The superior antimicrobial properties of silver nanoparticles (Ag NPs) are well-documented, but the exact mechanisms underlying Ag-NP microbial toxicity remain the subject of intense debate. Here, we ...show that Ag-NP concentrations as low as 10 ppm exert significant toxicity against Bacillus subtilis, a beneficial bacterium ubiquitous in the soil. Growth arrest and chromosomal DNA degradation were observed, and flow cytometric quantification of propidium iodide (PI) staining also revealed that Ag-NP concentrations of 25 ppm and above increased membrane permeability. RedoxSensor content analysis and Phag-GFP expression analysis further indicated that reductase activity and cytosolic protein expression decreased in B. subtilis cells treated with 10-50 ppm of Ag NPs. We conducted X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analyses to directly clarify the valence and fine structure of Ag atoms in B. subtilis cells placed in contact with Ag NPs. The results confirmed the Ag species in Ag NP-treated B. subtilis cells as Ag2O, indicating that Ag-NP toxicity is likely mediated by released Ag+ ions from Ag NPs, which penetrate bacterial cells and are subsequently oxidized intracellularly to Ag2O. These findings provide conclusive evidence for the role of Ag+ ions in Ag-NP microbial toxicity, and suggest that the impact of inappropriately disposed Ag NPs to soil and water ecosystems may warrant further investigation.
Zinc oxide nanoparticles (ZnO NPs) are an important antimicrobial additive in many industrial applications. However, mass-produced ZnO NPs are ultimately disposed of in the environment, which can ...threaten soil-dwelling microorganisms that play important roles in biodegradation, nutrient recycling, plant protection, and ecological balance. This study sought to understand how ZnO NPs affect Bacillus subtilis, a plant-beneficial bacterium ubiquitously found in soil. The impact of ZnO NPs on B. subtilis growth, FtsZ ring formation, cytosolic protein activity, and biofilm formation were assessed, and our results show that B. subtilis growth is inhibited by high concentrations of ZnO NPs (≥ 50 ppm), with cells exhibiting a prolonged lag phase and delayed medial FtsZ ring formation. RedoxSensor and Phag-GFP fluorescence data further show that at ZnO-NP concentrations above 50 ppm, B. subtilis reductase activity, membrane stability, and protein expression all decrease. SDS-PAGE Stains-All staining results and FT-IR data further demonstrate that ZnO NPs negatively affect exopolysaccharide production. Moreover, it was found that B. subtilis biofilm surface structures became smooth under ZnO-NP concentrations of only 5-10 ppm, with concentrations ≤ 25 ppm significantly reducing biofilm formation activity. XANES and EXAFS spectra analysis further confirmed the presence of ZnO in co-cultured B. subtilis cells, which suggests penetration of cell membranes by either ZnO NPs or toxic Zn+ ions from ionized ZnO NPs, the latter of which may be deionized to ZnO within bacterial cells. Together, these results demonstrate that ZnO NPs can affect B. subtilis viability through the inhibition of cell growth, cytosolic protein expression, and biofilm formation, and suggest that future ZnO-NP waste management strategies would do well to mitigate the potential environmental impact engendered by the disposal of these nanoparticles.
Parkinson disease (PD) is a neurodegenerative process that leads to a selective loss of dopaminergic neurons, mainly in the basal ganglia of the brain. Numerous studies have analyzed the ability of ...optical coherence tomography (OCT) to detect retinal nerve fiber layer (RNFL) thickness abnormalities and changes in PD, but the results have not always been consistent. Therefore, we carried out a meta-analysis to evaluate the RNFL thickness measured with OCT in PD.
Case-control studies were selected through an electronic search of the Cochrane Controlled Trials Register, PUBMED and EMBASE. For the continuous outcomes, we calculated the weighted mean difference (WMD) and 95% confidence interval (CI). The statistical analysis was performed by RevMan 5.0 software. Thirteen case-control studies were included in the present meta-analysis, containing a total of 644 eyes in PD patients and 604 eyes in healthy controls. The results of our study showed that there was a significant reduction in average RNFL thickness in patients with PD compared to healthy controls (WMD = -5.76, 95% CI: -8.99 to -2.53, P = 0.0005). Additionally, differences of RNFL thickness in superior quadrant (WMD = -4.44, 95% CI: -6.93 to -1.94, P = 0.0005), inferior quadrant (WMD = -7.56, 95% CI: -11.33 to -3.78, P<0.0001), nasal quadrant (WMD = -3.12, 95% CI: -5.63 to -0.61, P = 0.01) and temporal quadrant (WMD = -4.63, 95% CI: -7.20 to -2.06, P = 0.0004) were all significant between the two groups.
In view of these results and the noninvasive nature of OCT technology, we surmise that OCT could be a useful tool for evaluating the progression of the Parkinson disease.
ClinicalTrials.gov NCT01928212.
Aims
The evidence of hepatotoxicity of antithyroid drugs (ATDs) is limited to case reports or spontaneous reporting. This study aimed to quantify the incidence and comparative risks of hepatotoxicity ...for methimazole (MMI)/carbimazole (CBM) vs. propylthiouracil (PTU) in a population‐based manner.
Methods
We conducted a cohort study of hyperthyroidism patients initially receiving MMI/CBM or PTU between 1 January 2004 and 31 December 2008 using the Taiwan National Health Insurance Research Database. The examined hepatotoxicity consisted of cholestasis, non‐infectious hepatitis, acute liver failure and liver transplant, with the incidences and relative risks being quantified by Poisson exact methods and Cox proportional hazard models, respectively.
Results
The study cohort comprised 71 379 ATD initiators, with a median follow‐up of 196 days. MMI/CBM vs. PTU users had a higher hepatitis incidence rate (3.17/1000 vs. 1.19/1000 person‐years) but a lower incidence of acute liver failure (0.32/1000 vs. 0.68/1000 person‐years). The relative risk analysis indicated that any use of MMI/CBM was associated with a 2.89‐fold (95% CI 1.81, 4.60) increased hepatitis risk compared with PTU, with the risk increasing to 5.08‐fold for high dose MMI/CBM (95% CI 3.15, 8.18). However, any MMI/CBM use vs. PTU was not related to an increased risk of cholestasis (adjusted hazard ratio HR 1.14, 95% CI 0.40, 3.72) or acute liver failure (adjusted HR 0.54, 95% CI 0.24, 1.22).
Conclusions
MMI/CBM and PTU exert dissimilar incidence rates of hepatotoxicity. Compared to PTU, MMI/CBM are associated in a dose‐dependent manner with an increased risk for hepatitis while the risks are similar for acute liver failure and cholestasis.
Maintaining spatial orientation when carrying out goal-directed movements requires an animal to perform angular path integration. Such functionality has been recently demonstrated in the ellipsoid ...body (EB) of fruit flies, though the precise circuitry and underlying mechanisms remain unclear. We analyze recently published cellular-level connectomic data and identify the unique characteristics of the EB circuitry, which features coupled symmetric and asymmetric rings. By constructing a spiking neural circuit model based on the connectome, we reveal that the symmetric ring initiates a feedback circuit that sustains persistent neural activity to encode information regarding spatial orientation, while the asymmetric rings are capable of integrating the angular path when the body rotates in the dark. The present model reproduces several key features of EB activity and makes experimentally testable predictions, providing new insight into how spatial orientation is maintained and tracked at the cellular level.Ellipsoid body (EB) neurons in the fruit fly represent the animal heading through a bump-like activity dynamics. Here the authors report a connectome-driven spiking neural circuit model of the EB and the protocerebral bridge (PB) that can maintain and update an activity bump related to the spatial orientation.
To unravel pairing mechanism of a superconductor from limited, indirect experimental data is always a difficult task. It is common but sometimes dubious to explain by a theoretical model with some ...tuning parameters. In this work, we propose that the machine learning might infer pairing mechanism from observables like superconducting gap functions. For superconductivity within the Migdal-Eliashberg theory, we perform supervised learning between superconducting gap functions and electron-boson spectral functions. For simple spectral functions, the neural network can easily capture the correspondence and predict perfectly. For complex spectral functions, an autoencoder is utilized to reduce the complexity of the spectral functions to be compatible to that of the gap functions. After this complexity-reduction process, relevant information of the spectral function is extracted and good performance restores. Our proposed method can extract relevant information from data and can be applied to general function-to-function mappings with asymmetric complexities either in physics or other fields.
Graphene oxide (GO) composites with various metal nanoparticles (NPs) are attracting increasing interest owing to their broad scope in biomedical applications. Here, microwave-assisted chemical ...reduction was used to deposit nano-silver and zinc oxide NPs (Ag and ZnO NPs) on the surface of reduced GO (rGO) at the following weight percentages: 5.34% Ag/rGO, 7.49% Ag/rGO, 6.85% ZnO/rGO, 16.45% ZnO/rGO, 3.47/34.91% Ag/ZnO/rGO, and 7.08/15.28% Ag/ZnO/rGO. These materials were tested for antibacterial activity, and 3.47/34.91% Ag/ZnO/rGO and 7.08/15.28% Ag/ZnO/rGO exhibited better antibacterial activity than the other tested materials against the gram-negative bacterium
K12
At 1000 ppm, both these Ag/ZnO/rGO composites had better killing properties against both
K12 and the gram-positive bacterium
SA113 than Ag/rGO and ZnO/rGO did. RedoxSensor flow cytometry showed that 3.47/34.91% Ag/ZnO/rGO and 7.08/15.28% Ag/ZnO/rGO decreased reductase activity and affected membrane integrity in the bacteria. At 100 ppm, these two composites affected membrane integrity more in
, while 7.08/15.28% Ag/ZnO/rGO considerably decreased reductase activity in
. Thus, the 3.47/34.91% and 7.08%/15.28% Ag/ZnO/rGO nanocomposites can be applied not only as antibacterial agents but also in a variety of biomedical materials such as sensors, photothermal therapy, drug delivery, and catalysis, in the future.
The objective of this study was to evaluate the effects of a hot‐water extract of defatted Camellia oleifera seeds (CSE) in carbon tetrachloride (CCl4)‐induced liver damage in rats. Wistar rats were ...separated into four groups including the normal (N) and CCl4 control (C) groups, which are fed a control diet, and the CCL (low‐dose CSE) and CCH (high‐dose CSE) groups, which are fed with a control diet plus different amount of CSE for an 8‐week experimental period. Liver injury in the C, CCL, and CCH groups was induced by injecting CCl4 (i.p.) twice a week from the 5th week to the end of the study. In CCl4‐treated rats, the alanine transaminase (ALT) and aspartate transaminase (AST) activities and malondialdehyde (MDA) concentration significantly increased compared to the normal group. Lower antioxidative enzyme activities and higher proinflammatory cytokines, transforming growth factor‐β (TGF‐β) and hydroxyproline concentrations in the liver were also found in the CCl4‐treated group compared to the normal group. In contrast, the administration of CSE alleviated the biochemical and histopathological changes including inflammation, liver cell damage, and fibrosis caused by CCl4 in rats. Our results indicated that CSE exhibited hepatoprotective effects in CCl4‐induced liver hepatotoxicity through alleviating hepatic inflammation and fibrosis in rats.
Practical Application
Camellia oleifera are widely used for edible oil production while the defatted seeds pomace is often discarded. We found that extract of C. oleifera pomace containing phenolic compounds, saponins, and polysaccharides showed protective effects chemical‐driven liver damage and, therefore, may be used in further studies and developing functional foods.
Abstract
Study Objectives
To examine the effect of sleep timing intervention on sleep quality, attention, and sleepiness at work among night shift workers with shift work disorder.
Methods
We ...recruited 60 real-life night shift workers through advertisements to participate this cross-over clinical trial. Shift work disorder was confirmed with interview and sleep log. Participants were designated to follow evening sleep (15:00–23:00) and morning sleep (09:00–17:00) schedules in a randomized order. Chronotype was confirmed by the Munich Chronotype Questionnaire. Sleep behaviors and light exposure were recorded using actigraphy. Outcome measures were sleepiness evaluated by the Karolinska Sleepiness Scale, sleep quality evaluated by the Pittsburgh Sleep Quality Index, and attention performance assessed with psychomotor vigilance test. Differences in outcome between the morning and evening sleep schedules were compared using repeated measures ANOVA.
Results
The participants slept for longer durations during evening sleep schedules compared with morning sleep schedules. Lower sleepiness scores, higher sleep quality, and shorter reaction times and less lapse numbers in the psychomotor vigilance test were observed for participants during evening sleep schedules than morning sleep schedules after adjustment for light exposure and sleep duration. Significant interaction effects were observed for reaction time and lapse number between chronotype and sleep schedule, where the differences between sleep schedules were most prominent among those with late chronotypes.
Conclusions
It is recommended that night shift workers with shift work disorder arrange to sleep in the evening instead of the morning for better sleep and attention performance, especially those with late chronotypes.
Trial registration
Sleep Schedule Intervention Study Among Night Shift Workers, https://clinicaltrials.gov/ct2/show/NCT04160572, ClinicalTrials.gov Identifier: NTC04160572.
Colorectal cancer (CRC) presents a significant global health burden, characterized by a heterogeneous molecular landscape and various genetic and epigenetic alterations. Programmed cell death (PCD) ...plays a critical role in CRC, offering potential targets for therapy by regulating cell elimination processes that can suppress tumor growth or trigger cancer cell resistance. Understanding the complex interplay between PCD mechanisms and CRC pathogenesis is crucial. This study aims to construct a PCD-related prognostic signature in CRC using machine learning integration, enhancing the precision of CRC prognosis prediction.
We retrieved expression data and clinical information from the Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Fifteen forms of PCD were identified, and corresponding gene sets were compiled. Machine learning algorithms, including Lasso, Ridge, Enet, StepCox, survivalSVM, CoxBoost, SuperPC, plsRcox, random survival forest (RSF), and gradient boosting machine, were integrated for model construction. The models were validated using six GEO datasets, and the programmed cell death score (PCDS) was established. Further, the model's effectiveness was compared with 109 transcriptome-based CRC prognostic models.
Our integrated model successfully identified differentially expressed PCD-related genes and stratified CRC samples into four subtypes with distinct prognostic implications. The optimal combination of machine learning models, RSF + Ridge, showed superior performance compared with traditional methods. The PCDS effectively stratified patients into high-risk and low-risk groups, with significant survival differences. Further analysis revealed the prognostic relevance of immune cell types and pathways associated with CRC subtypes. The model also identified hub genes and drug sensitivities relevant to CRC prognosis.
The current study highlights the potential of integrating machine learning models to enhance the prediction of CRC prognosis. The developed prognostic signature, which is related to PCD, holds promise for personalized and effective therapeutic interventions in CRC.
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