Protective role of madecassoside from Centella asiatica against protein L-isoaspartyl methyltransferase deficiency-induced neurodegeneration.

Protein L-isoaspartyl methyltransferase (PIMT/PCMT1) could repair l-isoaspartate (L-isoAsp) residues formed by deamidation of asparaginyl (Asn) residues or isomerization of aspartyl (Asp) residues in peptides and proteins during aging. Aside from abnormal accumulation of L-isoAsp, PIMT knockout (KO) mice mirrors some neuropathological hallmarks such as anxiety-like behaviors, impaired spatial memory and aberrant synaptic plasticity in the hippocampus of neurodegenerative diseases (NDs), including Alzheimer's disease (AD) and related dementias, and Parkinson's disease (PD). While some reports indicate the neuroprotective effect of madecassoside (MA) as a triterpenoid saponin component of Centella asiatica, its role against NDs-related anxiety and cognitive impairment remains unclear. Therefore, we investigated the effect of MA against anxiety-related behaviors in PIMT deficiency-induced mouse model of NDs. Results obtained from the elevated plus maze (EPM) test revealed that MA treatment alleviated anxiety-like behaviors in PIMT knockout mice. Furthermore, Real-time PCR, electroencephalogram (EEG) recordings, transmission electron microscopy analysis and ELISA were carried out to evaluate the expression of clock genes, sleep and synaptic function, respectively. The PIMT knockout mice were characterized by abnormal clock patterns, sleep disturbance and synaptic dysfunction, which could be improved by MA administration. Collectively, these findings suggest that MA exhibits neuroprotective effects associated with improved circadian rhythms sleep-wake cycle and synaptic plasticity in PIMT deficient mice, which could be translated to ameliorate anxiety-related symptoms and cognitive impairments in NDs.

Single-cell RNA sequencing shows the immune cell landscape in the kidneys of patients with idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN) is a leading pathological type of the adult primary nephrotic syndrome. Some patients develop end-stage renal disease due to poor response to treatment with steroid and immunosuppressive agents. In order to explore the molecular mechanism of IMN, we collected renal tissue samples from IMN patients and healthy controls and performed analysis by single-cell RNA sequencing (scRNA-seq). A total of 11 kidney cell clusters were identified, including multiple myeloid cell clusters, NK/T cell clusters, and B cell clusters. Most kidney parenchymal and immune cells were enriched in the regulation of immune response, inflammation, fibrosis and endoplasmic reticulum stress. The macrophage population in the IMN group showed a highly activated profile with up-regulated genes related to chemotaxis, inflammation, phagocytosis and fibrosis. CD8+ T cells continued to be cytotoxic in IMN; however, a transition to "inflammageing" GZMK+ CD8+ T cells was observed. The proportion of activated B cells in renal tissues of IMN patients was much higher than that of normal controls, indicating that B cells in IMN might be activated by constant antigenic stimulation. Moreover, the cell-cell interaction analysis revealed the potential communication between renal glomerular cells and immune cells in IMN. Overall, scRNA-seq was applied to IMN to unravel the characteristics of immune cells and elucidate possible underlying mechanisms involved in the pathogenesis of IMN.

Recovery of high-grade copper from metal-rich particles of waste printed circuit boards by ball milling and sieving.

In this paper, a method of ball milling and sieving is proposed for recovery of high-grade copper from waste printed circuit boards (WPCBs). The effects of the milling time on the metals grade and recovery of the Cu, Sn and Pb during mechanical treatment were investigated. The results showed that, after 3 cycles of ball milling and sieving, the content of Cu was enriched to 94.72 wt.% from the initial 74.22 wt.% with a high recovery rate of 86.78%. Moreover, the contents of Sn and Pb were enriched to 28.27 wt.% and 18.86 wt.% from 10.13 wt.% and 6.63 wt.% in the by-products, respectively. However, excessive grinding occurred when the milling time was longer than 3 h and led to a sharp decrease in Cu recovery. The X-ray diffraction (XRD) patterns indicated that the metal phases mainly comprised pure Cu, Sn, Pb in the WPCB particles, while a Cu-Sn alloy was formed during the milling process, and the Cu-Sn alloy was also enriched in the tailings. The results presented here establish that ball milling and sieving is an alternative approach to recovering high-grade copper from WPCBs.

Etiology, risk factors, and prognosis of patients with syncope: A single-center analysis.

OBJECTIVE: To investigate the main causes, risk factors, and prognosis of patients hospitalized with syncope. METHODS: The patients admitted due to syncope were included. We analyzed the etiology, risk factors, and prognosis of patients with an average follow-up of 15.3 months. RESULTS: High-risk factors for cardiogenic syncope included age ≥60, male, hypertension, palpitation, troponin T-positive, abnormal ECG, CHD history, and syncope-related trauma. Mortality rate was 4.6%, recurrence rate of syncope was 10.5%, and the rehospitalization rate was 8.5%. Univariate analysis showed that prognosis of syncope was related to age ≥60 years old, hypertension, positive troponin T, abnormal electrocardiogram, and coronary heart disease (p < .05). Multivariate Cox proportional hazard analysis showed that age ≥60 years old (p = .021) and high-sensitivity troponin-positive (p = .024) were strongly related to the prognosis of syncope. Kaplan-Meier curve showed statistical difference in the survival rate between the groups divided by age ≥60 years (p = .028), hs-TnT-positive (p < .001), abnormal ECG (p = .027), and history of CHD (p = .020). CONCLUSION: High-risk factors for cardiogenic syncope included age ≥60, male, hypertension, palpitation, troponin T-positive, abnormal ECG, CHD family history, and syncope-related trauma. Age, hypertension, troponin T-positive, abnormal ECG, and CHD history were associated with the prognosis of syncope.

Differential expression of microRNAs associated with neurodegenerative diseases and diabetic nephropathy in protein l-isoaspartyl methyltransferase-deficient mice.

Protein l-isoaspartyl methyltransferase (PIMT/PCMT1), an enzyme repairing isoaspartate residues in peptides and proteins that result from the spontaneous decomposition of normal l-aspartyl and l-asparaginyl residues during aging, has been revealed to be involved in neurodegenerative diseases (NDDs) and diabetes. However, the molecular mechanisms for a putative association of PIMT dysfunction with these diseases have not been clarified. Our study aimed to identify differentially expressed microRNAs (miRNAs) in the brain and kidneys of PIMT-deficient mice and uncover the epigenetic mechanism of PIMT-involved NDDs and diabetic nephropathy (DN). Differentially expressed miRNAs by sequencing underwent target prediction and enrichment analysis in the brain and kidney of PIMT knockout (KO) mice and age-matched wild-type (WT) littermates. Sequence analysis revealed 40 differentially expressed miRNAs in the PIMT KO mouse brain including 25 upregulated miRNAs and 15 downregulated miRNAs. In the PIMT KO mouse kidney, there were 80 differentially expressed miRNAs including 40 upregulated miRNAs and 40 downregulated miRNAs. Enrichment analysis and a systematic literature review of differentially expressed miRNAs indicated the involvement of PIMT deficiency in the pathogenesis in NDDs and DN. Some overlapped differentially expressed miRNAs between the brain and kidney were quantitatively assessed in the brain, kidney, and serum-derived exosomes, respectively. Despite being preliminary, these results may aid in investigating the pathological hallmarks and identify the potential therapeutic targets and biomarkers for PIMT dysfunction-related NDDs and DN.

The Influence of A Mo Addition on the Interfacial Morphologies and Corrosion Resistances of Novel Fe-Cr-B Alloys Immersed in Molten Aluminum.

The influence of a Mo addition on the interfacial morphologies and corrosion resistances of novel Fe-Cr-B alloys in molten aluminum at 750 °C was systematically investigated using scanning electron microscopy, X-ray diffractometer, electron probe microanalysis, and transmission electron microscopy. The results indicated that Mo could not only strengthen the matrix but also facilitate the formation of borides. Furthermore, the microstructures of Mo-rich M2B boride changed from a local eutectic net-like structure to a typical coarse dendritic structure and a blocky hypereutectic structure with increasing Mo addition. This was true of the blocky Mo-rich M2B boride, rod-like Cr-rich M2B boride and the corrosion products, which had a synergistic effect on retarding of the diffusion of molten aluminum. Notably, the corrosion resistance of the Fe-Cr-B-Mo alloy, with an 8.3 wt.% Mo addition, was 3.8 times higher than that of H13 steel.