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ADP ribosylation factor-like GTPase 2 (Arl2) is crucial for controlling mitochondrial fusion and microtubule assembly in various organisms. Arl2 regulates the asymmetric division of neural stem cells in Drosophila via microtubule growth. However, the function of mammalian Arl2 during cortical development was unknown. Here, we demonstrate that mouse Arl2 plays a new role in corticogenesis via regulating microtubule growth, but not mitochondria functions. Arl2 knockdown (KD) leads to impaired proliferation of neural progenitor cells (NPCs) and neuronal migration. Arl2 KD in mouse NPCs significantly diminishes centrosomal microtubule growth and delocalization of centrosomal proteins Cdk5rap2 and γ-tubulin. Moreover, Arl2 physically associates with Cdk5rap2 by in silico prediction using AlphaFold multimer, which was validated by co-immunoprecipitation and proximity ligation assay. Remarkably, Cdk5rap2 overexpression significantly rescues the neurogenesis defects caused by Arl2 KD. Therefore, Arl2 plays an important role in mouse cortical development through microtubule growth via the centrosomal protein Cdk5rap2.
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Proteínas de Ciclo Celular , Centrosoma , Microtúbulos , Proteínas del Tejido Nervioso , Células-Madre Neurales , Neurogénesis , Animales , Microtúbulos/metabolismo , Ratones , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Neurogénesis/genética , Células-Madre Neurales/metabolismo , Centrosoma/metabolismo , Proliferación Celular , Movimiento Celular , Corteza Cerebral/metabolismo , Corteza Cerebral/embriología , Corteza Cerebral/crecimiento & desarrollo , Tubulina (Proteína)/metabolismo , Proteínas de Unión al GTP/metabolismo , Proteínas de Unión al GTP/genética , Factores de Ribosilacion-ADP/metabolismo , Factores de Ribosilacion-ADP/genéticaRESUMEN
BACKGROUND: Straw incorporation serves as an effective strategy to enhance soil fertility and soil microbial biomass carbon (SMBC), which in turn improves maize yield and agricultural sustainability. However, our understanding of nitrogen (N) fertilization and straw incorporation into soil microenvironment is still evolving. This study explored the impact of six N fertilization rates (N0, N100, N150, N200, N250, and N300) with and without straw incorporation on soil fertility, SMBC, enzyme activities, and maize yield. RESULTS: Results showed that both straw management and N fertilization significantly affected soil organic carbon (SOC), total N, SMBC, soil enzyme activities, and maize yield. Specifically, the N250 treatment combined with straw incorporation significantly increased SOC, total N, and SMBC compared to lower fertilization rates. Additionally, enzyme activities such as urease, cellulase, sucrose, catalase, and acid phosphatase reached their peak during the V6 growth stage in the N200 treatment under for both straw management conditions. Compared to N250 and N300 treatments of traditional planting, the N200 treatment with residue incorporation significantly increased yield by 8.30 and 4.22%, respectively. All measured parameters, except for cellulase activity, were significantly higher in spring than in the autumn across both study years, with notable increases observed in 2021. CONCLUSIONS: These findings suggest that optimal levels of SOC, soil total N (STN), and SMBC, along with increased soil enzyme activities, is crucial for sustaining soil fertility and enhancing maize grain yield under straw incorporation and N200 treatments.
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Fertilizantes , Nitrógeno , Suelo , Zea mays , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Suelo/química , Nitrógeno/metabolismo , Producción de Cultivos/métodos , Carbono/metabolismo , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/metabolismo , Biomasa , Microbiología del Suelo , Agricultura/métodosRESUMEN
FeâNâC is the most promising alternative to platinum-based catalysts to lower the cost of proton-exchange-membrane fuel cell (PEMFC). However, the deficient durability of FeâNâC has hindered their application. Herein, a TiN-doped FeâNâC (FeâNâC/TiN) is elaborately synthesized via the sol-gel method for the oxygen-reduction reaction (ORR) in PEMFC. The interpenetrating network composed by FeâNâC and TiN can simultaneously eliminate the free radical intermediates while maintaining the high ORR activity. As a result, the H2O2 yields of FeâNâC/TiN are suppressed below 4%, ≈4 times lower than the FeâNâC, and the half-wave potential only lost 15 mV after 30 kilo-cycle accelerated durability test (ADT). In a H2âO2 fuel cell assembled with FeâNâC/TiN, it presents 980 mA cm-2 current density at 0.6 V, 880 mW cm-2 peak power density, and only 17 mV voltage loss at 0.80 A cm-2 after 10 kilo-cycle ADT. The experiment and calculation results prove that the TiN has a strong adsorption interaction for the free radical intermediates (such as *OH, *OOH, etc.), and the radicals are scavenged subsequently. The rational integration of Fe single-atom, TiN radical scavenger, and highly porous network adequately utilize the intrinsic advantages of composite structure, enabling a durable and active Pt-metal-free catalyst for PEMFC.
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BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG. METHODS: By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk. RESULTS: We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk. CONCLUSIONS: This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.
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Predisposición Genética a la Enfermedad , Miastenia Gravis , Humanos , Multiómica , Estudio de Asociación del Genoma Completo , Miastenia Gravis/genética , Sitios de Carácter Cuantitativo/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T-cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore -specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV-specific T cells. In line with Taiwanese dominant HLA-alleles, we also evaluated ex vivo HBVcore -specific T cells by pMHC-tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD-1. Our parallel study showed HBV-specific CD8 T cells were more activated with greater PD-1 expression than CMV-specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD-1 fluctuation pattern of HBVcore -specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen-mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD-1 levels of HBVcore -specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.
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Hepatitis B Crónica , Hepatitis B , Humanos , Virus de la Hepatitis B/genética , Receptor de Muerte Celular Programada 1/genética , Estudios Longitudinales , Antígenos del Núcleo de la Hepatitis B , Linfocitos T CD8-positivosRESUMEN
The recurrence and metastasis in breast cancer within 3 years after the chemotherapies or surgery leads to poor prognosis with approximately 1-year overall survival. Large-scale scanning research studies have shown that taking lipid-lowering drugs may assist to reduce the risk of death from many cancers, since cholesterol in lipid rafts are essential for maintain integral membrane structure and functional signaling regulation. In this study, we examined five lipid-lowering drugs: swertiamarin, gemfibrozil, clofibrate, bezafibrate, and fenofibrate in triple-negative breast cancer, which is the most migration-prone subtype. Using human and murine triple-negative breast cancer cell lines (Hs 578 t and 4 T1), we found that fenofibrate displays the highest potential in inhibiting the colony formation, wound healing, and transwell migration. We further discovered that fenofibrate reduces the activity of pro-metastatic enzymes, matrix metalloproteinases (MMP)-9 and MMP-2. In addition, epithelial markers including E-cadherin and Zonula occludens-1 are increased, whereas mesenchymal markers including Snail, Twist and α-smooth muscle actin are attenuated. Furthermore, we found that fenofibrate downregulates ubiquitin-dependent GDF-15 degradation, which leads to enhanced GDF-15 expression that inhibits cell migration. Besides, nuclear translocation of FOXO1 is also upregulated by fenofibrate, which may responsible for GDF-15 expression. In summary, fenofibrate with anti-cancer ability hinders TNBC from migration and invasion, and may be beneficial to repurposing use of fenofibrate.
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Fenofibrato , Neoplasias de la Mama Triple Negativas , Animales , Humanos , Ratones , Neoplasias de la Mama Triple Negativas/metabolismo , Fenofibrato/farmacología , Fenofibrato/uso terapéutico , Factor 15 de Diferenciación de Crecimiento/farmacología , Factor 15 de Diferenciación de Crecimiento/uso terapéutico , Línea Celular Tumoral , Movimiento Celular , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Transición Epitelial-Mesenquimal , Lípidos , Proliferación CelularRESUMEN
BACKGROUND: Studies have shown that the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR) are related to the outcomes in patients with breast cancer receiving specific chemotherapies. However, the reports have focussed on the initial blood test and there is a lack of evidence or data to support that dynamic changes of ALC or NLR are associated with the patients' survival outcomes. METHODS: We retrospectively reviewed electronic medical records from patients with breast cancer treated with eribulin from 2015 to 2019 at our institution. Blood test data were available prior to starting eribulin (baseline), and at 1, 3 and 6 months after initiating eribulin. We classified the patients into ALC and NLR high and low groups using the following cut-offs: 1000/µl for ALC and 3 for NLR. We defined ALC and NLR trends as increasing or decreasing compared with the initial data. We assessed the associations between the ALC and NLR with progression-free survival and overall survival. RESULTS: There were 136 patients with breast cancer treated with eribulin. Of these patients, 60 had complete blood tests and follow-up data. Neither a high ALC nor a low baseline NLR was associated with the survival outcome. One month after initiating eribulin treatment, a high ALC and a low NLR were significantly associated with longer progression-free survival (p = 0.044 for each). Three months after initiating eribulin, a high ALC was significantly associated with better overall survival (p = 0.006). A high NLR at 3 or 6 months after initiating eribulin was associated with worse overall survival (p = 0.017 and p = 0.001, respectively). The ALC and NLR trends across times were not associated with survivals. CONCLUSION: We showed that 1, 3 and 6 months after initiating eribulin, a high ALC and a low NLR may be related to the patients' survival outcomes. The ALC and NLR trends were not associated with survival. Accordingly, we believe patients who maintain a high ALC and a low NLR may have better clinical outcomes after initiating eribulin.
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Neoplasias de la Mama , Furanos , Cetonas , Policétidos Poliéteres , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neutrófilos , Estudios Retrospectivos , Linfocitos , Recuento de LinfocitosRESUMEN
Hypertrophic scars (HS) still remain an urgent challenge in the medical community. Traditional Chinese medicine (TCM) has unique advantages in the treatment of HS. However, due to the natural barrier of the skin, it is difficult for the natural active components of TCM to more effectively penetrate the skin and exert therapeutic effects. Therefore, the development of an efficient drug delivery system to facilitate enhanced transdermal absorption of TCM becomes imperative for its clinical application. In this study, we designed a compound Salvia miltiorrhiza-Blumea balsamifera nanoemulsion gel (CSB-NEG) and investigated its therapeutic effects on rabbit HS models. The prescription of CSB-NEG was optimized by single-factor, pseudoternary phase diagram, and central composite design experiments. The results showed that the average particle size and PDI of the optimized CSB-NE were 46.0 ± 0.2 nm and 0.222 ± 0.004, respectively, and the encapsulation efficiency of total phenolic acid was 93.37 ± 2.56%. CSB-NEG demonstrated excellent stability and skin permeation in vitro and displayed a significantly enhanced ability to inhibit scar formation compared to the CSB physical mixture in vivo. After 3 weeks of CSB-NEG treatment, the scar appeared to be flat, pink, and flexible. Furthermore, this treatment also resulted in a decrease in the levels of the collagen I/III ratio and TGF-ß1 and Smad2 proteins while simultaneously promoting the growth and remodeling of microvessels. These findings suggest that CSB-NEG has the potential to effectively address the barrier properties of the skin and provide therapeutic benefits for HS, offering a new perspective for the prevention and treatment of HS.
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Cicatriz Hipertrófica , Emulsiones , Geles , Salvia miltiorrhiza , Absorción Cutánea , Conejos , Animales , Cicatriz Hipertrófica/tratamiento farmacológico , Salvia miltiorrhiza/química , Absorción Cutánea/efectos de los fármacos , Emulsiones/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Modelos Animales de Enfermedad , Piel/efectos de los fármacos , Piel/patología , Piel/metabolismo , Administración Cutánea , Tamaño de la Partícula , Masculino , Nanopartículas/química , Medicina Tradicional China/métodos , Oído/patología , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Molecules with high point-group symmetry are interesting prototype species in the textbook. As transition metal-centered boron clusters tend to have highly symmetric structures to fulfill multicenter bonding and high stability, new boron clusters with rare point-group symmetry may be viable. Through in-depth scrutiny over the structures of experimentally already observed transition metal-centered boron-wheel complexes, geometric and electronic design principles are summarized, based on which we studied M©B11k- (M = Y, La; Zr, Hf; k = 1, 2) clusters and found that a Y©B112- boron-wheel complex has an unprecedented D11h point-group symmetry. The remarkable stability of the planar Y©B112- complex is illustrated via extensive global-minimum structural search as well as comprehensive chemical bonding analyses. Similar to other boron-wheel complexes, the Y©B112- complex is shown to possess σ and π double aromaticity, indeed following the electronic design principle previously summarized. This new compound is expected to be experimentally identified, which will extend the currently known largest possible planar molecular symmetry and enrich the metal-centered boron-wheel class.
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Pulmonary inflammation may lead to neuroinflammation resulting in neurological dysfunction, and it is associated with a variety of acute and chronic lung diseases. Paeonol is a herbal phenolic compound with anti-inflammatory and anti-oxidative properties. The aim of this study is to understand the beneficial effects of paeonol on cognitive impairment, pulmonary inflammation and its underlying mechanisms. Pulmonary inflammation-associated cognitive deficit was observed in TNFα-stimulated mice, and paeonol mitigated the cognitive impairment by reducing the expressions of interleukin (IL)-1ß, IL-6, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) in hippocampus. Moreover, elevated plasma miR-34c-5p in lung-inflamed mice was also reduced by paeonol. Pulmonary inflammation induced by intratracheal instillation of TNFα in mice resulted in immune cells infiltration in bronchoalveolar lavage fluid, pulmonary edema, and acute fibrosis, and these inflammatory responses were alleviated by paeonol orally. In MH-S alveolar macrophages, tumor necrosis factor (TNF) α- and phorbol myristate acetate (PMA)-induced inflammasome activation was ameliorated by paeonol. In addition, the expressions of antioxidants were elevated by paeonol, and reactive oxygen species production was reduced. In this study, paeonol demonstrates protective effects against cognitive deficits and pulmonary inflammation by exerting anti-inflammatory and anti-oxidative properties, suggesting a powerful benefit as a potential therapeutic agent.
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Acetofenonas , Disfunción Cognitiva , Enfermedades Pulmonares , Enfermedades Pulmonares/complicaciones , Acetofenonas/farmacología , Acetofenonas/uso terapéutico , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Macrófagos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratones Endogámicos C57BL , Masculino , Animales , Ratones , Factor de Necrosis Tumoral alfa , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , MicroARNs/sangre , MicroARNs/genética , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Boron has been found to be able to form multiple bonds with lead. To probe Pb-B bonding, here we report an investigation of three Pb-doped boron clusters, PbB2-, PbB3O-, and PbB4O2-, which are produced by a laser ablation cluster source and characterized by photoelectron spectroscopy and ab initio calculations. The most stable structures of PbB2-, PbB3O-, and PbB4O2- are found to follow the formula, [PbB2(BO)n]- (n = 0-2), with zero, one, and two boronyl ligands coordinated to a triangular and aromatic PbB2 core, respectively. The PbB2- cluster contains a BîB double bond and two Pb-B single bonds. The coordination of BO is observed to weaken Pb-B bonding but strengthen the BîB bond in [PbB2(BO)n]- (n = 1, 2). The anionic [PbB2(BO)2]- and its corresponding neutral closed-shell [PbB2(BO)2] contain a BîB triple bond. A low-lying Y-shaped isomer is also observed for PbB4O2-, consisting of a central sp2 hybridized B atom bonded to two boronyl ligands and a PbB unit.
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In recent years, Varicocele (VC) has been recognized as a common cause of male infertility that can be treated by surgery or drugs. How to reduce the damage of VC to testicular spermatogenic function has attracted extensive attention in recent years. Among them, overexpressed ROS and high levels of inflammation may play a key role in VC-induced testicular damage. As the key mediated innate immune pathways, cGAS-STING shaft under pathological conditions, such as in cell and tissue damage stress can be cytoplasmic DNA activation, induce the activation of NLRP3 inflammatory corpuscle, triggering downstream of the inflammatory cascade reaction. Chlorogenic acid (CGA), as a natural compound from a wide range of sources, has strong anti-inflammatory and antioxidant activities, and is a potential effective drug for the treatment of varicocele infertility. The aim of this study is to investigate the role of CGA in the spermatogenic dysfunction of the rat testis induced by VC and the potential mechanisms. The results of this study have shown that CGA gavage treatment ameliorated the pathological damage of seminiferous tubules, increased the number of sperm in the lumen, and increased the expression levels of Occludin and ZO-1, which indicated the therapeutic effect of CGA on spermatogenic dysfunction in the testis of VC rats. Meanwhile, the damage of mitochondrial structure was alleviated and the expression levels of ROS, NLRP3 and pro-inflammatory cytokines (IL-1ß, IL-6, IL-18) were significantly reduced in the testicular tissues of model rats after CGA treatment. In addition, we demonstrated for the first time the high expression status of cGAS and STING in testicular tissues of VC model rats, and this was ameliorated to varying degrees after CGA treatment. In conclusion, this study suggests that CGA can improve the spermatogenic function of the testis by reducing mitochondrial damage and inhibiting the activation of the cGAS-STING axis, inhibiting the activation of the NLRP3 inflammasome, and improving the inflammatory damage of the testis, highlighting the potential of CGA as a therapeutic agent for varicocele infertility.
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Ácido Clorogénico , ADN Mitocondrial , Inflamasomas , Proteínas de la Membrana , Mitocondrias , Proteína con Dominio Pirina 3 de la Familia NLR , Nucleotidiltransferasas , Varicocele , Animales , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Ratas , Varicocele/tratamiento farmacológico , Varicocele/metabolismo , ADN Mitocondrial/metabolismo , Inflamasomas/metabolismo , Inflamasomas/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Nucleotidiltransferasas/antagonistas & inhibidores , Nucleotidiltransferasas/metabolismo , Ácido Clorogénico/farmacología , Ácido Clorogénico/química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ratas Sprague-Dawley , Espermatogénesis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Homeostasis/efectos de los fármacos , Relación Estructura-Actividad , Estructura MolecularRESUMEN
Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney transplant recipients has not yet been established in Taiwan. The Transplantation Society of Taiwan aimed to develop a consensus by expert opinion on the prevention and management of CMV infection. Based on the results of Consensus Conference, we suggested low-dose valganciclovir prophylaxis (450 mg once daily) for kidney transplant recipients. The prophylaxis duration was ≥6 months for high-risk (D+/R-) patients and 3 months for moderate-risk (R+) patients. Even for low-risk (D-/R-) patients, prophylaxis for at least 3 months is recommended because of the high seroprevalence of CMV in Taiwan. CMV prophylaxis was suggested after anti-thymocyte globulin treatment but not after methylprednisolone pulse therapy. Routine surveillance after prophylaxis, secondary prophylaxis after CMV disease treatment, and mTOR inhibitors for primary CMV prophylaxis were not recommended. Letermovir and marabavir are emerging CMV agents used for prophylaxis and refractory CMV disease. CMV immunoglobulins have been used to treat refractory CMV disease in Taiwan. We hope this consensus will help professionals manage patients with CMV in Taiwan to improve the quality of care.
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Methamphetamine (METH) abuse inflicts both physical and psychological harm. While our previous research has established the regulatory role of miR-29c-3p in behavior sensitization, the underlying mechanisms and target genes remain incompletely understood. In this study, we employed the isobaric tags for relative and absolute quantitation (iTRAQ) technique in conjunction with Ingenuity pathway analysis (IPA) to probe the putative molecular mechanisms of METH sensitization through miR-29c-3p inhibition. Through a microinjection of AAV-anti-miR-29c-3p into the nucleus accumbens (NAc) of mice, we observed the attenuation of METH-induced locomotor effects. Subsequent iTRAQ analysis identified 70 differentially expressed proteins (DEPs), with 22 up-regulated potential target proteins identified through miR-29c-3p target gene prediction and IPA analysis. Our focus extended to the number of neuronal branches, the excitatory synapse count, and locomotion-related pathways. Notably, GPR37, NPC1, and IREB2 emerged as potential target molecules for miR-29c-3p regulation, suggesting their involvement in the modulation of METH sensitization. Quantitative PCR confirmed the METH-induced aberrant expression of Gpr37, Npc1, and Ireb2 in the NAc of mice. Specifically, the over-expression of miR-29c-3p led to a significant reduction in the mRNA level of Gpr37, while the inhibition of miR-29c-3p resulted in a significant increase in the mRNA level of Gpr37, consistent with the regulatory principle of miRNAs modulating target gene expression. This suggests that miR-29c-3p potentially influences METH sensitization through its regulation of neuroplasticity. Our research indicates that miR-29c-3p plays a crucial role in regulating METH-induced sensitization, and it identified the potential molecular of miR-29c-3p in regulating METH-induced sensitization.
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Trastornos Relacionados con Anfetaminas , Metanfetamina , MicroARNs , Enfermedad de Niemann-Pick Tipo C , Animales , Ratones , Núcleo Accumbens , Metanfetamina/farmacología , MicroARNs/genética , Plasticidad Neuronal/genética , ARN Mensajero , Receptores Acoplados a Proteínas GRESUMEN
In this study, we developed a green and multifunctional bioactive nanoemulsion (BBG-NEs) of Blumea balsamifera oil using Bletilla striata polysaccharide (BSP) and glycyrrhizic acid (GA) as natural emulsifiers. The process parameters were optimized using particle size, PDI, and zeta potential as evaluation parameters. The physicochemical properties, stability, transdermal properties, and bioactivities of the BBG-NEs under optimal operating conditions were investigated. Finally, network pharmacology and molecular docking were used to elucidate the potential molecular mechanism underlying its wound-healing properties. After parameter optimization, BBG-NEs exhibited excellent stability and demonstrated favorable in vitro transdermal properties. Furthermore, it displayed enhanced antioxidant and wound-healing effects. SD rats wound-healing experiments demonstrated improved scab formation and accelerated healing in the BBG-NE treatment relative to BBO and emulsifier groups. Pharmacological network analyses showed that AKT1, CXCL8, and EGFR may be key targets of BBG-NEs in wound repair. The results of a scratch assay and Western blotting assay also demonstrated that BBG-NEs could effectively promote cell migration and inhibit inflammatory responses. These results indicate the potential of the developed BBG-NEs for antioxidant and skin wound applications, expanding the utility of natural emulsifiers. Meanwhile, this study provided a preliminary explanation of the potential mechanism of BBG-NEs to promote wound healing through network pharmacology and molecular docking, which provided a basis for the mechanistic study of green multifunctional nanoemulsions.
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Antioxidantes , Emulsionantes , Emulsiones , Ácido Glicirrínico , Simulación del Acoplamiento Molecular , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Emulsiones/química , Emulsionantes/química , Emulsionantes/farmacología , Ratas , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Ácido Glicirrínico/farmacología , Ácido Glicirrínico/química , Polisacáridos/química , Polisacáridos/farmacología , Tecnología Química Verde , Humanos , Ratas Sprague-Dawley , Nanopartículas/química , Aceites de Plantas/química , Aceites de Plantas/farmacología , Fabaceae/química , Masculino , Tamaño de la Partícula , Movimiento Celular/efectos de los fármacosRESUMEN
Bacterial infection is a thorny problem, and it is of great significance to developing green and efficient biological antibacterial agents that can replace antibiotics. This study aimed to rapidly prepare a new type of green antibacterial nanoemulsion containing silver nanoparticles in one step by using Blumea balsamifera oil (BBO) as an oil phase and tea saponin (TS) as a natural emulsifier and reducing agent. The optimum preparation conditions of the AgNPs@BBO-TS NE were determined, as well as its physicochemical properties and antibacterial activity in vitro being investigated. The results showed that the average particle size of the AgNPs@BBO-TS NE was 249.47 ± 6.23 nm, the PDI was 0.239 ± 0.003, and the zeta potential was -35.82 ± 4.26 mV. The produced AgNPs@BBO-TS NE showed good stability after centrifugation and 30-day storage. Moreover, the AgNPs@BBO-TS NE had an excellent antimicrobial effect on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. These results demonstrated that the AgNPs@BBO-TS NE produced in this study can be used as an efficient and green antibacterial agent in the biomedical field.
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Antibacterianos , Emulsiones , Tecnología Química Verde , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Plata , Antibacterianos/farmacología , Antibacterianos/química , Plata/química , Plata/farmacología , Nanopartículas del Metal/química , Staphylococcus aureus/efectos de los fármacos , Aceites de Plantas/química , Aceites de Plantas/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Saponinas/química , Saponinas/farmacologíaRESUMEN
Odontogenic infections can spread to the respiratory tract. Despite the known role of Tannerella forsythia as the primary pathogen in periodontitis, the association between T. forsythia infection and risk of pneumonia or lung abscess remains unknown. In this report, we present a case of lung abscess caused by T. forsythia infection. The pathogen was detected by metagenomic next-generation sequencing (mNGS) in the bronchoalveolar lavage fluid of the patient. The clinical characteristics and possible mechanisms of the infection are discussed. T. forsythia is a conditional pathogen that can cause lung abscess in the presence of helper bacteria and reduced host immune status. The course of treatment should be personalized and might be longer than 3 months.
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The versatile reactivity of isothiocyanate intermediates enabled the diversity-oriented synthesis (DOS) of N-heterocycles in a DNA-compatible manner. We first reported a mild in situ conversion of DNA-conjugated amines to isothiocyanates. Subsequently, a set of diverse transformations was successfully developed to construct 2-thioxo-quinazolinones, 1,2,4-thiadiazoles, and 2-imino thiazolines. Finally, the feasibility of these approaches in constructing DELs was further demonstrated through enzymatic ligation and mock pool preparation. This study demonstrated the advantages of combining in situ conversion strategies with DOS, which effectively broadened the chemical and structural diversity of DELs.
Asunto(s)
ADN , Compuestos Heterocíclicos , Isotiocianatos , Isotiocianatos/química , ADN/química , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/síntesis química , Estructura Molecular , Aminas/química , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/síntesis químicaRESUMEN
Direct ethanol fuel cells (DEFCs) play an indispensable role in the cyclic utilization of carbon resources due to its high volumetric energy density, high efficiency, and environmental benign character. However, owing to the chemically stable carbon-carbon (CâC) bond of ethanol, its incomplete electrooxidation at the anode severely inhibits the energy and power density output of DEFCs. The efficiency of CâC bond cleaving on the state-of-the-art Pt or Pd catalysts is reported as low as 7.5%. Recently, tremendous efforts are devoted to this field, and some effective strategies are put forward to facilitate the cleavage of the CâC bond. It is the right time to summarize the major breakthroughs in ethanol electrooxidation reaction. In this review, some optimization strategies including constructing core-shell nanostructure with alloying effect, doping other metal atoms in Pt and Pd catalysts, engineering composite catalyst with interface synergism, introducing cascade catalytic sites, and so on, are systematically summarized. In addition, the catalytic mechanism as well as the correlations between the catalyst structure and catalytic efficiency are further discussed. Finally, the prevailing limitations and feasible improvement directions for ethanol electrooxidation are proposed.
RESUMEN
The design of a low-platinum (Pt) proton-exchange-membrane fuel cell (PEMFC) can reduce its high cost. However, the development of a low-Pt PEMFC is severely hindered by the high oxygen transfer resistance in the catalyst layer. Herein, a carbon with interconnected and hierarchical pores is synthesized as a support for the low-Pt catalyst to lower the oxygen transfer resistance. A H2-air fuel cell assembled by Pt/hierarchical porous carbon shows 1610 mW/cm2 peak power density, 2230 mA/cm2 current density at 0.60 V, and only 18.4 S/m local oxygen transfer resistance with 0.10 mgPt/cm2 Pt loading at the cathode, which far exceeds those of various carbon black supports and commercially used Pt/C catalysts. Both the experimental and simulation results have shown the advancement of hierarchical pores toward the high efficiency of oxygen transportation.