Mitochondrial pyruvate carrier 1 regulates fatty acid synthase lactylation and mediates treatment of nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: NAFLD has become a major metabolic disease worldwide. A few studies have reported the potential relationship between mitochondrial pyruvate carrier 1 (MPC1) and inflammation, fibrosis, and insulin sensitivity in obese or NASH mouse models. However, the impact of MPC1 on NAFLD-related liver lipid metabolism and its role in the NAFLD progression require further investigation. APPROACH AND RESULTS: MPC1 expression was measured in liver tissues from normal controls and patients with NAFLD. We characterized the metabolic phenotypes and expression of genes involved in hepatic lipid accumulation in MPC1 systemic heterozygous knockout (MPC1 +/- ) mice. Hepatic protein lactylation was detected using Tandem Mass Tags proteomics and verified by the overexpression of lactylation mutants in cells. Finally, the effect of MPC1 inhibition on liver inflammation was examined in mice and AML-12 cells. Here, we found that MPC1 expression was positively correlated to liver lipid deposition in patients with NAFLD. MPC1 +/- mice fed with high-fat diet had reduced hepatic lipid accumulation but no change in the expression of lipid synthesis-related genes. MPC1 knockout affected the lactylation of several proteins, especially fatty acid synthase, through the regulation of lactate levels in hepatocytes. Lactylation at the K673 site of fatty acid synthase inhibited fatty acid synthase activity, which mediated the downregulation of liver lipid accumulation by MPC1. Moreover, although MPC1 knockout caused lactate accumulation, inflammation level was controlled because of mitochondrial protection and macrophage polarization. CONCLUSIONS: In NAFLD, MPC1 levels are positively correlated with hepatic lipid deposition; the enhanced lactylation at fatty acid synthase K673 site may be a downstream mechanism.

Cluster-Locating Algorithm Based on Deep Learning for Silicon Pixel Sensors.

The application of silicon pixel sensors provides an excellent signal-to-noise ratio, spatial resolution, and readout speed in particle physics experiments. Therefore, high-performance cluster-locating technology is highly required in CMOS-sensor-based systems to compress the data volume and improve the accuracy and speed of particle detection. Object detection techniques using deep learning technology demonstrate significant potential for achieving high-performance particle cluster location. In this study, we constructed and compared the performance of one-stage detection algorithms with the representative YOLO (You Only Look Once) framework and two-stage detection algorithms with an RCNN (region-based convolutional neural network). In addition, we also compared transformer-based backbones and CNN-based backbones. The dataset was obtained from a heavy-ion test on a Topmetal-M silicon pixel sensor at HIRFL. Heavy-ion tests were performed on the Topmetal-M silicon pixel sensor to establish the dataset for training and validation. In general, we achieved state-of-the-art results: 68.0% AP (average precision) at a speed of 10.04 FPS (Frames Per Second) on Tesla V100. In addition, the detection efficiency is on the same level as that of the traditional Selective Search approach, but the speed is higher.

Comparison of the biometric parameters in patients with high myopia and anisometropia.

BACKGROUND: To compare biometric parameters, especially lens parameters, in patients with high myopia and anisometropia. METHODS: Patients with spherical equivalent greater than -6D and at least one eye with an axial length greater than 26 mm and a difference in binocular axial length greater than 2 mm were included in this study. In each patient, the eye with a relatively shorter axial length was assigned to Group S, and the other eye was assigned to Group L. In patients whose binocular axial length difference was greater than 4 mm, the eye with the shorter axial length was assigned to Group S1 and the other eye was assigned to Group L1. In patients whose shorter eye axial was less than 26 mm, the eye with the shorter axial was assigned to Group S2 and the other eye was assigned to Group L2. Central corneal thickness, corneal curvature radius, axial length, anterior chamber depth, lens thickness, white-to-white corneal diameter and the radius of the anterior and posterior lens capsules were compared between Group S and Group L, Groups S1 and L1, and Groups S2 and L2. RESULTS: Sixty-four people were enrolled in the study. There were 26 people with an axial length difference more than 4 mm (Group S1 and Group L1) and 34 patients with an axial length less than 26 mm (Group S2 and Group L2). No significant differences were found in any parameters except axial length between Group S and Group L, Groups S1 and L1, or Groups S2 and L2 (p > 0.05). CONCLUSIONS: The anterior parameters of patients with high myopia did not change with the axial length.

Gynostemma pentaphyllum and Gypenoside-IV Ameliorate Metabolic Disorder and Gut Microbiota in Diet-Induced-Obese Mice.

Gynostemma pentaphyllum (G. pentaphyllum) is a perennial liana herb of the Cucurbitaceae family which has both nutraceutical and pharmacological functions. The objective of the current study was to investigate the preventative effects of G. pentaphyllum and Gypenoside-IV (GP-IV, a saponin monomer in G. pentaphyllum) on metabolic symptoms in high fat diet induced obese (DIO) mice with gut microbiota dysbiosis. G. pentaphyllum water extract (GPWE, 150 mg/kg•d- 1) and GP-IV (50 mg/kg•d- 1) were orally administered to DIO mice by gavage for 10 weeks. The results showed that both GPWE and GP-IV prevented obesity development by decreasing body weight gain, reducing fat mass/body weight ratio and inhibiting adipocyte hypertrophy. GPWE and GP-IV also improved lipid profile and glucose tolerance effectively. Moreover, GPWE and GP-IV treatments partly restored gut microbiota in DIO mice. Typically, GPWE and GP-IV reduced Firmicutes to Bacteroidetes ratio, increased the abundance of certain health-promoting bacteria and reduced the abundance of microbiota that were associated with metabolic disorders. We conclude that GPWE and GP-IV can ameliorate metabolic symptoms possibly via modulating gut microbiota in DIO mice.

TWIST1 transcriptionally regulates glycolytic genes to promote the Warburg metabolism in pancreatic cancer.

Reprogrammed glucose metabolism is essential for tumor initiation and development, especially for pancreatic ductal adenocarcinoma (PDAC). Most cancer cells rely on aerobic glycolysis, a phenomenon termed "the Warburg effect", to support uncontrolled proliferation and evade apoptosis. However, the direct regulators of the Warburg effect remain areas of active investigation. In this study, we found that the highly conserved transcription factor, TWIST1, is a crucial regulator of aerobic glycolysis in PDAC. Genetic silencing of TWIST1 significantly inhibited the glycolytic phenotypes of PDAC cells as revealed by reduced glucose uptake, lactate production, and extracellular acidification rate, which can be restored by re-expression of siRNA-resistant TWIST1. Moreover, tamoxifen-inducible expression of TWIST1 promoted the Warburg metabolism of PDAC cells. Mechanistically, by luciferase reporter assay and chromatin immunoprecipitation experiment, we showed that TWIST1 can directly increase the expression of several glycolytic genes, including SLC2A1, HK2, ENO1, and PKM2. Of note, the transcriptional regulation by TWIST1 was not dependent on HIF1α or c-Myc. In The Cancer Genome Atlas and Gene Expression Omnibus accession GSE15471, we confirmed that TWIST1 was closely associated with the glycolysis pathway. Collectively, our findings indicate that TWIST1 is likely to act as important regulator of the Warburg effect in PDAC.

Fe-Catalyzed decarbonylative cascade reaction of N-aryl cinnamamides with aliphatic aldehydes to construct 3,4-dihydroquinolin-2(1H)-ones.

A practical Fe-catalyzed decarbonylative cascade reaction of N-aryl cinnamamides with aliphatic aldehydes to provide C3 alkylated 3,4-dihydroquinolin-2(1H)-ones is developed. Aliphatic aldehydes were oxidatively decarbonylated into 1°, 2° and 3° alkyl radicals conveniently, allowing for the subsequent cascade construction of C(sp3)-C(sp3) and C(sp3)-C(sp2) bonds via radical addition and HAS-type cyclization. The importance of the amide linkage and the selectivity of the 6-endo-trig over 5-exo-trig cyclization pathway were elucidated by experimental results and DFT calculations.

Coreopsis tinctoria improves energy metabolism in obese hyperglycemic mice.

Coreopsis tinctoria (CT) improves energy metabolism. However, the role of CT in alleviating obesity-induced hyperglycemia by targeting the liver remains unknown. Therefore, this article aims to explore the mechanism by which CT improves energy metabolism and resists hyperglycemia. The water and ethanol extracts of CT were administered to high-fat diet-induced (HFD) obese C57BL/6J mice at a dose of 4 g/kg.bw (low-dose water extract, WL; low-dose ethanol extract, EL) or 10 g/kg.bw (high-dose water extract, WH; high-dose ethanol extract, EH). Mice that consumed a maintenance diet (LFD) were included as blank controls. Network pharmacology, liquid chromatography-mass spectrometry (LC-MS), L02 cell cultivation, and liver transcriptomics were used to examine the mechanism and functional components of CT against obesity-induced hyperglycemia. The results indicated that WL significantly (p < 0.05) alleviated glucose intolerance and insulin resistance in obesity-induced hyperglycemia. Kaempferol is the main active compound of CT, which demonstrated significant (p < 0.05) anti-hyperglycemic effects in obese mice and L02 cells. Finally, kaempferol significantly (p < 0.05; fold change >1.2) shifted the genes involved in carbon metabolism, glycolysis/gluconeogenesis, and the mitogen-activated protein kinase (MAPK) pathways toward the trend of LFD, indicating that it exerts an anti-hyperglycemic effect through these molecular mechanisms. Overall, oral intake of CT lowers blood glucose and improves insulin sensitivity in mice with obesity-induced hyperglycemia. Kaempferol is the primary functional component of CT.

Comparison of Different Intraocular Lens Power Calculation Formulas in Eyes with Primary Angle Closure.

PURPOSE: To compare the accuracy of six intraocular lens power calculation formulas, Barrett Universal Ⅱ (BU Ⅱ), Haigis, Hoffer QST, HolladayⅠ, Kane and SRK/T, in eyes with primary angle closure disease (PACD). SETTING: Xiamen University Affiliated Xiamen Eye center, Xiamen, Fujian, China. DESIGN: Prospective case series. METHODS: Patients diagnosed with PACD and cataract and met the indication for cataract surgery were enrolled in the study. Six intraocular lens power calculation formulas were used to calculate refractive diopter. Percentage of eyes with prediction error (PE) within ±0.50D, and the median absolute prediction error (MedAE) were compared to determine the accuracy of different formulas in PACD patients. Subgroup analysis was performed according to axial length (AL). The accuracy of Barrett Universal Ⅱ was compared between PACD patients and age-related cataract patients. RESULTS: 105 patients (105 eyes) with PACD and 35 patients (35 eyes) with age-related cataract were enrolled in the study. Haigis, Kane and Barrett Universal Ⅱ formula achieved a comparable outcome and outperformed over the other three formulas in PACD patients. Subgroup analysis showed that the group with long AL has lower values of MedAE. PE was significantly positively correlated with AL and negatively correlated with relative lens position (RLP) when calculated use Barrett Universal Ⅱ and Kane. CONCLUSIONS: Haigis, Kane and Barrett Universal Ⅱ formula achieved a comparable outcome and outperformed over the other three formulas in PACD patients.

Protective effect of leukemia inhibitory factor on the retinal injury induced by acute ocular hypertension in rats.

Glaucoma is one of the leading causes of irreversible blindness worldwide. As such, neuroprotective therapy is essential for the treatment of this disease. Leukemia inhibitory factor (LIF) is a member of the IL-6 cytokine family and the LIF signaling pathway is considered to be one of the major endogenous factors mediating neuroprotection in the retina. Therefore, the present study aimed to investigate the possible effects of LIF in acute ocular hypertension (AOH). The intraocular pressure in rat eyes was raised to 110 mmHg for 1 h by infusing the anterior chamber with normal saline to establish the AOH model. In the treatment group, LIF was then injected into the vitreous cavity after AOH was ceased. The retinal tissues were obtained after the termination of AOH, and H&E staining was conducted to assess the morphological damage. The number of retinal ganglion cells (RGCs) was counted using the Fluoro-Gold retrograde staining method. TUNEL staining was used to determine the extent of apoptosis among the retinal cells. In addition, the protein expression levels of cleaved caspase-3, poly (ADP-ribose) polymerase (PARP), STAT3 and components of the AKT/mTOR/70-kDa ribosomal protein S6 kinase (p70S6K) signaling pathway were examined by western blotting. The results showed that AOH induced tissue swelling and structural damage in the retina, which were reversed by LIF injection. In the LIF treatment group, RGC loss was significantly inhibited and the quantity of TUNEL-stained cells was also significantly reduced, whereas the expression of cleaved caspase-3 and PARP was decreased. Furthermore, increased phosphorylation of STAT3, AKT, mTOR and p70S6K was observed after LIF treatment. By contrast, pretreatment with the STAT3 inhibitor C188-9 or the PI3K/AKT/mTOR inhibitor LY3023414 reversed the LIF-induced inhibition of RGC loss. These results suggested that exogenous LIF treatment inhibited the retinal damage induced by AOH, which was associated with the activation of STAT3 and mTOR/p70S6K signaling. Therefore, LIF may serve a role in neuroprotection for glaucoma treatment.

Sulforaphane Ameliorates Nonalcoholic Fatty Liver Disease Induced by High-Fat and High-Fructose Diet via LPS/TLR4 in the Gut-Liver Axis.

The gut-liver axis has emerged as a key player in the progression of non-alcoholic fatty liver disease (NAFLD). Sulforaphane (SFN) is a bioactive compound found in cruciferous vegetables; however, it has not been reported whether SFN improves NAFLD via the gut-liver axis. C57BL/6 mice were fed a high-fat and high-fructose (HFHFr) diet, with or without SFN gavage at doses of 15 and 30 mg·kg-1 body weight for 12 weeks. The results showed that SFN reduced weight gain, hepatic inflammation, and steatosis in HFHFr mice. SFN altered the composition of gut microbes. Moreover, SFN enhanced the intestinal tight junction protein ZO-1, reduced serum LPS, and inhibited LPS/TLR4 and ERS pathways to reduce intestinal inflammation. As a result, SFN protected the intestinal integrity and declined the gut-derived LPS translocations to the liver in HFHFr diet-induced mice. SFN decreased the liver LPS levels and inhibited the LPS/TLR4 pathway activations, thus inhibiting the pro-inflammatory cytokines. Notably, Spearman correlation analysis showed that the protective effect of SFN on intestinal barrier integrity and its anti-inflammatory effect on the liver was associated with improved intestinal dysbiosis. Above all, dietary intervention with SFN attenuates NAFLD through the gut-liver axis.

Neuroprotective effect of mesenchymal stem cell-derived extracellular vesicles on optic nerve injury in chronic ocular hypertension.

Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors, and which may be mediated by extracellular vesicles (or exosomes) released by mesenchymal stem cells. To investigate the neuroprotective effect of extracellular vesicles derived from umbilical cord mesenchymal stem cells on glaucoma, we established rat models of chronic ocular hypertension by injecting conjunctival fibroblasts into the anterior chamber to mimic optic nerve injury caused by glaucoma. One week after injury, extracellular vesicles derived from umbilical cord-derived mesenchymal stem cells were injected into the vitreous cavity. We found that extracellular vesicles derived from mesenchymal stem cells substantially reduced retinal damage, increased the number of retinal ganglion cells, and inhibited the activation of caspase-3. These findings suggest that mesenchymal stem cell-derived extracellular vesicles can help alleviate optic nerve injury caused by chronic ocular hypertension, and this effect is achieved by inhibiting cell apoptosis.

Influence of Pilocarpine Eyedrops on the Ocular Biometric Parameters and Intraocular Lens Power Calculation.

Objective: To evaluate the influence of pilocarpine eyedrops on the ocular biometric parameters and whether these parameter changes affect the intraocular lens (IOL) power calculation in patients with primary angle-closure glaucoma (PACG). Methods: Twenty-two PACG patients and fifteen normal subjects were enrolled. Ocular biometric parameters including the axial length (AL), anterior chamber depth (ACD), lens thickness (LT), mean keratometry (Km), and white-to-white distance (WTW) were measured by using a Lenstar LS 900 device before and at least 30 minutes after instillation of 2% pilocarpine eyedrops. Lens position (LP) was calculated, and the IOL power prediction based on the ocular biometric parameters was performed using the Barrett Universal II, Haigis, Hoffer Q, Holladay I, or SRK/T formulas before and after pilocarpine application. Results: In both PACG and normal groups, pilocarpine eyedrops induced a slight but statistically significant increase in the mean AL (0.01 mm for both groups) and mean LT (0.02 mm and 0.03 mm, respectively) but a significant decrease in the mean ACD (0.03 mm and 0.05 mm, respectively) and mean LP (0.02 mm and 0.04 mm, respectively). No significant changes in the mean Km and WTW were noticed in both groups. In addition, the IOL power calculation revealed insignificant changes before and after the pilocarpine instillation in both groups, regardless of the formula used. Conclusions: Pilocarpine eyedrops can induce slight changes in the ocular biometric parameters including the AL, ACD, LT, and LP. However, these parameter changes will not result in a significant difference in IOL power estimation.

Sphincter of Oddi Dysfunction Induces Gallstone by Inhibiting the Expression of ABCB11 via PKC-α.

The abnormal increase of Oddi sphincter pressure and total bile duct pressure may play an important role in the formation of cholesterol stones, but the specific molecular mechanism is still unclear. This study aims to investigate it through in vitro and in vivo experiments. A mouse model of Oddi sphincter dysfunction was constructed by stone-inducing diet. We compared the two groups with PKC-α inhibitor GÖ6976 and PKC-α agonist thymeleatoxin. Oddi sphincter pressure and total bile duct pressure were measured. Biochemical analysis of total cholesterol, bile acid and bilirubin was then conducted. The histopathologic changes of bile duct were observed by HE staining and the ultrastructure of liver cells and surrounding tissues was observed by transmission electron microscopy. Through the above experiments, we found that the change of PKC-α expression may affect the formation process of gallstones. The relationship between PKC-α and ABCB11 was further verified by in vitro and in vivo experiments. Our results suggest that ABCB11 and PKC-α are co-expressed in the tubule membrane of hepatocytes and interact with each other in hepatocytes. The high cholesterol diet further enhances the activation of PKC-α and thus reduces the expression of ABCB11. The formation of cholesterol stones is associated with the down-regulation of ABCB11 expression in the tubule membrane of hepatocytes due to kinase signaling. This is the first study to demonstrate that sphincter of Oddi dysfunction induces gallstones through PKC-α inhibition of ABCB11 expression.

Coreopsis tinctoria and Its Flavonoids Ameliorate Hyperglycemia in Obese Mice Induced by High-Fat Diet.

With the prevalence of obesity all over the world, human health has been seriously affected. In particular, the number of diabetic and cardiovascular diseases has increased dramatically. The herb Coreopsis tinctoria (C. tinctoria) shows diverse biological and pharmacological activities, which are mainly attributed to its flavonoids. However, the specific functional substances that play an active role in C. tinctoria remain unclear, and its mechanism has not been deeply explored. In this study, we established a diet-induced obesity (DIO) mice model and treated mice with C. tinctoria or kaempferol for 8 weeks. The results showed that both C. tinctoria and kaempferol lowered body weight, reduced fasting blood glucose, and improved glucose tolerance and insulin resistance to alleviate obesity in DIO mice. The level of hemoglobin A1c also decreased significantly after treatment with C. tinctoria and kaempferol. Moreover, the administration of C. tinctoria and kaempferol also restored gut microbiota imbalance and significantly increased Desulfovibrio and Butyricimonas levels, which have been reported to improve glucose metabolism and intestinal health. In general, our study shows that C. tinctoria is a potential hypoglycemic substance for obesity and may reduce blood glucose by regulating gut microbiota, and that kaempferol is one of the effective substances of C. tinctoria.

Aptamer-Functionalized Binary-Drug Delivery System for Synergetic Obesity Therapy.

The targeted delivery of phytochemicals that promote energy expenditure for obesity therapy remains a challenge. This study assembled a functionalized adipo-8 aptamer loaded with allicin using isothermal rolling-circle techniques to form a synergistic adipocyte-targeted binary-drug delivery system for treating obesity. The functionalized adipo-8 aptamer efficiently protected allicin from adsorption, showing significant potential to encapsulate, transport, and release molecular cargos into white adipose tissue. Introducing the negatively charged allicin, a phytochemical able to induce adipose tissue browning, reduced the diameters of DNA-nanoflower from 770 to 380 nm and increased cellular uptake efficiency up to 118.7%. The intracellular distribution observed via confocal microscopy confirmed the successful receptor recognition mediated by aptamers in the DNA-nanoflower-allicin (NFA) framework as well as its excellent stability to escape from lysosomes. In vivo results demonstrated that subcutaneous administration of NFA effectively promoted adipocyte browning and systematic energy expenditure with minimal side effects. Furthermore, the G-quadruplex in the mitochondrial uncoupling protein-1 promoter was found to be an interactive allicin target for regulating thermogenesis to combat obesity.

Diallyl Trisulfide Prevents Adipogenesis and Lipogenesis by Regulating the Transcriptional Activation Function of KLF15 on PPARγ to Ameliorate Obesity.

SCOPE: Diallyl trisulfide (DATS) is a bioactive compound in garlic. The anti-obesity effect of garlic oil has been reported, but the role and mechanism of DATS in preventing obesity remain to be explored. METHODS AND RESULTS: Studies with high-fat-diet-induced obese mice and 3T3-L1 adipocytes are performed. The results show that DATS significantly reduces lipid accumulation and repairs disordered metabolism in vivo by restraining adipogenesis and lipogenesis, and promoting lipolysis and fatty acid oxidation in white adipose tissue. In cells, DATS plays different roles at different stages of adipocyte differentiation. Notably, DATS reduces lipid accumulation mainly by inhibiting adipogenesis and lipogenesis at the late stage. KLF15 is knocked down in 3T3-L1 cells, which eliminate the inhibitory effect of DATS on adipogenesis and lipogenesis. The dual-luciferase reporter and ChIP assays indicate that DATS can inhibit the transcriptional activation function of KLF15 on PPARγ by inhibiting the binding of KLF15 to PPARγ promoter. The function comparison of structural analogs and the intervention of dithiothreitol show that disulfide bond is crucial for DATS to work. CONCLUSION: DATS prevents obesity by regulating the transcriptional activation function of KLF15 on PPARγ.

The KLF4-p62 axis prevents vascular endothelial cell injury via the mTOR/S6K pathway and autophagy in diabetic kidney disease.

INTRODUCTION: Diabetic kidney disease (DKD) is a complication of systemic diabetic microangiopathy, which has a high risk of developing into end-stage renal disease and death. This study explored the mechanism underlying autophagy in DKD vascular endothelial cell injury. MATERIAL AND METHODS: DKD and vascular endothelial cell injury models were established using Sprague Dawley rats and human umbilical vein endothelial cells (HUVECs). HUVECs overexpressing Kruppel-like factor 4 (KLF4) were constructed by transient transfection of plasmids. Biochemical determination of urinary protein and blood urea nitrogen (BUN), superoxide dismutase (SOD), and creatinine (Scr) levels was performed. Renal pathology was observed by periodic acid-Schiff (PAS) staining. Cell Counting Kit-8 (CCK8), terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), and immunocytochemistry (ICC) were used to analyse the growth and apoptosis of HUVECs. Microtubule-associated protein light chain 3 (LC3) expression was observed by immunofluorescence (IF). The reactive oxygen species (ROS) levels were measured using flow cytometry. Monocyte chemoattractant protein-1 (MCP-1), KLF4, and tumour necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA). The expression of KLF4, p62 protein, and LC3 was analysed using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). S6 kinase (S6K), p70 ribosomal S6 kinase (p-S6K), Beclin1, ATG5, LC3, p62, Caspase-3, mammalian target of rapamycine (mTOR), and phsophorylated mTOR (p-mTOR) expressions were detected by western blotting. RESULTS: PAS-positive substances (polysaccharide and glycogen) and S6K protein levels increased, and LC3 protein expression decreased in DKD rats. The levels of urinary protein, BUN, and Scr increased, and KLF4 decreased in DKD rats. High glucose (HG) levels decreased the proliferation and increased the apoptosis rate of HUVECs. The expression of ROS, TNF-α, MCP-1, and p62 increased, while the expression of SOD, KLF4, Beclin1, ATG5, and LC3 decreased in HG-induced HUVECs. KLF4 overexpression significantly increased Beclin1, ATG5, and LC3 protein expression and decreased p62 protein expression compared to the oe-NC group in HG-induced HUVECs. KLF4 overexpression inhibits the expression of Caspase-3, p-mTOR, and p-S6K in HG-induced HUVECs. CONCLUSIONS: KLF4-p62 axis improved vascular endothelial cell injury by regulating inflammation and the mTOR/S6K pathway in DKD.