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Background Signal transducer and activator of transcription 3 (STAT3), a multifaceted transcription factor, modulates host immune responses by activating cellular response to signaling ligands. STAT3 has a pivotal role in the pathophysiology of kidney injury by counterbalancing resident macrophage phenotypes under inflammation conditions. However, STAT3’s role in acute kidney injury (AKI), particularly in macrophage migration, and in chronic kidney disease (CKD) through fibrosis development, remains unclear. Methods Stattic (a JAK2/STAT3 inhibitor, 5 mg/kg or 10 mg/kg) was administered to evaluate the therapeutic effect on LPS-induced AKI (L-AKI) and LPS-induced CKD (L-CKD), with animals sacrificed 6–24 h and 14 days post-LPS induction, respectively. The immune mechanisms of STAT3 blockade were determined by comparing the macrophage phenotypes and correlated with renal function parameters. Also, the transcriptomic analysis was used to confirm the anti-inflammatory effect of L-AKI, and the anti-fibrotic role was further evaluated in the L-CKD model. Results In the L-AKI model, sequential increases in BUN and blood creatinine levels were time-dependent, with a marked elevation of 0–6 h after LPS injection. Notably, two newly identified macrophage subpopulations (CD11b high F4/80 low and CD11b low F4/80 high ), exhibited population changes, with an increase in the CD11b high F4/80 low population and a decrease in the CD11b low F4/80 high macrophages. Corresponding to the FACS results, the tubular injury score, NGAL, F4/80, and p-STAT3 expression in the tubular regions were elevated. STAT3 inhibitor injection in L-AKI and L-CKD mice reduced renal injury and fibrosis. M2-type subpopulation with CD206 in CD11b low F4/80 high population increased in the Stattic-treated group compared with that in the LPS-alone group in the L-AKI model. Additionally, STAT3 inhibitor reduced inflammation driven by LPS-stimulated macrophages and epithelial cells injury in the co-culture system. Transcriptomic profiling identified 3 common genes in the JAK-STAT, TLR, and TNF signaling pathways and 11 common genes in the LPS with macrophage response. The PI3K-AKT ( IL-6 , Akt3 , and Pik3r1 ) and JAK-STAT pathways were determined as potential Stattic targets. Further confirmation through mRNA and protein expressions analyses showed that Stattic treatment reduced inflammation in the L-AKI and fibrosis in the L-CKD mice. Conclusions STAT3 blockade effectively mitigated inflammation by retrieving the CD11b low F4/80 high population, further emphasizing the role of STAT3-associated macrophage-driven inflammation in kidney injury. Plain English summary This study investigated the role of STAT3 in LPS-induced acute kidney injury (AKI) and its prolonged pathophysiological effect. In a mouse model, blocking STAT3 with Stattic reduced inflammation and fibrosis, decreased the levels of inflammatory and extracellular matrix (ECM) substances, reduced the number of certain immune cells (macrophages), and influenced specific genes related to inflammation. The findings suggest that targeting STAT3 is a promising approach to treat AKI and CKD by controlling the inflammation and the immune response as well as ECM accumulation. This study provides novel insights into AKI and CKD progression and will facilitate the development of new treatments for kidney injuries at various stages.

We developed and designed a bifacial four-terminal perovskite (PVK)/crystalline silicon (c-Si) heterojunction (HJ) tandem solar cell configuration albedo reflection in which the c-Si HJ bottom sub-cell absorbs the solar spectrum from both the front and rear sides (reflected light from the background such as green grass, white sand, red brick, roofing shingle, snow, etc.). Using the albedo reflection and the subsequent short-circuit current density, the conversion efficiency of the PVK-filtered c-Si HJ bottom sub-cell was improved regardless of the PVK top sub-cell properties. This approach achieved a conversion efficiency exceeding 30%, which is higher than those of both the top and bottom sub-cells. Notably, this efficiency is also greater than the Schockley–Quiesser limit of the c-Si solar cell (approximately 29.43%). The proposed approach has the potential to lower industrial solar cell production costs in the near future.

Patients with end-stage kidney disease (ESKD) frequently experience anemia, and maintaining hemoglobin (Hb) levels within a targeted range using erythropoiesis-stimulating agents (ESAs) is challenging. This study introduces a gated recurrent unit-attention-based module (GAM) for efficient anemia management among patients undergoing chronic dialysis and proposes a novel alert system for anticipating the need for red blood cell transfusions. Data on demographic characteristics, dialysis metrics, drug administration, laboratory tests, and transfusion history were retrospectively collected from patients undergoing hemodialysis at Kangwon National University Hospital between 2017 and 2022. After preprocessing, a final dataset of 252 patients was used for model training. Our model functions in two major phases: (1) Hb level prediction and ESA dose recommendation and (2) transfusion alert framework. The GAM model outperformed traditional machine learning algorithms, including linear regression, XGBoost, and multilayer perceptron, in predicting Hb levels (R-squared value = 0.60). The model also demonstrated a recommendation accuracy of 0.78 compared to that of clinical experts, indicating a high degree of concordance with the ESA dosing recommendations. Additionally, the model exhibited considerably high accuracy (0.99) for transfusion alarms. Thus, the GAM model holds promise for improving anemia management in patients with ESKD by optimizing ESA dosages and providing timely transfusion alerts.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne illness with a notable morality risk that is becoming increasingly prevalent in East Asia (14–36%). Increasing evidence indicates a more direct role of the SFTS virus in renal impairment. However, few studies have explored the risk factors for and clinical outcomes of AKI in patients with SFTS. Therefore, in this study, we aimed to investigate risk factors and outcomes associated with AKI in patients with SFTS. In this retrospective cohort study, we included the data of 53 patients who were diagnosed with SFTS virus infection at Kangwon National University Hospital between 2016 and 2020. We incorporated laboratory data and medical information including comorbidities, complications, and mortality. Baseline characteristics, clinical features, laboratory parameters, and mortality rates of the non-AKI and AKI groups were compared. Patient survival of non-AKI and AKI groups were compared using the Kaplan–Meier method. To identify the population with poor prognosis, Cox regression analysis was used to identify the independent risk factors for in-hospital mortality in patients with SFTS. Of the 53 individuals, 29 (54.7%) were male, with an average age of 66.5 years. Nine patients (15.1%) died of SFTS. Twenty-seven (50.9%) patients exhibited AKI; the average time interval from fever onset to AKI occurrence was 3.6 days. Notably, 24 (88.9%) patients developed AKI within the first week of fever onset. Patients in the AKI group exhibited a significantly higher prevalence of diabetes and were older than those in the non-AKI group. The mortality rate was notably higher (29.6%) in the AKI group than in the non-AKI group (3.8%). Within the AKI cohort, advanced stages (stages 2 and 3) showed a 50% mortality rate, which was significantly higher than the 17.6% mortality rate in patients with stage 1 AKI. Additionally, Kaplan–Meier curves revealed lower survival rates among patients with AKI than among those without AKI ( P  = 0.017). Cox regression analysis identified leukopenia and elevated serum creatinine levels as significant risk factors for mortality. AKI is a common complication associated with SFTS. Moreover, the mortality rate was significantly higher in the patients who developed AKI than in those who did not. Our findings underscore the pivotal role of AKI as a prognostic marker of disease severity in patients with SFTS.

Various mechanisms, including inflammation, oxidative stress, and apoptosis, are involved in the transition from acute kidney injury to chronic kidney disease (AKI-to-CKD). In this study, we aimed to determine the pathway linking acute injury and fibrosis under static magnetic fields (SMFs). Human tubular epithelial cells (hTECs) were cultured on SMF platforms (119 mT; outward vs. inward direction) for 3 days, followed by treatment with adenine and p38 mitogen-activated protein kinase (MAPK) inhibitor to verify the role of MAPK pathway. In-vivo, mice were orally administered adenine (2mg/mouse/day) for 14 days to induce tubular injury, and p38 MAPK inhibitor (iP38, 10mg/kg) was injected intraperitoneally to evaluate its therapeutic effect. Inward SMF exposure significantly increased phospho-p38 (pp38) expression compared to outward SMFs. p38 MAPK inhibition reduced G1/S arrest and oxidative stress, apoptosis, and expression of fibrosis markers under inward SMFs. Additionally, iP38 treatment alleviated inflammation and fibrosis in adenine-induced tubular nephropathy (AITN). This study revealed that SMF-related AKI-to-CKD transition progresses with the direction of SMFs affecting the severity of injury, whereas p38 MAPK inhibition attenuates SMF-induced kidney injury and prevents fibrosis.

Although the engineering of T cells to co-express immunostimulatory cytokines has been shown to enhance the therapeutic efficacy of adoptive T cell therapy, the uncontrolled systemic release of potent cytokines can lead to severe adverse effects. To address this, we site-specifically inserted the (IL-12) gene into the PDCD1 locus in T cells using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based genome editing to achieve T-cell activation-dependent expression of IL-12 while ablating the expression of inhibitory PD-1. New York esophageal squamous cell carcinoma 1(NY-ESO-1)-specific TCR-T cells was investigated as a model system. We generated ΔPD-1-IL-12 -edited NY-ESO-1 TCR-T cells by sequential lentiviral transduction and CRISPR knock-in into activated human primary T cells. We showed that the endogenous regulatory elements can tightly control the secretion of recombinant IL-12 in a target cell-dependent manner, at an expression level that is more moderate than that obtained using a synthetic NFAT-responsive promoter. The inducible expression of IL-12 from the locus was sufficient to enhance the effector function of NY-ESO-1 TCR-T cells, as determined by upregulation of effector molecules, increased cytotoxic activity, and enhanced expansion upon repeated antigen stimulation in vitro. Mouse xenograft studies also revealed that PD-1-edited IL-12-secreting NY-ESO-1 TCR-T cells could eliminate established tumors and showed significantly greater in vivo expansion capacity than control TCR-T cells. Our approach may provide a way to safely harness the therapeutic potential of potent immunostimulatory cytokines for the development of effective adoptive T cell therapies against solid tumors.

Long waiting time for deceased donor kidney transplant is inevitable due to the scarcity of donor, resulting in highlighting the importance of waiting time care. We analyzed the Korean Network for Organ Sharing (KONOS) database to assess the impact of waiting time on post-transplant survival outcomes and investigate risk factors for mortality by waiting time based on a complete enumeration survey in Korea. We analyzed all persons aged over 18 years in deceased donor kidney transplant cases enrolled in the Korean Network for Organ Sharing (KONOS) database from January 2000 to January 2015. The primary end point was all-cause mortality after enrollment. Of the 24,296 wait-listed subjects on dialysis, 5,255 patients received kidney transplants from deceased donors, with a median waiting time of 4.5 years. Longer waiting times had distinct deleterious effects on overall survival after transplantation. While waiting for a transplant, patients with diabetes were more likely to die before transplantation (HR 1.515, 95% CI 1.388-1.653, p<0.001). Age was another significant risk factor for mortality. Only 56% of people aged 65 years survived after 10 years of waiting, whereas 86% of people aged 35 years survived after 10 years. Moreover, women on the waiting list were more likely to live longer than men on the list. More attention should be focused on patients with a higher risk of mortality while waiting for a deceased donor kidney transplant, such as patients with diabetes, those of advanced age, and those who are male.

We aimed to determine the metabolomic profile of kidney cells under high glucose conditions and following sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. Targeted metabolomics using the Absolute IDQ-p180 kit was applied to quantify metabolites in kidney cells stimulated with high glucose (25 and 50 mM) and treated with SGLT2 inhibitor, dapagliflozin (2 µM). Primary cultured human tubular epithelial cells and podocytes were used to identify the metabolomic profile in high glucose conditions following dapagliflozin treatment. The levels of asparagine, PC ae C34:1, and PC ae C36:2 were elevated in tubular epithelial cells stimulated with 50 mM glucose and were significantly decreased after 2 µM dapagliflozin treatment. The level of PC aa C32:0 was significantly decreased after 50 mM glucose treatment compared with the control, and its level was significantly increased after dapagliflozin treatment in podocytes. The metabolism of glutathione, asparagine and proline was significantly changed in tubular epithelial cells under high-glucose stimulation. And the pathway analysis showed that aminoacyl-tRNA biosynthesis, arginine and proline metabolism, glutathione metabolism, valine, leucine and isoleucine biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, beta-alanine metabolism, phenylalanine metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism were altered in tubular epithelial cells after dapagliflozin treatment following 50 mM glucose compared to those treated with 50 mM glucose.

Mammography is essential for reducing breast cancer mortality; however, its performance varies globally. This study aimed to evaluate mammography screening outcomes in Korea over 12 years and investigate regional variations. We analyzed mammography data from 42 million Korean women, aged 40 years and older, who participated in the Korean National Cancer Screening Program (KNCSP) from 2009 to 2020. Performance metrics-including recall rate (RR), positive predictive value (PPV), sensitivity, specificity, false positive rate (FPR), cancer detection rate (CDR), interval cancer rate (ICR), and dense breast rate (DBR), were computed. Twelve-year trends in these metrics were analyzed using Joinpoint regression. Regional variations were also examined across Korea's 237 districts, stratified by age groups. From 2009 to 2020, 42165405 mammography screenings were conducted through the KNCSP, increasing from 2821132 screenings in 2009 to 3596204 in 2020. The RR decreased from 17.2% in 2009 to 11.2% in 2020 (average annual percent change [AAPC] = -3.7%), while the PPV increased from 0.8% to 2.8%; AAPC = 10.7%), the CDR increased from 1.5 to 3.1 per 1000; AAPC = 7.3%), and the ICR rose from 0.9 to 1.6 per 1000; (AAPC = 5.2%). Regional variations were noted; however, differences in the RR, sensitivity, specificity, and FPR decreased over time. While mammography performance improved from 2009 to 2020, the PPV and sensitivity remain suboptimal, underscoring the need for continuous monitoring. Regional disparities in performance, although reduced, persist. These findings provide essential baseline data for improving mammography quality and addressing inequities in breast cancer screening.

This study investigated the correlation between the degree of disorder of the post-hydrogen plasma treatment (HPT) of the intrinsic hydrogenated amorphous silicon (a-Si:H(i)) and the device characteristics of the a-Si:H/c-Si heterojunction (HJ) solar cells. The reduction in the degree of disorder helps to improve interface defects and to enhance the effective carrier lifetime of the a-Si:H/c-Si heterojunction. The highest effective minority carrier lifetime of 2.08 ms was observed in the film with the lowest degree of disorder of 2.03. The devices constructed with HPT a-Si:H(i) having a lower degree of disorder demonstrated higher device performance in terms of open-circuit voltage (Voc), fill factor (FF), and subsequent conversion efficiency. An a-Si:H(i) with a lower degree of disorder (2.03) resulted in a higher Voc of 728 mV and FF of 72.33% and achieved a conversion efficiency of up to 20.84% for the a-Si:H/c-Si HJ silicon solar cell.