Influence of diffraction distance on image restoration in deep learning networks.

In recent years, significant advancements have been made in the field of computational imaging, particularly due to the application of deep learning methods to imaging problems. However, only a few studies related to deep learning have examined the impact of diffraction distance on image restoration. In this paper, the effect of diffraction distance on image restoration is investigated based on the PhysenNet neural network. A theoretical framework for diffraction images at various diffraction distances is provided along with the applicable propagators. In the experiment, the PhysenNet network is selected to train on diffraction images with different distances and the impact of using different propagators on network performance is studied. Optimal propagators required to recover images at different diffraction distances are determined. Insights obtained through these experiments can expand the scope of neural networks in computational imaging.

Immunosuppressive Microenvironment in H3K27 Mutant Pediatric Diffuse Midline Glioma: Single-Cell and Bioinformatics Insights on CD8A, IL7R, and ICAM1.

BACKGROUND: Diffuse midline gliomas (DMG) pose a grave threat as a malignant tumor primarily affecting children in the pons region. These tumors exhibit a distinct and heightened resistance to therapeutic interventions, coupled with exceptionally aggressive behavior. METHODS: In this study, we accessed DMG data from the Gene Expression Omnibus (GEO) database. Subsequently, we performed functional annotation and conducted pathway enrichment analysis as well as gene set enrichment analysis (GSEA). Constructing a protein-protein interaction (PPI) network, we identified pivotal hub genes. To evaluate the impact of these hub genes on immune infiltration, we employed the CIBERSORT algorithm. Furthermore, to bolster our findings, we conducted a single-cell analysis. RESULTS: Our findings indicate the involvement of CD8A, IL7R, and ICAM1 in immune responses targeting diverse immune cell types, such as T cells, neutrophils, NK cells, dendritic cells, γδ T cells, and Macrophages M1. Additionally, the presence of immune checkpoints, including IDO1 and TIGIT, likely contributes to intratumoral immunosuppression, thereby fostering the development of an aggressive phenotype and resistance in pediatric DMG. CONCLUSION: In conclusion, the collective findings of our study suggest the potential role of CD8A, IL7R, and ICAM1 as innovative biomarkers for diagnosing and prognosticating pediatric DMG. Moreover, these molecules hold promise as therapeutic targets in the management of this disease. The implications of our research underscore the importance of exploring these novel avenues for improved patient outcomes.

Ketamine exerts dual effects on the apoptosis of primary cultured hippocampal neurons from fetal rats in vitro.

Ketamine, a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. The neuroprotective and neurotoxic effects of ketamine on brain neurons during development remain controversial. The reason may be related to the different concentrations of ketamine used in practice and the small range of concentrations used in previous studies. In this study, cultured hippocampal neurons were treated with ketamine in a wide range of concentrations to comprehensively observe the effects of different concentrations of ketamine on neurons. We demonstrated that low concentrations of ketamine (10 µM, 100 µM and 1000 µM) promoted neuronal survival (p < 0.05) and reduced neuronal apoptosis (p < 0.05) compared with those of the control group. High concentrations of ketamine (2000 µM, 2500 µM and 3000 µM) reduced neuronal survival (p < 0.05) and promoted neuronal apoptosis (p < 0.05). The p38 MAPK inhibitor SB203580 reduced neuronal apoptosis induced by high concentrations of ketamine (2500 µM) (p < 0.05). Our findings indicate that ketamine exerts a dual effect on the apoptosis of primary cultured fetal rat hippocampal neurons in vitro and that the neurotoxic effects of ketamine are related to activation of the p38 MAPK signaling pathway.

scRNA-seq and proteomics reveal the distinction of M2-like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence.

AIMS: Tumor-associated macrophages (TAMs) in the immune microenvironment play an important role in the increased drug resistance and recurrence of malignant glioma, but the mechanism remains incompletely inventoried. The focus of this study was to investigate the distinctions of M2-like TAMs in the immune microenvironment between primary and recurrent malignant glioma and its influence in the recurrence. METHODS: We employed single-cell RNA sequencing to construct a single-cell atlas for a total of 23,010 individual cells from 6 patients with primary or recurrent malignant glioma and identified 5 cell types, including TAMs and malignant cells. Immunohistochemical techniques and proteomics analysis were performed to investigate the role of intercellular interaction between malignant cells and TAMs in the recurrence of malignant glioma. RESULTS: Six subgroups of TAMs were annotated and M2-like TAMs were found to increase in recurrent malignant glioma significantly. A pseudotime trajectory and a dynamic gene expression profiling during the recurrence of malignant glioma were reconstructed. Up-regulation of several cancer pathways and intercellular interaction-related genes are associated with the recurrence of malignant glioma. Moreover, the M2-like TAMs can activate the PI3K/Akt/HIF-1α/CA9 pathway in the malignant glioma cells via SPP1-CD44-mediated intercellular interaction. Interestingly, high expression of CA9 can trigger the immunosuppressive response in the malignant glioma, thus promoting the degree of malignancy and drug resistance. CONCLUSION: Our study uncovers the distinction of M2-like TAMs between primary and recurrent glioma, which offers unparalleled insights into the immune microenvironment of primary and recurrent malignant glioma.

Rare-earth nanoparticles induce depression, anxiety-like behavior, and memory impairment in mice.

Rare-earth nanoparticles have been widely studied for disease diagnosis, in vivo optical imaging, biosensing, and drug delivery. However, the effects of rare-earth nanoparticles on a central nervous system remain unclear. Here, we report that the continuous exposure to rare-earth nanoparticles in mice can cause behavioral alterations including cognitive deficits, anxiety, and depression-like behavior. Using an open-field test and a morris water maze, we showed that long-term exposure to rare-earth nanoparticles may lead to significant depression, anxiety-like behavior, and memory impairment. The histopathological investigation on the neurotoxicological effects of nanoparticles indicated a significant decrease in cell viability after seven days' nanoparticle exposure. Western blotting analysis suggested that the changes of ATP-citrate lyase (ACLY) and O-linked N-acetylglucosamine transferase (OGT, a unique glycosyltransferase enzyme) played important roles in neurobehavioral disorders in mice. These findings provide a pathway to understand the cytotoxicity of rare-earth nanoparticles for medial applications and offer insights into the risk of these nanoparticles in biological systems.

A Perovskite-Based Paper Microfluidic Sensor for Haloalkane Assays.

Detection of haloalkanes is of great industrial and scientific importance because some haloalkanes are found serious biological and atmospheric issues. The development of a flexible, wearable sensing device for haloalkane assays is highly desired. Here, we develop a paper-based microfluidic sensor to achieve low-cost, high-throughput, and convenient detection of haloalkanes using perovskite nanocrystals as a nanoprobe through anion exchanging. We demonstrate that the CsPbX3 (X = Cl, Br, or I) nanocrystals are selectively and sensitively in response to haloalkanes (CH2Cl2, CH2Br2), and their concentrations can be determined as a function of photoluminescence spectral shifts of perovskite nanocrystals. In particular, an addition of nucleophilic trialkyl phosphines (TOP) or a UV-photon-induced electron transfer from CsPbX3 nanocrystals is responsible for achieving fast sensing of haloalkanes. We further fabricate a paper-based multichannel microfluidic sensor to implement fast colorimetric assays of CH2Cl2 and CH2Br2. We also demonstrate a direct experimental observation on chemical kinetics of anion exchanging in lead-halide perovskite nanocrystals using a slow solvent diffusion strategy. Our studies may offer an opportunity to develop flexible, wearable microfluidic sensors for haloalkane sensing, and advance the in-depth fundamental understanding of the physical origin of anion-exchanged nanocrystals.

Chemical operations on a living single cell by open microfluidics for wound repair studies and organelle transport analysis.

Single cells are increasingly recognized to be capable of wound repair that is important for our mechanistic understanding of cell biology. The lack of flexible, facile, and friendly subcellular treatment methods has hindered single-cell wound repair studies and organelle transport analyses. Here we report a laminar flow based approach, we call it fluid cell knife (Fluid CK), that is capable of precisely cutting off or treating a portion of a single cell from its remaining portion in its original adherent state. Local operations on portions of a living single cell in its adherent culture state were applied to various types of cells. Temporal wound repair was successfully observed. Moreover, we successfully stained portions of a living single cell to measure the organelle transport speed (mitochondria as a model) inside a cell. This technique opens up new avenues for cellular wound repair and subcellular behavior analyses.

Reconstituting Glioma Perivascular Niches on a Chip for Insights into Chemoresistance of Glioma.

In this work, we report the direct diagnosing chemoresistance of glioma stem cells (GSCs) during chemotherapy on a biomimetric microsystem that reconstitutes glioma perivascular niches on a chip. Glioma stem cells and endothelial cells were specially cocultured onto the biomimetric system to precisely control stem cell coculture for the proof-of-principle studies. The expression levels of 6- O-methylguanine was confirmed by mass spectrometer, and Bmi-1 gene was also investigated to uncover the chemoresistance of GSCs. The results demonstrated that the formation of perivascular niches effectively maintains the glioma stem cells at a pluripotent status owing to their successful cellular interactions. A stronger chemoresistance of glioma stem cells was confirmed by the formation of the GSCs neurosphere, the expression levels of 6- O-methylguanine and Bmi-1 gene. The vital role of endothelial cells in chemoresistance was demonstrated. The chemoresistance reported in this work will contribute to glioma therapy.

Effects of Increased Intracranial Pressure Gradient on Cerebral Venous Infarction in Rabbits.

BACKGROUND: Cerebral venous infarction (CVI) is a rare vascular disease most commonly caused by cerebral venous thrombosis that leads to hemorrhage or infarct formation. A rabbit model of CVI was established by placing a recoverable epidural sacculus to research effects of increased pressure on CVI. METHODS: Rabbits were randomly divided into the following groups: A, CVI; B, 0.2-mL epidural sacculus placed on the basis of CVI; C, 0.4-mL epidural sacculus; D, 0.6-mL epidural sacculus; E, sham operation. Two sacculus-release groups were then added, 8 hours (group F) and 24 hours (group G), on the basis of group D. Brain water content, extent of cerebral infarction, hemorheology indexes, D dimer, and fibrinogen were observed at 8, 24, and 48 hours after surgery. RESULTS: Brain water content was higher in groups A-D compared with group E with the exception of the 24-hour A group. Brain water content was significantly lower in sacculus-release groups compared with the 48-hour D group. Extent of cerebral infarction in group D was significantly higher at 24 and 48 hours compared with groups A and E. Extent of cerebral infarction in sacculus-release groups was significantly lower compared with group D at 48 hours. Hemorheology indexes and fibrinogen were significantly higher in group D compared with groups A and E at corresponding time points and increased with increasing intracranial pressure. CONCLUSIONS: In the rabbit model of CVI, degree of brain edema, extent of cerebral infarction, hemorheology indexes, and fibrinogen increased as intracranial pressure gradient increased, which may promote formation of a hypercoagulable state. Early removal of intracranial hypertension reduced degree of edema and extent of cerebral infarction in rabbits.

Potential Clinical Risk of Inflammation and Toxicity from Rare-Earth Nanoparticles in Mice.

BACKGROUND: Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models. METHODS: We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group. RESULTS: We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 109/L at the 28th day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF4:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] µmol/L) at the 28th day, particularly those injected with 1.5 mg/kg NaYbF4:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney. CONCLUSION: The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.

Rare-earth Nanoparticle-induced Cytotoxicity on Spatial Cognition Memory of Mouse Brain.

BACKGROUND: Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure. METHODS: Adult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice. RESULTS: Two different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain. CONCLUSIONS: This study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.