Pd/IPrBIDEA-Catalyzed Hydrodefluorination of gem-Difluorocyclopropanes: Regioselective Synthesis of Terminal Fluoroalkenes.

Developing new strategies to enable chemo- and regioselective reductions is an important topic in chemical research. Herein, an efficient and regioselective Pd/IPrBIDEA-catalyzed ring-opening hydrodefluorination of gem-difluorocyclopropanes to access terminal fluoroalkenes is developed. The success of this transformation was attributed to the use of 3,3-dimethylallyl Bpin as a novel hydride donor. DFT calculations suggest that a direct 3,4'-hydride transfer via a 9-membered cyclic transition state is more favorable, which combined with the irreversibility of the reaction enables the unusual selectivity for the less thermodynamically stable terminal alkene isomer. This reaction mode is also applicable to a variety of regioselective allylic and propargyl reductions.

Efficacy and safety of surufatinib plus toripalimab, a chemotherapy-free regimen, in patients with advanced gastric/gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, or biliary tract cancer.

BACKGROUND: The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib showed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumors in a phase I study. METHODS: This open-label, multi-cohort study in China enrolled patients with advanced solid tumors who had failed or were intolerable to standard treatment into tumor-specific cohorts. Patients received surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every three weeks). Results for three cohorts (gastric/gastroesophageal junction [GC/GEJ] adenocarcinoma, esophageal squamous cell carcinoma [ESCC], and biliary tract carcinoma [BTC]) are reported here. The primary endpoint was investigator-assessed objective response rate (ORR) per Response Evaluation criteria in Solid Tumors version 1.1. RESULTS: Between December 17, 2019, and January 29, 2021, 60 patients were enrolled (GC/GEJ, n = 20; ESCC, n = 20; BTC, n = 20). At data cutoff (February 28, 2023), ORRs were 31.6%, 30.0%, and 11.1%, respectively. Median progression-free survival was 4.1, 2.7, and 2.9 months, respectively. Median overall survival was 13.7, 10.4, and 7.0 months, respectively. Overall, grade ≥ 3 treatment-related adverse events occurred in 28 (46.7%) patients. CONCLUSIONS: Surufatinib plus toripalimab showed promising antitumor activity and a tolerable safety profile in immunotherapy-naïve patients with GC/GEJ adenocarcinoma, ESCC, or BTC. These findings warrant further study in larger randomized trials comparing surufatinib plus toripalimab with standard therapies in these tumors. CLINICALTRIALS: gov NCT04169672.

A colorimetric and electrochemical dual-mode Hg2+ sensor utilizing oxidase-like activity arising from the combination of Hg2+ and palladium metal-organic framework@graphene.

Developing convenient and reliable methods for Hg2+ monitoring is highly important. Some precious metal nanomaterials with intriguing peroxidase-like activity have been used for highly sensitive Hg2+ detection. However, H2O2 must be added during these detections, which impedes practical applications of Hg2+ sensors due to its susceptible decomposition by environmental factors. Herein, we discovered that the combination of Hg2+ and palladium metal-organic framework@graphene (Pd-MOF@GNs) exhibits oxidase-like activity (OXD). In the absence of H2O2, this activity not only catalyzes the oxidation of chromogenic substrates such as 3,3',5,5'-tetramethylbenzidine (TMB) or o-phenylenediamine (OPD) to produce a color change but also enhances the electrical signals during OPD oxidation. Based on these properties, an effective and convenient dual-mode colorimetric and electrochemical sensor for Hg2+ has been developed. The colorimetric and amperometric linear relationships for Hg2+ were 0.045 µM-0.25 mM and 0.020 µM-2.0 mM, respectively. The proposed strategy shows good recovery in real sample tests, indicating promising prospects for multiple environmental sample detection of Hg2+ without relying on H2O2. The colorimetric and electrochemical dual-mode Hg2+ sensor is expected to hold great potentials in applications such as environmental monitoring, rapid field detection, and integration into smartphone detection of Hg2+.

Designing low-carbon fly ash based geopolymer with red mud and blast furnace slag wastes: Performance, microstructure and mechanism.

In order to tackle the environmental problems induced by Portland cement production and industrial solid wastes landfilling, this study aims to develop novel ternary cementless fly ash-based geopolymer by recycling red mud and blast furnace slag industrial solid wastes. The fresh-state properties, mechanical strength, water permeability, phase assemblage and microstructure were systematically investigated to evaluate the performance variation and reveal the hydration mechanism for geopolymers with different mixing proportions. The results showed that a higher slag content or a lower red mud content could result in the higher fluidity and shorter setting time for fresh mixture. The existence of slag promoted the transformation of N-A-S-H to C-A-S-H gel, which contributed to higher compressive strength and better resistance to water penetration. However, an excessive incorporation of 30% red mud may impede the generation of N-A-S-H gel and form more flocculent-like loose hydrates, thus to mildly degrade the mechanical strength and anti-permeability. The synergetic utilization of red much and blast furnace slag in fly ash-based geopolymer led to much less CO2 emission compared with the condition that red much or slag was singly added, which demonstrated prominent environmental advantages for such kind of ternary cementless geopolymer with equivalent mechanical strength.

Regulation of PM2.5 on mitochondrial damage in H9c2 cells through miR-421/SIRT3 pathway and protective effect of miR-421 inhibitor and resveratrol.

Fine particulate matter (PM2.5) exposure is associated with cardiovascular disease (CVD) morbidity and mortality. Mitochondria are sensitive targets of PM2.5, and mitochondrial dysfunction is closely related to the occurrence of CVD. The epigenetic mechanism of PM2.5-triggered mitochondrial injury of cardiomyocytes is unclear. This study focused on the miR-421/SIRT3 signaling pathway to investigate the regulatory mechanism in cardiac mitochondrial dynamics imbalance in rat H9c2 cells induced by PM2.5. Results illustrated that PM2.5 impaired mitochondrial function and caused dynamics homeostasis imbalance. Besides, PM2.5 up-regulated miR-421 and down-regulated SIRT3 gene expression, along with decreasing p-FOXO3a (SIRT3 downstream target gene) and p-Parkin expression and triggering abnormal expression of fusion gene OPA1 and fission gene Drp1. Further, miR-421 inhibitor (miR-421i) and resveratrol significantly elevated the SIRT3 levels in H9c2 cells after PM2.5 exposure and mediated the expression of SOD2, OPA1 and Drp1, restoring the mitochondrial morphology and function. It suggests that miR-421/SIRT3 pathway plays an epigenetic regulatory role in mitochondrial damage induced by PM2.5 and that miR-421i and resveratrol exert protective effects against PM2.5-incurred cardiotoxicity.

A lifetime economic research of universal HLA-B*58:01 genotyping or febuxostat initiation therapy in Chinese gout patients with mild to moderate chronic kidney disease.

OBJECTIVE: To evaluate Chinese long-term economic impact of universal human leukocyte antigen B (HLA-B)*58:01 genotyping-guided urate-lowering therapy or febuxostat initiation therapy for gout patients with mild to moderate chronic kidney disease (CKD) from perspective of healthcare system. METHODS: A Markov model embedded in a decision tree was structured including four mutually exclusive health states (uncontrolled-on-therapy, controlled-on-therapy, uncontrolled-off-therapy, and death). Mainly based on Chinese real-world data, the incremental costs per quality-adjusted life years (QALYs) gained were evaluated from three groups (universal HLA-B*58:01 testing strategy, and no genotyping prior to allopurinol or febuxostat initiation therapy) at 25-year time horizon. All costs were adjusted to 2021 levels based on Chinese Consumer Price Index and were discounted by 5% annually. One-way and probability sensitivity analysis were performed. RESULTS: Among these three groups, universal HLA-B*58:01 genotyping was the most cost-effective strategy in base-case analysis according to Chinese average willingness-to-pay threshold of $37 654.50 per QALY. The based incremental cost-effectiveness ratio was $31784.55 per QALY, associated with 0.046 additional QALYs and $1463.81 increment costs per patient at a 25-year time horizon compared with no genotyping prior to allopurinol initiation strategy. Sensitivity analysis showed 64.3% robustness of these results. CONCLUSION: From Chinese perspective of healthcare system, HLA-B*58:01 genotyping strategy was cost-effective for gout patients with mild to moderate CKD in mainland China, especially in the most developed area, such as Beijing and Shanghai. Therefore, we suggest China's health authorities choose the genotyping strategy and make different recommendations according to the differences of local conditions.

Amine-Induced Selective C-C Bond Cleavage of 2,2,2-Trifluoroethyl Carbonyls for the Synthesis of Ureas and Amides.

An efficient and selective transformation of 2,2,2-trifluoroethyl carbonyls into ureas/amides with amines is reported. This protocol allows the selective cleavage of the C-C bond of 2,2,2-trifluoroethyl carbonyls under transition metal-free and oxidant-free conditions, which is in contrast to the analogous C-F or C-CF3 bond functionalization. This reaction reveals the unexplored reactivity of 2,2,2-trifluoroethyl carbonyls and exhibits a broad substrate range and good functional group tolerance.

Pd-IHept-Catalyzed Ring-Opening of gem-Difluorocyclopropanes with Malonates Via Selective C-C Bond Cleavage: Synthesis of Monofluoroalkenes.

Monofluoroalkene scaffolds are frequently found in various functional molecules. Herein, we report a Pd-IHept-catalyzed (NHC = N-heterocyclic carbene) defluorinative functionalization approach for the synthesis of monofluoroalkenes from gem-difluorocyclopropanes and malonates. The flexible yet sterically hindered N,N'-bis(2,6-di(4-heptyl)phenyl)imidazol-2-ylidene ligand plays a key role in ensuring the high reaction efficiency. In addition, sterically hindered 1,1- and 1,2-disubstituted gem-difluorocyclopropanes could also be used in this transformation.

Stuttering as a signal of encephalopathy associated with toripalimab in a pancreatic ductal adenocarcinoma patient: a case report.

BACKGROUND: Immune checkpoint inhibitor (ICI) combined with chemotherapy has exhibited promising results in small sample studies of pancreatic cancer patients. The efficacy of toripalimab, a programmed cell death protein 1 (PD-1) monoclonal antibody has been explored in the previous studies and it was established that immune-related adverse events (irAEs) associated with administration of this drug deserve proper attention and adequate management. CASE PRESENTATION: A 43-year-old female patient with advanced pancreatic ductal adenocarcinoma (PDAC) was treated with toripalimab in combination with gemcitabine and nab-paclitaxel (T-GA) as the first-line treatment. She developed immune-related encephalopathy with stuttering as the main clinical symptom and Magnetic resonance imaging (MRI) showed multiple cerebral white matter demyelination changes, concomitant with asymptomatic cardiac enzyme elevation and hypothyroidism. The symptoms resolved after the discontinuation of toripalimab and corticosteroid treatment. CONCLUSIONS: Stuttering might be an early sign of neurotoxicity which can be easily neglected during the treatment. These findings provide guidance for the identification of these rare and occult neurological irAEs (n-irAEs) in the clinical practice.

Formyl peptide receptor 2 as a potential therapeutic target for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a global health burden whose existing treatment is largely dependent on anti-inflammatory agents. Despite showing some therapeutic actions, their clinical efficacy and adverse events are unacceptable. Resolution as an active and orchestrated phase of inflammation involves improper inflammatory response with three key triggers, specialized pro-resolving mediators (SPMs), neutrophils and phagocyte efferocytosis. The formyl peptide receptor 2 (FPR2/ALX) is a human G protein-coupled receptor capable of binding SPMs and participates in the resolution process. This receptor has been implicated in several inflammatory diseases and its association with mouse model of IBD was established in some resolution-related studies. Here, we give an overview of three reported FPR2/ALX agonists highlighting their respective roles in pro-resolving strategies.

Chemo-, Stereo- and Regioselective Fluoroallylation/Annulation of Hydrazones with gem-Difluorocyclopropanes via Tunable Palladium/NHC Catalysis.

Defluorinative manipulation of polyfluorinated molecules has shown great promise due to its granting of synthetic versatility to inert C-F bonds. The development of chemo-, stereo- and regioselective strategies to realize highly efficient formation of either the linear/branched or E/Z products from gem-difluorocyclopropanes (gem-F2 CPs) is a challenging task. Herein, we have realized palladium/NHC-catalyzed fluoroallylation/annulation of hydrazones with gem-F2 CPs that incorporate the hydrazone N2 moiety into the products. The thermodynamically unstable fluorinated E-allylation products with aryl ketone hydrazones were obtained for the first time, while the di-alkyl ketone hydrazones yielded the monofluorinated products with branched selectivity under similar reaction conditions. With aldehyde hydrazones, two kinds of pyrazoles were obtained via a defluorinative allylation/annulation cascade, in which different carbon atoms of gem-F2 CPs could be incorporated into the pyrazole rings regiospecifically. DFT calculations revealed that the divergent selectivity was kinetically controlled and the final C-C bond formation proceeded through a 7-membered TS.

Baseline radiologic features as predictors of efficacy in patients with pancreatic neuroendocrine tumors with liver metastases receiving surufatinib.

Objective: Currently, pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases (PNELM) receiving surufatinib treatment was unsatisfying. Our objective was to examine the association between radiological characteristics and efficacy/prognosis. Methods: We enrolled patients with liver metastases in the phase III, SANET-p trial (NCT02589821) and obtained contrast-enhanced computed tomography (CECT) images. Qualitative and quantitative parameters including hepatic tumor margins, lesion volumes, enhancement pattern, localization types, and enhancement ratios were evaluated. The progression-free survival (PFS) and hazard ratio (HR) were calculated using Cox's proportional hazard model. Efficacy was analyzed by logistic-regression models. Results: Among 152 patients who had baseline CECT assessments and were included in this analysis, the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters. In the multivariable analysis of patients receiving surufatinib (N=100), those with higher arterial phase standardized enhancement ratio-peri-lesion (ASER-peri) exhibited longer PFS [HR=0.039; 95% confidence interval (95% CI): 0.003-0.483; P=0.012]. Furthermore, patients with a high enhancement pattern experienced an improvement in the objective response ratio [31.3% vs. 14.7%, odds ratio (OR)=3.488; 95% CI: 1.024-11.875; P=0.046], and well-defined tumor margins were associated with a higher disease control rate (DCR) (89.3% vs. 68.2%, OR=4.535; 95% CI: 1.285-16.011; P=0.019) compared to poorly-defined margins. Conclusions: These pre-treatment radiological features, namely high ASER-peri, high enhancement pattern, and well-defined tumor margins, have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib.

CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma.

BACKGROUND: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it's role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. METHODS: In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. RESULTS: As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05). CONCLUSION: In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.

High PD-L1 level of advanced hepatic lymphoepithelioma-like carcinoma response favorably to lenvatinib plus toripalimab.

Lymphoepithelioma-like carcinoma (LELC) is an uncommon subtype of primary liver cancer with predominant lymphocyte infiltration and a relatively favorable outcome. However, no standard treatment for advanced hepatic LELC has been established. Here, we give a first report of a 60-year-old man with advanced hepatic LELC who had a high expression of PD-L1 in tumor cells and a high level of tumor-infiltrating leukocytes (TILs) in the tumor microenvironment (TME). After receiving six cycles of multiple receptor tyrosine kinase inhibitor (rTKI) with lenvatinib plus PD-1 inhibitor toripalimab treatment, the patient achieved persistent partial response (PR). Our report indicates that advanced hepatic LELC with high expression of PD-L1 may benefit from the combination of rTKI and PD-L1/PD-1 blockade. Therefore, this potential strategy should be considered when treating those rare liver cancers.

Biweekly Raltitrexed Combined With Irinotecan as Second-Line Therapy for Patients With Metastatic Colorectal Cancer: A Phase II Trial.

OBJECTIVE: Irinotecan-based doublet chemotherapy strategy was standard second-line backbone for patients with oxaliplatin-refractory metastatic colorectal cancer. The aim of this study was to evaluate tolerability and efficacy of raltitrexed combined with irinotecan biweekly administered as the second-line therapy for mCRC patients. METHODS: The study was a prospective, single-center, non-randomized, open-label phase II clinical trial. Patients with mCRC after failure with oxaliplatin and fluoropyrimidine or its derivatives were enrolled. Irinotecan (180 mg/m2) and raltitrexed (2.5 mg/m2) were given intravenously on day 1. Cycles were repeated every 2 weeks. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events (AEs). RESULTS: Between December 2012 and October 2016, 33 and 35 patients enrolled were assessed for response and safety, respectively. The ORR was 8.6%, and the DCR was 71.4%. The median PFS was 4.5 months (95% CI 3.8-5.2). The median OS was 12.0 months (95% CI 8.5-15.5). Four patients received conversion therapy to no evidence of disease (NED), and 2 patients were still alive with beyond 24 months survival. The most common grade 3/4 AEs were anorexia (14.3%), vomiting (14.3%), nausea (11.4%), fatigue (8.6%), and leukopenia (8.6%). No one died from treatment-related events. The incidence and severity of toxicity were irrelevant to UGT1A1 status. CONCLUSIONS: The combination of irinotecan with raltitrexed is an efficient, convenient, and acceptable toxic regimen for second-line treatment for mCRC patients.

ß-Perfluoroalkyl Peroxides as Fluorinated C3-Building Blocks for the Construction of Benzo[4,5]imidazo[1,2-a]pyridines.

An efficient and selective protocol for the synthesis of perfluoroalkyl-group-substituted benzo[4,5]imidazo[1,2-a]pyridines has been developed in which ß-perfluoroalkyl peroxides act as novel fluorinated C3-building blocks to implement regioselective [3 + 3] annulation with 2-cyanomethyl benzimidazole under metal-free conditions. The application of the synthesized perfluoroalkylated BIPs as potent anticancer reagents versus the nonfluorinated ones demonstrated the biological utility of this method.

Response to chemotherapy combined with anlotinib plus anlotinib maintenance in intra-abdominal desmoplastic small round cell tumors (IADSRCT): a case report and literature review.

BACKGROUND: Intra-abdominal desmoplastic small round cell tumors (IADSRCT) are rare and aggressive neoplasia that are resistant to chemotherapy. Anlotinib is an oral multi-target tyrosine kinase inhibitor that also has anti-angiogenic and anti-proliferative properties. In this article, we report on a case showing effective and durable responses to chemotherapy combined with anlotinib in a young man with IADSRCT. CASE PRESENTATION: A 27-year-old man was admitted to our hospital complaining of a palpable periumbilical mass that had been present for longer than 4 months. The diagnosis of IADSRCT was confirmed by biopsy and immunohistochemistry. An extensive unresectable metastasis was found on the initial diagnosis. The patient received six cycles of chemotherapy combined with anlotinib, and maintenance therapy with anlotinib was recommended. Hematochezia, proteinuria and hypertension were observed, however, long-term maintenance therapy was well tolerated. A partial response was observed after two cycles of combined therapy and the patient was still alive with stable disease at the time of reporting. CONCLUSIONS: Chemotherapy combined with anlotinib plus anlotinib maintenance showed promising efficacy and manageable toxicity in the treatment of advanced IADSRCT.

Population pharmacokinetic and dose optimization of mycophenolic acid in children with anti-neutrophilic cytoplasmic antibody-associated nephritis.

PURPOSE: Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis is a rare autoimmune disease. Mycophenolic acid (MPA) is widely used for ANCA-associated nephritis (AAN) but with large pharmacokinetic variability. This study aims to investigate clinical factors impacting MPA disposition in pediatric AAN. METHODS: We retrospectively collected 391 MPA concentrations from 25 children diagnosed with AAN. A population pharmacokinetic model was developed to explore the potential effects of demographics and biochemical covariates on MPA. Monte Carlo simulations were performed to optimize dosage regimen. RESULTS: MPA pharmacokinetics best fitted a two-compartment model with first-order absorption and linear elimination. The pharmacokinetic parameters for Ka, CL/F, Vc/F, Vp/F, and Q/F were 0.45 h-1, 9.86 L/h, 19.69 L, 408.32 L, and 23.01 L/h. Dosage form significantly affected drug absorption. CL/F significantly decreased with increasing cystatin C, while decreasing with myeloperoxidase. Cystatin C was superior to serum creatinine in predicting apparent clearance of MPA. A dose regimen of 650 mg/m2 twice daily was required to achieve target exposure in children with normal renal function and no inflammation. The combined effects of myeloperoxidase concentration and renal function resulted in a sixfold range of MPA dose. CONCLUSION: This was the first study of MPA population pharmacokinetic model in children with AAN. Myeloperoxidase was not only a biomarker of AAN, but also an inflammatory factor to impact drug CL. The influence of renal function and underlying diseases on drug metabolism should be fully considered in personalized medication for AAN.

Study on antibiotics, antibiotic resistance genes, bacterial community characteristics and their correlation in the landfill leachates.

AIM: This study aimed to investigate the contamination levels of antibiotics and antibiotic resistance genes (ARGs) in the landfill leachates and their correlations with the bacteria. METHODS AND RESULTS: Using HPLC-MS, quantitative PCR and high-throughput sequencing, we measured the pollution levels of 14 antibiotics and 10 ARGs in the leachates of the landfill in Taiyuan, China, and analysed changes in the bacterial community and the correlations of bacteria with antibiotics and ARGs. The main results showed high levels of antibiotics (like enrofloxacin, pefloxacin and oxytetracycline) and ARGs (like sulfonamides, tetracycline, macrolides, quinolones and ß-lactam-resistance genes) in the landfill leachates, along with higher diversity and richness of the bacteria. Some types of antibiotics had positive correlations with their corresponding ARGs. The dominant bacteria in the landfill leachates were Pseudomonas, Defluviitoga and Sulfurimonas, which correlated with the antibiotics and ARGs and might have potential effects on degrading them. CONCLUSIONS: Antibiotics and ARG pollution existed in the landfill leachates, while bacteria were closely associated with them. SIGNIFICANCE AND IMPACT OF THE STUDY: It will provide helpful information for the potential application of the bacteria in antibiotics and ARGs pollution control and landfill leachate management.

MicroRNA-494-3p Exacerbates Renal Epithelial Cell Dysfunction by Targeting SOCS6 under High Glucose Treatment.

BACKGROUND: Diabetic nephropathy is a common complication of the kidneys induced by diabetes and is the main cause of end-stage renal disease. MicroRNA-494-3p was reported to be upregulated in renal tissues collected from db/db mice, but its specific role in diabetic nephropathy was still unclear. This study aimed to explore the effect of miR-494-3p on renal fibrosis using an in vitro cell model of diabetic nephropathy. METHODS: After human renal tubular epithelial cells (HK-2) were treated with high glucose (HG), the viability and apoptosis of cells were examined by CCK-8 assays and flow cytometry analyses. Additionally, protein levels of fibronectin, collagen I, collagen III, collagen IV, and epithelial-mesenchymal transition (EMT) markers in HG-induced HK-2 cells were quantified by Western blotting. miR-494-3p expression in HK-2 cells was detected by reverse-transcription quantitative polymerase chain reaction. The binding relation between miR-494-3p and the messenger RNA suppressor of cytokine signaling 6 (SOCS6) was detected by luciferase reporter assays. RESULTS: HG reduced cell viability and enhanced cell apoptosis in a time- or concentration-dependent manner. Additionally, HG induced collagen accumulation and triggered the EMT process. miR-494-3p was upregulated in HG-treated HK-2 cells. miR-494-3p inhibition alleviated HG-induced cell dysfunction. Mechanistically, miR-494-3p bound with SOCS6 and negatively regulated SOCS6 expression. Moreover, silencing SOCS6 rescued the suppressive effect of miR-499-5p inhibition on HG-induced cell dysfunction. CONCLUSION: miR-494-3p aggravates renal fibrosis, EMT process, and cell apoptosis by targeting SOCS6, suggesting that the miR-494-3p/SOCS6 axis may become a potential strategy for the treatment of diabetic nephropathy.