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Osteopetrosis is an inherited metabolic disease, characterized by increased bone density and narrow marrow cavity. Patients with severe osteopetrosis exhibit abnormal bone brittleness, anemia, and infection complications, which commonly cause death within the first decade of life. Pathologically, osteopetrosis impairs not only the skeletal system, but also the hemopoietic and immune systems during development, while the underlying osteoimmunological mechanisms remain unclear. Osteoclastic mutations are regarded as the major causes of osteopetrosis, while osteoclast non-autonomous theories have been proposed in recent years with unclear underlying mechanisms. Retinoic acid (RA), the metabolite of Vitamin A, is an essential requirement for skeletal and hematopoietic development, through the activation of retinoic acid signaling. RA can relieve osteopetrosis symptoms in some animal models, while its effect on bone health is still controversial and the underlying mechanisms remain unclear. In this study, we constructed an osteoblast-specific inhibitory retinoic acid signaling mouse model and surprisingly found it mimicked the symptoms of osteopetrosis found in clinical cases: dwarfism, increased imperfectly-formed trabecular bone deposition with a reduced marrow cavity, thin cortical bone with a brittle skeleton, and hematopoietic and immune dysfunction. Micro-CT, the three-point bending test, and histological analysis drew a landscape of poor bone quality. Single-cell RNA sequencing (scRNA-seq) of the femur and RNA-seq of osteoblasts uncovered an atlas of pathological skeletal metabolism dysfunction in the mutant mice showing that osteogenesis was impaired in a cell-autonomous manner and osteoclastogenesis was impaired via osteoblast-osteoclast crosstalk. Moreover, scRNA-seq of bone marrow and flow cytometry of peripheral blood, spleen, and bone marrow uncovered pathology in the hematopoietic and immune systems in the mutant mice, mimicking human osteopetrosis. Results showed that hematopoietic progenitors and B lymphocyte differentiation were affected and the osteoblast-dominated cell crosstalk was impaired, which may result from transcriptional impairment of the ligands Pdgfd and Sema4d. In summary, we uncovered previously unreported pathogenesis of osteopetrosis-like disorder in mice with skeletal, hematopoietic, and immune system dysfunction, which was induced by the inhibition of retinoic acid signaling in osteoblasts, and sheds new insights into a potential treatment for osteopetrosis. [ABSTRACT FROM AUTHOR]

Purpose: Large-scale, contemporary studies assessing the spectrum of kidney diseases in northwest China are lacking. Therefore, we aimed to assess the profile of 30-year temporal changes in biopsy-proven kidney diseases in northwest China. Methods: This cross-sectional study included all patients with a native kidney biopsy specimen in the First Affiliated Hospital of Xi'an Jiaotong University between 1989 and 2018. Data on demographic characteristics and pathological diagnosis were extracted from medical records and pathological reports. Changing patterns of kidney diseases over the study period and disease distributions in different gender and age groups were examined. Results: This study included 13,620 patients with a mean age of 38.5 ± 16.5 years and included 58.2% of men. Primary glomerulonephritis (PGN), second glomerulonephritis (SGN), tubulointerstitial disease, and other renal diseases accounted for 79.1, 18.3, 2.4, and 0.2% of all kidney diseases, respectively. In PGN, IgA nephropathy (IgAN) (25.1%) was the most common type, followed by non-IgA mesangial proliferative glomerulonephritis (MsPGN) (24.9%) and membranous nephropathy (MN) (17.4%). The frequency of MN dramatically increased (p < 0.001) over the course of the study. Lupus nephritis (6.2%) and Henoch-Schönlein purpura nephritis (HSPN) (4.9%) were leading SGN diagnosis. The frequencies of IgAN, non-IgA MsPGN, and HSPN declined, while those of ANCA/pauci-immune glomerulonephritis and diabetic nephropathy significantly increased. Conclusion: PGN continues to be the predominant kidney disease in northwest China, and IgAN is the most common type. The frequencies of MN and diabetic nephropathy significantly increased. These findings might be explained by behavioral and environmental exposures and provide implications on future hypothesis-driven research. [ABSTRACT FROM AUTHOR]

Blood blister-like aneurysm (BBA) of the internal carotid artery (ICA) is highly challenging to treat owing to its variable morphology and tendency for rupture and regrowth. In this study, we attempted to discuss the key techniques for overlapping low-profile visualized intraluminal support (LVIS) stent-assisted coil embolization, which is used for treating BBAs in our center. Clinical characteristics, endovascular treatment details, outcomes, and follow-up results of 13 patients with BBA treated at our center were retrospectively evaluated in this study. Overlapping LVIS stent-assisted coil embolization was successfully performed in all 13 patients of ruptured BBAs located in the ICAs. Recurrence of aneurysm was observed in 4 cases (30.8%) during the angiographic follow-up; in 2 of these cases, spontaneous healing was observed after discontinuation of antiplatelet therapy. Further, 2 patients with recurrence underwent endovascular treatment with complete obliteration of the aneurysm in one and occlusion of the parent artery after Onyx embolization and stent placement in the other. The overall obliteration rate of the BBAs was 92.3% (12/13). One patient (7.7%) developed intraoperative rupture of the aneurysm with coils protruding outside; however, no severe hemorrhage or neurological dysfunction occurred owing to timely embolization. Overlapping LVIS stent-assisted coil embolization is effective for management of BBA of the ICA. Appropriate adjustment in antiplatelet therapy may improve healing in recurrent cases. [ABSTRACT FROM AUTHOR]

Severe injury of renal tubular epithelial cells may cause acute renal failure, the progression of which results in renal fibrosis, and obstructive nephropathy. Transforming growth factor β 1 and bone morphogenic protein 7 (BMP7) play contradicting roles in and coordinate the process of epithelial-to-mesenchymal transition of renal tubular epithelial cells, but the molecular regulation of BMP7 remains ill-defined. Here, we addressed this question. We found that after induction of unilateral ureteral obstruction (UUO) in mice, the increases in BMP7 mRNA were much more pronounced than BMP7 protein in kidney, suggesting the presence of post-transcriptional control of BMP7. Moreover, significant increases in a BMP7-targeting microRNA, miR-384-5p, were detected in the mouse kidney post UUO. Overexpression of miR-384-5p significantly decreased BMP7 protein, while depletion of miR-384-5p significantly increased BMP7 protein in renal epithelial cells. Bioinformatics study showed that miR-384-5p appeared to suppress BMP7 protein translation, through its direct binding to the 3′-UTR of BMP7 mRNA. Furthermore, suppression of miR-384-5p in vivo attenuated severity of renal injury by UUO. Together, our study sheds light on miR-384-5p as a crucial factor that regulates the fibrosis-related pathogenesis after renal injury, and points to miR-384-5p as a promising innovative therapeutic target for prevention of renal fibrosis. [ABSTRACT FROM AUTHOR]

Tracking-by-detection methods have been widely studied and some promising results have been obtained. These methods use discriminative appearance models to train and update online classifiers. They also use a sliding window to detect samples which will then be classified. Then, the location of the sample with the maximum classifier response will be selected as the new location. Compressive tracking was recently proposed with an appearance model based on features extracted in the compressed domain. However, CT uses a fixed-size tracking box to detect samples, and this is unsuitable for practice applications. CT detects samples around the selected region of the previous frame within a fixed radius. Here, the classifier may become inaccurate if the selected region drifts. The fixed radius is also not suitable for tracking targets that experience abrupt acceleration changes. Furthermore, CT updates the classifier parameters with constant learning rate. If the target is fully occluded for an extended period, the classifier will instead learn the features of the cover object and the target will ultimately be lost. In this paper, we present a multi-scale compressive tracker. This tracker integrates an improved appearance model based on normalized rectangle features extracted in the adaptive compressive domain into the bootstrap filter. This type of feature extraction is efficient, and the computation complexity does not increase as the tracking regions become larger. The classifier response is utilized to generate particle importance weight and a re-sample procedure preserves samples according to weight. A 2-order transition model considers the target velocity to estimate the current position and scale status. In this way, the sampling is not limited to a fixed range. Here, feedback strategies are adopted to adjust learning rate for occlusion. Experimental results on various benchmark challenging sequences have demonstrated the superior performance of our tracker when compared with several state-of-the-art tracking algorithms. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMSCs) have the ability of self-renewal and multi-directional differentiation. Recent reports showed that BMSCs could differentiate into endocrine cells of pancreas. However, the differentiation is not efficient enough to produce insulin-producing cells for the future therapeutic use. Pdx-1 is a crucial regulator for pancreatic development. Therefore we constructed a eukaryotic expression vector containing Pdx-1 to determine the effect of Pdx-1 expression on differentiation of BMSCs in vitro. The results showed that BMSCs could self-assemble to form functional pancreatic islet-like structures after differentiation in vitro. The proportion of insulin-producing cells differentiated from Pdx-1+BMSCs was 28.23%±2.56%, higher than that from BMSCs transfected with vacant vector and Pdx-1 − BMSCs (7.23%±1.56% and 4.08%±2.69% respectively) by flow cytometry. Immunocytochemical examination also testified the expression of multiple β-cells-specific genes such as insulin, glucagons, somatostatin in differentiated BMSCs. The results also revealed that the expressions of genes mentioned above in Pdx-1+BMSCs were higher than that in Pdx-1−BMSCs, which was confirmed by Western blotting analysis and RT-PCR. Glucose-induced insulin secretion from Pdx-1+BMSCs in 5mmol/L and 25mmol/L glocuse was (56.61±4.82) µU/mL and (115.29±2.56) µU/mL respectively, which were much higher than those from Pdx-1−BMSCs((25.53±6.49) µU/mL and (53.26±7.56) µU/mL respectively). Grafted animals were able to maintain their body weight and survive for relatively longer periods of time than hyperglycemic sham-grafted controls, which demonstrated an overall beneficial effect of the grafted cells on the health of the animals. These findings thus suggested that exogenous expression of Pdx-1 should provide a promising approach for efficiently producing islet-like cells from BMSCs for the future therapeutic use in diabetic patients. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide exists widely in mammalian tissues and plays a vital role in physiological and pathophysiological processes. However, striking differences with orders of magnitude were observed for the detected hydrogen sulfide concentrations in biological matrices among different measurements in literature, which lead to the uncertainty for examination the biological relevance of hydrogen sulfide. Here, we developed and validated a liquid chromatography- mass spectrometry (LC-MS/MS) method for the determination of hydrogen sulfide in various biological matrices by determination of a derivative of hydrogen sulfide and monobromobimane named sulfide dibimane (SDB). 36S-labeled SDB was synthesized and validated for using as an internal standard. This method has been successfully used to measure hydrogen sulfide levels in a broad range of biological matrices, such as blood, plasma, tissues, cells, and enzymes, across different species. Moreover, a novel mode that hydrogen sulfide could loosely and non-covalently bind to human serum protein (HSA) and hemoglobin (HB) was revealed by using the developed method. [ABSTRACT FROM AUTHOR]