Effects of Reactive Nitrogen Scavengers on NK-Cell-Mediated Killing of K562 Cells

This study explored the effects of reactive nitrogen metabolites (RNMS) on natural-killer- (NK-) cell-mediated killing of K562 cells and the influence of RNM scavengers, such as tiopronin (TIP), glutamylcysteinylglycine (GSH), and histamine dihydrochloride (DHT), on reversing the suppressing effect of RNM. We administered exogenous and endogenous RNM in the NK + K562 culture system and then added RNM scavengers. The concentrations of RNM, TNF-β and IFN-γ, and NK-cell cytotoxicity (NCC) and the percentage of living NK cells were then examined. We found that both exogenous and endogenous RNM caused the KIR to decrease (P < 0.01); however, RNM scavengers such as TIP and GSH rescued this phenomenon dose dependently. In conclusion, our data suggests that RNM scavengers such as TIP and GSH enhance the antineoplasmic activity of NK cells

Preparation of Iron-nickel Alloy Nanostructures via Two Cationic Pyridinium Derivatives as Soft Templates

In this paper, crystalline iron-nickel alloy nanostructures were successfully prepared from two cationic pyridinium derivatives as soft templates in solution. The crystal structure and micrograph of FeNi alloy nanostructures were characterized by X-ray diffraction, scanning electron microscopy and transmission electron microscopy, and the content was confirmed by energy-dispersive spectrometry. The results indicated that the as-prepared nanostructures showed slightly different diameter ranges with the change of cationic pyridinium derivatives on the surface. The experimental data indicated that the adsorption of cationic pyridinium compounds on the surface of particles reduces the surface charge, leading to an isotropic distribution of the residual surface charges. The magnetic behaviours of as-prepared FeNi alloy nanostructures exhibited disparate behaviours, which could be attributed to their grain sizes and distinctive structures. The present work may give some insight into the synthesis and character of new alloy nanomaterials with special nanostructures using new soft templates

3D cell nuclei segmentation based on gradient flow tracking

<p>Abstract</p> <p>Background</p> <p>Reliable segmentation of cell nuclei from three dimensional (3D) microscopic images is an important task in many biological studies. We present a novel, fully automated method for the segmentation of cell nuclei from 3D microscopic images. It was designed specifically to segment nuclei in images where the nuclei are closely juxtaposed or touching each other. The segmentation approach has three stages: 1) a gradient diffusion procedure, 2) gradient flow tracking and grouping, and 3) local adaptive thresholding.</p> <p>Results</p> <p>Both qualitative and quantitative results on synthesized and original 3D images are provided to demonstrate the performance and generality of the proposed method. Both the over-segmentation and under-segmentation percentages of the proposed method are around 5%. The volume overlap, compared to expert manual segmentation, is consistently over 90%.</p> <p>Conclusion</p> <p>The proposed algorithm is able to segment closely juxtaposed or touching cell nuclei obtained from 3D microscopy imaging with reasonable accuracy.</p

Knowledge-Guided Robust MRI Brain Extraction for Diverse Large-Scale Neuroimaging Studies on Humans and Non-Human Primates

Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55 approximately 90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18 approximately 96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5 approximately 18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness.published_or_final_versio

Ba6RE2Ti4O17 (RE= Nd, Sm,Gd, Dy-Yb): A family of quasi-two-dimensional triangular lattice magnets

Rare-earth-based triangular-lattice magnets provide the fertile ground to explore the exotic quantum magnetic state. Herein, we report a new family of RE-based triangular-lattice magnets Ba6RE2Ti4O17(RE= rare earth ions) crystallized into the hexagonal structure with space group of P63 mmc, where magnetic rare earth ions form an ideal triangular lattice within the ab-plane and stack in an AA -type fashion along the c-axis. The low-temperature magnetic susceptibility results reveal all the serial compounds have the dominant antiferromagnetic interactions and an absence of magnetic ordering down to 1.8 K. The magnetization and electron spin resonance results indicate distinct magnetic anisotropy for the compounds with different RE ions. Moreover, Ba6Nd2Ti4O17 single crystal is successfully grown and it exhibits strong Ising like anisotropy with magnetic easy-axis perpendicular to the triangle-lattice plane, being a candidate to explore quantum spin liquid state with dominant Ising-type interaction.Comment: 18 pages, 8 figure

Knowledge-Guided Robust MRI Brain Extraction for Diverse Large-Scale Neuroimaging Studies on Humans and Non-Human Primates

Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55∼90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18∼96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5∼18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness

The oral cancer microbiome contains tumor space–specific and clinicopathology-specific bacteria

The crosstalk between the oral microbiome and oral cancer has yet to be characterized. This study recruited 218 patients for clinicopathological data analysis. Multiple types of specimens were collected from 27 patients for 16S rRNA gene sequencing, including 26 saliva, 16 swabs from the surface of tumor tissues, 16 adjacent normal tissues, 22 tumor outer tissue, 22 tumor inner tissues, and 10 lymph nodes. Clinicopathological data showed that the pathogenic bacteria could be frequently detected in the oral cavity of oral cancer patients, which was positively related to diabetes, later T stage of the tumor, and the presence of cervical lymphatic metastasis. Sequencing data revealed that compared with adjacent normal tissues, the microbiome of outer tumor tissues had a greater alpha diversity, with a larger proportion of Fusobacterium, Prevotella, and Porphyromonas, while a smaller proportion of Streptococcus. The space-specific microbiome, comparing outer tumor tissues with inner tumor tissues, suggested minor differences in diversity. However, Fusobacterium, Neisseria, Porphyromonas, and Alloprevotella were more abundant in outer tumor tissues, while Prevotella, Selenomonas, and Parvimonas were enriched in inner tumor tissues. Clinicopathology-specific microbiome analysis found that the diversity was markedly different between negative and positive extranodal extensions, whereas the diversity between different T-stages and N-stages was slightly different. Gemella and Bacillales were enriched in T1/T2-stage patients and the non-lymphatic metastasis group, while Spirochaetae and Flavobacteriia were enriched in the extranodal extension negative group. Taken together, high-throughput DNA sequencing in combination with clinicopathological features facilitated us to characterize special patterns of oral tumor microbiome in different disease developmental stages

Epigenetic regulation of programmed cell death in hypoxia-induced pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a severe progressive disease that may cause early right ventricular failure and eventual cardiac failure. The pathogenesis of PAH involves endothelial dysfunction, aberrant proliferation of pulmonary artery smooth muscle cells (PASMCs), and vascular fibrosis. Hypoxia has been shown to induce elevated secretion of vascular endothelial growth factor (VEGF), leading to the development of hypoxic PAH. However, the molecular mechanisms underlying hypoxic PAH remain incompletely understood. Programmed cell death (PCD) is a natural cell death and regulated by certain genes. Emerging evidence suggests that apoptotic resistance contributes to the development of PAH. Moreover, several novel types of PCD, such as autophagy, pyroptosis, and ferroptosis, have been reported to be involved in the development of PAH. Additionally, multiple diverse epigenetic mechanisms including RNA methylation, DNA methylation, histone modification, and the non-coding RNA molecule-mediated processes have been strongly linked to the development of PAH. These epigenetic modifications affect the expression of genes, which produce important changes in cellular biological processes, including PCD. Consequently, a better understanding of the PCD processes and epigenetic modification involved in PAH will provide novel, specific therapeutic strategies for diagnosis and treatment. In this review, we aim to discuss recent advances in epigenetic mechanisms and elucidate the role of epigenetic modifications in regulating PCD in hypoxia-induced PAH

Inhibition of GABAA receptors in intestinal stem cells prevents chemoradiotherapy-induced intestinal toxicity.

peer reviewedLethal intestinal tissue toxicity is a common side effect and a dose-limiting factor in chemoradiotherapy. Chemoradiotherapy can trigger DNA damage and induce P53-dependent apoptosis in LGR5+ intestinal stem cells (ISCs). Gamma-aminobutyric acid (GABA) and its A receptors (GABAAR) are present in the gastrointestinal tract. However, the functioning of the GABAergic system in ISCs is poorly defined. We found that GABAAR α1 (GABRA1) levels increased in the murine intestine after chemoradiotherapy. GABRA1 depletion in LGR5+ ISCs protected the intestine from chemoradiotherapy-induced P53-dependent apoptosis and prolonged animal survival. The administration of bicuculline, a GABAAR antagonist, prevented chemoradiotherapy-induced ISC loss and intestinal damage without reducing the chemoradiosensitivity of tumors. Mechanistically, it was associated with the reduction of reactive oxygen species-induced DNA damage via the L-type voltage-dependent Ca2+ channels. Notably, flumazenil, a GABAAR antagonist approved by the U.S. Food and Drug Administration, rescued human colonic organoids from chemoradiotherapy-induced toxicity. Therefore, flumazenil may be a promising drug for reducing the gastrointestinal side effects of chemoradiotherapy.Taishan Pandeng Scholar Program of Shandong Provinc