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Intact autophagy-lysosomal pathway (ALP) in neuronal survival is crucial. However, it remains unclear whether ALP is intact after subarachnoid hemorrhage (SAH). Ten-eleven translocation (TET) 3 primarily regulates genes related to autophagy in neurons in neurodegenerative diseases. This study aims to investigate the role of TET3 in the ALP following SAH. The results indicate that the ALP is impaired after SAH, with suppressed autophagic flux and an increase in autophagosomes. This is accompanied by a decrease in TET3 expression. Activation of TET3 by α-KG can improve ALP function and neural function to some extent. Silencing TET3 in neurons significantly inhibited the ALP function and increased apoptosis. Inhibition of miR-93-5p, which is elevated after SAH, promotes TET3 expression. This suggests that the downregulation of TET3 after SAH is, at least in part, due to elevated miR-93-5p. This study clarifies the key role of TET3 in the functional impairment of the ALP after SAH. The preliminary exploration revealed that miR-93-5p could lead to the downregulation of TET3, which could be a new target for neuroprotective therapy after SAH.
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BACKGROUND AND OBJECTIVE: Continuous prediction of late-onset sepsis (LOS) could be helpful for improving clinical outcomes in neonatal intensive care units (NICU). This study aimed to develop an artificial intelligence (AI) model for assisting the bedside clinicians in successfully identifying infants at risk for LOS using non-invasive vital signs monitoring. METHODS: In a retrospective study from the NICU of the Máxima Medical Center in Veldhoven, the Netherlands, a total of 492 preterm infants less than 32 weeks gestation were included between July 2016 and December 2018. Data on heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) at 1 Hz were extracted from the patient monitor. We developed multiple AI models using 102 extracted features or raw time series to provide hourly LOS risk prediction. Shapley values were used to explain the model. For the best performing model, the effect of different vital signs and also the input type of signals on model performance was tested. To further assess the performance of applying the best performing model in a real-world clinical setting, we performed a simulation using four different alarm policies on continuous real-time predictions starting from three days after birth. RESULTS: A total of 51 LOS patients and 68 controls were finally included according to the patient inclusion and exclusion criteria. When tested by seven-fold cross-validations, the mean (standard deviation) area under the receiver operating characteristic curve (AUC) six hours before CRASH was 0.875 (0.072) for the best performing model, compared to the other six models with AUC ranging from 0.782 (0.089) to 0.846 (0.083). The best performing model performed only slightly worse than the model learning from raw physiological waveforms (0.886 [0.068]), successfully detecting 96.1 % of LOS patients before CRASH. When setting the expected alarm window to 24 h and using a multi-threshold alarm policy, the sensitivity metric was 71.6 %, while the positive predictive value was 9.9 %, resulting in an average of 1.15 alarms per day per patient. CONCLUSIONS: The proposed AI model, which learns from routinely collected vital signs, has the potential to assist clinicians in the early detection of LOS. Combined with interpretability and clinical alarm management, this model could be better translated into medical practice for future clinical implementation.
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Bilateral repetitive transcranial magnetic stimulation (B-rTMS) has been largely used in the treatment of major depressive disorder (MDD). Nonetheless, information on the acute treatment by B-rTMS combined with antidepressants (ADs) on the plasma fatty acids in MDD is limited. The present study focused on depressive symptoms; Plasma was obtained from 27 adult patients with MDD at baselinephase (MDD), after 2 weeks of treatment (MDD-2w), and 27 healthy controls (HC). Meanwhile, we evaluated the composition of short-chain fatty acids (SCFAs) and medium-and long-chain fatty acids (MLCFAs) in the plasma. Consequently, the levels of Isobutyric acid, Caproic acid, and Propionic acid were low both in the MDD and MDD-2w groups and negatively correlated with the scores of HAMD and HAMA. Besides, minimal changes were observed between the MDD and HC groups, whereas significant MLCFA levels were high in the MDD-2w group. Moreover, we developed combined panels that could effectively differentiate MDD from HCs (AUC=0.99), MDD-2w from HC (AUC=0.983), and MDD from MDD-2w (AUC=0.852). These findings may provide a reference for the use of B-rTMS combined with ADs against the acute phase of depressive episodes and shed light on the relationship between plasma FAs and MDD.
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Background: Urolithiasis is a prevalent condition encountered in urology. Over the past decade, its global incidence has been on an upward trajectory; paired with a high recurrence rate, this presents considerable health and economic burdens. Although inflammatory factors are pivotal in the onset and progression of urolithiasis, their causal linkages remain elusive. Method: Mendelian randomization (MR) is predicated upon genome-wide association studies (GWASs). It integrates bioinformatics analyses to reveal causal relationships between exposures and outcomes, rendering it an effective method with minimized bias. Drawing from a publicly accessible GWAS meta-analysis comprising 8,293 samples, we identified 41 genetic variations associated with inflammatory cytokines as instrumental variables. Outcome data on upper urinary tract stones, which included renal and ureteral stones (9,713 cases and 366,693 controls), and lower urinary tract stones, including bladder and urethral stones (1,398 cases and 366,693 controls), were derived from the FinnGen Consortium R9 dataset. By leveraging the bidirectional MR methodology, we aimed to decipher the causal interplay between inflammatory markers and urolithiasis. Results: Our study comprehensively elucidated the association between genetic inflammatory markers and urolithiasis via bidirectional Mendelian randomization. Post-MR analysis of the 41 genetic inflammation markers revealed that elevated levels of circulating interleukin-2 (IL-2) (OR = 0.921, 95% CI = 0.848-0.999) suggest a reduced risk for renal stone disease, while heightened stem cell growth factor beta (SCGF-ß) (OR = 1.150, 95% CI = 1.009-1.310) and diminished macrophage inflammatory protein 1 beta (MIP-1ß) (OR = 0.863, 95% CI = 0.779-0.956) levels suggest an augmented risk for lower urinary tract stones. Furthermore, renal stone disease appeared to elevate IL-2 (ß = 0.145, 95% CI = 0.013-0.276) and cutaneous T cell-attracting chemokine (CTACK) (ß = 0.145, 95% CI = 0.013-0.276) levels in the bloodstream, whereas lower urinary tract stones were linked to a surge in interleukin-5 (IL-5) (ß = 0.142, 95% CI = 0.057-0.226), interleukin-7 (IL-7) (ß = 0.108, 95% CI = 0.024-0.192), interleukin-8 (IL-8) (ß = 0.127, 95% CI = 0.044-0.210), growth regulated oncogene alpha (GRO-α) (ß = 0.086, 95% CI = 0.004-0.169), monokine induced by interferon-gamma (MIG) (ß = 0.099, 95% CI = 0.008-0.191) and macrophage inflammatory protein 1 alpha (MIP-1α) (ß = 0.126, 95% CI = 0.044-0.208) levels. Conclusion: These discoveries intimate the instrumental role of IL-2 in the onset and progression of upper urinary tract stones. SCGF-ß and MIP-1ß influence the development of lower urinary tract stones. Urolithiasis also impacts the expression of cytokines such as IL-2, CTACK, IL-5, IL-7, IL-8, GRO-α, MIG, and MIP-1α. There is a pressing need for further investigation to ascertain whether these biomarkers can be harnessed to prevent or treat urolithiasis.
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This study explored the regulatory role of bta-miR-149-3p in the inflammatory response induced by microcystin-leucine arginine (MC-LR) exposure in bovine Sertoli cells. The research endeavored to enhance the comprehension of the epigenetic mechanisms underlying MC-LR-induced cytotoxicity in Sertoli cells and establish a foundation for mitigating these effects in vitro. In this study, we elucidated the regulatory mechanism of bta-miR-149-3p in the MC-LR-induced inflammatory response by verifying the target gene of bta-miR-149-3p through luciferase assays and treating the cells with a bta-miR-149-3p inhibitor for 24â¯h. The results demonstrate that nuclear factor κB (NF-κB) acts as a downstream target gene of bta-miR-149-3p, which inhibits the MC-LR-induced inflammatory response in bovine Sertoli cells. This inhibition occurs by regulating the downregulation of tight junction constitutive proteins of the blood-testis barrier (BTB) through the suppression of the TLR-4/NF-κB signaling pathway (p < 0.05) and the up-regulation of the adhesion junction protein ß-catenin (p < 0.05). Notably, MC-LR exposure resulted in the up-regulation (p < 0.05) of inflammatory cytokines (IL-6, IL-1ß, and NLRP3) and the down-regulation (p < 0.05) of BTB tight junction constitutive proteins (ZO-1, Occludin) in Sertoli cells. Furthermore, the BTB constitutive protein ZO-1 exhibited significant down-regulation in Sertoli cells pretreated with the bta-miR-149-3p inhibitor compared to controls (p < 0.05), while Occludin showed no significant difference from CTNNB1 (p > 0.05). In summary, our findings suggest that bta-miR-149-3p suppresses the MC-LR-induced inflammatory response and alterations in the expression of BTB proteins in bovine Sertoli cells by inhibiting the TLR-4/NF-κB signaling pathway.
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Toxinas Marinas , MicroARNs , Microcistinas , FN-kappa B , Células de Sertoli , Transducción de Señal , Receptor Toll-Like 4 , Animales , Bovinos , Masculino , Microcistinas/toxicidad , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Inflamación/inducido químicamente , Leucina/farmacologíaRESUMEN
Multi-mode multiplexing optical interconnection (MMOI) has been widely used as a new technology that can significantly expand communication bandwidth. However, the constant-on state of each channel in the existing MMOI systems leads to serious interference for receivers when extracting and processing information, necessitating introducing real-time selective-on function for each channel in MMOI systems. To achieve this goal, combining several practical requirements, we propose a real-time selective mode switch based on phase-change materials, which can individually tune the passing/blocking of different modes in the bus waveguide. We utilize our proposed particle swarm optimization algorithm with embedded neural network surrogate models (NN-in-PSO) to design this mode switch. The proposed NN-in-PSO significantly reduces the optimization cost, enabling multi-dimensional simultaneous optimization. The resulting mode switch offers several advantages, including ultra-compactness, rapid tuning, nonvolatility, and large extinction ratio. Then, we demonstrate the real-time channel selection function by integrating the mode switch into the MMOI system. Finally, we prove the fabricating robustness of the proposed mode switch, which paves the way for its large-scale application.
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BACKGROUND: Gut dysbiosis has been established as a characteristic of schizophrenia (SCH). However, the signatures regarding SCH patients with prominent negative symptoms (SCH-N) in young adults have been poorly elucidated. METHODS: Stool samples were obtained from 30 young adults with SCH-N, 32 SCH patients with prominent positive symptoms (SCH-P) along with 36 healthy controls (HCs). Microbial diversity and composition were analyzed by 16S rRNA gene sequencing. Meanwhile, psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). RESULTS: There is a significant difference in ß-diversity but not α-diversity indexes among the three groups. Moreover, we found a higher abundance of Fusobacteria and Proteobacteria phyla and a lower abundance of Firmicutes phyla in SCH-N when compared with HC. Besides, we identified a diagnostic potential panel comprising six genera (Coprococcus, Monoglobus, Prevotellaceae_NK3B31_group, Escherichia-Shigella, Dorea, and Butyricicoccus) that can distinguish SCH-N from HC (area under the curve = 0.939). However, the difference in microbial composition between the SCH-N and SCH-P is much less than that between SCH-N and the HC, and SCH-N and SCH-P cannot be effectively distinguished by gut microbiota. CONCLUSION: The composition of gut microbiota was changed in the patients with SCH-N, which may help in further understanding of pathogenesis in young adults with SCH-N.
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Heces , Microbioma Gastrointestinal , ARN Ribosómico 16S , Esquizofrenia , Humanos , Esquizofrenia/microbiología , ARN Ribosómico 16S/genética , Masculino , Adulto Joven , Femenino , Adulto , Heces/microbiología , Disbiosis/microbiologíaRESUMEN
With the elucidation of community structures and assembly mechanisms in various fermented foods, core communities that significantly influence or guide fermentation have been pinpointed and used for exogenous restructuring into synthetic microbial communities (SynComs). These SynComs simulate ecological systems or function as adjuncts or substitutes in starters, and their efficacy has been widely verified. However, screening and assembly are still the main limiting factors for implementing theoretic SynComs, as desired strains cannot be effectively obtained and integrated. To expand strain screening methods suitable for SynComs in food fermentation, this review summarizes the recent research trends in using SynComs to study community evolution or interaction and improve the quality of food fermentation, as well as the specific process of constructing synthetic communities. The potential for novel screening modalities based on genes, enzymes and metabolites in food microbial screening is discussed, along with the emphasis on strategies to optimize assembly for facilitating the development of synthetic communities.
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Fermentación , Alimentos Fermentados , Microbiología de Alimentos , Microbiología de Alimentos/métodos , Alimentos Fermentados/microbiología , Bacterias/genética , Bacterias/metabolismo , Bacterias/clasificación , Microbiota , Consorcios MicrobianosRESUMEN
Agglomeration and passivation restrict the using zero-valent iron nanoparticles (nZVI). Enhancing the reactivity of nZVI is often accomplished by sulfurization. In this work, nZVI was sulfurized using SRB to produce biosulfurized nano zero-valent iron (BP-S-nZVI), which was then utilized as a catalyst to investigating its performance in an advanced oxidation process based on activated peroxomonosulfate (PMS). When the S/Fe was 0.05, 0.4 g/L of catalyst and 0.5 mM PMS were added to a 20 mg/L ciprofloxacin solution. In 120 min, a 90.4% clearance rate was reached. When the initial pH of the solution was within the range of 3-11, all exhibited acceptable degradation performance and were minimally affected by co-existing anions. In this activation system, hydroxyl, superoxide and sulfate radicals (â¢OH, O2â¢- and SO4â¢-, respectively) have been proven to be the main active species. Seven intermediates in the degradation process of CIP were identified by LC-MS analysis and two possible degradation pathways were proposed. In addition, the degradation rate of CIP was still able to reach 87.0% after five cycles, and the removal rate remained unchanged in the CIP solution with actual water samples as background. This study demonstrated that BP-S-nZVI as a catalyst for the activation of PMS for CIP degradation can still show good reactivity, which provides more possibilities for the practical application of BP-S-nZVI in the degradation of pollutants.
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Ciprofloxacina , Hierro , Nanopartículas del Metal , Oxidación-Reducción , Contaminantes Químicos del Agua , Hierro/química , Ciprofloxacina/química , Contaminantes Químicos del Agua/química , Nanopartículas del Metal/química , Catálisis , Sulfatos/química , Purificación del Agua/métodos , Concentración de Iones de HidrógenoRESUMEN
Atractylodes lancea is a perennial herb whose rhizome (AR) is a valuable traditional Chinese medicine with immense market demand. The cultivation of Atractylodes lancea faces outbreaks of root rot and deterioration in herb quality due to complex causes. Here, we investigated the effects of Trichoderma spp., well-known biocontrol agents and plant-growth-promoters, on ARs. We isolated Trichoderma strains from healthy ARs collected in different habitats and selected three T. harzianum strains (Th2, Th3 and Th4) with the strongest antagonizing effects on root rot pathogens (Fusarium spp.). We inoculated geo-authentic A. lancea plantlets with Th2, Th3 and Th4 and measured the biomass and quality of 70-day-old ARs. Th2 and Th3 promoted root rot resistance of A. lancea. Th2, Th3 and Th4 all boosted AR quality: the concentration of the four major medicinal compounds in ARs (atractylon, atractylodin, hinesol and ß-eudesmol) each increased 1.6- to 18.2-fold. Meanwhile, however, the yield of ARs decreased by 0.58- to 0.27-fold. Overall, Th3 dramatically increased the quality of ARs at a relatively low cost, namely lower yield, showing great potential for practical application. Our results showed selectivity between A. lancea and allochthonous Trichoderma isolates, indicating the importance of selecting specific microbial patches for herb cultivation.
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In the past 40 years, the incidence of esophagogastric junction cancer has been gradually increasing worldwide. Currently, surgical resection remains the main radical treatment for early gastric cancer. Due to the rise of functional preservation surgery, proximal gastrectomy has become an alternative to total gastrectomy for surgeons in Japan and South Korea. However, the methods of digestive tract reconstruction after proximal gastrectomy have not been fully unified. At present, the principal methods include esophagogastrostomy, double flap technique, jejunal interposition, and double tract reconstruction. Related studies have shown that double tract reconstruction has a good anti-reflux effect and improves postoperative nutritional prognosis, and it is expected to become a standard digestive tract reconstruction method after proximal gastrectomy. However, the optimal anastomoses mode in current double tract reconstruction is still controversial. This article aims to review the current status of double tract reconstruction and address the aforementioned issues.
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Anastomosis Quirúrgica , Gastrectomía , Procedimientos de Cirugía Plástica , Neoplasias Gástricas , Humanos , Gastrectomía/métodos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Anastomosis Quirúrgica/métodos , Procedimientos de Cirugía Plástica/métodos , Unión Esofagogástrica/cirugía , Colgajos Quirúrgicos , Yeyuno/cirugíaRESUMEN
Objective.Electroencephalography (EEG) has been widely used in motor imagery (MI) research by virtue of its high temporal resolution and low cost, but its low spatial resolution is still a major criticism. The EEG source localization (ESL) algorithm effectively improves the spatial resolution of the signal by inverting the scalp EEG to extrapolate the cortical source signal, thus enhancing the classification accuracy.Approach.To address the problem of poor spatial resolution of EEG signals, this paper proposed a sub-band source chaotic entropy feature extraction method based on sub-band ESL. Firstly, the preprocessed EEG signals were filtered into 8 sub-bands. Each sub-band signal was source localized respectively to reveal the activation patterns of specific frequency bands of the EEG signals and the activities of specific brain regions in the MI task. Then, approximate entropy, fuzzy entropy and permutation entropy were extracted from the source signal as features to quantify the complexity and randomness of the signal. Finally, the classification of different MI tasks was achieved using support vector machine.Main result.The proposed method was validated on two MI public datasets (brain-computer interface (BCI) competition III IVa, BCI competition IV 2a) and the results showed that the classification accuracies were higher than the existing methods.Significance.The spatial resolution of the signal was improved by sub-band EEG localization in the paper, which provided a new idea for EEG MI research.