Severe renal impairment is a common complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and is associated with poor prognosis and shorter survival. It is urgent to ...find effective treatments to improve the prognosis of AAV patients. This study was designed to assess the efficacy and safety of protein A immunoadsorption (PAIA) and therapeutic plasma exchange (TPE) for AAV with severe renal involvement.
A total of 48 AAV patients with renal involvement admitted to the Second Xiangya Hospital from January 2018 to February 2021 were selected. Clinical data, myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), remission at 6 months, and outcomes were evaluated. The primary outcomes of interest were death and renal survival as defined by the occurrence of end-stage renal disease (ESRD).
PAIA was effective in the removal of MPO-ANCA and IgG, and showed superior over TPE in the clearance of MPO-ANCA within 1 month after treatment. After a median follow-up of 14.5 months, PAIA therapy showed an advantage in reducing mortality over TPE. There was no difference in the development of ESRD between the two groups. Multivariate Cox regression analysis indicated that higher serum creatinine (SCr) and lower haemoglobin level were independent risks of ESRD. Age > 60, lower serum albumin (ALB), and failure to achieve remission at 6 months were independent risks of death.
PAIA treatment reduces MPO-ANCA and IgG as well as mortality in AAV patients, and may be beneficial for severe AAV in clinical practice. Higher SCr, lower serum ALB or haemoglobin levels, age > 60, and failure to achieve remission at 6 months independently predict the ESRD or death of AAV patients with severe renal involvement.
KEY MESSAGES
Compared with therapeutic plasma exchange, protein A immunoadsorption treatment eliminates myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and IgG better and reduces mortality in ANCA-associated vasculitis (AAV) patients with severe renal involvement.
Higher serum creatinine, lower serum albumin or haemoglobin levels, age > 60, and failure to achieve remission at 6 months independently predict the end-stage renal disease (ESRD) or death of AAV patients with severe renal involvement.
Abstract To emulate the ordered arrangement of monomer units found in natural macromolecules, single-unit monomer insertion (SUMI) have emerged as a potent technique for synthesizing ...sequence-controlled vinyl polymers. Specifically, numerous applications necessitate vinyl polymers encompassing both radically and cationically polymerizable monomers, posing a formidable challenge due to the distinct thiocarbonylthio end-groups required for efficient control over radical and cationic SUMIs. Herein, we present a breakthrough in the form of interconvertible radical and cationic SUMIs achieved through the manipulation of thiocarbonylthio end-groups. The transition from a trithiocarbonate (for radical SUMI) to a dithiocarbamate (for cationic SUMI) is successfully accomplished via a radical-promoted reaction with bis(thiocarbonyl) disulfide. Conversely, the reverse transformation utilizes the reaction between dithiocarbamate and bistrithiocarbonate disulfide under a cationic mechanism. Employing this strategy, we demonstrate a series of synthetic examples featuring discrete oligomers containing acrylate, maleimide, vinyl ether, and styrene, compositions unattainable through the SUMI of a single mechanism alone.
Microstructures and mechanical properties of a high-strength extruded Mg-3.5Sm-0.6Zn-0.5Zr alloy were thoroughly investigated. The results indicate that the dominant intermetallic phase in both ...as-cast and extruded samples is not the widely reported Mg41Sm5 phase but Mg3Sm phase. After extrusion, the microstructures are composed of fine equiaxed dynamically recrystallized (DRXed) grains, coarse elongated unDRXed grains with ultrafine sub-grains, disintegrated intermetallic particles, and numerous small dynamically precipitated particles. Also, there are amounts of particularly < a + c > dislocations in the Mg matrix after extrusion. Finally, numerous nano-scale plate β′ particles and lamellae β″ particles homogeneously precipitated in the matrix during artificial aging treatments. Therefore, the studied alloy exhibits very high ultimate tensile strength and yield strength, whose maximum values at room temperature are approximately 427MPa and 416MPa, respectively, much greater than most conventional Mg–RE based alloys with comparative or even much higher RE additions.
The personalized recommendation system is a useful tool adopted by e-retailers to help consumers to find items in line with their preferences. Existing methods focus on learning user preferences from ...a user-item matrix or online reviews after purchasing, and they ignore the interactive features in the process of users’ learning about product information through search queries before they make a purchase. To this end, this study develops a topic augmented hypergraph neural network framework to predict the user’s purchase intention by connecting the latent topics embedded in a consumer’s online queries to their click, purchase, and online review behavior, which aims at mining the connection information existing in the interaction graph domain. Meanwhile, in order to reduce the influence of text noise words by fusing topic information, we integrate the topic distribution and convolutional embedding to better represent each user and item, which can make up for the lack of topic information in traditional convolutional neural networks. Extensive empirical evaluations on real-world datasets demonstrate that the proposed framework improves the novelty of recommendation items as well as accuracy. From a managerial perspective, recommending diversified and novel items to consumers may increase the users’ satisfaction, which is conducive to the sustainable development of e-commerce enterprises.
Melamine detection has attracted much attention since the discovery of the damage of melamine to human health. Herein, we have developed a sensitive homogeneous electroanalytical platform for ...melamine detection, which is relied on the formation of triplex molecular beacon integrated with exonuclease III (Exo III)-mediated signal amplification. The formation of triplex molecular beacon was triggered by the recognition and incorporation of melamine to the abasic (AP) site contained in the triplex stem. The stem of the triplex molecular beacon was designed to have a protruding double-strand DNA, which can be recognized and hydrolyzed by Exo III for releasing methylene blue (MB)-labeled mononucleotide. These released MB molecules exhibit high diffusivity toward indium tin oxide electrode with negative charge, thus producing a significantly increased electrochemical response. Taking advantages of the high binding affinity of the DNA triplex structure containing AP sites towards melamine and the unique features of Exo III, this sensing platform is capable for sensitive and selective melamine assay with a detection limit as low as 8.7 nM. Furthermore, this strategy shows good applicability for melamine assay in real samples. Therefore, this strategy broadens the application of triplex DNA and presents a new method for sensitive detection of melamine.
T cells engineered with chimeric antigen receptor （CAR） have been successfully applied to treat advanced refractory B cell malignancy. However, many challenges remain in extending its application ...toward the treatment of solid tumors. The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CART efficacy. One negative regulator of T cell activity is lymphocyte activation gene-3 （LAG-3）. We successfully generated LAG-3 knockout T and CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture. LAG-3 knockout CART cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model, which is comparable to standard CAR-T cells. Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing.
During the processes of primary and secondary endosymbiosis, different microalgae evolved to synthesis different storage polysaccharides. In stramenopiles, the main storage polysaccharides are ...β-1,3-glucan, or laminarin, in vacuoles. Currently, laminarin is gaining considerable attention due to its application in the food, cosmetic and pharmaceuticals industries, and also its importance in global biogeochemical cycles (especially in the ocean carbon cycle). In this review, the structures, composition, contents, and bioactivity of laminarin were summarized in different algae. It was shown that the general features of laminarin are species-dependence. Furthermore, the proposed biosynthesis and catabolism pathways of laminarin, functions of key genes, and diel regulation of laminarin were also depicted and comprehensively discussed for the first time. However, the complete pathways, functions of genes, and diel regulatory mechanisms of laminarin require more biomolecular studies. This review provides more useful information and identifies the knowledge gap regarding the future studies of laminarin and its applications.
Oxidative stress and inflammation are important pathogenic factors of diabetic retinopathy (DR). DR remains the most common ocular complication caused by diabetes mellitus (DM) and is the leading ...cause of visual impairment in working-aged people worldwide. Melatonin has attracted extensive attention due to its potent antioxidant and anti-inflammatory effects. In the present study, melatonin inhibited oxidative stress and inflammation by enhancing the expression and activity of silent information regulator factor 2-related enzyme 1 (Sirt1) both in in vitro and in vivo models of DR, and the Sirt1 inhibitor EX-527 counteracted melatonin-mediated antioxidant and anti-inflammatory effects on Müller cells. Moreover, melatonin enhanced Sirt1 activity through the maternally expressed gene 3 (MEG3)/miR-204 axis, leading to the deacetylation of the Sirt1 target genes forkhead box o1 (Foxo1) and nuclear factor kappa B (NF-κB) subunit p65, eventually contribute to the alleviation of oxidative stress and inflammation. The study revealed that melatonin promotes the Sirt1 pathway, thereby protecting the retina from DM-induced damage.
Auxin response factors (ARFs) play important roles in various plant physiological processes; however, knowledge of the exact role of ARFs in plant responses to water deficit is limited. In this ...study, SlARF4, a member of the ARF family, was functionally characterized under water deficit. Real-time fluorescence quantitative polymerase chain reaction (PCR) and
-glucuronidase (GUS) staining showed that water deficit and abscisic acid (ABA) treatment reduced the expression of
.
was expressed in the vascular bundles and guard cells of tomato stomata. Loss of function of SlARF4 (
) by using Clustered Regularly Interspaced Short Palindromic Repeats/Cas 9 (CRISPR/Cas 9) technology enhanced plant resistance to water stress and rehydration ability. The
mutant plants exhibited curly leaves and a thick stem. Malondialdehyde content was significantly lower in
mutants than in wildtype plants under water stress; furthermore,
mutants showed higher content of antioxidant substances, superoxide dismutase, actual photochemical efficiency of photosystem II (PSII), and catalase activities. Stomatal and vascular bundle morphology was changed in
mutants. We identified 628 differentially expressed genes specifically expressed under water deficit in
mutants; six of these genes, including ABA signaling pathway-related genes, were differentially expressed between the wildtype and
mutants under water deficit and unlimited water supply. Auxin responsive element (AuxRE) elements were found in these genes' promoters indicating that SlARF4 participates in ABA signaling pathways by regulating the expression of
and
, thereby influencing stomatal morphology and vascular bundle development and ultimately improving plant resistance to water deficit.
Apoptosis induced by oxidative stress blocks the recovery of heart function in myocardial ischemia reperfusion injury (MIRI). Peroxiredoxin 1 (Prdx1) inhibits oxidative stress. However, the ...expression and function of Prdx1 in MIRI are unclear. In present study, Prdx1 protein level increased in rat MIRI model, associated with cardiomyocyte apoptosis. Cultured rat embryonic ventricular myocardial H9c2 cells with hypoxia/reoxygenation (H/R) treatment was utilized to mimic MIRI in vitro, showing that H/R treatment increased the ratio of p-p38/p38, p-JNK/JNK and apoptosis index. But Prdx1 ameliorate the up-regulation of p-p38/p38 ratio and p-JNK/JNK ratio, as well as decreased H9c2 cell apoptosis. SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor) inhibited H9c2 cell apoptosis, and at the same time Prdx1 down-regulated the activation of p38 MAPK and JNK during H/R treatment. In addition, a ROS scavenger N-acetyl-l-cysteine (NAC) down-regulated the protein level of p-p38, p-JNK and Prdx1, and H9c2 cell apoptosis. In summary, these findings indicated that Prdx1 inhibited MAPK pathway induced cells apoptosis, and ROS is the upstream regulator of H/R induced apoptosis.
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