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BACKGROUND: Interpregnancy interval (IPI) is associated with the risk of GDM in a second pregnancy. However, an optimal IPI is still need to be determined based on the characteristics of the population. This study aimed to analyze the effect of interpregnancy interval (IPI) on the risk of gestational diabetes mellitus (GDM) in the Chinese population. METHODS: We conducted a retrospective cohort study on female participants who had consecutive deliveries at Peking University Shenzhen Hospital from 2013 to 2021. The IPI was categorized into 7 groups and included into the multivariate logistic regression model with other confound factors. Analysis was also stratified based on age of first pregnancy, BMI, and history of GDM. Adjusted OR values (aOR) and 95% confidence intervals (CI) calculated. The regression coefficient of IPI months on GDM prediction risk was analyzed using a linear regression model. RESULTS: A total of 2,392 participants were enrolled. The IPI of the GDM group was significantly greater than that of the non-GDM group (P < 0.05). Compared with the 18-24 months IPI category, participants with longer IPIs (24-36 months, 36-48 months, 48-60 months, and ≥ 60 months) had a higher risk of GDM (aOR:1.585, 2.381, 2.488, and 2.565; 95% CI: 1.021-2.462, 1.489-3.809, 1.441-4.298, and 1.294-5.087, respectively). For participants aged < 30 years or ≥ 30 years or without GDM history, all longer IPIs (≥ 36 months) were all significantly associated with the GDM risk in the second pregnancy (P < 0.05), while any shorter IPIs (< 18 months) was not significantly associated with GDM risk (P > 0.05). For participants with GDM history, IPI 12-18 months, 24-36 months, 36-48 months, and ≥ 60 months were all significantly associated with the GDM risk (aOR: 2.619, 3.747, 4.356, and 5.373; 95% CI: 1.074-6.386, 1.652-8.499, 1.724-11.005, and 1.078-26.793, respectively), and the slope value of linear regression (0.5161) was significantly higher compared to participants without a history of GDM (0.1891) (F = 284.168, P < 0.001). CONCLUSIONS: Long IPI increases the risk of GDM in a second pregnancy, but this risk is independent of maternal age. The risk of developing GDM in a second pregnancy for women with GDM history is more significantly affected by IPI.
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Intervalo entre Nacimientos , Diabetes Gestacional , Humanos , Femenino , Diabetes Gestacional/epidemiología , Embarazo , Estudios Retrospectivos , Intervalo entre Nacimientos/estadística & datos numéricos , Adulto , China/epidemiología , Factores de Riesgo , Número de EmbarazosRESUMEN
Chirality, a fundamental principle in chemistry, biology, and medicine, is prevalent in nature and in organisms. Chiral molecules, such as DNA, RNA, and proteins, are crucial in biomolecular synthesis, as well as in the development of functional materials. Among these, 1,1'-binaphthyl-2,2'-diol (BINOL) stands out for its stable chiral configuration, versatile functionality, and commercial availability. BINOL is widely employed in asymmetric catalysis and chiral materials. This review mainly focuses on recent research over the past five years concerning the use of BINOL derivatives for constructing chiral macrocycles and cages. Their contributions to chiral luminescence, enantiomeric separation, transmembrane transport, and asymmetric catalysis were examined.
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Several soil functions of alpine wetland depend on microbial communities, including carbon storage and nutrient cycling, and soil microbes are highly sensitive to hydrological conditions. Wetland degradation is often accompanied by a decline in water table. With the water table drawdown, the effects of microbial network complexity on various soil functions remain insufficiently understood. In this research, we quantified soil multifunctionality of flooded and non-flooded sites in the Lalu Wetland on the Tibetan Plateau. We employed high-throughput sequencing to investigate the microbial community responses to water table depth changes, as well as the relationships between microbial network properties and soil multifunctionality. Our findings revealed a substantial reduction in soil multifunctionality at both surface and subsurface soil layers (0-20 cm and 20-40 cm) in non-flooded sites compared to flooded sites. The α-diversity of bacteria in the surface soil of non-flooded sites was significantly lower than that in flooded sites. Microbial network properties (including the number of nodes, number of edges, average degree, density, and modularity of co-occurrence networks) exhibited significant correlations with soil multifunctionality. This study underscores the adverse impact of non-flooded conditions resulting from water table drawdown on soil multifunctionality in alpine wetland soils, driven by alterations in microbial community structure. Additionally, we identified soil pH and moisture content as pivotal abiotic factors influencing soil multifunctionality, with microbial network complexity emerging as a valuable predictor of multifunctionality.
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Microbiología del Suelo , Humedales , Microbiota , Suelo/química , Tibet , Agua Subterránea/microbiología , Agua Subterránea/química , Bacterias , InundacionesRESUMEN
HPK1 also referred to as MAP4K1, belongs to the category of mammalian STE20-like protein serine/threonine kinases. Its physiological function involves the down-regulation of T cell signals, and it is regarded as a new immune checkpoint of tumor immunology. In this study, we commenced our investigation with the hit compounds, focusing the efforts on structural optimization and SAR exploration to identify a novel class of 2,4-diaminopyrimidine HPK1 inhibitors. Notably, compound 14g exhibited a remarkable inhibitory effect on HPK1 kinase (IC50 = 0.15 nM), significantly suppressed the phosphorylation of the downstream adaptor protein SLP76 (pSLP76 IC50 = 27.92 nM), and effectively stimulated the secretion of the T cell activation marker IL-2 (EC50 = 46.64 nM). In vitro microsomal stability assay, compound 14g showed moderate stability in HLMs with T1/2 = 38.2 min and CLint = 36.4 µL·min-1·mg-1 proteins. In vivo pharmacokinetic studies, compound 14g demonstrated heightened plasma exposure (AUC0-inf = 644 ng·h·mL-1), extended half-life (T1/2 = 9.98 h), and reduced plasma clearance (CL = 52.3 mL·min-1·kg-1) compared to the reference compound after a single intravenous dose of 2 mg/kg in rats. These results indicated that compound 14g emerged as a promising inhibitor of HPK1.
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Diseño de Fármacos , Inhibidores de Proteínas Quinasas , Proteínas Serina-Treonina Quinasas , Pirimidinas , Pirimidinas/farmacología , Pirimidinas/química , Pirimidinas/síntesis química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Humanos , Relación Estructura-Actividad , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Estructura Molecular , Ratas , Relación Dosis-Respuesta a Droga , Masculino , Simulación del Acoplamiento Molecular , Ratas Sprague-DawleyRESUMEN
Background: Ewing sarcoma remains the second most prevalent primary aggressive bone tumor in teens and young adults. The aim of our study was to develop and validate a web-based nomogram to predict the overall survival for Ewing sarcoma in children. Methods: A total of 698 patients, with 640 cases from the Surveillance, Epidemiology, and End Results (the training set) and 58 cases (the external validation set), were included in this study. Cox analyses were carried out to determine the independent prognostic indicators, which were further included to establish a web-based nomogram. The predictive abilities were tested through the concordance index, calibration curve, decision curve analysis, and area under the receiver operating characteristic curve. Results: As suggested by univariate and multivariate Cox analyses, age, primary site, tumor size, metastasis stage (M stage), and chemotherapy were included as the independent predictive variables. The area under the receiver operating characteristic curve values, calibration curves, concordance index, and decision curve analysis from training and validation groups suggested the model has great clinical applications. Conclusion: We developed a convenient and precise web-based nomogram to evaluate overall survival for Ewing sarcoma in children. The application of this nomogram would assist physicians and patients in making decisions.
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Drought and nitrogen deposition are two major climate challenges, which can change the soil microbial community composition and ecological strategy and affect soil heterotrophic respiration (Rh). However, the combined effects of microbial community composition, microbial life strategies, and extracellular enzymes on the dynamics of Rh under drought and nitrogen deposition conditions remain unclear. Here, we experimented with an alpine swamp meadow to simulate drought (50% reduction in precipitation) and multilevel addition of nitrogen to determine the interactive effects of microbial community composition, microbial life strategy, and extracellular enzymes on Rh. The results showed that drought significantly reduced the seasonal mean Rh by 40.07%, and increased the Rh to soil respiration ratio by 22.04%. Drought significantly altered microbial community composition. The ratio of K- to r-selected bacteria (BK:r) and fungi (FK:r) increased by 20 and 91.43%, respectively. Drought increased hydrolase activities but decreased oxidase activities. However, adding N had no significant effect on microbial community composition, BK:r, FK:r, extracellular enzymes, or Rh. A structural equation model showed that the effects of drought and adding nitrogen via microbial community composition, microbial life strategy, and extracellular enzymes explained 84% of the variation in Rh. Oxidase activities decreased with BK:r, but increased with FK:r. Our findings show that drought decreased Rh primarily by inhibiting oxidase activities, which is induced by bacterial shifts from the r-strategy to the K-strategy. Our results highlight that the indirect regulation of drought on the carbon cycle through the dynamic of bacterial and fungal life history strategy should be considered for a better understanding of how terrestrial ecosystems respond to future climate change.
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Hydroxyl radicals (·OH) generated during the flooding-drought transformation process play a vital role in affecting nutrient cycles at riparian zone. However, information on the processes and mechanisms for ·OH formation under the influence of microplastics (MPs) remains unclear. In this study, the effects of MPs on ·OH production from riparian sediments with different biomass [e.g., vegetation lush (VL) and vegetation barren (VB)] were studied. The results showed that presence of MPs inhibited the production of ·OH by 27 % and 7.5 % for VB and VL sediments, respectively. The inhibition was mainly resulted from the MP-induced reduction of the biotic and abiotic mediated Fe redox processes. Spectral analysis revealed that VL sediments contained more high-molecular-weight humic-like substances. Presence of MPs increased the abundances and activities of Proteobacteria, Acidobacteria and Actinobacteria, which were conducive to the changes in humification and polar properties of organic matters. The reduced humic- and fulvic-like substances were accumulated in the flooding period and substantially oxidized during flooding/drought transformation due to the enhanced MP-mediated electron transfer abilities, thus mitigated the MP-induced inhibition effects. Therefore, in order to better understanding the biogeochemical cycling of contaminants as influenced by ·OH and MPs in river ecosystems, humic substances should be considered systematically.
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Phytoalexin sakuranetin functions in resistance against rice blast. However, the mechanisms underlying the effects of sakuranetin remains elusive. Here, we report that rice lines expressing resistance (R) genes were found to contain high levels of sakuranetin, which correlates with attenuated endocytic trafficking of plasma membrane (PM) proteins. Exogenous and endogenous sakuranetin attenuates the endocytosis of various PM proteins and the fungal effector PWL2. Moreover, accumulation of the avirulence protein AvrCO39, resulting from uptake into rice cells by Magnaporthe oryzae, was reduced following treatment with sakuranetin. Pharmacological manipulation of clathrin-mediated endocytic (CME) suggests that this pathway is targeted by sakuranetin. Indeed, attenuation of CME by sakuranetin is sufficient to convey resistance against rice blast. Our data reveals a mechanism of rice against M. oryzae by increasing sakuranetin levels and repressing the CME of pathogen effectors, which is distinct from the action of many R genes that mainly function by modulating transcription.
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Ascomicetos , Resistencia a la Enfermedad , Endocitosis , Flavonoides , Oryza , Fitoalexinas , Enfermedades de las Plantas , Proteínas de Plantas , Oryza/microbiología , Oryza/metabolismo , Oryza/efectos de los fármacos , Oryza/genética , Enfermedades de las Plantas/microbiología , Endocitosis/efectos de los fármacos , Resistencia a la Enfermedad/genética , Resistencia a la Enfermedad/efectos de los fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Sesquiterpenos/farmacología , Sesquiterpenos/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Plantas Modificadas Genéticamente , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genéticaRESUMEN
⤠The concept of anteromedial cortical support (AMCS) serves as valuable guidance for the intraoperative reduction of trochanteric hip fractures.⤠Positive medial cortical support (MCS) and positive or neutral anterior cortical support (ACS) are desirable. Some evidence has suggested that positive MCS is potentially superior to neutral MCS.⤠Experimental studies underscore the vital importance of the anteromedial wall and reveal why positive MCS potentially outperforms neutral MCS.⤠Incorporating the AMCS concept, the Chang reduction quality criteria (CRQC) are a reliable alternative approach to evaluate the reduction quality of trochanteric hip fractures.
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Fracturas de Cadera , Humanos , Fracturas de Cadera/cirugía , Fijación Interna de Fracturas/métodosRESUMEN
OBJECTIVE: This study aimed to evaluate the influence of herniation of cartilaginous endplates on postoperative pain and functional recovery in patients undergoing percutaneous endoscopic lumbar discectomy (PELD) for lumbar disc herniation (LDH). METHODS: A retrospective analysis was conducted on 126 patients with LDH treated with PELD at the Third Hospital of Hebei Medical University from January 2021 to January 2022. Whether cartilaginous endplates had herniated was identified by analyzing these specific findings from MRI scans: posterior marginal nodes, posterior osteophytes, mid endplate irregularities, heterogeneous low signal intensity of extruded material, and Modic changes in posterior corners and mid endplates. Patients were assessed for postoperative pain using the Visual Analogue Scale (VAS) and functional recovery using the Oswestry Disability Index (ODI) and Modified MacNab criteria. Statistical analyses compared outcomes based on the presence of herniation of cartilaginous endplates. RESULTS: Patients with herniation of cartilaginous endplates experienced higher pain scores early postoperatively but showed significant improvement in pain and functional status over the long term. The back pain VAS scores showed significant differences between the groups with and without herniation of cartilaginous endplates on postoperative day 1 and 1 month (P < 0.05). Leg pain VAS scores showed significant differences on postoperative day 1 (P < 0.05). Modic changes were significantly associated with variations in postoperative recovery, highlighting their importance in predicting patient outcomes. In patients with herniation of cartilaginous endplates, there were statistically significant differences in the back pain VAS scores at 1 month postoperatively and the ODI functional scores on postoperative day 1 between the groups with and without Modic changes (P < 0.05). There were no significant differences in the surgical outcomes between patients with and without these conditions regarding the Modified MacNab criteria (P > 0.05). CONCLUSION: Herniation of cartilaginous endplates significantly affect early postoperative pain and functional recovery in LDH patients undergoing PELD. These findings emphasize the need for clinical consideration of these imaging features in the preoperative planning and postoperative management to enhance patient outcomes and satisfaction.
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Discectomía Percutánea , Endoscopía , Desplazamiento del Disco Intervertebral , Vértebras Lumbares , Recuperación de la Función , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Masculino , Femenino , Discectomía Percutánea/métodos , Estudios Retrospectivos , Vértebras Lumbares/cirugía , Vértebras Lumbares/diagnóstico por imagen , Persona de Mediana Edad , Adulto , Endoscopía/métodos , Dolor Postoperatorio/etiología , Resultado del Tratamiento , Dimensión del Dolor , Cartílago/diagnóstico por imagen , Anciano , Imagen por Resonancia MagnéticaRESUMEN
African Swine Fever (ASF), caused by the African swine fever virus (ASFV), has inflicted significant economic losses on the pig industry in China. The key to mitigating its impact lies in accurate screening and strict biosecurity measures. In this regard, the development of colloidal gold immunochromatographic test strips (CGITS) has proven to be an effective method for detecting ASFV antibodies. These test strips are based on the ASFV p30 recombinant protein and corresponding monoclonal antibodies. The design of the test strip incorporates a high-concentration colloidal gold-labeled p30 recombinant protein as the detection sensor, utilizing Staphylococcal Protein A (SPA) as the test line (T line), and p30 monoclonal antibody as the control line (C line). The sensitivity and specificity of the test strip were evaluated after optimizing the labeling concentration, pH, and protein dosage. The research findings revealed that the optimal colloidal gold labeling concentration was 0.05 %, the optimal pH was 8.4, and the optimal protein dosage was 10 µg/mL. Under these conditions, the CGITS demonstrated a detection limit of 1:512 dilution of ASFV standard positive serum, without exhibiting cross-reactivity with antibodies against other viral pathogens. Furthermore, the test strips remained stable for up to 20 days when stored at 50 °C and 4 °C. Comparatively, the CGITS outperformed commercial ELISA kits, displaying a sensitivity of 90.9 % and a specificity of 96.2 %. Subsequently, 108 clinical sera were tested to assess its performance. The data showed that the coincidence rate between the CGITS and ELISA was 93.5 %. In conclusion, the rapid colloidal gold test strip provides an efficient and reliable screening tool for on-site clinical detection of ASF in China. Its accuracy, stability, and simplicity make it a valuable asset in combating the spread of ASF and limiting its impact on the pig industry.
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N6-methyladenosine (m6A), the most prevalent internal modification in mRNA, is related to the pathogenesis of osteoporosis (OP). Although methyltransferase Like-3 (METTL3), an m6A transferase, has been shown to mitigate OP progression, the mechanisms of METTL3-mediated m6A modification in osteoblast function remain unclear. Here, fluid shear stress (FSS) induced osteoblast proliferation and differentiation, resulting in elevated levels of METTL3 expression and m6A modification. Through Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) and Transcriptomic RNA Sequencing (RNA-seq), SRY (Sex Determining Region Y)-box 4 (SOX4) was screened as a target of METTL3, whose m6A-modified coding sequence (CDS) regions exhibited binding affinity towards METTL3. Further functional experiments demonstrated that knockdown of METTL3 and SOX4 hampered osteogenesis, and METTL3 knockdown compromised SOX4 mRNA stability. Via RNA immunoprecipitation (RIP) assays, we further confirmed the direct interaction between METTL3 and SOX4. YTH N6-Methyladenosine RNA Binding Protein 3 (YTHDF3) was identified as the m6A reader responsible for modulating SOX4 mRNA and protein levels by affecting its degradation. Furthermore, in vivo experiments demonstrated that bone loss in an ovariectomized (OVX) mouse model was reversed through the overexpression of SOX4 mediated by adeno-associated virus serotype 2 (AAV2). In conclusion, our research demonstrates that METTL3-mediated m6A modification of SOX4 plays a crucial role in regulating osteoblast proliferation and differentiation through its recognition by YTHDF3. Our research confirms METTL3-m6A-SOX4-YTHDF3 as an essential axis and potential mechanism in OP.
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Metiltransferasas , Osteoblastos , Animales , Ratones , Proliferación Celular , Metiltransferasas/metabolismo , Osteoblastos/metabolismo , ARN , ARN Mensajero/metabolismoRESUMEN
Background: Osteochondral injuries (OCIs) are common in patients with acute lateral patellar dislocation, which can produce both short- and long-;term adverse effects. However, the pattern of these injuries warrants further analysis, especially in relation to patient age. Purpose: To determine the overall prevalence of concomitant OCIs as well as the prevalence differences based on location and age after acute lateral patellar dislocations. Study Design: Systematic review; Level of evidence, 4. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library was completed from inception to July 20, 2022. All articles reporting the prevalence of OCI were included. The sample characteristics such as age, study design, magnetic resonance imaging diagnostic data, and the number of patients with OCI were extracted. The Methodological Index for Non-Randomized Studies (MINORS) was used for quality assessment. The overall and per-;site injury rates were calculated, and the prevalence was stratified by age-;group (≤16 and >16 years) and compared. Results: The systematic review included 39 studies involving 3354 patients. MINORS scores were 11.94 ± 1.98 and 16 ± 3.46 in the noncomparative and comparative studies, respectively. The overall prevalence of bone bruises and OCI was 89.6% (95% CI, 77.4%-97.7%) and 48.8% (95% CI, 39.0%-58.7%), respectively. In both overall and >16-year-old patients, the lateral femoral condyle (LFC) was the most common site of bone bruise (90.5% [95% CI, 84.0%-95.6%] and 91.5% [95% CI, 84.3%-96.9%], respectively); however, the medial patellar bruise was more common in patients ≤16 years (89.2% [95% CI, 82.9%-94.4%]). Among the pooled sites of OCI, the medial patella accounted for the largest proportion (36.9% [95% CI, 28.0%-46.3%]). OCIs were more common in patients >16 years (52.6% [95% CI, 39.4%-65.6%]) than in patients ≤16 years (46.6% [95% CI, 33.2%-60.3%]). Conclusion: Bone bruises on the LFC were most prevalent overall and in patients >16 years, whereas bone bruises on the medial patella were more prevalent in patients ≤16 years. OCIs were frequently seen in patients >16 years, with the most common site being the medial patella.
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MAIN CONCLUSION: The divergence of subsect. Gerardianae was likely triggered by the uplift of the Qinghai-Tibetan Plateau and adjacent mountains. Pinus bungeana might have probably experienced expansion since Last Interglacial period. Historical geological and climatic oscillations have profoundly affected patterns of nucleotide variability, evolutionary history, and species divergence in numerous plants of the Northern Hemisphere. However, how long-lived conifers responded to geological and climatic fluctuations in East Asia remain poorly understood. Here, based on paternally inherited chloroplast genomes and maternally inherited mitochondrial DNA markers, we investigated the population demographic history and molecular evolution of subsect. Gerardianae (only including three species, Pinus bungeana, P. gerardiana, and P. squamata) of Pinus. A low level of nucleotide diversity was found in P. bungeana (π was 0.00016 in chloroplast DNA sequences, and 0.00304 in mitochondrial DNAs). The haplotype-based phylogenetic topology and unimodal distributions of demographic analysis suggested that P. bungeana probably originated in the southern Qinling Mountains and experienced rapid population expansion since Last Interglacial period. Phylogenetic analysis revealed that P. gerardiana and P. squamata had closer genetic relationship. The species divergence of subsect. Gerardianae occurred about 27.18 million years ago (Mya) during the middle to late Oligocene, which was significantly associated with the uplift of the Qinghai-Tibetan Plateau and adjacent mountains from the Eocene to the mid-Pliocene. The molecular evolutionary analysis showed that two chloroplast genes (psaI and ycf1) were under positive selection, the genetic lineages of P. bungeana exhibited higher transition and nonsynonymous mutations, which were involved with the strongly environmental adaptation. These findings shed light on the population evolutionary history of white pine species and provide striking insights for comprehension of their species divergence and molecular evolution.
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Genoma del Cloroplasto , Pinus , Filogenia , Pinus/genética , Genoma del Cloroplasto/genética , Evolución Molecular , ADN de Cloroplastos/genética , ADN Mitocondrial/genética , Nucleótidos , Demografía , Variación GenéticaRESUMEN
Propolis is a gelatinous substance processed by western worker bees from the resin of plant buds and mixed with the secretions of the maxillary glands and beeswax. Propolis has extensive biological activities and antitumor effects. There have been few reports about the antitumor effect of propolis against human cutaneous squamous cell carcinoma (CSCC) A431 cells and its potential mechanism. CCK-8 assays, label-free proteomics, RT-PCR, and a xenograft tumor model were employed to explore this possibility. The results showed that the inhibition rate of A431 cell proliferation by the ethanol extract of propolis (EEP) was dose-dependent, with an IC50 of 39.17 µg/mL. There were 193 differentially expressed proteins in the EEP group compared with the control group (p < 0.05), of which 103 proteins (53.37%) were upregulated, and 90 proteins (46.63%) were downregulated. The main three activated and suppressed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were extracellular matrix (ECM)-receptor interaction, amoebiasis, cell adhesion molecules (CAMs), nonalcoholic fatty liver disease (NAFLD), retrograde endocannabinoid signaling, and Alzheimer's disease. The tumor volume of the 100 mg/kg EEP group was significantly different from that of the control group (p < 0.05). These results provide a theoretical basis for the potential treatment of human CSCC A431 cell tumors using propolis.
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Carcinoma de Células Escamosas , Própolis , Neoplasias Cutáneas , Humanos , Línea Celular Tumoral , Própolis/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Extractos Vegetales/farmacología , Etanol/farmacología , Proliferación CelularRESUMEN
Background: Tamarix chinensis Lour. is a 3-6-meter-tall small tree with high salt- and alkali- tolerance and aggressive invasiveness, mainly distributed in the eastern part of China in warm-temperate and subtropical climate zones, yet there is little information available regarding genetic diversity and population structure. Methods: A total of 204 individuals of nine T. chinensis populations were investigated for genetic diversity and population structure using a set of 12 highly polymorphic microsatellite markers. Results: The total number of alleles detected was 162, the average number of effective allele was 4.607, the average polymorphism information content (PIC) value of the 12 loci was 0.685, and the mean observed heterozygosity (Ho) and the mean expected heterozygosity (He) was 0.653 and 0.711, respectively. Analysis of molecular variance (AMOVA) showed a 5.32% genetic variation among T. chinensis populations. Despite a low population differentiation, Bayesian clustering analysis, discriminant analysis of principal components (DAPC) and the unweighted pair group method with arithmetic mean (UPGMA) clearly identified three genetic clusters correlated to the populations' geographic origin: the northern populations including those from Yellow River Delta, the Fangshan (FS) population from Beijing, the Changyi (CY) population from Bohai Bay, the Huanjiabu (HHJ) population from Hangzhou Bay, and the remaining two populations from Hangzhou Bay. There was a significant relationship between the genetic distance and geographical distance of the paired populations. Gene flow (Nm) was 4.254 estimated from FST. Conclusion: T. chinensis possessed high genetic diversity comparable to tree species, and although the population differentiation is shallow, our results classified the sampled populations according to sampling localities, suggesting the different origins of the study populations.
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Tamaricaceae , Humanos , Teorema de Bayes , Tamaricaceae/genética , Repeticiones de Microsatélite/genética , Agresión , Variación Genética/genéticaRESUMEN
BACKGROUND: Renal clear cell carcinoma (RCC) is a common cancer in urinary system with increasing incidence. At present, targeted therapy and immunotherapy are the main therapeutic programs in clinical therapy. To develop novel drugs and provide new ideas for clinical therapy, the identification of potential ccRCC subtypes and potential target genes or pathways has become a current research focus. AIM: The aim of this study was to explore the underlying mechanisms of mitochondrial function in ccRCC. This regulatory pathway is closely related to tumor development and metastasis in ccRCC patients, and their abnormal changes may affect the prognosis of cancer patients. Therefore, we decided to construct a prognostic model of ccRCC patients based on mitochondrial regulatory genes, aiming to provide new methods and ideas for clinical therapy. RESULT: The 5-year survival prediction model based on iterative LASSO reached 0.746, and the cox model based on coxph reached C-index = 0.77, integrated c/D AUC = 0.61, and integrated brier score = 0.14. The rsf model based on randomForestSRC was built with C-index = 0.82, integrated c/D AUC = 0.69, and integrated brier score = 0.11. The results show that mitochondrial regulatory pathway is a potential target pathway for clinical therapy of ccRCC, which can provide guidelines for clinical targeted therapy, immunotherapy and other first-line therapy.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/terapia , Inmunoterapia , Aprendizaje Automático , Mitocondrias/genética , Neoplasias Renales/genética , Neoplasias Renales/terapia , PronósticoRESUMEN
Propolis is a well-known natural antibacterial substance with various biological activities, such as anti-inflammatory and antioxidant activity. However, applications of propolis are limited due to its low water solubility. In this study, propolis microcapsules were developed with a core material of ethanol extract of propolis and shell materials of gum arabic and ß-cyclodextrin using a spray-drying technique. The optional processing formula, particle size distribution, morphology, dissolution property, and antibacterial activity of propolis microcapsules were determined. The results showed that the optional processing obtained an embedding rate of 90.99% propolis microcapsules with an average particle size of 445.66 ± 16.96 nm. The infrared spectrogram and thermogravimetric analyses showed that propolis was embedded in the shell materials. The propolis microcapsules were continuously released in water and fully released on the eighth day, and compared to propolis, the microcapsules exhibited weaker antibacterial activity. The minimum inhibitory concentrations (MICs) of propolis microcapsules against Escherichia coli and Staphylococcus aureus were 0.15 and 1.25 mg/mL, and their minimum bactericidal concentrations (MBCs) were 0.3 and 1.25 mg/mL, respectively. This water-soluble propolis microcapsule shows the potential for use as a sustained-release food additive, preservative, or drug.
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Accurate characterization of molecular representations plays an important role in the property prediction based on deep learning (DL) for drug discovery. However, most previous researches considered only one type of molecular representations, resulting in that it difficult to capture the full molecular feature information. In this study, a novel DL framework called multi-modal molecular representation learning fusion network (MMRLFN) is developed, which could simultaneously learn and integrate drug molecular features from molecular graphs and SMILES sequences. The developed MMRLFN method is composed of three complementary deep neural networks to learn various features from different molecular representations, such as molecular topology, local chemical background information, and substructures at varying scales. Eight public datasets involving various molecular properties used in drug discovery were employed to train and evaluate the developed MMRLFN. The obtained models showed better performances than the existing models based on mono-modal molecular representations. Additionally, a thorough analysis of the noise resistance and interpretability of the MMRLFN has been carried out. The generalization ability and effectiveness of the MMRLFN has been verified by case studies as well. Overall, the MMRLFN can accurately predict molecular properties and provide potentially valuable information from large datasets, thereby maximizing the possibility of successful drug discovery.
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Descubrimiento de Drogas , Redes Neurales de la ComputaciónRESUMEN
Background: Regarding trochanteric hip fractures, one type of posterior coronal fragments was described as the "banana-shaped fragment", while the impact of the banana-shaped fragment on mechanical stability has not been further studied. The current study investigated the association between the banana-shaped fragment and mechanical complications after surgery. Methods: This retrospective cohort study included 273 patients treated by proximal femoral nail antirotation (PFNA) in the full analysis. The age, the sex, the fracture side, the follow-up time, the American Society of Anesthesiologists classification, the operators, the fracture classification, the tip-apex distance, the blade positions, the reduction quality and the bone mineral density were analyzed in relation to mechanical complications, through univariate and multivariate approaches. Results: Mechanical complications happened in 33 patients. The banana-shaped fragment (adjusted odds ratio 5.240, 95% CI 2.172 to 12.641; p < 0.001), the tip-apex distance and the reduction quality showed significant association with mechanical complications in both univariate and multivariate analysis. Moreover, for 118 patients with the banana-shaped fragment, we found that the use of wire cerclage couldn't significantly lower the rates of mechanical complications (p = 0.648). Conclusions: The banana-shaped fragment had a negative impact on mechanical stability of trochanteric hip fractures treated by PFNA. In the perioperative period, the BSF should be carefully evaluated, and its specific handling deserves further study.