Abstract
Photobiomodulation, by utilizing low-power light in the visible and near-infrared spectra to trigger biological responses in cells and tissues, has been considered as a possible therapeutic ...strategy for Alzheimer’s disease (AD), while its specific mechanisms have remained elusive. Here, we demonstrate that cognitive and memory impairment in an AD mouse model can be ameliorated by 1070-nm light via reducing cerebral β-amyloid (Aβ) burden, the hallmark of AD. The glial cells, including microglia and astrocytes, play important roles in Aβ clearance. Our results show that 1070-nm light pulsed at 10 Hz triggers microglia rather than astrocyte responses in AD mice. The 1070-nm light-induced microglia responses with alteration in morphology and increased colocalization with Aβ are sufficient to reduce Aβ load in AD mice. Moreover, 1070-nm light pulsed at 10 Hz can reduce perivascular microglia and promote angiogenesis to further enhance Aβ clearance. Our study confirms the important roles of microglia and cerebral vessels in the use of 1070-nm light for the treatment of AD mice and provides a framework for developing a novel therapeutic approach for AD.
Abstract
Circulating tumor cells (CTCs) is an established biomarker of cancer metastasis. The circulation dynamics of CTCs are important for understanding the mechanisms underlying tumor cell ...dissemination. Although studies have revealed that the circadian rhythm may disrupt the growth of tumors, it is generally unclear whether the circadian rhythm controls the release of CTCs. In clinical examinations, the current in vitro methods for detecting CTCs in blood samples are based on a fundamental assumption that CTC counts in the peripheral blood do not change significantly over time, which is being challenged by recent studies. Since it is not practical to draw blood from patients repeatedly, a feasible strategy to investigate the circadian rhythm of CTCs is to monitor them by in vivo detection methods. Fluorescence in vivo flow cytometry (IVFC) is a powerful optical technique that is able to detect fluorescent circulating cells directly in living animals in a noninvasive manner over a long period of time. In this study, we applied fluorescence IVFC to monitor CTCs noninvasively in an orthotopic mouse model of human prostate cancer. We observed that CTCs exhibited stochastic bursts over cancer progression. The probability of the bursting activity was higher at early stages than at late stages. We longitudinally monitored CTCs over a 24-h period, and our results revealed striking daily oscillations in CTC counts that peaked at the onset of the night (active phase for rodents), suggesting that the release of CTCs might be regulated by the circadian rhythm.
Luteolin (LUT) is a naturally occurring compound found in a various of plants. Few recent studies have reported LUT antimicrobial activities against bacterial pathogens, however, the fundamental LUT ...mediated antimicrobial mechanism has never been elucidated. This study aimed to investigate the antimicrobial activities of LUT and its mode of action against Staphylococcus aureus and Listeria monocytogenes, either as planktonic cells or as biofilms. Here, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of LUT against S. aureus and L. monocytogenes were determined using the broth microdilution method, and the antimicrobial mode of LUT was elucidated by evaluating the variations in both cell membrane integrity and cell morphology. Moreover, the biofilm inhibition was measured by crystal violet staining assay, while its qualitative imaging was achieved by confocal laser scanning microscope and field emission scanning electron microscope. MIC and MBC values of LUT against S. aureus were 16–32 and 32–64 μg/mL, and 32–64 and 64–128 μg/mL for L. monocytogenes. LUT destroyed the cell membrane integrity, as evidenced by a significant increase in the number of non-viable cells, and well-defined variations in cell morphology. Moreover, LUT presented robust inhibitory effects on the biofilm formation, enhanced antibiotics diffusion within biofilms and killed efficiently mono- and dual-species biofilm cells. Overall, LUT demonstrates potent antimicrobial properties on planktonic and biofilm cells, and the biofilm formation, and thus has the potential use as a natural food preservative in foods.
•The antimicrobial and antibiofilm activity of luteolin against S. aureus and L. monocytogenes was investigated.•Luteolin presents impairment effect on S. aureus and L. monocytogenes cell membrane.•Luteolin restrains biofilm formation of S. aureus and L. monocytogenes.•Luteolin can kill biofilm cells of S. aureus and L. monocytogenes.
Candida albicans
and
Enterococcus faecalis
biofilm-associated infections have been a huge challenge to the medical community. However, the efficacy of natural products against mixed biofilms of
C. ...albicans
and
E. faecalis
still remains largely unexploited. The aim of this study was to evaluate the efficacy of luteolin against planktonic cell growth, adhesion, and biofilm formation of
C. albicans
and
E. faecalis
in single and mixed cultures
in vitro
. The results showed that the minimum inhibitory concentrations of luteolin against planktonic cells of
C. albicans
,
E. faecalis
, and mixed cultures were 32 and 64 μg ml
–1
, respectively. The results displayed that a remarkable variation in biofilm biomass, viability, structure, and composition of single and dual-species biofilms formed by mono- and dual-species biofilms of
C. albicans
and
E. faecalis
in the presence of luteolin was confirmed by mainly crystal violet staining assay (CVSA), optical microscope, field emission scanning electron microscope (FESEM), and confocal laser scanning microscope (CLSM). The tolerance of luteolin-treated single- and dual-species biofilms to antibiotics was found to obviously decrease, and the loss of biofilm matrix components (mainly polysaccharides and proteins) was revealed by CLSM. Moreover, luteolin was effective at inactivating biofilm cells, as well as destructing preformed biofilm structures by single and dual species by CVSA, FESEM, and CLSM. Collectively, these data indicate the potential of luteolin as a promising antibiofilm agent for the therapeutic management of biofilm-related infections induced by single and dual species of
C. albicans
and
E. faecalis
.
The Qinghai–Tibet Plateau is an area with frequent landslide hazards due to its unique geology, topography, and climate conditions, posing severe threats to engineering construction and human ...settlements. The primary purpose of this paper is to map the landslide susceptibility of the Ya’an–Lin branch of the Sichuan–Tibet Railway using two deep learning (DL) algorithms, convolutional neural network (CNN) and deep neural network (DNN). Initially, a geospatial database was generated based on 587 landslide hazards determined by Interferometric Synthetic Aperture Radar (InSAR) Stacking technology and field geological hazard surveys; thus, 18 landslide-influencing factors were selected. Subsequently, the landslides were randomly divided into training (70%) and validation data (30%) for model training and testing. Next, a Pearson correlation coefficient and information gain (IG) method were used to perform the correlation analysis and feature selection of the 18 influencing factors. Afterward, landslide susceptibility maps were generated for the two models. Finally, the performance of the model is validated using the receiver-operating characteristic (ROC) curve and confusion matrix. The results show that the CNN model (AUC = 0.88) provided better performance in both the training and testing phases compared to the DNN model (AUC = 0.84). In addition, the high landslide susceptibility is primarily distributed in the Jinsha, Lancang and Nu River basins along the railway. The slope, altitude and rainfall are the main factors for the formation of the landslides. Furthermore, the two deep learning models can accurately map the landslide susceptibility, providing important information for landslide risk reduction and prevention.
Real-time acquisition of location information for agricultural robotic systems is a prerequisite for achieving high-precision intelligent navigation. This paper proposes a data filtering and combined ...positioning method, and establishes an active screening model. The dynamic and static positioning drift points of the carrier are eliminated or replaced, reducing the complexity of the original Global Navigation Satellite System (GNSS) output data in the positioning system. Compared with the traditional Kalman filter combined positioning method, the proposed active filtering-Kalman filter algorithm can reduce the maximum distance deviation of the carrier along a straight line from 0.145 m to 0.055 m and along a curve from 0.184 m to 0.0640 m. This study focuses on agricultural robot positioning technology, which has an important influence on the development of smart agriculture.
Breast cancer is the most commonly diagnosed cancer in women. The high incidence of breast cancer, which is continuing to rise, makes treatment a significant challenge. The PI3K-AKT pathway and its ...downstream targets influence various cellular processes. In recent years, mounting evidence has shown that natural products and synthetic drugs targeting PI3K-AKT signaling have the potential to treat breast cancer. In this review, we discuss the role of the PI3K-AKT signaling pathway in the occurrence and development of breast cancer and highlight PI3K-AKT-targeting natural products and drugs in clinical trials for the treatment of breast cancer.
Diabetic kidney disease (DKD) is a leading factor in end-stage renal disease. The complexity of its pathogenesis, combined with the limited treatment efficacy, necessitates deeper insights into ...potential causes. Studies suggest that ferroptosis-driven renal tubular damage contributes to DKD's progression, making its counteraction a potential therapeutic strategy. Quercetin, a flavonoid found in numerous fruits and vegetables, has demonstrated DKD mitigation in mouse models, though its protective mechanism remains ambiguous. In this study, we delved into quercetin's potential anti-ferroptotic properties, employing a DKD rat model and high glucose (HG)-treated renal tubular epithelial cell models. Our findings revealed that HG prompted unusual ferroptosis activation in renal tubular epithelial cells. However, quercetin counteracted this by inhibiting ferroptosis and activating NFE2-related factor 2 (Nrf2) expression in both DKD rats and HG-treated HK-2 cells, indicating its renal protective role. Further experiments, both
and
, validated that quercetin stimulates Nrf2. Thus, our research underscores quercetin's potential in DKD treatment by modulating the ferroptosis process
activating Nrf2 in a distinct DKD rat model, offering a fresh perspective on quercetin's protective mechanisms.
Abstract
Anyang, the last capital of the Chinese Shang dynasty, became one of the largest metal consumers in Eurasia during the second millennium BCE. However, it remains unclear how Anyang people ...managed to sustain such a large supply of metal. By considering the chemical analysis of bronze objects within archaeological contexts, this paper shows that the casting and circulation of metal at Anyang was effectively governed by social hierarchy. Objects belonging to the high elites such as Fuhao, particularly the bronze ritual vessels, were made by carefully controlled alloying practice (primary) using very pure copper, whereas the lower elites only had access to bronzes made by secondary alloying practice and copper with more impurities. Such contrasts allow scholars to identify those objects which are less likely to have been made by mixing and recycling, which has very important implications for the chemical and isotopic determination of provenance for future studies.
Magang geese are typical short-day breeders whose reproductive behaviors are significantly influenced by photoperiod. Exposure to a long-day photoperiod results in testicular regression and ...spermatogenesis arrest in Magang geese. To investigate the epigenetic influence of DNA methylation on the seasonal testicular regression in Magang geese, we conducted whole-genome bisulfite sequencing and transcriptome sequencing of testes across 3 reproductive phases during a long-day photoperiod. A total of 250,326 differentially methylated regions (DMR) were identified among the 3 comparison groups, with a significant number showing hypermethylation, especially in intronic regions of the genome. Integrating bisulfite sequencing with transcriptome sequencing data revealed that DMR-associated genes tend to be differentially expressed in the testes, highlighting a potential regulatory role for DNA methylation in gene expression. Furthermore, there was a significant negative correlation between changes in the methylation of CG DMRs and changes in the expression of their associated genes in the testes. A total of 3,359 DMR-associated differentially expressed genes (DEG) were identified; functional enrichment analyses revealed that motor proteins, MAPK signaling pathway, ECM-receptor interaction, phagosome, TGF-beta signaling pathway, and calcium signaling might contribute to the testicular regression process. GSEA revealed that the significantly enriched activated hallmark gene set was associated with apoptosis and estrogen response during testicular regression, while the repressed hallmark gene set was involved in spermatogenesis. Our study also revealed that methylation changes significantly impacted the expression level of vitamin A metabolism-related genes during testicular degeneration, with hypermethylation of STRA6 and increased calmodulin levels indicating vitamin A efflux during the testicular regression. These findings were corroborated by pyrosequencing and real-time qPCR, which revealed that the vitamin A metabolic pathway plays a pivotal role in testicular degeneration under long-day conditions. Additionally, metabolomics analysis revealed an insufficiency of vitamin A and an abnormally high level of oxysterols accumulated in the testes during testicular regression. In conclusion, our study demonstrated that testicular degeneration in Magang geese induced by a long-day photoperiod is linked to vitamin A homeostasis disruption, which manifests as the hypermethylation status of STRA6, vitamin A efflux, and a high level of oxysterol accumulation. These findings offer new insights into the effects of DNA methylation on the seasonal testicular regression that occurs during long-day photoperiods in Magang geese.
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