Study on the color-changing mechanism and law of visual formaldehyde sensing system based on hyperbranched polyamines.

This study focuses on addressing the limitations associated with most chemical derivatization methods commonly used for formaldehyde detection. These methods often suffer from prolonged derivative times (≥30 min) and complex procedures, which hinder their ability to meet the requirements of real-time and accurate sensing. In this research, a novel formaldehyde indicator system based on hyperbranched polyamine molecule was developed, and its mechanism and principles of color change were investigated. The findings revealed that hyperbranched polyamine molecule effectively reacts with formaldehyde, leading to a reduction in electron cloud density in the amine group N and subsequently causing a decrease in pH value. This reaction enables the visualization of formaldehyde detection through changes in the indicator spectrum. Moreover, the spectral variation pattern exhibits a strong linear correlation with the formaldehyde concentration when the PAMAM concentration is optimized. The detection limit of this method was determined to be 1.8 ppm. Notably, the reaction between PAMAM and formaldehyde is almost instantaneous, the color change is insensitive to temperature, and the method demonstrates high selectivity. Overall, this research contributes to the advancement of real-time formaldehyde monitoring technology and provides insights for future developments in this field.

Damage to the macula associated with LED-derived blue laser exposure: A case report.

BACKGROUND: Light emitting diodes laser is emerging as an important source of light replacing conventional lights. It is widely used for illumination in the bar where young people love to go. But not everyone knows about the light damage to the eye especially to the macula. In this article, we report the case of a macular damage induced by LED-derived blue laser in a bar, studied with optical coherence tomography (OCT) to evaluate the retinal lesion and multifocal electroretinography (mfERG) to evaluate functional damage. CASE PRESENTATION: Four days after the photo injury to the right eye, the visual acuity was 0.5. Funduscopy revealed a round red lesion in the macula of the right eye. Fluorescein angiography (FA) revealed no leakage. OCT revealed a deficiency in the center of the fovea. MfERG revealed a reduction of the peak value in the right eye compared to the left eye. One month later, although the vision was 1.0 in the right eye, OCT revealed a hyporeflectivity of the ellipsoid zone. MfERG still showed a reduction of the peak value in the right eye compared to the left eye. CONCLUSION: We believe that general knowledge about laser injuries to the eye should be realized widely. We also think in cases of macular laser damage, the recovery of vision can not demonstrate the recovery of the function of photoreceptors.

In vivo confocal microscopy of pre-Descemet corneal dystrophy associated with X-linked ichthyosis: a case report.

BACKGROUND: Pre-Descemet corneal dystrophy (PDCD) is characterized by the presence of numerous, tiny, polymorphic opacities immediately anterior to Descemet membrane, which is a rare form of corneal stromal dystrophy and hard to be diagnosed. In vivo confocal microscopy (IVCM) is a useful tool to examine the minimal lesions of the cornea at the cellular level. In this article, we report a rare case of PDCD associated with X-linked ichthyosis and evaluate IVCM findings. CASE PRESENTATION: We present a 34-year-old male Chinese patient with PDCD associated with X-linked ichthyosis. Slit-lamp biomicroscopy showed the presence of tiny and pleomorphic opacities in the posterior stroma immediately anterior to Descemet membrane bilaterally. IVCM revealed regular distributed hyperreflective particles inside the enlarged and activated keratocytes in the posterior stroma. Hyperreflective particles were also observed dispersedly outside the keratocytes in the anterior stroma. Dermatological examination revealed that the skin over the patient's entire body was dry and coarse, with thickening and scaling of the skin in the extensor side of the extremities. PCR results demonstrated that all ten exons and part flanking sequences of STS gene failed to produce any amplicons in the patient. CONCLUSIONS: IVCM is useful for analyzing the living corneal structural changes in rare corneal dystrophies. We first reported the IVCM characteristics of PDCD associated with X-linked ichthyosis, which was caused by a deletion of the steroid sulfatase (STS) gene, confirmed by gene analysis.

The in vitro pharmacology of GS-5759, a novel bifunctional phosphodiesterase 4 inhibitor and long acting ß2-adrenoceptor agonist.

Inhaled long-acting ß(2)-adrenoceptor agonists (LABA) that act as bronchodilators and the oral anti-inflammatory phosphodiesterase 4 (PDE4) inhibitor roflumilast are both approved therapies for chronic obstructive pulmonary disease (COPD). Here we describe the activity of a novel, inhaled, bifunctional, small molecule (R)-6-[(3-{[4-(5-{[2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}pent-1-yn-1-yl)phenyl]carbamoyl}phenyl)sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methylquinoline-3-carboxamide (GS-5759), which has specific ß(2) agonist and PDE4 inhibitory activity. GS-5759 demonstrated potent and full agonist activity at ß(2) adrenoceptors (EC(50) = 8 ± 4 nM) and is a potent inhibitor of the PDE4 enzyme (IC(50) = 5 ± 3 nM). In cell assays, GS-5759 inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNFα) production in human peripheral mononuclear cells (PBMC) with an IC(50) = 0.3 nM [confidence interval (CI) 0.1-0.6] and in human neutrophils formyl-methionyl-leucyl-phenylalanine (fMLP)-induced super oxide anion production with an IC(50) = 3 nM (CI 0.8-8). The addition of the ß(2) antagonist ICI 118551 shifted the IC(50) in these cell assays to 4 and 38 nM, respectively, demonstrating the contribution of both ß(2) agonist and PDE4 inhibitory activity to GS-5759. GS-5759 was also a potent inhibitor of profibrotic and proinflammatory mediator release from human lung fibroblasts. GS-5759 relaxed guinea pig airway smooth muscle strips precontracted with carbachol in a concentration-dependent manner with an EC(50) = 0.5 µM (CI 0.2-2) and had slow dissociation kinetics with an Off T(1/2) > 720 minutes at an EC(80) concentration of 3 µM. GS-5759 is a novel bifunctional molecule with both potent ß(2) agonist and PDE4 inhibitor activity that could provide inhaled bronchodilator and anti-inflammatory therapy for COPD.

Swarm intelligence in bioinformatics: methods and implementations for discovering patterns of multiple sequences.

As a promising and innovative research field, bioinformatics has attracted increasing attention recently. Beneath the enormous number of open problems in this field, one fundamental issue is about the accurate and efficient computational methodology that can deal with tremendous amounts of data. In this paper, we survey some applications of swarm intelligence to discover patterns of multiple sequences. To provide a deep insight, ant colony optimization, particle swarm optimization, artificial bee colony and artificial fish swarm algorithm are selected, and their applications to multiple sequence alignment and motif detecting problem are discussed.

Designing a multistage supply chain in cross-stage reverse logistics environments: application of particle swarm optimization algorithms.

This study designed a cross-stage reverse logistics course for defective products so that damaged products generated in downstream partners can be directly returned to upstream partners throughout the stages of a supply chain for rework and maintenance. To solve this reverse supply chain design problem, an optimal cross-stage reverse logistics mathematical model was developed. In addition, we developed a genetic algorithm (GA) and three particle swarm optimization (PSO) algorithms: the inertia weight method (PSOA_IWM), V(Max) method (PSOA_VMM), and constriction factor method (PSOA_CFM), which we employed to find solutions to support this mathematical model. Finally, a real case and five simulative cases with different scopes were used to compare the execution times, convergence times, and objective function values of the four algorithms used to validate the model proposed in this study. Regarding system execution time, the GA consumed more time than the other three PSOs did. Regarding objective function value, the GA, PSOA_IWM, and PSOA_CFM could obtain a lower convergence value than PSOA_VMM could. Finally, PSOA_IWM demonstrated a faster convergence speed than PSOA_VMM, PSOA_CFM, and the GA did.

Hybrid algorithms for fuzzy reverse supply chain network design.

In consideration of capacity constraints, fuzzy defect ratio, and fuzzy transport loss ratio, this paper attempted to establish an optimized decision model for production planning and distribution of a multiphase, multiproduct reverse supply chain, which addresses defects returned to original manufacturers, and in addition, develops hybrid algorithms such as Particle Swarm Optimization-Genetic Algorithm (PSO-GA), Genetic Algorithm-Simulated Annealing (GA-SA), and Particle Swarm Optimization-Simulated Annealing (PSO-SA) for solving the optimized model. During a case study of a multi-phase, multi-product reverse supply chain network, this paper explained the suitability of the optimized decision model and the applicability of the algorithms. Finally, the hybrid algorithms showed excellent solving capability when compared with original GA and PSO methods.

Heterogeneous differential evolution for numerical optimization.

Differential evolution (DE) is a population-based stochastic search algorithm which has shown a good performance in solving many benchmarks and real-world optimization problems. Individuals in the standard DE, and most of its modifications, exhibit the same search characteristics because of the use of the same DE scheme. This paper proposes a simple and effective heterogeneous DE (HDE) to balance exploration and exploitation. In HDE, individuals are allowed to follow different search behaviors randomly selected from a DE scheme pool. Experiments are conducted on a comprehensive set of benchmark functions, including classical problems and shifted large-scale problems. The results show that heterogeneous DE achieves promising performance on a majority of the test problems.

Trilobatin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice via the NF-κB pathway and alterations in gut microbiota.

OBJECTIVE: This study aimed to evaluate the effects of trilobatin (TLB) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and further explore the underlying mechanisms from the perspectives of signaling pathway and gut microbiota. METHODS: A mouse model of UC was established using DSS. Trilobatin was administered via oral gavage. Disease severity was assessed based on body weight, disease activity index (DAI), colon length, histological detection, inflammation markers, and colonic mucosal barrier damage. Alternations in the NF-κB and PI3K/Akt pathways were detected by marker proteins. High-throughput 16S rRNA sequencing was performed to investigate the gut microbiota of mice. RESULTS: In the DSS-induced UC mice, TLB (30 µg/g) treatment significantly increased the body weight, reduced the DAI score, alleviated colon length shortening, improved histopathological changes in colon tissue, inhibited the secretion and expression of inflammation factors (TNF-α, IL-1ß, and IL-6), and increased the expression of tight-junction proteins (ZO-1 and occludin). Furthermore, TLB (30 µg/g) treatment significantly suppressed the activation of NF-κB pathway and altered the composition and diversity of the gut microbiota, as observed in the variations of the relative abundances of Proteobacteria, Actinobacteriota, and Bacteroidota, in UC mice. CONCLUSION: TLB effectively alleviates DSS-induced UC in mice. Regulation of the NF-κB pathway and gut microbiota contributes to TLB-mediated therapeutic effects. Our study not only identified a novel drug candidate for the treatment of UC, but also enhanced our understanding of the biological functions of TLB.

An application of AHP and fuzzy entropy-TOPSIS methods to optimize upstream petroleum investment in representative African basins.

The growing demand of China for petroleum heightens the complexities and prospects in worldwide investments, necessitating refined and strategic investment approaches. Evaluating the potential of different hydrocarbon-potential areas needs more comprehensive scientific evaluation models. This study aims to establish a Comprehensive Investment Potential of Petroleum (CIPP) framework for targeted sedimentary basins by using an integrated approach that combines the Analytic Hierarchy Process (AHP) and the Entropy-Weighted Fuzzy TOPSIS models. We focus particularly on representative African basins to inform strategic decision-making for the Chinese overseas petroleum enterprises. We firstly interpret the geological condition of these petroleum basins by researching multiple databases and proprietary research data. Then, we use a combined approach of ranking-classification-correlation analysis to evaluate 17 representative basins, taking into account both overall and individual key performance indicators. Our findings suggest the Illizi Basin and the Offshore Côte d'Ivoire Basin could be the most favorable for investment and development. Those like Southwest African Basin warrant cautious consideration. The new evaluation model and computational workflow offer an effective workflow for assessing multiple petroleum basins. This work provides not just practical investment strategies for companies aiming for African petroleum basins, but also a transferable methodology for optimizing investment decisions.

A survey on federated learning: challenges and applications.

Federated learning (FL) is a secure distributed machine learning paradigm that addresses the issue of data silos in building a joint model. Its unique distributed training mode and the advantages of security aggregation mechanism are very suitable for various practical applications with strict privacy requirements. However, with the deployment of FL mode into practical application, some bottlenecks appear in the FL training process, which affects the performance and efficiency of the FL model in practical applications. Therefore, more researchers have paid attention to the challenges of FL and sought for various effective research methods to solve these current bottlenecks. And various research achievements of FL have been made to promote the intelligent development of all application areas with privacy restriction. This paper systematically introduces the current researches in FL from five aspects: the basics knowledge of FL, privacy and security protection mechanisms in FL, communication overhead challenges and heterogeneity problems of FL. Furthermore, we make a comprehensive summary of the research in practical applications and prospect the future research directions of FL.

Consistency and adversarial semi-supervised learning for medical image segmentation.

Medical image segmentation based on deep learning has made enormous progress in recent years. However, the performance of existing methods generally heavily relies on a large amount of labeled data, which are commonly expensive and time-consuming to obtain. To settle above issue, in this paper, a novel semi-supervised medical image segmentation method is proposed, in which the adversarial training mechanism and the collaborative consistency learning strategy are introduced into the mean teacher model. With the adversarial training mechanism, the discriminator can generate confidence maps for unlabeled data, such that more reliable supervised information for the student network is exploited. In the process of adversarial training, we further propose a collaborative consistency learning strategy by which the auxiliary discriminator can assist the primary discriminator in achieving supervised information with higher quality. We extensively evaluate our method on three representative yet challenging medical image segmentation tasks: (1) skin lesion segmentation from dermoscopy images in the International Skin Imaging Collaboration (ISIC) 2017 dataset; (2) optic cup and optic disk (OC/OD) segmentation from fundus images in the Retinal Fundus Glaucoma Challenge (REFUGE) dataset; and (3) tumor segmentation from lower-grade glioma (LGG) tumors images. The experimental results validate the superiority and effectiveness of our proposal when compared with the state-of-the-art semi-supervised medical image segmentation methods.

Ellagic acid inhibits cell proliferation, migration, and invasion of anaplastic thyroid cancer cells via the Wnt/ß-catenin and PI3K/Akt pathways.

Anaplastic thyroid cancer (ATC) is a rare but lethal human malignant cancer with no known cure. Ellagic acid (EA), a natural plant extract, has shown antitumor activity against multiple cancers; however, its effects on the malignant phenotypes of ATC cells remain unknown. This study aimed to evaluate the effects of EA on proliferation, migration, and invasion of ATC cells and further explore the associated signaling mechanisms. The normal human thyroid cell line Nthy-ori3-1 and ATC cell line BHT-101 were used. Cytotoxicity assay was performed using the Cell Counting kit-8 (CCK-8) assay. Cell proliferation, migration, and invasion assays were performed using the CCK-8 and colony formation, wound healing, and Transwell invasion assays, respectively. Western blotting was used to detect the levels of related proteins. ß-catenin nuclear protein levels were measured to evaluate the Wnt/ß-catenin pathway. The phosphorylation level of the Akt protein was measured and calculated to evaluate the PI3K/Akt pathway. LiCl and IGF-1 were used as pathway agonists to determine the involvement of the corresponding pathway. The results showed that EA inhibited the proliferation, migration, and invasion of ATC cells. Furthermore, both the Wnt/ß-catenin and PI3K/Akt pathways were suppressed by EA treatment, and activation of these two pathways reversed the EA-induced inhibition of the pathological phenotypes of ATC cells. These findings demonstrate that EA inhibits proliferation, migration, and invasion of ATC cells by suppressing the Wnt/ß-catenin and PI3K/Akt pathways, suggesting that EA is a potential drug candidate for treating ATC and provides a theoretical basis for further in vivo experiments and clinical applications.

Impacts of air pollution and meteorological conditions on dry eye disease among residents in a northeastern Chinese metropolis: a six-year crossover study in a cold region.

The purpose of this study is to explore the associations among dry eye disease (DED), air pollution, and meteorological conditions in the cold region of a northeastern Chinese metropolis (i.e., Changchun). Data on ambient air pollutants and meteorological parameters as well as diagnosed DED outpatients during 2015-2021 were collected. The associations between DED and environmental factors were analysed at multiple time scales using various statistical methods (i.e., correlation, regression and machine learning). Among the 10,809 DED patients (21,617 eyes) studied, 64.60% were female and 35.40% were male. A higher frequency of DED was observed in March and April, followed by January, August and October. Individual and multiple factor models showed the positive importance of particles with aerodynamic diameters <10 µm (PM10), carbon monoxide (CO), and ozone (O3) among normal air pollutants and air pressure (AP), air temperature (AT) and wind speed (WS) among normal meteorological parameters. Air pollutants (PM10, nitrogen dioxide: NO2) and meteorological parameters (AT, AP) have combined impacts on DED occurrence. For the first time, we further explored the associations of detailed components of atmospheric particles and DED, suggesting potential emission sources, including spring dust from bare soil and roads and precursor pollutants of summer O3 formation from vehicles and industry in Northeast China. Our results revealed the quantitative associations among air pollutants, meteorological conditions and DED outpatients in cold regions, highlighting the importance of coordinated policies in air pollution control and climate change mitigation.

Evaluation and management of systemic corticosteroids-induced ocular hypertension in children with non-Hodgkin lymphoma.

Purpose: To investigate the effect of systemic corticosteroids (CSs) on ocular hypertension (OHT) and to evaluate the management of OHT in children with non-Hodgkin lymphoma (NHL). Methods: Medical records of children with NHL treated in our institution between October 2016 and October 2019 were reviewed. The enrolled patients were divided into the mature B-cell lymphoma (MBL) group and lymphoblastic lymphoma (LBL) group based on pathology. Data on routine ophthalmic examinations and management of OHT were recorded. Results: Of the 54 recruited patients, 38 patients (70.4%) had LBL, and 16 (29.6%) had MBL. Thirty-one patients (57.4%) developed OHT, 24 patients (77.4%) in the LBL group, and 7 (22.6%) in the MBL group. Twelve patients (38.7%) were identified as high responders (10 with LBL and 2 with MBL). Symptomatic patients had a higher mean peak IOP than asymptomatic patients (p=0.006). A total of 74.2% of OHT was controlled with antiglaucoma medications (100% in the MBL group vs. 66.7% in the LBL group, significant variation, p < 0.001). In total, 8 patients (25.8%) underwent tapering of the CSs dose. The duration of OHT was shorter in the MBL group than in the LBL group (p = 0.003). No patients were found to have glaucomatous damage or cataracts. Conclusions: Patients receiving systemic CSs had a higher risk of developing OHT, but the pattern of CSs administration might be a critical factor in the risk and severity of OHT. Tapering of CSs dose should be considered the first line for the management of OHT during high-dose CSs therapy.

Corrigendum: Evaluation and management of systemic corticosteroids-induced ocular hypertension in children with non-Hodgkin lymphoma.

[This corrects the article DOI: 10.3389/fped.2022.982224.].

Enhanced efficacy of recombinant FVIII in noncovalent complex with PEGylated liposome in hemophilia A mice.

Recombinant FVIII formulated in PEG-ylated liposomes (rFVIII-PEG-Lip) was reported to increase the bleed-free days from 7 to 13 days (at 35 IU/kg rFVIII) in severe hemophilia A patients. To understand the underlying mechanism, we sought to recapitulate its efficacy in hemophilia A mice. Animals treated with rFVIII-PEG-Lip achieved approximately 30% higher survival relative to rFVIII after tail vein transection inflicted 24 hours after dosing. The efficacy of rFVIII-PEG-Lip represents an approximately 2.5-fold higher "apparent" FVIII activity, which is not accounted for by its modestly increased (13%) half-life. The enhanced efficacy requires complex formation between rFVIII and PEG-Lip before the administration. Furthermore, PEG-Lip associates with the majority of platelets and monocytes in vivo, and results in increased P-selectin surface expression on platelets in response to collagen. Rotational thromboelastometry (ROTEM) analysis of whole blood from rFVIII-PEG-Lip-treated animals at 5 minutes up to 72 hours after dosing recapitulated the 2- to 3-fold higher apparent FVIII activity. The enhanced procoagulant activity is fully retained in plasma unless microparticles are removed by ultracentrifugation. Taken together, the efficacy of rFVIII-PEG-Lip is mediated mainly by its sensitization of platelets and the generation of procoagulant microparticles that may express sustained high-affinity receptors for FVIII.

Upregulated neuregulin-1 protects against optic nerve injury by regulating the RhoA/cofilin/F-actin axis.

OBJECTIVE: In recent years, the roles of Neuregulin-1 (NRG-1) in optic nerve injury and retinal cells have been investigated. However, the molecular mechanism by which NRG-1 affects optic nerve injury remains elusive and merits deeper exploration. Hence, this study examined the specific function of NRG-1 in the RhoA/cofilin/F-actin axis in optic nerve injury. METHODS: Retinal cells were isolated and identified for subsequent experimental uses. Reverse transcription quantitative polymerase chain reaction and Western blot assays were performed to measure NRG-1 expression in retinal cells which were cultured under elevated pressure. TUNEL staining was used to detect the cell apoptosis rate, and Western blot assay was performed to detect the expression of related genes. The axon growth was examined by immunofluorescence. The effects of NRG-1 on RhoA activity, cofilin phosphorylation, and F-actin were detected by Western blot assay. In other studies we established a rat model of acute optic nerve injury, and tested for beneficial effects of NRG-1 in vivo. RESULTS: High expression of NRG-1 was evident in the retinal tissues of rats with optic nerve injury. Overexpressing NRG-1 successfully inhibited RhoA activity and the phosphorylation of cofilin and promoted F-actin expression. In cell experiments, overexpressed NRG-1 suppressed the apoptosis of retinal cells and promoted axon growth through the RhoA/cofilin/F-actin axis. In animal experiments, overexpressed NRG-1 relieved retinal injury. CONCLUSION: Our results strongly suggest that overexpressed NRG-1 is highly effective in the protection of normal optic nerve function by suppressing RhoA activity and the phosphorylation of cofilin and rescuing F-actin function.

Prospective study of clinical characteristics of melanoma patients with retinopathy caused by a high-dose interferon α-2b.

Retinopathy is a rare side effect of interferon α-2b treatment. The goal of this study was to prospectively investigate the clinical characteristics of Chinese patients with melanomas who developed retinopathy following high doses of interferon α-2b (HD-IFN) therapy. The study included 56 melanoma stage I-III patients that were treated with HD-IFN. Fourty-three patients developed HD-IFN-induced retinopathies. Forty-three melanoma patients (76%) developed retinopathy after being treated with HD-IFN. Among these patients, 49% had cotton-wool spots, 19% had retinal hemorrhage, and 30% had retinal hemorrhage. The median time of occurrence of retinopathy was 4 weeks after treatment, and the median time of duration was 4 weeks. No patient showed other symptoms except one who had blurred vision. A comparison of clinical characteristics (age, gender, primary site, stage, and ulceration) and laboratory examinations (white blood cell and platelet counts, hemoglobin, serum lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, triiodothyronine, thyroxine, thyroid-stimulating hormone, and lipid) between the HD-IFN-induced retinopathy patients and nonretinopathy patients did not show any significant differences (P > 0.05). Although all patients that developed retinopathy had diabetes or hypertension, an equal percentage of patients were without retinopathy had diabetes or hypertension. HD-IFN therapy in patients with melanomas may induce mild retinopathy. Our results; however, do not necessarily suggest to discontinue the HD-IFN treatment because retinopathy is a reversible disorder.

Characterization of the mechanism of action of lanraplenib, a novel spleen tyrosine kinase inhibitor, in models of lupus nephritis.

BACKGROUND: B cells are critical mediators of systemic lupus erythematosus (SLE) and lupus nephritis (LN), and antinuclear antibodies can be found in the serum of approximately 98% of patients with SLE. Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase that mediates signaling from immunoreceptors, including the B cell receptor. Active, phosphorylated SYK has been observed in tissues from patients with SLE or cutaneous lupus erythematosus, and its inhibition is hypothesized to ameliorate disease pathogenesis. We sought to evaluate the efficacy and characterize the mechanism of action of lanraplenib, a selective oral SYK inhibitor, in the New Zealand black/white (NZB/W) murine model of SLE and LN. METHODS: Lanraplenib was evaluated for inhibition of primary human B cell functions in vitro. Furthermore, the effect of SYK inhibition on ameliorating LN-like disease in vivo was determined by treating NZB/W mice with lanraplenib, cyclophosphamide, or a vehicle control. Glomerulopathy and immunoglobulin G (IgG) deposition were quantified in kidneys. The concentration of proinflammatory cytokines was measured in serum. Splenocytes were analyzed by flow cytometry for B cell maturation and T cell memory maturation, and the presence of T follicular helper and dendritic cells. RESULTS: In human B cells in vitro, lanraplenib inhibited B cell activating factor-mediated survival as well as activation, maturation, and immunoglobulin M production. Treatment of NZB/W mice with lanraplenib improved overall survival, prevented the development of proteinuria, and reduced blood urea nitrogen concentrations. Kidney morphology was significantly preserved by treatment with lanraplenib as measured by glomerular diameter, protein cast severity, interstitial inflammation, vasculitis, and frequency of glomerular crescents; treatment with lanraplenib reduced glomerular IgG deposition. Mice treated with lanraplenib had reduced concentrations of serum proinflammatory cytokines. Lanraplenib blocked disease-driven B cell maturation and T cell memory maturation in the spleen. CONCLUSIONS: Lanraplenib blocked the progression of LN-like disease in NZB/W mice. Human in vitro and murine in vivo data suggest that lanraplenib may be efficacious in preventing disease progression in patients with LN at least in part by inhibiting B cell maturation. These data provide additional rationale for the use of lanraplenib in the treatment of SLE and LN.