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Plants employ distinct mechanisms to respond to environmental changes. Modification of mRNA by N 6-methyladenosine (m6A), known to affect the fate of mRNA, may be one such mechanism to reprogram mRNA processing and translatability upon stress. However, it is difficult to distinguish a direct role from a pleiotropic effect for this modification due to its prevalence in RNA. Through characterization of the transient knockdown-mutants of m6A writer components and mutants of specific m6A readers, we demonstrate the essential role that m6A plays in basal resistance and pattern-triggered immunity (PTI). A global m6A profiling of mock and PTI-induced Arabidopsis plants as well as formaldehyde fixation and cross-linking immunoprecipitation-sequencing of the m6A reader, EVOLUTIONARILY CONSERVED C-TERMINAL REGION2 (ECT2) showed that while dynamic changes in m6A modification and binding by ECT2 were detected upon PTI induction, most of the m6A sites and their association with ECT2 remained static. Interestingly, RNA degradation assay identified a dual role of m6A in stabilizing the overall transcriptome while facilitating rapid turnover of immune-induced mRNAs during PTI. Moreover, polysome profiling showed that m6A enhances immune-associated translation by binding to the ECT2/3/4 readers. We propose that m6A plays a positive role in plant immunity by destabilizing defense mRNAs while enhancing their translation efficiency to create a transient surge in the production of defense proteins.
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Adenosina , Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Inmunidad de la Planta , Biosíntesis de Proteínas , Estabilidad del ARN , ARN Mensajero , Arabidopsis/genética , Arabidopsis/inmunología , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Inmunidad de la Planta/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/genética , ARN de Planta/genética , ARN de Planta/metabolismo , Reconocimiento de Inmunidad InnataRESUMEN
OBJECTIVE: To assess the efficacy and safety of Sanjie Analgesic Capsule (SAC) in Chinese patients with endometriosis-associated pain. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial conducted at 15 centers between November 2013 and July 2017 in China. Eligible 323 patients with endometriosis were randomized at a 3:1 ratio to the SAC group (241 cases) and placebo group (82 cases) by stratified block randomization. Patients in the SAC or placebo groups were given SAC or placebo 1.6 g 3 times per day, orally, respectively since the first day of menstruation for 3 consecutive menstrual cycles. The primary endpoint was clinical response to dysmenorrhea evaluated using a 10-point Visual Analogue Scale at 3 and 6 months. The secondary endpoint was the pain score evaluated by VAS (chronic pelvic pain, defecation pain, and dyspareunia) at 3 and 6 months, and the pain recurrence rate at 6 months. Adverse events (AEs) were recorded during the study. RESULTS: A total of 241 women were included in the SAC group, and 82 were in the placebo group. Among these women, 217 (90.0%) and 71 (86.6%) completed the intervention, respectively. At 3 months, overall response rate (ORR) was significantly higher in women administered SAC (80.1%) compared with those who received a placebo (30.5%, P<0.01). Six months after treatment, the ORR for dysmenorrhea was 62.7% in the SAC group and 31.7% in the placebo group (P<0.01). Chronic pelvic pain and defecation pain were significantly improved by SAC compared with placebo (both P<0.05). The incidence rates of total AEs events in the SAC and placebo groups were 6.6% and 9.8%, respectively, and no significant difference was shown between the two groups (P=0.339). CONCLUSION: SAC is well-tolerated and may improve dysmenorrhea in women with endometriosis-associated pain. (Trial registration: ClinicalTrials.gov, No. NCT02031523).
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BACKGROUND: To compare the application of conventional MRI analysis and MRI-based radiomics to identify the circumferential resection margin (CRM) status of rectal cancer (RC). METHODS: A cohort of 301 RC patients with 66 CRM invloved status and 235 CRM non-involved status were enrolled in this retrospective study between September 2017 and August 2022. Conventional MRI characteristics included gender, age, diameter, distance to anus, MRI-based T/N phase, CEA, and CA 19 - 9, then the relevant logistic model (Logistic-cMRI) was built. MRI-based radiomics of rectal cancer and mesorectal fascia were calculated after volume of interest segmentation, and the logistic model of rectal cancer radiomics (Logistic-rcRadio) and mesorectal fascia radiomics (Logistic-mfRadio) were constructed. And the combined nomogram (nomo-cMRI/rcRadio/mfRadio) containing conventional MRI characteristics, radiomics of rectal cancer and mesorectal fascia was developed. The receiver operator characteristic curve (ROC) was delineated and the area under curve (AUC) was calculated the efficiency of models. RESULTS: The AUC of Logistic-cMRI was 0.864 (95%CI, 0.820 to 0.901). The AUC of Logistic-rcRadio was 0.883 (95%CI, 0.832 to 0.928) in the training set and 0.725 (95%CI, 0.616 to 0.826) in the testing set. The AUCs of Logistic-mfRadio was 0.891 (95%CI, 0.838 to 0.936) in the training set and 0.820 (95%CI, 0.725 to 0.905) in the testing set. The AUCs of nomo-cMRI/rcRadio/mfRadio were the highest in both the training set of 0.942 (95%CI, 0.901 to 0.969) and the testing set of 0.909 (95%CI, 0.830 to 0.959). CONCLUSION: MRI-based radiomics of rectal cancer and mesorectal fascia showed similar efficacy in predicting the CRM status of RC. The combined nomogram performed better in assessment.
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Imagen por Resonancia Magnética , Márgenes de Escisión , Neoplasias del Recto , Humanos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Nomogramas , Curva ROC , Fascia/diagnóstico por imagen , Fascia/patología , Recto/diagnóstico por imagen , Recto/patología , Adulto , Modelos Logísticos , Área Bajo la Curva , RadiómicaRESUMEN
Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N6-methyladenosine (m6A), the most abundant mammalian mRNA modification. However, which and how gut microbiota-derived metabolites reprogram host transcriptome and m6A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota-derived metabolites impact host transcriptome and m6A epitranscriptome using multiple mouse models and multi-omics approaches. Various antibiotics-induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ-free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid-producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m6A epitranscriptome in multiple tissues. Mechanistically, the expression of m6A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m6A biology. Collectively, these results demonstrate that antibiotic-induced gut dysbiosis regulates the landscape of host transcriptome and m6A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.
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Adenosina , Antibacterianos , Ácidos y Sales Biliares , Disbiosis , Microbioma Gastrointestinal , Transcriptoma , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/genética , Ácidos y Sales Biliares/metabolismo , Disbiosis/metabolismo , Disbiosis/microbiología , Disbiosis/genética , Ratones , Transcriptoma/genética , Antibacterianos/farmacología , Adenosina/análogos & derivados , Adenosina/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , MasculinoRESUMEN
Polyamides represent one class of materials that is important in modern society. Because of the numerous potential applications of polyamides in various fields, there is a high demand for new polyamide structures, which necessitates the development of new polymerization methods. Herein, we report a novel and efficient palladium-catalyzed hydroaminocarbonylative polymerization of dienes and diamines for the synthesis of cycloaliphatic polyamides. The method employs readily available starting materials, proceeds in an atom-economic manner, and creates a series of new functional polyamides in high yields and high molecular weights. In contrast with the traditional polyamides based on adipic acid, the cycloaliphatic polyamides have superior thermal resistance, higher glass-transition temperature, and better solubility in common organic solvents, thus probably featuring the merits of high-performance and good processability.
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As an important functional monosaccharide, glucosamine (GlcN) is widely used in fields such as medicine, food nutrition, and health care. Here, we report a distinct GlcN biosynthesis method that utilizes engineered Bacillus subtilis glucosamine-6-phosphate synthase (BsGlmS) to convert D-fructose to directly generate GlcN. The best variant obtained by using a combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy was a quadruple mutant S596D/V597G/S347H/G299Q (BsGlmS-BK19), which has a catalytic activity 1736-fold that of the wild type toward D-fructose. Upon using mutant BK19 as a whole-cell catalyst, D-fructose was converted into GlcN with 65.32% conversion in 6 h, whereas the wild type only attained a conversion rate of 0.31% under the same conditions. Molecular docking and molecular dynamics simulations were implemented to provide insights into the mechanism underlying the enhanced activity of BK19. Importantly, the BsGlmS-BK19 variant specifically catalyzes D-fructose without the need for phosphorylated substrates, representing a significant advancement in GlcN biosynthesis.
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Bacillus subtilis , Glucosamina , Glutamina-Fructosa-6-Fosfato Transaminasa (Isomerizadora) , Ingeniería de Proteínas , Glucosamina/biosíntesis , Glucosamina/metabolismo , Glucosamina/química , Glutamina-Fructosa-6-Fosfato Transaminasa (Isomerizadora)/metabolismo , Glutamina-Fructosa-6-Fosfato Transaminasa (Isomerizadora)/genética , Glutamina-Fructosa-6-Fosfato Transaminasa (Isomerizadora)/química , Bacillus subtilis/enzimología , Bacillus subtilis/metabolismo , Bacillus subtilis/genética , Simulación del Acoplamiento Molecular , Fructosa/metabolismo , Fructosa/química , Fructosa/biosíntesis , Simulación de Dinámica Molecular , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Dominio CatalíticoRESUMEN
To study the hydrochemical characteristics, controlling factors, and groundwater quality of the Tan-Lu fault zone (Anhui section), 86 groundwater samples were taken from the areas surrounding the Tan-Lu fault zone (Anhui section), which included the Jianghuai Wavy Plain, the Yanjiang Hill Plain, and the Dabie Mountains in western Anhui. Descriptive statistics, Piper diagram, Gibbs diagram, ion ratio analysis, saturation index, chloride-alkalinity index, and entropy weight water quality index (EWQI) were used to comprehensively study the hydrochemical characteristics and controlling factors of groundwater and to evaluate its quality. The results showed that the shallow groundwater in the Tan-Lu fault zone (Anhui section) was weakly alkaline, with dominant anions and cations of HCO3-, Ca2+ and Na+, respectively, and the hydrochemical types were mainly HCO3-Ca·Mg and HCO3-Na·Ca. The solute source of groundwater was mainly controlled by water-rock interactions, and the weathering of silicate and carbonate rocks jointly contributed to the formation of the chemical components of groundwater. Strong cation exchange adsorption was an important factor causing Na+ enrichment. The overall quality of groundwater in the study area was good but was polluted to a certain extent by human activities. Most of the groundwater in the Jianghuai Wavy Plain and Yanjiang Hill Plain was not suitable for direct drinking. The results of this research have important implications for the sustainable development and utilization of shallow groundwater resources and environmental protection in the Tan-Lu fault zone (Anhui section).
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In contrast to the kinetically favored outward isomerization-hydrocarbonylation of alkenes, the disfavored inward isomerization-hydrocarbonylation of alkenes remains an important challenge. Herein, we have developed a novel and effective palladium-catalyzed inward isomerization-hydroaminocarbonylation of unactivated alkenes and aniline hydrochlorides for the formation of synthetically valuable α-aryl carboxylic amides in high yields and high site-selectivities. The high efficiency of the reaction is attributed to a relay catalysis strategy, in which the Markovnikov-favored [PdH]-PtBu3 catalyst is responsible for inward isomerization, while the [PdH]-Ruphos catalyst is responsible for hydroaminocarbonylation of the resulting conjugated aryl alkenes. The reaction exhibits highly functional group tolerance and provides a new method for formal carbonylation of remote C(sp3)-H bond.
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OBJECTIVE: This retrospective study investigated the effects of uterine manipulator use during minimally invasive radical hysterectomy on prognosis in patients with cervical cancer. METHODS: We collected clinical data on 762 patients with stage IA2 to IIB cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy in Chinese PLA General Hospital from 2009 to 2019. Kaplan-Meier analysis and log-rank tests were used to compare the 5-year overall survival rates between patients treated with and without a uterine manipulator. RESULTS: Patient demographics did not differ between the two groups. In addition, the incidence of lymphovascular space invasion, tumor size, pathologic types, the International Federation of Gynecology and Obstetrics stage, the histologic grade, and the rate of lymphatic metastases did not differ between the groups. Meanwhile, perioperative clinical indicators were similar in the groups. Furthermore, no significant differences in 5-year survival rates and survival curves were recorded between the groups among both all patients (84.5% vs. 85.6%) and early-stage patients (89.1% vs. 89.2%). CONCLUSIONS: The use of uterine manipulators during minimally invasive radical hysterectomy for cervical cancer did not affect clinicopathological markers or increase the risk of death.
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Laparoscopía , Neoplasias del Cuello Uterino , Femenino , Humanos , Estudios Retrospectivos , Estadificación de Neoplasias , Supervivencia sin Enfermedad , Neoplasias del Cuello Uterino/patología , Pronóstico , Escisión del Ganglio Linfático , HisterectomíaRESUMEN
Rectal cancer (RC) is the third most frequently diagnosed cancer worldwide, and the status of its circumferential resection margin (CRM) is of paramount significance for treatment strategies and prognosis. CRM involvement is defined as tumor touching or within 1 mm from the outermost part of tumor or outer border of the mesorectal or lymph node deposits to the resection margin. The incidence of involved CRM varied from 5.4 % to 36 %, which may associate with an in consistent definition of CRM, the quality of surgeries, and the different examination modalities. Although T and N status are essential factors in determining whether a patient should receive neoadjuvant therapy before surgery, CRM status is a powerful predictor of local and distant recurrence as well as survival rate. This review explores the significance of CRM, the various assessment methods, and the role of magnetic resonance imaging (MRI) and artificial intelligence-based MRI in predicting CRM status. MRI showed potential advantage in predicting CRM status with a high sensitivity and specificity compared to computed tomography (CT). We also discuss MRI advancements in RC imaging, including conventional MRI with body coil, high-resolution MRI with phased-array coil, and endorectal MRI. Along with a discussion of artificial intelligence-based MRI techniques to predict the CRM status of RCs before and after treatments.
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Imagen por Resonancia Magnética , Márgenes de Escisión , Neoplasias del Recto , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Neoplasias del Recto/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Valor Predictivo de las Pruebas , Pronóstico , Inteligencia Artificial , Sensibilidad y Especificidad , Recurrencia Local de Neoplasia/diagnóstico por imagenRESUMEN
BACKGROUND AND OBJECTIVE: Ulcerative colitis (UC) is a chronic disease characterized by recurrent symptoms and significant morbidity. The exact cause of the disease remains unknown. The selection of current treatment options for ulcerative colitis depends on the severity and location of the disease in each patient. Therefore, developing a fully automated endoscopic images for evaluating UC is crucial for guiding treatment plans and facilitating early prevention efforts. METHODS: We propose a network called ulcerative colitis evaluation based on fine-grained lesion learner and noise suppression gating (UCFNNet). UCFNNet contains three novel modules. Firstly, a fine-grained lesion feature learner (FG-LF Learner) is proposed by integrating local features and a Softmax category prediction (SCP) module to improve the feature accuracy in small lesion areas. Subsequently, a graph convolutional feature combiner (GCFC) is developed to connect features across adjacent convolutional layers and to incorporate short connections between input and output, thereby mitigating feature loss during transmission. Thereafter, a noise suppression gating (NS gating) technique is designed by implementing a grid attention mechanism and a feature gating (FG) module to prioritize significant lesion features and suppress irrelevant and noisy regions in the input feature map. RESULTS: We evaluate the performance of the proposed network on both privately-collected and publicly-available datasets. The evaluation of UC achieves excellent results on privately-collected dataset, with an accuracy (ACC) of 89.57 %, Matthews correlation coefficient (MCC) of 85.52 %, precision of 89.26 %, recall of 89.48 %, and F1-score of 89.78 %. The results are also impressive on publicly-available dataset, with ACC of 85.47 %, MCC of 80.42 %, precision of 85.62 %, recall of 84.00 %, and F1-score of 84.53 %, surpassing the performance of state-of-the-art techniques. CONCLUSION: Our proposed model introduces three innovative algorithm modules, which outperform the current state-of-the-art methods and achieve high ACC and F1-score. This indicates that our method has superior performance compared to traditional machine learning and existing deep methods, which means that our method has good application prospects. Meanwhile, it has been verified that the proposed model demonstrates good interpretability. The source code is available at github.com/YinLeRenNB/UCFNNet.
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Dehydrosqualene synthase (CrtM), as a squalene synthase-like enzyme from Staphylococcus aureus, can naturally utilize farnesyl diphosphate to produce dehydrosqualene (C30H48). However, no study has documented the natural production of squalene (C30H50) by CrtM. Here, based on an HPLC-Q-Orbitrap-MS/MS study, we report that the expression of crtM in vitro or in Bacillus subtilis 168 both results in the output of squalene, dehydrosqualene, and phytoene (C40H64). Notably, wild-type CrtM exhibits a significantly higher squalene yield compared to squalene synthase (SQS) from Bacillus megaterium with an approximately 2.4-fold increase. Moreover, the examination of presqualene diphosphate's stereostructures in both CrtM and SQS enzymes provides further understanding into the presence of multiple identified terpenoids. In summary, this study not only provides insights into the promiscuity demonstrated by squalene synthase-like enzymes but also highlights a new strategy of utilizing CrtM as a potential replacement for SQS in cell factories, thereby enhancing squalene production.
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Farnesil Difosfato Farnesil Transferasa , Escualeno , Escualeno/análogos & derivados , Escualeno/metabolismo , Farnesil Difosfato Farnesil Transferasa/genética , Farnesil Difosfato Farnesil Transferasa/metabolismo , Espectrometría de Masas en Tándem , Terpenos/metabolismo , Óxido Nítrico SintasaRESUMEN
Periodontal ligament stem cells (PDLSCs), which are considered promising stem cells for regeneration of periodontal bony tissue, can also manipulate alveolar bone remodeling by exosomes. In this study, we investigated interactions between PDLSCs under osteogenic differentiation and osteoclast precursors. The results showed that conditioned medium from PDLSCs under 5d osteogenic induction promoted osteoclastogenesis of RAW264.7 cells. The exosomes extracted from those conditioned media showed similar effects on osteoclastogenesis. Furthermore, exosomes from PDLSCs under 5d of osteogenic induction showed significantly high expression of circ_0000722, compared with exosomes from PDLSCs before osteogenic induction. Downregulation of circ_0000722 significantly attenuated the effect of PDLSC-derived exosomes on the osteoclastogenesis of RAW264.7 cells. Our findings suggested that exosomal circ_0000722 derived from periodontal ligament stem cells undergoing osteogenic differentiation might promote osteoclastogenesis by upregulating TRAF6 expression and activating downstream NF-κB and AKT signaling pathways.
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Osteogénesis , Ligamento Periodontal , Células Cultivadas , Células Madre , Diferenciación CelularRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. is a well-known and highly regarded resource in Chinese traditional medicine due to its effectiveness and safety. Ginkgo Folium, the leaf of Ginkgo biloba L., contains biologically active constituents with diverse pharmacological activities. Recent studies have shown promising antitumor effects of the bioactive constituents found in Ginkgo Folium against various types of cancer cells, highlighting its potential as a natural source of antitumor agents. Further research is needed to elucidate the underlying mechanisms and optimize its therapeutic potential. AIM OF THE REVIEW: To provide a detailed understanding of the pharmacological activities of Ginkgo Folium and its potential therapeutic benefits for cancer patients. MATERIALS AND METHODS: In this study, we conducted a thorough and systematic search of multiple online databases, including PubMed, Web of Science, Medline, using relevant keywords such as "Ginkgo Folium," "flavonoids," "terpenoids," "Ginkgo Folium extracts," and "antitumor" to cover a broad range of studies that could inform our review. Additionally, we followed a rigorous selection process to ensure that the studies included in our review met the predetermined inclusion criteria. RESULTS: The active constituents of Ginkgo Folium primarily consist of flavonoids and terpenoids, with quercetin, kaempferol, isorhamnetin, ginkgolides, and bilobalide being the major compounds. These active constituents exert their antitumor effects through crucial biological events such as apoptosis, cell cycle arrest, autophagy, and inhibition of invasion and metastasis via modulating diverse signaling pathways. During the process of apoptosis, active constituents primarily exert their effects by modulating the caspase-8 mediated death receptor pathway and caspase-9 mediated mitochondrial pathway via regulating specific signaling pathways. Furthermore, by modulating multiple signaling pathways, active constituents effectively induce G1, G0/G1, G2, and G2/M phase arrest. Among these, the pathways associated with G2/M phase arrest are particularly extensive, with the cyclin-dependent kinases (CDKs) being most involved. Moreover, active constituents primarily mediate autophagy by modulating certain inflammatory factors and stressors, facilitating the fusion stage between autophagosomes and lysosomes. Additionally, through the modulation of specific chemokines and matrix metalloproteinases, active constituents effectively inhibit the processes of epithelial-mesenchymal transition (EMT) and angiogenesis, exerting a significant impact on cellular invasion and migration. Synergistic effects are observed among the active constituents, particularly quercetin and kaempferol. CONCLUSION: Active components derived from Ginkgo Folium demonstrate a comprehensive antitumor effect across various levels and pathways, presenting compelling evidence for their potential in new drug development. However, in order to facilitate their broad and adaptable clinical application, further extensive experimental investigations are required to thoroughly explore their efficacy, safety, and underlying mechanisms of action.
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Ginkgo biloba , Quercetina , Humanos , Quercetina/farmacología , Quempferoles , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , FlavonoidesRESUMEN
Pseudomonas aeruginosa harbors sophisticated transcription factor (TF) networks to coordinately regulate cellular metabolic states for rapidly adapting to changing environments. The extraordinary capacity in fine-tuning the metabolic states enables its success in tolerance to antibiotics and evading host immune defenses. However, the linkage among transcriptional regulation, metabolic states and antibiotic tolerance in P. aeruginosa remains largely unclear. By screening the P. aeruginosa TF mutant library constructed by CRISPR/Cas12k-guided transposase, we identify that rccR (PA5438) is a major genetic determinant in aminoglycoside antibiotic tolerance, the deletion of which substantially enhances bacterial tolerance. We further reveal the inhibitory roles of RccR in pyruvate metabolism (aceE/F) and glyoxylate shunt pathway (aceA and glcB), and overexpression of aceA or glcB enhances bacterial tolerance. Moreover, we identify that 2-keto-3-deoxy-6-phosphogluconate (KDPG) is a signal molecule that directly binds to RccR. Structural analysis of the RccR/KDPG complex reveals the detailed interactions. Substitution of the key residue R152, K270 or R277 with alanine abolishes KDPG sensing by RccR and impairs bacterial growth with glycerol or glucose as the sole carbon source. Collectively, our study unveils the connection between aminoglycoside antibiotic tolerance and RccR-mediated central carbon metabolism regulation in P. aeruginosa, and elucidates the KDPG-sensing mechanism by RccR.
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Proteínas Bacterianas , Carbono , Pseudomonas aeruginosa , Aminoglicósidos/farmacología , Antibacterianos/farmacología , Antibacterianos/metabolismo , Carbono/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Proteínas Bacterianas/metabolismo , Redes Reguladoras de GenesRESUMEN
BACKGROUND: Elderly patients often exhibit postoperative cognitive dysfunction (POCD), a postsurgical decline in memory and executive function. Oxidative stress and neuroinflammation, both pathological characteristics of the aged brain, contribute to this decline. This study posits that electroacupuncture (EA) stimulation, an effective antioxidant and anti-inflammatory modality, may enhance telomerase reverse transcriptase (TERT) function, the catalytic subunit of telomerase known for its protective properties against cellular senescence and oxidative damage, to alleviate POCD in aged mice. METHODS: The animal POCD model was created by subjecting aged mice to abdominal surgery, followed by EA pretreatment at the Baihui acupoint (GV20). Postoperative cognitive function was gauged using the Morris water maze (MWM) test. Hippocampal TERT mRNA levels and telomerase activity were determined through qPCR and a Telomerase PCR ELISA kit, respectively. Oxidative stress was assessed through superoxide dismutase (SOD), reactive oxygen species (ROS), and malondialdehyde (MDA) levels. Iba-1 immunostaining determined the quantity of hippocampal microglia. Additionally, western blotting assessed TERT, autophagy markers, and proinflammatory cytokines at the protein level. RESULTS: Abdominal surgery in aged mice significantly decreased telomerase activity and TERT mRNA and protein levels, but increased oxidative stress and neuroinflammation and decreased autophagy in the hippocampus. EA-pretreated mice demonstrated improved postoperative cognitive performance, enhanced telomerase activity, increased TERT protein expression, improved TERT mitochondrial localization, and reduced oxidative damage, autophagy dysfunction, and neuroinflammation. The neuroprotective benefits of EA pretreatment were diminished following TERT knockdown. CONCLUSIONS: Our findings underscore the significance of TERT function preservation in alleviating surgery-induced oxidative stress and neuroinflammation in aged mice. A novel neuroprotective mechanism of EA stimulation is highlighted, whereby modulation of TERT and telomerase activity reduces oxidative damage and neuroinflammation. Consequently, maintaining TERT function via EA treatment could serve as an effective strategy for managing POCD in elderly patients.
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Disfunción Cognitiva , Electroacupuntura , Complicaciones Cognitivas Postoperatorias , Telomerasa , Animales , Ratones , Disfunción Cognitiva/etiología , Disfunción Cognitiva/terapia , Disfunción Cognitiva/metabolismo , Hipocampo/metabolismo , Enfermedades Neuroinflamatorias , Estrés Oxidativo/fisiología , Complicaciones Cognitivas Postoperatorias/metabolismo , ARN Mensajero/metabolismoRESUMEN
OBJECTIVE: Olfactory disturbance is one of the main symptoms of coronavirus disease-2019 (COVID-19). Various olfactory disorders caused by viral infections are treated with nasal corticosteroids. This study aimed to evaluate the safety and efficacy of nasal corticosteroids in the treatment of olfactory disorders caused by the severe acute respiratory syndrome coronavirus 2. DATA SOURCES: We searched the Web of Science, Embase, PubMed, and Cochrane Library databases for clinical trials of nasal corticosteroids for treating COVID-19 olfactory dysfunction. REVIEW METHODS: We assessed the effect of nasal corticosteroids on olfactory function in COVID-19-affected individuals using a Meta-analysis of published studies, considering the number of patients who fully recovered from olfactory dysfunction, olfactory scores following treatment, and olfactory recovery time. RESULTS: Seven studies involving 930 patients were analyzed. The Meta-analysis results revealed that the olfactory score of the experimental group was 1.40 points higher than that of the control group (standardized mean difference [MD]: 1.40, 95% confidence interval [95% CI]: 0.34-2.47, P < .00001). However, the differences in the outcomes of cure rate (risk ratio: 1.18, 95% CI: 0.89-1.69, P = .21) and recovery time (MD: -1.78, 95% CI: -7.36 to 3.81, P = .53) were not statistically significant. Only 1 study reported adverse effects of nasal steroid treatment, namely tension, anger, and stomach irritation. CONCLUSION: Although nasal steroid therapy does not result in significant adverse effects, it proves ineffective in the treatment of COVID-19 olfactory dysfunction.
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Administración Intranasal , COVID-19 , Trastornos del Olfato , Humanos , Trastornos del Olfato/tratamiento farmacológico , Trastornos del Olfato/etiología , Trastornos del Olfato/virología , COVID-19/complicaciones , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19 , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Resultado del Tratamiento , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificaciónRESUMEN
A continuous-time exhaustive-limited (K = 2) two-level polling control system is proposed to address the needs of increasing network scale, service volume and network performance prediction in the Internet of Things (IoT) and the Long Short-Term Memory (LSTM) network and an attention mechanism is used for its predictive analysis. First, the central site uses the exhaustive service policy and the common site uses the Limited K = 2 service policy to establish a continuous-time exhaustive-limited (K = 2) two-level polling control system. Second, the exact expressions for the average queue length, average delay and cycle period are derived using probability generating functions and Markov chains and the MATLAB simulation experiment. Finally, the LSTM neural network and an attention mechanism model is constructed for prediction. The experimental results show that the theoretical and simulated values basically match, verifying the rationality of the theoretical analysis. Not only does it differentiate priorities to ensure that the central site receives a quality service and to ensure fairness to the common site, but it also improves performance by 7.3 and 12.2%, respectively, compared with the one-level exhaustive service and the one-level limited K = 2 service; compared with the two-level gated- exhaustive service model, the central site length and delay of this model are smaller than the length and delay of the gated- exhaustive service, indicating a higher priority for this model. Compared with the exhaustive-limited K = 1 two-level model, it increases the number of information packets sent at once and has better latency performance, providing a stable and reliable guarantee for wireless network services with high latency requirements. Following on from this, a fast evaluation method is proposed: Neural network prediction, which can accurately predict system performance as the system size increases and simplify calculations.
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As the demand for the internet of things (IoT) continues to grow, there is an increasing need for low-latency networks. Mobile edge computing (MEC) provides a solution to reduce latency by offloading computational tasks to edge servers. However, this study primarily focuses on the integration of back propagation (BP) neural networks into the realm of MEC, aiming to address intricate network challenges. Our innovation lies in the fusion of BP neural networks with MEC, particularly for optimizing task scheduling and processing. Firstly, we introduce a drone-assisted MEC model that categorizes computation offloading into synchronous and asynchronous modes based on task scheduling. Secondly, we employ Markov chains and probability-generation functions to accurately compute parameters such as average queue length, cycle time, throughput, and average delay in the synchronous mode. We also derive the first and second-order derivatives of the probability-generation function to support these computations. Finally, we establish a BP neural network to solve for the average queue length and latency in the asynchronous mode. Our results from the BP neural network closely align with the theoretical values obtained through the probability-generation function, demonstrating the effectiveness of our approach. Additionally, our proposed UAV-assisted MEC model outperforms the synchronous mode. Overall, our MEC scheduling approach significantly reduces latency, enhances speed, and improves throughput, with our model reducing latency by approximately 11.72$ \% $ and queue length by around 9.45$ \% $.
RESUMEN
Infrared and visible image fusion (IVIF) aims to obtain an image that contains complementary information about the source images. However, it is challenging to define complementary information between source images in the lack of ground truth and without borrowing prior knowledge. Therefore, we propose a semisupervised transfer learning-based method for IVIF, termed STFuse, which aims to transfer knowledge from an informative source domain to a target domain, thus breaking the above limitations. The critical aspect of our method is to borrow supervised knowledge from the multifocus image fusion (MFIF) task and to filter out task-specific attribute knowledge by using a guidance loss Lg , which motivates its cross-task use in IVIF tasks. Using this cross-task knowledge effectively alleviates the limitation of the lack of ground truth on fusion performance, and the complementary expression ability under the constraint of supervised knowledge is more instructive than prior knowledge. Moreover, we designed a cross-feature enhancement module (CEM) that utilizes self-attention and mutual-attention features to guide each branch to refine features and then facilitate the integration of cross-modal complementary features. Extensive experiments demonstrate that our method has good advantages in terms of visual quality and statistical metrics, as well as the docking of high-level vision tasks, compared with other state-of-the-art methods.