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Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are anti-hyperglycemic agents that prevent glucose reabsorption in proximal tubular cells. SGLT2i improves renal outcomes in both diabetic and non-diabetic patients, indicating it may have beneficial effects beyond glycemic control. Here, we demonstrate that SGLT2i affects energy metabolism and podocyte lipotoxicity in experimental Alport syndrome (AS). In vitro, we found that the SGLT2 protein was expressed in human and mouse podocytes to a similar extent in tubular cells. Newly established immortalized podocytes from Col4a3 knockout mice (AS podocytes) accumulate lipid droplets along with increased apoptosis when compared to wild-type podocytes. Treatment with SGLT2i empagliflozin reduces lipid droplet accumulation and apoptosis in AS podocytes. Empagliflozin inhibits the utilization of glucose/pyruvate as a metabolic substrate in AS podocytes but not in AS tubular cells. In vivo, we demonstrate that empagliflozin reduces albuminuria and prolongs the survival of AS mice. Empagliflozin-treated AS mice show decreased serum blood urea nitrogen and creatinine levels in association with reduced triglyceride and cholesterol ester content in kidney cortices when compared to AS mice. Lipid accumulation in kidney cortices correlates with a decline in renal function. In summary, empagliflozin reduces podocyte lipotoxicity and improves kidney function in experimental AS in association with the energy substrates switch from glucose to fatty acids in podocytes.

Impaired cellular cholesterol efflux is a key factor in the progression of renal, cardiovascular, and autoimmune diseases. Here we describe a class of 5-arylnicotinamide compounds, identified through phenotypic drug discovery, that upregulate ABCA1-dependent cholesterol efflux by targeting Oxysterol Binding Protein Like 7 (OSBPL7). OSBPL7 was identified as the molecular target of these compounds through a chemical biology approach, employing a photoactivatable 5-arylnicotinamide derivative in a cellular cross-linking/immunoprecipitation assay. Further evaluation of two compounds (Cpd A and Cpd G) showed that they induced ABCA1 and cholesterol efflux from podocytes in vitro and normalized proteinuria and prevented renal function decline in mouse models of proteinuric kidney disease: Adriamycin-induced nephropathy and Alport Syndrome. In conclusion, we show that small molecule drugs targeting OSBPL7 reveal an alternative mechanism to upregulate ABCA1, and may represent a promising new therapeutic strategy for the treatment of renal diseases and other disorders of cellular cholesterol homeostasis. This study describes a class of small molecule compounds that promote ABCA1-dependent cholesterol efflux via a non-transcriptional mechanism, the identification of the molecular target by a chemical biology approach, and the potential of these agents for the treatment of chronic kidney diseases and potentially other diseases where lipid accumulation drives disease progression.

The excessive use of herbicides in agricultural fields has emerged as a critical environmental concern. This study innovatively synthesized a ZIF-8@TPPa composite through a solvothermal method for the efficient removal of herbicides from aqueous environment. The material exhibited remarkable adsorption capacities for butachlor (232.56 mg/g), anilofos (188.68 mg/g), and pendimethalin (285.71 mg/g), along with excellent acid–base stability (pH 3–9), strong anti-ion interference capability, and good reusability (adsorption efficiency >80% after five cycles). The adsorption processes were well-described by the two isotherm models and the pseudo-second-order model, indicating that the dominant mechanism is a synergistic effect between monolayer chemical adsorption and multilayer physical adsorption, primarily driven by π-π stacking, hydrogen bonding, and coordination. The material maintained outstanding adsorption efficiency (>85%) in real water samples (tap water, seawater, and river water). This study not only provides a sustainable and effective strategy for herbicide remediation from aqueous environment but also expands the practical applications of MOF@COF in aqueous environment.

Rotation-invariant (RI) point cloud models aim to reduce sensitivity to viewpoint changes, but their performance still drops noticeably in real-world settings when local geometry is degraded by noise, occlusion, and uneven sampling. Once these disturbances propagate through deeper layers, they can lead to significant robustness degradation, especially for high-capacity RI backbones. To address this problem, we propose AGSM-CPA (Adaptive Geometric Signal Modulation with Cross-Perturbation Alignment), a lightweight and plug-and-play framework that enhances the robustness of RI models without altering their core convolutional operators. It integrates two complementary modules: the Geometric Signal-to-Noise Ratio (G-SNR) modulation mechanism, which adaptively suppresses unreliable neighborhoods based on local coordinate variance, and the Cross-Perturbation Semantic Consistency Alignment (CP-SCL) module, which enforces prediction consistency between weakly augmented inputs and strongly corrupted ones. We evaluate AGSM-CPA on ModelNet40, ScanObjectNN, and ShapeNetPart. Across standard corruption protocols, AGSM-CPA consistently improves robustness while maintaining competitive clean accuracy with negligible computational overhead. These results indicate that AGSM-CPA offers a practical, reliability-aware adapter for robust rotation-invariant point cloud learning.

To mitigate explosion hazards arising from hydrogen leakage and subsequent mixing with air, the injection of inert gases can substantially diminish explosion risk. However, prevailing research has predominantly characterized inert gas dilution effects on explosion behavior under quiescent conditions, largely neglecting the turbulence-mediated explosion enhancement inherent to dynamic mixing scenarios. A comprehensive investigation was conducted on the combustion behavior of 30%, 50%, and 70% H2-air mixtures subjected to jet-induced (CO2, N2, He) turbulent flow, incorporating quantitative characterization of both the evolving turbulent flow field and flame front dynamics. Research has demonstrated that both an increased H2 concentration and a higher jet medium molecular weight increase the turbulence intensity: the former reduces the mixture molecular weight to accelerate diffusion, whereas the latter results in more pronounced disturbances from heavier molecules. In addition, when CO2 serves as the jet medium, a critical flame radius threshold emerges where the flame propagation velocity decreases below this threshold because CO2 dilution effects suppress combustion, whereas exceeding it leads to enhanced propagation as initial disturbances become the dominant factor. Furthermore, at reduced H2 concentrations (30–50%), flow disturbances induce flame front wrinkling while preserving the spherical geometry; conversely, at 70% H2, substantial flame deformation occurs because of the inverse correlation between the laminar burning velocity and flame instability governing this transition. Through systematic quantitative analysis, this study elucidates the evolutionary patterns of both turbulent fields and flame fronts, offering groundbreaking perspectives on H2 combustion and explosion propagation in turbulent environments.

Fibroblasts from patients with Tangier disease carrying ATP-binding cassette A1 (ABCA1) loss-of-function mutations are characterized by cardiolipin accumulation, a mitochondrial-specific phospholipid. Suppression of ABCA1 expression occurs in glomeruli from patients with diabetic kidney disease (DKD) and in human podocytes exposed to DKD sera collected prior to the development of DKD. We demonstrated that siRNA ABCA1 knockdown in podocytes led to reduced oxygen consumption capabilities associated with alterations in the oxidative phosphorylation (OXPHOS) complexes and with cardiolipin accumulation. Podocyte-specific deletion of Abca1 (Abca1fl/fl) rendered mice susceptible to DKD, and pharmacological induction of ABCA1 improved established DKD. This was not mediated by free cholesterol, as genetic deletion of sterol-o-acyltransferase-1 (SOAT1) in Abca1fl/fl mice was sufficient to cause free cholesterol accumulation but did not cause glomerular injury. Instead, cardiolipin mediates ABCA1-dependent susceptibility to podocyte injury, as inhibition of cardiolipin peroxidation with elamipretide improved DKD in vivo and prevented ABCA1-dependent podocyte injury in vitro and in vivo. Collectively, we describe a pathway definitively linking ABCA1 deficiency to cardiolipin-driven mitochondrial dysfunction. We demonstrated that this pathway is relevant to DKD and that ABCA1 inducers or inhibitors of cardiolipin peroxidation may each represent therapeutic strategies for the treatment of established DKD.

The UHRF1 protein is pivotal for DNA methylation and heterochromatin formation, leading to decreased expressions of tumor suppressor genes and contributing to tumorigenesis. However, the factors that modulate UHRF1 expression in colorectal cancer (CRC) remain unclear. Here we showed that, compared with corresponding normal tissues, UHRF1 was upregulated and microRNA‐9 (miR‐9) was downregulated in CRC tissues. The expression of UHRF1 was inversely correlated with overall survival rates of patients with CRC. Overexpression of miR‐9 in CRC cell lines significantly attenuated CRC cell proliferation and promoted cell apoptosis. The expression of UHRF1 was markedly reduced in pre‐miR‐9 transfected CRC cells. Using luciferase reporter assay, we confirmed that miR‐9 was a direct upstream regulator of UHRF1. Finally, analysis of miR‐9 and UHRF1 levels in human CRC tissues revealed that expression of miR‐9 was inversely correlated with UHRF1 expression. Collectively, our results offer in vitro validation of the concept that miR‐9 could repress the expression of UHRF1, and function as a tumor‐suppressive microRNA in CRC. It may serve as a prognostic and therapeutic marker for CRC. Our results showed that UHRF1 is modulated by miR‐9, which could represses the proliferation of colorectal cancer cells and function as an oncomiRNA. miR‐9 is downregulated in colorectal cancer and associated with the prognosis of colorectal cancer.

Decreased ATP Binding Cassette Transporter A1 (ABCA1) expression and caspase-4-mediated noncanonical inflammasome contribution have been described in podocytes in diabetic kidney disease (DKD). To investigate a link between these pathways, we evaluated pyroptosis-related mediators in human podocytes with stable knockdown of ABCA1 (siABCA1) and found that mRNA levels of IRF1, caspase-4, GSDMD, caspase-1 and IL1β were significantly increased in siABCA1 compared to control podocytes and that protein levels of caspase-4, GSDMD and IL1β were equally increased. IRF1 knockdown in siABCA1 podocytes prevented increases in caspase-4, GSDMD and IL1β. Whereas TLR4 inhibition did not decrease mRNA levels of IRF1 and caspase-4, APE1 protein expression increased in siABCA1 podocytes and an APE1 redox inhibitor abrogated siABCA1-induced expression of IRF1 and caspase-4. RELA knockdown also offset the pyroptosis priming, but ChIP did not demonstrate increased binding of NFκB to IRF1 promoter in siABCA1 podocytes. Finally, the APE1/IRF1/Casp1 axis was investigated in vivo. APE1 IF staining and mRNA levels of IRF1 and caspase 11 were increased in glomeruli of BTBR ob/ob compared to wildtype. In conclusion, ABCA1 deficiency in podocytes caused APE1 accumulation, which reduces transcription factors to increase the expression of IRF1 and IRF1 target inflammasome-related genes, leading to pyroptosispriming.

The separator is a key component of sodium-ion battery, which greatly affects the electrochemical performances and safety characteristics of the battery. Conventional glass fiber separator cannot meet the requirements of large-scale application because of high cost and poor mechanical properties. Herein, the novel composite separators are prepared by a simple slurry sieving process using glass fiber separator scraps and ordinary qualitative filter paper as raw materials. As the composite mass ratio is 1:1, the composite separator has excellent comprehensive properties, including tensile strength of 15.8 MPa, porosity of 74.3%, ionic conductivity of 1.57 × 10 −3 S·cm −1 and thermal stability at 210°C. The assembled sodium-ion battery shows superior cycling performance (capacity retention of 94.1% after 500 cycles at 1C) and rate capacity (retention rate of 87.3% at 10C), and it maintains fine interface stability. The above results provide some new ideas for the separator design of high-performance and low-cost sodium-ion batteries.

Although dyslipidemia is associated with chronic kidney disease (CKD), it is more common in nephrotic syndrome (NS), and guidelines for the management of hyperlipidemia in NS are largely opinion-based. In addition to the role of circulating lipids, an increasing number of studies suggest that intrarenal lipids contribute to the progression of glomerular diseases, indicating that proteinuric kidney diseases may be a form of “fatty kidney disease” and that reducing intracellular lipids could represent a new therapeutic approach to slow the progression of CKD. In this review, we summarize recent progress made in the utilization of lipid-modifying agents to lower renal parenchymal lipid accumulation and to prevent or reduce kidney injury. The agents mentioned in this review are categorized according to their specific targets, but they may also regulate other lipid-relevant pathways.