Search

Gallic acid (GA) is a common phenolic acid that is widely used as an antibacterial agent in the food industry. In order to increase its applicability, this study investigated the antibacterial effects and mechanisms of GA on Escherichia coli O157:H7 (E. coli O157:H7) after UV-C light treatment combined with photodynamic therapy. This study evaluated the photodynamic effects of GA after UV-C irradiation (UVC-GA) based on changes in substances and ROS generation. Using E. coli O157:H7 as a model bacterium, the antibacterial effects were evaluated from various aspects, including MIC, MBC, time-kill curve, cell membrane damage, DNA damage, protein damage, motility changes, biofilm formation, and activity. In addition, the antibacterial mechanisms were further investigated by combining RT-qPCR analysis of gene expression. The results of this study demonstrated that GA has the ability to exert photodynamic effects, even after the removal of the UV-C light source, and can effectively reduce the number of viable E. coli O157:H7 cells. Moreover, UVC-GA caused significant damage to the cell membrane, DNA, and proteins, and according to the RT-qPCR results, the antibacterial mechanisms of UVC-GA and GA on E. coli O157:H7 were completely different. Based on the above results, food-sterilizing detergents can be developed and applied to contaminated oyster to provide an effective food cleaning effect. [ABSTRACT FROM AUTHOR]

Background: For patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH), cardiopulmonary exercise testing (CPET) can reflect cardiopulmonary reserve function. However, CPET may not be readily accessible for patients with high-risk conditions or limited mobility due to disability. Echocardiography, on the other hand, serves as a widely available diagnostic tool for all CHD-PAH patients. This study was aimed to identify the parameters of echocardiography that could serve as indicators of cardiopulmonary function and exercise capacity. Methods: A cohort of 70 patients contributed a total of 110 paired echocardiogram and CPET results to this study, with 1 year interval for repeated examinations. Echocardiography and exercise testing were conducted following standardized procedures, and the data were collected together with clinically relevant indicators for subsequent statistical analysis. Demographic comparisons were performed using t-tests and chi-square tests. Univariate and multivariate analyses were conducted to identify potential predictors of peak oxygen uptake (peak VO2) and the carbon dioxide ventilation equivalent slope (VE/VCO2 slope). Receiver operating characteristic (ROC) analysis was used to assess the performance of the parameters. Results: The ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) was found to be the only independent indicator significantly associated with both peak VO2 and VE/VCO2 slope (both p < 0.05). Additionally, left ventricular ejection fraction (LVEF) and right ventricular fractional area change (FAC) were independently correlated with the VE/VCO2 slope (both p < 0.05). TAPSE/PASP showed the highest area under the ROC curve (AUC) for predicting both a peak VO2 ≤ 15 mL/kg/min and a VE/VCO2 slope ≥ 36 (AUC = 0.91, AUC = 0.90, respectively). The sensitivity and specificity of TAPSE/PASP at the optimal threshold exceeded 0.85 for both parameters. Conclusions: TAPSE/PASP may be a feasible echocardiographic indicator for evaluating exercise tolerance. [ABSTRACT FROM AUTHOR]

Urine is a complex biofluid that reflects both overall physiologic state and the state of the genitourinary tissues through which it passes. It contains both secreted proteins and proteins encapsulated in tissue-derived extracellular vesicles (EVs). To understand the population variability and clinical utility of urine, we quantified the secreted and EV proteomes from 190 men, including a subset with prostate cancer. We demonstrate that a simple protocol enriches prostatic proteins in urine. Secreted and EV proteins arise from different subcellular compartments. Urinary EVs are faithful surrogates of tissue proteomes, but secreted proteins in urine or cell line EVs are not. The urinary proteome is longitudinally stable over several years. It can accurately and non-invasively distinguish malignant from benign prostatic lesions and can risk-stratify prostate tumors. This resource quantifies the complexity of the urinary proteome and reveals the synergistic value of secreted and EV proteomes for translational and biomarker studies. Urine can be used to easily analyse the health of patients. Here, the authors identify proteins in urinary extracellular vesicles that distinguish prostate cancer from benign lesions. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that oxidative stress and its resistance plays important roles in the process of tumor metastasis, and mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) damage is an important molecular event in oxidative stress. In lung cancer, the normal fibroblasts (NFs) are activated as cancer-associated fibroblasts (CAFs), and act in the realms of the tumor microenvironment (TME) with consequences for tumor growth and metastasis. However, its activation mechanism and whether it participates in tumor metastasis through antioxidative stress remain unclear. Methods: The role and signaling pathways of tumor cell derived extracellular vesicles (EVs) activating NFs and the characteristic of induced CAFs (iCAFs) were measured by the transmission electron microscopy, nanoparticle tracking analysis, immunofluorescence, collagen contraction assay, quantitative PCR, immunoblotting, luciferase reporter assay and mitochondrial membrane potential detection. Mitochondrial genome and single nucleotide polymorphism sequencing were used to investigate the transport of mtDNA from iCAFs to ρ0 cells, which were tumor cells with mitochondrial dysfunction caused by depletion of mtDNA. Further, the effects of iCAFs on mitochondrial function, growth and metastasis of tumor cells were analysed in co-culture models both in vitro and in vivo, using succinate dehydrogenase, glutathione and oxygen consumption rate measurements, CCK-8 assay, transwell assay, xenotransplantation and metastasis experiments as well as in situ hybridization and immunohistochemistry. Results: Our findings revealed that EVs derived from high-metastatic lung cancer cells packaged miR-1290 that directly targets MT1G, leading to activation of AKT signaling in NFs and inducing NFs conversion to CAFs. The iCAFs exhibit higher levels of autophagy and mitophagy and more mtDNA release, and reactive oxygen species (ROS) could further promote this process. After cocultured with the conditioned medium (CM) of iCAFs, the ρ0 cells may restore its mitochondrial function by acquisition of mtDNA from CAFs, and further promotes tumor metastasis. Conclusions: These results elucidate a novel mechanism that CAFs activated by tumor-derived EVs can promote metastasis by transferring mtDNA and restoring mitochondrial function of tumor cells which result in resistance of oxidative stress, and provide a new therapeutic target for lung cancer metastasis. [ABSTRACT FROM AUTHOR]

Background: Accurately stratifying patients with pulmonary arterial hypertension (PAH) is very important, and traditional risk scores still have internal heterogeneity. This study aimed to construct a risk stratification model that can accurately identify clinical worsening (CW) events in conventional low‐intermediate risk patients with pulmonary hypertension under targeted drug treatment by using echocardiographic parameters. Methods: This study is a single‐center, prospective study, including 105 PAH patients who underwent regular follow‐up at Guangdong Provincial People's Hospital from October 2021 to April 2023. The primary endpoint was the occurrence of CW, including death, hospitalization due to pulmonary hypertension, escalation of targeted drug therapy, and worsening of PAH. The predictive value of the echocardiography‐based three‐strata risk model was assessed using Kaplan‐Meier curves and COX regression analysis. Results: A total of 98 PAH patients were ultimately included in this study. The median follow‐up duration was 26 months (range 7–28 months). The echocardiography‐based three‐strata model included the ratio of tricuspid annular plane systolic excursion and pulmonary artery systolic pressure (TAPSE/PASP) and inferior vena cava (IVC). The echocardiography‐based three‐strata model had higher diagnostic value (C‐index =.76) compared to the 2022 ESC/ERS three‐strata model and four‐strata model (C‐index =.66 and C‐index =.61, respectively). PAH patients with lower TAPSE/PASP and wider IVC showed a higher CW rate compared to patients with higher TAPSE/PASP and normal IVC (HR = 15.1, 95%CI:4.4‐51.9, p <.001). Conclusion: The echocardiography‐based three‐strata model based on TAPSE/PASP and IVC can effectively improve the stratification of low‐intermediate risk PAH patients under targeted treatment. [ABSTRACT FROM AUTHOR]

In recent years, the drone swarm has experienced remarkable growth, finding applications across diverse domains such as agricultural surveying, disaster rescue and logistics delivery. However, the rapid expansion of drone swarm usage underscores the necessity for innovative approaches in the field. Traditional algorithms face challenges in adapting to complex tasks, environmental modeling and computational complexity, highlighting the need for more advanced solutions like multi-agent deep reinforcement learning to enhance efficiency and robustness in drone swarm. Our proposed approach tackles this challenge by embracing temporal and spatial. In terms of the temporal, the proposed approach builds upon historical data, it enhances the predictive capabilities regarding future behaviors. In the spatial, the proposed approach leverage graph theory to model the swarm's features, while attention mechanisms strengthen the relationships between individual drones. The proposed approach addresses the unique characteristics of drone swarms by incorporating temporal dependencies, spatial structures and attention mechanisms. Extensive experiments validate the effectiveness of the proposed approach. [ABSTRACT FROM AUTHOR]

Simple Summary: Model-based decision-making guides organism behavior by representing the relationships between states. Previous studies have shown that the mammalian hippocampus (Hp) plays a key role in model-based learning. However, the hippocampal neural mechanisms of birds for model-based learning are largely unknown. We trained pigeons to perform a two-step task. Using a combination of neural analysis and computational modeling, we show that the pigeons use model-based inferences to learn multi-step tasks, and multiple LFP frequency bands collaboratively contribute to model-based learning. Specifically, the high-frequency (12–100 Hz) oscillations represent model-based valuations, while the low-frequency (1–12 Hz) neural similarity is influenced by the relationship between temporal context states. These findings expand the understanding of the hippocampus' role in avian model-based learning. Model-based decision-making guides organism behavior by the representation of the relationships between different states. Previous studies have shown that the mammalian hippocampus (Hp) plays a key role in learning the structure of relationships among experiences. However, the hippocampal neural mechanisms of birds for model-based learning have rarely been reported. Here, we trained six pigeons to perform a two-step task and explore whether their Hp contributes to model-based learning. Behavioral performance and hippocampal multi-channel local field potentials (LFPs) were recorded during the task. We estimated the subjective values using a reinforcement learning model dynamically fitted to the pigeon's choice of behavior. The results show that the model-based learner can capture the behavioral choices of pigeons well throughout the learning process. Neural analysis indicated that high-frequency (12–100 Hz) power in Hp represented the temporal context states. Moreover, dynamic correlation and decoding results provided further support for the high-frequency dependence of model-based valuations. In addition, we observed a significant increase in hippocampal neural similarity at the low-frequency band (1–12 Hz) for common temporal context states after learning. Overall, our findings suggest that pigeons use model-based inferences to learn multi-step tasks, and multiple LFP frequency bands collaboratively contribute to model-based learning. Specifically, the high-frequency (12–100 Hz) oscillations represent model-based valuations, while the low-frequency (1–12 Hz) neural similarity is influenced by the relationship between temporal context states. These results contribute to our understanding of the neural mechanisms underlying model-based learning and broaden the scope of hippocampal contributions to avian behavior. [ABSTRACT FROM AUTHOR]

Objective We aimed to explore the mechanism of action of cervical transverse process tip acupuncture in a rat model of posterior circulation ischemic vertigo (PCIV) based on the G protein-coupled receptor (Mas)/protein kinase A(PKA)/cyclophosphoadenosine effector binding protein (CREB) pathway. Methods According to the random number table method, 32 male SD rats were divided into the sham operation group (n=8), the model group (n=8), the nimodipine group (n=8), and the electroacupuncture group (n=8). In all groups except for the sham operation group, the PCIV model was established by ligating the right common carotid artery (CCA) and the right subclavian artery (SCA). In the sham operation group, only the right CCA and the right SCA were removed and sutured directly without ligation. The nimodipine group was given intragastric administration of nimodipine suspension (12 mg/kg), and the electroacupuncture group selected C2, C4, and C6 transverse process tip for acupuncture, and performed electroacup uncture treatment on both sides of C2 and C6, 20 minutes each time. There was no intervention in the sham operation group and the model group. The intervention was given once a day for 14 days. Cerebral blood flow, the decrease decline rate of cerebral blood flow, and the step-down avoidance time were recorded in each group. Apoptosis of neurons in the vestibular nucleus of the right brainstem was observed by TUNEL staining, and the protein expression levels of Mas, PKA-Ca, CREB, p-CREB, Bcl-2, and Bax in the vestibular nucleus of the right brainstem were determined by Western blotting. Results Before intervention, compared with the sham operation group, cerebral blood flow in the right vestibular nucleus was decreased and decline rate of cerebral blood flow in the right vestibular nucleus was increased in the remaining three groups (P<0.05), which suggested that the model was successfully established. After intervention, compared with the sham operation group, the model group showed lower cerebral blood flow in the right vestibular nucleus, larger decline rate of cerebral blood flow in the right vestibular nucleus, apoptosis rate in the vestibular nucleus of the right brainstem and protein expression level of Bax increased, and reduced protein expression levels of Bcl-2, Mas, PKA-Ca, and p-CREB/CREB (P<0.05). Compared with the model group, the electroacupuncture group and the nimodipine group showed increased cerebral blood flow in the right vestibular nucleus, a smaller decline rate of cerebral blood flow in the right vestibular nucleus, a shorter step-down avoidance time, a decrease in apoptosis rate in the vestibular nucleus of the right brainstem, decreased protein expression level of Bax, and increased protein expression levels of Bcl-2, Mas, PKA-Ca, and p-CREB/CREB (P<0.05). Compared with the nimodipine group, the electroacupuncture group had increased cerebral blood flow in the right vestibular nucleus, a smaller decline rate of cerebral blood flow in the right vestibular nucleus, a shorter step-down avoidance time, a decrease in apoptosis rate in the vestibular nucleus of the right brainstem, decreased protein expression level of Bax, and increased protein expression levels of Bcl-2, Mas, PKA-Ca, and p-CREB/CREB (P<0.05). Conclusion Cervical transverse process tip acupuncture can effectively inhibit apoptosis in the vestibular nucleus in rats with PCIV. Its mechanism may be related to improving cerebral blood flow of the vestibular nucleus and activation of the Mas/PKA/CREB signaling pathway, followed by the modulation of the levels of relevant proteins to inhibit apoptosis in the vestibular nucleus. [ABSTRACT FROM AUTHOR]

Simple Summary: The hippocampus (Hp) is involved in various aspects of spatial cognition during navigation, reflected in multiple neural oscillations across different frequencies. Given the structure homology between the avian and mammalian Hp, does it exhibit similar cross-frequency interaction mechanisms? Unlike rodents, birds can navigate by walking and flying. So, does the avian Hp share the same information interaction under different locomotor modes? In this study, we employed rock pigeons with exceptional spatial navigation abilities and conducted two goal-directed navigational experiments: a ground maze task with a circuitous paradigm and an outdoor homing flight task. These experiments were designed to explore the interactions between different frequency bands in the avian Hp during walking and flying navigation. The study revealed that phase–amplitude coupling (PAC) existed in the avian Hp during the navigational active phases. Meanwhile, the sub-frequency bands modulated by theta oscillations are different in different modes of locomotion. These findings support evidence for cross-frequency interactions in the avian Hp during spatial navigation and contribute to explaining the role of coupling, at least partially, in the ongoing cognitive demands during the navigation process. Navigation is a complex task in which the hippocampus (Hp), which plays an important role, may be involved in interactions between different frequency bands. However, little is known whether this cross-frequency interaction exists in the Hp of birds during navigation. Therefore, we examined the electrophysiological characteristics of hippocampal cross-frequency interactions of domestic pigeons (Columba livia domestica) during navigation. Two goal-directed navigation tasks with different locomotor modes were designed, and the local field potentials (LFPs) were recorded for analysis. We found that the amplitudes of high-frequency oscillations in Hp were dynamically modulated by the phase of co-occurring theta-band oscillations both during ground-based maze and outdoor flight navigation. The high-frequency amplitude sub-frequency bands modulated by the hippocampal theta phase were different at different tasks, and this process was independent of the navigation path and goal. These results suggest that phase–amplitude coupling (PAC) in the avian Hp may be more associated with the ongoing cognitive demands of navigational processes. Our findings contribute to the understanding of potential mechanisms of hippocampal PAC on multi-frequency informational interactions in avian navigation and provide valuable insights into cross-species evolution. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DCM) is a chronic microvascular complication of diabetes that is generally defined as ventricular dysfunction occurring in patients with diabetes and unrelated to known causes. Several mechanisms have been proposed to contribute to the occurrence and persistence of DCM, in which oxidative stress and autophagy play a non‐negligible role. Diabetic cardiomyopathy is involved in a variety of physiological and pathological processes. The 5′ adenosine monophosphate‐activated protein kinase/nuclear factor‐erythroid 2‐related factor 2 (AMPK/Nrf2) are expressed in the heart, and studies have shown that asiaticoside (ASI) and activated AMPK/Nrf2 have a protective effect on the myocardium. However, the roles of ASI and AMPK/Nrf2 in DCM are unknown. The intraperitoneal injection of streptozotocin (STZ) and high‐fat feed were used to establish the DCM models in 100 C57/BL mice. Asiaticoside and inhibitors of AMPK/Nrf2 were used for intervention. Cardiac function, oxidative stress, and autophagy were measured in mice. DCM mice displayed increased levels of oxidative stress while autophagy levels declined. In addition, AMPK/Nrf2 was activated in DCM mice with ASI intervention. Further, we discovered that AMPK/Nrf2 inhibition blocked the protective effect of ASI by compound C and treatment with ML‐385. The present study demonstrates that ASI exerts a protective effect against DCM via the potential activation of the AMPK/Nrf2 pathway. Asiaticoside is a potential therapeutic target for DCM. [ABSTRACT FROM AUTHOR]

Abnormal microglial activation has been suggested as "driven force" promoting brain aging. Lipid droplets accumulating microglia (LDAM), identified as a novel inflammatory phenotype, elevate neuroinflammation and exaggerate neuronal injuries in aging and multiple neurodegenerative diseases. Since chronic HIV (human immunodeficiency virus) (+) individuals show an accelerated brain aging and higher incidence of neurological symptoms compared to age-matched HIV (-) population, we hypothesize that LDAM are also involved in such phenomenon. For validating the hypothesis, we employed HIV transgenic (HIV-Tg) and wilt type (WT) rats to check lipid droplets (LDs) accumulation in the brains at mature (6 months) and middle age (12 months). Our results showed that HIV-Tg rats possess higher levels of LDs formation in the hippocampus (HP) and prefrontal cortex (PFc) than controls at middle age. Increased LDs are mainly presented in microglia in the HP but largely co-localized with astrocytes in the PFc. Interestingly, increased LDs are associated with upregulation on Iba1 but not with GFAP levels. HIV-Tg rats reveal an accelerated LDs accumulation during normal aging. Purified microglia from HIV-Tg rats (12 month) show higher expression of neuroimmune signaling than microglia from controls. HIV-Tg rats showed dysregulation on cholesterol synthesis in the brain HP as well as deficiency on locomotion coordination compared to controls. Overall, our results demonstrate substantial LDs accumulation in the brains of HIV-Tg rats which is associated with abnormal microglial activation and accelerated decline on locomotion coordination during aging. Dysregulation on lipid metabolism might underlie accelerated brain aging in the context of chronic HIV infection.

Prostate cancer is a significant health problem in the United States. It is remarkably heterogenous, ranging from slow growing disease amenable to active surveillance to highly aggressive forms requiring active treatments. Therefore, being able to precisely determine the nature of disease and appropriately match patients to available and/or novel therapeutics is crucial to improve patients' overall outcome and quality of life. Recently small extracellular vesicles (sEVs), a subset of nanoscale membranous vesicles secreted by various cells, have emerged as important analytes for liquid biopsy and promising vehicles for drug delivery. sEVs contain various biomolecules such as genetic material, proteins, and lipids that recapitulate the characteristics and state of their donor cells. The application of existing and newly developed technologies has resulted in an increased depth of knowledge about biophysical structures, biogenesis, and functions of sEVs. In prostate cancer patients, tumor-derived sEVs can be isolated from biofluids, commonly urine and blood. They mediate intercellular signaling within the tumor microenvironment and distal organ-specific sites, supporting cancer initiation, progression, and metastasis. A mounting body of evidence suggests that sEV components can be potent biomarkers for prostate cancer diagnosis, prognosis, and prediction of disease progression and treatment response. Due to enhanced circulation stability and bio-barrier permeability, sEVs can be also used as effective drug delivery carriers to improve the efficacy and specificity of anti-tumor therapies. This review discusses recent studies on sEVs in prostate cancer and is focused on their role as biomarkers and drug delivery vehicles in the clinical management of prostate cancer., (Copyright © 2024. Published by Elsevier Inc.)