV S1 gene into the genome of alanine racemase-deficient Lactobacillus paracasei △Alr HLJ-27 (L. paracasei △Alr HLJ-27) at the thymidylate synthase (thyA) site, generating a strain, S1/△Alr HLJ-27. We conducted immunization assays in mice and piglets to evaluate the level of immune response and evaluated its protective effect against PEDV through challenge tests in piglets. Oral administration of the strain S1/△Alr HLJ-27 in mice and piglets elicited mucosal, humoral, and cellular immune responses. The strain also exhibited a certain level of resistance against PEDV infection in piglets. These results demonstrate the potential of S1/△Alr HLJ-27 as an oral vaccine candidate for PEDV control. KEY POINTS: • A strain S1/△Alr HLJ-27 was constructed as the candidate for an oral vaccine. • Immunogenicity response and challenge test was carried out to analyze the ability of the strain. • The strain S1/△Alr HLJ-27 could provide protection for piglets to a certain extent.


Assuntos
Vírus da Diarreia Epidêmica Suína , Vacinas Virais , Animais , Suínos , Camundongos , Anticorpos Antivirais , Vírus da Diarreia Epidêmica Suína/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Antibacterianos
20.
ACS Appl Mater Interfaces ; 16(10): 13316-13325, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38427779

RESUMO

The application of rechargeable lithium metal batteries is challenged by intractable issues of uncontrollable Li dendrite growth that result in poor cycle life and safety risks. In this work, an air-stable interphase is developed to protect the lithium metal anode (LMA) via a facile solution-based approach. The Ag-embedded fluoride-rich interphase not only creates abundant lithiophilic sites for homogenizing Li nucleation and growth but also resists severe air erosion to protect the LMA beneath and enable decent cycling stability. As a result, the Ag-F-rich interphase enables flat Li deposition on LMA, which is clearly observed in the operando Li plating experiments. Paired with a LiFePO4 cathode (11.8 mg cm-2), the Ag-F-rich interphase-modified LMA enables 300 stable cycles at 0.5 C, delivering a capacity retention ratio as high as 91.4%. Even after being exposed to air for 1 h, the modified LMA still runs smoothly for over 120 cycles with ignorable capacity decay, exhibiting great air stability. This work proves the concept of functionalizing the interphase on the LMA to enable good cycling performance even under severe air erosion.

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