HIF-1 induced tiRNA-Lys-CTT-003 is protective against cisplatin induced ferroptosis of renal tubular cells in mouse AKI model.

HIF-1 activation is protective in acute kidney injury (AKI), but its underlying mechanism is not fully understood. Stress-induced tRNA derived small RNAs play an emerging role in cellular processes. This study investigated the role of HIF-1 associated tiRNA-Lys-CTT-003 (tiR-Lys) in an AKI mouse model. Our sequencing results showed that ischemia can promote the production of renal tiR-Lys by activating HIF-1α. FG-4592, a HIF-1 inducer, can also upregulate the expression of tiR-Lys in renal tubular cells. Both overexpression of tiR-Lys and FG-4592 pre-treatment could improve mitochondrial damage and lipid peroxidation with alleviated renal function and morphological damage in cisplatin-induced AKI mice. While the anti-ferroptosis effect of FG-4592 were largely eliminated by tiR-Lys inhibitor. Notably, tiR-Lys directly alleviated cell death and MDA accumulation induced by the ferroptosis inducer Erastin, accompanied with restored expression of GPX4. RNA-Pulldown and RIP-qPCR results revealed that tiR-Lys can interact with the RNA-binding protein GRSF1.tiR-lys overexpression can preserve protein expression of GRSF1 decreased by cisplatin. Inhibiting Grsf1 via shRNA eliminated the upregulation of GPX4 by tiR-Lys. In conclusion, our study demonstrates that HIF-1α-induced tiR-Lys is protective in cisplatin-induced AKI, primarily by upregulating the level of GPX4 through interaction with GRSF1, thereby inhibiting ferroptosis in renal tubular epithelial cells.

Identification of key genes as potential diagnostic biomarkers in sepsis by bioinformatics analysis.

Background: Sepsis, an infection-triggered inflammatory syndrome, poses a global clinical challenge with limited therapeutic options. Our study is designed to identify potential diagnostic biomarkers of sepsis onset in critically ill patients by bioinformatics analysis. Methods: Gene expression profiles of GSE28750 and GSE74224 were obtained from the Gene Expression Omnibus (GEO) database. These datasets were merged, normalized and de-batched. Weighted gene co-expression network analysis (WGCNA) was performed and the gene modules most associated with sepsis were identified as key modules. Functional enrichment analysis of the key module genes was then conducted. Moreover, differentially expressed gene (DEG) analysis was conducted by the "limma" R package. Protein-protein interaction (PPI) network was created using STRING and Cytoscape, and PPI hub genes were identified with the cytoHubba plugin. The PPI hub genes overlapping with the genes in key modules of WGCNA were determined to be the sepsis-related key genes. Subsequently, the key overlapping genes were validated in an external independent dataset and sepsis patients recruited in our hospital. In addition, CIBERSORT analysis evaluated immune cell infiltration and its correlation with key genes. Results: By WGCNA, the greenyellow module showed the highest positive correlation with sepsis (0.7, p = 2e - 19). 293 DEGs were identified in the merged datasets. The PPI network was created, and the CytoHubba was used to calculate the top 20 genes based on four algorithms (Degree, EPC, MCC, and MNC). Ultimately, LTF, LCN2, ELANE, MPO and CEACAM8 were identified as key overlapping genes as they appeared in the PPI hub genes and the key module genes of WGCNA. These sepsis-related key genes were validated in an independent external dataset (GSE131761) and sepsis patients recruited in our hospital. Additionally, the immune infiltration profiles differed significantly between sepsis and non-sepsis critical illness groups. Correlations between immune cells and these five key genes were assessed, revealing that plasma cells, macrophages M0, monocytes, T cells regulatory, eosinophils and NK cells resting were simultaneously and significantly associated with more than two key genes. Conclusion: This study suggests a critical role of LTF, LCN2, ELANE, MPO and CEACAM8 in sepsis and may provide potential diagnostic biomarkers and therapeutic targets for the treatment of sepsis.

Single-cell transcriptomic profiling reveals decreased ER protein Reticulon3 drives the progression of renal fibrosis.

Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.

VDR restores the expression of PINK1 and BNIP3 in TECs of streptozotocin-induced diabetic mice.

Defective mitophagy in renal tubular epithelial cells is one of the main drivers of renal fibrosis in diabetic kidney disease. Our gene sequencing data showed the expression of PINK1 and BNIP3, two key molecules of mitophagy, was decreased in renal tissues of VDR-knockout mice. Herein, streptozotocin (STZ) was used to induce renal interstitial fibrosis in mice. VDR deficiency exacerbated STZ-induced renal impairment and defective mitophagy. Paricalcitol (pari, a VDR agonist) and the tubular epithelial cell-specific overexpression of VDR restored the expression of PINK1 and BNIP3 in the renal cortex and attenuated STZ-induced kidney fibrosis and mitochondrial dysfunction. In HK-2 cells under high glucose conditions, an increased level of α-SMA, COL1, and FN and a decreased expression of PINK1 and BNIP3 with severe mitochondrial damage were observed, and these alterations could be largely reversed by pari treatment. ChIP-qPCR and luciferase reporter assays showed VDR could positively regulate the transcription of Pink1 and Bnip3 genes. These findings reveal that VDR could restore mitophagy defects and attenuate STZ-induced fibrosis in diabetic mice through regulation of PINK1 and BNIP3.

RTN3 deficiency exacerbates cisplatin-induced acute kidney injury through the disruption of mitochondrial stability.

Reticulum 3 (RTN3) is an endoplasmic reticulum (ER) protein that has been reported to act in neurodegenerative diseases and lipid metabolism. However, the role of RTN3 in acute kidney injury (AKI) has not been explored. Here, we employed public datasets, patient data, and animal models to explore the role of RTN3 in AKI. The underlying mechanisms were studied in primary renal tubular epithelial cells and in the HK2 cell line. We found reduced expression of RTN3 in AKI patients, cisplatin-induced mice, and cisplatin-treated HK2 cells. RTN3-null mice exhibit more severe AKI symptoms and kidney fibrosis after cisplatin treatment. Mitochondrial dysfunction was also found in cells with RTN3 knockdown or knockout. A mechanistic study revealed that RTN3 can interact with HSPA9 in kidney cells. RTN3 deficiency may disrupt the RTN3-HSPA9-VDAC2 complex and affect MAMs during ER-mitochondrion contact, which further leads to mitochondrial dysfunction and exacerbates cisplatin-induced AKI. Our study indicated that RTN3 was important in the kidney and that a decrease in RTN3 in the kidney might be a risk factor for the aggravation of AKI.

Reticulon 3 regulates sphingosine-1-phosphate synthesis in endothelial cells to control blood pressure.

The discovery of the endothelium as a major regulator of vascular tone triggered intense research among basic and clinical investigators to unravel the physiologic and pathophysiologic significance of this phenomenon. Sphingosine-l-phosphate (S1P), derived from the vascular endothelium, is a significant regulator of blood pressure. However, the mechanisms underlying the regulation of S1P biosynthetic pathways in arteries remain to be further clarified. Here, we reported that Reticulon 3 (RTN3) regulated endothelial sphingolipid biosynthesis and blood pressure. We employed public datasets, patients, and mouse models to explore the pathophysiological roles of RTN3 in blood pressure control. The underlying mechanisms were studied in human umbilical vein endothelial cells (HUVECs). We reported that increased RTN3 was found in patients and that RTN3-null mice presented hypotension. In HUVECs, RTN3 can regulate migration and tube formation via the S1P signaling pathway. Mechanistically, RTN3 can interact with CERS2 to promote the selective autophagy of CERS2 and further influence S1P signals to control blood pressure. We also identified an RTN3 variant (c.116C>T, p.T39M) in a family with hypertension. Our data provided the first evidence of the association between RTN3 level changes and blood pressure anomalies and preliminarily elucidated the importance of RTN3 in S1P metabolism and blood pressure regulation.

[Advances in post-translational modifications of cGAS in innate immunity].

As a member of the nucleotidyltransferase family, cyclic guanosine monophosphate-adenosine monophosphate synthase (cyclic GMP-AMP synthase, or cGAS) is primarily involved in innate immunity as a nucleic acids sensor that activates its downstream pathway and regulates type I interferon synthesis. The regulation of cGAS function is correlated with the bacterial and viral infections, autoimmune diseases, tumors, and other diseases. Besides, post-translational modification is one of the most in-depth and extensive ways of cGAS function adjustment. There are mainly six types of post-translational modifications (PTMs) of cGAS, including phosphorylation, acetylation, ubiquitination, sumoylation, peptide chain cleavage, and glutamylation. This article not only systematically summarizes how PTMs of cGAS regulate the functions of cGAS under different physiological and pathological conditions, but also probes deep into the potential of PTMs as therapeutic targets.

Upregulation of the protein kinase Lyn is associated with renal injury in type 2 diabetes patients.

BACKGROUND: The role of inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) is well established. Lyn, a member of the nonreceptor protein tyrosine kinase Src family, has been reported to modulate inflammatory signaling pathways. METHODS: Lyn expression was assessed in kidney biopsies of 11 patients with diabetic kidney disease (DKD) and in kidney tissues of streptozotocin (STZ)-induced DKD mice. 102 recruited T2DM patients were divided into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Twenty-one healthy volunteers were recruited as a control group. Clinical data, blood and urine samples of all individuals were collected for analysis. RESULTS: Lyn expression was augmented in the kidneys of DKD patients and STZ-induced diabetic mice. Compared with control and normoalbuminuria groups, both mRNA and protein expression of Lyn in peripheral blood mononuclear cells (PBMCs) in the macroalbuminuria group were significantly increased (p < .05). Elevated Lyn levels were independently related to urine albumin/urine creatinine ratio and were positively associated with key inflammatory factors, namely interleukin-1ß, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Additionally, Lyn exhibited a noteworthy connection with renal tubular injury indicators, specifically urinary neutrophil gelatinase-associated lipocalin and urinary retinol binding protein. ROC curve analysis showed that Lyn could predict albuminuria in diabetic patients with an area under the curve of 0.844 (95% CI: 0.764-0.924). CONCLUSION: Lyn levels in PBMCs exhibited a positive correlation with the severity of albuminuria, renal tubular damage, and inflammatory responses. Hence, Lyn may be a compelling candidate for predicting albuminuria levels in diabetes.

Low-dose apatinib in subjects with renal impairment: A pharmacokinetics study.

OBJECTIVE: In patients with renal impairment, we studied apatinib and its major metabolites (M1-1, M1-2, M1-6, and M9-2) for pharmacokinetics. METHODS: Subjects with different renal functions were given a single oral dose of apatinib mesylate tablets of 250 mg. Pharmacokinetic samples were collected at 1 hour before dosing,0.25, 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, and 96 h after dosing. The pharmacokinetic parameters of apatinib and its major metabolites were calculated by noncompartmental analysis. RESULTS: Comparing PK parameters of the mild or moderate renal impairment group with the healthy group: the geometric mean ratios of maximum observed drug concentration (Cmax), the area under the plasma drug concentration-time curve from time 0 to the final quantifiable time (AUC0-t), and the area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) were all about one. No significant effect of mild and moderate renal impairment on apatinib pharmacokinetics was observed. Mild and moderate renal impairment was also not observed to have a significant effect on the pharmacokinetics of metabolites M1-1, M1-2, and M1-6. However, mild and moderate renal impairment had a certain increase in exposure to the metabolite M9-2. Considering that M9-2 has no inhibitory effect on protein tyrosine kinase, it has no clinical significance. In addition, the proportion of cumulative excretion of apatinib and its major metabolites was small and almost negligible in all three groups of subjects. CONCLUSION: Patients with mild and moderate renal impairment do not need to adjust the dose of apatinib when using low dose (250 mg) apatinib.

Lyn attenuates sepsis-associated acute kidney injury by inhibition of phospho-STAT3 and apoptosis.

Sepsis-associated acute kidney injury (SA-AKI) is a life-threatening condition associated with high mortality and morbidity. However, the underlying pathogenesis of SA-AKI is still unclear. Lyn belongs to Src family kinases (SFKs), which exert numerous biological functions including modulation in receptor-mediated intracellular signaling and intercellular communication. Previous studies demonstrated that Lyn gene deletion obviously aggravates LPS-induced lung inflammation, but the role and possible mechanism of Lyn in SA-AKI have not been reported yet. Here, we found that Lyn protected against renal tubular injury in cecal ligation and puncture (CLP) induced AKI mouse model by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation and cell apoptosis. Moreover, Lyn agonist MLR-1023 pretreatment improved renal function, inhibited STAT3 phosphorylation and decreased cell apoptosis. Thus, Lyn appears to play a crucial role in orchestrating STAT3-mediated inflammation and cell apoptosis in SA-AKI. Hence, Lyn kinase may be a promising therapeutic target for SA-AKI.

Immune landscape and the key role of APOE+ monocytes of lupus nephritis under the single-cell and spatial transcriptional vista.

BACKGROUND: Lupus nephritis (LN) is among the most common complication of systemic lupus erythematosus (SLE) with high mortality and morbidity. The analysis of LN kidney's local immune response through single-cell and spatial transcriptome enables the study of potential therapeutic targets. METHODS: By single cell sequencing and spatial transcriptome, we profile cells from LN kidney and normal kidney tissues to characterize cellular composition and elucidate the potential upstream monocyte/macrophage (Mono/MΦ) initiating the auto-immune response. After the high-throughput synergy screening, we performed the immunofluorescence to identify the specific cells in LN patients. The function experiments were finished by flow cytometry and Elisa. RESULTS: By immunofluorescence and spatial transcriptome, we identified differential subsets of Mono/MΦ and demonstrated that they exhibit temporal expression of TIMP1, IL1B, SPP1 and APOE. With the function experiments, we found that the APOE+ Mono may be compensatorily increased in LN, and the capacity of antigen presenting was decreased with the overexpression of APOE. Furthermore, how do the LN-specific Mono/MΦ transport in and out the glomerulus to active the local immune response remains unclear. Our results showed that lymphangiogenesis occurred in LN kidneys but not in normal kidneys, suggesting the presence of a new lymphatic vessel may serve as a 'green channel' for LN-specific Mono/MΦ. CONCLUSIONS: In LN, APOE+ Mono are compensatorily elevated, with decreased antigen presenting ability and reduced secretion of interferons. The lymphangiogenesis in LN prompts the trafficking of Mono/MΦ in LN kidney.

Vitamin D-VDR (vitamin D receptor) alleviates glucose metabolism reprogramming in lipopolysaccharide-induced acute kidney injury.

Background: Our previous study showed that vitamin D (VD)-vitamin D receptor (VDR) plays a nephroprotective role in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Recently, glucose metabolism reprogramming was reported to be involved in the pathogenesis of AKI. Objective: To investigate the role of VD-VDR in glucose metabolism reprogramming in LPS-induced AKI. Methods: We established a model of LPS-induced AKI in VDR knockout (VDR-KO) mice, renal proximal tubular-specific VDR-overexpressing (VDR-OE) mice and wild-type C57BL/6 mice. In vitro, human proximal tubular epithelial cells (HK-2 cells), VDR knockout and VDR overexpression HK-2 cell lines were used. Results: Paricalcitol (an active vitamin D analog) or VDR-OE reduced lactate concentration, hexokinase activity and PDHA1 phosphorylation (a key step in inhibiting aerobic oxidation) and simultaneously ameliorated renal inflammation, apoptosis and kidney injury in LPS-induced AKI mice, which were more severe in VDR-KO mice. In in vitro experiments, glucose metabolism reprogramming, inflammation and apoptosis induced by LPS were alleviated by treatment with paricalcitol or dichloroacetate (DCA, an inhibitor of p-PDHA1). Moreover, paricalcitol activated the phosphorylation of AMP-activated protein kinase (AMPK), and an AMPK inhibitor partially abolished the protective effect of paricalcitol in LPS-treated HK-2 cells. Conclusion: VD-VDR alleviated LPS-induced metabolic reprogramming in the kidneys of AKI mice, which may be attributed to the inactivation of PDHA1 phosphorylation via the AMPK pathway.

Vitamin D-vitamin D receptor alleviates oxidative stress in ischemic acute kidney injury via upregulating glutathione peroxidase 3.

Vitamin D receptor was previously reported to be protective in acute kidney injury (AKI) with the mechanism unclear, while the role of renal localized glutathione peroxidase 3 (GPX3) was not illustrated. The present study aims to investigate the role of GPX3 as well as its correlation with vitamin D-vitamin D receptor (VD-VDR) in ischemia-reperfusion (I/R)-induced renal oxidative stress injury. We showed that the expression of GPX3 and VDR were consistently decreased in renal tissues of I/R-related AKI patients and mice models. VDR agonist paricalcitol could reverse GPX3 expression and inhibit oxidative stress in I/R mice or hypoxia-reoxygenation (H/R) insulted HK-2 cells. VDR deficiency resulted in aggregated oxidative stress and severer renal injury accompanied by further decreased renal GPX3, while tubular-specific VDR overexpression remarkably reduced I/R-induced renal injury with recovered GPX3 in mice. Neither serum selenium nor selenoprotein P was affected by paricalcitol administration nor Vdr modification in vivo. In addition, inhibiting GPX3 abrogated the protective effects of VD-VDR in HK-2 cells, while GPX3 overexpression remarkably attenuated H/R-induced oxidative stress and apoptosis. Mechanistic probing revealed the GPX3 as a VDR transcriptional target. Our present work revealed that loss of renal GPX3 may be a hallmark that promotes renal oxidative stress injury and VD-VDR could protect against I/R-induced renal injury via inhibition of oxidative stress partly by trans-regulating GPX3. In addition, maintenance of renal GPX3 could be a therapeutic strategy for ischemic AKI.

Novel heterozygous mutation in COL4A4 responsible for Alport syndrome in a Chinese family.

Background: Chronic kidney disease, a global public health problem, results in kidney damage or a gradual decline in the glomerular filtration rate. Alport syndrome is commonly characterized by chronic glomerulonephritis caused by a structural disorder in the glomerular basement membrane. Currently, three disease-causing genes, namely collagen type IV alpha 3-5 (COL4A3, COL4A4, and COL4A5), have been associated with the occurrence of Alport syndrome. Methods: We enrolled a Chinese family where the affected individuals suffered from recurrent hematuria and proteinuria. The proband was selected for whole-exome sequencing to identify the pathogenic mutations in this family. Results: After data filtering, a novel heterozygous COL4A4 variant (NM_000092: c.853G>A/p. G285A) was identified as the putative genetic lesion in the affected individuals. Further co-segregation analysis using Sanger sequencing confirmed that this novel COL4A4 mutation (c.853G>A/p. G285A) exists only in the affected individuals and is absent in other healthy family members as well as in the control cohort of 200 individuals from the same locality. According to American College of Medical Genetics and Genomics guidelines, the mutation was classified as 'potentially pathogenic'. A bioinformatics-based prediction analysis revealed that this mutation is pathogenic and may disrupt the structure and function of type IV collagen. This variant is located at an evolutionarily conserved site of COL4A4. Conclusion: In this study, we identified a novel heterozygous COL4A4 variant (c.853G>A) in a Chinese AS family and assisted to diagnose this AS proband as autosomal-dominant Alport syndrome (ADAS). Our study expands the spectrum of Alport syndrome mutations and contributes to the genetic counseling and diagnosis of patients with Alport syndrome.

Src Family Kinases: A Potential Therapeutic Target for Acute Kidney Injury.

Src family kinases (SFKs) are non-receptor tyrosine kinases and play a key role in regulating signal transduction. The mechanism of SFKs in various tumors has been widely studied, and there are more and more studies on its role in the kidney. Acute kidney injury (AKI) is a disease with complex pathogenesis, including oxidative stress (OS), inflammation, endoplasmic reticulum (ER) stress, autophagy, and apoptosis. In addition, fibrosis has a significant impact on the progression of AKI to developing chronic kidney disease (CKD). The mortality rate of this disease is very high, and there is no effective treatment drug at present. In recent years, some studies have found that SFKs, especially Src, Fyn, and Lyn, are involved in the pathogenesis of AKI. In this paper, the structure, function, and role of SFKs in AKI are discussed. SFKs play a crucial role in the occurrence and development of AKI, making them promising molecular targets for the treatment of AKI.

Loss of RTN3 phenocopies chronic kidney disease and results in activation of the IGF2-JAK2 pathway in proximal tubular epithelial cells.

Reticulon 3 (RTN3) is an endoplasmic reticulum protein that has previously been shown to play roles in neurodegenerative diseases, but little is known about its function in the kidneys. The aim of the present study was to clarify the roles of RTN3 in chronic kidney disease (CKD) and kidney fibrosis. In this study, RTN3 levels were measured in kidney tissues from healthy controls and CKD or kidney fibrosis patients. An RTN3-null mouse model was generated to explore the pathophysiological roles of RTN3 in the kidneys. The underlying mechanisms were studied in primary proximal tubular epithelial cells and HEK293 cells in vitro. The results showed that (1) a reduction in RTN3 in mice induces CKD and kidney fibrosis; (2) decreased RTN3 expression is found in patients with CKD; (3) RTN3 plays critical roles in regulating collagen biosynthesis and mitochondrial function; and (4) mechanistically, RTN3 regulates these phenotypes by interacting with GC-Rich Promoter Binding Protein 1 (GPBP1), which activates the IGF2-JAK2-STAT3 pathway. Our study indicates that RTN3 might play crucial roles in CKD and kidney fibrosis and that a reduction in RTN3 in the kidneys might be a risk factor for CKD and kidney fibrosis.

Case Report: Congenital Brain Dysplasia, Developmental Delay and Intellectual Disability in a Patient With a 7q35-7q36.3 Deletion.

7q terminal deletion syndrome is a rare condition presenting with multiple congenital malformations, including abnormal brain and facial structures, developmental delay, intellectual disability, abnormal limbs, and sacral anomalies. At least 40 OMIM genes located in the 7q34-7q36.3 region act as candidate genes for these phenotypes, of which SHH, EN2, KCNH2, RHEB, HLXB9, EZH2, MNX1 and LIMR1 may be the most important. In this study, we discuss the case of a 2.5-year-old male patient with multiple malformations, congenital brain dysplasia, developmental delay, and intellectual disability. A high-resolution genome-wide single nucleotide polymorphism array and real-time polymerase chain reaction were performed to detect genetic lesions. A de novo 9.4 Mb deletion in chromosome region 7q35-7q36.3 (chr7:147,493,985-156,774,460) was found. This chromosome region contains 68 genes, some of which are candidate genes for each phenotype. To the best of our knowledge, this is a rare case report of 7q terminal deletion syndrome in a Chinese patient. Our study identifies a rare phenotype in terms of brain structure abnormalities and cerebellar sulcus widening in patients with deletion in 7q35-7q36.3.

Effect of Electroless Coatings on the Mechanical Properties and Wear Behavior of Oriented Multiwall Carbon Nanotube-Reinforced Copper Matrix Composites.

The effects of electroless coatings on the microstructure and composition of the interface between multi-walled carbon nanotubes (MWCNTs) and a Cu matrix and the mechanical properties and wear behavior of the resulting copper matrix composites were investigated. Ni and Cu coatings were electrolessly plated on MWCNTs and mixed subsequently with copper powder. Then copper matrix composites were prepared by sintering, hot extrusion and cold drawing processes. The results showed that MWCNTs were straight, long, uniformly dispersed and aligned in the composites. The Ni coating is more continuous, dense and complete than a Cu coating. The tensile strength, compressive strength, microhardness and tribological properties of Ni@MWCNTs/Cu composite along the drawing direction were enhanced most. The ultimate tensile strength and compressive strength were 381 MPa and 463 MPa, respectively. The friction coefficient and wear rate were reduced by 59% and 77%, respectively, compared with pure Cu samples. This study provides a new insight into the regulation of tribological properties of composites by their interface.

A preliminary study of KAT2A on cGAS-related immunity in inflammation amplification of systemic lupus erythematosus.

Previous studies demonstrated that cGAS pathway is related to the inflammation amplification in a variety of autoimmune diseases. Lysine acetyltransferase family (KATs) can regulate the nuclear transcription or cytoplasmic activation of cGAS through different mechanisms. However, its role and related immunity patterns in systemic lupus erythematosus (SLE) have not been explored. In this study, RNA-seq and scRNA-seq profiling were performed for peripheral blood mononuclear cells (PBMCs) from patients with SLE. R packages were used for bioinformatic analysis. Cell culture, RT-PCR, western blotting, immunofluorescence, immunohistochemistry, and ELISA were used to explore gene expression in vitro or clinical specimens. Plasmid transfection and mass spectrometry were used to detect protein modifications. Eight acetyltransferase and deacetylase family members with significantly differential expression in SLE were found. Among them, KAT2A was abnormally upregulated and positively correlated with disease activity index. Further, KAT2A-cGAS pathway was aberrantly expressed in specific immune cell subsets in SLE. In vitro studies showed KAT2A modulated cGAS through increasing expression and post-translational modification. Our research provides novel insights for accurately positioning specific immune-cell subgroups in which KAT2A-cGAS reaction mainly works and KAT2A regulation patterns.

Erratum: Use of whole-exome sequencing to identify a novel ADCY10 mutation in a patient with nephrolithiasis.

[This corrects the article on p. 4576 in vol. 12, PMID: 32913531.].