Scientific Reports最新文献

In an effort to identify novel antibacterial agents, we presented two series of aminoguanidine derivatives that were designed by incorporating 1,2,4-triazol moieties. All compounds exhibited strong in vitro antibacterial activity against a variety of testing strains. Compound 5f was identified as a potent antibacterial agent with a minimum inhibitory concentration (MIC) of 2-8 µg/mL against S. aureus, E. coli, S. epidermidis, B. subtilis, C. albicans, multi-drug resistant Staphylococcus aureus and multi-drug resistant Escherichia coli and low toxicity (Hela > 100 µM). Membrane permeability and transmission electron microscopy (TEM) image studies demonstrated that compound 5f permeabilized bacterial membranes, resulting in irregular cell morphology and the rapid death of bacteria. The results of the present study suggested that aminoguanidine derivatives with 1,2,4-triazol moieties were the intriguing scaffolds for the development of bactericidal agents.

Uremic Encephalopathy results from the elevation of toxins and blood-brain barrier (BBB) disruption. Renal Ischemia/Reperfusion (I/R) injury is the principal cause of acute kidney injury and brain tissue injury. The present study was crafted to estimate the restorative impact of platelet-rich plasma (PRP) and exosome injection before the reperfusion phase on the kidney following renal I/R injury and its influence on brain tissue by tracking the histopathological, biochemical, and Doppler ultrasonography alternations in both kidney and brain tissue. Forty mature male rats were divided into five groups as follows: control, I/R, PRP, exosome, and Exosome + PRP. Renal Doppler ultrasonography was traced for all rats. Serum kidney functions and acetylcholine esterase enzyme (AchE) were evaluated. Both Gamma-aminobutyric acid (GABA) and glutamate were assessed in brain tissues. The oxidative stress (malondialdehyde), anti-oxidative (glutathione and catalase), and pro-inflammatory (Tumor necrosis factor- α and interleukin-6) markers were estimated in renal tissues. Additionally, morphometric histological examination was performed in both renal and brain tissues. Both PRP and exosome-received rats exhibited a significant improvement in both serum kidney functions and AchE compared to I/R rats. There was a 3.39-fold increase in GABA and a 2.27-fold decrease in glutamate levels in the brain tissue of PRP rats compared to the I/R rats. A significant elevation (P ≤ 0.0001) of glutathione and catalase besides a significant reduction in the expression of TNF-α and IL-6 was observed in renal tissue compared to I/R rats. A significant severe reduction (P < 0.0001) in the number of Purkinje cells, pyramidal cells in the cerebellar cortex, and the CA1 region in the hippocampus was observed in I/R rats which was significantly alleviated by both PRP and exosome. Furthermore, there was a significant improvement in Doppler parameters. PRP exerted a significant superior impact on the restoration of kidney functions and repairing uremic-induced damage in brain tissue.

The distinct spatiotemporal characteristics of the hourly intense precipitation (HIP) over the Pearl River Delta (PRD) and the impact of urbanization before and after the monsoon onset from 1972 to 2021 have been investigated using the hourly rain gauge data, nighttime lights data, and land use data. The results show a significant decreasing trend of HIP during the pre-monsoon onset period and a notable increasing trend during the post-monsoon onset period over the past five decades. However, compared to rural areas, rapid urbanization in the PRD after the mid-1990s weakens the HIP reduction, especially in the inland cities of PRD before the onset of the monsoon and enhances the HIP increase, particularly in the southeast inland and west coast cities after the onset of the monsoon. After rapid urbanization, the peak time of HIP has been postponed from 14 LST to 17 LST during the pre-monsoon onset period. HIP tends to occur more frequently in urban areas in the morning (10-12 LST) and evening (19-24 LST) compared to rural areas. In contrast, the impact of urbanization on the diurnal variation of HIP is not obvious during the post-monsoon period, despite higher frequencies of HIP occurring during the daytime (10-15 LST) in the urban areas after rapid urbanization. These findings provide valuable insights for forecasting HIP in urban agglomerations.

Compounds that can induce oxidative stress in cancer cells while remaining nontoxic to healthy cells are extremely promising for potential anticancer drugs. 2,2':6',2''-terpyridine-metal complexes possess these properties. The high level of activity (IC₅₀ = 0.605 µM) of 2,2':6',2''-terpyridine-metal complexes on lung, breast, pancreatic, and glioblastoma multiforme cancer lines and their selectivity (SI > 41.32) on human normal fibroblasts were confirmed and presented in this paper. The mechanism of action of these compounds is associated with the generation of reactive oxygen species, which affects several cellular pathways and signals. The results demonstrate that 2,2':6',2''-terpyridine-metal complexes affect cell cycle inhibition in the G0/G1 phase as well as the activation of apoptosis and autophagy cell death. These results were confirmed in several independent studies, including experiments measuring the fluorescence levels of reactive oxygen species, flow cytometry, and gene and protein analysis.

This study analyzes the optimization of Extra High Voltage (EHV) transmission line design parameters by Uttar Pradesh Power Corporation Limited (UPPCL) in India to improve power grid efficiency and reliability. UPPCL reduced insulation specifications for 400 kV lines from 27 to 21 disc insulators and decreased live metal clearance from 2600 to 2400 mm, resulting in 7-9% cost savings per line and reduced right-of-way requirements. While initial test lines performed satisfactorily for over 5 years, longer lines experienced operational challenges related to insulator quality, bird activity, and design margins. Tripping issues emerged during adverse weather conditions, particularly in foggy winter periods. Root cause analysis revealed the need for stringent insulator quality control, regular cleaning to mitigate bird dropping contamination, and potential corona ring design improvements. This case study demonstrates how targeted EHV transmission line optimization can yield significant cost and environmental benefits, while highlighting the importance of balancing economic gains with reliability and safety considerations. The findings provide valuable insights for future EHV transmission line designs and upgrades across India's power grid.

Alzheimer's disease (AD) is the most prevalent type of dementia. Its causes are not fully understood, but it is now known that factors like mitochondrial dysfunction, oxidative stress, and compromised ion channels contribute to its onset and progression. Flickering light therapy has shown promise in AD treatment, though its mechanisms remain unclear. In this study, we used a rat model of streptozotocin (STZ)-induced AD to evaluate the effects of 40 Hz flickering light therapy. Rats received intracerebroventricular (ICV) STZ injections, and 7 days after, they were exposed to 40 Hz flickering light for 15 min daily over seven days. Cognitive and memory functions were assessed using Morris water maze, novel object recognition, and passive avoidance tests. STZ-induced AD rats exhibited cognitive decline, elevated reactive oxygen species, amyloid beta accumulation, decreased serotonin and dopamine levels, and impaired mitochondrial function. However, light therapy prevented these effects, preserving cognitive function and synaptic plasticity. Additionally, flickering light restored mitochondrial metabolites and normalized ATP-insensitive mitochondrial calcium-sensitive potassium (mitoBKCa) channel activity, which was otherwise downregulated in AD rats. Our findings suggest that 40 Hz flickering light therapy could be a promising treatment for neurodegenerative disorders like AD by preserving synaptic and mitochondrial function.

We propose a fully automatic multi-task Bayesian model, named Bayesian Sequential Network (BSN), for predicting high-grade (Gleason  $\ge$  8) prostate cancer (PCa) prognosis using pre-prostatectomy FDG-PET/CT images and clinical data. BSN performs one classification task and five survival tasks: predicting lymph node invasion (LNI), biochemical recurrence-free survival (BCR-FS), metastasis-free survival, definitive androgen deprivation therapy-free survival, castration-resistant PCa-free survival, and PCa-specific survival (PCSS). Experiments are conducted using a dataset of 295 patients. BSN outperforms widely used nomograms on all tasks except PCSS, leveraging multi-task learning and imaging data. BSN also provides automated prostate segmentation, uncertainty quantification, personalized feature-based explanations, and introduces dynamic predictions, a novel approach that relies on short-term outcomes to refine long-term prognosis. Overall, BSN shows great promise in its ability to exploit imaging and clinicopathological data to predict poor outcome patients that need treatment intensification with loco-regional or systemic adjuvant therapy for high-risk PCa.

Cardiorenal fibrosis is a common feature of chronic cardiovascular disease and recent data suggests that cytokines and chemokines may also drive fibrosis. Here we tested the hypothesis that CXCR7, a highly conserved chemokine receptor, contributes to cardiac and renal fibrosis. We generated an anti-mouse CXCR7-specific monoclonal antibody (CXCR7 mAb) and tested its anti-fibrotic actions in cardiorenal fibrosis induced using the deoxycorticosterone acetate/uni-nephrectomy (DOCA-UNX) model. CXCR7 mAb treatment (10 mg/kg, twice weekly for 6 weeks) significantly attenuated the development of cardiac and renal fibrosis, and reduced fibrotic and inflammatory gene expression levels, in the absence of an effect on blood pressure. Immunohistochemical analysis demonstrated an increase in the vascular expression of CXCR7 in DOCA-UNX-treated mice. This study demonstrated that a CXCR7 mediated pathway plays a significant role in cardiac and renal fibrosis induced by DOCA-UNX treatment. Accordingly, antagonism of CXCR7 may provide a therapeutic opportunity to mitigate against fibrosis in the setting of mineralocorticoid excess.

Ex vivo studies of the brain are often employed as experimental systems in neuroscience. In general, brains for ex vivo MRI studies are usually fixed with paraformaldehyde to preserve molecular structure and prevent tissue destruction during long-term storage. As a result, fixing brain tissue causes microstructural changes and a decrease in brain volume. Therefore, the purpose of this study was to investigate the regional effect of brain volume and microstructural changes on the restricted diffusion of water molecules in the common marmoset brain using in vivo and ex vivo brains from the same individual. We used 9.4T magnetic resonance imaging and also compared the T2-weighted images and diffusion-weighted imaging (DWI) data between in vivo and ex vivo brains to investigate changes in brain volume and diffusion of water molecules in 12 common marmosets. We compared fractional anisotropy, mean diffusivity, AD (axial diffusivity), and radial diffusivity values in white matter and gray matter between in vivo and ex vivo brains. We observed that AD showed the strongest correlation with regional volume changes in gray matter. The results showed a strong correlation between AD and changes in brain volume. By comparing the in vivo and ex vivo brains of the same individual, we identified significant correlations between the local effects of perfusion fixation on microstructural and volumetric changes of the brain and alterations in the restricted diffusion of water molecules within the brain. These findings provide valuable insights into the complex relationships between tissue fixation, brain structure, and water diffusion properties in the marmoset brain.