Clinicopathological characteristics and outcomes of PLA2R related idiopathic membranous nephropathy in patients with seronegative PLA2R antibodies

Idiopathic membranous nephropathy (IMN) with deposits of phospholipase A2 receptor (PLA2R) antigen in glomerular tissue (GAg+) but no circulating serum PLA2R antibody (SAb−) has been reported. However, little is known about the clinicopathological characteristics and prognosis of this subtype. A total of 74 IMN patients with GAg + identified by kidney biopsy were enrolled in this study. We categorized patients into two groups based on the presence or absence of serum PLA2R antibody. Data on clinical features, pathological features, and outcomes were collected. Kaplan–Meier analysis of complete remission (CR) and partial remission (PR) comparing SAb−/GAg + and SAb+/GAg + patients. Cox proportional hazards models was used to examine factors associated with CR and PR. Among 74 IMN patients, 14 were SAb−/GAg+. Compared with SAb+/GAg + patients, SAb−/GAg + patients presented with higher levels of albumin, lower levels of cholesterol and low density lipoprotein cholesterol (all p p = .01) and high cholesterol (1.81 [95%CI: 1.02–3.19], p = .04) were correlated with seropositivity of PLA2R antibody. SAb−/GAg + patients exhibited a significantly higher probability of CR (p = .03) than patients who were SAb+/GAg+. However, no difference was found in the PR rate. Cox regression analyses showed that compared to SAb+/GAg + patients, SAb−/GAg + was more predictive of complete remission (4.28 [95%CI: 1.01–18.17], p = .04). IMN with PLA2R staining on kidney biopsy but without serum PLA2R antibody has milder clinical manifestations and a better prognosis.</p

Locations of microinjection sites.

<p>A: Schematic drawing at a level of 2 mm rostral to the obex. Microinjection sites were indicated with ★. Control injection sites were indicated by ◆. B: A representative photomicrograph showing the actual injection site marked with a lesion (arrow).</p

Phosphotyrosine and GluR1 immunopositive neurons in VRC/NA.

<p>Photomicrographs showing that the phosphotyrosine immunopositive neurons (FITC, green) were also immunopositive to GluR1 (cy3, red). Arrows indicated the double-labeled neurons. Scale bar, 10μm.</p

Effects of microinjection of different drugs into VRC/NA on hypoxic respiratory response.

<p>A-C: Hypoxic respiratory response (the increases of ∫Phr and <i>f</i> during hypoxia test) was decreased after microinjection of genistein (A, n = 10) or CNQX (B, n = 10), but not after daidzein (C, n = 6). D-E: CNQX and/or genistein, when microinjected together or one after another, did not cause stronger suppression of hypoxic respiratory response than when microinjected alone.</p

Effects of microinjections of genistein and CNQX at VRC/NA on hypoxic respiratory response.

<p>Effects of microinjections of genistein and CNQX at VRC/NA on hypoxic respiratory response.</p

Entropy-Driven Pattern Formation of Hybrid Vesicular Assemblies Made from Molecular and Nanoparticle Amphiphiles

Although an analogy has been drawn between them, organic molecular amphiphiles (MAMs) and inorganic nanoparticle (NP) amphiphiles (NPAMs) are significantly different in dimension, geometry, and composition as well as their assembly behavior. Their concurrent assembly can synergetically combine the inherent properties of both building blocks, thus leading to new hybrid materials with increasing complexity and functionality. Here we present a new strategy to fabricate hybrid vesicles with well-defined shape, morphology, and surface pattern by coassembling MAMs of block copolymers (BCPs) and NPAMs comprising inorganic NPs tethered with amphiphilic BCPs. The assembly of binary mixtures generated unique hybrid Janus-like vesicles with different shapes, patchy vesicles, and heterogeneous vesicles. Our experimental and computational studies indicate that the different nanostructures arise from the delicate interplay between the dimension mismatch of the two types of amphiphiles, the entanglement of polymer chains, and the mobility of NPAMs. In addition, the entropic attraction between NPAMs plays a dominant role in controlling the lateral phase separation of the two types of amphiphiles in the membranes. The ability to utilize multiple distinct amphiphiles to construct discrete assemblies represents a promising step in the self-assembly of structurally complex functional materials

Image_2_ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model.tif

AimWe evaluated a novel treatment for obesity-related renal, an ATP-citrate lyase (ACL) inhibitor, to attenuate ectopic lipid accumulation (ELA) in the kidney and the ensuing inflammation.Materials and methodsAn ACL inhibitor was administered intragastrically to 12-week-old db/db mice for 30 days. The appearance of ELA was observed by staining kidney sections with Oil Red O, and the differences in tissue lipid metabolites were assessed by mass spectrometry. The anti-obesity and renoprotection effects of ACL inhibitors were observed by histological examination and multiple biochemical assays.ResultsUsing the AutoDock Vina application, we determined that among the four known ACL inhibitors (SB-204990, ETC-1002, NDI-091143, and BMS-303141), BMS-303141 had the highest affinity for ACL and reduced ACL expression in the kidneys of db/db mice. We reported that BMS-303141 administration could decrease the levels of serum lipid and renal lipogenic enzymes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), HMG-CoA reductase (HMGCR), and diminish renal ELA in db/db mice. In addition, we found that reducing ELA improved renal injuries, inflammation, and tubulointerstitial fibrosis.ConclusionACL inhibitor BMS-303141 protects against obesity-related renal injuries.</p

Jahn–Teller Effect on Framework Flexibility of Hybrid Organic–Inorganic Perovskites

Here we study the Jahn–Teller (JT) effect on framework flexibility of two analogous hybrid organic–inorganic perovskites, [C­(NH₂)₃]­[Zn­(HCOO)₃] (1-Zn) and [C­(NH₂)₃]­[Cu­(HCOO)₃] (2-Cu). Single-crystal nanoindentation measurements show that the elastic moduli and hardnesses of 1-Zn are up to ∼52.0% and ∼25.0% greater than those of the JT active 2-Cu. Temperature-dependent X-ray diffraction measurements indicate that the thermal expansion along the <i>b-</i>axis is switched from negative to positive by replacing Zn²⁺ with Cu²⁺ on the B-site. These stark distinctions in framework flexibility are primarily attributed to the ∼10.0% elongation of Cu–O bonds induced by the JT effect and associated alterations in octahedral tilting and hydrogen-bonding. Our results demonstrate the prominence of the JT effect in the emerging hybrid perovskites and highlight the possibilities of tuning materials’ properties using orbital order

Table_1_ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model.docx

AimWe evaluated a novel treatment for obesity-related renal, an ATP-citrate lyase (ACL) inhibitor, to attenuate ectopic lipid accumulation (ELA) in the kidney and the ensuing inflammation.Materials and methodsAn ACL inhibitor was administered intragastrically to 12-week-old db/db mice for 30 days. The appearance of ELA was observed by staining kidney sections with Oil Red O, and the differences in tissue lipid metabolites were assessed by mass spectrometry. The anti-obesity and renoprotection effects of ACL inhibitors were observed by histological examination and multiple biochemical assays.ResultsUsing the AutoDock Vina application, we determined that among the four known ACL inhibitors (SB-204990, ETC-1002, NDI-091143, and BMS-303141), BMS-303141 had the highest affinity for ACL and reduced ACL expression in the kidneys of db/db mice. We reported that BMS-303141 administration could decrease the levels of serum lipid and renal lipogenic enzymes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), HMG-CoA reductase (HMGCR), and diminish renal ELA in db/db mice. In addition, we found that reducing ELA improved renal injuries, inflammation, and tubulointerstitial fibrosis.ConclusionACL inhibitor BMS-303141 protects against obesity-related renal injuries.</p

DHA inhibits the CER production increased by LPS and PA.

<p>A. Diagram for CER de novo synthesis and sphingomyelin hydrolysis pathways. SPT, serine palmitoyltransferase; CerS, ceramide synthase; SMase, sphingomyelinase. B and C. LPS and PA synergistically stimulate total (B) and dhC16-CER production (C). RAW264.7 macrophages were treated with 100 μM of OA, DHA or PA in the absence or presence of 1 ng/ml of LPS for 12 h. After treatment, total and dhC16-CER were quantified using lipidomics. + vs. *, <i>p</i><0.01; # vs. +, <i>p</i><0.01. D-F. Either DHA or OA inhibited PA- or LPS plus PA-stimulated CER production. RAW264.7 macrophages were treated with 1 ng/ml LPS, 100 μM PA or both LPS and PA in the absence or presence of 100 μM DHA or OA for 12 h. After treatment, total CER (D), C16-CER (E) and dhC16-CER (F) were quantified using lipidomics. + vs. *, <i>p</i><0.01; # vs. +, <i>p</i><0.01; ++ vs. +, <i>p</i><0.01; ## vs. #, <i>p</i><0.01. G. DHA inhibits SPT1 mRNA expression stimulated by LPS and PA. RAW264.7 macrophages were treated with 1 ng/ml LPS, 100 μM PA or both LPS and PA in the absence or presence of 100 μM of DHA for 12 h. After treatment, SPT1 mRNA was quantified using real-time PCR. * vs. +, <i>p</i><0.05; * vs. #, <i>p</i><0.05; * vs. ^, <i>p</i><0.05; ^^ vs. ^, <i>p</i><0.01.</p