Acute kidney injury predisposes patients to the development of both chronic kidney disease and end-stage renal failure, but the molecular details underlying this important clinical association remain obscure. We report that kidney injury molecule-1 (KIM-1), an epithelial phosphatidylserine receptor expressed transiently after acute injury and chronically in fibrotic renal disease, promotes kidney fibrosis. Conditional expression of KIM-1 in renal epithelial cells (Kim1 RECtg ) in the absence of an injury stimulus resulted in focal epithelial vacuolization at birth, but otherwise normal tubule histology and kidney function. By 4 weeks of age, Kim1 RECtg mice developed spontaneous and progressive interstitial kidney inflammation with fibrosis, leading to renal failure with anemia, proteinuria, hyperphosphatemia, hypertension, cardiac hypertrophy, and death, analogous to progressive kidney disease in humans. Kim1 RECtg kidneys had elevated expression of proinflammatory monocyte chemotactic protein-1 (MCP-1) at early time points. Heterologous expression of KIM-1 in an immortalized proximal tubule cell line triggered MCP-1 secretion and increased MCP-1-dependent macrophage chemotaxis. In mice expressing a mutant, truncated KIM-1 polypeptide, experimental kidney fibrosis was ameliorated with reduced levels of MCP-1, consistent with a profibrotic role for native KIM-1. Thus, sustained KIM-1 expression promotes kidney fibrosis and provides a link between acute and recurrent injury with progressive chronic kidney disease.
Articles you may be interested inMorphology and microstructure evolution of Al x Ga 1 − x N epilayers grown on GaN/sapphire templates with AlN interlayers observed by transmission electron microscopy Morphology and microstructure of dislocation etch pits in GaN epilayers etched by molten KOH have been investigated by atomic force microscopy, scanning electron microscopy, and transmission electron microscopy ͑TEM͒. Three types of etch pits ͑␣, , and ␥͒ are observed. The ␣ type etch pit shows an inversed trapezoidal shape, the  one has a triangular shape, and the ␥ type one has a combination of triangular and trapezoidal shapes. TEM observation shows that ␣, , and ␥ types etch pits originate from screw, edge, and mixed-type threading dislocations ͑TDs͒, respectively. For the screw-type TD, it is easily etched along the steps that the dislocation terminates, and consequently, a small Ga-polar plane is formed to prevent further vertical etching. For the edge-type TD, it is easily etched along the dislocation line. Since the mixed-type TDs have both screw and edge components, the ␥ type etch pit has a combination of ␣ and  type shapes. It is also found that the chemical stabilization of Ga-polar surface plays an important role in the formation of various types of dislocation etch pits.
New treatment paradigms that slow or reverse progression of chronic kidney disease (CKD) are needed to relieve significant patient and healthcare burdens. We have shown that a population of selected renal cells (SRCs) stabilized disease progression in a mass reduction model of CKD. Here, we further define the cellular composition of SRCs and apply this novel therapeutic approach to the ZSF1 rat, a model of severe progressive nephropathy secondary to diabetes, obesity, dyslipidemia, and hypertension. Injection of syngeneic SRCs into the ZSF1 renal cortex elicited a regenerative response that significantly improved survival and stabilized disease progression to renal structure and function beyond 1 year posttreatment. Functional improvements included normalization of multiple nephron structures and functions including glomerular filtration, tubular protein handling, electrolyte balance, and the ability to concentrate urine. Improvements to blood pressure, including reduced levels of circulating renin, were also observed. These functional improvements following SRC treatment were accompanied by significant reductions in glomerular sclerosis, tubular degeneration, and interstitial inflammation and fibrosis. Collectively, these data support the utility of a novel renal cell-based approach for slowing renal disease progression associated with diabetic nephropathy in the setting of metabolic syndrome, one of the most common causes of end-stage renal disease.
A highly efficient
hybrid photocatalytic system consisting of Ni(HCO3)2 and mesoporous TiO2 microrods was
successfully fabricated by a hydrothermal approach. The involvement
of Ni(HCO3)2 cocatalyst resulted in significant
improvement of the hydrogen evolution on the host TiO2 photocatalyst
under artificial sunlight irradiation. The optimized hybrid photocatalysis
system with 2.5% (mole ratio) Ni(HCO3)2 loading
displayed the highest hydrogen evolution rate of 1798.0 μmol
g–1 h–1, which was more than 18
times higher than that of pure mesoporous TiO2. On the
basis of the photoluminescence spectroscopy and photoelectrochemical
measurement results, it is proposed that the enhancement of photocatalytic
hydrogen evolution capability on the TiO2–Ni(HCO3)2 host photocatalyst–cocatalyst is not
only attributed to the efficient separation of photoinduced electron–hole
pairs, but also derived from the Ni(HCO3)2 cocatalyst
acting as active reaction sites toward hydrogen production.
The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study was to determine the clinical course and risk factors for patients showing recurrent SARS-CoV-2 RNA positivity. A total of 1087 COVID-19 patients confirmed by RT-PCR from February 24, 2020 to March 31, 2020 were retrospectively enrolled. Advanced age was significantly associated with mortality. In addition, 81 (7.6%) of the discharged patients tested positive for SARS-CoV-2 RNA during the isolation period. For patients with recurrent RT-PCR positivity, the median duration from illness onset to recurrence was 50 days. Multivariate regression analysis identified elevated serum IL-6, increased lymphocyte counts and CT imaging features of lung consolidation during hospitalization as the independent risk factors of recurrence. We hypothesized that the balance between immune response and virus toxicity may be the underlying mechanism of this phenomenon. For patients with a high risk of recurrence, a prolonged observation and additional preventative measures should be implemented for at least 50 days after illness onset to prevent future outbreaks.
The yellow luminescence (YL) in as-grown high-resistance (HR) and unintentional-doped (UID) GaN films grown by metal organic chemical vapor deposition has been investigated by means of photoluminescence and monoenergetic positron annihilation spectroscopy. It is found there is stronger YL in UID-GaN with higher concentration of gallium vacancy (VGa), suggesting that VGa-involved defects are the origin responsible for the YL in UID-GaN. Contrastly, there is much stronger YL in HR-GaN that is nearly free from VGa, suggesting that there is another origin for the YL in HR-GaN, which is thought as the carbon-involved defects. Furthermore, it is found that the HR-GaN film with shorter positron diffusion length Ld exhibits stronger YL. It is suggested that the increased wave function overlap of electrons and holes induced by the extremely strong space localization effect of holes deduced from the short Ld is the vital factor to enhance the YL efficiency in HR-GaN.
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