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Finger seals have a good application prospect in gas and steam turbine for power generation as an advanced contact flexible seal. The wear and friction heat generation properties of the finger seal have significant effects on leakage and life. In this study, a bilateral wear model and friction heat generation model were established to calculate the wear volume and temperature of the finger seal and rotor. In particular, the friction heat generation model considered the effect of wear and deformation (centrifugal and thermal) of both the finger seal and rotor. Both models were expressed as functions of the finger seal configuration, material properties, operating conditions, and several relevant parameters. To determine these parameters, a ball-disk friction and wear experiment and a finger seal wear and friction heat generation experiment were conducted. Both models were validated with experimental data, and both errors were less than 12%. [ABSTRACT FROM AUTHOR]

Highly stable and multicolor photoluminescent (PL) quantum dots (QDs) have attracted widespread attention as ideal probe materials in the field of in vitro diagnostics (IVD), especially the fluorescence-linked immunosorbent assay (FLISA), due to their advantages of high-throughput, high stability, and high sensitivity. However, the size of QDs as fluorescent probes have significant effects on antigen-antibody performance. Therefore, it is critical to design suitable QDs for obtain excellent quantitative detection-based biosensors. In this paper, we prepared different sizes of aqueous QDs (30 nm, 116 nm, 219 nm, and 320 nm) as fluorescent probes to optimize the competitive FLISA platform. The SARS-CoV-2 neutralizing antibody (NTAB) assay was used as an example, and it was found that the size of the QDs has a significant impact on the antigen-antibody binding efficiency and detection sensitivity in competitive FLISA platform. The results showed that these QD nanobeads (QBs, ∼219 nm) could be used as a labeled probe for competitive FLISA, with half-maximal inhibitory concentration (IC50) of 1.34 ng/mL and limit of detection (LOD) of 0.21 pg/mL for NTAB detection. More importantly, the results showed good specificity and accuracy, and the QB 219 probe was able to efficiently bind NTAB without interference from other substances in the serum. Given the above advantages, the nanoprobe material (∼200 nm) offers considerable potential as a competitive FLISA platform in the field of IVD. [Display omitted] • A series of SiO 2 spheres (ranging from 54 to 360 nm) were designed to precisely synthesis. • For competitive FLISA platform in high sensitivity detection, we tailored different sizes aqueous QBs-probes. • Significant size dependence on competitive FLISA platforms have been founded to affect detection performance. • The detection sensitivity can be optimized to as high as 0.21 pg/mL when 219 nm QBs-probe had been preferably selected. [ABSTRACT FROM AUTHOR]

Introduction: Eosinophilia (eosinophil fraction of leukocytes >5%), an indicative parameter for bioincompatibility in various circumstances, is well established in hemodialysis. However, change in eosinophil count (EOC) and its association with death-censored technique failure among peritoneal dialysis (PD) patients remain unclear. Methods: We compared eosinophils before and after PD initiation among 1,432 eligible continuous ambulatory PD patients regularly followed up in our PD center during 2007–2018. Risk factors of early-stage eosinophilia were examined by the logistic regression test. The relationship of early-stage eosinophilia and EOC with death-censored technique failure was examined using the Cox proportional hazards model for overall patients and for men and women separately. Results: After PD initiation, the EOC and percentage of patients with eosinophilia were significantly increased compared with baseline. Being male (odds ratio [OR]: 2.26; 95% confidence interval [CI]: 1.55–3.31; p < 0.001) and higher EOC at baseline (100 cells/μL increase, OR: 1.62; 95% CI: 1.45–1.82; p < 0.001) were risk factors of early-stage eosinophilia after PD initiation. During follow-up, 204 death-censored technique failures were recorded. In fully adjusted models, each with 100 cells/μL increase in EOC, the adjusted hazard ratios (HRs) of technique failure were 1.11 (95% CI: 1.03–1.20; p = 0.009) in the whole cohort, 1.29 (95% CI: 1.10–1.51; p = 0.002) in women, and 1.07 (95% CI: 0.97–1.17; p = 0.196) in men. Eosinophilia was significantly associated with the risk of technique failure for women (HR: 2.24; 95% CI: 1.07–4.70; p = 0.033), which was especially significant for women aged <55 years (HR: 7.61; 95% CI: 1.88–30.90; p = 0.005). Conclusion: EOC was increased significantly after PD initiation, and increased numbers of eosinophils were associated with higher death-censored technique failure in PD patients, especially women. [ABSTRACT FROM AUTHOR]

The immune system has a central role in eliminating detrimental factors, by frequently launching inflammatory responses towards pathogen infection and inner danger signal outbreak. Acute and chronic inflammatory responses are critical determinants for consequences of kidney diseases, in which inflammasomes were inevitably involved. Inflammasomes are closely linked to many kidney diseases such as acute kidney injury and chronic kidney diseases. Inflammasomes are macromolecules consisting of multiple proteins, and their formation initiates the cleavage of procaspase-1, resulting in the activation of gasdermin D as well as the maturation and release of interleukin-1β and IL-18, leading to pyroptosis. Here, we discuss the mechanism in which inflammasomes occur, as well as their roles in inflammatory kidney diseases, in order to shed light for discovering new therapeutical targets for the prevention and treatment of inflammatory kidney diseases and consequent end-stage renal disease. [ABSTRACT FROM AUTHOR]

Background/Aims: The relationship between peritoneal protein clearance (PPCl) and nutritional status in peritoneal dialysis (PD) population have not been clarified. This study aims to investigate the relationship between PPCl and nutritional status in PD population. Methods: Prevalent PD patients were enrolled in the cross-sectional survey in a single center from April to November 2013. The total amount of protein loss in the dialysate was calculated. PPCl reflects the individual differences of peritoneal protein loss, and is calculated by the formula, that PPCl (ml/day)=24-h dialysate protein loss / (albumin/0.4783). Nutritional status measured by lean body mass index (LBMI) was assessed by multi-frequency bioelectrical impedance analysis (BIA). Results: Totally 351 PD patients (55% male, 17.1% with diabetes, mean age 47.7±14.3 years) were included. The median PPC l was 58 ml/day. Patients were divided into four groups for comparison according to the PPC quartiles. Compared with lower PPCl quartiles, patients with higher PPCl had higher body mass index (BMI) (P< 0.001), body surface area (BSA) (P < 0.001), LBMI (P<0.001), 4-hour D/P creatinine ratio (P< 0.001), and lower residual renal CCl (P<0.001). Compared with conventional body index (BMI and BSA) in ROC analysis, LBMI (area under curve: 0.71, 95% confidence interval [CI]: 0.66-0.77) had better performance in predicting higher PPCl. After adjustment in logistic regression models, each 1 kg/m2 increase of LBMI (odd ratio[OR] =1.37; 95% CI: 1.17-1.60), each 0.1 increase of 4-hour D/P creatinine ratio (OR =1.47; 95% CI: 1.11-1.93), and every 1 L/week/1.73m2 decrease of residual renal CCl (OR =0.98; 95% CI: 0.96-0.99) were independently associated with higher PPCl (> 58 ml/day). Conclusion: Higher LBMI was independently associated with higher , indicating that better nutritional status dominates peritoneal protein metabolism in PD patients. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Sodium glucose cotransporter-2 was found in both the human peritoneum and peritoneal mesothelial cells. • Sodium glucose cotransporter-2 inhibitors reduced the glucose uptake and increased ultrafiltration through the peritoneum. Abstract Background Sodium glucose cotransporter-2 (SGLT-2) inhibitors have been widely used in the clinic to reduce blood glucose levels by enhancing glucose excretion. However, whether such agents might also reduce glucose absorption via the peritoneal function of human peritoneal mesothelial cells (HPMCs) that also express SGLT-2 is not clear. Methods An acute peritoneal dialysis (PD) model in nonuremic rats was established. Ratios of peritoneal glucose uptake at D4/D0 of Sprague-Dawley rats treated with the SGLT-2 inhibitor, empagliflozin were tested to evaluate the effect of this inhibitor on peritoneal glucose absorption. An in vitro model of HPMCs obtained from peritoneal dialysate effluent in patients undergoing PD was used. HPMCs were exposed to high glucose (60 mM) in the presence and absence of empagliflozin. Glucose uptake and glucose consumption, which were used to estimate the activity of SGLT-2 in HPMCs, were measured by flow cytometry and hexokinase respectively. The expression of SGLT-2 in both peritoneum and HPMCs was also observed by real-time polymerase chain reaction (PCR), western blot, and immunofluorescence staining. Results Both ratios of peritoneal glucose uptake at D4/D0 and ultrafiltration of rats treated with 3 mg kg−1 of empagliflozin for 3 days increased significantly compared to those of the control group (0.32 ± 0.40 vs. 0.11 ± 0.11 mM, P = 0.001；17.00 ± 3.58 vs. -13.67 ± 17.25 ml, P = 0.002). Compared to the control group, the expression of mRNA and protein in SGLT-2 increased significantly in the rats treated with 3 mg kg−1 of empagliflozin for 3 days. Both glucose consumption and uptake of HPMCs incubated with 1 μM of empagliflozin for 24 h decreased significantly compared to control values (8.69 ± 1.77 vs. 11.48 ± 1.00 mM, P = 0.004; 31.97 ± 4.81 vs. 43.98 ± 1.38, P = 0.002). Conclusion An SGLT-2 inhibitor was able to exert a glucose-lowering effect in peritoneum exposed to PD solution by inhibiting the activity of SGLT-2. [ABSTRACT FROM AUTHOR]

Colloidal quantum dots (QDs) have been widely used as fluorescent labeling materials in the field of in vitro diagnostics (IVD). In spite of the significant development of direct single-signal response fluorescent immunosensors, it is still a challenge to obtain the high accuracy and sensitivity of quantitative results of these sensors due to the influence of several factors unrelated to the analysis. Herein, we present a delicate design and synthesis of dual-color QDs bilayer nanobeads (red and green QDs nanobeads, R&G-QD nanobeads), achieving the precisely control of growth of the silicon layer with different proportions of ammonia, and inhibiting fluorescence resonance energy transfer (FRET) successfully. The dual-color QDs bilayer nanobeads have realized dual-channel detection (the acquisition of two emission wavelengths) of the target, and avoided the problems of low analytical accuracy and imprecise sensitivity of single-signal response. A proof-of-concept demonstration of a fluorescence-linked immunosorbent assay (FLISA) platform is conducted for the quantitative detection of prostate-specific antigen (PSA) with a sensitivity of 49 pg/mL and a linear range of 0.2–800 ng/mL. The dual-color QDs bilayer nanobeads FLISA platform with high sensitivity and accuracy holds great potential for early diagnosis of cancer or other diseases and provides a new approach for IVD. [Display omitted] • Dual-color QDs bilayer nanobeads were designed to synthesize by layer-by-layer assembly method. • Controlled growth of alternate red and green QD layers on pre-synthesized SiO 2 beads can suppress energy transfer. • Such dual-color QDs nanobeads deliver dual single calibration and can avoid errors caused from the single signal response. • A proof-of-concept demonstration of a FLISA platform is conducted for detecting PSA with high sensitivity and accuracy. [ABSTRACT FROM AUTHOR]

Objectives The extract of Tupistra chinensis ( TCE) is traditionally used for the treatment of inflammatory diseases in southwestern China for hundreds of years. The present study was designed to investigate the effects of the TCE against experimental hepatitis and to illustrate its potential mechanisms. Methods Effects of TCE were investigated on Con A-induced hepatitis. Profiles of multiple cytokines were measured with biometric immuno-sandwich ELISA. Proliferation, activation and apoptosis of T lymphocytes were evaluated using Western blot, MTT analysis and flow cytometry. Key findings TCE significantly inhibited levels of serum transaminases and lactic dehydrogenase in mice with Con A-induced hepatitis, accompanied with marked alleviation of the liver microscopic appearances. Moreover, it decreased levels of inflammatory cytokines in a concentration-dependent manner both in vivo and in vitro. It also suppressed mitogen-activated protein kinases and NF-κ B-signalling in liver. These effects of TCE are attributed to its inhibition on activated T cells but not to hepatocytes protection. Flow cytometry and immunoblot assay data showed its effects on STAT1/ NF-κ B-signalling blockage and apoptosis induction in activated T cells. Conclusion Our findings illustrate the significant potential of TCE as a novel approach for treatment of T cell-mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

Abstract: Endophilin, one of the main accessory proteins involved in clathrin-mediated endocytosis, interacts with other endocytic proteins, such as dynamin, by its SH3 domain. We previously reported that voltage-gated Ca2+ channels are an integral part of the synaptic vesicle (SV) endocytosis machinery through their interaction with endophilin. Formation of the endophilin–channel complex is Ca2+ dependent. A glutamate residue, E264, in endophilin is part of the primary Ca2+ sensor for Ca2+-dependent formation of the channel–endophilin complex. We proposed that endophilin exists in two distinct modes (conformations), an open mode in the absence of Ca2+, and a closed mode in the presence of Ca2+. Binding of Ca2+ switches endophilin from its open mode to the closed mode, resulting in dissociation of endophilin from other proteins. The present study is aimed at understanding the functional roles of endophilin in its two different modes, by creating two endophilin mutants, E264A and E264R, to mimic endophilin in its permanent open mode and permanent closed mode respectively. Here, we show that these two modes of endophilin have different effects on how endophilin interacts with other proteins, such as dynamin or β1-adrenergic receptors. In living cells, endophilin in its permanent closed mode does not show obvious effects on agonist-induced internalization of β1-adrenergic receptors. Endophilin, when in its permanent open mode, enhances the short-term synaptic depression in cultured hippocampal neurons, due partly to its failure to dissociate from Ca2+ channels in the presence of Ca2+. Our results show that modal switching by Ca2+ allows endophilin to regulate, more effectively, the clathrin-mediated endocytosis of SV at the nerve terminal. [Copyright &y& Elsevier]

In this paper, a differential equation for wear volume of brush seal has been established and the theoretical model of wear volume has been obtained. Wear volume of a brush seal was a function of interference, pressure drop, rotating speed, gas temperature, inner diameter of brush seal, diameter of a bristle, lay angle of the bristle, and thickness of the bristle pack. Besides, abrasive resistance and mechanical property of bristle and coating materials could also influence significantly. Testing has been conducted to determine the correction factor in the model and verify the model, and the theoretical results were in good agreement with the experimental results. • Brush seals can enhance aero-engine performance and decrease specific fuel consumption. • Wear can increase the leakage, even worse, cause failure of brush seal. • The mathematic model of wear volume of brush seal is proposed. • The most wear occurs in the initial period, sharp wear. [ABSTRACT FROM AUTHOR]

Background: Bacterial translocation was observed in critical illness and patients with chronic diseases such as liver cirrhosis and chronic kidney disease (CKD). Hypokalemia is a common complication in these diseases. Whether low potassium diet may increase intestinal permeability and result in bacterial translocation lack of evidence. The present study was aimed to investigate the potential effects of LK on intestinal permeability.Methods: Grade 8-week-old male Bal B/C mice were randomly placed either on a normal potassium (NK) mouse chow or a low potassium (LK) diet for 28 days. Intestinal permeability and expression of tight junction proteins were compared between the two groups.Results: Compared with the NK group, the mice in LK group had significantly lower serum potassium level, increased levels of plasmas endotoxin and plasma D-lactate. The bacterial translocation was higher and in occurred mainly in mesenteric lymph nodes (MLN), liver and spleen. The pathologic change of small intestine was obvious with thinner villus lamina propria, shorter crypt depth and thinner intestinal wall. Slight increases in the expression of proteins and mRNA levels of both claudin-1 and claudin-2 were observed in LK group.Conclusions: Low potassium diet could increase intestinal permeability and thereby lead to bacterial translocation, which was suspected to result from impaired intestinal epithelial barrier and biological barrier. [ABSTRACT FROM AUTHOR]

Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay‐guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti‐renal fibrotic lead. DA shows significant anti‐kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down‐regulates its downstream phospho‐protein kinase Cζ(p‐PKCζ)/phospho‐glycogen synthase kinase‐3β (p‐GSK‐3β), thereby promoting β‐catenin Ser33/37/Thr41 phosphorylation and ubiquitin‐dependent proteolysis to block classical pro‐fibrotic β‐catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs. [ABSTRACT FROM AUTHOR]

Purpose. It was reported that gut-kidney axis may play an important role in IgA nephropathy (IgAN). Previous five GWASs of different populations for IgAN have discovered several genes related to intestinal immunity, including DEFA gene. However, the roles of the encoded proteins of DEFA5/6 which were called intestinal antimicrobial peptides HD5 and HD6 were not clear in kidney disease, such as IgAN. The purpose of this study was to clarify the association of HD5 and HD6 with IgAN. Methods. We measured HD5 and HD6 in serum, urine, and kidney of IgAN patients and normal controls by ELISA, Western blot, and immunofluorescence. The association of HD5 or HD6 levels with clinical and pathologic phenotypes was analyzed. Results. Serum levels of HD5 and HD6 were significantly higher in IgAN patients than those in normal controls. Baseline serum HD5 levels were significantly associated with eGFR (P = 0.002) and tubular atrophy/interstitial fibrosis (P = 0.004) by stepwise multivariate regression analysis. Compared to the patients with serum HD5 below the median level, patients with elevated serum HD5 above the median level had a significantly worse renal outcome (log-rank test, P = 0.009) by Kaplan-Meier analysis. A Cox regression model showed that serum HD5 was an independent prognostic factor (HR = 1.239 , P = 0.029) after adjusting for the well-known predictors of outcome in IgAN patients. In renal biopsies of IgAN patients, HD5 was significantly expressed in the damaged proximal tubules, while no immunoreactive HD6 was found. Interestingly, the serum HD6 level of IgAN patients was significantly associated with gender. Conclusions. In IgAN patients, an elevated serum HD5 level at the time of renal biopsy was associated with poor renal outcomes. HD5 rather than HD6 was probably associated with renal function of IgAN patients. [ABSTRACT FROM AUTHOR]

In Figure 3, the term " HT ht , HT ht " should read as " HT ht , HT ht ." In the article titled "Upregulated Expression of Intestinal Antimicrobial Peptide HD5 Associated with Renal Function in IgA Nephropathy" [[1]], the authors identified an error in Figure 3. [Extracted from the article]

The roles of pDC and IFN-α have not been well defined in IgA nephropathy (IgAN). In this study, we investigated the abundance of pDCs and IFN-α in IgAN patients and the response of peripheral blood mononuclear cells (PBMCs) after stimulation of the pDC-preferred TLR9 ligand CpG2216. The effects of IFN-α on plasma cell differentiation and leukocyte migration were also investigated. Here, we found that the percentages of pDCs were increased in PBMCs of IgAN patients, than in those of healthy controls. Plasma levels of IFN-α proteins and abundance of plasma cells were higher in IgAN patients than in healthy donors. Plasma IFN-α levels were positively associated with proteinuria, renal IgM deposition, and renal tubular atrophy/interstitial fibrosis grade in IgAN patients. Ex vivo activation of TLR9 on pDCs resulted in increased IFN-α production and enhanced plasma cell differentiation in IgAN patients as compared with healthy donors. IFN-α treatment led to increased plasma cell differentiation in vitro. IFN-α also significantly promoted expression of chemokines IP-10 and MCP-1 in human mesangial cells, which subsequently facilitated the transendothelial migration of human CD4+ and CD14+ cells. In conclusion, pDC and its secreted cytokine IFN-α may play important roles in pathological changes of IgA nephropathy. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). The chronic graft versus host disease (cGVHD) mouse model is a well‐established model of SLE. LC3‐associated autophagy plays a critical role in extracellular particle clearance, including pathogens and apoptotic cells. Lupus Recipe (LR) is a Chinese herbal compound that has been proven to be effective in treating SLE. In the study, we investigated the protective effects of LR or LR combined with prednisone on cGVHD mouse model and LC3‐associated autophagy in the kidney. The mice were subjected to six groups. The LR treatment group received LR at the dosage of 1.15 and 2.3 g/kg/day, respectively. The corticosteroid treatment group received prednisone at a dosage of 5 mg/kg/day. The combination treatment group received LR at a dosage of 2.3 g/kg/day, and prednisone at 2.5 mg/kg/day. LR treatment reduced proteinuria and serum triglyceride levels, as well as spleen weight. LR also alleviated pathologic damage and immunoglobulin G deposition in the kidney. LR combined with a low dose of prednisone significantly improved kidney function and decreased serum triglyceride, total cholesterol, and spleen weight. In addition, combination treatment relieved kidney injury more effectively than LR alone. Western blot revealed that LR treatment or LR combined with prednisone increased the LC3‐associated autophagy protein of Rubicon and Nox2, as well as LC3I levels in the kidney tissues. In conclusion, LR inhibited the manifestation of cGVHD‐induced LN, which may attribute to the increased levels of LC3‐associated autophagy. [ABSTRACT FROM AUTHOR]

Purpose Smad3 is a critical signaling protein in renal fibrosis. Proteolysis targeting chimeric molecules (PROTACs) are small molecules designed to degrade target proteins via ubiquitination. They have three components: (1) a recognition motif for E3 ligase; (2) a linker; and (3) a ligand for the target protein. We aimed to design a new PROTAC to prevent renal fibrosis by targeting Smad3 proteins and using hydroxylated pentapeptide of hypoxia-inducible factor-1α as the recognition motif for von Hippel–Lindau (VHL) ubiquitin ligase (E3). Methods Computer-aided drug design was used to find a specific ligand targeting Smad3. Surface plasmon resonance (SPR) was used to verify and optimize screening results. Synthesized PROTAC was validated by two-stage mass spectrometry. The PROTAC’s specificity for VHL (E3 ligase) was proved with two human renal carcinoma cell lines, 786-0 (VHL − ) and ACHN (VHL + ), and its anti-fibrosis effect was tested in renal fibrosis cell models. Results Thirteen small molecular compounds (SMCs) were obtained from the Enamine library using GLIDE molecular docking program. SPR results showed that #8 SMC (EN300-72284) combined best with Smad3 ( K D = 4.547 × 10 −5 M). Mass spectrometry showed that synthesized PROTAC had the correct peptide molecular weights. Western blot showed Smad3 was degraded by PROTAC with whole-cell lysate of ACHN but not 786-0. Degradation, but not ubiquitination, of Smad3 was inhibited by proteasome inhibitor MG132. The upregulation of fibronectin and Collagen I induced by TGF-β1 in both renal fibroblast and mesangial cells were inhibited by PROTAC. Conclusion The new PROTAC might prevent renal fibrosis by targeting Smad3 for ubiquitination and degradation. [ABSTRACT FROM AUTHOR]

Background: Renal fibrosis is the pathological foundation of various chronic kidney diseases progressing to end stage renal failure. However, there are currently no nephroprotective drugs targeted to the fibrotic process in clinical practice. Proteolytic targeting chimeras (PROTACs), which reversibly degrade target proteins through the ubiquitin–proteasome pathway, is a novel therapeutic modality. Smad3 is a key pathogenic factor in fibrogenesis while HIF-2α exhibits prominent renal protective effects, which is the natural substrate of von Hippel–Lindau (VHL) E3 Ligase. We hypothesied the construction of VHL-recruiting, Smad3-targeting PROTAC might combine the effects of Smad3 degradation and HIF-2α stabilization, which not only improving the clinical efficacy of PROTAC but also avoiding its potential off-target effects, could greatly improve the possibility of its translation into clinical drugs. Methods: By joining the Smad3-binding small molecule compound (SMC) to VHL-binding SMC with a linker, we designed and synthesized a Smad3-targeting, VHL-based PROTAC. The effects of this PROTAC on targeted proteins were verified both in vitro and in vivo. The toxicity and pharmacokinetic (PK) evaluations were conducted with both male and female mice. The renal protection effects and mechanism of PROTAC were evaluated in unilateral ureteral obstruction (UUO) and 5/6 subtotal nephrectomy (5/6Nx) mouse model. Results: By optimizing the linker and the Smad3-binding SMC, we got a stable and high efficient PROTAC which simultaneously degraded Smad3 and stabilized HIF-2α both in vivo and in vitro. The acute toxicity evaluation showed a pretty large therapeutic window of the PROTAC. The prominent renal protection effects and its underlying mechanism including anti-fibrosis and anti-inflammatory, improving renal anemia and promoting kidney repair, had all been verified in UUO and 5/6Nx mouse model. Conclusion: By accurate combination of PROTAC targeted protein and E3 ligase, we got a Smad3-targeting, VHL-recruting PROTAC which caused Smad3 degradation and HIF-2α stabilization effects simultaneously, and led to the strong renal function protection effects. [ABSTRACT FROM AUTHOR]

The development of functionalized surfaces with low non-specific adsorption is important for their biomedical applications. To inhibit non-specific adsorption on glass substrate, we designed a novel optical biochip by modifying a layer of dense negatively charged film (SO 3 2−) on its substrate surface via self-assembly. Compared with the untreated glass substrate, it reduced the adsorption by about 300-fold or 400-fold by poly (styrene sulfonic acid) sodium salt (PSS), or meso -tetra (4-sulfonatophenyl) porphine dihydrochloride (TSPP) on individually the modified glass substrate. Considering the effect of fluorescence resonance energy transfer (FRET) between TSPP and the QDs in solution by mixing, a strategy of 2-layer of TSPP followed by 4-layer of PSS was designed to modify the glass for preparing biochips. Under the optimized conditions, the biochip on functionalized glass substrate co-treated with TSPP and PSS realized the sensitive quantitative detection of C-reactive protein (CRP) based on a quantum dot fluorescence immunosorbent assay (QD-FLISA). The limit of detection (LOD) for CRP achieved 0.69 ng/mL with the range of 1-1,000 ng/mL using TSPP and PSS co-treated glass substrate surface, which was respectively about 1.9-fold and 7.5-fold more sensitive to the PSS-modified biochip and the TSPP-modified biochip. This work demonstrated an effective and convenient strategy to obtain biochips with low non-specific adsorption properties on functionalized surfaces, thus providing a new approach for creating ultra-high sensitivity microchannels or microarrays on glass substrates. [Display omitted] • The causes of non-specific adsorption on glass substrates were studied. • The dense negatively charged polymer substrates (SO 3 2−) were prepared and evaluated. • A novel optical biochip co-treated with TSPP and PSS was constructed to inhibit non-specific adsorption. • The designed biochip can realize the sensitive quantitative detection of CRP based on QD-FLISA. [ABSTRACT FROM AUTHOR]

Lignite, a low-quality fossil fuel with high moisture and ash content, leads to considerable carbon emissions during electricity generation. Such carbon emissions routinely result in smog. Humic acids (HAs) derived from lignite as by-products can be used to prepare sulphonated HA resin (SHAR) to adsorb heavy metals from wastewater. SHAR exhibits an excellent adsorption capacity because of its high ligand density and abundant macroporous structure. The adsorption capacities of SHAR for Pb2+, Cd2+, and Cu2+ can reach 621, 366, and 141 mg/g, respectively, which are considerably higher than those of many reported adsorbents. Multifunctional binding chemistry of SHAR for heavy metals in water was comprehensively investigated. Ion exchange, complexation, adsorption precipitation, and π-electrons interaction between SHAR and heavy metals were experimentally confirmed. In the solution with multiple metal ions (Cu2+, Pb2+, and Cd2+), synergistic or competitive adsorption among these heavy metal ions on SHAR was controlled using solution pH. The adsorption selectivity of SHAR to lead was proved by real wastewater, and the highly efficient adsorption was associated with S- and O-containing multi-dentate ligands structure. In this study, a green utilisation of lignite and a promising candidate for the purification of heavy metal polluted water were proposed. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes. [Copyright &y& Elsevier]

The excellent optical properties of quantum dots (QDs) make them as an ideal fluorescent probe for multiplexed detection, however, the interference between different emission spectra, the dependence of excitation wavelengths, and the sharp decrease of quantum yield (QY) during surface modification are issues that cannot be ignored. Herein, a dual protection scheme of polymer and silica was proposed to prepare high-quality three-color QDs nanobeads using QDs with different ligands. In comparison with single-core QDs, the fluorescence signal of the prepared QD nanobeads (QBs) is increased by more than 1,000 times and has better stability. Considering the excitation efficiency of QDs, we tailor three-color QBs as fluorescent probes based on fluorescence-linked immunosorbent assays (tQBs-FLISA) to detect multiple inflammatory biomarkers simultaneously with tunable detection ranges. This resulted in highly sensitive detection of three inflammatory biomarkers in comparison to the single-core QD-FLISA, the sensitivities of C-reactive protein (CRP), serum amyloid A (SAA), and procalcitonin (PCT) were increased by 16-fold, 19-fold, and 5-fold, respectively, to 0.48 ng/mL, 0.42 ng/mL, and 10 pg/mL. Furthermore, the tQBs-FLISA showed good accuracy without interference from common serum factors. In this strategy, a three-color QBs suitable for multilevel sensitivity and tunable detection range was tailored using the versatile polymer and silica dual protection method, building high-performance immunosensor for in vitro diagnostics (IVD). [Display omitted] • The QBs with different surface ligands were prepared by double protection method. • Fluorescence intensity of QBs increased exponentially compared with single-core QDs. • Fluorescent signal amplification sensor was designed based on excitation efficiency. • A tQBs-FLISA has tunable detection range and multilevel sensitivity. [ABSTRACT FROM AUTHOR]

Aristolochic acid (AA) can accumulate in the tubulointerstitium and cause kidney-specific injuries. However, the mechanism by which AA induces nephropathy remains largely unknown. This study explored the effect of AA-I on tight junctions (TJs), and the fence function in a renal epithelial cell (REC). NRK-52E cells were exposed to different concentrations of AA-I for 4 h or 25 μM AA-I for different time. Cell viability was detected by MTT, cell apoptosis by flow cytometric analysis, the expression of zonula occludens-1 (ZO-1), E-cadherin and polarity scaffold (Par3) by western blot and immunofluorescence, cell membrane permeability by transepithelial electrical resistance (TEER). It was found that AA-I reduced the expression of ZO-1, E-cadherin, and Par3 in a concentration- and time-dependent fashion, and altered the distribution of ZO-1 and Par3 from cell membrane to cell plasma. In parallel to the reduced expression of TJ proteins, TEER exhibited a significant reduction in response to AA-I treatment in a time- and concentration-dependent manner. Meanwhile, α-SMA expression in cells was increased following AA-I treatment. In contrast, cell viability and apoptosis were unaltered with the doses of AA-I tested. Our findings show for the first time that AA-I treatment in cultured RECs induced a rapid disruption of TJ and the fence function preceding apoptosis, which indicated that aberrant expression of TJ proteins within RECs may be involved in initiating the renal tubulointerstitial disorders. [ABSTRACT FROM AUTHOR]

Platelet activation is a hallmark of severe preeclampsia, and platelet PGH synthase 1-derived (PGHS1-derived) thromboxane A(2) (TxA(2)) has been implicated in its pathogenesis. However, genetic disruption of PGHS1 delays parturition. We created hypomorphic PGHS1 (PGHS1(Neo/Neo)) mice, in which the substantial but tissue-dependent variability in the inhibition of PGHS1-derived eicosanoids achieved by low-dose aspirin treatment is mimicked, to assess the relative impact of this strategy on hemostatic and reproductive function. Depression of platelet TxA(2) by 98% in PGHS1(Neo/Neo) mice decreased platelet aggregation and prevented thrombosis. Similarly, depression of macrophage PGE(2) by 75% was associated with selectively impaired inflammatory responses. PGF(2alpha) at 8% WT levels was sufficient to induce coordinated temporal oxytocin receptor (OTR) expression in uterus and normal ovarian luteolysis in PGHS1(Neo/Neo) mice at late gestation, while absence of PGHS1 expression in null mice delayed OTR induction and the programmed decrease of serum progesterone during parturition. Thus, extensive but tissue-dependent variability in PG suppression, as occurs with low-dose aspirin treatment, prevents thrombosis and impairs the inflammatory response but sustains parturition. PGHS1(Neo/Neo) mice provide a model of low-dose aspirin therapy that elucidates how prevention or delay of preeclampsia might be achieved without compromising reproductive function. [ABSTRACT FROM AUTHOR]

Aristolochic acid nephropathy is a rapidly progressive tubulointerstitial disease induced by aristolochic acid (AA) and effective treatment is lacking. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been proven to be protective in acute kidney injury and chronic kidney disease progression. But its role in AA-induced renal tubular epithelial cell injury has not been determined. This study aimed to investigate the role of Nrf2 in AA-induced renal tubular epithelial cell injury in vitro. NRK-52E cells were incubated with 5–50 μM AA to evaluate cell viability, reactive oxygen species (ROS) production, cell apoptosis/necrosis, and Nrf2 signaling pathway protein levels. We found that AA reduced cell viability and induced cell apoptosis in a time-dependent manner, accompanied by increased production of intracellular ROS. Meanwhile, the expression of Nrf2 signaling pathway proteins was significantly decreased. Downregulation of Nrf2 by Nrf2 siRNA decreased its downstream antioxidant proteins HO-1 and NQO1 and resulted in increased AA-induced ROS production and cell death. On the contrary, overexpression of Nrf2 increased HO-1 and NQO1 expression and resulted in decreased cell death. In conclusion, Nrf2 plays an important role in AA-induced injury. Enhanced Nrf2 signaling pathway could ameliorate AA-induced renal tubular epithelial cell injury, while downregulation of Nrf2 signaling exacerbated the injury. [ABSTRACT FROM AUTHOR]

Context: The proximal tubular epithelial cells (PTECs) are the primary target of aristolochic acids and especially vulnerable to mitochondrial injury from insults of toxic xenobiotics.Objectives: This study aimed to investigate the possible role of mitochondrial injury in CaulisAristolochia manshuriensis(CAM)-induced aristolochic acid nephropathy (AAN).Materials and methods: Male Sprague-Dawley rats were gavaged with CAM extract every other week for 1, 4, 8 and 12 weeks, respectively.Results: The rats in the model group showed chronic AAN as evidenced by worsening kidney function evaluated by blood urea nitrogen, creatinine and proteinuria levels, and severe tubulointerstitial injury marked by massive tubular atrophy and interstitial fibrosis in kidney tissues. Moreover, overt apoptosis and impaired regeneration of PTECs were observed in AAN rats. Furthermore, the study revealed that mitochondria in PTECs were fragmented into small, punctuate suborganelles in AAN rats. Two mitochondrial respiratory chain proteins, mitochondrial DNA (mtDNA)-encoded cytochrome c oxidase subunit І (COX-І) and nuclear DNA-encoded nicotinamide adenine dinucleotide dehydrogenase (ubiquinone)-1β subcomplex 8 (NDUFβ8), were both down-regulated after one week of CAM treatment. However, with AAN progression, NDUFβ8 level restored, while COX-І level maintained low. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), master regulator of mitochondrial biogenesis, was significantly down-regulated at week 4 and week 8, but significantly up-regulated at week 12. In addition, mtDNA copy number reduced markedly along with AAN progression.Discussion and conclusion: A rat model of chronic AAN was successfully reproduced by gavage with CAM extract. Dynamic changes of mitochondrial injury induced by CAM might contribute to the AAN progression. [ABSTRACT FROM PUBLISHER]

Objective: Several studies have reported that tacrolimus (TAC) significantly reduced proteinuria in lupus nephritis (LN) patients and mouse models. However, the mechanism for this effect remains undetermined. This study explored the mechanism of how TAC protects podocytes from injury to identify new targets for protecting renal function. Methods: MRL/lpr mice were given TAC at a dosage of 0.1 mg/kg per day by intragastric administration for 8 weeks. Urine and blood samples were collected. Kidney sections (2μm) were stained with hematoxylin-eosin (HE), periodic acid-Schiff base (PAS) and Masson's trichrome stain. Mouse podocyte cells (MPC5) were treated with TAC and/or TGF-β1 for 48h. The mRNA levels and protein expression of synaptopodin and Wilms’ tumor 1 (WT1) were determined by real-time PCR, Western blotting and/or immunofluorescence, respectively. Flow cytometry was used to detect cell apoptosis with annexin V. Podocyte foot processes were observed under transmission electron microscopy. IgG and C3 deposition were assessed with immunofluorescence assays and confocal microscopy. Results: Synaptopodin expression significantly decreased in MRL/lpr disease control mice, accompanied by increases in 24-h proteinuria, blood urea nitrogen, and serum creatinine. TAC, however, reduced proteinuria, improved renal function, attenuated renal pathology, restored synaptopodin expression and preserved podocyte numbers. In MPC5 cells, TGF-β1 enhanced F-actin damage in podocytes and TAC stabilized it. TAC also decreased TGF-β1-induced podocyte apoptosis in vitro and inhibited foot process fusion in MRL/lpr mice. In addition, our results also showed TAC inhibited glomerular deposition of IgG and C3. Conclusion: This study demonstrated that TAC reduced proteinuria and preserved renal function in LN through protecting podocytes from injury partly by stabilizing podocyte actin cytoskeleton and inhibiting podocyte apoptosis. [ABSTRACT FROM AUTHOR]

Growth cone collapse is a critical repulsive response to various guidance cues for axon guidance. Protein kinase C epsilon (PKCε) plays important regulation roles in such responses. Translocation of PKCε from cytoplasm to membrane is crucial to archive its regulatory roles in this process. We previously reported that PDLIM5 could selectively recruit PKCε to its specific substrate in neurons. However, the molecular mechanism of PKCε translocation in the neuronal growth cone collapse remains elusive. Here, we demonstrated that PDLIM5 and PKCε co-existed in the nerve growth cones. By interacting with α-actinin, but not β-actin or β-tubulin, PDLIM5 might contribute to regulation of remodeling of the microfilaments in neurons. Meanwhile, PDLIM5 could also bind to PKCε to form PDLIM5-PKCε complexes in growth cones. In the primary cultured neurons, activation of PKCε by PMA resulted in translocation of both PKCε and PDLIM5 from cytoplasm to the membrane. Knockdown of either PDLIM5 or PKCε rescued the neuron from PMA-induced growth cone collapse. Furthermore, in neurons, application of PDLIM5 shRNA or over-expression of PDLIM5 LIM1-3 mutants reduced the amount of PKCε in the membrane. Together, these results suggest that PDLIM5 acts as a scaffold protein by mediated PKCε translocated to the membrane in PMA-induced growth cone collapse. [ABSTRACT FROM AUTHOR]

[Display omitted] The fulvic acid (FA) with more oxygen-containing functional groups was extracted from lignite, which was used to remove the heavy metals in water and realize the utilization of environmental substances of low-rank coal. However, because of the heterogeneous nature, the chemical structure of FA was hard to be described, which seriously limited its application. Therefore, in this study, FA was divided into four fractions according to its solubility in different solvents—ethyl acetate (FA-1), ethanol (FA-2), methanol (FA-3), and H 2 O (FA-4) to decrease its heterogeneity. The results showed that the oxygen content and the proportion of aliphatic chains decreased from FA-1 to FA-4, while the proportion of cyclic compounds showed an opposite trend. Then, the adsorbents of FA and its fractions were prepared by the cross-linking reaction with phenolic resin, and their removal rate of lead: FA-1 > FA-2 > FA-3 > FA-4 > FA. The results of FT-IR and XPS showed that the binding sites of lead were mainly provided by oxygen-containing functional groups (phenolic groups and carboxyl groups). FA-1 had a higher adsorption capacity (675.70 mg g−1) and faster adsorption rate, this is because it had chain-like structures which help to carry out adsorption more efficiently. The adsorption isotherms and kinetics were described by the Langmuir model and pseudo-second-order rate equation, respectively. The results of this study contribute to understanding the adsorption behavior of natural organic matter on heavy metals and its environmental effects. [ABSTRACT FROM AUTHOR]

To investigate the effect of simvastatin on the migration and invasion of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and its cellular signal mechanisms, FLS from active RA patients were stimulated with 3 % FBS or GM-CSF in the presence or absence of simvastatin. Cells migration and invasion in vitro were measured by the Boyden chamber method. RhoA activity was assessed by a pull-down assay. Matrix metalloproteinases-2 (MMP-2) activity was evaluated by zymography. Simvastatin inhibits FBS- or GM-CSF-induced migration in a dose-dependent manner by RA FLS, and this inhibitory effect is independent of cell apoptosis. We also found that simvastatin suppressed in vitro invasion, adhesion, MMP-2 activity, cytoskeletal reorganization and RhoA activation. Furthermore, mevalonate or GGPP treatment reversed the inhibitory effect of simvastatin not only on migration and invasion in vitro but also on RhoA activation, and inhibition of RhoA by specific siRNA transfection reduced migration, adhesion and invasion of RA FLS. This study shows that simvastatin reduces RA FLS migration and invasion through the prevention of protein geranylgeranylation and RhoA activation. These findings provide a novel evidence that statin may be benefit for preventing RA arthritic destruction, and also indicate that RhoA may be a new target for the modulation of RA FLS migration and invasion. [ABSTRACT FROM AUTHOR]

To investigate whether anti-inflammatory effects of HMG-CoA reductase inhibitor simvastatin (SMV) in rheumatoid arthritis (RA) is mediated by Toll-like receptor-2 (TLR-2) signal via inhibiting activation of RhoA, a small Rho GTPase that plays an important role in inflammatory responses. Peripheral blood monocytes from active RA patients were treated with Staphylococcus aureus peptidoglycan (PG), a ligand of TLR-2, in the presence or absence of SMV. RhoA activity was assessed by a pull-down assay. DNA-binding activity was measured by a sensitive multi-well colorimetric assay. Cytokine secretion was measured by ELISA. PG stimulation increased the level of active GTP-bound RhoA compared with unstimulated monocytes, and the effect of PG on RhoA activity was suppressed with anti-TLR-2 monoclonal antibody. RhoA inhibition either with a specific inhibitor or by siRNA transfection inhibited activation of NF-κB and secretion of TNFα and IL-1β in PG-induced RA monocytes. SMV mitigated PG-induced increase in RhoA activity and NF-κB activation as well as secretion of TNFα and IL-1β. The inhibitory effects of SMV were completely reversed by mevalonate and geranylgeranyl pyrophosphate. Our results indicate the modulation of RhoA on TLR-2-mediated inflammatory signaling in RA and provide a novel evidence for anti-inflammatory effects of statins through influencing TLR-2 signaling via RhoA in RA. [ABSTRACT FROM AUTHOR]

Objectives. Increasing evidence indicates that ezrin/radixin/moesin (ERM) proteins may play a critical role in cell proliferation. This study examined the role of ERM proteins in proliferation of fibroblast-like synoviocytes (FLS) from patients with RA.Methods. Synovial tissues (STs) were obtained from 18 RA and 6 OA patients. The expression of ERM and its phosphorylated proteins in cultured FLS and ST was assessed by western blots or IF staining. Small interference RNA (siRNA)-mediated ERM knockdown was used to inhibit phosphorylation of ERM. Proliferation of FLS was measured by bromodeoxyuridine (BrdU) incorporation into cell DNA and by PCNA immunoblotting.Results. Our study showed that increased phosphorylation of ERM proteins was found in ST and FLS from patients with RA as compared with OA patients and non-arthritis controls. Treatment with TNF-α, IL-1β or PDGF-induced phosphorylation of ERM proteins in dose- and time-dependent manner by RA FLS, but did not affect the expression of total ERM protein. Rho kinase and p38MAPK signal pathways were involved in TNF-α-induced ERM phosphorylation. We further showed that inhibition of ERM phosphorylation by siRNA-mediated ERM knockdown suppressed TNF-α- or IL-1β-induced BrdU incorporation and PCNA expression in RA FLS.Conclusions. This study provides the novel evidence that increased phosphorylation of ERM proteins may contribute to proliferation of RA FLS, suggesting that specific inhibition of ERM phosphorylation may be a new therapeutic approach for RA. [ABSTRACT FROM PUBLISHER]

Abstract: Ligand-of-Numb protein X (LNX) was initially characterized as a RING finger type E3 ubiquitin ligase that targeted the intrinsic cell fate determinant Numb for ubiquitination dependent degradation. However, the physiological function of LNX remains largely unknown. In the present study, we demonstrate that ectopic expression of LNX in human proximal tubular epithelial cells (HK-2 cells) significantly enhanced TGF-β1 induced epithelial to mesenchymal transition (EMT). The EMT-promoting effect of LNX manifested as strong inhibition of E-cadherin expression, enhanced expression of vimentin, fibronectin or PAI-1, and increased cell migration. This function of LNX was shown to be independent of its ligase activity because ectopic expression of a mutant form of LNX (C48ALNX) that lacks E3 ligase activity had the similar effect as the wild-type LNX. Overexpression of E-cadherin could inhibit LNX augmented EMT. This study suggests a potential role for LNX in promoting EMT in human proximal tubular epithelial cells. [Copyright &y& Elsevier]

Activation of the 5-lipoxygenase (5-LO) pathway leads to the biosynthesis of proinflammatory leukotriene lipid mediators. Genetic studies have associated 5-LO and its accessory protein, 5-LO-activating protein, with cardiovascular disease, myocardial infarction and stroke. Here we show that 5-LO-positive macrophages localize to the adventitia of diseased mouse and human arteries in areas of neoangiogenesis and that these cells constitute a main component of aortic aneurysms induced by an atherogenic diet containing cholate in mice deficient in apolipoprotein E. 5-LO deficiency markedly attenuates the formation of these aneurysms and is associated with reduced matrix metalloproteinase-2 activity and diminished plasma macrophage inflammatory protein-1α (MIP-1α; also called CCL3), but only minimally affects the formation of lipid-rich lesions. The leukotriene LTD4 strongly stimulates expression of MIP-1α in macrophages and MIP-2 (also called CXCL2) in endothelial cells. These data link the 5-LO pathway to hyperlipidemia-dependent inflammation of the arterial wall and to pathogenesis of aortic aneurysms through a potential chemokine intermediary route. [ABSTRACT FROM AUTHOR]

[Display omitted] • Develop new magnetic nanocomposites material. • The material exhibited a faster adsorption rate and higher adsorption capacity. • Adsorption by cation exchange at low pH and complexation at high pH. Magnetic nanoparticles require a protective coating to enable them to be used to adsorb heavy metals from wastewater, given their oxidation properties and instability in acidic media. Humic acid (HA) has an affinity for magnetic nanoparticles, but its adsorption capacity is low. To improve adsorption capacity, we synthesized a novel adsorbent (HA-O/Fe 3 O 4) through chemical modification and examined its adsorption of Pb (II), Cu (II), Cd (II), and Ni (II) ions. The effects of pH competition, adsorption mechanism, isotherm, kinetics, regeneration, and stability were investigated. The HA-O/Fe 3 O 4 exhibited faster kinetic performance (10 min), conforming to the pseudo-two kinetics equation, and the adsorption isotherm conforms to the Langmuir model with maximum adsorption capacities of 111.10, 76.92, 71.43, and 33.33 mg/g, respectively. The interaction between metal ions and functional groups of the adsorbent was further characterized by Fourier-transform infrared spectroscopy, and the results indicated that adsorption by cation exchange at low pH and complexation at high pH. Additionally, the adsorbent was recycled four times, and the removal rate was not significantly affected. A recycling efficiency of more than 90 % indicates good sustainability and reusability. The stability test shows that the amount of organic matter and heavy metals desorbed by the adsorbent were negligible. Most importantly, at low concentrations, all four metal ions meet the industrial emission standards, and Pb (II) and Cu (II) meet the drinking water standards. [ABSTRACT FROM AUTHOR]

• IPSC-MSCs, which play a key role in immunomodulation. • IPSC-MSCs downregulated the levels of M1 macrophages and upregulated the level of M2 macrophage. • The neuroprotective effects of iPS-MSCs in a rat model of cardiac arrest. Previous in vitro experiments have demonstrated the immunomodulatory functions of mesenchymal stem cells derived from induced pluripotent stem cells (iPSC-MSCs) in brain injury. We have tried to further understand these functions by investigating the neuroprotective effects of iPSC-MSCs in a rat model of cardiac arrest (CA). CA was induced in adult Sprague-Dawley rats by transcutaneous electrical epicardium stimulation. The rats were divided into four groups. In a separate cohort of sham operation animals, iPSC-MSCs or PBS was infused via the femoral vein after restoration of spontaneous circulation. Survival was evaluated every 2 h until 24 h after CA. Markers of classically activated macrophages (M1) and alternatively activated (M2) macrophages were assessed by qPCR and western blot analysis, and the gene expression profiles of the macrophages were studied in order to identify differentially expressed proteins. The 24-h survival rate was significantly different between the CPR group and iPSC-MSC group (P = 0.033). Additionally, a significant number of mRNAs were differentially expressed between the iPSC-MSC and PBS group. Compared with the sham operation group, both M1 (27/29) and M2 (2/29) mRNAs showed a significant increase in expression in the CPR group, while only M2 (22) mRNAs showed a significant increase in expression in the iPSC-MSC group. Western blotting analysis showed that the expression of Arg-1 and CD14 (M2 macrophage markers) was increased in the iPSC-MSC group (P < 0.05), while CD86 and iNOS (M1 macrophage markers) expression was increased in the CPR group (P < 0.05). IPSC-MSCs, which play a key role in immunomodulation, downregulate the level of M1 macrophages and upregulate the level of M2 macrophages after CA. [ABSTRACT FROM AUTHOR]