The optical temperature sensor utilizing the fluorescence intensity ratio (FIR) has garnered significant attention in the past few years due to its rapid response, robust anti-interference ...capability, remote control feature, and other advantages. In this study, the high-temperature solid-phase approach was used to fabricate a variety of double perovskite-structured La2MgSnO6: Bi3+, Sm3+ (LMS: Bi3+, Sm3+) phosphors. The Rietveld refinement data of XRD and the Gaussian fitting of the emission peak of LMS: 0.02Bi3+ phosphor indicated Bi3+ occupies three lattice sites. The calculation and analysis of average lifetime and energy transfer efficiency substantiated the presence of energy transfer from Bi3+ to Sm3+, with a transfer efficiency of up to 59.07%. The emission intensity of LMS: 0.02Bi3+, 0.05Sm3+ at 403 K maintains 50.2% at the condition of room temperature. The FIR fitting and calculation demonstrated that LMS: 0.02Bi3+, 0.05Sm3+ phosphor possessed good optical temperature sensitivity, with a maximum absolute sensitivity Sa-max of 0.0055 K−1 and a maximum relative sensitivity Sr-max of 0.88% K−1, demonstrating its valuable potential applications for optical temperature sensors.
Detailed knowledge of the diverse immunoglobulin germline genes is critical for the study of humoral immunity. Hundreds of alleles have been discovered by analyzing antibody repertoire sequencing ...(Rep-seq or Ig-seq) data
multiple novel allele detection tools (NADTs). However, the performance of these NADTs through antibody sequences with intrinsic somatic hypermutations (SHMs) is unclear. Here, we developed a tool to simulate repertoires by integrating the full spectrum features of an antibody repertoire such as germline gene usage, junctional modification, position-specific SHM and clonal expansion based on 2152 high-quality datasets. We then systematically evaluated these NADTs using both simulated and genuine Ig-seq datasets. Finally, we applied these NADTs to 687 Ig-seq datasets and identified 43 novel allele candidates (NACs) using defined criteria. Twenty-five alleles were validated through findings of other sources. In addition to the NACs detected, our simulation tool, the results of our comparison, and the streamline of this process may benefit further humoral immunity studies
Ig-seq.
ObjectivesSystemic lupus erythematosus (SLE) is a chronic autoimmune disease of considerable genetic predisposition. Genome-wide association studies have identified tens of common variants for SLE. ...However, the majority of them reside in non-coding sequences. The contributions of coding variants have not yet been systematically evaluated.MethodsWe performed a large-scale exome-wide study in 5004 SLE cases and 8179 healthy controls in a Han Chinese population using a custom exome array, and then genotyped 32 variants with suggestive evidence in an independent cohort of 13 246 samples. We further explored the regulatory effect of one novel non-coding single nucleotide polymorphism (SNP) in ex vivo experiments.ResultsWe discovered four novel SLE gene regions (LCT, TPCN2, AHNAK2 and TNFRSF13B) encompassing three novel missense variants (XP_016859577.1:p.Asn1639Ser, XP_016859577.1:p.Val219Phe and XP_005267356.1:p.Thr4664Ala) and two non-coding variants (rs10750836 and rs4792801) with genome-wide significance (pmeta <5.00×10−8). These variants are enriched in several chromatin states of primary B cells. The novel intergenic variant rs10750836 exhibited an expression quantitative trait locus effect on the TPCN2 gene in immune cells. Clones containing this novel SNP exhibited gene promoter activity for TPCN2 (P=1.38×10−3) whose expression level was reduced significantly in patients with SLE (P<2.53×10−2) and was suggested to be further modulated by rs10750836 in CD19+ B cells (P=7.57×10−5) in ex vivo experiments.ConclusionsThis study identified three novel coding variants and four new susceptibility gene regions for SLE. The results provide insights into the biological mechanism of SLE.
TLR7 has been linked to the pathogenesis of glomerulonephritis, but its precise roles are not clear. In this study, we evaluated the roles of TLR7 in IgA nephropathy (IgAN). TLR7 proteins were ...abundant in CD19+ B cells infiltrated in the kidneys of patients with IgAN. The intensities of both intrarenal TLR7 and CD19 proteins were closely associated with kidney function (estimated glomerular filtration rate eGFR and serum creatinine concentration) and renal histopathology (tubular atrophy, leukocyte infiltration, tubulointerstitial fibrosis, and global glomerulosclerosis) in patients with IgAN. Meanwhile, TLR7 mRNA levels were significantly increased in peripheral blood B cells of patients with IgAN. TLR7+CD19+ B cells expressed inflammatory cytokines (IL-6 and IL-12) in kidneys and produced high levels of IgA1 and galactose deficient-IgA1 (Gd-IgA1) in peripheral blood of patients with IgAN. Mechanistically, TLR7 activated B cells to produce high levels of Gd-IgA1 via the TLR7-GALNT2 axis in IgAN. Protein levels of GALNT2 were increased by overexpression of TLR7, while they were reduced by TLR7 knockdown in B cells. GALNT2 overexpression augmented Gd-IgA1 production in B cells derived from patients with IgAN. Taken together, high TLR7 expression in B cells has dual roles in the development and progression of IgAN, by facilitating renal inflammation and Gd-IgA1 antibody synthesis.
Background: Hyperuricemia is an independent risk factor for renal progression in IgA nephropathy (IgAN). However, no study has evaluated the effect of allopurinol on the clinical outcome in ...hyperuricemic IgAN. Methods: First,a retrospective cohort study of 353 IgAN patients was conducted to explore the relationship between uric acid (UA) and the progression of renal disease over a mean period of 5 years. Then, 40 hyperuricemic IgAN patients were randomized to receive allopurinol (100–300 mg/day) or usual therapy for 6 months. The study outcomes were renal disease progression and/or blood pressure. Results: Hyperuricemia independently predicted renal survival at 1, 3, and 5 years after adjustment for different baseline estimated glomerular filtration rates. In the randomized controlled trial, allopurinol did not significantly alter renal progression or proteinuria. The antihypertensive drug dosage was reduced in 7 of 9 cases with hypertension in the allopurinol group compared to 0 of 9 cases in the control group (p < 0.01). UA levels correlated with mean arterial pressure in normotensive patients (r = 0.388, p < 0.001). Conclusion: Hyperuricemia predicts the progression of IgAN independently of baseline estimated glomerular filtration rate. Allopurinol may improve the control of blood pressure. Further studies are required to explore the effects of lowering UA on renal protection in IgAN.
The high incidence and mortality of idiopathic pulmonary fibrosis (IPF) have led to the widespread use of antifibrotic drugs such as pirfenidone; however, the associated adverse reactions greatly ...vary among individuals and the dose is not fixed. To date, no reliable blood concentration range of pirfenidone is available to monitor adverse reactions and clinical efficacy. This real study assessed the efficacy and safety of different plasma concentrations of pirfenidone in patients with IPF. The study included 99 patients with IPF orally treated with pirfenidone capsules for at least 52 weeks. Ultra-performance liquid chromatography-mass spectrometry was used to analyze drug plasma concentrations. The annual rate of forced vital capacity (FVC) decline, assessed at week 52, was set as the primary end point. Secondary end points were the change from the baseline in the 6-min walk distance (6 MWD) and the time to the first acute exacerbation of IPF, both of which evaluated over 52 weeks. In the total population, the annual FVC decline in the high-concentration group was -90.0 ml per year versus -260.0 ml per year in the low-concentration group, for a between-group difference of 190.3 ml per year. The proportion of patients treated with high plasma concentrations of pirfenidone who showed an absolute decline of ≥10% in FVC% predicted, with a 6 MWD reduction of ≥50 m, or died, was lower than that of patients treated with low plasma concentrations of pirfenidone. High concentrations of pirfenidone reduced the risk of acute exacerbation in patients with IPF. Considerable differences were not observed for the total St. George's Respiratory Questionnaire score or the rates of death between the high- and low-concentration groups. Mild to moderate adverse events, mainly involving the gastrointestinal system and the skin, were more common in the high-concentration group than in the low-concentration group but did not lead to termination of treatment in most cases. Our results suggest that treatment of IPF with high blood concentration of pirfenidone is both safe and effective. In the case of tolerable adverse reactions, patients with IPF may benefit from high concentrations of pirfenidone.
Genome-wide association studies (GWAS) had discovered several genetic risk loci for IgA nephropathy (IgAN), where the susceptibility genes of CARD9 and HORMAD2 for IgAN were also implicated in ...inflammatory bowel disease (IBD), suggesting a shared genetic etiology of these two diseases. The aim of this study is to explore the common susceptibility loci between IgAN and IBD and provide evidences to elucidate the shared pathogenesis between these two autoimmune diseases. Nineteen single-nucleotide polymorphisms (SNPs) associated with IBD in Asian populations were selected through the National Human Genome Research Institute (NHGRI) GWAS Catalog, and 2078 IgAN patients and 2085 healthy individuals of Chinese Han ancestry were included in the two-stage case-control association study. Serum levels of complement factor B (CFB) and complement split product C3a were detected by enzyme-linked immunosorbent assay (ELISA). One significant shared association at rs4151657 (OR = 1.28, 95%CI = 1.13-1.45, P = 1.42 × 10
) was discovered between these two diseases, which implicated CFB as a susceptibility gene for IgAN. Genotype-phenotype correlation analysis found significant association of the rs4151657-C allele with decreased serum C3 levels. In addition, the rs4151657-C allele was also associated with higher CFB levels and C3a levels, which suggested a certain degree of systemic complement activation in IgAN patients with the rs4151657-CT or CC genotypes. Our study identified one risk locus (CFB) shared by IgAN and IBD, and genetic variants of CFB may affect complement activation and associate with the predisposition to IgAN.
Background
Diabetic nephropathy (DN) is one of the most prevalent complications of diabetes mellitus (DM). However, there is still a lack of effective methods for non-invasive diagnosis of DN in ...clinical practice. We aimed to explore biomarkers from plasma cell-free DNA as a surrogate of renal biopsy for the differentiation of DN patients from patients with DM.
Materials and methods
The plasma cell-free DNA (cfDNA) was sequenced from 53 healthy individuals, 53 patients with DM but without DN, and 71 patients with both DM and DN. Multidimensional features of plasma DNA were analyzed to dissect the cfDNA profile in the DM and DN patients and identify DN-specific cfDNA features. Finally, a classification model was constructed by integrating all informative cfDNA features to demonstrate the clinical utility in DN detection.
Results
In comparison with the DM patients, the DN individuals exhibited significantly increased cfDNA concentration in plasma. The cfDNA from the DN patients showed a distinct fragmentation pattern with an altered size profile and preferred motifs that start with “CC” in the cfDNA ending sites, which were associated with deoxyribonuclease 1 like 3 (
DNASE1L3
) expression in the kidney. Moreover, patients with DM or DN were found to carry more alterations in whole-genome cfDNA coverage when compared with healthy individuals. We integrated DN-specific cfDNA features (cfDNA concentration, size, and motif) into a classification model, which achieved an area under the receiver operating characteristic curve (AUC) of 0.928 for the differentiation of DN patients from DM patients.
Conclusion
Our findings showed plasma cfDNA as a reliable non-invasive biomarker for differentiating DN patients from DM patients. The utility of cfDNA in clinical practice in large prospective cohorts is warranted.
"Cytokine storm" is common in critically ill COVID-19 patients, however, mechanisms remain largely unknown. Here, we reported that overexpression of SARS-CoV-2 N protein in diabetic db/db mice ...significantly increased tubular death and the release of HMGB1, one of the damage-associated molecular patterns (DAMPs), to trigger M1 proinflammatory macrophage activation and production of IL-6, TNF-α, and MCP-1 via a Mincle-Syk/NF-κB-dependent mechanism. This was further confirmed
that overexpression of SARS-CoV-2 N protein caused the release of HMGB1 from injured tubular cells under high AGE conditions, which resulted in M1 macrophage activation and production of proinflammatory cytokines via a Mincle-Syk/NF-κB-dependent mechanism. This was further evidenced by specifically silencing macrophage Mincle to block HMGB1-induced M1 macrophage activation and production of IL-6, TNF-α, and MCP-1
. Importantly, we also uncovered that treatment with quercetin largely improved SARS-CoV-2 N protein-induced AKI in db/db mice. Mechanistically, we found that quercetin treatment significantly inhibited the release of a DAMP molecule HMGB1 and inactivated M1 pro-inflammatory macrophage while promoting reparative M2 macrophage responses by suppressing Mincle-Syk/NF-κB signaling
and
. In conclusion, SARS-CoV-2 N protein-induced AKI in db/db mice is associated with Mincle-dependent M1 macrophage activation. Inhibition of this pathway may be a mechanism through which quercetin inhibits COVID-19-associated AKI.
Background:
Exit-site infection (ESI) is a common complication in peritoneal dialysis (PD) patients. Clearly understanding the risk factors may be useful for the prevention of ESI. This study was to ...explore the prevalence and risk factors of ESI in incident PD patients.
Methods:
We evaluated ESI in incident PD patients who had catheter insertion in our center between 1 January 2009 and 31 December 2013, with follow-up for 1 year. We collected data on demographics, clinical features, and nursing care methods of the exit site (ES).
Results:
We recruited 1133 incident PD patients (687 male (60.6%); mean age 47.0 ± 15.1 years), and 245 (21.6%) had diabetes. Median follow-up was 12.0 months. One hundred and thirty-one patients had 139 episodes of ESI with a rate of 92.8 patient-months per episode (0.13 episodes per year). Coagulase-negative staphylococcus was the main pathogen, accounting for 33.8% of the ESIs. Gram-positive rods, Staphylococcus aureus, Pseudomonas, fungi, and other organisms accounted for 23.0%, 15.8%, 1.4%, 1.4%, and 2.9%, respectively. No bacterial growth was found in 15.1%. There were no differences in demographic and laboratory data (age, gender, primary kidney disease, hemoglobin, white blood cell, serum albumin, blood urea nitrogen, serum creatinine, and C-reactive protein) between the ESI and non-ESI groups. Poor competency of ES care, poor catheter immobilization, history of catheter-pulling injury, and mechanical stress on the ES were significantly associated with increased risk of ESI.
Conclusions:
The prevalence of ESI was 0.13 episodes per year. Poor competency of ES care, catheter mobilization, history of catheter-pulling injury, and mechanical stress by waist belt or the protective bag of PD on ES were risk factors for ESI.
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