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BACKGROUND: Pea protein isolate (PPI) is gaining increasing popularity in the food industry. It provides a diverse range of health benefits, such as hypoallergenic and gluten-free characteristics. However, the functional performance of PPI is hindered by its low solubility and poor stability. Therefore, in this article, PPI and dextran (DX) of different molecular weights were grafted to investigate the effects of grafting DX with different molecular weights on the interface properties and antioxidant properties of PPI. Additionally, the stability and digestive properties of the glycated PPI nanoemulsion system were explored. RESULTS: The result showed that the grafting degree of PPI-DX conjugates (PPI-DC) decreased with an increase in the molecular weight of DX. Surface hydrophobicity, antioxidant activity and solubility of PPI-DC were significantly improved after grafting compared with PPI and PPI-DX mixtures (PPI-DM). Astaxanthin-loaded emulsions stabilized by grafted conjugates had smaller droplets and higher astaxanthin encapsulation rate compared to PPI emulsions. In vitro digestion demonstrated that the bioavailability of PPI-DC emulsions was higher than of PPI emulsion. Furthermore, after 24 days of storage, retention rate of astaxanthin-loaded emulsions prepared by conjugates remained above 70%, surpassing that of PPI emulsion. CONCLUSION: These results indicated that DX grafting can improve the emulsion properties of PPI. In addition, the DX with a molecular weight of 5 kDa showed the most significant improvement. This study contributes to the advancement of natural emulsifiers by modifying PPI through glycation, and furnishes a valuable reference for its utilization in functional foods. © 2024 Society of Chemical Industry.
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Oxygen production within human cells plays a critical role in cellular metabolism and is implicated in various diseases, including cancer. Investigating cellular heterogeneity under oxygen stimulation is crucial for elucidating disease mechanisms and advancing early therapeutic design. In this study, the platinum-based wireless nanopore electrode (WNE) with a diameter of ≈200 nm is employed as a powerful tool to produce oxygen molecules near the cell nucleus. The oxygen production can be quantitatively controlled by adjusting the applied voltage. Through delivering oxygen near the cancer cell nucleus, this technique shows the capacity to alleviate the hypoxia microenvironment, a key factor in chemotherapy resistance. Furthermore, by modulating oxygen levels within individual living cells and delivering chemotherapeutic agents to the cancer cell nucleus, this approach offers significant potential for single-cell manipulation and the investigation of cellular heterogeneity under oxygen stimulation.
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The emergence of multidrug-resistant bacterial have caused severe burden for public health. Particularly, Staphylococcus aureus as one of ESKAPE pathogens have induced various infectious diseases and resulted in increasing deaths. Developing new antibacterial agents is still urgent and challenging. Fortunately, in this study, based on aggregation-induced emission (AIE) ruthenium complexes were designed and synthesized, which realized the high efficiency of reactive oxygen species generation and remarkably killed S. aureus unlike conventional antibiotics action. Significantly, owing to good singlet oxygen production ability, Ru1 at only 4 µg/mL of concentration displayed good antibacterial photodynamic therapy effect upon white light irradiation and could deplete essential coenzyme NADH to disrupt intracellular redox balance. Also, the electrostatic interaction between Ru1 and bacteria enhanced the possibility of antibacterial. Under light irradiation, Ru1 could efficiently inhibit the biofilm growth and avoid the development of drug-resistant. Furthermore, Ru1 possessed excellent biocompatibility and displayed remarkable therapy effect in treating mice-wound infections in vivo. These findings indicated that AIE-based ruthenium complexes as new antibacterial agent had great potential in photodynamic therapy of bacteria and addressing the drug-resistance crisis.
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Soil salinity poses a major threat to crop growth, microbial activity, and organic matter accumulation in agroecosystems in arid and semiarid regions. The limitations of carbon (C) accrual due to salinity can be partly mitigated by the application of organic fertilizers. Although microorganisms are crucial for soil organic carbon (SOC) stabilization, the relationships between living and dead microbial C pools and the community features of SOC accrual in saline soils are not known. A two-year field experiment was conducted to examine the effects of organic fertilizers on the microbial regulatory mechanisms of C sequestration in saline soil (chloride-sulfate salinity). Compared to manure addition alone, manure plus commercial humic acid increased SOC stock by 11% and decreased CO2 emissions by 10%, consequently facilitated soil C sequestration. We explain these results by greater bacterial necromass formation due to the dominance of r-strategists with faster turnover rate (growth and death), as well as larger necromass stability as supported by the increased aggregate stability under the addition of humic acids with manure. Humic acids increased the abundance of bacterial phylum Proteobacteria (copiotrophs) and decreased Acidobacteria (oligotrophs) compared with straw, indicating that r-strategists outcompeted K-strategists, leading to bacterial necromass accumulation. With larger C/N ratio (88), straw increased leucine aminopeptidase to mine N-rich substrates (i.e., from necromass and soil organic matter) and consequently reduced SOC stock by 8%. The decreased salinity and increased organic C availability under straw with manure addition also led to a 13% higher CO2 flux compared with manure application alone. Thus, humic acids added with manure benefited to SOC accumulation by raising bacterial necromass C and reducing CO2 emissions.
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An exploration of antibacterial components from the whole plant of Euphorbia humifusa led to the isolation of 14 new triterpenoids, euphohumifusoids A-N (1-7 and 9-15), as well as four known analogues (8 and 16-18). Their structures were elucidated by extensively analysis of the spectroscopic data and X-ray crystallography using Cu Kα radiation. Among them, euphohumifusoid A (1) bears an unique 6(7 â 8)abeo scaffold originated from a D:C-friedo-oleanane skeleton for the first time, euphohumifusoids H and I (9 and 10) possess a rare α,ß-unsaturated-γ-lactone chain originated from 25,26,27-trinordammaranes, and euphohumifusoid L (13) is a highly modified 3,4-seco-25,26,27-trinorcycloartane. Notably, in antibacterial bioassay, compound 1 displayed excellent antibacterial activities against Bacillus cereus, Staphylococcus aureus, and S.epidermidis with MIC of 12.5, 25, and 25 µg/mL, comparable to the positive controls. Upon exposure to 1 and 2 MIC of 1, B.cereus underwent drastic morphological changes, resulting in complete disruption of the cells. Meanwhile, compound 1 also exhibited remarkable antibiofilm activity against B.cereus at 1 MIC and 2 MIC.
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KEY MESSAGE: Parental combinations determined by genomic estimated usefulness and parental contributions of the lines in bridging population can enhance the genetic gain of traits of interest in maternal haploid inducer breeding. Parent selection in crosses aligns well with the quantitative trait performance in the progenies. We herein take advantage of estimated genetic values (EGV) and usefulness criteria (UC) of bi-parental combinations by genomic prediction (GP) to compare the empirical performance of doubled haploid inducer (DHI) progenies of eight elite inducers crosses in a half-diallel. We used parental contribution and discovery of superiors from elite-by-historical bridging populations to enhance genetic gain for long-term selection. In this empirical study, the narrow-sense heritabilities of four traits of interest (Days to flowering, DTF; haploid induction rate, HIR; plant height, PHT; Total primary branch length, PBL) in DHI population were 0.81, 0.71, 0.45 and 0.46, respectively. The genomic estimated EGV_Mid/Mean and EGV/UC_Inferior was significantly correlated with the sample mean of progenies and inferiors in four traits in the breeding and bridging population. EGV/UC_Superior were significantly correlated with the mean of superiors in DTF, PHT, and PBL in breeding and bridging populations. The genomic estimated parent contributions in DH progenies of bridging populations enabled discovery of favorable genome region from historical inducers to improve the genetic gain of HIR for long-term selection.
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Haploidia , Melhoramento Vegetal , Seleção Genética , Zea mays , Zea mays/genética , Fenótipo , Cruzamentos Genéticos , Genoma de Planta , Genômica/métodos , Genótipo , Modelos GenéticosRESUMO
BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS: Using resources from colorectal cancer consortia including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score including 141 variants associated with CRC risk. RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking [RERI = 0.24, 95% confidence interval, CI, (0.13, 0.36)], ever smoking [0.11 (0.05, 0.16)], high BMI [female 0.09 (0.05, 0.13), male 0.10 (0.05, 0.14)], or high red meat intake [highest versus lowest quartile 0.18 (0.09, 0.27)] was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/NSAID use [-0.16 (-0.20, -0.11)] or higher intake of fruit, fiber, or calcium [highest quartile versus lowest quartile -0.12 (-0.18, -0.050); -0.16 (-0.23, -0.09); -0.11 (-0.18, -0.05), respectively] than those with average genetic susceptibility. CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.
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Retinal degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), initially manifest as dysfunction or death of the retinal pigment epithelium (RPE). Subretinal transplantation of human pluripotent stem cell (hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration. However, RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials. The development of hPSC-derived RPE cell differentiation protocols using xeno-free biomaterials is urgently needed for clinical applications. In this study, two protocols (the activin A and NIC84 protocols) were selected for modification and use in the differentiation of hiPSCs into RPE cells; the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells. The xeno-free extracellular matrix (ECM) proteins, laminin-511, laminin-521 and recombinant vitronectin, were selected as plate-coating substrates, and a Matrigel (xeno-containing ECM)-coated surface was used as a positive control. Healthy, mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons (RCS) rats, a model of retinal degeneration disease. The visual function of RCS rats was evaluated by optomotor response (qOMR) and electroretinography after transplantation of hPSC-derived RPE cells. Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 protocol, and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats.
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Ag modified ZnO nanoflowers were successfully prepared by sunlight induced solvent reduction method. The samples were characterized by x-ray diffractometer, field emission scanning electron microscope, transmission electron microscope and energy dispersive x-ray spectrum, and the results confirmed the presence of Ag nanoparticles on the ZnO nanoflower. The gas sensing performance of the materials was studied at different operating temperatures and different n-butanol concentrations. The results showed that the Ag modified ZnO nanoflower sensor responded to 50 ppm n-butanol up to 147.17 at 280 °C, and the Ag modified ZnO nanoflower sensor exhibited excellent repeatability, stability and response recovery time. In addition, different target gases were employed for the selectivity study of the Ag modified ZnO nanoflower. It can be found that the Ag modified ZnO nanoflower had good selectivity for n-butanol. The improved response of the Ag modified ZnO nanoflower sensor was attributed to the catalytic effect of Ag nanoparticles. The results indicate that the Ag modified ZnO nanoflower will become a very promising sensing material for n-butanol gas detection.
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Age-related hearing loss (ARHL) is a disease that impacts human quality of life and contributes to the progression of other neuronal problems. Various stressors induce an increase in free radicals, destroy mitochondria to further contribute to cellular malfunction, and compromise cell viability, ultimately leading to functional decline. Cisd2, a master gene for Marfan syndrome, plays an essential role in maintaining mitochondrial integrity and functions. As shown by our data, specific deletion of Cisd2 in the cochlea exacerbated the hearing impairment of ARHL in C57BL/6 mice. Increased defects in mitochondrial function, potassium homeostasis and synapse activity were observed in the Cisd2-deleted mouse models. These mechanistic phenotypes combined with oxidative stress contribute to cell death in the whole cochlea. Human patients with obviously deteriorated ARHL had low Cisd2 expression; therefore, Cisd2 may be a potential target for designing therapeutic methods to attenuate the disease progression of ARHL.
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Rosmarinic acid (RA) has demonstrated anticancer effects on several types of malignancies. However, whether RA promotes the anticancer effect of cisplatin on colorectal cancer cells remains sketchy. This study aimed to explore whether RA potentiates the cytotoxicity of cisplatin against colon cancer cells and the underlying mechanism. Cell viability, cell cycle progression, and apoptosis was evaluated using sulforhodamine B (SRB) assay, flow cytometric analysis, and propidium iodide/Annexin V staining, respectively. Western blotting was utilized to analyze signaling pathways. Our findings showed that RA significantly enhanced the inhibitory effect on cell viability and the induction of apoptosis on the colon cancer cell lines DLD-1 and LoVo. Signaling cascade analysis revealed that the combination of RA and cisplatin jointly induced Bax and caspase activation while downregulating Bcl-2, glutathione peroxidase 4 (GPX4), and SLC7A11 in DLD-1 cells. Moreover, caspase inhibitor and ferroptosis inhibitor significantly reversed the inhibition of cell viability in response to RA combined with cisplatin. Collectively, these findings demonstrate that RA enhances the cytotoxicity of cisplatin against colon cancer cells, attributing to the promotion of apoptosis and ferroptosis.
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Quaternization of ruthenium complexes may be a promising strategy for the development of new antibiotics. In response to the increasing bacterial resistance, we integrated the quaternary amine structure into the design of ruthenium complexes and evaluated their antibacterial activity. All the ruthenium complexes showed good antibacterial activity against the tested Staphylococcus aureus (S. aureus). Ru-8 was the most effective antibacterial agent that displayed excellent antibacterial activity against S. aureus (MIC = 0.78-1.56 µg/mL). In vitro experiments showed that all nine ruthenium complexes had low hemolytic toxicity to rabbit erythrocytes. Notably, Ru-8 was found to disrupt bacterial cell membranes, alter their permeability, and induce ROS production in bacteria, all the above leading to the death of bacteria without inducing drug resistance. To further explore the antibacterial activity of Ru-8in vivo, we established a mouse skin wound infection model and a G. mellonella larvae infection model. Ru-8 exhibited significant antibacterial efficacy against S. aureus in vivo and low toxicity to mouse tissues. The Ru-8 showed low toxicity to Raw264.7 cells (mouse monocyte macrophage leukemia cells). This study indicates that the ruthenium complex ruthenium quaternary was a promising strategy for the development of new antibacterial agents.
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Antibacterianos , Complexos de Coordenação , Testes de Sensibilidade Microbiana , Piridinas , Rutênio , Staphylococcus aureus , Tiazóis , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Animais , Camundongos , Rutênio/química , Rutênio/farmacologia , Piridinas/química , Piridinas/farmacologia , Piridinas/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Coelhos , Relação Estrutura-Atividade , Tiazóis/química , Tiazóis/farmacologia , Tiazóis/síntese química , Estrutura Molecular , Células RAW 264.7 , Descoberta de Drogas , Relação Dose-Resposta a Droga , Infecções Estafilocócicas/tratamento farmacológico , Hemólise/efeitos dos fármacosRESUMO
Plantago asiatica seeds (PS) are commonly used as a medicinal plant. This study investigates the efficacy of PS against heavy metal toxicity in white shrimp (Penaeus vannamei). After feeding PS diet (5 g/kg) or basal diet (control group) for 7 days, shrimps were exposed to sublethal concentrations of heavy metals in seawater (As: 12 mg/L, Pb: 250 mg/L, Hg: 0.4 mg/L). The 7-day survival observation showed that the survival in groups fed with PS were significantly higher than that in the control group, revealing that dietary PS had the efficacy to mitigate heavy metal toxicity in white shrimp. Under the same feeding condition, white shrimps were exposed to safety dose of heavy metals (1/10 of sublethal concentrations) to understand the mechanism of mitigation. The metal accumulations in haemolymph, gills, hepatopancreas, and muscle tissues as well as the immune, anti-oxidative, stress related gene expressions in haemocytes, gills and hepatopancreas were measured for 14 days. The As accumulation in gills and hepatopancreas of groups fed with PS were significantly lower than those of control group on day 7 and 14, respectively; The Pb concentration in haemolymph of group fed with PS was significantly lower than that of control group on day 7 and 14; The Hg concentration in hepatopancreas of the group fed with PS was significantly lower than that of control group on day 7. Dietary PS could mitigate heavy metal-induced immune suppression, oxidative stress, and stress response by positively regulating immune (proPO I, Toll, IMD), antioxidant (SOD, GST, Trx), and negatively regulating stress response genes (HSP70, MT). The present study demonstrated that dietary PS could protect white shrimp against metal toxicity by reducing metal accumulations and regulating the immune, antioxidant, and stress response gene expressions in specific tissue. Therefore, PS may serve as a beneficial feed additive in the aquaculture.
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Ração Animal , Dieta , Penaeidae , Plantago , Sementes , Poluentes Químicos da Água , Animais , Penaeidae/imunologia , Penaeidae/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Sementes/química , Ração Animal/análise , Dieta/veterinária , Plantago/química , Metais Pesados/toxicidade , Suplementos Nutricionais/análise , Substâncias Protetoras/farmacologia , Substâncias Protetoras/administração & dosagem , Arsênio/toxicidade , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Brânquias/imunologiaRESUMO
Importance: Information on long-term benefits and harms of screening with digital breast tomosynthesis (DBT) with or without supplemental breast magnetic resonance imaging (MRI) is needed for clinical and policy discussions, particularly for patients with dense breasts. Objective: To project long-term population-based outcomes for breast cancer mammography screening strategies (DBT or digital mammography) with or without supplemental MRI by breast density. Design, Setting, and Participants: Collaborative modeling using 3 Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer simulation models informed by US Breast Cancer Surveillance Consortium data. Simulated women born in 1980 with average breast cancer risk were included. Modeling analyses were conducted from January 2020 to December 2023. Intervention: Annual or biennial mammography screening with or without supplemental MRI by breast density starting at ages 40, 45, or 50 years through age 74 years. Main outcomes and Measures: Lifetime breast cancer deaths averted, false-positive recall and false-positive biopsy recommendations per 1000 simulated women followed-up from age 40 years to death summarized as means and ranges across models. Results: Biennial DBT screening for all simulated women started at age 50 vs 40 years averted 7.4 vs 8.5 breast cancer deaths, respectively, and led to 884 vs 1392 false-positive recalls and 151 vs 221 false-positive biopsy recommendations, respectively. Biennial digital mammography had similar deaths averted and slightly more false-positive test results than DBT screening. Adding MRI for women with extremely dense breasts to biennial DBT screening for women aged 50 to 74 years increased deaths averted (7.6 vs 7.4), false-positive recalls (919 vs 884), and false-positive biopsy recommendations (180 vs 151). Extending supplemental MRI to women with heterogeneously or extremely dense breasts further increased deaths averted (8.0 vs 7.4), false-positive recalls (1088 vs 884), and false-positive biopsy recommendations (343 vs 151). The same strategy for women aged 40 to 74 years averted 9.5 deaths but led to 1850 false-positive recalls and 628 false-positive biopsy recommendations. Annual screening modestly increased estimated deaths averted but markedly increased estimated false-positive results. Conclusions and relevance: In this model-based comparative effectiveness analysis, supplemental MRI for women with dense breasts added to DBT screening led to greater benefits and increased harms. The balance of this trade-off for supplemental MRI use was more favorable when MRI was targeted to women with extremely dense breasts who comprise approximately 10% of the population.
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Densidade da Mama , Neoplasias da Mama , Detecção Precoce de Câncer , Imageamento por Ressonância Magnética , Mamografia , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Imageamento por Ressonância Magnética/métodos , Idoso , Adulto , Mama/diagnóstico por imagem , Mama/patologia , Estados Unidos/epidemiologia , Programas de Rastreamento/métodosRESUMO
OBJECTIVES: This work aimed to evaluate the effect of music-based intervention (MBI) on anxiety and stress-related vital signs (heart rate, respiratory rate and blood pressure) in patients undergoing cardiac catheterization. DESIGN: A systematic review and meta-analysis. METHODS: This systematic review and meta-analysis was conducted according to PRISMA guidelines. PubMed, Cochrane Library, Embase and CINAHL were systematically searched from inception to October 31, 2023. Two authors independently searched electronic databases, selected literature, extracted data and assessed the risk of bias according to the eligibility criteria. The Review Manager software (RevMan version 5.4.1) was used to perform meta-analysis. RESULTS: Eleven randomized controlled trials (RCTs) with adult patients (n = 1204) (passive music therapy, 8 studies; passive music listening, 3 studies) were enrolled and brought into qualitative assessment. Nine of these RCTs (n = 868) were taken into quantitative analysis. Meta-analysis using the random-effects model revealed that the difference in the pre-post anxiety level in the music group was significantly greater than that in the control group. However, meta-analysis results for heart rate, respiratory rate, systolic blood pressure and diastolic blood pressure did not show significant differences. CONCLUSION: The findings suggested that MBI had a significant effect on reducing anxiety in patients undergoing cardiac catheterization. However, the limited quantity and quality of included studies highlight the need for additional research to comprehensively analyze the influence of MBI on anxiety reduction in this patient population.
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Ansiedade , Cateterismo Cardíaco , Musicoterapia , Estresse Psicológico , Humanos , Ansiedade/terapia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Musicoterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa Respiratória/fisiologia , Estresse Psicológico/terapia , Sinais Vitais/fisiologiaRESUMO
BACKGROUND: Sanqi, the root of Panax notoginseng, has long been recognized for its therapeutic effects on cardiovascular diseases. Saponins, including ginsenosides and notoginsenosides, are the main bioactive components of P. notoginseng. The biosynthesis of saponins is closely related to the defense responses orchestrated by endogenous hormones. RESULTS: To provide new insights into the underlying role of phytohormone jasmonic acid (JA) in the synthesis and regulation of saponins, we performed an ultra-performance liquid chromatography analysis of different tissues of P. notoginseng aged 2-4 years. Moreover, by combined evaluation of saponin content and transcriptome profiling of each tissue, the spatial and temporal distribution of saponins was analyzed. N notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rd accumulated in the underground tissues, including the root, tuqi, fibril and rhizome. In agreement with this data, the corresponding genes of the endogenous hormone JAs, especially coronatine insensitive 1 (COI1) and myelocytomatosis proteins 2 (MYC2), were predominantly expressed in the underground tissues. The tissue- and age-specific distribution of saponins was consistent with the expression of genes involved in JA biosynthetic, metabolic and signaling pathways. CONCLUSION: The present study has revealed the temporal and spatial effects of endogenous phtohormones in the synthesis and regulation of notoginsenosides, which will provide a significant impact on improving the ecological planting technology, cultivating new high-quality varieties and protecting the rare resources of medicinal P. notoginseng. © 2024 Society of Chemical Industry.
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Understanding single-molecule multivalent ligand-receptor interactions is crucial for comprehending molecular recognition at biological interfaces. However, label-free identifications of these transient interactions during multistep binding processes remains challenging. Herein, we introduce a ligand-receptor-anchored nanopore that allows the protein to maintain structural flexibility and favorable orientations in native states, mapping dynamic multivalent interactions. Using a four-state Markov chain model, we clarify two concentration-dependent binding pathways for the Omicron spike protein (Omicron S) and soluble angiotensin-converting enzyme 2 (sACE2): sequential and concurrent. Real-time kinetic analysis at the single-monomeric subunit level reveals that three S1 monomers of Omicron S exhibit a consistent and robust binding affinity toward sACE2 (-13.1 ± 0.2 kcal/mol). These results highlight the enhanced infectivity of Omicron S compared to other homologous spike proteins (WT S and Delta S). Notably, the preceding binding of sACE2 to Omicron S facilitates the subsequent binding steps, which was previously obscured in bulk measurements. Our single-molecule studies resolve the controversy over the disparity between the measured spike protein binding affinity with sACE2 and the viral infectivity, offering valuable insights for drug design and therapies.
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PURPOSE: To investigate the protective effect of intravesical glucosamine in treating overactive bladder (OAB). METHODS: Ninety-two female Sprague-Dawley (SD) rats were divided into 4 groups i.e. protamine sulfate (PS), N-acetylcysteine (NAC), and glucosamine-treated PS (GPS), and normal saline control (NC) were used. We induced hyperactivity in rats via intravesical infusion of PS and potassium chloride (KCl), whereas the NC group underwent a sustained intravesical saline infusion for 1 h. N-acetylcysteine (NAC), a potential antioxidant as well as anti-inflammatory agent was employed as positive control. Cystometrography (CMG) was then conducted to determine urodynamic parameters, i.e., leak point pressure (LPP, n = 48) and inter-contractile interval, the duration between two voids (ICI, n = 32). RESULTS: LPP was significantly elevated in the GPS group (mean ± SD: 110.9 ± 6.2 mmHg) compared to the NC (81.0 ± 32.5 mmHg), PS (40.3 ± 10.9 mmHg), and NAC group (70.3 ± 19.4 mmHg). The cystometrogram data also reveals a prolonged ICI in the GPS group (241.3 ± 40.2 s) compared to the NC group (216.0 ± 41.7 s), PS group (128.8 ± 23.6 s), and NAC group (193.8 ± 28.3 s). CONCLUSION: This preliminary study implies the ameliorative impact of GPS treatment on OAB in terms of improved urodynamic parameters, including LPP and ICI.
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Modelos Animais de Doenças , Glucosamina , Cloreto de Potássio , Protaminas , Ratos Sprague-Dawley , Bexiga Urinária Hiperativa , Animais , Bexiga Urinária Hiperativa/tratamento farmacológico , Feminino , Ratos , Administração Intravesical , Glucosamina/farmacologia , Glucosamina/uso terapêutico , Glucosamina/administração & dosagemRESUMO
Nurses need to be competent in clinical nursing knowledge and skills via engagement in continuing education. The knowledge of nurses should be updated especially in caring for diabetes disease. The potential for immersive experience provision by 360-degree video. This study aims to design an immersive interactive learning experience based on 360° immersive videos and pilot testing on nursing students receiving diabetes education.
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Diabetes Mellitus , Autoeficácia , Estudantes de Enfermagem , Realidade Virtual , Humanos , Competência Clínica , Instrução por Computador/métodos , Conhecimentos, Atitudes e Prática em Saúde , Avaliação EducacionalRESUMO
BACKGROUND: Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1). METHODS: Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 µg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout (Clec7a-/-) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons. RESULTS: Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx. CONCLUSIONS: Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization. SIGNIFICANCE STATEMENT: This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission.