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SNX32 is a member of the evolutionarily conserved Phox (PX) homology domain- and Bin/Amphiphysin/Rvs (BAR) domain- containing sorting nexin (SNX-BAR) family of proteins, which play important roles in sorting and membrane trafficking of endosomal cargoes. Although SNX32 shares the highest amino acid sequence homology with SNX6, and has been believed to function redundantly with SNX5 and SNX6 in retrieval of the cation-independent mannose-6-phosphate receptor (CI-MPR) from endosomes to the trans-Golgi network (TGN), its role(s) in intracellular protein trafficking remains largely unexplored. Here, we report that it functions in parallel with SNX1 in mediating epidermal growth factor (EGF)-stimulated postendocytic trafficking of the epidermal growth factor receptor (EGFR). Moreover, SNX32 interacts directly with EGFR, and recruits SNX5 to promote sorting of EGF-EGFR into multivesicular bodies (MVBs) for lysosomal degradation. Thus, SNX32 functions distinctively from other SNX-BAR proteins to mediate signaling-coupled endolysosomal trafficking of EGFR.
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Factor de Crecimiento Epidérmico , Receptores ErbB , Lisosomas , Transporte de Proteínas , Nexinas de Clasificación , Nexinas de Clasificación/metabolismo , Nexinas de Clasificación/genética , Receptores ErbB/metabolismo , Lisosomas/metabolismo , Humanos , Transporte de Proteínas/fisiología , Factor de Crecimiento Epidérmico/metabolismo , Células HeLa , Endosomas/metabolismo , Red trans-Golgi/metabolismo , Cuerpos Multivesiculares/metabolismoRESUMEN
Splicing factors (SFs) are the major RNA-binding proteins (RBPs) and key molecules that regulate the splicing of mRNA molecules through binding to mRNAs. The expression of splicing factors is frequently deregulated in different cancer types, causing the generation of oncogenic proteins involved in cancer hallmarks. In this study, we investigated the genes that encode RNA-binding proteins and identified potential splicing factors that contribute to the aberrant splicing applying a random forest classification model. The result suggested 56 splicing factors were related to the prognosis of 13 cancers, two SF complexes in liver hepatocellular carcinoma, and one SF complex in esophageal carcinoma. Further systematic bioinformatics studies on these cancer prognostic splicing factors and their related alternative splicing events revealed the potential regulations in a cancer-specific manner. Our analysis found high ILF2-ILF3 expression correlates with poor prognosis in LIHC through alternative splicing. These findings emphasize the importance of SFs as potential indicators for prognosis or targets for therapeutic interventions. Their roles in cancer exhibit complexity and are contingent upon the specific context in which they operate. This recognition further underscores the need for a comprehensive understanding and exploration of the role of SFs in different types of cancer, paving the way for their potential utilization in prognostic assessments and the development of targeted therapies.
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Empalme Alternativo , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Aprendizaje Automático , Neoplasias , Factores de Empalme de ARN , Humanos , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo , Pronóstico , Empalme Alternativo/genética , Neoplasias/genética , Biología Computacional/métodos , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Empalme del ARN/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/genéticaRESUMEN
Rapid visualization of latent fingerprints, preferably at their point of origin, is essential for effective crime scene evaluation. Here, we present a new class of green fluorescent protein chromophore-based fluorescent dyes (LFP-Yellow and LFP-Red) that can be used for real-time visualization of LFPs within 10 s. Compared with traditional chemical reagents for LFPs, these fluorescent dyes are completely water-soluble, exhibit low cytotoxicity, and are harmless to users. Level 1-3 details of the LFPs could be clearly revealed through "off-on" fluorescence signal readout. Additionally, the fluorescent dyes were constructed based on an imidazolinone core and so do not contain pyridine groups or metal ions, which ensures that the DNA is not contaminated during extraction and identification after the LFPs are treated with the dyes. Combined with our as-developed portable system for capturing LFPs, LFP-Yellow and LFP-Red enabled the rapid capture of LFPs. Therefore, these green fluorescent protein chromophore-based probes provide an approach for the rapid identification of individuals who were present at a crime scene.
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Colorantes Fluorescentes , Humanos , Proteínas Fluorescentes Verdes , FluorescenciaRESUMEN
Biomolecule-functionalized nanoparticles represent a type of promising biomaterials in biomedical applications owing to their excellent biocompatibility and versatility. DNA-based reactions on nanoparticles have enabled emerging applications including intelligent biosensors, drug delivery, and biomimetic devices. Among the reactions, strand hybridization is the critical step to control the sensitivity and specificity of biosensing, and the efficiency of drug delivery. However, a comprehensive understanding of DNA hybridization on nanoparticles is still lacking, which may differ from the process in homogeneous solutions. To address this limitation, coarse-grained model-based molecular dynamic simulation is harnessed to disclose the critical factors involved in intermolecular hybridization. Based on simulation guidance, DNA walker-based smart theranostic platform (DWTP) based on "on-particle" hybridization is developed, showing excellent consistency with simulation. DWTP is successfully applied for highly sensitive miRNA 21 detection and tumor-specific miRNA 21 imaging, driven by tumor-endogenous APE 1 enzyme. It enables the precise release of antisense oligonucleotide triggered by tumor-endogenous dual-switch miRNA 21 and APE 1, facilitating effective gene silencing therapy with high biosafety. The simulation of "on-particle" DNA hybridization has improved the corresponding biosensing performance and the release efficiency of therapeutic agents, representing a conceptually new approach for DNA-based device design.
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ADN , MicroARNs , Nanomedicina Teranóstica , ADN/química , Nanomedicina Teranóstica/métodos , Humanos , Hibridación de Ácido Nucleico , Nanopartículas/química , Simulación de Dinámica Molecular , Técnicas Biosensibles/métodosRESUMEN
The polar auxin transport is required for proper plant growth and development. D6 PROTEIN KINASE (D6PK) is required for the phosphorylation of PIN-FORMED (PIN) auxin efflux carriers to regulate auxin transport, while the regulation of D6PK stabilization is still poorly understood. Here, we found that Cytosolic ABA Receptor Kinases (CARKs) redundantly interact with D6PK, and the interactions are dependent on CARKs' kinase activities. Similarly, CARK3 also could interact with paralogs of D6PK, including D6PKL1, D6PKL2, and D6PKL3. The genetic analysis shows that D6PK acts the downstream of CARKs to regulate Arabidopsis growth, including hypocotyl, leaf area, vein formation, and the length of silique. Loss-of-function of CARK3 in overexpressing GFP-D6PK plants leads to reduce the level of D6PK protein, thereby rescues plant growth. In addition, the cell-free degradation assays indicate that D6PK is degraded through 26 S proteasome pathway, while the phosphorylation by CARK3 represses this process in cells. In summary, D6PK stabilization by the CARK family is required for auxin-mediated plant growth and development.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/crecimiento & desarrollo , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/enzimología , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Fosforilación , Ácidos Indolacéticos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Citosol/metabolismo , Ácido Abscísico/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas Quinasas/metabolismo , Proteínas Quinasas/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Plantas Modificadas GenéticamenteRESUMEN
A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX. Moreover, compound 9o exhibited superior antitumor activities against breast cancer cells under hypoxia than that of normoxia conditions. Mechanism studies revealed that compound 9o could act as DNA intercalator and effectively suppressed cell migration, arrested the cell cycle at G1/S phase and induced apoptosis in MDA-MB-231 cells, while inducing ferroptosis accompanied by the dissipation of MMP and the elevation intracellular levels of ROS. Notably, in vivo studies demonstrated that 9o effectively inhibited tumor growth and metastasis in a highly metastatic murine breast cancer 4 T1 xenograft model. Taken together, this study suggests that compound 9o represents a potent and selective CA IX inhibitor and ferroptosis inducer for the treatment of TNBC.
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Antineoplásicos , Bencenosulfonamidas , Anhidrasa Carbónica IX , Inhibidores de Anhidrasa Carbónica , Proliferación Celular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Ferroptosis , Naftalimidas , Sulfonamidas , Neoplasias de la Mama Triple Negativas , Humanos , Anhidrasa Carbónica IX/antagonistas & inhibidores , Anhidrasa Carbónica IX/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Inhibidores de Anhidrasa Carbónica/farmacología , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/síntesis química , Ferroptosis/efectos de los fármacos , Sulfonamidas/farmacología , Sulfonamidas/química , Sulfonamidas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Animales , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Ratones , Femenino , Naftalimidas/química , Naftalimidas/farmacología , Naftalimidas/síntesis química , Descubrimiento de Drogas , Apoptosis/efectos de los fármacos , Simulación del Acoplamiento Molecular , Piperazinas/farmacología , Piperazinas/química , Piperazinas/síntesis química , Línea Celular Tumoral , Antígenos de NeoplasiasRESUMEN
The proliferation of nitrile mixtures has significantly exacerbated environmental pollution. This study employed metagenomic analysis to investigate the short-term effects of nitrile mixtures on soil microbial communities and their metabolic functions. It also examined the responses of indigenous microorganisms and their functional metabolic genes across various land use types to different nitrile stressors. The nitrile compound treatments in this study resulted in an increase in the abundance of Proteobacteria, Actinobacteria, and Firmicutes, while simultaneously reducing overall microbial diversity. The key genes involved in the denitrification process, namely, nirK, nosZ, and hao, were down-regulated, and NO3--N, NO2--N, and NH4+-N concentrations decreased by 7.7%-12.3%, 11.1%-21.3%, and 11.3%-30.9%, respectively. Notably, pond sludge samples exhibited a significant increase in the abundance of nitrogen fixation-related genes nifH, vnfK, vnfH, and vnfG following exposure to nitrile compounds. Furthermore, the fumarase gene fumD, which is responsible for catalyzing fumaric acid into malic acid in the tricarboxylic acid cycle, showed a substantial increase of 7.2-10.6-fold upon nitrile addition. Enzyme genes associated with the catechol pathway, including benB-xylY, dmpB, dmpC, dmpH, and mhpD, displayed increased abundance, whereas genes related to the benzoyl-coenzyme A pathway, such as bcrA, dch, had, oah, and gcdA, were notably reduced. In summary, complex nitrile compounds were found to significantly reduce the species diversity of soil microorganisms. Nitrile-tolerant microorganisms demonstrated the ability to degrade and adapt to nitrile pollutants by enhancing functional enzymes involved in the catechol pathway and fenugreek conversion pathway. This study offers insights into the specific responses of microorganisms to compound nitrile contamination, as well as valuable information for screening nitrile-degrading microorganisms and identifying nitrile metabolic enzymes.
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The intentional binding effect refers to the phenomenon where the perceived temporal interval between a voluntary action and its sensory consequence is subjectively compressed. Prior research revealed the importance of tactile feedback from the keyboard on this effect. Here we examined the necessity of such tactile feedback by utilizing a touch-free key-press device without haptic feedback, and explored how initial/outcome sensory modalities (visual/auditory/tactile) and their consistency influence the intentional binding effect. Participants estimated three delay lengths (250, 550, or 850 ms) between the initial and outcome stimuli. Results showed that regardless of the combinations of sensory modalities between the initial and the outcome stimuli (i.e., modal consistency), the intentional binding effect was only observed in the 250 ms delay condition. This findings indicate a stable intentional binding effect both within and across sensory modalities, supporting the existence of a shared mechanism underlying the binding effect in touch-free voluntary actions.
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Retroalimentación Sensorial , Intención , Desempeño Psicomotor , Percepción del Tacto , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Percepción del Tacto/fisiología , Retroalimentación Sensorial/fisiología , Desempeño Psicomotor/fisiología , Percepción Visual/fisiología , Percepción del Tiempo/fisiología , Percepción Auditiva/fisiología , Volición/fisiologíaRESUMEN
BACKGROUND: With the improvements in laparoscopic or robotic surgical techniques and instruments, a growing number of surgeons have attempted to complete all digestive tract reconstruction intracorporeally; these procedures include totally robotic gastrectomy (TRG) and totally laparoscopic gastrectomy (TLG). This study aimed to evaluate the safety and feasibility of the TRG and compare the short-term outcomes of the TRG and TLG in patients with gastric cancer. METHODS: Between January 2018 and June 2023, 346 consecutive patients who underwent TRG or TLG at a high-volume academic gastric cancer specialty center were included. 1:1 propensity score matching (PSM) was performed to reduce confounding bias. The surgical outcomes, postoperative morbidity, and surgical burden were compared in PSM cohort. RESULTS: After PSM, a well-balanced cohort of 194 patients (97 in each group) was included in the analysis. The total operation time of the TRG group was significantly longer than that of the TLG group (244.9 vs. 213.0 min, P < 0.001). There was no significant difference in the effective operation time between the 2 groups (217.8 vs. 207.2 min, P = 0.059). The digestive tract reconstruction time of the TRG group was significantly shorter than that of the TLG group (39.4 vs. 46.7 min, P < 0.001). The mean blood loss in the TRG group was less than that in the TLG group (101.1 vs. 126.8 mL, P = 0.014). The TRG group had more retrieved lymph nodes in the suprapancreatic area than that in the TLG group (16.6 vs 14.2, P = 0.002). The TRG group had a lower surgery task load index (38.9 vs. 43.1, P < 0.001) than the TLG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.4% vs. 16.5%, P = 0.691). CONCLUSION: This study demonstrated that TRG is a safe and feasible procedure, and is preferable to TLG in terms of invasion and ergonomics. The TRG may maximize the superiority of robotic surgical systems and embodies the theory of minimally invasive surgery.
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Gastrectomía , Laparoscopía , Tempo Operativo , Puntaje de Propensión , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Gastrectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Laparoscopía/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Estudios de Factibilidad , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
Cervical cancer (CC) is a gynaecological malignancy tumour that seriously threatens women's health. Recent evidence has identified that interferon regulatory factor 5 (IRF5), a nucleoplasm shuttling protein, is a pivotal transcription factor regulating the growth and metastasis of various human tumours. This study aimed to investigate the function and molecular basis of IRF5 in CC development. IRF5, protein phosphatase 6 catalytic subunit (PPP6C) and methyltransferase-like 3 (METTL3) mRNA levels were evaluated by quantitative real-time (qRT)-polymerase chain reaction (PCR). IRF5, PPP6C, METTL3, B-cell lymphoma 2 and Bax protein levels were detected using western blot. Cell proliferation, migration, invasion, angiogenesis and apoptosis were determined by using colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, tube formation assay and flow cytometry assay, respectively. Glucose uptake and lactate production were measured using commercial kits. Xenograft tumour assay in vivo was used to explore the role of IRF5. After JASPAR predication, binding between IRF5 and PPP6C promoter was verified using chromatin immunoprecipitation and dual-luciferase reporter assays. Moreover, the interaction between METTL3 and IRF5 was verified using methylated RNA immunoprecipitation (MeRIP). IRF5, PPP6C and METTL3 were highly expressed in CC tissues and cells. IRF5 silencing significantly inhibited cell proliferation, migration, invasion, angiogenesis and glycolytic metabolism in CC cells, while induced cell apoptosis. Furthermore, the absence of IRF5 hindered tumour growth in vivo. At the molecular level, IRF5 might bind with PPP6C to positively regulate the expression of PPP6C mRNA. Meanwhile, IRF5 was identified as a downstream target of METTL3-mediated m6A modification. METTL3-mediated m6A modification of mRNA might promote CC malignant progression by regulating PPP6C, which might provide a promising therapeutic target for CC treatment.
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Proliferación Celular , Factores Reguladores del Interferón , Metiltransferasas , Fosfoproteínas Fosfatasas , Regulación hacia Arriba , Neoplasias del Cuello Uterino , Animales , Femenino , Humanos , Ratones , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Ratones Desnudos , Invasividad Neoplásica , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Neovascularización Patológica/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Fosfoproteínas Fosfatasas/genética , Fosfoproteínas Fosfatasas/metabolismoRESUMEN
BACKGROUND: Since May 2022, mpox outbreaks have been occurring in non-mpox endemic areas, with the main population affected being men who have sex with men (MSM). Outbreak prevention and control depend not only on the effectiveness of vaccines but also on people's willingness to receive these vaccines. Currently, there is lack of synthesis on the overall rates and influence factors of MSMs' willingness to vaccinate against mpox. Therefore, we systematically reviewed studies that assessed the willingness of MSM to receive mpox vaccine. METHODS: Studies reporting mpox vaccination intentions among MSM were included by searching five databases (PubMed, Web of Science, EMBASE, CINAHL, and SCOPUS) from inception to May 12, 2024. The quality of the included literature was assessed using Joanna Briggs Institute's critical appraisal tool. The data analysis software is Stata17. The systematic review has been registered with Prospero (registration ID: CRD42023452357). RESULTS: Twenty cross-sectional studies were included in the review. Meta-analysis results showed that the pooled willingness rate of vaccinate against mpox was 77.0% (95% CI: 73-81%, I2 = 99.4%). According to subgroup analysis, study countries (P = 0.002), research sample size (P = 0.001), and whether participants were infected with HIV (P = 0.002) may be sources of heterogeneity. The results of the meta-analysis of influencing factors showed that more number of sexual partners (OR: 2.24, 95%CI: 1.86-2.69), pre-exposure prophylaxis use (OR: 6.04, 95%CI: 4.80-7.61), history of sexually transmitted infections (OR: 2.96, 95%CI: 2.33-3.76), confidence in the vaccine's effectiveness (OR: 2.79, 95%CI: 2.04-3.80) and safety (OR: 10.89, 95%CI: 5.22-22.72), fear of mpox infection (OR: 2.47, 95%CI: 2.11-2.89) and epidemics (OR: 2.87, 95%CI: 2.22-3.70), high mpox knowledge (OR: 2.35, 95%CI: 1.51-3.66), and the belief that people at high risk should be prioritized for vaccination (OR: 3.09, 95%CI: 1.40-6.84) were the facilitators of vaccine willingness. In addition, as a secondary outcome, meta-analysis results showed a pooled unwillingness rate of 16% (95% CI: 13-20%, I2 = 98.1%, 9 studies). CONCLUSION: Willingness to vaccinate mpox was high among MSM, but some participants still had negative attitudes towards vaccination. Therefore, the Ministry of Public Health should develop targeted and effective strategies against those influencing factors to prevent and manage mpox outbreaks.
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Homosexualidad Masculina , Humanos , Masculino , Homosexualidad Masculina/psicología , Homosexualidad Masculina/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicologíaRESUMEN
Background: Deep vein thrombosis is a common complication after surgery, particularly in cancer patients, necessitating efficient diagnostic methods for timely intervention. Objective: This study aimed to investigate the potential of combining C-reactive protein (CRP) and interleukin-6 (IL-6) tests in diagnosing deep vein thrombosis (DVT) following endometrial cancer surgery. Methods: A cohort of 60 patients who developed DVT post-endometrial cancer surgery and were admitted to the First Hospital of Hebei Medical University between March 2018 and March 2022 constituted the DVT group. Additionally, 60 patients who underwent endometrial cancer surgery during the same period but did not develop DVT formed the non-DVT group. Serum levels of CRP and IL-6 were quantified and compared between the two groups using reliable laboratory techniques. Subsequently, the diagnostic accuracy of single-parameter testing (CRP or IL-6 alone) versus combined testing (CRP and IL-6) for postoperative DVT was assessed. Results: Analysis revealed significantly elevated levels of CRP and IL-6 in the serum of patients in the DVT group compared to those in the non-DVT group (P < .05). Furthermore, combined testing of CRP and IL-6 exhibited heightened sensitivity (0.85%), specificity (0.917%), and area under the curve (AUC) (0.952) compared to single-parameter testing alone, indicating its superiority in diagnosing postoperative DVT. Conclusions: The combination of CRP and IL-6 testing presents a promising diagnostic strategy for identifying postoperative DVT in endometrial cancer patients. Implementing this approach in clinical practice could facilitate early detection and prompt management of DVT, thereby potentially reducing associated morbidity and mortality.
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Objective: Investigating the application effectiveness of using loop-mediated isothermal amplification (LAMP) on a microfluidic chip to detect the pathogens associated with ventilator-associated pneumonia (VAP). Methods: Eighty samples of bronchoalveolar lavage fluid from patients with ventilator-associated pneumonia (VAP) were collected at The First Hospital of Hebei Medical University from July 2022 to July 2023. The bacterial culture technique and the LAMP method were used to detect the nucleic acid of the pathogens in the patient samples. The positivity rates of bacterial culture and LAMP method in detecting VAP pathogens were analyzed. Results: A total of 80 specimens were examined, with 73 positive specimens detected using the LAMP method (positivity rate of 91.25%) and 60 positive specimens detected using bacterial culture (positivity rate of 75.00%). The LAMP method exhibited a higher number of positive detections compared to bacterial culture. Both methods showed a high level of concordance and were virtually identical in detecting methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterobacter aerogenes, Haemophilus influenzae, and Streptococcus pneumoniae. Conclusion: The LAMP method demonstrates significantly improved performance in the detection of pathogens for VAP, with a higher pathogen positivity rate compared to bacterial culture. This method holds promising prospects for clinical application.
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Erianin, a bibenzyl compound found in dendrobium extract, has demonstrated broad anticancer activity. However, its mechanism of action in gastric cancer (GC) remains poorly understood. LKB1 is a tumor-suppressor gene, and its mutation is an important driver of various cancers. Yet some studies have reported contradictory findings. In this study, we combined bioinformatics and in vitro and in vivo experiments to investigate the effect and potential mechanism of Erianin in the treatment of GC. The results show that LKB1 was highly expressed in patients' tumor tissues and GC cells, and it was associated with poor patient prognosis. Erianin could promote GC cell apoptosis and inhibit the scratch repair, migration, invasion, and epithelial-mesenchymal transition (EMT) characteristics. Erianin dose-dependently inhibited the expression of LKB1, SIK2, SIK3, and PARD3 but had no significant effect on SIK1. Erianin also inhibited tumor growth in CDX mice model. Unexpectedly, 5-FU also exhibited a certain inhibitory effect on LKB1. The combination of Erianin and 5-FU significantly improved the anti-tumor efficacy of 5-FU in the growth of GC cells and xenograft mouse models. In summary, Erianin is a potential anti-GC compound that can inhibit GC growth and EMT properties by targeting the LKB1-SIK2/3-PARD3-signaling axis. The synergistic effect of Erianin and 5-FU suggests a promising therapeutic strategy for GC treatment.
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Quinasas de la Proteína-Quinasa Activada por el AMP , Bibencilos , Proliferación Celular , Dendrobium , Transición Epitelial-Mesenquimal , Proteínas Serina-Treonina Quinasas , Neoplasias Gástricas , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Dendrobium/química , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Animales , Bibencilos/farmacología , Bibencilos/química , Ratones , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , FenolRESUMEN
To investigate the effect of active immunisation with gonadotropin-releasing hormone (GnRH) on the reproductive function in male Sprague Dawley (SD) rats, 24 42-day-old rats were randomly assigned to treatment with GnRH6-MAP, GnRH-OVA, a surgical castration group, and a blank control group. Each rat in the treatment groups was intramuscularly injected at 6, 8, and 10 weeks of age. The serum concentrations of testosterone (T), follicle-stimulating hormone (FSH), luteinising hormone (LH), and anti-GnRH antibodies were determined using enzyme-linked immunosorbent assays. The results showed that active immunisation with recombinant GnRH6-MBP and GnRH-OVA significantly increased the serum levels of anti-GnRH antibodies and reduced the serum concentrations of testosterone compared to the black control. Eight weeks after immunisation, the rats' testes were surgically removed for morphological evaluation, showing atrophy of the convoluted vasculature, relative emptying of the lumen, and insignificant differentiation of spermatogonial cells, which were increased in weight and volume compared with the blank control group. These findings indicated that active immunisation with GnRH can lead to testicular atrophy and reduce gonadal hormone concentrations, suggesting that GnRH is a highly effective immunogen.
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Hormona Folículo Estimulante , Hormona Liberadora de Gonadotropina , Masculino , Ratas , Animales , Ratas Sprague-Dawley , Vacunación , Testosterona , Anticuerpos , AtrofiaRESUMEN
Rice (Oryza sativa) is a significant crop worldwide with a genome shaped by various evolutionary factors. Rice centromeres are crucial for chromosome segregation, and contain some unreported genes. Due to the diverse and complex centromere region, a comprehensive understanding of rice centromere structure and function at the population level is needed. We constructed a high-quality centromere map based on the rice super pan-genome consisting of a 251-accession panel comprising both cultivated and wild species of Asian and African rice. We showed that rice centromeres have diverse satellite repeat CentO, which vary across chromosomes and subpopulations, reflecting their distinct evolutionary patterns. We also revealed that long terminal repeats (LTRs), especially young Gypsy-type LTRs, are abundant in the peripheral CentO-enriched regions and drive rice centromere expansion and evolution. Furthermore, high-quality genome assembly and complete telomere-to-telomere (T2T) reference genome enable us to obtain more centromeric genome information despite mapping and cloning of centromere genes being challenging. We investigated the association between structural variations and gene expression in the rice centromere. A centromere gene, OsMAB, which positively regulates rice tiller number, was further confirmed by expression quantitative trait loci, haplotype analysis and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 methods. By revealing the new insights into the evolutionary patterns and biological roles of rice centromeres, our finding will facilitate future research on centromere biology and crop improvement.
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ADN Satélite , Oryza , ADN Satélite/metabolismo , Oryza/genética , Oryza/metabolismo , Secuencia de Bases , Centrómero/genética , Genoma de Planta/genéticaRESUMEN
BACKGROUND: This study aimed to analyse the expression of microRNA-223 (miR-223) in embryo culture medium and its correlation with pregnancy outcomes. METHODS: Two hundred and two patients undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) were divided into clinical pregnancy group (n = 101) and non-pregnant group (n = 101). The baseline data, clinical indicators, and the expression level of miR-223 in the embryo medium were compared between the two groups. Logistic regression analysis was used to analyse the relationship between each index and the pregnancy outcome. Receiver operator characteristic curve was carried out to evaluate the differential ability of miR-223 in pregnancy status. Bioinformatics methods were used to identify the target genes of miR-223 and elucidate their functions. RESULTS: Compared with pregnancy group, the non-pregnancy group exhibited a reduction in miR-223 expression (p < 0.001). Multivariate analysis revealed that miR-223 reduction was an independent factor for pregnancy failure (p < 0.05). The ROC curve demonstrated the discriminative capability of miR-223 in distinguishing pregnancy and non-pregnancy. In addition, bioinformatics analysis indicated that the target genes of miR-223 were predominantly located in the endocytic vesicle membrane and were primarily enriched in adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathways. CONCLUSION: In this study, levels of miR-223 in the embryo culture medium predicted pregnancy outcomes in subjects undergoing IVF/ICSI. Low expression of miR-223 was a risk factor for adverse pregnancy outcomes in subjects.
In this study, 202 patients who underwent IVF/ICSI were retrospectively analysed and categorised into pregnant and non-pregnant groups based on their pregnancy status. The examination of embryo culture medium samples from both groups revealed that the non-pregnant group exhibited lower miR-223 expression compared to the pregnant group. Subsequent ROC analysis demonstrated the clinical relevance of miR-223 in effectively distinguishing between pregnant and non-pregnant states. Multi-factor analysis further established that the diminished expression of miR-223 independently influenced the likelihood of successful pregnancy.
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Fertilización In Vitro , MicroARNs , Resultado del Embarazo , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Femenino , Embarazo , MicroARNs/genética , MicroARNs/metabolismo , Adulto , Fertilización In Vitro/métodos , Pronóstico , Curva ROC , Técnicas de Cultivo de EmbrionesRESUMEN
Electromagnetic radiation (EM) pollution has a certain impact on human life and health, and the reconstruction of the EM space field in this paper is of great practical significance for EM analysis and research. The radial basis function (RBF) sufficiently considers the influence of each sampling point and is more suitable for reconstructing the EM space field than other spatial interpolation methods. Currently, when RBF is used to reconstruct the EM space field, the optimal determination of the basis function and shape parameter (SP) is rarely considered. This ultimately leads to low reconstruction accuracy of the EM space field. Therefore, in this paper, the particle swarm optimization (PSO) is used to calculate the optimal SP of the RBF. On this basis, reliable EM space field reconstruction is performed, which helps people understand the EM distribution characteristics in actual situations from a visual perspective. The EM sampling data of a region on the Yunnan Normal University campus are used as the data source, and the RBF under the optimal parameters is used for EM reconstruction. The accuracy of its interpolation results is evaluated and compared and analyzed with inverse distance weighting (IDW) after distance index optimization. The results show that the RBF under optimal parameters reconstructs the EM space field with high accuracy and good effect, which can truly reflect the actual distribution of EM.
Electromagnetic radiation (EM) pollution has a great impact on the surrounding environment. Therefore, EM space field reconstruction can help us analyze the characteristics of the electromagnetic environment in a visual way. Radial Basis Function (RBF) is a method more suitable for EM space field reconstruction than other methods because it fully considers the influence of each sampling point. However, when currently using RBF to reconstruct the EM space field, few researchers consider how to choose the most appropriate basis function and shape parameter (SP). This results in low reconstruction accuracy. Therefore, this study uses particle swarm optimization (PSO) to find the optimal SP parameters for reliable EM space field reconstruction. The study used the EM sampling data of an area within the campus of Yunnan Normal University as the study material, and a parameter-optimized RBF method was adopted for the reconstruction of the EM space field. The reconstruction results were then evaluated for accuracy and compared and analyzed with the IDW method optimized with a distance index. Research results show that using RBF with optimal parameters to reconstruct the EM space field has high accuracy and can effectively reflect the actual EM distribution, thereby helping people better understand the characteristics of the electromagnetic environment.
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Radiación ElectromagnéticaRESUMEN
BACKGROUND: Poor oral health is an independent risk factor for upper-aerodigestive tract cancers, including esophageal cancer. Several studies have investigated short-term outcomes after esophagectomy and the impact of periodontal disease, but few have examined the impact of periodontal disease on long-term outcomes. The purpose of this study was to investigate the rate of periodontitis among esophagectomy patients and the prognostic value of periodontitis and its effect on prognosis after esophagectomy. METHODS: A total of 508 patients who underwent esophagectomy received oral health care from a dentist before cancer treatment at Akita University Hospital between January 2009 and December 2021. We assessed the presence and severity of the patients' periodontitis and divided them into no-periodontitis, mild periodontitis, severe periodontitis and edentulous jaw groups. We then assessed 10-year overall survival (OS) and disease-specific survival (DSS) and determined whether periodontitis was an independent prognostic factor affecting OS and DSS. RESULTS: We found that 101 (19.9%) patients had no periodontitis, 207 (40.8%) had mild periodontitis, 176 (34.6%) had severe periodontitis requiring tooth extraction, and 24 (4.7%) had edentulous jaw. Both OS and DSS were significantly poorer in the periodontitis than no-periodontitis group (p < 0.001). In detail, the edentulous jaw group had the poorest prognosis (p < 0.001). Multivariate analysis showed that periodontitis was an independent risk factor affecting OS and DSS. CONCLUSION: Esophageal cancer patients had a high prevalence of periodontitis. Moreover, the presence of periodontitis and severity of periodontitis are independent risk factors contributing to a poorer prognosis after esophagectomy.
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Neoplasias Esofágicas , Arcada Edéntula , Periodontitis , Humanos , Esofagectomía/efectos adversos , Estadificación de Neoplasias , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/cirugía , Pronóstico , Periodontitis/complicaciones , Periodontitis/epidemiología , Periodontitis/cirugía , Arcada Edéntula/cirugíaRESUMEN
Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced ANXA1 levels promoted monocyte differentiation toward M1 macrophages and inflammatory responses, whereas during malignant progression, upregulated ANXA1 fostered M2 macrophage polarization and cancer-associated fibroblast transformation by increasing TGF-ß production. Our spatiotemporal analysis further provided insights into mechanisms responsible for immunosuppression and a potential target to control evolution of precancer and mitigate the risk for cancer development.