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Ailanthone (AIL), a monomer derived from ailanthus in Chinese medicine, has been demonstrated to have antitumor effects, albeit the underlying mechanism is unknown. Autophagy and ferroptosis are two modes of cell death that have been championed as potential mechanisms implicated in the antitumor effects of various drugs. The present study demonstrated that AIL effectively suppresses the Lewis cell proliferation in non-small cell lung cancer using MTT and colony formation assays. Autophagy and ferroptosis were verified using western blotting, immunofluorescence and ferroptosis detection. Additionally, the findings revealed that regulating the AMPK/mTOR/p70S6k signaling pathway may be the underlying mechanism for the antitumor effect of AIL. The present study established a theoretical foundation for further research into the utilization of AIL as a novel antitumor approach.
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Exposure to cadmium (Cd), a toxic heavy metal classified as an environmental endocrine disruptor, can exert significant toxicity in both animals and humans. However, the potential effects of Cd exposure on socioemotional behaviors are still poorly understood, as are the underlying mechanisms. In the present study, employing a series of behavioral tests as well as 16â¯S rRNA sequencing analysis, we investigated the long-term effects of Cd exposure on socioemotional behaviors and their associated mechanisms in mice based on the brain-gut interaction theory. The results showed that postweaning exposure to Cd reduced the ability to resist depression, decreased social interaction, subtly altered sexual preference, and changed the composition of the gut microbiota in male mice during adolescence. These findings provided direct evidence for the deleterious effects of exposure to Cd in the postweaning period on socioemotional behaviors later in adolescence, and suggested that these effects of Cd exposure may be linked to changes in the gut microbiota.
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Cadmio , Microbioma Gastrointestinal , Humanos , Masculino , Animales , Ratones , Adolescente , Cadmio/toxicidadRESUMEN
Uncertainty quantification of the remaining useful life (RUL) for degraded systems under the big data era has been a hot topic in recent years. A general idea is to execute two separate steps: deep-learning-based health indicator (HI) construction and stochastic process-based degradation modeling. However, there exists a critical matching defect between the constructed HI and a degradation model, which seriously affects the RUL prediction accuracy. Toward this end, this article proposes an interactive prognosis framework between deep learning and a stochastic process model for the RUL prediction. First, we resort to stacked contractive autoencoders to fuse multiple sensor information of historical systems for constructing the HI in a typical unsupervised manner. Then, considering the nonlinear characteristic of the constructed HI, an exponential-like degradation model is introduced to construct its degradation evolving model, and theoretical expressions of the prediction results are derived under the concept of the first hitting time. Furthermore, we design an optimization objective function by integrating the HI construction and degradation modeling for the RUL prediction. To minimize the designed objective function of the proposed interactive prognosis framework, a gradient descent algorithm is employed to update the model parameters. Based on the well-trained interactive prognosis model, we can obtain the HI of a field system from stacked contractive autoencoders with sensor data and the probability density function (pdf) of the predicted RUL on the basis of the estimated parameters. Finally, the effectiveness and superiority of the proposed interactive prognosis method are verified by two case studies associated with turbofan engines.
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Huddling behavior, a typical social interaction among animals, has the benefits of obtaining social support and adapting environment. Huddling behavior is determined by social (social hierarchy), environmental factors (stress events), and the neuroendocrine system. Nevertheless, the huddling behavior of different social hierarchies and the underlying mechanisms have not been fully elucidated. In the present study, acute 2-methyl-2-thiazoline (2 MT) can induce huddling behavior and significantly increase serum levels of testosterone (T) in mice; and the increased T level was positively correlated with huddling behavior. Further, the T treatment significantly increased the huddling behavior in mice under 2 MT exposure condition. More interestingly, T can quickly promote dominant individuals to occupy safe positions when huddling together under predator odor. Collectively, T can rapidly regulate the individual's adaptive response to threats in a social rank-dependent manner, which provides a new perspective for the in-depth study of the influencing factors and underlying mechanisms of huddling behavior.
RESUMEN
OBJECTIVE: To analysis the risk factors and safety of administration of norepinephrine (NE) via peripheral vein line (PVL) in patients with septic shock. METHODS: A single-center retrospective study was conducted. According to the Lanzhou University Second Hospital information system (HIS) and nursing adverse events report cards, patients with septic shock administrated with NE via PVL to correct the hypotension from January 1st 2015 to December 31st, 2019 were enrolled. The patients' general information, placement location of peripheral venous catheter and venousneedle type, characteristics of NE usage and patient general condition when extravasation occurred were collected. The univariate analysis and Logistic regression were used to analyze risk factors associated with extravasation. Also, the receiver operator characteristic curve (ROC curve) was drawn, and the predictive value of risk factors for extravasation was analyzed. RESULTS: A total of 1 022 cases with NE were enrolled. After a preliminary screening, a total of 910 cases with NE were used to correct low blood pressure, including 116 cases of peripheral venous infusion. The average age was (52.91±18.69) years old, with majority of female (77 cases, 66.4%). Basic diseases were mainly chronic obstructive pulmonary disease (COPD, 100 cases, 86.2%), followed by hypertension (91 cases, 78.4%), coronary heart disease (87 cases, 75.0%), type 2 diabetes (74 cases, 63.8%) respectively, the primary disease was septic shock in 109 cases (94.0%). A total of 147 peripheral venous catheters were inserted, and the most common site of puncture was the forearm [78.9% (116/147)], followed by the hand [12.2% (18/147)] and the median cubital vein [8.8% (13/147)]. 89.9% of the needles were 20 G in diameter, and 75 cases (64.7%) were converted to central venous catheters (CVC) during subsequent treatment due to continuous infusion of NE. Six patients (5.2%) had extravasation, the median time of extravasation was 29 (23-39) hours, and the median time of NE was 23 (11-53) hours, including 2 patients with an infusion concentration of 60 mg/L and 4 patients with an infusion concentration of 120 mg/L.The infusion speed was 0.5-1.0 µg×kg-1×min-1, and the average speed of infusion was (0.75±0.04) µg×kg-1×min-1 when extravasation. Univariate and binary Logistic regression analysis showed that the risk factors related to the occurrence of extravasation included: (1) patient factors: the presence of basic diseases, hypertension [odds ratio (OR) = 3.11, 95% confidence interval (95%CI) was 3.09-3.12, P = 0.001] and edema (OR = 1.79, 95%CI was 1.32-2.99, P = 0.032). (2) Factors of infusion fluid itself: long-term (> 24 hours) infusion (OR = 2.91, 95%CI was 1.04-5.96, P = 0.040), infusion concentration > 60 mg/L (OR = 1.88, 95%CI was 1.32-3.99, P = 0.024), infusion speed > 0.3 µg×kg-1×min-1 (OR = 2.43, 95%CI was 2.38-2.51, P = 0.029) and diameter of needles < 20 G (OR = 3.11, 95%CI was 3.09-3.22, P = 0.033). (3) Medical personnel factors: lack of observation and assessment (OR = 1.09, 95%CI was 1.03-6.77, P = 0.043). The ROC curve analysis showed that: edema, long-term infusion (> 24 hours), infusion rate > 0.3 µg×kg-1×min-1 and diameter of needles < 20 G had a certain predictive value for extravasation of NE through peripheral venous infusion in patients with septic shock, the area under ROC curve (AUC) was 0.610, 0.762, 0.672, 0.629, 95%CI was 0.508-0.713, 0.675-0.849, 0.571-0.772, 0.525-0.732, and P values were 0.044, 0.000, 0.002, 0.019, respectively. CONCLUSIONS: Hypertension, edema, long-term infusion (> 24 hours), infusion concentration > 60 mg/L, infusion speed > 0.3 µg×kg-1×min-1, diameter of needle < 20 G, and lack of observation and evaluation by medical staff regularly were risk factors affecting the safety of peripheral intravenous NE in patients with septic shock. Peripheral NE should be avoided in the presence of the above risk factors.