Registration-free 3D super-resolution generative deep-learning network for fluorescence microscopy imaging.

Volumetric fluorescence microscopy has a great demand for high-resolution (HR) imaging and comes at the cost of sophisticated imaging solutions. Image super-resolution (SR) methods offer an effective way to recover HR images from low-resolution (LR) images. Nevertheless, these methods require pixel-level registered LR and HR images, posing a challenge in accurate image registration. To address these issues, we propose a novel registration-free image SR method. Our method conducts SR training and prediction directly on unregistered LR and HR volume neuronal images. The network is built on the CycleGAN framework and the 3D UNet based on attention mechanism. We evaluated our method on LR (5×/0.16-NA) and HR (20×/1.0-NA) fluorescence volume neuronal images collected by light-sheet microscopy. Compared to other super-resolution methods, our approach achieved the best reconstruction results. Our method shows promise for wide applications in the field of neuronal image super-resolution.

Serum miR-129 functions as a biomarker for colorectal cancer by targeting estrogen receptor (ER) ß.

Aberrantly expressed miRNAs widely participate in the signaling cascades of colorectal carcinogenesis. The present study aimed to identify a potential miRNA that serves as effective biomarker for colorectal cancer (CRC). The expression of estrogen receptorß (ERß) was explored using immunohistochemistry. The possible miRNAs targeting ERß were predicted by TargetScan, and their expression patterns were validated using real time PCR. Dual luciferase reporter assays were performed to determine the potential binding of miR-129 in the 3' untranslated region (3'UTR) of ERß. In vitro scratch assays and flow cytometry assays were conducted to determine the role of miR-129 on colon cancer cell migration and apoptosis. Proteins related to cell proliferation were determined using western blots. Compared with adjacent non-cancer tissues, the protein level of ERß was significantly decreased in CRC tissues, and compared with NC the level of miR-129 was significantly increased in blood and tissue samples. Dual luciferase reporter assays demonstrated that ERß was a direct target gene of miR-129. Further study showed that inhibition of miR-129 decreases HCT116 cell migration and enhances cell apoptosis. More importantly, we found that the silencing of ERß significantly decreased the activation of caspase3 but increased the protein expression of PCNA. Interestingly, miR-129 inhibitor-induced protein expression pattern changes could be reversed by the siRNA targeting ERß. The high expression level of circulating miR-129 in the tissue and blood samples of CRC patients contributes to aberrant colon cancer cell proliferation and migration mainly by targeting ERß.

Puerarin Attenuates Anoxia/Reoxygenation Injury Through Enhancing Bcl-2 Associated Athanogene 3 Expression, a Modulator of Apoptosis and Autophagy.

BACKGROUND: Puerarin has protective effects on ischemia-reperfusion injury, but the underlying mechanisms are not fully revealed. This study explored the effect of puerarin on the expression of Bcl-2 associated athanogene 3 (BAG3) in an in vitro model of anoxia/reoxygenation injury (A/RI) in neonate rat primary cardiomyocytes and the functions of BAG3 in A/RI. MATERIAL/METHODS: BAG3 expression in cardiomyocytes with or without puerarin pre-treatment was quantified using qRT-PCR and Western blot analysis. The effects of BAG3 on A/RI were studied by measuring the activity of lactate dehydrogenase (LDH) and creatine phosphate kinase (CPK), the concentration of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). The effects of BAG3 on autophagy and apoptosis of the cardiomyocytes after A/RI were further studied. RESULTS: Puerarin significantly promoted BAG3 expression in the rat primary cardiomyocytes after A/RI. Enforced BAG3 expression presented similar effects as puerarin pre-treatment in attenuating A/RI in terms of CPK, LDH, MDA, SOD, GSH-Px, ROS generation, and cell viability. BAG3 overexpression significantly stimulated autophagy in cardiomyocytes after A/RI, which presented protective effects on A/RI in terms of cell viability and apoptosis. Autophagy inhibition partly abrogated the protective effects of BAG3. CONCLUSIONS: Puerarin can directly increase BAG3 transcription and translation in cardiomyocytes after A/RI. The elevated BAG3 expression presents protective effects on A/RI at least through enhancing autophagy and reducing apoptosis, which is a novel protective mechanism of puerarin in ARI.

Causal relationship between immune cells and neurodegenerative diseases: a two-sample Mendelian randomisation study.

Background: There is increasing evidence that the types of immune cells are associated with various neurodegenerative diseases. However, it is currently unclear whether these associations reflect causal relationships. Objective: To elucidate the causal relationship between immune cells and neurodegenerative diseases, we conducted a two-sample Mendelian randomization (MR) analysis. Materials and methods: The exposure and outcome GWAS data used in this study were obtained from an open-access database (https://gwas.mrcieu.ac.uk/), the study employed two-sample MR analysis to assess the causal relationship between 731 immune cell features and four neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). All immune cell data was obtained from Multiple MR methods were used to minimize bias and obtain reliable estimates of the causal relationship between the variables of interest and the outcomes. Instrumental variable selection criteria were restricted to ensure the accuracy and effectiveness of the causal relationship between species of immune cells and the risk of these neurodegenerative diseases. Results: The study identified potential causal relationships between various immune cells and different neurodegenerative diseases. Specifically, we found that 8 different types of immune cells have potential causal relationships with AD, 1 type of immune cells has potential causal relationships with PD, 6 different types of immune cells have potential causal relationships with ALS, and 6 different types of immune cells have potential causal relationships with MS. Conclusion: Our study, through genetic means, demonstrates close causal associations between the specific types of immune cells and AD, PD, ALS and MS, providing useful guidance for future clinical researches.

Hypertension linked to Alzheimer's disease via stroke: Mendelian randomization.

This study aimed to investigate the relationship between hypertension and Alzheimer's disease (AD) and demonstrate the key role of stroke in this relationship using mediating Mendelian randomization. AD, a neurodegenerative disease characterized by memory loss, cognitive impairment, and behavioral abnormalities, severely affects the quality of life of patients. Hypertension is an important risk factor for AD. However, the precise mechanism underlying this relationship is unclear. To investigate the relationship between hypertension and AD, we used a mediated Mendelian randomization method and screened for mediating variables between hypertension and AD by setting instrumental variables. The results of the mediated analysis showed that stroke, as a mediating variable, plays an important role in the causal relationship between hypertension and AD. Specifically, the mediated indirect effect value for stroke obtained using multivariate mediated MR analysis was 54.9%. This implies that approximately 55% of the risk of AD owing to hypertension can be attributed to stroke. The results suggest that the increased risk of AD owing to hypertension is mediated through stroke. The finding not only sheds light on the relationship between hypertension and AD but also indicates novel methods for the prevention and treatment of AD. By identifying the critical role of stroke in the link between hypertension and AD, this study provides insights into potential interventions that could mitigate the impact of hypertension on AD. This could help develop personalized treatments and help improve the quality of life of patients with AD who suffer from hypertension.