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Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus and a leading cause of kidney failure worldwide. Despite its prevalence, the mechanisms underlying early kidney damage in DKD remain poorly understood. In this study, we used single nucleus RNA-seq to construct gene regulatory networks (GRNs) in the kidney cortex of patients with early DKD. By comparing these networks with those of healthy controls, we identify cell type-specific changes in genetic regulation associated with diabetic status. The regulon activities of FXR (NR1H4) and CREB5 were found to be upregulated in kidney proximal convoluted tubule epithelial cells (PCTs), which were validated using immunofluorescence staining in kidney biopsies from DKD patients. In vitro experiments using cultured HK2 cells showed that FXR and CREB5 protected cells from apoptosis and epithelial–mesenchymal transition. Our findings suggest that FXR and CREB5 may be promising targets for early intervention in patients with DKD.

Glucocorticoids are commonly used to treat anti-GBM crescentic glomerulonephritis, however, the mechanism underlying its therapeutic effectiveness is not completely understood. Since podocyte EGFR/STAT3 signaling is known to mediate the development of anti-GBM glomerulonephritis, we investigated the effect of glucocorticoids on EGFR/STAT3 signaling in podocytes. We found that the levels of phosphorylated (activated) EGFR and STAT3 in podocytes were markedly elevated in anti-GBM patients without glucocorticoids treatment, but were normalized in patients with glucocorticoids treatment. In a rat model of anti-GBM glomerulonephritis, glucocorticoids treatment significantly attenuated the proteinuria, crescent formation, parietal epithelial cell (PEC) activation and proliferation, accompanied by elimination of podocyte EGFR/STAT3 signaling activation. In cultured podocytes, glucocorticoids were found to inhibit HB-EGF-induced EGFR and STAT3 activation. The conditioned medium from podocytes treated with HB-EGF in the absence but not presence of glucocorticoids was capable of activating Notch signaling (which is known to be involved in PEC proliferation and crescent formation) and enhancing proliferative activity in primary PECs, suggesting that glucocorticoids prevent podocytes from producing secreted factors that cause PEC proliferation and crescent formation. Furthermore, we found that glucocorticoids can downregulate the expression of EGFR ligands, EGF and HB-EGF, while upregulate the expression of EGFR inhibitor, Gene 33, explaining how glucocorticoids suppress EGFR signaling. Taken together, glucocorticoids exert therapeutic effect on anti-GBM crescentic glomerulonephritis through inhibiting podocyte EGFR/STAT3 signaling and the downstream pathway that leads to PEC proliferation and crescent formation.

Background This study is to investigate the effect of fenofibrate on the bone quality of Type 2 diabetes mellitus (T2DM) mouse model. Methods T2DM mouse model was induced by high-fat-diet, and the mice were treated with fenofibrate (100 mg/kg) (DIO-FENO) or PBS (DIO-PBS) for 4 weeks. The bone microstructure and biomechanical properties of femora were analyzed by micro-CT and 3-Point bending test. The protein expression was detected by immunohistochemical staining and Western blot. The cell apoptosis was evaluated by TUNEL staining. The Bcl2, caspase 3, and osteoblast marker genes were detected by RT-qPCR. Results The biomechanical properties of bones from DIO-FENO group were significantly lower than those in the control and DIO-PBS groups. Besides, the trabecular number was lower than those of the other groups, though the cortical porosity was decreased compared with that of DIO-PBS group because of the increase of apoptotic cells. The expression of osteocalcin and collagen I were decreased after treatment with fenofibrate in T2DM mice. Moreover, the cell viability was decreased after treated with different concentrations of fenofibrate, and the expression of Runx2 decreased after treated with high dose of fenofibrate. Conclusion Fenofibrate decreases the bone quality of T2DM mice through decreasing the expression of collagen I and osteocalcin, which may be resulted from the down regulation of Runx2 expression.

Purpose The purpose of this study is to investigate the two-dimensional unsteady inclined stagnation point flow and thermal transmission of Maxwell fluid on oscillating stretched/contracted plates. First, based on the momentum equation at infinity, pressure field is modified by solving first-order differential equation. Meanwhile, thermal relaxation characteristic of fluid is described by Cattaneo–Christov thermal diffusion model. Design/methodology/approach Highly coupled model equations are transformed into simpler partial differential equations (PDE) via appropriate dimensionless variables. The approximate analytical solutions of unsteady inclined stagnation point flow on oscillating stretched and contracted plates are acquired by homotopy analysis method for the first time, to the best of the authors’ knowledge. Findings Results indicate that because of tensile state of plate, streamline near stagnation point disperses to both sides with stagnation point as center, while in the case of shrinking plate, streamline near stagnation point is concentrated near stagnation point. The enhancement of velocity ratio parameter leads to increasing of pressure variation rate, which promotes flow of fluid. In tensile state, surface friction coefficient on both sides of stagnation point has opposite symbols; when the plate is in shrinkage state, there is reflux near the right side of the stagnation point. In addition, although the addition of unsteady parameters and thermal relaxation parameters reduce heat transfer efficiency of fluid, heat transfer of fluid near the plate can also be enhanced by considering thermal relaxation effect when plate shrinks. Originality/value First, approximate analytical solutions of unsteady inclined stagnation point flow on oscillating stretched and contracted plates are researched, respectively. Second, pressure field is further modified. Finally, based on this, thermal relaxation characteristic of fluid is described by Cattaneo–Christov thermal diffusion model.

Nickel is the most widely used inexpensive active metal center of the heterogeneous catalysts for CO 2 hydrogenation to methane. However, Ni-based catalysts suffer from severe deactivation in CO 2 methanation reaction due to the irreversible sintering and coke deposition caused by the inevitable localized hotspots generated during the vigorously exothermic reaction. Herein, we demonstrate the inverse CeAlO x /Ni composite constructed on the Ni-foam structure support realizes remarkable CO 2 methanation catalytic activity and stability in a wide operation temperature range from 240 to 600 °C. Significantly, CeAlO x /Ni/Ni-foam catalyst maintains its initial activity after seven drastic heating-cooling cycles from RT to 240 to 600 °C. Meanwhile, the structure catalyst also shows water resistance and long-term stability under reaction condition. The promising thermal stability and water-resistance of CeAlO x /Ni/Ni-foam originate from the excellent heat and mass transport efficiency which eliminates local hotspots and the formation of Ni-foam stabilized CeAlO x /Ni inverse composites which effectively anchored the active species and prevents carbon deposition from CH 4 decomposition. An inverse CeAlO x /Ni/Ni-foam structured catalyst with high thermal stability and water resistance is shown to be effective at CO 2 methanation across a wide temperature range because of efficient heat/mass transport.

Key messageOur results confirmed that SlERF.F5 can directly regulate the promoter activity of ACS6 and interact with SlMYC2 to regulate tomato leaf senescence.The process of plant senescence is complex and highly coordinated, and is regulated by many endogenous and environmental signals. Ethylene and jasmonic acid are well-known senescence inducers, but their molecular mechanisms for inducing leaf senescence have not been fully elucidated. Here, we isolated an ETHYLENE RESPONSE FACTOR F5 (SlERF.F5) from tomato. Silencing of SlERF.F5 causes accelerated senescence induced by age, darkness, ethylene, and jasmonic acid. However, overexpression of SlERF.F5 would not promote senescence. Moreover, SlERF.F5 can regulate the promoter activity of ACS6 in vitro and in vivo. Suppression of SlERF.F5 resulted in increased sensitivity to ethylene and jasmonic acid, decreased accumulation of chlorophyll content, and inhibited the expression of chlorophyll- and light response-related genes. Compared with the wild type, the qRT-PCR analysis showed the expression levels of genes related to the ethylene biosynthesis pathway and the jasmonic acid signaling pathway in SlERF.F5-RNAi lines increased. Yeast two-hybrid experiments showed that SlERF.F5 and SlMYC2 (a transcription factor downstream of the JA receptor) can interact physically, thereby mediating the role of SlERF.F5 in jasmonic acid-induced leaf senescence. Collectively, our research provides new insights into how ethylene and jasmonic acid promote leaf senescence in tomato.

Over the past three decades, considerable efforts have been expended on understanding the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in leukemia, following the identification of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs). The aim of this review is to summarize the latest progress in our understanding of the involvement of the JAK/STAT signaling pathway in the development of leukemia. We also attempt to provide insights into the current use of JAK/STAT inhibitors in leukemia therapy and explore pertinent clinical trials in this field.

During evolutionary adaptation, the mechanisms for self-regulation are established between the normal growth and development of plants and environmental stress. The phytohormone jasmonate (JA) is a key tie of plant defence and development, and JASMONATE-ZIM DOMAIN (JAZ) repressor proteins are key components in JA signalling pathways. Here, we show that JAZ expression was affected by leaf senescence from the transcriptomic data. Further investigation revealed that SlJAZ10 and SlJAZ11 positively regulate leaf senescence and that SlJAZ11 can also promote plant regeneration. Moreover, we reveal that the SlJAV1-SlWRKY51 (JW) complex could suppress JA biosynthesis under normal growth conditions. Immediately after injury, SlJAZ10 and SlJAZ11 can regulate the activity of the JW complex through the effects of electrical signals and Ca 2+ waves, which in turn affect JA biosynthesis, causing a difference in the regeneration phenotype between SlJAZ10-OE and SlJAZ11-OE transgenic plants. In addition, SlRbcs-3B could maintain the protein stability of SlJAZ11 to protect it from degradation. Together, SlJAZ10 and SlJAZ11 not only act as repressors of JA signalling to leaf senescence, but also regulate plant regeneration through coordinated electrical signals, Ca 2+ waves, hormones and transcriptional regulation. Our study provides critical insights into the mechanisms by which SlJAZ11 can induce regeneration.

This qualitative study aimed to gain an in-depth understanding of the communication experiences of young couples with breast cancer as they navigate the challenges of raising underage children. Semi-structured interviews were conducted with 13 couples with breast cancer recruited through purposive sampling in the inpatient ward of a tertiary hospital in Sichuan Province, China. The interviews, conducted face-to-face between May 2024 and June 2024, were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. This study was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Two researchers independently coded the data using NVivo 12.0, developing major themes and subthemes through an inductive process and constant comparison. The analysis revealed two main themes, each encompassing three to four subthemes. The first theme, dyadic coparenting through constructive communication: a shared journey of navigating parenting challenges, which includes open communication of parenting experiences, emotional co-regulation in parenting, and positive communication of parenting plans; The second theme, negative co-parenting communication: protect parenting emotions or not provide emotional support, which includes “instrumental support” and emotional avoidance, avoid communication to prevent emotional fluctuations, communication concealment to avoid increasing parenting pressure, and invalid communication without providing parenting emotional support. These findings highlight the diverse communication strategies employed by young couples with breast cancer in parenting their underage children. The study underscores the need for healthcare professionals to develop targeted interventions to enhance communication between young breast cancer couples, with the aim of improving their ability to co-parent effectively during this challenging time.

Mesalamine has been well used in the improvement of ulcerative colitis (UC) in clinics, however, the underlying mechanisms were not well illustrated. To explore its efficacy from the perspective of gut microbiota and related metabolites, we employed 16S rRNA sequencing and metabolomics approaches in stool samples across 14 normal healthy controls (NC group), 10 treatment-naïve UC patients (UC group) and 14 UC patients responded to mesalamine treatment (mesalamine group). We noted that the gut microbiota diversity and community composition were remarkably perturbed in UC group and partially restored by mesalamine treatment. The relative abundance of 192 taxa in genus level were significantly changed in UC group, and 168 genera were significantly altered after mesalamine intervention. Meanwhile, a total of 127 metabolites were significantly changed in UC group and 129 metabolites were significantly altered after mesalamine treatment. Importantly, we observed that many candidates including 49 genera (such as Escherichia-shigella, Enterococcus and Butyricicoccus ) and 102 metatoblites (such as isoleucine, cholic acid and deoxycholic acid) were reversed by mesalamine. Spearman correlation analysis revealed that most of the candidates were significantly correlated with Mayo score of UC, and the relative abundance of specific genera were significant correlated with the perturbation of metabolites. Pathway analysis demonstrated that genera and metabolites candidates were enriched in many similar molecular pathways such as amino acid metabolism and secondary metabolites biosynthesis. Importantly, ROC curve analysis identified a gut microbiota signature composed of five genera including Escherichia-Shigella, Streptococcus, Megamonas, Prevotella_9 and [ Eubacterium ] _coprostanoligenes _group which might be used to distinguish UC group from both NC and mesalamine group. In all, our results suggested that mesalamine might exert a beneficial role in UC by modulating gut microbiota signature with correlated metabolites in different pathways, which may provide a basis for developing novel candidate biomarkers and therapeutic targets of UC.