Negative mixing enthalpy solid solutions deliver high strength and ductility.

Body-centred cubic refractory multi-principal element alloys (MPEAs), with several refractory metal elements as constituents and featuring a yield strength greater than one gigapascal, are promising materials to meet the demands of aggressive structural applications1-6. Their low-to-no tensile ductility at room temperature, however, limits their processability and scaled-up application7-10. Here we present a HfNbTiVAl10 alloy that shows remarkable tensile ductility (roughly 20%) and ultrahigh yield strength (roughly 1,390 megapascals). Notably, these are among the best synergies compared with other related alloys. Such superb synergies derive from the addition of aluminium to the HfNbTiV alloy, resulting in a negative mixing enthalpy solid solution, which promotes strength and favours the formation of hierarchical chemical fluctuations (HCFs). The HCFs span many length scales, ranging from submicrometre to atomic scale, and create a high density of diffusive boundaries that act as effective barriers for dislocation motion. Consequently, versatile dislocation configurations are sequentially stimulated, enabling the alloy to accommodate plastic deformation while fostering substantial interactions that give rise to two unusual strain-hardening rate upturns. Thus, plastic instability is significantly delayed, which expands the plastic regime as ultralarge tensile ductility. This study provides valuable insights into achieving a synergistic combination of ultrahigh strength and large tensile ductility in MPEAs.

Renal Fibrosis Is Alleviated through Targeted Inhibition of IL-11-Induced Renal Tubular Epithelial-to-Mesenchymal Transition.

Renal fibrosis is a pathologic process that leads to irreversible renal failure without effective treatment. Epithelial-to-mesenchymal transition (EMT) plays a key role in this process. The current study found that aberrant expression of IL-11 is critically involved in tubular EMT. IL-11 and its receptor subunit alpha-1 (IL-11Rα1) were significantly induced in renal tubular epithelial cells (RTECs) in unilateral ureteral obstruction (UUO) kidneys, co-localized with transforming growth factor-ß1. IL-11 knockdown ameliorated UUO-induced renal fibrosis in vivo and transforming growth factor-ß1-induced EMT in vitro. IL-11 intervention directly induced the transdifferentiation of RTECs to the mesenchymal phenotype and increased the synthesis of profibrotic mediators. The EMT response induced by IL-11 was dependent on the sequential activation of STAT3 and extracellular signal-regulated kinase 1/2 signaling pathways and the up-regulation of metadherin in RTECs. Micheliolide (MCL) competitively inhibited the binding of IL-11 with IL-11Rα1, suppressing the activation of STAT3 and extracellular signal-regulated kinase 1/2-metadherin pathways, ultimately inhibiting renal tubular EMT and interstitial fibrosis induced by IL-11. In addition, treatment with dimethylaminomicheliolide, a pro-drug of MCL for in vivo use, significantly ameliorated renal fibrosis exacerbated by IL-11 in the UUO model. These findings suggest that IL-11 is a promising target in renal fibrosis and that MCL/dimethylaminomicheliolide exerts its antifibrotic effect by suppressing IL-11/IL-11Rα1 interaction and blocking its downstream effects.

Brown planthopper infestation on rice reduces plant susceptibility to Meloidogyne graminicola by reducing root sugar allocation.

Plants are simultaneously attacked by different pests that rely on sugars uptake from plants. An understanding of the role of plant sugar allocation in these multipartite interactions is limited. Here, we characterized the expression patterns of sucrose transporter genes and evaluated the impact of targeted transporter gene mutants and brown planthopper (BPH) phloem-feeding and oviposition on root sugar allocation and BPH-reduced rice susceptibility to Meloidogyne graminicola. We found that the sugar transporter genes OsSUT1 and OsSUT2 are induced at BPH oviposition sites. OsSUT2 mutants showed a higher resistance to gravid BPH than to nymph BPH, and this was correlated with callose deposition, as reflected in a different effect on M. graminicola infection. BPH phloem-feeding caused inhibition of callose deposition that was counteracted by BPH oviposition. Meanwhile, this pivotal role of sugar allocation in BPH-reduced rice susceptibility to M. graminicola was validated on rice cultivar RHT harbouring BPH resistance genes Bph3 and Bph17. In conclusion, we demonstrated that rice susceptibility to M. graminicola is regulated by BPH phloem-feeding and oviposition on rice through differences in plant sugar allocation.

Identification and molecular characterization of two novel viruses from Allamanda cathartica in China.

Allamanda cathartica is an ornamental medicinal plant that grows widely in the tropics. In the present study, two novel viruses, Allamanda chlorotic virus A (AlCVA) and Allamanda chlorotic virus B (AlCVB), were identified in an A. cathartica plant with interveinal chlorosis by ribosomal RNA-depleted total-RNA sequencing. Phylogenetic analysis and sequence comparisons confirmed that AlCVA and AlCVB belong to the families Closteroviridae and Betaflexiviridae, respectively. Long, flexuous, filamentous virus particles approximately 12 nm in diameter and 784-2291 nm in length were observed using transmission electron microscopy. A specific RT-PCR assay was used to demonstrate a consistent association of viral infection with symptoms.

Brahma-related gene 1 acts as a profibrotic mediator and targeting it by micheliolide ameliorates peritoneal fibrosis.

BACKGROUND: Progressive peritoneal fibrosis is a worldwide public health concern impacting patients undergoing peritoneal dialysis (PD), yet there is no effective treatment. Our previous study revealed that a novel compound, micheliolide (MCL) inhibited peritoneal fibrosis in mice. However, its mechanism remains unclear. Brahma-related gene 1 (BRG1) is a key contributor to organ fibrosis, but its potential function in PD-related peritoneal fibrosis and the relationship between MCL and BRG1 remain unknown. METHODS: The effects of MCL on BRG1-induced fibrotic responses and TGF-ß1-Smads pathway were examined in a mouse PD model and in vitro peritoneal mesothelial cells. To investigate the targeting mechanism of MCL on BRG1, coimmunoprecipitation, MCL-biotin pulldown, molecular docking and cellular thermal shift assay were performed. RESULTS: BRG1 was markedly elevated in a mouse PD model and in peritoneal mesothelial cells cultured in TGF-ß1 or PD fluid condition. BRG1 overexpression in vitro augmented fibrotic responses and promoted TGF-ß1-increased-phosphorylation of Smad2 and Smad3. Meanwhile, knockdown of BRG1 diminished TGF-ß1-induced fibrotic responses and blocked TGF-ß1-Smad2/3 pathway. MCL ameliorated BRG1 overexpression-induced peritoneal fibrosis and impeded TGF-ß1-Smad2/3 signaling pathway both in a mouse PD model and in vitro. Mechanically, MCL impeded BRG1 from recognizing and attaching to histone H3 lysine 14 acetylation by binding to the asparagine (N1540) of BRG1, in thus restraining fibrotic responses and TGF-ß1-Smad2/3 signaling pathway. After the mutation of N1540 to alanine (N1540A), MCL was unable to bind to BRG1 and thus, unsuccessful in suppressing BRG1-induced fibrotic responses and TGF-ß1-Smad2/3 signaling pathway. CONCLUSION: Our research indicates that BRG1 may be a crucial mediator in peritoneal fibrosis and MCL targeting N1540 residue of BRG1 may be a novel therapeutic strategy to combat PD-related peritoneal fibrosis.

Remnant cholesterol as a risk factor for all-cause and cardiovascular mortality in incident peritoneal dialysis patients.

BACKGROUND AND AIMS: Remnant cholesterol (RC) adversely contributes to cardiovascular disease (CVD) and overall survival in various diseases. However, its role in CVD outcomes and all-cause mortality in patients undergoing peritoneal dialysis (PD) is limited. Therefore, we aimed to investigate the association between RC and all-cause and CVD mortality in patients undergoing PD. METHODS AND RESULTS: Based on lipid profiles recorded using standard laboratory procedures, fasting RC levels were calculated in 2710 incident patients undergoing PD who were enrolled between January 2006 and December 2017 and followed up until December 2018. Patients were divided into four groups according to the quartile distribution of baseline RC levels (Q1: <0.40 mmol/L, Q2: 0.40 to <0.64 mmol/L, Q3: 0.64 to <1.03 mmol/L, and Q4: ≥1.03 mmol/L). Associations between RC and CVD and all-cause mortality were evaluated using multivariable Cox models. During the median follow-up period of 35.4 months (interquartile range, 20.9-57.2 months), 820 deaths were recorded, of which 438 were CVD-related. Smoothing plots showed non-linear relationships between RC and adverse outcomes. The risks of all-cause and CVD mortality increased progressively through the quartiles (log-rank, p < 0.001). Using adjusted proportional hazard models, a comparison of the highest (Q4) to lowest (Q1) quartiles revealed significant increases in the hazard ratio (HR) for all-cause mortality (HR 1.95 [95% confidence interval (CI), 1.51-2.51]) and CVD mortality risk (HR 2.60 [95% CI, 1.80-3.75]). CONCLUSION: An increased RC level was independently associated with all-cause and CVD mortality in patients undergoing PD, suggesting that RC was important clinically and required further research.

Occurrence of Root-Knot Nematode (Meloidogyne spp.) on Peppers in Hainan, China, and M. enterolobii and M. incognita Resistance of Common Cultivars.

Root-knot nematodes (Meloidogyne spp.) are the most economically damaging group of plant-parasitic nematodes. They are considered to be a major constraint of pepper (Capsicum annuum L.) crops worldwide. In China, Hainan Island is the main producer of pepper, where the climatic conditions and cropping patterns are favorable for infection by Meloidogyne spp. In this study, we conducted a detailed investigation of the occurrence, severity, and population distribution of root-knot nematodes infesting pepper throughout Hainan Island. We also tested the level of resistance to M. enterolobii and M. incognita of the common pepper cultivars in Hainan. Our results showed that root-knot nematodes belonging to M. enterolobii, M. incognita, and M. javanica were found in Hainan, and the dominant population was M. enterolobii, which is the predominant species in the tropical area. Notably, all the pepper cultivars in this study were highly susceptible to M. enterolobii, which is probably a reason for its rapid spread throughout Hainan. The pepper cultivars exhibited different levels of resistance to M. incognita. This study promotes the comprehensive understanding of the root-knot nematode distribution and host resistance level of Meloidogyne in Hainan, which will guide the effective control of root-knot nematodes.

Morphological and molecular characterization of a new root-knot nematode, Meloidogyne limonae n. sp. (Nematoda: Meloidogynidae) parasitizing lemon in China.

Root-knot nematodes of the genus Meloidogyne parasitize the roots of thousands of plants and can cause severe damage and yield loss. Here, we report a new root-knot nematode, Meloidogyne limonae n. sp., parasitizing "lemon" (Citrus limon) in Hainan Province, South China. Lemon trees infected by the root-knot nematode showed poor-quality lemons, chlorosis of foliage, weak growth, and numerous root galls with white females and egg masses protruding outside. Phylogenetic trees of sequences within the ribosomal and mitochondria DNA demonstrated that this species differs clearly from other previously described root-knot nematodes. Morphologically, the new species is characterized by an oval-shaped perineal pattern and the lateral field marked by a ridge of cuticle on one or both sides, the dorsal arch is low with fine to coarse, smooth cuticle striae, vulva slit centrally located at the unstriated area; spicules of males are arcuate, curved ventrally; gubernaculum is distinct and curved; labial disc of second-stage juveniles is prominent and dumbbell-shaped; stylet knobs oval and sloping backwardly; pharyngeal glands not filling the body cavity, overlapping intestine ventrally; conical tail gradually tapering. Phylogenetic trees based on ITS1-5.8S-ITS2, D2-D3 of the 28S rDNA, and the COI and COII-16S rRNA genes of the mtDNA showed that Meloidogyne limonae n. sp. belongs to an undescribed root-knot nematode lineage that is separated from other species with the resemblance in morphology, such as M. floridensis M. hispanica, M. acronea, and M. paranaenis.

Association of Globodera rostochiensis (Nematoda) with Stunted and Chlorotic Potato Plants in Yunnan and Sichuan Provinces in China.

On a global basis, potato cyst nematodes (Globodera spp. Skarbilovich 1959 [Behrens 1975]) are one of the most serious soilborne pathogens in potato (Solanum tuberosum L.) production. In 2019 to 2020, 188 soil samples were taken from rhizosphere soil associated with the roots of stunted and chlorotic potato plants in the main potato-growing areas of Yunnan and Sichuan Provinces of China. Globodera rostochiensis Wollenweber 1923 (Skarbilovich 1959) was recovered from 112 of the samples. Nematode identification was as confirmed by morphometric, light microscopy, electron microscopy, and molecular methodologies. Population densities of G. rostochiensis ranged from 47.0 to 69.0 eggs/g of soil. A BLASTn homology search program was used to compare the sequences of populations of G. rostrochienses from Yunnan and Sichuan Provinces with populations of other Heteroderinae spp. and populations of G. rostochiensis from other nations. Although potato has been grown in China for at least 400 years and the nation produces more potato than any other country, potato cyst nematodes were not reported in China until 2022.

Clinical significance of serum glucose to lymphocyte ratio as a prognostic marker in peritoneal dialysis patients.

BACKGROUND: The glucose-to-lymphocyte ratio (GLR), a glucose metabolism and systemic inflammatory response parameter, is associated with an adverse prognosis for various diseases. However, the association between serum GLR and prognosis in patients undergoing peritoneal dialysis (PD) is poorly understood. METHODS: In this multi-center cohort study, 3236 PD patients were consecutively enrolled between 1 January 2009 and 31 December 2018. Patients were divided into four groups according to the quartiles of baseline GLR levels (Q1: GLR ≤ 2.91, Q2:2.91 < GLR ≤ 3.91, Q3:3.91 < GLR < 5.59 and Q4: GLR ≥ 5.59). The primary endpoint was all-cause and cardiovascular disease (CVD) related mortality. The correlation between GLR and mortality was examined using Kaplan-Meier and multivariable Cox proportional analyses. RESULTS: During the follow-up period of 45.93 ± 29.01 months, 25.53% (826/3236) patients died, of whom 31% (254/826) were in Q4 (GLR ≥ 5.59). Multivariable analysis revealed that GLR was significantly associated with all-cause mortality (adjusted HR 1.02; CI 1.00 ∼ 1.04, p = .019) and CVD mortality (adjusted HR 1.02; CI 1.00 ∼ 1.04, p = .04). Compared with the Q1 (GLR ≤ 2.91), placement in Q4 was associated with an increased risk of all-cause mortality (adjusted HR: 1.26, 95% CI: 1.02 ∼ 1.56, p = .03) and CVD mortality (adjusted HR 1.76; CI 1.31 ∼ 2.38, p < .001). A nonlinear relationship was found between GLR and all-cause or CVD mortality in patients undergoing PD (p = .032). CONCLUSION: A higher serum GLR level is an independent prognostic factor for all-cause and CVD mortality in patients undergoing PD, suggesting that more attention should be paid to GLR.

Parthenolide alleviates peritoneal fibrosis by inhibiting inflammation via the NF-κB/ TGF-ß/Smad signaling axis.

Peritoneal fibrosis is a common complication of peritoneal dialysis (PD) with a complicated pathogenesis and limited treatments. Parthenolide (PTL), a recognized nuclear factor-κB (NF-κB) inhibitor extracted from Tanacetum balsamita, has been widely used to treat various inflammatory diseases and has been proven to improve peritoneal fibrosis in PD mice by selectively inhibiting the phosphorylation of Smad2/3. Transforming growth factor-ß1 (TGF-ß1), via Smad-dependent signaling, has a pivotal role in promoting pathogenic of fibrosis. To investigate whether PTL can inhibit peritoneal fibrosis, we affected the interaction between NF-κB and the TGF-ß/Smad2/3 pathway. Long dwell peritoneal dialysis fluid (PDF) and peritoneum tissues were collected from continuous ambulatory peritoneal dialysis (CAPD) patients. PTL was administered intragastrically into a PD mouse model by daily infusion of 4.25% dextrose-containing PDF. Treated HMrSV5 cells or rat peritoneal mesothelial cells (RPMCs) were treated with high glucose(138 mM) at the same concentration as 2.5% dextrose-containing PDF and PTL. PD-related peritoneal fibrosis samples indicated an increase in inflammation, and PTL decreased the levels of inflammatory cytokines (L-6, TNF-α, and MCP-1). PTL inhibited high glucose-induced mesothelial-to-mesenchymal transition (MMT), as indicated by a reduced expression of fibrosis markers (fibronectin, collagen I, and α-SMA) and increased expression of the epithelial marker E-cadherin. PTL also significantly decreased TGF-ß1 expression and the phosphorylation of IκBα and NF-κBp65. The changes in the levels of TGF-ß1 expression and p-p65 or p65 showed similar trends according to western blot, immunohistochemistry, and immunofluorescence assays in vitro and in vivo. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to confirm that PTL regulates the transcription of TGF-ß1 induced by high glucose through NF-κBp65. In summary, PTL induces a therapeutic effect in peritoneal fibrosis by inhibiting inflammation via the NF-κB/ TGF-ß/Smad signaling axis.

Development of a Novel Primer-TaqMan Probe Set for Diagnosis and Quantification of Meloidogyne enterolobii in Soil Using qPCR and Droplet Digital PCR Assays.

Early detection of pathogens before the planting season is valuable to forecast disease occurrence. Therefore, rapid and reliable diagnostic approaches are urgently needed, especially for one of the most aggressive root knot nematodes, Meloidogyne enterolobii. In this study, we developed a novel primer-TaqMan probe set aimed at M. enterolobii. The primer-probe set was successfully applied in the identification and quantification of M. enterolobii via qPCR technology. It was also suitable for improved PCR technology, known as ddPCR analyses, and this work presents the first application of this technology for plant parasitic nematodes. Compared with qPCR, ddPCR exhibited better performance with regard to analytical sensitivity, which can provide a more accurate detection of M. enterolobii concealed in field soil. In addition, we generated standard curves to calculate the number of eggs in soil using the qPCR and ddPCR platforms. Hopefully, the results herein will be helpful for forecasting disease severity of M. enterolobii infection and adopting effective management strategies.

Brahma-related gene-1 promotes tubular senescence and renal fibrosis through Wnt/ß-catenin/autophagy axis.

Although accelerated cellular senescence is closely related to the progression of chronic kidney disease (CKD) and renal fibrosis, the underlying mechanisms remain largely unknown. Here, we reported that tubular aberrant expression of Brahma-related gene 1 (BRG1), an enzymatic subunit of the SWItch/Sucrose Non-Fermentable complex, is critically involved in tubular senescence and renal fibrosis. BRG1 was significantly up-regulated in the kidneys, predominantly in tubular epithelial cells, of both CKD patients and unilateral ureteral obstruction (UUO) mice. In vivo, shRNA-mediated knockdown of BRG1 significantly ameliorated renal fibrosis, improved tubular senescence, and inhibited UUO-induced activation of Wnt/ß-catenin pathway. In mouse renal tubular epithelial cells (mTECs) and primary renal tubular cells, inhibition of BRG1 diminished transforming growth factor-ß1 (TGF-ß1)-induced cellular senescence and fibrotic responses. Correspondingly, ectopic expression of BRG1 in mTECs or normal kidneys increased p16INK4a, p19ARF, and p21 expression and senescence-associated ß-galactosidase (SA-ß-gal) activity, indicating accelerated tubular senescence. Additionally, BRG1-mediated pro-fibrotic responses were largely abolished by small interfering RNA (siRNA)-mediated p16INK4a silencing in vitro or continuous senolytic treatment with ABT-263 in vivo. Moreover, BRG1 activated the Wnt/ß-catenin pathway, which further inhibited autophagy. Pharmacologic inhibition of the Wnt/ß-catenin pathway (ICG-001) or rapamycin (RAPA)-mediated activation of autophagy effectively blocked BRG1-induced tubular senescence and fibrotic responses, while bafilomycin A1 (Baf A1)-mediated inhibition of autophagy abolished the effects of ICG-001. Further, BRG1 altered the secretome of senescent tubular cells, which promoted proliferation and activation of fibroblasts. Taken together, our results indicate that BRG1 induces tubular senescence by inhibiting autophagy via the Wnt/ß-catenin pathway, which ultimately contributes to the development of renal fibrosis.

FOXO3a accumulation and activation accelerate oxidative stress-induced podocyte injury.

Podocyte injury is the primary cause of glomerular injury in diabetic nephropathy (DN). Advanced oxidation protein products (AOPPs), the triggers and markers of oxidative stress in DN, have been linked to podocyte damage. However, the underlying mechanism is not yet clear. Here, we investigated the potential role of FOXO3a, a key transcription factor in the response to stress, in mediating AOPPs-induced podocyte injury. We found that FOXO3a expression was increased in the glomeruli of kidney biopsies from patients with DN and it was positively correlated with proteinuria. The serum from patients with DN significantly increased FOXO3a and its downstream genes FasL and Bim, thereby inducing the high level of cleaved caspase3 and the loss of nephrin and podocin expressions in podocytes. Blockade of AOPPs signaling by a neutralizing antibody against the receptor of advanced glycation end products (αRAGE) abolished the effect of DN serum on podocytes, confirming the pathogenic role of AOPPs in DN serum. Downregulation of FOXO3a decreased AOPPs-induced podocyte apoptosis and restored the levels of podocyte markers nephrin and podocin, and upregulation of FOXO3a exacerbated these changes in podocytes after AOPPs treatment. Furthermore, FOXO3a specifically activated proapoptotic genes in podocytes only in the presence of AOPPs. Mechanistically, AOPPs increased the FOXO3a protein levels by inhibiting their autophagic degradation in a ROS/mTOR-dependent manner. Moreover AOPPs activated the accumulated FOXO3a by maintaining FOXO3a in the nucleus, and this process was dependent on ROS-mediated AKT signaling deactivation. These studies suggest that FOXO3a plays a critical role in mediating AOPPs-induced podocyte injury and reveal a new mechanistic linkage of oxidative stress, FOXO3a activation and podocyte injury in DN.

MicroRNA-145 promotes the epithelial-mesenchymal transition in peritoneal dialysis-associated fibrosis by suppressing fibroblast growth factor 10.

Peritoneal fibrosis is a common complication of long-term peritoneal dialysis (PD) and the principal cause of ultrafiltration failure during PD. The initial and reversible step in PD-associated peritoneal fibrosis is the epithelial-mesenchymal transition (EMT). Although the mechanisms in the EMT have been the focus of many studies, only limited information is currently available concerning microRNA (miRNA) regulation in peritoneal fibrosis. In this study, we aimed to characterize the roles of microRNA-145 (miR-145) and fibroblast growth factor 10 (FGF10) in peritoneal fibrosis. After inducing EMT with transforming growth factor-ß1 (TGF-ß1) in vitro, we found that miR-145 is significantly up-regulated, whereas FGF10 is markedly down-regulated, suggesting a close link between miR-145 and FGF10 in peritoneal fibrosis, further confirmed in luciferase reporter experiments. Furthermore, in human peritoneal mesothelial cells (i.e. HMrSV5 cells), miR-145 mimics induced EMT, whereas miR-145 inhibition suppressed EMT, and we also observed that miR-145 suppressed FGF10 expression. In vivo, we found that the exogenous delivery of an miR-145 expression plasmid both blocked FGF10 and intensified the EMT, whereas miR-145 inhibition promoted the expression of FGF10 and reversed the EMT. In conclusion, miR-145 promotes the EMT during the development of peritoneal fibrosis by suppressing FGF10 activity, suggesting that miR-145 represents a potential therapeutic target for managing peritoneal fibrosis.

Correction: Micheliolide ameliorates renal fibrosis by suppressing the Mtdh/BMP/MAPK pathway.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The relationship between neutrophil-to-lymphocyte ratio and the first occurrence of pneumonia in peritoneal dialysis patients.

BACKGROUND: Although neutrophil-to-lymphocyte ratio (NLR) is closely associated with pneumonia in the general population, its relationship is unclear in peritoneal dialysis (PD) patients. METHODS: This is a cohort study consisting of 739 PD patients and dividing into two groups. Kaplan-Meier curves were applied to observe the incidence of the first occurrence of pneumonia, competitive risk analysis was conducted to compare whether there was a significant difference in each NLR group in the presence of other competing events, multivariable COX regression analysis was used to evaluate the hazard ratios (HRs), as well as forest plot was used to analyze the relationship between NLR and the first occurrence of pneumonia in different subgroups. RESULTS: Of all the patients, 116 cases of first-time pneumonia were recorded. The first-time pneumonia incidence rate was 71.67/1000 patient-years in high NLR group, which was markedly higher than that of 45.81/1000 patient-years in low NLR group. Kaplan-Meier curves indicated significant differences in the incidence of the first occurrence of pneumonia between two groups (log-rank test p = 0.015). The competitive risk model suggested a significant difference in the cumulative incidence of first pneumonia between the two groups (p = 0.032). Compared to low NLR group, adjusted Cox model showed that high NLR group was associated with increased risk of pneumonia incidence (HR, 1.51; 95% CI 1.04-2.21; p = 0.031). Forest plot showed no interaction was found in subgroups. CONCLUSIONS: The risk of pneumonia was significantly increasing in PD patients with high NLR, which may have a certain guiding significance for the clinic.

Albumin-globulin ratio and mortality in patients on peritoneal dialysis: a retrospective study.

BACKGROUND: Albumin-globulin ratio (AGR), a variable based on serum albumin and non-albumin proteins, has been demonstrated as a predictor of mortality in patients with malignant neoplasm. The aim of this study was to evaluate the prognostic value of AGR on peritoneal dialysis (PD) patients. METHODS: We retrospectively analyzed 602 incident PD patients from January 1st, 2008, to December 31st, 2017, at our center and followed them until December 31st, 2018. Kaplan-Meier curves and multivariate Cox regression models were applied to analyze the association between AGR and all-cause of mortality and cardiovascular mortality. RESULTS: The median follow-up time was 32.17 (interquartile range = 32.80) months. During follow-up, 131 (21.8%) patients died, including 57 patients (43.5%) who died due to cardiovascular diseases. Kaplan-Meier curves showed that patients with AGR > 1.26 had better rates of survival than those with AGR ≤ 1.25 (p < 0.001). After adjusting for potential confounders, the lower AGR level was significantly associated with an increased all-cause and cardiovascular mortality [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.07-2.32, p = 0.022 and HR: 2.01, 95% CI: 1.10-3.69, p = 0.023 respectively]. CONCLUSIONS: Patients with a low AGR level had an increased all-cause and cardiovascular mortality. AGR may be a useful index in identifying patients on PD at risk for CVD and all-cause of mortality.

Micheliolide Attenuates Lipopolysaccharide-Induced Inflammation by Modulating the mROS/NF-κB/NLRP3 Axis in Renal Tubular Epithelial Cells.

Chronic kidney disease is a common disease closely related to renal tubular inflammation and oxidative stress, and no effective treatment is available. Activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important factor in renal inflammation, but the mechanism remains unclear. Micheliolide (MCL), which is derived from parthenolide, is a new compound with antioxidative and anti-inflammatory effects and has multiple roles in tumors and inflammatory diseases. In this study, we investigated the effect of MCL on lipopolysaccharide- (LPS-) induced inflammation in renal tubular cells and the related mechanism. We found that MCL significantly suppressed the LPS-induced NF-κB signaling and inflammatory expression of cytokines, such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in a rat renal proximal tubular cell line (NRK-52E). MCL also prevented LPS- and adenosine triphosphate-induced NLRP3 inflammasome activation in vitro, as evidenced by the inhibition of NLRP3 expression, caspase-1 cleavage, and interleukin-1ß and interleukin-18 maturation and secretion. Additionally, MCL inhibited the reduction of mitochondrial membrane potential and decreases the release of reactive oxygen species (ROS). Moreover, MCL can prevent NLRP3 inflammasome activation induced by rotenone, a well-known mitochondrial ROS (mROS) agonist, indicating that the mechanism of MCL's anti-inflammatory effect may be closely related to the mROS. In conclusion, our study indicates that MCL can inhibit LPS-induced renal inflammation through suppressing the mROS/NF-κB/NLRP3 axis in tubular epithelial cells.

Neutrophil to Lymphocyte Ratio Predicts Adverse Cardiovascular Outcome in Peritoneal Dialysis Patients Younger than 60 Years Old.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) is a new inflammatory marker; the relationship between NLR and adverse cardiovascular (CV) prognosis has been gradually emphasized in the general population. However, their association in peritoneal dialysis (PD) patients remains unclear. METHODS: From January 1, 2010, to May 31, 2017, a total of 1652 patients were recruited. NLR was categorized in triplicates: NLR ≤ 2.74, 2.74 < NLR ≤ 3.96, and NLR > 3.96. Kaplan-Meier cumulative incidence curve and multivariable COX regression analysis were used to determine the relationship between NLR and the incidence of adverse CV outcome, while a competitive risk model was applied to assess the effects of other outcomes on adverse CV prognosis. Besides, forest plot was investigated to analyze the adverse CV prognosis in different subgroups. RESULTS: During follow-up, 213 new-onset CV events and 153 CV disease (CVD) deaths were recorded. Multivariable COX regression models showed that the highest tertile of NLR level was associated with increased risk of CV events (HR = 1.39, 95%CI = 1.01-1.93, P = 0.046) and CVD mortality (HR = 1.81, 95%CI = 1.22-2.69, P = 0.003), while compared to the lowest tertile. Competitive risk models showed that the differences in CV event (P < 0.001) and CVD mortality (P = 0.004) among different NLR groups were still significant while excluding the effects of other outcomes. In subgroups, with each 1 increased in the NLR level, adjusted HR of new-onset CV event was 2.02 (95%CI = 1.26 - 3.23, P = 0.003) and CVD mortality was 2.98 (95%CI = 1.58 - 5.62, P = 0.001) in the younger group (age < 60 years). CONCLUSIONS: NLR is an independent risk factor for adverse CV prognosis in PD patients younger than 60 years old.