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As a rapidly developing information technology in recent years, the metaverse has significantly transformed how we live, learn, and work. In order to accelerate the use of metaverse technology and promote users' acceptance of the metaverse, this study constructs an integrated model based on flow theory and use and satisfaction theory, to further explore the factors affecting users' acceptance of the metaverse. A total of 265 valid questionnaires were obtained through a situational questionnaire survey. Considering the limitations of a single analysis technique, we use two methods to analyze the data. Among them, the symmetric PLS-SEM method is mainly used to analyze the effects of single variables, while the asymmetric fsQCA method is used to analyze the combined effects of variables. The PLS-SEM results manifest that flow experience, perceived risk, and personal innovation directly influence users' acceptance of the metaverse, while perceived cost has no effect. Simultaneously, interactivity, presence, and social presence indirectly affect users' acceptance of the metaverse, while informativeness and enjoyment have no indirect effect. Significantly, fsQCA unveiled five configurations resulting in a high user acceptance of the metaverse, as well as six configurations leading to a negative acceptance. The complementary findings from PLS-SEM and fsQCA offer valuable insights for both theoretical understanding and practical implementation.
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BACKGROUND: Heart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. METHODS: The active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model. RESULTS: We initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated. CONCLUSIONS: Mechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF.
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Lenvatinib (LVN) is a potentially effective multiple-targeted receptor tyrosine kinase inhibitor approved for treating hepatocellular carcinoma, metastatic renal cell carcinoma and thyroid cancer. Nonetheless, poor pharmacokinetic properties including poor water solubility and rapid metabolic, complex tumor microenvironment, and drug resistance have impeded its satisfactory therapeutic efficacy. This article comprehensively reviews the uses of nanotechnology in LVN to improve antitumor effects. With the characteristic of high modifiability and loading capacity of the nano-drug delivery system, an active targeting approach, controllable drug release, and biomimetic strategies have been devised to deliver LVN to target tumors in sequence, compensating for the lack of passive targeting. The existing applications and advances of LVN in improving therapeutic efficacy include improving longer-term efficiency, achieving higher efficiency, combination therapy, tracking and diagnosing application and reducing toxicity. Therefore, using multiple strategies combined with photothermal, photodynamic, and immunoregulatory therapies potentially overcomes multi-drug resistance, regulates unfavorable tumor microenvironment, and yields higher synergistic antitumor effects. In brief, the nano-LVN delivery system has brought light to the war against cancer while at the same time improving the antitumor effect. More intelligent and multifunctional nanoparticles should be investigated and further converted into clinical applications in the future.
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Antineoplásicos , Sistema de Administración de Fármacos con Nanopartículas , Compuestos de Fenilurea , Quinolinas , Humanos , Quinolinas/química , Quinolinas/farmacocinética , Quinolinas/administración & dosificación , Quinolinas/farmacología , Compuestos de Fenilurea/química , Compuestos de Fenilurea/farmacocinética , Compuestos de Fenilurea/administración & dosificación , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Sistema de Administración de Fármacos con Nanopartículas/química , Animales , Microambiente Tumoral/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Nanopartículas/químicaRESUMEN
This study delves into the aroma characteristics and microbial composition of filler tobacco leaves (FTLs) sourced from six distinct cigar-growing regions within Yunnan, China, following standardized fermentation. An integrated approach using gas chromatography-mass spectrometry (GC-MS), electronic nose (E-nose), and microbiome analysis was employed for comprehensive profiling. Results derived from Linear Discriminant Analysis (LDA) using E-nose data confirmed the presence of notable variability in flavor substance profiles among the FTLs from six regions. Additionally, GC-MS was used to discern disparities in volatile organic compound (VOC) distribution across FTLs from these regions, identifying 92, 81, 79, 58, 69, and 92 VOCs within each respective sample set. Significantly, 24 VOCs emerged as pivotal determinants contributing to the heterogeneity of flavor profiles among FTLs from diverse origins, as indicated by Variable Importance for the Projection (VIP) analysis. Furthermore, distinctions in free amino acid content and chemical constituents were observed across FTLs. Of noteworthy significance, solanone, isophorone, durene, (-)-alpha-terpineol, and 2,3'-bipyridine exhibited the strongest correlations with microbiome data, with fungal microorganisms exerting a more pronounced influence on metabolites, as elucidated through two-way orthogonal partial least-squares (O2PLS) modeling. These findings provide a theoretical and technical basis for accurately evaluating the synchronization of FTLs in aromas and fermentation processes, and they will enhance the quality of fermented FTLs and foster the growth of the domestic cigar tobacco industry ultimately.
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To elucidate the significant influence of microorganisms on geographically dependent flavor formation by analyzing microbial communities and volatile flavor compounds (VFCs) in cigar tobacco leaves (CTLs) obtained from China, Dominica, and Indonesia. Microbiome analysis revealed that the predominant bacteria in CTLs were Staphylococcus, Aerococcus, Pseudomonas, and Lactobacillus, while the predominant fungi were Aspergillus, Wallemia, and Sampaiozyma. The microbial communities of CTLs from different origins differed to some extent, and the diversity and abundance of bacteria were greater than fungi. Metabolomic analysis revealed that 64 VFCs were identified, mainly ketones, of which 23 VFCs could be utilized to identify the geographical origins of CTLs. Sixteen VFCs with OAV greater than 1, including cedrol, phenylacetaldehyde, damascone, beta-damascone, and beta-ionone, play important roles in shaping the flavor profile of CTLs from different origins. Combined with the correlation analysis, bacterial microorganisms were more closely related to key VFCs and favored a positive correlation. Bacillus, Vibrio, and Sphingomonas were the main flavor-related bacteria. The study demonstrated that the predominant microorganisms were essential for the formation of key flavor qualities in CTLs, which provided a theoretical reference for flavor control of CTLs by microbial technology. KEY POINTS: ⢠It is the high OAV VFCs that determine the flavor profile of CTLs. ⢠The methylerythritol phosphate (MEP) pathway and the carotenoid synthesis pathway are key metabolic pathways for the formation of VFCs in CTLs. ⢠Microbial interactions influence tobacco flavor, with bacterial microorganisms contributing more to the flavor formation of CTLs.
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Bacillus , Productos de Tabaco , Norisoprenoides , Correlación de Datos , NicotianaRESUMEN
Variations in industrial fermentation techniques have a significant impact on the fermentation of cigar tobacco leaves (CTLs), consequently influencing the aromatic attributes of the resulting cigars. The entire fermentation process of CTLs can be categorized into three distinct phases: phase 1 (CTLs prior to moisture regain), phase 2 (CTLs post-moisture regain and pile fermentation), and phase 3 (CTLs after fermentation and drying). These phases were determined based on the dynamic changes in microbial community diversity. During phase 2, there was a rapid increase in moisture and total acid content, which facilitated the proliferation of Aerococcus, a bacterial genus capable of utilizing reducing sugars, malic acid, and citric acid present in tobacco leaves. In contrast, fungal microorganisms exhibited a relatively stable response to changes in moisture and total acid, with Aspergillus, Alternaria, and Cladosporium being the dominant fungal groups throughout the fermentation stages. Bacterial genera were found to be more closely associated with variations in volatile compounds during fermentation compared to fungal microorganisms. This association ultimately resulted in higher levels of aroma components in CTLs, thereby improving the overall quality of the cigars. These findings reinforce the significance of industrial fermentation in shaping CTL quality and provide valuable insights for future efforts in the artificial regulation of secondary fermentation in CTLs. KEY POINTS: ⢠Industrial fermentation processes impact CTLs microbial communities. ⢠Moisture and total acid content influence microbial community succession in fermentation. ⢠Bacterial microorganisms strongly influence CTLs' aldehyde and ketone flavors over fungi.
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Microbiota , Productos de Tabaco , Fermentación , Nicotiana , AldehídosRESUMEN
BACKGROUND: Many clinical trials have shown that postoperative adjuvant chemotherapy can provide a survival benefit for patients with stage IB non-small cell lung cancer. However, whether adjuvant chemotherapy should be routinely given after surgery remains controversial. Therefore, we performed a meta-analysis to investigate the efficacy of adjuvant chemotherapy versus surgery alone for stage IB non-small cell lung cancer (NSCLC). METHODS: Relevant retrospective studies or randomized controlled trial comparing the efficacy of postoperative adjuvant chemotherapy versus observation on the survival outcomes of NSCLC patients up to October 30, 2023 were searched in PubMed, Web of Science, EMBASE, Cochrane Library, VIP database, Wanfang database, and China National Knowledge Internet database. Patient survival data, population characteristics, and other relevant information were extracted, and data were analyzed using Review Manager 5.4. The primary endpoints included overall survival, disease-free survival, and recurrence-free survival. RESULTS: A total of 13 randomized controlled trials or cohort studies including 19,442 patients were included. The results of the meta-analysis showed that postoperative adjuvant chemotherapy in patients with stage IB NSCLC had better overall survival (odds ratio [OR]â =â 1.25, 95% confidence interval [CI] 1.19-1.31, Pâ <â .00001) and disease-free survival or recurrence-free survival (ORâ =â 1.57, 95% CI 1.3-1.9, Pâ <â .00001) compared with observation; and the 4-year survival rate of patients who received postoperative adjuvant chemotherapy was better than the observation group (ORâ =â 1.52, 95% CI 1.05-2.18, Pâ =â .03); and the 8-year survival rate of patients receiving postoperative adjuvant chemotherapy (ORâ =â 1.5, 95% CI 0.94-2.4, Pâ =â .09) was comparable to the observation group. CONCLUSION: Receiving postoperative adjuvant chemotherapy improved people's survival and prolonged disease-free survival and recurrence-free survival in patients with stage IB non-small cell lung cancer compared with surgery alone.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Estudios Retrospectivos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Adyuvantes Inmunológicos , Adyuvantes Farmacéuticos , Quimioterapia Adyuvante , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Purpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus donafenib with immune checkpoint inhibitors (ICIs) (T+D+I) versus TACE plus donafenib (T+D) as the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). Methods: This retrospective study included patients with unresectable HCC who received T+D+I or T+D between June 2021 and February 2023. The tumor response was analyzed according to the modified Response Evaluation Criteria in Solid Tumors. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) in the two groups were compared before and after propensity score matching (PSM). Cox's proportional-hazards regression model was used to analyze factors affecting PFS and OS. Results: This study included 69 patients: 41 patients in the T+D group and 28 patients in the T+D+I group. After PSM, 26 patients in each group were analyzed. Patients in the T+D+I group had a higher DCR (96.2% vs 73.1%, P = 0.021), longer median PFS (13.1 vs 7.2 months, P = 0.017), and longer median OS (23.1 vs 14.7 months, P = 0.021) than those in the T+D group. The ORR in the two groups was similar (53.8% vs 50.0%, P = 0.781). Multivariate analyses revealed that T+D+I treatment and total bilirubin levels of <20 µmol/L were independent prognostic factors for long PFS. T+D+I treatment, Child-Pugh class A, and single-lobe tumor distribution were independent prognostic factors for long OS. The incidence of TRAEs in the two groups was similar (P > 0.05). Conclusion: In comparison with TACE plus donafenib, TACE plus donafenib with ICIs could significantly improve DCR, PFS, and OS as a potential first-line treatment for unresectable HCC with an acceptable safety profile.
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Understanding the impact of environmental factors on antibiotic sensitivity and the emergence of antibiotic resistance in microorganism is crucial for antibiotics management and environmental risk assessment. Natural materials, like mineral particles, are prevalent in aquatic and terrestrial ecosystems. However, it remains unclear how microorganism adapt to the physical stress of mineral particles and whether this adaptation influences antibiotic sensitivity and the evolution of antibiotic resistance. In this study, the model bacterium Escherichia coli (E. coli) was exposed to the mineral particle goethite for 30 generations. Adaptive morphogenesis, including an increase in the fraction of spherical bacteria, variations in bacterial mobility, a slightly increased cell membrane thickness, and genome-wide changes in the transcriptomic profile, were observed in adapted E. coli samples to counteract the stress. Moreover, the goethite adapted E. coli showed increased susceptibility to antibiotics including amoxicillin and tetracycline, and decreased susceptibility to kanamycin compared to its ancestral counterparts. These alterations in antibiotic susceptibility in the adapted E. coli were not heritable, as evidenced by the gradual recovery of antibiotic tolerance in cells with the cessation of goethite exposure. Transcriptomic data and a series of experiments suggested that these changes may be associated with variations in cell membrane property and iron metabolism. In addition, the evolution of antibiotic resistance in adapted cells occurred at a slower rate compared to their ancestral counterparts. For instance, E. coli adapted to goethite at a concentration of 1 mg/mL did not acquire antibiotic resistance even after 13 generations, probably due to its poor biofilm-formation capacity. Our findings underscore the occurrence of microbial adaptation to goethite, which influenced antibiotic sensitivity and decelerated the development of resistance in microorganisms. This insight contributes to our comprehension of the natural dynamics surrounding the evolution of antibiotic resistance and opens new perspectives for addressing this issue through nanotechnology-based approaches.
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Ecosistema , Escherichia coli , Compuestos de Hierro , Farmacorresistencia Bacteriana/genética , Antibacterianos/farmacología , Minerales , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: The plant Ainsliaea fragrans Champ. (A. fragrans) named "Xingxiang Tuerfeng", is a traditional herb with a long history of therapeutic practice in southern China in the treatment of gynecological diseases. PURPOSE: The anti-inflammatory extract of Ainsliaea fragrans Champ. (AF-ext) exhibited anti-primary dysmenorrhea (PD) activity in oxytocin-induced mice. This study aimed to unravel the underlying mechanisms of AF-ext on PD by the integrative approach of network pharmacology and experimental verification. METHODS: First, the therapeutic targets of AF-ext are predicted using network pharmacology and molecular docking methods. Second, activity screening and immunoblotting methods were used for target validation. Then, the therapeutic effect of AF-ext on PD was evaluated using oxytocin-induced mice and uterine strips model. RESULTS: AF-p1, and AF-p2, the active ingredients of AF-ext, showed inhibitory effects on COX1/2 and EGFR, and all five active components showed antagonistic activity on TRPV1. AF-ext (25, 50, 100 mg/kg) could significantly reduce the number of writhing times and prolong writhing latencies in a dose-dependent manner. AF-ext inhibited spasmolytic activity in uterine strips induced by oxytocin and Ca2+ stimulation. AF-ext inhibited NF-κB/COX-2/PG pathway and activation of the NLRP3 inflammasome in PD mice. It significantly downregulated the PD-induced overexpression of p-p65/p65, p-IκBα, and COX-2 by inhibiting the NF-κB pathway. Moreover, the overexpression of NLRP3, p20/pro-Caspase 1, and p17/pro-IL-1ß was greatly downregulated. CONCLUSIONS: AF-ext demonstrated anti-inflammatory, analgesic, and spasmolytic activity in the treatment of PD. It inhibited the NF-κB/COX-2/PG pathway and NLRP3 inflammasome activation in PD mice with a multi-target approach.
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Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Femenino , Ratones , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , FN-kappa B/metabolismo , Oxitocina/farmacología , Dismenorrea/tratamiento farmacológico , Farmacología en Red , Parasimpatolíticos , Ciclooxigenasa 2 , Simulación del Acoplamiento Molecular , Antiinflamatorios/farmacologíaRESUMEN
Objective: Although radiation workers are exposed to much lower doses of neutron-γ rays than those suffered in nuclear explosions and accidents, it does not mean that their health is not affected by radiation. Lower doses of radiation do not always cause morphological aberrations in chromosomes, so more sophisticated tests must be sought to specific alterations in the exposed cells. Our goal was to characterize the specific gene expression in lymphocytes from logging workers who were continuously exposed to low doses of neutron-γ radiation. We hypothesized that the combination of cell type-specific transcriptomes and open chromatin profiles would identify lymphocyte-specific gene alterations induced by long-term radiation with low-dose neutron-γ-rays and discover new regulatory pathways and transcriptional regulatory elements. Methods: Lymphocytes were extracted from workers who have been occupationally exposed to neutron-γ and workers unexposed to radiation in the same company. mRNA-seq and ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) were performed, followed integrative analysis to identify specific gene regulatory regions induced by neutron-γ radiation. A qPCR assay was then performed to verify the downregulation of RNA coding for ribosomal proteins and flow cytometry was used to detect ribosomal protein expression and cell cycle alterations. Results: We identified transcripts that were specifically induced by neutron-γ radiation and discovered differential open chromatin regions that correlated with these gene activation patterns. Notably, we observed a downward trend in the expression of both differentially expressed genes and open chromatin peaks. Our most significant finding was that the differential peak upregulated in ATAC-seq, while the differential gene was downregulated in the ribosome pathway. We confirmed that neutron-γ radiation leads to transcriptional inhibition by analyzing the most enriched promoters, examining RPS18 and RPS27A expression by qPCR, and analyzing protein-protein interactions of the differential genes. Ribosomal protein expression and cell cycle were also affected by neutron-γ as detected by flow cytometry. Conclusion: We have comprehensively analyzed the genetic landscape of human lymphocytes based on chromatin accessibility and transcript levels, enabling the identification of novel neutron-γ induced signature genes not previously known. By comparing fine-mapping of open chromatin and RNA reads, we have determined that neutron-γ specifically leads to downregulation of genes in the ribosome pathway, with pseudogenes potentially playing a crucial role.
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The relative position of the orchard robot to the rows of fruit trees is an important parameter for achieving autonomous navigation. The current methods for estimating the position parameters between rows of orchard robots obtain low parameter accuracy. To address this problem, this paper proposes a machine vision-based method for detecting the relative position of orchard robots and fruit tree rows. First, the fruit tree trunk is identified based on the improved YOLOv4 model; second, the camera coordinates of the tree trunk are calculated using the principle of binocular camera triangulation, and the ground projection coordinates of the tree trunk are obtained through coordinate conversion; finally, the midpoints of the projection coordinates of different sides are combined, the navigation path is obtained by linear fitting with the least squares method, and the position parameters of the orchard robot are obtained through calculation. The experimental results show that the average accuracy and average recall rate of the improved YOLOv4 model for fruit tree trunk detection are 5.92% and 7.91% higher, respectively, than those of the original YOLOv4 model. The average errors of heading angle and lateral deviation estimates obtained based on the method in this paper are 0.57° and 0.02 m. The method can accurately calculate heading angle and lateral deviation values at different positions between rows and provide a reference for the autonomous visual navigation of orchard robots.
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Manganese dioxide (MnO2) has been recognized as one of the natural systems' most active mineral oxidants. However, when it comes to catalytic oxidation of antibiotic applications, pure MnO2 falls short in delivering satisfactory performance. Hence, a set of Fe3+-doped porous MnO2 (0.02Fe-MnO2, 0.1Fe-MnO2, and 0.14Fe-MnO2) nanoparticles were synthesized here via a convenient and energy-efficient one-step reaction method. A series of experiments revealed that Fe-doping strategy enhances the properties of MnO2 host by suppressing the crystalline structure, increasing the amount of surface oxygen defects, and modifying the Mn3+/Mn4+ ratio. Specifically, the tetracycline (TC) removal efficiency of 0.14Fe-MnO2 reaches 92% without the need for any additional co-oxidant, representing a 20% improvement over pristine MnO2 nanoparticles. Moreover, this process shows a fast dynamic (achieving 70% of TC removal in just 5 min) and demonstrates pH-resistance, maintaining high TC removal efficiency (≥90%) over a wide pH range of 3.0-9.0. Mechanical studies reveal that the degradation of TC can be attributed to the oxidation by reactive oxygen radicals and Mn3+, with 1O2 being the primary radical involved in the reaction, accounting for 55% of TC removal. Importantly, cytotoxicity testing indicates that the biotoxicity of TC toward organisms can be effectively mitigated using 0.14Fe-MnO2 nanomaterial. This study presents a readily applicable candidate for economically and conveniently eliminating of environmental TC pollution, thereby reducing the threat posed by TC pollution to the ecosystem.
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Nanopartículas , Óxidos , Óxidos/química , Compuestos de Manganeso/química , Ecosistema , Antibacterianos/farmacología , Antibacterianos/química , Tetraciclina/química , OxidantesRESUMEN
Rare earth elements (REEs) are exploited for global use in manufacturing. Such activities result in their release into the environment and the transformation into more stable phosphate deposition. The objective of this study was to evaluate molecular and behavioral changes of zebrafish exposed to the synthesized terbium phosphate (TbPO4) at concentrations of 10, 20, and 50 mg/L and to determine its potential for neurotoxicity. Metabolomics related to neurotransmitters, and assessment of transcripts and proteins were conducted to uncover the molecular mechanisms underlying TbPO4 with emphasis on neurotransmitter systems. Exposure to 20 mg/L TbPO4 induced larval hyperactivity and perturbed the cholinergic system in zebrafish. Based on metabolomics related to neurotransmitters, dopamine (DA), serotonin (5-HT), and many of their precursors and metabolites were decreased in abundance by TbPO4. In addition, the expression levels of transcripts related to the synthesis, transport, receptor binding, and metabolism of DA and 5-HT were analyzed at the mRNA and protein levels. Transcript and protein levels for tyrosine hydroxylase (TH), the rate-limiting enzyme for DA synthesis, were down-regulated in larval fish. Monoamine oxidase (MAO), an enzyme that catabolizes monoamines DA and 5-HT, was also reduced in mRNA abundance. We hypothesize that DA synthesis and monoamine metabolism are associated with behavioral alterations. This study elucidates putative mechanisms and exposure risks to wildlife and humans by characterizing phosphatic REE-induced neurotoxicity in developing zebrafish.
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Síndromes de Neurotoxicidad , Pez Cebra , Animales , Humanos , Dopamina , Serotonina , Fosfatos , Aminas , LarvaRESUMEN
INTRODUCTION: Skin is exposed to a wide range of environmental risk factors including ultraviolet (UV) and all kinds of pollutants. Excessive UV exposure contributes to many disorders, such as photoaging, skin inflammation, and carcinogenesis. Previous studies have shown that Tremella fuciformis polysaccharides (TFPS) have protective effects on oxidative stress in cells, but the specific protective mechanism has not been clarified. METHODS: To determine the effects of TFPS on UV-irritated human skin, we conducted a variety of studies, including Cell Counting Kit-8 (CCK-8), trypan blue, Western blot, apoptosis assays, reactive oxygen species (ROS) detection in primary skin keratinocytes, and chronic UV-irradiated mouse model. RESULTS: We first determined that TFPS protects human skin keratinocytes against UV radiation-induced apoptosis and ROS production. Moreover, TFPS regulates thioredoxin interacting protein (TXNIP) and thioredoxin reductase 2 (TXNRD2) levels in primary skin keratinocytes for photoprotection. Last, we found that topical TFPS treatment could alleviate the UV-induced skin damage in chronic UV-irradiated mouse model. CONCLUSION: Collectively, our work indicates the beneficial role of TFPS in UV-induced skin cell damage and provides a novel therapeutic reagent to prevent or alleviate the progress of photoaging and other UV-provoked skin diseases.
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Piel , Tiorredoxina Reductasa 2 , Animales , Humanos , Ratones , Queratinocitos/metabolismo , Estrés Oxidativo , Polisacáridos/farmacología , Polisacáridos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tiorredoxina Reductasa 2/metabolismo , Tiorredoxinas/metabolismo , Rayos Ultravioleta/efectos adversosRESUMEN
Cutaneous squamous cell carcinoma (cSCC), a type of non-melanoma skin cancer (NMSC), is the most common malignancy worldwide. Thioredoxin (TXN) domain-containing protein 9 (TXNDC9) is a member of the TXN family that is important in cell differentiation. However, the biological function of this protein in cancer, particularly cSCC, is still unknown. In the present study, our experiments revealed the protective effects of TXNDC9 on UV-B-irritated cSCC cells. The initial findings showed that TXNDC9 is significantly upregulated in cSCC tissue and cells compared to normal skin tissue and keratinocytes. UV-B radiation robustly induces the expression of TXNDC9, and UV-B-induced cSCC cell death is boosted by TXNDC9 deficiency. Moreover, cSCC cells lacking TXNDC9 displayed attenuated activation of the NF-κB pathway. Additional studies by inhibiting TXNDC9 confirmed this finding, as TXNDC9 deficiency attenuated UV-B radiation-induced translocation of NF-κB p65 from the cytoplasm to the nucleus of cSCC. In conclusion, our work demonstrates the biological roles of TXNDC9 in cSCC progression and may provide a novel therapeutic target to treat cSCC in the future.
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Carcinoma de Células Escamosas , Neoplasias Cutáneas , Tiorredoxinas , Humanos , Apoptosis , Carcinoma de Células Escamosas/genética , FN-kappa B , Neoplasias Cutáneas/genética , Tiorredoxinas/genéticaRESUMEN
In order to obtain long-lived charge separated (CS) states in electron donor-acceptor dyads, herein we prepared a series of anthraquinone (AQ)-phenothiazine (PTZ) dyads, with adamantane as the linker. UV-vis absorption spectra show negligible electronic interaction between the AQ and PTZ units at ground state, yet charge transfer (CT) emission bands were observed. Nanosecond transient absorption shows that the 3 AQ state is populated upon photoexcitation for AQ-PTZ in cyclohexane (CHX), but in acetonitrile (ACN) a 3 CS state is formed. Similar results were observed for AQ-PTZ-M. The 3 CS state lifetimes were determined as 0.52â µs and 0.49â µs, respectively. Upon oxidation of the PTZ unit, the 3 AQ state was observed in both polar and non-polar solvents. For AQ-PTZ, femtosecond transient absorption spectra show fast formation of the 3 AQ state in all solvents, with no charge separation in CHX, while formation of the 3 CS state takes 106â ps in ACN. For AQ-PTZ-M, a 3 CS state is formed in CHX within 241â ps. Time-resolved electron paramagnetic resonance (TREPR) spectra show that a radical ion pair with electron exchange energy of |2â J|≥5.68â mT was observed for AQ-PTZ and AQ-PTZ-M, whereas in the dyads with the PTZ unit oxidized, only the 3 AQ state was observed.
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Terahertz (THz) technology has emerged as a promising tool for the qualitative and quantitative identification of markers containing major diseases, enabling early diagnosis and staged treatment of diseases. Nevertheless, the detection of water-containing biological samples is facing significant challenges due to limitations in high-power THz radiation sources and high-sensitivity detection devices. In this paper, we present a designed and constructed set of Terahertz-Attenuated Total Reflection (THz-ATR) spectrometer for high-sensitivity detection of liquid biological samples, which can dynamically maintain the signal-to-noise ratio (SNR) of THz detection signal of liquid biological samples at 40-60 dB. Our high-power THz-ATR spectroscopy can identify and quantitatively detect α-lactose aqueous solution with a minimum concentration of 0.292 mol/L. Moreover, we observed that the rate of change in the absorption peak position varied greatly between high and low concentration samples. Our high-power, high-sensitivity THz-ATR spectroscopy detection provides a rapid, accurate, and low-cost method for detecting disease markers such as blood and urine indicators. Additionally, this approach offers new perspectives for the refinement and in-depth detection of biomedical samples.