Concentration-Dependent Diversification Effects of Free Cholesterol Loading on Macrophage Viability and Polarization

Background/Aims: The accumulation of free cholesterol in atherosclerotic lesions has been well documented in both animals and humans. In studying the relevance of free cholesterol buildup in atherosclerosis, contradictory results have been generated, indicating that free cholesterol produces both pro- and anti-atherosclerosis effects in macrophages. This inconsistency might stem from the examination of only select concentrations of free cholesterol. In the present study, we sought to investigate the implication of excess free cholesterol loading in the pathophysiology of atherosclerosis across a broad concentration range from (in µg/ml) 0 to 60. Methods:Macrophage viability was determined by measuring formazan formation and flow cytometry viable cell counting. The polarization of M1 and M2 macrophages was differentiated by FACS (Fluorescence-Activated Cell Sorting) assay. The secretion of IL-1β in macrophage culture medium was measured by ELISA kit. Macrophage apoptosis was detected by flow cytometry using a TUNEL kit. Results: Macrophage viability was increased at the treatment of lower concentrations of free cholesterol from (in µg/ml) 0 to 20, but gradually decreased at higher concentrations from 20 to 60. Lower free cholesterol loading induced anti-inflammatory M2 macrophage polarization. The activation of the PPARγ (Peroxisome Proliferator-Activated Receptor gamma) nuclear factor underscored the stimulation of this M2 phenotype. Nevertheless, higher levels of free cholesterol resulted in pro-inflammatory M1 activation. Moreover, with the application of higher free cholesterol concentrations, macrophage apoptosis and secretion of the inflammatory cytokine IL-1β increased significantly. Conclusion: These results for the first time demonstrate that free cholesterol could render concentration-dependent diversification effects on macrophage viability, polarization, apoptosis and inflammatory cytokine secretions, thereby reconciling the pros and cons of free cholesterol buildup in macrophages to the pathophysiology of atherosclerosis

MarS3D: A Plug-and-Play Motion-Aware Model for Semantic Segmentation on Multi-Scan 3D Point Clouds

3D semantic segmentation on multi-scan large-scale point clouds plays an important role in autonomous systems. Unlike the single-scan-based semantic segmentation task, this task requires distinguishing the motion states of points in addition to their semantic categories. However, methods designed for single-scan-based segmentation tasks perform poorly on the multi-scan task due to the lacking of an effective way to integrate temporal information. We propose MarS3D, a plug-and-play motion-aware module for semantic segmentation on multi-scan 3D point clouds. This module can be flexibly combined with single-scan models to allow them to have multi-scan perception abilities. The model encompasses two key designs: the Cross-Frame Feature Embedding module for enriching representation learning and the Motion-Aware Feature Learning module for enhancing motion awareness. Extensive experiments show that MarS3D can improve the performance of the baseline model by a large margin. The code is available at https://github.com/CVMI-Lab/MarS3D

HI content of massive red spiral galaxies observed by FAST

A sample of 279 massive red spirals was selected optically by Guo et al. (2020), among which 166 galaxies have been observed by the ALFALFA survey. In this work, we observe HI content of the rest 113 massive red spiral galaxies using the Five-hundred-meter Aperture Spherical radio Telescope (FAST). 75 of the 113 galaxies have HI detection with a signal-to-noise ratio (S/N) greater than 4.7. Compared with the red spirals in the same sample that have been observed by the ALFALFA survey, galaxies observed by FAST have on average a higher S/N, and reach to a lower HI mass. To investigate why many red spirals contain a significant amount of HI mass, we check color profiles of the massive red spirals using images observed by the DESI Legacy Imaging Surveys. We find that galaxies with HI detection have bluer outer disks than the galaxies without HI detection, for both ALFALFA and FAST samples. For galaxies with HI detection, there exists a clear correlation between galaxy HI mass and g-r color at outer radius: galaxies with higher HI masses have bluer outer disks. The results indicate that optically selected massive red spirals are not fully quenched, and the HI gas observed in many of the galaxies may exist in their outer blue disks.Comment: 11 pages, 9 figures, accepted by MNRAS; Table 1 is available in the source file

Accuracy of the Short-Form Montreal Cognitive Assessment Chinese Versions

Background: There is a strong need for short and effective methods to screen for cognitive impairment. Recent studies have created short forms of the Montreal Cognitive Assessment (s-MoCA) in English-speaking populations. It is also important to develop a validated Chinese short version to detect cognitive impairment.Methods: Item response theory and computerized adaptive testing analytics were used to construct abbreviated MoCAs across a large neurological sample comprising 6,981 community-dwelling Chinese veterans.Results: Six MoCA items with high discrimination and appropriate difficulty were included in the s-MoCA. The Chinese short versions (sensitivity 0.89/0.90, specificity 0.72/0.77) are similar in performance to the full MoCA in identifying cognitive impairment (sensitivity 0.91, specificity 0.82).Conclusions: These short variants of the MoCA may serve as quick and effective instruments when the original MoCA cannot be feasibly administered in clinical services with a high patient burden and limited cognitive testing resources

Functional Divergence of Glioblastoma Stem Cells

Genetic heterogeneity in cancer is well-established using genomic sequencing, while functional assays of prospectively isolated cancer subsets have demonstrated the existence of developmental programs in many hematological and solid malignancies. CD133 expressing cells have a unique propensity for initiating and sustaining hierarchical growth in human glioblastoma, a property analogous to that of neural stem cells. However, it remains unclear whether putative cancer stem cells exhibit further intratumoral variations in functional properties as a consequence of genetic or epigenetic heterogeneity. Here, we describe two complementary approaches to characterize functional intratumoral heterogeneity of human glioblastoma within the glioma stem cell (GSC) compartment at single cell resolution. In the first approach, we generated cohorts of single-cell derived stem cell cultures from primary glioblastoma and subjected them to in depth functional analyses. We demonstrate that multiple clones derived from the same GBM are capable of tumour initiation, yet differ in key functional properties such as proliferation, differentiation, and response to temozolomide chemotherapy. Genetic mutations unique to each clone could also be applied to reconstruct tumour phylogeny, indicating that the self-renewing compartment is reflective of complex tumour evolutionary histories. In the second approach, we labelled primary GBM cells with permanent genetic barcodes for the characterization of their functional properties in vivo. Using this approach, we demonstrated that self-renewal is restricted to a subset of GBM xenograft forming cells thereby confirming the maintenance of a stable developmental hierarchy within human GBMs at initial presentation. We also show that functional divergence of GBM clones emerges over time as a small subset of clones become more proliferative, and that intrinsically chemotherapy resistant clones may be selected for by frontline therapies. Furthermore, we show differential targeting of proliferative and relatively non-proliferative clones within the same tumour using epigenetic compounds. Our findings demonstrate the relevance of clonal heterogeneity in GBM pathogenesis, and suggest that complete elimination of all GSCs is possible using a combination of epigenetic compounds.Ph.D.2018-11-03 00:00:0

Exploring the Relationship between Obesity, Metabolic Syndrome and Neuroendocrine Neoplasms

Obesity is a major burden for modern medicine, with many links to negative health outcomes, including the increased incidence of certain cancer types. Interestingly, some studies have supported the concept of an “Obesity Paradox”, where some cancer patients living with obesity have been shown to have a better prognosis than non-obese patients. Neuroendocrine neoplasms (NENs) are malignancies originating from neuroendocrine cells, in some cases retaining important functional properties with consequences for metabolism and nutritional status. In this review, we summarize the existing evidence demonstrating that obesity is both a risk factor for developing NENs as well as a good prognostic factor. We further identify the limitations of existing studies and further avenues of research that will be necessary to optimize the metabolic and nutritional status of patients living with NENs to ensure improved outcomes

MMRGait-1.0: A Radar Time-frequency Spectrogram Dataset for Gait Recognition under Multi-view and Multi-wearing Conditions

As a biometric technology, gait recognition is usually considered a retrieval task in real life. However, because of the small scale of the existing radar gait recognition dataset, the current studies mainly focus on classification tasks and only consider the situation of a single walking view and the same wearing condition, limiting the practical application of radar-based gait recognition. This paper provides a radar gait recognition dataset under multi-view and multi-wearing conditions; the dataset uses millimeter-wave radar as a sensor to collect the time-frequency spectrogram data of 121 subjects walking along views under multiple wearing conditions. Eight views were collected for each subject, and ten sets were collected for each view. Six of the ten sets are dressed normally, two are dressed in coats, and the last two are carrying bags. Meanwhile, this paper proposes a method for radar gait recognition based on retrieval tasks. Experiments are conducted on this dataset, and the experimental results can be used as a benchmark to facilitate further research by related scholars on this dataset

Concentration-Dependent Diversifcation Effects of Free Cholesterol Loading on Macrophage Viability and Polarization

Background/Aims: The accumulation of free cholesterol in atherosclerotic lesions has been well documented in both animals and humans. In studying the relevance of free cholesterol buildup in atherosclerosis, contradictory results have been generated, indicating that free cholesterol produces both pro- and anti-atherosclerosis effects in macrophages. This inconsistency might stem from the examination of only select concentrations of free cholesterol. In the present study, we sought to investigate the implication of excess free cholesterol loading in the pathophysiology of atherosclerosis across a broad concentration range from (in µg/ml) 0 to 60. Methods: Macrophage viability was determined by measuring formazan formation and flow cytometry viable cell counting. The polarization of M1 and M2 macrophages was differentiated by FACS (Fluorescence-Activated Cell Sorting) assay. The secretion of IL-1β in macrophage culture medium was measured by ELISA kit. Macrophage apoptosis was detected by flow cytometry using a TUNEL kit. Results: Macrophage viability was increased at the treatment of lower concentrations of free cholesterol from (in µg/ml) 0 to 20, but gradually decreased at higher concentrations from 20 to 60. Lower free cholesterol loading induced anti-inflammatory M2 macrophage polarization. The activation of the PPARγ (Peroxisome Proliferator-Activated Receptor gamma) nuclear factor underscored the stimulation of this M2 phenotype. Nevertheless, higher levels of free cholesterol resulted in pro-inflammatory M1 activation. Moreover, with the application of higher free cholesterol concentrations, macrophage apoptosis and secretion of the inflammatory cytokine IL-1β increased significantly. Conclusion: These results for the first time demonstrate that free cholesterol could render concentration-dependent diversification effects on macrophage viability, polarization, apoptosis and inflammatory cytokine secretions, thereby reconciling the pros and cons of free cholesterol buildup in macrophages to the pathophysiology of atherosclerosis

Challenges in Diagnosis and Treatment of Pancreatic Exocrine Insufficiency among Patients with Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas and is associated with an extremely poor prognosis. Many PDAC patients suffer from profound nutritional complications such as nutrient deficiencies, weight loss, malnutrition, and cancer cachexia. These complications cause barriers to effective anticancer treatments, gravely influence their quality of life, and decrease their overall survival. Pancreatic exocrine insufficiency (PEI) is defined as impaired digestion due to inadequate secretion of pancreatic enzymes and is a common cause of malnutrition in PDAC. This review first summarizes the existing literature around malnutrition in PDAC, with a particular focus on PEI and its management with pancreatic enzyme replacement therapy (PERT). Second, we summarize existing guidelines and recommendations for the management of PEI among patients with PDAC. Lastly, we highlight potential gaps of knowledge of PEI among healthcare providers resulting in underdiagnosis and treatment, which may have implications for the quality of life and overall survival of PDAC patients

Cost-Effective Fabrication of Transparent Strain Sensors via Micro-Scale 3D Printing and Imprinting

The development of strain sensors with high sensitivity and stretchability is essential for health monitoring, electronic skin, wearable devices, and human-computer interactions. However, sensors that combine high sensitivity and ultra-wide detection generally require complex preparation processes. Here, a novel flexible strain sensor with high sensitivity and transparency was proposed by filling a multiwalled carbon nanotube (MWCNT) solution into polydimethylsiloxane (PDMS) channel films fabricated via an electric field-driven (EFD) 3D printing and molding hybrid process. The fabricated flexible strain sensor with embedded MWCNT networks had superior gauge factors of 90, 285, and 1500 at strains of 6.6%, 14%, and 20%, respectively. In addition, the flexible strain sensors with an optical transparency of 84% offered good stability and durability with no significant change in resistance after 8000 stretch-release cycles. Finally, the fabricated flexible strain sensors with embedded MWCNT networks showed good practical performance and could be attached to the skin to monitor various human movements such as wrist flexion, finger flexion, neck flexion, blinking activity, food swallowing, and facial expression recognition. These are good application strategies for wearable devices and health monitoring