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Neutrophils are the earliest master inflammatory regulator cells recruited to target tissues after direct infection or injury. Although inflammatory factors are present in muscle that has been indirectly disturbed by peripheral nerve injury, whether neutrophils are present and play a role in the associated inflammatory process remains unclear. Here, intravital imaging analysis using spinning-disk confocal intravital microscopy was employed to dynamically identify neutrophils in denervated muscle. Slice digital scanning and 3D-view reconstruction analyses demonstrated that neutrophils escape from vessels and migrate into denervated muscle tissue. Analyses using reactive oxygen species (ROS) inhibitors and flow cytometry demonstrated that enhanced ROS activate neutrophils after denervation. Transcriptome analysis revealed that the vast majority of neutrophils in denervated muscle were of the CXCR2 subtype and were recruited by CXCL1. Most of these cells gradually disappeared within 1 week via P53-mediated apoptosis. Experiments using specific blockers confirmed that neutrophils slow the process of denervated muscle atrophy. Collectively, these results indicate that activated neutrophils are recruited via chemotaxis to muscle tissue that has been indirectly damaged by denervation, where they function in delaying atrophy.

The objective of this study is to describe the typical and atypical clinical and neuroimaging features of ALD in Chinese patients, which will help early diagnosis and intervention to improve prognosis of ALD.Forty-one patients in the Leukoencephalopathy Clinic of Neurology Department, Peking Union Medical College Hospital were enrolled. Detailed clinical manifestations and MRI features were analyzed. The relationship between phenotype and genotype as well as biochemical analysis was observed.The patients were classified according to phenotype and onset age, including 14 childhood cerebral ALD (CCALD), 8 adolescent cerebral ALD (adoCALD), 3 adult cerebral ALD (ACALD), 14 adrenomyeloneuropathy (AMN), and 2 ALD in women. AMN was the main presentation in adults. Visual impairment was usual onset symptom in CCALD and cognitive decline and psychiatric symptoms were found in adoCALD and ACALD. Typical MRI feature of CALD was symmetrical peri-ventricular "butterfly wings" like lesions in frontal and/or occipital lobe with peripheral DWI hyperintensities and Gd enhancement. Corpus callosum and internal capsule were always involved. Unilateral lesions were also possible. Cerebral AMN presented with centrum semiovale diffuse involvement. Spinocerebellar variant was a special subtype of AMN with obvious cerebellar and brainstem lesions. No relationships between phenotype and genotype as well as biochemical VLCFAs analysis were found.We emphasize that corpus callosum and internal capsule are always involved in ALD. A unilateral lesion is also possible. Neuroimaging of cerebral AMN is different from typical CALD with more centrum semiovale involvement. We support spinocerebellar variant was a rare subtype of AMN.

Background Progerin elevates atrophic gene expression and helps modify the nuclear membrane to cause severe muscle pathology, which is similar to muscle weakness in the elderly, to alter the development and function of the skeletal muscles. Stress-induced premature senescence (SIPS), a state of cell growth arrest owing to such stimuli as oxidation, can be caused by progerin. However, evidence for whether SIPS-induced progerin accumulation is connected to denervation-induced muscle atrophy is not sufficient. Methods Flow cytometry and a reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) inhibitors were used to assess the effect of oxidation on protein (p53), progerin, and nuclear progerin–p53 interaction in the denervated muscles of models of mice suffering from sciatic injury. Loss-of-function approach with the targeted deletion of p53 was used to assess connection among SIPS, denervated muscle atrophy, and fibrogenesis. Results The augmentation of ROS and iNOS-derived NO in the denervated muscles of models of mice suffering from sciatic injury upregulates p53 and progerin. The abnormal accumulation of progerin in the nuclear membrane as well as the activation of nuclear progerin–p53 interaction triggered premature senescence in the denervated muscle cells of mice. The p53-dependent SIPS in denervated muscles contributes to their atrophy and fibrogenesis. Conclusion Oxidative stress-triggered premature senescence via nuclear progerin–p53 interaction that promotes denervated skeletal muscular atrophy and fibrogenesis.

Exciton localization phenomena are considered here to comprehend the high internal quantum efficiency in InGaN/GaN multiple-quantum-well structures having discrete quantum dots (QDs) prepared by metal–organic-chemical-vapor deposition method on c-sapphire substrates. Spectroscopic results from the variable-temperature steady-state-photoluminescence and time-resolved photoluminescence (TRPL) are investigated. While the exciton localization is enhanced by strong localized states within the InGaN/GaN QDs–the impact of free carrier recombination cannot be ignored. The observed non-exponential decay in TRPL measurements is explained using a model by meticulously including localized exciton, non-radiative and free carrier recombination rates. A new method is proposed to calculate the internal quantum efficiency, which is supplementary to the traditional approach based on temperature-dependent photoluminescence measurement.