RESUMEN
Swine wastewater application can introduce antibiotics, antibiotic resistance genes (ARGs) into environments. Herein, the full-scale transmission of antibiotics, ARGs and their potential carriers from an intensive swine feedlot to its surroundings were explored. Results showed that lincomycin and doxycycline hydrochloride were dominant antibiotics in this ecosystem. Lincomycin concentration were strongly associated with soil bacterial communities. According to the risk quotient (RQ), lincomycin was identified as posing higher ecological risk in aquatic environments. ARGs and mobile genetic elements (MGEs) abundance in wastewater were reduced after anaerobic treatment. Notably, ARGs composition of environmental samples were clustered into two groups based on if they were directly affected by the wastewater. However, there were no remarkable difference of ARGs abundance among environmental samples. The total abundance of ARGs was positively related to that of MGEs. Pathogens Escherichia coli and Enterococcus revealed strong connection with qnrS, tet and sul. Overall, this study highlights the importance of responsible antibiotics use in livestock production and appropriate treatment technology before agricultural application and discharge.
RESUMEN
Chelidonium majus L. (C. majus), commonly known as "Bai Qu Cai" in China, belongs to the genus Chelidonium of the Papaveraceae family. It has rich medicinal value, such as alleviating coughs, asthma, spasms and pain. Recent studies have demonstrated that C. majus is abundant in various alkaloids, which are the primary components of C. majus and have a range of pharmacological effects, including anti-microbial, anti-inflammatory, anti-viral, and anti-tumor effects. So far, 94 alkaloids have been isolated from C. majus, including benzophenanthridine, protoberberine, aporphine, protopine and other types of alkaloids. This paper aims to review the research progress in phytochemistry, pharmacology and toxicology of C. majus alkaloids, in order to provide a theoretical basis for the application of C. majus in the field of medicinal chemistry and to afford reference for further research and development efforts.
RESUMEN
The poor operational stability of perovskite light-emitting diodes (PeLEDs) remains a major obstacle to their commercial application. Achieving high brightness and quantum efficiency at low driving voltages, thus effectively reducing heat accumulation, is key to enhancing the operational lifetime of PeLEDs. Here, we present a breakthrough, attaining a record-low driving voltage while maintaining high brightness and efficiency. By thoroughly suppressing interface recombination and ensuring excellent charge transport, our PeLEDs, with an emission peak at 515 nanometers, achieve a maximum brightness of 90,295 candelas per square meter and a peak external quantum efficiency of 27.8% with an ultralow turn-on voltage of 1.7 volts (~70% bandgap voltage). Notably, Joule heat is nearly negligible at these low driving voltages, substantially extending the operational lifetime to 7691.1 hours. Our optimized strategies effectively tackle stability issue through thermal management, paving the way for highly stable PeLEDs.
RESUMEN
The Arabidopsis thaliana aluminum-activated malate transporter 9 (AtALMT9) functions as a vacuolar chloride channel that regulates the stomatal aperture. Here, we present the cryoelectron microscopy (cryo-EM) structures of AtALMT9 in three distinct states. AtALMT9 forms a dimer, and the pore is lined with four positively charged rings. The apo-AtALMT9 state shows a putative endogenous citrate obstructing the pore, where two W120 constriction residues enclose a gate with a pore radius of approximately 1.8 Å, representing an open state. Interestingly, channel closure is solely controlled by W120. Compared to wild-type plants, the W120A mutant exhibits more sensitivity to drought stress and is unable to restore the visual phenotype on leaves upon water recovery, reflecting persistent stomatal opening. Furthermore, notable variations are noted in channel gating and substrate recognition of Glycine max ALMT12, AtALMT9, and AtALMT1. In summary, our investigation enhances comprehension of the interplay between structure and function within the ALMT family.
RESUMEN
Cannabis sativa fruit (Cannabis Fructus) refers to the dried and ripe fruit of Cannabis sativa L. It is widely distributed in the northeast, North, and South China. It has medicinal, ecological, and economic values. This study aimed to review the chemical constituents and pharmacological activities of Cannabis Fructus, providing a reference for further exploration of Cannabis Fructus. Comprehensive information on Cannabis Fructus was collected via electronic searches (e.g., Google Scholar, PubMed, Sci Finder, and Web of Science) and from books on phytochemistry. Cannabis Fructus contains various compounds such as phenylpropanoids, flavonoids, steroids and terpenoids, cannabinoids, fatty acids, alkaloids, phenanthrenes, proteins, and polysaccharides. Its active ingredients exhibit anti-inflammatory, anti-oxidant, anti-bacterial, anti-aging, anti-fatigue, anti-tumor, anti-constipation, neuroprotective, lipoid-regulating, hepatoprotective, and immunomodulatory properties.
RESUMEN
BACKGROUND: The mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer's Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity. METHODS: This is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography-functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization. RESULTS: A total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus. CONCLUSION: Effects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03920826; Registration Date: 2019-04-19.
Asunto(s)
Enfermedad de Alzheimer , Electroencefalografía , Hipocampo , Imagen por Resonancia Magnética , Estimulación Transcraneal de Corriente Directa , Humanos , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/diagnóstico por imagen , Masculino , Femenino , Estimulación Transcraneal de Corriente Directa/métodos , Anciano , Método Doble Ciego , Hipocampo/diagnóstico por imagen , Hipocampo/fisiopatología , Electroencefalografía/métodos , Resultado del Tratamiento , Persona de Mediana Edad , Ritmo Gamma/fisiología , Pruebas Neuropsicológicas , Cognición/fisiologíaRESUMEN
Photoelectric dual-mode sensors, which respond to strain signal through photoelectric dual-signals, hold great promise as wearable sensors in human motion monitoring. In this work, a photoelectric dual-mode sensor based on photonic crystals hydrogel was developed for human joint motion detection. The optical signal of the sensor originated from the structural color of photonic crystals, which was achieved by tuning the polymethyl methacrylate (PMMA) microspheres diameter. The reflective peak of the sensor, based on 250 nm PMMA PCs, shifted from 623 nm to 492 nm with 100% strain. Graphene was employed to enhance the electrical signal of the sensor, resulting in a conductivity increase from 9.33 × 10-4 S/m to 2 × 10-3 S/m with an increase in graphene from 0 to 8 mg·mL-1. Concurrently, the resistance of the hydrogel with 8 mg·mL-1 graphene increased from 160 kΩ to 485 kΩ with a gauge factor (GF) = 0.02 under 100% strain, while maintaining a good cyclic stability. The results of the sensing and monitoring of finger joint bending revealed a significant shift in the reflective peak of the photoelectric dual-mode sensor from 624 nm to 526 nm. Additionally, its resistance change rate was measured at 1.72 with a 90° bending angle. These findings suggest that the photoelectric dual-mode sensor had the capability to detect the strain signal with photoelectric dual-mode signals, and indicates its great potential for the sensing and monitoring of joint motion.
RESUMEN
BACKGROUND: Oral Mucositis (OM) is a common and highly symptomatic complication of cancer therapy that affects patient function and quality of life. Jingzhi Niuhuangjiedu Tablet (JNT) is derived from the famous Chinese herbal formulas Huanglian Jiedu and Fangfeng Tongsheng decoctions, which have been widely used to treat heat toxin syndrome diseases, such as acute pharyngitis, periodontitis, oral ulcers, and oral mucositis (OM), but the underlying mechanism remains unclear. OBJECTIVES: This study validated the efficacy and explored the potential mechanisms of JNT in the treatment of OM by integrating network pharmacological analyses and experimental verification. METHODS: Network pharmacology and molecular docking techniques were used to predict the active components, key targets, and potential mechanisms of action of JNT against OM. The rat OM model was established by administering 5-Fluorouracil (5-FU) and acetic acid to the rat oral mucosa. Lipopolysaccharide (LPS)-treated human gingival fibroblasts (HGFs) were used as an inflammatory cell model. The GFP-NFκB HEK293T cell line was transfected to evaluate the anti-NFκB activity of JNT. RESULTS: A total of 236 Chinese herbal components and 201 corresponding targets were predicted for OM treatment using JNT. Bicuculine, luteolin, wogonin, and naringenin were identified as the important active compounds, while AKT1, ALB, IL6, MAPK3, and VEGFA were considered to be the major targets. Molecular docking revealed that these active compounds exhibited strong binding interactions with their targets. In vivo and in vitro experiments demonstrated that the anti-OM effect of JNT might be closely related to AKT1, NFκB, caspase-1, and NLRP3, as well as biological processes, such as inflammatory response and oxidative stress. CONCLUSION: Network pharmacological and experimental evidence indicates that JNT has a potential therapeutic effect on OM by regulating the Akt/NFκB/NLRP3 pathway.
RESUMEN
The coupled process of anammox and reduced-sulfur driven autotrophic denitrification can simultaneously remove nitrogen and sulfur from wastewater, while minimizing energy consumption and sludge production. However, the research on the coupled process for removing naturally toxic thiocyanate (SCN-) is limited. This work successfully established and operated a one-stage coupled system by co-cultivating mature anammox and SCN--driven autotrophic denitrification sludge in a single reactor. In this one-stage coupled system, the average total nitrogen removal efficiency was 89.68±3.33 %, surpassing that of solo anammox (81.80±2.10 %) and SCN--driven autotrophic denitrification (85.20±1.54 %). Moreover, the average removal efficiency of SCN- reached 99.50±3.64 %, exceeding that of solo SCN--driven autotrophic denitrification (98.80±0.65 %). The results of the 15N stable isotope tracer labeling experiment revealed the respective reaction rates of anammox and denitrification as 106.38±10.37 µmol/L/h and 69.07±8.07 µmol/L/h. By analyzing metagenomic sequencing data, Thiobacillus_denitrificans was identified as the primary contributor to SCN- degradation in this coupled system. Furthermore, based on the comprehensive analysis of nitrogen and sulfur metabolic pathways, as well as the genes associated with SCN- degradation, it can be inferred that the cyanate (CNO) pathway was responsible for SCN- degradation. This work provided a deeper insight into coupling anammox with SCN--driven autotrophic denitrification in a one-stage coupled system, thereby contributing to the development of an effective approach for wastewater treatment involving both SCN- and nitrogen.
Asunto(s)
Procesos Autotróficos , Desnitrificación , Nitrógeno , Tiocianatos , Tiocianatos/metabolismo , Nitrógeno/metabolismo , Reactores Biológicos , Aguas Residuales/química , Eliminación de Residuos Líquidos/métodos , Aguas del Alcantarillado , Oxidación-Reducción , AnaerobiosisRESUMEN
BACKGROUND: Irreversible pulmonary fibrosis induced by paraquat is the most prevalent cause of death in patients with paraquat poisoning. Pulmonary fibrosis is characterized by abnormal deposition of extracellular matrix (ECM). Currently, the role of fibrotic ECM microenvironment in paraquat-induced pulmonary fibrosis has not been established. METHODS: Rat pulmonary fibrosis model was induced by paraquat, ATN-161 (an integrin-ß1 antagonist) was given to investigate their effect on Rat survival and pulmonary fibrosis. Lungs were decellularized to generate normal and fibrotic acellular ECM scaffolds using Triton and SDS. Fibroblasts were cocultured with ECM scaffolds to established 3D culture systems to investigate the relationship between fibrotic ECM and the differentiation of fibroblasts. Then we explored the effect of fibrotic ECM microenvironment systematically promoting on integrin-ß1/FAK/ERK1/2 pathway and established 3D culture systems to investigate the relationship between fibrotic ECM and the differentiation of fibroblasts. RESULTS: Antagonism of integrin-ß1 could alleviate paraquat-induced pulmonary fibrosis and ameliorate survival status of rats. Compared to normal ECM, fibrotic extracellular microenvironment promoted the differentiation of fibroblasts to myofibroblasts. Antagonism of integrin-ß1 could also ameliorate the promotion of fibrotic extracellular microenvironment on differentiation of fibroblasts to myofibroblasts. Fibrotic ECM microenvironment promotes fibroblasts transforming into myofibroblasts through integrin-ß1/FAK/ERK1/2 signaling pathway. Moreover, this phenomenon holds independent on exogenous integrin-ß1. CONCLUSIONS: Activation of integrin-ß1/FAK/ERK1/2 pathway aggravates paraquat-induced pulmonary fibrosis depend on fibrotic ECM and integrin-ß1 may be a prospective therapeutic target for paraquat-induced pulmonary fibrosis in the future.
Asunto(s)
Matriz Extracelular , Fibroblastos , Integrina beta1 , Sistema de Señalización de MAP Quinasas , Paraquat , Fibrosis Pulmonar , Ratas Sprague-Dawley , Animales , Paraquat/toxicidad , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/metabolismo , Matriz Extracelular/metabolismo , Masculino , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Fibroblastos/metabolismo , Ratas , Integrina beta1/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Quinasa 1 de Adhesión Focal/metabolismo , Pulmón/patología , Pulmón/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patología , Miofibroblastos/efectos de los fármacos , Células Cultivadas , Modelos Animales de EnfermedadRESUMEN
Astragalus membranaceus (A. membranaceus) leaves can be used both as a medicine and food material. Their main chemical components are flavonoids and triterpenoid saponins. The pharmacokinetics of A. membranaceus leaves are rarely reported in the literature. This study aimed to investigate the pharmacokinetics of five major bioactive components of A. membranaceus leaves [rhamnocitrin 3-glucoside (RCG), tiliroside (TIL), rhamnocitrin 3-neohesperidoside (RNH), huangqiyenin R (HuR), and huangqiyenin I (HuI)]. Simultaneously using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. The extract of A. membranaceus leaves was administered orally to rats, and the rat plasma was subjected to a fast, sensitive, and specific UHPLC-MS/MS method. Butylparaben served as the internal standard. The plasma samples were pretreated using isopropanol/ethyl acetate (1:1, v/v) liquid-liquid extraction. Chromatographic separations were performed at a flow rate of 0.3â¯mL/min on a Waters ACQUITY HSS T3 Column (2.1â¯mm × 100â¯mm, 1.8 µm) using mobile phases of 0.1â¯% formic acid/water and 0.1â¯% formic acid/acetonitrile. Mass spectrometry detection was performed using an electrospray ionization ion source in the negative-ion mode and the multiple reaction monitoring mode. All analytes had an intraday and interday relative standard deviation of less than 14.10â¯%. The range of accuracy was -11.94-6.920â¯% and -15.22-5.800â¯%. The lower limits of quantification for RCG, TIL, RNH, HuR, HuI was 10.24, 10.27, 10.12, 5.137, and 5.841â¯ng/mL, respectively. The criteria were met by stability, matrix effects, and extraction recovery. The pharmacokinetic parameters of A. membranaceus leaf extract were ultimately obtained using this analytical method. The study provides a theoretical basis for future pharmacological research, clinical application, and development of healthy food from A. membranaceus leaves.
Asunto(s)
Astragalus propinquus , Flavonoides , Hojas de la Planta , Ratas Sprague-Dawley , Saponinas , Espectrometría de Masas en Tándem , Triterpenos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Hojas de la Planta/química , Animales , Flavonoides/farmacocinética , Flavonoides/sangre , Flavonoides/análisis , Saponinas/farmacocinética , Saponinas/sangre , Saponinas/análisis , Ratas , Triterpenos/farmacocinética , Triterpenos/sangre , Triterpenos/análisis , Masculino , Extractos Vegetales/farmacocinética , Extractos Vegetales/química , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Administración Oral , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Post coronavirus disease 2019 (COVID-19) pandemic, the widespread emergence and persistence of brain fog has led to a decline in people's productivity and quality of life. However, the clinical characteristics of COVID-19-associated brain fog are unclear, and standardized assessments are lacking. This study aims to develop a scale for brain fog assessment and support clinical practice and research. METHODS: The 17-item Brain Fog Assessment (BFA) scale was developed using a standardized methodology, including literature review, focus group discussions (FGDs), expert evaluation, and psychometric validation. Eighteen potential items were generated following the literature review. These items were subsequently refined during FGDs, which included input from patients, caregivers, and multidisciplinary experts in neurology, cognitive neuroscience, and psychology. After thorough deliberation and expert evaluation, the item pool was finalized into a 17-item scale. We recruited 1,325 patients recovered from COVID-19 from Chinese communities. Psychometric properties were assessed by reliability and validity analysis. RESULTS: Exploratory factor analysis of the BFA scale revealed a three-factor mode comprising 'cognitive decline' (nine items), 'confusion - disorientation' (five items), and 'fatigue' (three items). The internal consistency of each factor was strong (Cronbach's α: 0.82-0.92). Confirmatory factor analysis showed that the model fit, convergent validity, and discriminant validity of the scale were satisfactory. The test-retest reliability was strong (intraclass correlation coefficient = 0.84). Criterion-related validity analysis showed a strong correlation to the Wood Mental Fatigue Inventory (r = 0.70, p < 0.001). Individuals with a higher BFA score tended to score lower on the Montreal Cognitive Assessment (r = -0.23, p = 0.015). CONCLUSIONS: We established a novel BFA scale to quantify multiple clinical aspects of COVID-19-associated brain fog. Using the BFA scale, fatigue and declining performance in memory, attention, and thought were identified as the main symptoms of COVID-19-associated brain fog. This scale has potential implications for disease monitoring and therapy development for individuals with COVID-19-associated brain fog.
RESUMEN
The advent of polyadenosine diphosphate ribose polymerase inhibitors (PARPi) has brought about significant changes in the field of ovarian cancer treatment. However, in 2022, Rucaparib, Olaparib, and Niraparib, had their marketing approval revoked for third-line and subsequent therapies due to an increased potential for adverse events. Consequently, the exploration of new treatment modalities remains imperative. Recently, the integration of PARPi with immune checkpoint inhibitors (ICIs) has emerged as a potential remedy option within the context of ovarian cancer. This article offers a comprehensive examination of the mechanisms and applications of PARPi and ICIs in the treatment of ovarian cancer. It synthesizes the existing evidence supporting their combined use and discusses key considerations that merit attention in ongoing development efforts.
Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias Ováricas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Femenino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacologíaRESUMEN
BACKGROUND: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches. AIMS: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. METHODS: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. RESULTS: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate-induced HT22 cell damage model, 2.5 µM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid-ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti-ferroptotic effect of TGZ was confirmed in an erastin-induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus. CONCLUSION: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti-ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments.
Asunto(s)
Epilepsia , Ferroptosis , Fármacos Neuroprotectores , Troglitazona , Animales , Ratones , Epilepsia/tratamiento farmacológico , Epilepsia/inducido químicamente , Ferroptosis/efectos de los fármacos , Ferroptosis/fisiología , Fármacos Neuroprotectores/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/metabolismo , Ácido Glutámico/metabolismo , Masculino , Ácido Kaínico/toxicidad , Ratones Endogámicos C57BL , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéuticoRESUMEN
RSA-1 is a polysaccharide obtained from Raphani semen with a relatively clear structure and anti-colon cancer activity. In this study, high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy were applied to characterise the complex chain structure of RSA-1. Subsequently, the inhibitory effect on colon cancer growth through apoptosis induction in colon cancer cells was explored. The findings indicate that the main chain of RSA-1 consists of â3)-ß-D-Galp-(1 â and 3,6)-ß-D-Galp-(1 â substituted at C-6 with branched α-L-Araf side chains. RSA-1 disrupts the Bax/Bcl-2 ratio and thus inhibits the viability of colon cancer cells in vitro. Furthermore, it inhibits colon cancer migration by attenuating epithelial-mesenchymal transition. Notably, RSA-1 exhibited negligible impact on the growth of human intestinal epithelial cells within a relevant concentration range. This study establishes a theoretical foundation and provides technical support for the prospective development and application of RSA-1 as a dual-purpose anti-colon cancer drug and functional food.
Asunto(s)
Neoplasias del Colon , Galactanos , Humanos , Galactanos/química , Galactanos/farmacología , Galactanos/aislamiento & purificación , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacosRESUMEN
The partial-denitrification-anammox (PdNA) process exhibits great potential in enabling the simultaneous removal of NO3--N and NH4+-N. This study delved into the impact of exogenous nano zero-valent iron (nZVI) on the PdNA process. Adding 10 mg L-1 of nZVI increased nitrogen removal efficiency up to 83.12 % and maintained higher relative abundances of certain beneficial bacteria. The maximum relative abundance of Candidatus Brocadia (1.6 %), Candidatus Kuenenia (1.5 %), Ignavibacterium (1.3 %), and Azospira (1.2 %) was observed at 10 mg L-1 of nZVI. However, the greatest relative abundance of Thauera (1.3 %) was recorded under 50 mg L-1. Moreover, applying nZVI selectively enhanced the abundance of NO3--N reductase genes. So, keeping the nZVI concentration at 10 mg L-1 or below is advisable to ensure a stable PdNA process in mainstream conditions. Considering nitrogen removal efficiency, using nZVI in the PD-anammox process could be more cost-effective in enhancing its adoption in industrial and mainstream settings.
Asunto(s)
Hierro , Nitrógeno , Hierro/química , Hierro/farmacología , Bacterias , Metagenómica/métodos , Desnitrificación , Oxidación-Reducción , Nanopartículas del Metal/química , Compuestos de AmonioRESUMEN
This article systematically reviews the extraction and purification methods, structural characteristics, structure-activity relationship, and health benefits of C. speciosa polysaccharides, and their potential application in food, medicine, functional products, and feed, in order to provide a useful reference for future research. Chaenomeles speciosa (Sweet) Nakai. has attracted the attention of health consumers and medical researchers as a traditional Chinese medicine with edible, medicinal, and nutritional benefits. According to this study, C. speciosa polysaccharides have significant health benefits, such as anti-diaetic, anti-inflammatory and analgesic, anti-tumor, and immunomodulatory effects. Researchers determined the molecular weight, structural characteristics, and monosaccharide composition and ratio of C. speciosa polysaccharides by water extraction and alcohol precipitation. This study will lay a solid foundation for further optimization of the extraction process of C. speciosa polysaccharides and the development of their products. As an active ingredient with high value, C. speciosa polysaccharides are worthy of further study and full development. C. speciosa polysaccharides should be further explored in the future, to innovate their extraction methods, enrich their types and biological activities, and lay a solid foundation for further research and development of products containing polysaccharides that are beneficial to the human body.
Asunto(s)
Polisacáridos , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Rosaceae/química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Medicina Tradicional China , Monosacáridos/química , Monosacáridos/análisis , Relación Estructura-Actividad , AnimalesRESUMEN
Cancer represents one of the most significant health challenges currently facing humanity, and plant-derived antitumour drugs represent a prominent class of anticancer medications in clinical practice. Isovaleryl sucrose esters, which are natural constituents, have been identified as having potential antitumour effects. However, the mechanism of action remains unclear. In this study, 12 isovaleryl sucrose ester components, including five new (1-5) and seven known compounds (6-12), were isolated from the roots of Atractylodes japonica. The structures of the compounds were elucidated using 1D and 2D-NMR spectroscopy, complemented by HR-ESI-MS mass spectrometry. The cytotoxic activities of all the compounds against human colon cancer cells (HCT-116) and human lung adenocarcinoma cells (A549) were also evaluated using the CCK8 assay. The results demonstrated that compounds 2, 4, and 6 were moderately inhibitory to HCT-116 cells, with IC50 values of 7.49 ± 0.48, 9.03 ± 0.21, and 13.49 ± 1.45 µM, respectively. Compounds 1 and 6 were moderately inhibitory to A549, with IC50 values of 8.36 ± 0.77 and 7.10 ± 0.52 µM, respectively. Molecular docking revealed that compounds 1-9 exhibited a stronger affinity for FGFR3 and BRAF, with binding energies below -7 kcal/mol. Compound 2 exhibited the lowest binding energy of -10.63 kcal/mol to FGFR3. We screened the compounds with lower binding energies, and the protein-ligand complexes already obtained after molecular docking were subjected to exhaustive molecular dynamics simulation experiments, which simulated the dynamic behaviour of the molecules in close proximity to the actual biological environment, thus providing a deeper understanding of their functions and interaction mechanisms. The present study provides a reference for the development and use of iso-valeryl sucrose esters in the antitumour field.
Asunto(s)
Atractylodes , Ésteres , Simulación del Acoplamiento Molecular , Sacarosa , Humanos , Sacarosa/química , Sacarosa/análogos & derivados , Sacarosa/farmacología , Ésteres/química , Ésteres/farmacología , Atractylodes/química , Estructura Molecular , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Células HCT116 , Línea Celular Tumoral , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células A549 , Simulación de Dinámica Molecular , Proliferación Celular/efectos de los fármacosRESUMEN
White light-emitting diodes (WLEDs) with high color-rendering index (CRI, >90) are important for backlight displays and solid-state lighting applications. Although the well-developed colloidal quantum dots (QDs) based on heavy metals such as cadmium and lead are promising candidates for WLEDs, the low CRI still remains a significant limitation. In addition, the severe toxicity of heavy metals greatly limits their widespread use. Herein, the study demonstrates low-cost and environmentally friendly carbon quantum dots (CQDs)-based WLEDs that exhibit a high CRI of 94.33, surpassing that of conventional cadmium/lead-containing QD-based WLEDs. This achievement is attained through the employment of a binary host-induced exciplex strategy. The high hole/electron mobility and suitable energy levels of the donor and acceptor give rise to a broadband orange-yellow emission stemming from the exciplex. As the host, the binary exciplex is capable of contributing blue and orange-yellow emission components while efficiently mitigating the aggregation-induced quenching of CQDs. Meanwhile, CQDs effectively address the deep-red emission gap, enabling the realization of CQDs-based WLEDs with high CRI. These WLEDs also exhibit a remarkably low turn-on voltage of 2.8 V, a maximum luminance exceeding 2000 cd m- 2, a correlated color temperature of 4976 K, and Commission Internationale de l'Eclairage coordinates of (0.34, 0.32).
RESUMEN
OBJECTIVE: Aortic dissection (AD) is a prevalent and acute clinical catastrophe characterized by abrupt manifestation, swift progression, and elevated fatality rates. Despite smoking being a significant risk factor for AD, the precise pathological process remains elusive. This investigation endeavors to explore the mechanisms by which smoking accelerates AD through ferroptosis induction. METHODOLOGY: In this novel study, we detected considerable endothelial cell death by ferroptosis within the aortic inner lining of both human AD patients with a smoking history and murine AD models induced by ß-aminopropionitrile, angiotensin II, and nicotine. Utilizing bioinformatic approaches, we identified microRNAs regulating the expression of the ferroptosis inhibitor Glutathione peroxidase 4 (GPX4). Nicotine's impact on ferroptosis was further assessed in human umbilical vein endothelial cells (HUVECs) through modulation of miR-1909-5p. Additionally, the therapeutic potential of miR-1909-5p antagomir was evaluated in vivo in nicotine-exposed AD mice. FINDINGS: Our results indicate a predominance of ferroptosis over apoptosis, pyroptosis, and necroptosis in the aortas of AD patients who smoke. Nicotine exposure instigated ferroptosis in HUVECs, where the miR-1909-5p/GPX4 axis was implicated. Modulation of miR-1909-5p in these cells revealed its regulatory role over GPX4 levels and subsequent endothelial ferroptosis. In vivo, miR-1909-5p suppression reduced ferroptosis and mitigated AD progression in the murine model. CONCLUSIONS: Our data underscore the involvement of the miR-1909-5p/GPX4 axis in the pathogenesis of nicotine-induced endothelial ferroptosis in AD.