A self-aligned assembling terahertz metasurface microfluidic sensor for liquid detection.

This paper reports a new terahertz metasurface microfluidic sensor, which is actually a kind of reflective terahertz metasurface absorber with a microfluidic-channel structure located in the strong field energy region of the absorber. The metasurface structure is made on an ultra-thin quartz substrate as the cap layer, while a two-step structure is made on a silicon substrate as the pedestal layer. In order to precisely control the thickness of the microfluidic channel, the cap layer is self-aligned assembled with the pedestal layer to form the terahertz metasurface microfluidic sensor. The obtained sensor could enhance the light-matter interaction, resulting in high sensing performance. The measured results show that the sensor has a perfect absorption peak at 2.60 THz and a high Q-factor of 62.59, which are basically consistent with the simulated results. The sensitivity and FOM calculated based on the measured results of different liquids with different refractive indices is 0.733 THz per RIU and 16.4, respectively. Compared with some recently related work, the sensitivity is increased by about 40%, the Q-factor is increased by 3-5 times, and the FOM is increased by 5 times, which make the sensor have great application potential for solution detection in the terahertz frequency band.

Neferine Targeted the NLRC5/NLRP3 Pathway to Inhibit M1-type Polarization and Pyroptosis of Macrophages to Improve Hyperuricemic Nephropathy.

BACKGROUND: Neferine (Nef) has a renal protective effect. This research intended to explore the impact of Nef on hyperuricemic nephropathy (HN). METHODS: Adenine and potassium oxonate were administered to SD rats to induce the HN model. Bone marrow macrophages (BMDM) and NRK-52E were used to construct a transwell co-culture system. The polarization of BMDM and apoptosis levels were detected using immunofluorescence and flow cytometry. Renal pathological changes were detected using hematoxylin-eosin (HE) and Masson staining. Biochemical methods were adopted to detect serum in rats. CCK-8 and EDU staining were used to assess cell activity and proliferation. RT-qPCR and western blot were adopted to detect NLRC5, NLRP3, pyroptosis, proliferation, and apoptosis-related factor levels. RESULTS: After Nef treatment, renal injury and fibrosis in HN rats were inhibited, and UA concentration, urinary protein, BUN, and CRE levels were decreased. After Nef intervention, M1 markers, pyroptosis-related factors, and NLRC5 levels in BMDM stimulated with uric acid (UA) treatment were decreased. Meanwhile, the proliferation level of NRK-52E cells co-cultured with UA-treated BMDM was increased, but the apoptosis level was decreased. After NLRC5 overexpression, Nef-induced regulation was reversed, accompanied by increased NLRP3 levels. After NLRP3 was knocked down, the levels of M1-type markers and pyroptosis-related factors were reduced in BMDM. CONCLUSION: Nef improved HN by inhibiting macrophages polarized to M1-type and pyroptosis by targeting the NLRC5/NLRP3 pathway. This research provides a scientific theoretical basis for the treatment of HN.

Optical metasurfaces for multiplex high-performance grating-type structural colors.

Optical metasurfaces provide a significant approach for the production of structural colors due to their excellent optical control abilities. Herein, we propose trapezoidal structural metasurfaces for achieving multiplex grating-type structural colors with high comprehensive performance originating from the anomalous reflection dispersion in the visible band. Single trapezoidal metasurfaces with different x-direction periods can tune the angular dispersion regularly from 0.036 rad/nm to 0.224 rad/nm to generate various structural colors, and composite trapezoidal metasurfaces with three kinds of combinations can achieve multiplex sets of structural colors. The brightness can be controlled by adjusting the distance between the trapezoids in a pair accurately. The designed structural colors have higher saturation than traditional pigmentary colors, whose excitation purity can reach 1.00. The gamut is about 158.1% of the Adobe RGB standard. This research has application potential in ultrafine displays, information encryption, optical storage, and anti-counterfeit tagging.

Effects of Purine Metabolism-Related LINC01671 on Tumor Heterogeneity in Kidney Renal Clear Cell Carcinoma.

BACKGROUND: Renal cell carcinoma has several subtypes, with kidney renal clear cell carcinoma (KIRC) being the most common and heterogeneous. Purine metabolism is associated with cancer progression. However, the role of purine metabolism-related long non-coding RNAs (lncRNAs) in KIRC remains unknown. METHODS: KIRC were grouped into Cluster-1 and Cluster-2 based on purine genes. Limma package was used to identify differentially expressed lncRNAs between two classes of purine genes. Single-factor screening was used followed by random forest dimensionality reduction and Lasso method to screen lncRNAs. A risk score model (Purine Score) containing the 3 lncRNAs was developed using the Lasso method. RESULTS: A total of 22 differentially expressed lncRNAs were identified. These were reduced to a final set of three (LINC01671, ARAP1-AS1 and LINC02747). Age and metastasis (M) were identified as independent prognostic factors for KIRC using univariate and multivariate Cox analysis. An abnormal immune cell response was also associated with patient survival. The Purine Score correlated with abnormal expression of immune checkpoint genes. Genetic analysis of KIRC found somatic mutations in TP53, TRIOBP, PBRM1, PKHD1, VHL, NPHP3, TLN2, CABIN1, ABCC6, XIRP2, and CHD4. In vitro cell experiments showed that knockdown of LINC01671 promoted the proliferation and migration of 786-O cells, while inhibiting apoptosis. Overexpression of LINC01671 inhibited the proliferation and migration of CAKI-1 cells, while promoting apoptosis. Gene Set Enrichment Analysis (GSEA) analysis revealed that LINC01671 was significantly enriched in the MAPK, NF-kappa B, mTOR, PI3K-Akt, and Wnt signaling pathways. CONCLUSIONS: LINC01671 may be a novel prognostic marker with important therapeutic value for KIRC.

Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7.

INTRODUCTION: Transforming growth factor-ß (TGF-ß), a common outcome of various progressive chronic kidney diseases, can regulate and induce fibrosis. OBJECTIVE: The study aimed to identify downstream targets of lncRNA ENST00000453774.1 (lnc453774.1) and outline their functions on the development of renal fibrosis. METHODS: HK-2 cells were induced with 5 ng/mL TGF-ß1 for 24 h to construct a renal fibrosis cell model. Differentially expressed genes (DEGs) targeted by lnc453774.1 in TGF-ß1-induced renal fibrosis were identified using RNA sequencing. The dataset GSE23338 was employed to identify DEGs in 48-h TGF-ß1-stimulated human kidney epithelial cells, and these DEGs were intersected with genes in the key module using weighted gene co-expression network analysis to generate key genes associated with renal fibrosis. MicroRNAs (miRs) that had targeting relationship with keys genes and lnc453774.1 were predicted by using Miranda software, and important genes were intersected with key genes that had targeting relationship with these miRs. Key target genes by lnc453774.1 were identified in a protein-protein interaction network among lnc453774.1, important genes, and reported genes related to autophagy, oxidative stress, and cell adhesion. RESULTS: Key genes in the key module (turquoise) were intersected with DEGs in the dataset GSE23338 and yielded 20 key genes regulated by lnc453774.1 involved in renal fibrosis. Fourteen miRs had targeting relationship with lnc453774.1 and key genes, and 8 important genes targeted by these 14 miRs were identified. Fibrillin-1 (FBN1), insulin-like growth factor 1 receptor (IGF1R), and Kruppel-like factor 7 (KLF7) were identified to be involved in autophagy, oxidative stress, and cell adhesion and were elevated in the lnc453774.1-overexpressing TGF-ß1-induced cells. CONCLUSION: These results show FBN1, IGF1R, and KLF7 serve as downstream targets of lnc453774.1, and that lnc453774.1 may protect against renal fibrosis through competing endogenous miRs which target FBN1, IGF1R, and KLF7 mRNAs.

Identification of Prognostic Metabolism-Related Genes in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a cancer with abnormal metabolism. The purpose of this study was to investigate the effect of metabolism-related genes on the prognosis of ccRCC patients. METHODS: The data of ccRCC patients were downloaded from the TCGA and the GEO databases and clustered using the nonnegative matrix factorization method. The limma software package was used to analyze differences in gene expression. A random forest model was used to screen for important genes. A novel Riskscore model was established using multivariate regression. The model was evaluated based on the metabolic pathway, immune infiltration, immune checkpoint, and clinical characteristics. RESULTS: According to metabolism-related genes, kidney clear cell carcinoma (KIRC) datasets downloaded from TCGA were clustered into two groups and showed significant differences in prognosis and immune infiltration. There were 667 differentially expressed genes between the two clusters, of which 408 were screened by univariate analysis. Finally, 12 differentially expressed genes (MDK, SLC1A1, SGCB, C4orf3, MALAT1, PILRB, IGHG1, FZD1, IFITM1, MUC20, KRT80, and SALL1) were filtered out using the random forest model. The model of Riskscore was obtained by multiplying the expression levels of these 12 genes with the corresponding coefficients of the multivariate regression. We found that the Riskscore correlated with the expression of these 12 genes; the high Riskscore matched the low survival rate verified in the verification set. The analysis found that the Riskscore model was associated with most of the metabolic processes, immune infiltration of cells such as plasma cells, immune checkpoints such as PD-1, and clinical characteristics such as M stage. CONCLUSION: We established a new Riskscore model for the prognosis of ccRCC based on metabolism. The genes in the model provided several novel targets for the study of ccRCC.

Visit-to-visit blood pressure variability and risk of chronic kidney disease: A systematic review and meta-analyses.

OBJECTIVE: Previous studies have shown that visit-to-visit blood pressure variability (BPV) is associated with chronic kidney disease (CKD). However, the results have not been consistent among studies. This systematic review and meta-analysis was conducted to comprehensively assess the association between visit-to-visit BPV and the risk of CKD. METHODS: Medline, Embase, and the Cochrane Library were searched from the date of inception through 1 August 2019 using the terms "blood pressure variability," "chronic kidney disease," "nephropathy," and other comparable terms. The primary outcome was the development of CKD. Two reviewers extracted the data independently. Meta-analysis was performed using a random effects model. RESULTS: Fourteen studies were included in the systematic review and meta-analysis. The risk of CKD was significantly greater in patients with high baseline systolic blood pressure variability (SBPV) than in patients with low baseline SBPV: the standard deviation (SD) showed relative risk (RR) of 1.69 and 95% CI of 1.38-2.08, the coefficient of variation (CV) showed RR of 1.23 and 95% CI of 1.12-1.36, and variance independent of mean (VIM) showed RR of 1.40 and 95% CI of 1.15-1.71. RRs for each unit increase in visit-to-visit SBPV and risk of CKD were 1.05 (95% CI: 1.03-1.07) for SD, 1.06 (95% CI: 1.03-1.09) for CV, and 1.1 (95% CI: 0.96-1.25) for VIM. Diastolic BPV was similarly predictive of CKD based on SD and CV. CONCLUSIONS: Increased visit-to-visit BPV might be an independent risk factor for CKD. However, significant heterogeneity was present; thus, future prospective studies are needed to confirm our findings. Our results indicate that treatment of hypertension should control blood pressure levels and prevent abnormal fluctuations in blood pressure to reduce the risk of CKD.

Neferine Attenuates Acute Kidney Injury by Inhibiting NF-κB Signaling and Upregulating Klotho Expression.

Purpose: Morbidity associated with and mortality from acute kidney injury (AKI) is gradually increasing, and no efficient drug is available. We explored whether neferine, a bisbenzylisoquinoline alkaloid, attenuated AKI, and the possible mechanisms in play in vivo and in vitro. Methods: We induced AKI using ischemia-reperfusion (I/R) or lipopolysaccharide (LPS) in vivo. C57 BL/6 male mice were randomized into two groups each containing four subgroups: control, neferine, I/R or LPS, and I/R or LPS + neferine. Mice were sacrificed 24 h after AKI induction and kidneys and sera were collected. NRK-52E cells were exposed to hypoxia/reoxygenation (H/R) or LPS in vitro. Results: Neferine pretreatment significantly alleviated kidney functional loss and pathological damage. In the AKI mouse models induced by I/R or LPS, neferine inhibited the infiltration of inflammatory cells, including granulocytes and macrophages. Both in vivo and in vitro, neferine attenuated apoptosis, suppressed inflammatory cytokine production, decreased degradation of IκB-α, and inhibited nuclear translocation of NF-κB. Furthermore, it also upregulated Klotho expression in AKI. Conclusion: Neferine mitigated renal injury in AKI models, perhaps by suppressing the activation of NF-κB and upregulating the expression of Klotho.

MicroRNA-302c modulates peritoneal dialysis-associated fibrosis by targeting connective tissue growth factor.

Long-term peritoneal dialysis (PD) can lead to the induction of mesothelial/epithelial-mesenchymal transition (MMT/EMT) and fibrosis; these effects eventually result in ultrafiltration failure and the discontinuation of PD. MicroRNA-302c (miR-302c) is believed to be involved in regulating tumour cell growth and metastasis by suppressing MMT, but the effect of miR-302c on MMT in the context of PD is unknown. MiR-302c levels were measured in mesothelial cells isolated from the PD effluents of continuous ambulatory peritoneal dialysis patients. After miR-302c overexpression using lentivirus, human peritoneal mesothelial cell line (HMrSV5) and PD mouse peritoneum were treated with TGF-ß1 or high glucose peritoneal dialysate respectively. MiR-302c expression level and MMT-related factors alteration were observed. In addition, fibrosis of PD mouse peritoneum was alleviated by miR-302c overexpression. Furthermore, the expression of connective tissue growth factor (CTGF) was negatively related by miR-302c, and LV-miR-302c reversed the up-regulation of CTGF induced by TGF-ß1. These data suggest that there is a novel TGF-ß1/miR-302c/CTGF pathway that plays a significant role in the process of MMT and fibrosis during PD. MiR-302c might be a potential biomarker for peritoneal fibrosis and a novel therapeutic target for protection against peritoneal fibrosis in PD patients.

Streptococcus may aggravate inflammatory damage in chronic nephritis via the chemotaxis of Th22 cells.

BACKGROUND: Infection can induce and aggravate chronic kidney disease (CKD), and the chemotaxis of Th22 cells may aggravate CKD. However, the mechanism underlying group A Streptococcus (GAS) infections in CKD through the chemotaxis of Th22 cells remains unknown. METHODS: The experiment was divided into a normal control group, an IgAN model group, a GAS-treated normal group, a GAS-treated IgAN group and an anti-CCL intervention group. An IgA nephropathy model was established, and after the success of the IgA nephropathy model was confirmed, Streptococcus haemolyticus A was inoculated intranasally and compared with treatment with anti-CCL to detect changes in Th22 cells, related chemotaxis factors and kidney pathology before and after intervention. RESULTS: An immunoglobulin A nephropathy model was successfully established. Streptococcus was successfully inoculated into the nasal cavity of the normal group and the IgA nephropathy infection control group. After intervention, pulmonary inflammatory cell infiltration was more obvious in the IgA nephropathy group than in the normal control group after Streptococcus infection. Th22 cells were detected more frequently in IgA nephropathy; after streptococcal infection, the percentage of Th22 cells in the IgAN group was higher than that in the normal group but decreased significantly when chemotaxis was blocked, the expression of CCL27, CCR10 and IL-22 declined simultaneously, and improvements in pathological changes were observed. CONCLUSION: Streptococcus may cause the chemotaxis of Th22 cells to kidney tissue, leading to or aggravating nephritis injury.

LncRNA ENST00000453774.1 contributes to oxidative stress defense dependent on autophagy mediation to reduce extracellular matrix and alleviate renal fibrosis.

Although long noncoding RNA (LncRNA) are important players in the initiation and progression of many pathological processes, the role of LncRNAENST00000453774.1 (LncRNA 74.1) in renal fibrosis still remains unclear. Lentivirus mediated LncRNA 74.1 overexpressing HK2 cells and overexpression mice models were constructed. HK2 cells induced by transforming growth factor-ß (TGF-ß) in vitro, and the mice UUO model in vivo were used to simulate renal fibrosis. The expression of LncRNA 74.1 was significantly downregulated in the TGF-ß-induced HK-2 cell fibrosis and clinical renal fibrosis specimens. LncRNA 74.1 overexpression obviously attenuated renal fibrosis in vitro and unilateral ureteral obstruction-induced renal fibrosis in vivo. LncRNA 74.1 promoted reactive oxygen species defense by activating prosurvival autophagy then decreased ECM-related proteins fibronectin and collagen I involved in renal fibrosis. We also found that Nrf2-keap1 signaling played important roles in the remission of ECM mediated by LncRNA 74.1. This study indicates that LncRNA 74.1 downregulation would contribute to renal fibrosis and its overexpression might represent a novel anti-fibrotic treatment in renal diseases.

NLRC5: potential novel non-invasive biomarker for predicting and reflecting the progression of IgA nephritis.

BACKGROUND: The nucleotide oligomerization domain-like receptor subfamily C5 (NLRC5) is primarily expressed in the adaptive and innate immune systems. NLRC5 was recently discovered to regulate immunity and inflammatory responses. Abnormal immune and inflammatory responses are considered critical pathogenesis in IgA nephritis (IgAN). However, the role of NLRC5 in IgAN is unknown. We previously showed that NLRC5 can be detected in patients with IgAN; herein, we further examined the pathophysiological significance of NLRC5 in the serum and renal deposits of patients with IgAN. This study is the first to find that NLRC5 is closely correlated with IgAN. METHODS: IgAN patients (n = 50) who were diagnosed by renal biopsy provided blood and renal biopsy tissue, and age-matched healthy control subjects (blood donators n = 22; tissue donators n = 5) were included. Renal biopsies were diagnosed, and blood biochemical parameters were tested. Serum creatinine, urea, proteinuria, haematuria, albumin, and immunoglobulin A levels were recorded. Serum NLRC5 concentrations were detected by enzyme-linked immunosorbent assay, and tissue NLRC5 expression in kidney tissue was detected by immunohistochemical analysis. ROC curve analysis was used to evaluate the diagnostic value of the serum NLRC5 concentration in IgAN. RESULTS: Serum NLRC5 concentration was significantly decreased in the IgAN group compared to that in the healthy control group (P < 0.0001), especially in S1 (Oxford classification) patients (P < 0.0001). Furthermore, serum NLRC5 concentration had a negative correlation with Lee's grade (r = 0.3526, P = 0.0060) and proteinuria levels (r = 0.4571, P = 0.0004). Tissue NLRC5 expression was significantly increased in the IgAN group compared to that in the healthy control group (P < 0.0001); a more significant increase was identified in the S1 group (P < 0.05) and had a positive correlation with Lee's grade (r = 0.497, P < 0.0001). We proposed a cut-off value of 1415 pg/ml for serum NLRC5 concentration, which was able to predict IgAN with 77.27% sensitivity and 87.5% specificity. CONCLUSIONS: Serum NLRC5 concentrations in IgAN are significantly decreased, and tissue NLRC5 expression is significantly increased in IgAN renal tissue, which is consistent with pathological severity. This finding suggests that NLRC5 could potentially be a diagnostic index and represents a prognostic factor in IgAN patients.

Cordyceps sinensis may inhibit Th22 cell chemotaxis to improve kidney function in lgA nephropathy.

IgA nephropathy is the most common form of primary glomerulonephritis and an important cause of kidney failure. Cordyceps sinensis (CS) is a parasitic fungus that has a long history of use in Chinese medicine for the treatment of nephritis. Interleukin (IL)-22-producing helper T cells (Th22 cells) have been reported to be involved in lgA nephropathy. Th22 cells link the immune response to tissue inflammation. To elucidate the possible efficacy and mechanisms by which CS counteracts nephritis, we established an IgA nephropathy model in 6-week-old female BALB/c mice. The mice were randomly separated into 3 groups, the normal control, IgA nephropathy and CS (5 mg/kg/d) treatment groups. The Th22 cell frequencies and the relative pathological and cytokine changes were measured with flow cytometry, whereas the serum chemokine ligand 27 (CCL27) and IL-22 concentrations were detected with ELISA. The Th22 cell frequency decreased after 1 month of CS therapy. Additionally, mesangial cell proliferation decreased. Moreover, the chemokine receptor type 10 (CCR10), CCL27 and IL-22 expression levels were significantly reduced. In conclusion, CS may modulate the chemotaxis of Th22 cells to suppress inflammatory responses in IgA nephropathy.