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BACKGROUND: The accuracy of traditional knee MR imaging in diagnosing anterior cruciate ligament tears, especially partial tears, is relatively low, which may lead to misdiagnosis and missed diagnosis. This study aimed to assess the diagnostic performance of a novel imaging method, high-resolution oblique coronal MRI at an optimal flexed-knee Angle, for ACL tears. METHODS: 50 healthy volunteers were scanned with a scan-assisted device for the optimal flexion angle of ACL. For 92 knee trauma patients selected strictly according to inclusion and exclusion criteria, conventional extended-knee scans (control group) and high-resolution oblique coronal scans based on the optimal flexed-knee angle (experimental group) were conducted. Two observers rated ACL visibility blindly on a 5-point scale. Arthroscopy-defined outcomes determined diagnostic metrics for each method and sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. RESULTS: The average optimal flexion angle for healthy volunteers was approximately 30° (30.3° ± 5.0°). Imaging demonstrated complete visualization of the ACL in 96.7% of images in the experimental group versus 12.0% in the control group. The diagnostic indicators of the experimental group surpassed those of the control group: sensitivity (94.9% vs. 76.3%), specificity (97.0% vs. 81.8%), positive predictive value (98.2% vs. 88.2%), negative predictive value(91.4% vs. 65.9%), and accuracy (95.7% vs. 78.3%). ROC analysis indicated superior diagnostic performance in the experimental group, with an AUC of 0.945 compared with 0.776 for the control group (p < 0.0001). CONCLUSIONS: High-resolution oblique coronal imaging at the optimal 30° flexed-knee angle improved ACL visualization and diagnostic performance compared with conventional techniques.
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Lesiones del Ligamento Cruzado Anterior , Imagen por Resonancia Magnética , Humanos , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Femenino , Masculino , Adulto , Adulto Joven , Persona de Mediana Edad , Articulación de la Rodilla/diagnóstico por imagen , Adolescente , Artroscopía/métodosRESUMEN
BACKGROUND: Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients. METHODS: We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients. RESULTS: There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05). CONCLUSIONS: For HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more.
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Conductos Biliares Extrahepáticos , Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/complicaciones , Masculino , Femenino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/complicaciones , Persona de Mediana Edad , Pronóstico , Conductos Biliares Extrahepáticos/cirugía , Conductos Biliares Extrahepáticos/patología , Trombosis/cirugía , Trombosis/etiología , Trombosis/patología , Estudios Retrospectivos , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/mortalidad , Anciano , AdultoRESUMEN
BACKGROUND: Yunaconitine (YAC) is a hidden toxin that greatly threatens the life safety of patients who are prescribed herbal medicines containing Aconitum species; however, its underlying mechanism remains unclear. OBJECTIVE: The objective of this study is to elucidate the functions of P-glycoprotein (P-gp) in regulating the efficacy, toxicity, and pharmacokinetics of YAC. METHODS: The efflux function of P-gp on YAC was explored by using Caco-2 monolayers in combination with the P-gp inhibitor verapamil. The impact of P-gp on regulating the analgesic and anti-inflammatory effects, acute toxicity, tissue distribution, and pharmacokinetics of YAC was determined via male Mdr1a gene knocked-out mice and wild-type FVB mice. RESULTS: The presence of verapamil significantly decreased the efflux ratio of YAC from 20.41 to 1.07 in Caco- 2 monolayers (P < 0.05). Moreover, oral administration of 0.07 and 0.14 mg/kg YAC resulted in a notable decrease in writhing times in Mdr1a-/- mice by 23.53% and 49.27%, respectively, compared to wild-type FVB mice (P < 0.05). Additionally, the deficiency of P-gp remarkably decreased the half-lethal dose (LD50) of YAC from 2.13 to 0.24 mg/kg (P < 0.05). Moreover, the concentrations of YAC in the tissues of Mdr1a-/- mice were statistically higher than those in wild-type FVB mice (P < 0.05). Particularly, the brain accumulation of YAC in Mdr1a-/- mice significantly increased by 12- and 19-fold, respectively, after oral administration for 30 and 120 min, when compared to wild-type FVB mice (P < 0.05). There were no significant differences in the pharmacokinetic characteristics of YAC between Mdr1a-/- and wild-type FVB mice. CONCLUSION: YAC is a sensitive substrate of P-gp. The absence of P-gp enhances the analgesic effect and toxicity of YAC by upregulating its brain accumulation. Co-administration with a P-gp inhibitor may lead to severe YAC poisoning.
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Ataxia-telangiectasia mutated (ATM) was first discovered in patients with AT (ataxia telangiectasia), which is characteristic with cerebellar degeneration, immunodeficiency, being susceptible to malignant tumors and sensitive to radiation. ATM kinase could detect DNA double-strand breaks and play a vital role in the DNA damage response. Inhibiting the function of ATM could sensitize tumor cells to both ionizing radiation (IR) and chemotherapy, as well as improve the chemoresistance and radioresistance observed in some patients. As such, ATM is a novel and important target for the cancer therapy. We reviewed ATM inhibitors reported in the last two decades, focusing on their development process, structure-activity relationships, inhibitory efficacy, pharmacokinetics and pharmacodynamics characteristics in the preclinical and clinical studies. We summarized the clinical value of ATM inhibitors in tumors and some neurodegenerative diseases, as well as the main challenges to the development of the drugs, providing directions and references for the future development of ATM inhibitors.
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Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1-C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.
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Pancreatitis , Vasos Retinianos , Tomografía de Coherencia Óptica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Relevancia Clínica , Microvasos/diagnóstico por imagen , Microvasos/patología , Microvasos/fisiopatología , Pancreatitis/complicaciones , Pancreatitis/patología , Pancreatitis/fisiopatología , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Tomografía de Coherencia Óptica/métodos , Agudeza VisualRESUMEN
Cinnamomum camphora chvar. borneol, a rare camphor tree variant recently identified in China, is distinguished by its high concentration of D-borneol, also known as " plant gold" due to its significant value. The essential oil extracted from this variant,rich in monoterpenes and sesquiterpenes, demonstrates a broad spectrum of pharmacological activities, including analgesic, antiinflammatory, antioxidant, cognition-enhancing, anti-bacterial, and insecticidal effects. These properties, underscored by extensive research, highlight the oil's potential in the biomedical, chemical, and food sectors as a valuable commodity. Nonetheless, the safety profile of this valuable oil remains poorly characterized, with its chemical composition and therapeutic efficacy subject to variations in the factors like geographic origin, harvesting timing, part used for extraction, and processing techniques. Such variability poses challenges to its clinical application and hampers the efficient exploitation of this resource. This review synthesizes current studies on C. camphora chvar. borneol essential oil and provides a detailed examination of its chemical and pharmacological profiles. In this study, we discuss existing research gaps and propose strategies for advancing its clinical use and industrial application, aiming to provide a foundational reference for future investigations and the resolution of its commercial and therapeutic challenges.
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Canfanos , Cinnamomum camphora , Aceites Volátiles , Cinnamomum camphora/química , Aceites Volátiles/química , Aceites Volátiles/farmacología , Humanos , Animales , Antioxidantes/química , Antioxidantes/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacologíaRESUMEN
BACKGROUND: DNA methylation is an important epigenetic modification that plays a crucial role in the development and progression of various tumors. However, the association between methylationdriven genes and diagnosis, prognosis, and immune characteristics of head and neck squamous cell carcinoma (HNSCC) remains unclear. METHODS: We obtained transcriptome, methylation, and clinical data from HNSCC patients in TCGA database, and used MethylMix algorithm to identify methylation-driven genes. A methylation driven gene-related risk model was constructed using Lasso regression analysis, and validated using data from GEO database. Immune infiltration and immune function analysis of the expression profiles were conducted using ssGSEA. Differences in immune checkpoint-related genes were analyzed, and the efficacy of immunotherapy was evaluated using TCIA database. Finally, a series of cell functional experiments were conducted to validate the results. RESULTS: Five methylation-driven genes were identified and utilized to construct a prognostic risk model. Based on the median risk score, all patients were categorized into high-risk and low-risk groups. The K-M analysis revealed that patients in the high-risk group have a worse prognosis. Additionally, the risk model demonstrated better prognostic predictive value as indicated by ROC analysis. GSEA enrichment analysis indicated that gene sets in the high and low-risk groups were primarily enriched in pathways associated with tumor immunity and metabolism. Our subsequent investigations showed that high-risk patients exhibited more immunosuppressive phenotypes, while low-risk patients were more likely to respond positively to immunotherapy. CONCLUSION: These findings of our research have the potential to improve patient stratification, guide treatment decisions, and advance the development of personalized therapies for HNSCC.
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Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Transcriptoma , Humanos , Metilación de ADN/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Pronóstico , Transcriptoma/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/diagnóstico , Biomarcadores de Tumor/genética , Masculino , Femenino , Inmunoterapia , Perfilación de la Expresión Génica , Epigénesis Genética , Bases de Datos GenéticasRESUMEN
ß2 adrenergic receptor (ß2AR) is a G-protein-coupled receptor involved in cardiac protection. In chronic heart failure (CHF), persistent sympathetic nervous system activation occurs, resulting in prolonged ß2AR activation and subsequent receptor desensitization and downregulation. Notoginsenoside R1 (NGR1) has the functions of enhancing myocardial energy metabolism and mitigating myocardial fibrosis. The mechanisms of NGR1 against ischemic heart failure are unclear. A left anterior descending (LAD) artery ligation procedure was performed on C57BL/6â¯J mice for four weeks. From the 4th week onwards, they were treated with various doses (3, 10, 30â¯mg/kg/day) of NGR1. Subsequently, the impacts of NGR1 on ischemic heart failure were evaluated by assessing cardiac function, morphological changes in cardiac tissue, and the expression of atrial natriuretic peptide (ANP) and beta-myosin heavy chain (ß-MHC). H9c2 cells were protected by NGR1 when exposed to OGD/R conditions. H9c2 cells were likewise protected from OGD/R damage by NGR1. Furthermore, NGR1 increased ß2AR levels and decreased ß2AR ubiquitination. Mechanistic studies revealed that NGR1 enhanced MDM2 protein stability and increased the expression of MDM2 and ß-arrestin2 while inhibiting their interaction. Additionally, under conditions produced by OGD/R, the protective benefits of NGR1 on H9c2 cells were attenuated upon administration of the MDM2 inhibitor SP141. According to these findings, NGR1 impedes the interplay between ß-arrestin2 and MDM2, thereby preventing the ubiquitination and degradation of ß2AR to improve CHF.
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Ginsenósidos , Insuficiencia Cardíaca , Isquemia Miocárdica , Proteínas Proto-Oncogénicas c-mdm2 , Receptores Adrenérgicos beta 2 , Ubiquitinación , Arrestina beta 2 , Animales , Masculino , Ratones , Ratas , Arrestina beta 2/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Ginsenósidos/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Ratones Endogámicos C57BL , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Ubiquitinación/efectos de los fármacosRESUMEN
There are two main types of carbon nanotubes (CNTs): metallic and semiconducting. Naturally grown CNTs are randomly distributed, posing challenges in distinguishing between the two types. Here, a novel approach for nanoscale high-resolution imaging and identification of CNTs was introduced by incorporating the heterodyne technique into high-harmonic electrostatic force microscopy (HH-EFM) on an atomic force microscopy (AFM) platform. In the developed heterodyne HH-EFM, a more localized high-order gradient of tip-sample nonlinear interaction force is used as signal channels, resulting in an improved spatial resolution, compared to the conventional HH-EFM. Furthermore, the heterodyne HH-EFM also has the capability to visualize material carrier density and assess qualitative carrier transport performance. Our work not only presents a new approach to identifying/exploring electrical properties of low-dimensional nanomaterials but also provides a solution for optimizing resolution in long-range interaction-based functional AFM technologies.
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Organohalides are widespread pollutants that pose significant environmental hazards due to their high degree of halogenation and elevated redox potentials, making them resistant to natural attenuation. Traditional bioremediation approaches, primarily relying on bioaugmentation and biostimulation, often fall short of achieving complete detoxification. Furthermore, the emergence of complex halogenated pollutants, such as per- and polyfluoroalkyl substances (PFASs), further complicates remediation efforts. Therefore, there is a pressing need to reconsider novel approaches for more efficient remediation of these recalcitrant pollutants. This review proposes novel redox-potential-mediated hybrid bioprocesses, tailored to the physicochemical properties of pollutants and their environmental contexts, to achieve complete detoxification of organohalides. The possible scenarios for the proposed bioremediation approaches are further discussed. In anaerobic environments, such as sediment and groundwater, microbial reductive dehalogenation coupled with fermentation and methanogenesis can convert organohalides into carbon dioxide and methane. In environments with anaerobic-aerobic alternation, such as paddy soil and wetlands, a synergistic process involving reduction and oxidation can facilitate the complete mineralization of highly halogenated organic compounds. Future research should focus on in-depth exploration of microbial consortia, the application of ecological principles-guided strategies, and the development of bioinspired-designed techniques. This paper contributes to the academic discourse by proposing innovative remediation strategies tailored to the complexities of organohalide pollution.
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Biodegradación Ambiental , Oxidación-Reducción , Contaminantes Ambientales/metabolismo , Hidrocarburos Halogenados/metabolismo , Hidrocarburos Halogenados/química , Anaerobiosis , Metano/metabolismo , Halogenación , Bacterias/metabolismo , Bacterias/genéticaRESUMEN
Compared to conventional nucleic acid detection methods, label-free single nucleotide polymorphism (SNP) detection presents challenging due to the necessity of discerning single base mismatches, especially in the field of enzyme-free detection. In this study, we introduce a novel bulged-type DNA duplex probe designed to significantly amplify single-base differences. This probe is integrated with programmable DNA-based nanostructures to develop a sensitive, label-free biosensor for nonenzymatic SNP detection. The duplex probe with one bulge could selectively identify wild-typed DNA (WT) and mutant-type DNA (MT) based on a competitive strand displacement reaction mechanism. The hyperbranched HCR (HHCR) by incorporating of hairpin DNA into the DNA tetrahedron and surface-tethering on the portable screen printing electrode (SPCE) significantly favor the formation of negatively charged DNA nanostructure. We harnessed strong repulsion of DNA nanostructure towards the electroactive [Fe(CN)6]³â»/4â» in combination with electrochemical technique to create a label-free biosensor. This simple, enzyme-free and label-free biosensor could detect MT with a detection limit of 56 aM, even in multiple sequence backgrounds. The study served as the proof-of-concept for the integration of enzyme-free competitive mechanism and label-free strategy, which can be extended as a powerful tool to various fields.
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Técnicas Biosensibles , ADN , Técnicas Electroquímicas , Polimorfismo de Nucleótido Simple , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , ADN/genética , ADN/química , Límite de Detección , Nanoestructuras/química , Humanos , Sondas de ADN/química , Sondas de ADN/genéticaRESUMEN
Gut microbiota acts as a critical regulator in the development of nonalcoholic fatty liver disease (NAFLD), making probiotics a promise therapeutic strategy. Studies are needed to identify beneficial Bacteroides strains against NAFLD. Bacteroides ovatus (B. ovatus) may also exhibit therapy effect on NAFLD. The aim of this work was to evaluate the effect of B. ovatus on NAFLD and examine the mechanism. C57BL/6â¯J male mice were randomly divided into three groups: a control group (NCD) that received control standard diet, a model group (M) with high-fat and high-cholesterol (HFHC) diet, and M_Bo group that was fed HFFC supplemented with B. ovatus. Treatment with B. ovatus could reduce body weight, prevent hepatic steatohepatitis and liver injury. Mechanistically, B. ovatus induced changes of gut microbial diversity and composition, characterized by a decreased Firmicutes/Bacteroidetes (F/B) ratio in M_Bo group mice, a lower abundance of Proteobacteria, Verrucomicrobiota at phylum level and Ruminococcus_torques_group, Ruminococcus_gauvreauii_group, Erysipelatoclostridium at genus level, simultaneously a remarkablely higher fecal abundance of Lachnospiraceae_NK4A136_group, norank_f__Oscillospiraceae, Colidextribacter. Compared with M group, mice treated with B. ovatus showed an markedly altered fecal short chain fatty acids (SCFAs), a decline in serum levels of lipopolysaccharide (LPS), CD163, IL-1ß, TNF-α, reduced macrophages in livers. Additionally, B. ovatus treatment caused downregulation of genes involved in denovo lipogenesis (such as Srebfl, Acaca, Scd1, Fasn), which was accompanied by the upregulation of genes related with fatty acid oxidation (such as Ppara). In conclusion, this study provides evidence that B. ovatus could ameliorate NAFLD by modulating the gut-liver axis.
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Bacteroides , Dieta Alta en Grasa , Microbioma Gastrointestinal , Hígado , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Probióticos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Enfermedad del Hígado Graso no Alcohólico/microbiología , Animales , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Hígado/efectos de los fármacos , Hígado/metabolismo , Bacteroides/efectos de los fármacos , Probióticos/farmacología , Ratones , Colesterol en la Dieta/efectos adversosRESUMEN
Traditional solid phase extraction (SPE) suffers from a lack of specific adsorption. To overcome this problem, a combination of adsorption method and molecular imprinting technology by polydopamine modification was proposed to realize specific recognition of target compounds in SPE, which is of great significance to improve the separation efficiency of SPE. Cellulose hydrogel beads were prepared by dual cross-linking curing method and modified with polydopamine to make them hydrophilic and biocompatible. Subsequently, cellulose hydrogel-based molecularly imprinted beads (MIBs) were synthesized by surface molecular imprinting technology and used as novel column fillers in SPE to achieve efficient adsorption (34.16 mg·g-1) with specific selectivity towards camptothecin (CPT) in 120 min. The simulation and NMR analysis revealed that recognition mechanism of MIBs involved hydrogen bond interactions and Van der Waals effect. The MIBs were successful used in separating CPT from Camptotheca acuminata fruits, exhibiting impressive adsorption capacity (1.19 mg·g-1) and efficient recovery of CPT (81.54 %). Thus, an environmentally friendly column filler for SPE was developed, offering a promising avenue for utilizing cellulose-based materials in the selective separation of natural products.
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Camptotecina , Celulosa , Hidrogeles , Impresión Molecular , Extracción en Fase Sólida , Camptotecina/química , Camptotecina/aislamiento & purificación , Celulosa/química , Adsorción , Impresión Molecular/métodos , Hidrogeles/química , Extracción en Fase Sólida/métodos , Camptotheca/química , Polímeros/química , Interacciones Hidrofóbicas e Hidrofílicas , Indoles/química , Frutas/químicaRESUMEN
Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhibitors that block the active causes of MDR may provide a strategy for the treatment of colorectal cancer. In this study, we find that dorsomorphin (also known as compound C or BML-275) potently inhibits the transporter activity of ABCG2, thereby preserving the chemotherapeutic agents mitoxantrone and doxorubicin to antagonize MDR in ABCG2-overexpressing colorectal cancer cells. Additionally, dorsomorphin does not alter ABCG2 protein expression. The results of molecular docking studies show that dorsomorphin is bound stably to the ABCG2-binding pocket, suggesting that dorsomorphin is a potent ABCG2 inhibitor that attenuates ABCG2-mediated MDR in colorectal cancer.
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Grain weight, a key determinant of yield in rice (Oryza sativa L.), is governed primarily by genetic factors, whereas grain chalkiness, a detriment to grain quality, is intertwined with environmental factors such as mineral nutrients. Nitrogen (N) is recognized for its effect on grain chalkiness, but the underlying molecular mechanisms remain to be clarified. This study revealed the pivotal role of rice NODULE INCEPTION-LIKE PROTEIN 3 (OsNLP3) in simultaneously regulating grain weight and grain chalkiness. Our investigation showed that loss of OsNLP3 leads to a reduction in both grain weight and dimension, in contrast to the enhancement observed with OsNLP3 overexpression. OsNLP3 directly suppresses the expression of OsCEP6.1 and OsNF-YA8, which were identified as negative regulators associated with grain weight. Consequently, two novel regulatory modules, OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8, were identified as key players in grain weight regulation. Notably, the OsNLP3-OsNF-YA8 module not only increases grain weight but also mitigates grain chalkiness in response to N. This research clarifies the molecular mechanisms that orchestrate grain weight through the OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8 modules, highlighting the pivotal role of the OsNLP3-OsNF-YA8 module in alleviating grain chalkiness. These findings reveal potential targets for simultaneous enhancement of rice yield and quality.
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The invasion of alien plant and the pollution caused by soil microplastics have emerged as significant ecological threats. Recent studies have demonstrated aggravating effect of non-biodegradable microplastics on plant invasion. However, the impact of biodegradable microplastics (BMPs) on plant invasion remains unclear. Therefore, it is imperative to explore the impact of BMPs on plant invasion. In this study, a 30-day potting experiment with Trifolium repens L. (an invasive plant) and Oxalis corniculata L. (a native plant) was conducted to evaluate the influence of BMPs on T. repens's invasion. The findings revealed that BMPs results in a reduction in available N and P contents, thereby facilitating the colonization of arbuscular mycorrhizal fungi on T. repens 's roots. Consequently, T. repens adjusted its N and P foraging strategy by increasing P absorption ratio, and enhancing the accumulation of N and P in leaves. This ultimately led to the decrease of relative neighbor effect index of T. repens, indicating an aggravated invasion by T. repens. This study significantly enhances and expands the understanding of mechanisms by which microplastics aggravate plant invasion.
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Nitrógeno , Fósforo , Contaminantes del Suelo , Trifolium , Trifolium/efectos de los fármacos , Trifolium/metabolismo , Trifolium/crecimiento & desarrollo , Nitrógeno/metabolismo , Contaminantes del Suelo/toxicidad , Plásticos Biodegradables/química , Especies Introducidas , Micorrizas , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo , Microplásticos/toxicidad , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/microbiología , Biodegradación AmbientalRESUMEN
In the classical microbial isolation technique, the isolation process inevitably destroys all microbial interactions and thus makes it difficult to culture the many microorganisms that rely on these interactions for survival. In this study, we designed a simple coculture technique named the "sandwich agar plate method," which maintains microbial interactions throughout the isolation and pure culture processes. The total yield of uncultured species in sandwich agar plates based on eight helper strains was almost 10-fold that of the control group. Many uncultured species displayed commensal lifestyles. Further study found that heme was the growth-promoting factor of some marine commensal bacteria. Subsequent genomic analysis revealed that heme auxotrophies were common in various biotopes and prevalent in many uncultured microbial taxa. Moreover, our study supported that the survival strategies of heme auxotrophy in different habitats varied considerably. These findings highlight that cocultivation based on the "sandwich agar plate method" could be developed and used to isolate more uncultured bacteria.
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Lithium-sulfur batteries (LSBs) are still limited by some issues such as polysulfides shuttle and lithium dendrites. Recently, the concept "high-entropy" has been considered as the research hotspot and international frontier. Herein, a high entropy MXene (TiVCrMoC3Tx, HE-MXene) doped graphene is designed as the modified coating on commercial separators for LSBs. The HE-MXene affords multiple metal active sites, fast Li+ diffusion rate, and efficient adsorption toward polysulfide intermediates. Furthermore, strong lithophilic property is favorable for uniform Li+ deposition. The combination of in situ characterizations confirms TiVCrMoC3Tx effectively promotes the Li2S nucleation/dissolution kinetics, reduces the Li+ diffusion barrier, and exhibits favorable lithium uniform deposition behavior. This TiVCrMoC3Tx/G@PP provides a high-capacity retention rate after 1000 cycles at 1 C and 2 C, with a capacity decay rate of merely 0.021% and 0.022% per cycle. Surprisingly, the cell operates at a low potential of 48 mV while maintaining at 5 mA cm-2/5 mAh cm-2 for 4000 h. Furthermore, it still maintains a high-capacity retention rate under a high sulfur loading of 4.8/6.4 mg cm-2 and a low E/S ratio of 8.6/7.5 µg mL-1. This work reveals a technical roadmap for simultaneously addressing the cathode and anode challenge, thus achieving potential commercially viable LSBs.
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In this work, a new rapid and targeted method for screening α-glucosidase inhibitors from Hypericum beanii was developed and verified. Ten new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperlagarol A-J (1-10), and nine known PPAPs (11-19) were obtained from H. beanii. Their structures were identified by using comprehensive analyses involving mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and electron capture dissociation calculations. 1 and 2 are two new rare 2,3-seco-spirocyclic PPAPs, 3 and 4 are two novel 12,13-seco-spirocyclic PPAPs, 5 and 6 are two novel spirocyclic PPAPs, 7 and 8 are two new unusual spirocyclic PPAPs with complex bridged ring systems, and 9 and 10 are two novel nonspirocyclic PPAPs. α-GC inhibitory activities of all isolated compounds were tested. Most of them displayed inhibitory activities against α-glucosidase, with the IC50 values ranging from 6.85 ± 0.65 to 112.5 ± 9.03 µM. Moreover, the inhibitory type and mechanism of the active compounds were further analyzed using kinetic studies and molecular docking.
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Inhibidores de Glicósido Hidrolasas , Hypericum , Simulación del Acoplamiento Molecular , Extractos Vegetales , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , alfa-Glucosidasas/química , alfa-Glucosidasas/metabolismo , Hypericum/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Estructura Molecular , Ligandos , Relación Estructura-Actividad , CinéticaRESUMEN
CONTEXT: The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use. OBJECTIVE: The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases. METHODS: We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence. RESULTS: Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment. CONCLUSIONS: Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.