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G-protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small-molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often limited at the receptor, tissue and cellular levels. Antibodies have the potential to address these limitations but their properties as GPCR ligands remain poorly characterized. Here, using protein engineering, pharmacological assays and structural studies, we develop maternally selective heavy-chain-only antibody ('nanobody') antagonists against the angiotensin II type I receptor and uncover the unusual molecular basis of their receptor antagonism. We further show that our nanobodies can simultaneously bind to angiotensin II type I receptor with specific small-molecule antagonists and demonstrate that ligand selectivity can be readily tuned. Our work illustrates that antibody fragments can exhibit rich and evolvable pharmacology, attesting to their potential as next-generation GPCR modulators.
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Chromatin in eukaryotes folds into a complex three-dimensional (3D) structure that is essential for controlling gene expression and cellular function and is dynamically regulated in biological processes. Studies on plant phosphorus signaling have concentrated on single genes and gene interactions. It is critical to expand the existing signaling pathway in terms of its 3D structure. In this study, low-Pi treatment led to greater chromatin volume. Furthermore, low-Pi stress increased the insulation score and the number of TAD-like domains, but the effects on the A/B compartment were not obvious. The methylation levels of target sites (hereafter as RdDM levels) peaked at specific TAD-like boundaries, whereas RdDM peak levels at conserved TAD-like boundaries shifted and decreased sharply. The distribution pattern of RdDM sites originating from the Helitron transposons matched that of genome-wide RdDM sites near TAD-like boundaries. RdDM pathway genes were upregulated in the middle or early stages and downregulated in the later stages under low-Pi conditions. The RdDM pathway mutant ddm1a showed increased tolerance to low-Pi stress, with shortened and thickened roots contributing to higher Pi uptake from the shallow soil layer. ChIP-seq results revealed that ZmDDM1A could bind to Pi- and root development-related genes. Strong associations were found between interacting genes in significantly different chromatin-interaction regions and root traits. These findings not only expand the mechanisms by which plants respond to low-Pi stress through the RdDM pathway but also offer a crucial framework for the analysis of biological issues using 3D genomics.
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Cromatina , Zea mays , Cromatina/genética , Zea mays/genética , Metilación de ADN , Ensamble y Desensamble de Cromatina/genética , Silenciador del Gen , Regulación de la Expresión Génica de las PlantasRESUMEN
B-box containing proteins (BBXs) integrate light and various hormonal signals to regulate plant growth and development. Here, we demonstrate that the photomorphogenic repressors BBX28 and BBX29 positively regulate brassinosteroid (BR) signaling in Arabidopsis thaliana seedlings. Treatment with the BR brassinolide stabilized BBX28 and BBX29, which partially depended on BR INSENSITIVE1 (BRI1) and BIN2. bbx28 bbx29 seedlings exhibited larger cotyledon aperture than the wild-type when treated with brassinazole in the dark, which partially suppressed the closed cotyledons of brassinazole resistant 1-1D (bzr1-1D). Consistently, overexpressing BBX28 and BBX29 partially rescued the short hypocotyls of bri1-5 and bin2-1 in both the dark and light, while the loss-of-function of BBX28 and BBX29 partially suppressed the long hypocotyls of bzr1-1D in the light. BBX28 and BBX29 physically interacted with BR-ENHANCED EXPRESSION1 (BEE1), BEE2, and BEE3 and enhanced their binding to and activation of their target genes. Moreover, BBX28 and BBX29 as well as BEE1, BEE2, and BEE3 increased BZR1 accumulation to promote the BR signaling pathway. Therefore, both BBX28 and BBX29 interact with BEE1, BEE2, and BEE3 to orchestrate light and BR signaling by facilitating the transcriptional activity of BEE target genes. Our study provides insights into the pivotal roles of BBX28 and BBX29 as signal integrators in ensuring normal seedling development.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Brasinoesteroides/metabolismo , Brasinoesteroides/farmacología , Regulación de la Expresión Génica de las Plantas/genética , Proteínas Quinasas/metabolismo , Plantones/genética , Plantones/metabolismo , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
In the past two decades, machine learning potentials (MLPs) have driven significant developments in chemical, biological, and material sciences. The construction and training of MLPs enable fast and accurate simulations and analysis of thermodynamic and kinetic properties. This review focuses on the application of MLPs to reaction systems with consideration of bond breaking and formation. We review the development of MLP models, primarily with neural network and kernel-based algorithms, and recent applications of reactive MLPs (RMLPs) to systems at different scales. We show how RMLPs are constructed, how they speed up the calculation of reactive dynamics, and how they facilitate the study of reaction trajectories, reaction rates, free energy calculations, and many other calculations. Different data sampling strategies applied in building RMLPs are also discussed with a focus on how to collect structures for rare events and how to further improve their performance with active learning.
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C-reactive protein (CRP) is a highly conserved pentraxin with pattern recognition receptor-like activities. However, despite being used widely as a clinical marker of inflammation, the in vivo functions of CRP and its roles in health and disease remain largely unestablished. This is, to certain extent, due to the drastically different expression patterns of CRP in mice and rats, raising concerns about whether the functions of CRP are essential and conserved across species and how these model animals should be manipulated to examine the in vivo actions of human CRP. In this review, we discuss recent advances highlighting the essential and conserved functions of CRP across species, and propose that appropriately designed animal models can be used to understand the origin-, conformation-, and localization-dependent actions of human CRP in vivo. The improved model design will contribute to establishing the pathophysiological roles of CRP and facilitate the development of novel CRP-targeting strategies.
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Proteína C-Reactiva , Inflamación , Humanos , Animales , Ratones , Ratas , Modelos AnimalesRESUMEN
In acidic HZSM-5 zeolite, the reactivity of a methanol molecule interacting with the zeolite proton is amenable to modification via coadsorbing a stochiometric amount of an electron density donor E to form the [(E)(CH3OH)(HZ)] complex. The rate of the methanol in this complex undergoing dehydration to dimethyl ether was determined for a series of E with proton affinity (PA) ranging from 659 kJ mol-1 for C6F6 to 825 kJ mol-1 for C4H8O and was found to follow the expression: Ln(Rate) - Ln(RateN2) = ß(PA - PAN2)γ, where E = N2 is the reference and ß and γ are constants. This trend is probably due to the increased stability of the solvated proton in the [(E)(CH3OH)(HZ)] complex with increasing PA. Importantly, this is also observed in steady-state flow reactions when stoichiometric quantities of E are preadsorbed on the zeolite. As demonstrated with E being D2O, the effect on methanol reactivity diminishes when E is present in excess of the [(E)(CH3OH)(HZ)] complex. It is proposed that the methanol dehydration reaction involves [(E)(CH3OH)(CH3OH)(HZ)] as the transition state, which is supported by the isotopologue distribution of the initial dimethyl ether formed when a flow of CH3OH was passed over ZSM-5 containing one CD3OH per zeolite proton. The implication of this on the mechanism of catalytic methanol dehydration on HZSM-5 is discussed.
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The unique anionic redox mechanism provides, high-capacity, irreversible oxygen release and voltage/capacity degradation to Li-rich cathode materials (LRO, Li1.2Mn0.54Co0.13Ni0.13O2). In this study, an integrated stabilized carbon-rock salt/spinel composite heterostructured layers (C@spinel/MO) is constructed by in situ self-reconstruction, and the generation mechanism of the in situ reconstructed surface is elucidated. The formation of atomic-level connections between the surface-protected phase and bulk-layered phase contributes to electrochemical performance. The best-performing sample shows a high increase (63%) of capacity retention compared to that of the pristine sample after 100 cycles at 1C, with an 86.7% reduction in surface oxygen release shown by differential electrochemical mass spectrometry. Soft X-ray results show that Co3+ and Mn4+ are mainly reduce in the carbothermal reduction reaction and participate in the formation of the spinel/MO rock-salt phase. The results of oxygen release characterized by Differential electrochemical mass spectrometry (DEMS) strongly prove the effectiveness of surface reconstruction.
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KEY MESSAGE: Extensive and comprehensive phenotypic data from a maize RIL population under both low- and normal-Pi treatments were used to conduct QTL mapping. Additionally, we integrated parental resequencing data from the RIL population, GWAS results, and transcriptome data to identify candidate genes associated with low-Pi stress in maize. Phosphorus (Pi) is one of the essential nutrients that greatly affect the maize yield. However, the genes underlying the QTL controlling maize low-Pi response remain largely unknown. In this study, a total of 38 traits at both seedling and maturity stages were evaluated under low- and normal-Pi conditions using a RIL population constructed from X178 (tolerant) and 9782 (sensitive), and most traits varied significantly between low- and normal-Pi treatments. Twenty-nine QTLs specific to low-Pi conditions were identified after excluding those with common intervals under both low- and normal-Pi conditions. Furthermore, 45 additional QTLs were identified based on the index value ((Trait_under_LowPi-Trait_under_NormalPi)/Trait_under_NormalPi) of each trait. These 74 QTLs collectively were classified as Pi-dependent QTLs. Additionally, 39 Pi-dependent QTLs were clustered in nine HotspotQTLs. The Pi-dependent QTL interval contained 19,613 unique genes, 6,999 of which exhibited sequence differences with non-synonymous mutation sites between X178 and 9782. Combined with in silico GWAS results, 277 consistent candidate genes were identified, with 124 genes located within the HotspotQTL intervals. The transcriptome analysis revealed that 21 genes, including the Pi transporter ZmPT7 and the strigolactones pathway-related gene ZmPDR1, exhibited consistent low-Pi stress response patterns across various maize inbred lines or tissues. It is noteworthy that ZmPDR1 in maize roots can be sharply up-regulated by low-Pi stress, suggesting its potential importance as a candidate gene for responding to low-Pi stress through the strigolactones pathway.
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Mapeo Cromosómico , Fósforo , Sitios de Carácter Cuantitativo , Zea mays , Zea mays/genética , Zea mays/crecimiento & desarrollo , Mapeo Cromosómico/métodos , Fósforo/metabolismo , Fenotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Genes de Plantas , Genoma de Planta , Regulación de la Expresión Génica de las Plantas , Simulación por ComputadorRESUMEN
Examining the connection between P and starch-related signals can help elucidate the balance between nutrients and yield. This study utilized 307 diverse maize inbred lines to conduct multi-year and multi-plot trials, aiming to explore the relationship among P content, starch content, and 100-kernel weight (HKW) of mature grains. A significant negative correlation was found between P content and both starch content and HKW, while starch content showed a positive correlation with HKW. The starch granules in grains with high-P and low-starch content (HPLS) were significantly smaller compared to grains with low-P high-starch content (LPHS). Additionally, mian04185-4 (HPLS) exhibited irregular and loosely packed starch granules. A significant decrease in ZmPHOs genes expression was detected in the HPLS line ZNC442 as compared to the LPHS line SCML0849, while no expression difference was observed in AGPase encoding genes between these two lines. The down-regulated genes in ZNC442 grains were enriched in nucleotide sugar and fatty acid anabolic pathways, while up-regulated genes were enriched in the ABC transporters pathway. An accelerated breakdown of fat as the P content increased was also observed. This implied that HPLS was resulted from elevated lipid decomposition and inadequate carbon sources. The GWAS analysis identified 514 significantly associated genes, out of which 248 were differentially expressed. Zm00001d052392 was found to be significantly associated with P content/HKW, exhibiting high expression in SCML0849 but almost no expression in ZNC442. Overall, these findings suggested new approaches for achieving a P-yield balance through the manipulation of lipid metabolic pathways in grains.
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Fósforo , Almidón , Transcriptoma , Zea mays , Zea mays/genética , Zea mays/metabolismo , Almidón/metabolismo , Fósforo/metabolismo , Grano Comestible/genética , Grano Comestible/metabolismo , Regulación de la Expresión Génica de las Plantas , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , FenotipoRESUMEN
Phosphorus (P) is an essential element for plant growth, and its deficiency can cause decreased crop yield. This study systematically evaluated the low-phosphate (Pi) response traits in a large population at maturity and seedling stages, and explored candidate genes and their interrelationships with specific traits. The results revealed a greater sensitivity of seedling maize to low-Pi stress compared to that at maturity stage. The phenotypic response patterns to low-Pi stress at different stages were independent. Chlorophyll content was found to be a potential indicator for screening low-Pi-tolerant materials in the field. A total of 2900 and 1446 significantly associated genes at the maturity and seedling stages were identified, respectively. Among these genes, 972 were uniquely associated with maturity traits, while 330 were specifically detected at the seedling stage under low-Pi stress. Moreover, 768 and 733 genes were specifically associated with index values (low-Pi trait/normal-Pi trait) at maturity and seedling stage, respectively. Genetic network diagrams showed that the low-Pi response gene Zm00001d022226 was specifically associated with multiple primary P-related traits under low-Pi conditions. A total of 963 out of 2966 genes specifically associated with traits under low-Pi conditions or index values were found to be induced by low-Pi stress. Notably, ZmSPX4.1 and ZmSPX2 were sharply up-regulated in response to low-Pi stress across different lines or tissues. These findings advance our understanding of maize's response to low-Pi stress at different developmental stages, shedding light on the genes and pathways implicated in this response.
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Fenotipo , Fósforo , Plantones , Estrés Fisiológico , Zea mays , Zea mays/genética , Zea mays/crecimiento & desarrollo , Plantones/genética , Plantones/crecimiento & desarrollo , Estrés Fisiológico/genética , Fósforo/metabolismo , Genes de Plantas , Estudio de Asociación del Genoma Completo , Clorofila/metabolismo , Sitios de Carácter Cuantitativo , Regulación de la Expresión Génica de las Plantas , Estudios de Asociación Genética , Polimorfismo de Nucleótido SimpleRESUMEN
Effective emergency responses are crucial for preventing coal mine accidents and mitigating injuries. This paper aims to investigate the characteristics of emergency psychophysiological reactions to coal mine accidents and to explore the potential of key indicators for identifying emergency behavioral patterns. Initially, virtual reality technology facilitated a simulation experiment for emergency escape during coal mine accidents. Subsequently, the characteristics of emergency reactions were analyzed through correlation analysis, hypothesis testing, and analysis of variance. The significant changes in physiological indicators were then taken as input features and fed into the three classifiers of machine learning algorithms. These classifications ultimately led to the identification of behavioral patterns, including agility, defensiveness, panic, and rigidity, that individuals may exhibit during a coal mine accident emergency. The study results revealed an intricate relationship between the mental activities induced by accident stimuli and the resulting physiological changes and behavioral performances. During the virtual reality simulation of a coal mine accident, subjects were observed to experience significant physiological changes in electrodermal activity, heart rate variability, electromyogram, respiration, and skin temperature. The random forest classification model, based on SCR + RANGE + IBI + SDNN + LF/HF, outperformed all other models, achieving accuracies of up to 92%. These findings hold promising implications for early warning systems targeting abnormal psychophysiological and behavioral reactions to emergency accidents, potentially serving as a life-saving measure in perilous situations and fostering the sustainable growth of the coal mining industry.
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Adiponectin is an important adipokine involved in glucose and lipid metabolism, but its secretion and potential role in regulating glucose utilization during ovarian development remains unclear. This study aims to investigate the mechanism and effects of follicle-stimulating hormones (FSHs) on adiponectin secretion and its following impact on glucose transport in the granulosa cells of rat ovaries. A range of experimental techniques were utilized to test our research, including immunoblotting, immunohistochemistry, immunofluorescence, ELISA, histological staining, real-time quantitative PCR, and transcriptome analysis. The immunohistochemistry results indicated that adiponectin was primarily located in the granulosa cells of rat ovaries. In primary granulosa cells cultured in vitro, both Western blot and immunofluorescence assays demonstrated that FSH significantly induced adiponectin secretion within 2 h of incubation, primarily via the PKA signaling pathway rather than the PI3K/AKT pathway. Concurrently, the addition of the AdipoR1/AdipoR2 dual agonist AdipoRon to the culture medium significantly stimulated the protein expression of GLUT1 in rat granulosa cells, resulting in enhanced glucose absorption. Consistent with these in vitro findings, rats injected with eCG (which shares structural and functional similarities with FSH) exhibited significantly increased adiponectin levels in both the ovaries and blood. Moreover, there was a notable elevation in mRNA and protein levels of AdipoRs and GLUTs following eCG administration. Transcriptomic analysis further revealed a positive correlation between the expression of the intraovarian adiponectin system and glucose transporter. The present study represents a novel investigation, demonstrating that FSH stimulates adiponectin secretion in ovarian granulosa cells through the PKA signaling pathway. This mechanism potentially influences glucose transport (GLUT1) and utilization within the ovaries.
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Adiponectina , Hormona Folículo Estimulante , Glucosa , Células de la Granulosa , Receptores de Adiponectina , Transducción de Señal , Animales , Femenino , Adiponectina/metabolismo , Adiponectina/genética , Células de la Granulosa/metabolismo , Células de la Granulosa/efectos de los fármacos , Ratas , Hormona Folículo Estimulante/metabolismo , Glucosa/metabolismo , Receptores de Adiponectina/metabolismo , Receptores de Adiponectina/genética , Células Cultivadas , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 1/genética , Ratas Sprague-Dawley , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Ovario/metabolismo , PiperidinasRESUMEN
PURPOSE: Robotic surgery is becoming increasingly widely used in the field of pediatric surgery. The present study aimed to evaluate the safety and feasibility of robot-assisted resection of benign pediatric splenic tumors and to discuss the technical points. METHODS: A total of 32 patients who were diagnosed with benign splenic tumors and underwent minimally invasive surgery from January 2017 to September 2023 were included in the study. The clinical data including demographic criteria, operative details, and postoperative outcomes were analyzed retrospectively. RESULTS: Thirteen patients underwent robot-assisted surgery, and 19 patients underwent laparoscopic surgery. The median operation time was 150 min, with an interquartile range (IQR) of 120 to 200 min for the robot-assisted group and 140 min with an IQR of 105 to 180 min in the laparoscopic group (P = 0.318). Despite four cases in the laparoscopic group (21%) being converted to laparotomy because of intraoperative bleeding, compared with none in the robot-assisted group, there was no significant difference between two groups (P = 0.128). The intraoperative volume of blood loss was significantly less (P = 0.041), and the hospitalization expense was significantly higher (P = 0.000) in the robot-assisted group than for the laparoscopic group. There was no significant difference in patients' age, tumor size, postoperative feeding time, and the postoperative hospitalization time between two groups (P > 0.05). CONCLUSION: Robot-assisted benign splenic tumor resection was safe and feasible, and it reduced surgical trauma for the pediatric patient.
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Laparoscopía , Procedimientos Quirúrgicos Robotizados , Robótica , Neoplasias del Bazo , Humanos , Niño , Neoplasias del Bazo/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: There are few studies comparing robotic-assisted surgery (RAS) and laparoscopic-assisted surgery (LAS) in Hirschsprung's disease (HSCR). This study aimed to compare intraoperative and postoperative outcomes between RAS and LAS performed during the same period. METHODS: All consecutive 75 patients with pathologically diagnosed as HSCR who underwent Swenson pull-through surgery from April 2020 to Nov 2022, were included. Patients were divided into RAS group and LAS group and a retrospective analysis was performed based on clinical indexes and prognosis. RESULTS: A total of 75 patients were included, among which, 31 patients received RAS and 44 received LAS. The RAS and LAS groups had similar ages, sex, weight, postoperative hospital stays, and fasting times. Compared with LAS, blood loss (p = 0.002) and the incidence of Hirschsprung-associated enterocolitis (p = 0.046) were significantly lower in the RAS group. The first onset of Hirschsprung-associated enterocolitis in patients younger than 3 months occurred significantly earlier (p = 0.043). Two patients experienced anastomotic leakage in the LAS group and one patient experienced incisional hernia in the RAS group. The cost of RAS was significantly higher than that of LAS (p < 0.0001). CONCLUSIONS: RAS is a safe and effective alternative for HSCR children, and a delaying primary surgery until later in infancy (> 3 months) may improve outcomes.
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Enterocolitis , Enfermedad de Hirschsprung , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Humanos , Niño , Lactante , Enfermedad de Hirschsprung/cirugía , Enfermedad de Hirschsprung/complicaciones , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Laparoscopía/efectos adversos , Enterocolitis/etiología , Enterocolitis/cirugía , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
Molecular structures are commonly depicted in 2D printed forms in scientific documents such as journal papers and patents. However, these 2D depictions are not machine readable. Due to a backlog of decades and an increasing amount of printed literatures, there is a high demand for translating printed depictions into machine-readable formats, which is known as Optical Chemical Structure Recognition (OCSR). Most OCSR systems developed over the last three decades use a rule-based approach, which vectorizes the depiction based on the interpretation of vectors and nodes as bonds and atoms. Here, we present a practical software called MolMiner, which is primarily built using deep neural networks originally developed for semantic segmentation and object detection to recognize atom and bond elements from documents. These recognized elements can be easily connected as a molecular graph with a distance-based construction algorithm. MolMiner gave state-of-the-art performance on four benchmark data sets and a self-collected external data set from scientific papers. As MolMiner performed similarly well in real-world OCSR tasks with a user-friendly interface, it is a useful and valuable tool for daily applications. The free download links of Mac and Windows versions are available at https://github.com/iipharma/pharmamind-molminer.
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Algoritmos , Programas Informáticos , Estructura Molecular , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: Multiple magnetic foreign body ingestion in children is increasingly common and can cause serious injury. The present study aimed to analyze the clinical features of such cases and summarize treatment experiences. METHODS: A retrospective survey of 91 patients in the Children's Hospital, Zhejiang University School of Medicine with magnetic foreign body ingestion from October 2018 to October 2021 was performed, the data were collected including the clinical information of the patients, treatment details, and prognosis. RESULTS: Twenty-two (24.2%) patients were conservatively treated, with the foreign bodies discharged through the anus, 31 (34.1%) underwent laparoscopic surgery, including 18 cases converting from laparoscopic surgery to laparotomy, and 38 (41.8%) underwent laparotomy. In 13 (14.3%) patients, the foreign bodies were partially removed by gastroscope. The remaining foreign bodies were removed by laparoscopy in six patients, including three cases converting from laparoscopy to laparotomy, by laparotomy in four patients, and by conservative treatment in three patients. CONCLUSIONS: Multiple magnetic foreign body ingestion can cause significant harm to patients and different clinical techniques must be used for patients in different situations to reduce the harm to children.
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Cuerpos Extraños , Niño , Ingestión de Alimentos , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugía , Humanos , Laparotomía/métodos , Fenómenos Magnéticos , Estudios RetrospectivosRESUMEN
BACKGROUND: Occult metastases in axillary lymph nodes have been reported to be associated with poor prognosis in patients with breast cancer. However, studies on the prognostic value of occult metastases have shown controversial results. This meta-analysis aimed to evaluate the prognostic significance of occult lymph node metastases in breast cancer. METHODS: Studies published until May, 2020, which retrospectively examined negative lymph nodes by stepsectioning and/or immunohistochemistry, were retrieved from MEDLINE, EMBASE, CNKI, and Cochrane Library databases. The pooled Relative Risk (RR) with 95% confidence interval (95% CI) for overall survival (OS) and disease-free survival (DFS) were calculated to examine the associations between occult metastases and prognosis. RESULTS: Patients with occult metastases in axillary lymph nodes had poorer five-year DFS (RR = 0.930; 95% CI = 0.907-0.954) and OS (RR = 0.972; 95% CI = 0.954-0.990). Furthermore, the DFS (RR = 0.887; 95% CI = 0.810-0.972) and OS (RR = 0.896; 95% CI = 0.856-0.939) of patients with occult metastases were significantly lower after a ten-year follow-up. CONCLUSIONS: Occult metastases in the axillary lymph nodes are associated with poorer DFS andOS of patients with breast cancer. Occult metastases might serve as a predictive factor of survival outcomes in patients with breast cancer.
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Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Axila/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática , Pronóstico , Sesgo de Publicación , Recurrencia , RiesgoRESUMEN
BACKGROUND: The objective of this study is to quantify the prevalence and describe the utilization of an anatomic vascular variant in which the obturator artery (OA) arises from the trunk of the deep inferior epigastric artery (DIEA) in stacked/dual-pedicled autologous breast reconstruction. When this variant is identified preoperatively on computed tomography angiography (CTA), it may be utilized in a "flow-through" fashion to direct antegrade internal mammary artery (IMA) flow into a second free flap to facilitate anastomotic arrangement and optimize perfusion. METHODS: Preoperatively obtained abdomen/pelvis CTA imaging of 121 autologous breast reconstruction patients were retrospectively reviewed for the unilateral or bilateral presence of the OA branch arising from the DIEA (OA variant). The results were analyzed using descriptive statistics. RESULTS: Our analysis revealed the presence of the OA variant in 60 of the 121 (49.6%) breast reconstruction candidates, either unilaterally or bilaterally. Out of these patients, the variant was present unilaterally in 33 (55%) and bilaterally in 27 (45%) patients. Of the unilateral variants, 12 (36.4%) patients demonstrated right-sided laterality, while 21 (63.6%) patients demonstrated left-sided laterality. Clinically, this anatomic variant has been utilized in several cases of autologous breast reconstruction with flap survival in all cases. CONCLUSION: Utilization of this anatomic variant in stacked or dual-pedicled autologous breast reconstruction results in antegrade IMA perfusion of both primary and secondary flaps, as well as improved size match compared with other anastomotic options. Knowledge of the vascular anatomy and variations in the inferior epigastric system is crucial to both preventing complications and optimizing flap planning and outcome.
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Mamoplastia , Colgajo Perforante , Abdomen , Arterias Epigástricas/diagnóstico por imagen , Arterias Epigástricas/cirugía , Humanos , Pelvis , Prevalencia , Estudios RetrospectivosRESUMEN
Light hydrocarbons (C1 -C3 ) are used as basic energy feedstocks and as commodity organic compounds for the production of many industrially necessary chemicals. Due to the nature of the raw materials and production processes, light hydrocarbons are generated as mixtures, but the high-purity single-component products are of vital importance to the petrochemical industry. Consequently, the separation of these C1 -C3 products is a crucial industrial procedure that comprises a significant share of the total global energy consumption per year. As a complement to traditional separation methods (distillation, partial hydrogenation, etc.), adsorptive separations using porous solids have received widespread attention due to their lower energy costs and higher efficiency. Extensive research has been devoted to the use of porous materials such as zeolites and metal-organic frameworks (MOFs) as solid adsorbents for these key separations, owing to the high porosity, tunable pore structures, and unsaturated metal sites present in these materials. Recently, porous organic framework (POF) materials composed of organic building blocks linked by covalent bonds have also shown excellent properties in light hydrocarbon adsorption and separation, sparking interest in the use of these materials as adsorbents in separation processes. This Minireview summarizes the recent advances in the use of POFs for light hydrocarbon separations, including the separation of mixtures of methane/ethane, methane/propane, ethylene/ethane, acetylene/ethylene, and propylene/propane, while highlighting the relationships between the structural features of these materials and their separation performances. Finally, the difficulties, challenges, and opportunities associated with leveraging POFs for light hydrocarbon separations are discussed to conclude the review.
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Bioactive peptides derived from proteins generally need to be folded into secondary structures to activate downstream signaling pathways. However, synthetic peptides typically form random-coils, thus losing their bioactivities. Here, we show that by introducing a self-assembling peptide motif and using different preparation pathways, a peptide from insulin-like growth factor-I (IGF-1) can be folded into an α-helix and ß-sheet. The ß-sheet one exhibits a low dissociation constant to the IGF-1 receptor (IGF-1R, 11.5 nM), which is only about 3 times higher than that of IGF-1 (4.3 nM). However, the α-helical one and the peptide without self-assembling motif show weak affinities to IGF-1R ( KD = 179.1 and 321.6 nM, respectively). At 10 nM, the ß-sheet one efficiently activates the IGF-1 downstream pathway, significantly enhancing HUVEC proliferation and preventing cell apoptosis. The ß-sheet peptide shows superior performance to IGF-1 in vivo, and it improves ischemic hind-limb salvage by significantly reducing muscle degradation and enhancing limb vascularization. Our study provides a useful strategy to constrain peptides into different conformations, which may lead to the development of supramolecular nanomaterials mimicking biofunctional proteins.