Accumulating evidence indicates that cell death triggers sterile inflammation and that impaired clearance of dead cells causes nonresolving inflammation; however, the underlying mechanisms are still unclear. Here, we show that macrophage-inducible C-type lectin (Mincle) senses renal tubular cell death to induce sustained inflammation after acute kidney injury in mice. Mincle-deficient mice were protected against tissue damage and subsequent atrophy of the kidney after ischemia–reperfusion injury. Using lipophilic extract from the injured kidney, we identified β-glucosylceramide as an endogenous Mincle ligand. Notably, free cholesterol markedly enhanced the agonistic effect of β-glucosylceramide on Mincle. Moreover, β-glucosylceramide and free cholesterol accumulated in dead renal tubules in proximity to Mincle-expressing macrophages, where Mincle was supposed to inhibit clearance of dead cells and increase proinflammatory cytokine production. This study demonstrates that β-glucosylceramide in combination with free cholesterol acts on Mincle as an endogenous ligand to induce cell death–triggered, sustained inflammation after acute kidney injury.

Key Points: IgA nephropathy often requires KRT. Mesenchymal stem cells offer clinical benefits. Adipose-derived mesenchymal stem cells are safe and tolerable. Background: IgA nephropathy (IgAN) often requires KRT because of its refractoriness and because corticosteroids pose infection risks. However, mesenchymal stem cells offer clinical benefits because of their regenerative and immunomodulatory properties. This prospective clinical trial assessed the safety and tolerability of adipose-derived mesenchymal stem cell (ASC) therapy and evaluated its therapeutic efficacy. Methods: This phase 1 study included adult patients with refractory IgAN that was difficult to treat with traditional therapies. ASC therapy comprising one intravenous dose of 1×10⁸ cells was administered to three to six patients in Cohort 1. The same intravenous dose was administered twice with a 2-week interval to six patients in Cohort 2. Heparin was administered simultaneously. This study continued for 52 weeks, and the primary end points were safety and tolerability during the 6-week period after treatment administration. Secondary end points included adverse events and efficacy measures such as clinical remission, partial remission, urine protein remission, hematuria remission, time to remission, changes in the urine protein and hematuria levels, and changes in the eGFR. Results: The three patients in Cohort 1 and six patients in Cohort 2 who received ASC therapy achieved the primary end points. No severe adverse clinical events were observed. Therefore, the safety and tolerability of ASCs were confirmed. Improvements, such as significantly decreased kidney damage markers and urinary protein levels, were observed immediately after ASC administration. Conclusions: The safety and tolerability of ASCs are acceptable for patients with IgAN. Clinical Trial registry name and registration number: This trial was registered with the Japan Registry of Clinical Trials (jRCT2043200002; registration date: April 14, 2020) and ClinicalTrials.gov (NCT04342325; registration date: April 13, 2020).

Post-renal-transplant patients have a relatively low antibody-acquisition rate following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. In this study, antibody titers were measured 5–6 months and 3 weeks to 3 months after the second and third SARS-CoV-2 mRNA vaccinations, respectively. Post-renal-transplant patients visiting our hospital who had received three SARS-CoV-2 mRNA vaccine doses were included in the study. SARS-CoV-2 immunoglobulin G antibody titers were measured three times: between 3 weeks and 3 months after the second vaccination, 5–6 months after the second vaccination, and between 3 weeks and 3 months after the third vaccination. A total of 62 (40 men and 22 women) were included, 44 of whom (71.0%) were antibody positive after their third vaccination. On comparing the antibody-acquired and antibody-non-acquired groups, body mass index (BMI, odds ratio [OR]: 1.44, 95% confidence interval [CI]: 1.07–1.93, p < 0.05) and the estimated glomerular filtration rate (eGFR, OR: 1.14, 95% CI: 1.06–1.24, p < 0.01) were associated with antibody acquisition. Therefore, in Japanese post-kidney-transplant patients, increases in the antibody-acquisition rate and absolute antibody titer after the third vaccination were observed, with BMI and eGFR associated with the antibody-acquisition rate.

Artificial Intelligence (AI)-driven material design has been attracting great attentions as a groundbreaking technology across a wide spectrum of industries. Molecular design is particularly important owing to its broad application domains and boundless creativity attributed to progresses in generative models. The recent maturity of molecular generative models has stimulated expectations for practical use among potential users, who are not necessarily familiar with coding or scripting, such as experimental engineers and students in chemical domains. However, most of the existing molecular generative models are Python libraries on GitHub, that are accessible for only IT-savvy users. To fill this gap, we newly developed a graphical user interface (GUI)-based web application of molecular generative models, Molecule Generation Experience, that is open to the general public. This is the first web application of molecular generative models enabling users to work with built-in datasets to carry out molecular design. In this paper, we describe the background technology extended from our previous work. Our new online evaluation and structural filtering algorithms significantly improved the generation speed by 30 to 1,000 times with a wider structural variety, satisfying chemical stability and synthetic reality. We also describe in detail our Kubernetes-based scalable cloud architecture and user-oriented GUI that are necessary components to achieve a public service. Finally, we present actual use cases in industrial research to design new photoacid generators (PAGs) as well as release cases in educational events.