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Dihydrofolate reductase (DHFR), a housekeeping enzyme in primary metabolism, has been extensively studied as a model of acid-base catalysis and a clinic drug target. Herein, we investigated the enzymology of a DHFR-like protein SacH in safracin (SAC) biosynthesis, which reductively inactivates hemiaminal pharmacophore-containing biosynthetic intermediates and antibiotics for self-resistance. Furthermore, based on the crystal structure of SacH−NADPH−SAC-A ternary complexes and mutagenesis, we proposed a catalytic mechanism that is distinct from the previously characterized short-chain dehydrogenases/reductases-mediated inactivation of hemiaminal pharmacophore. These findings expand the functions of DHFR family proteins, reveal that the common reaction can be catalyzed by distinct family of enzymes, and imply the possibility for the discovery of novel antibiotics with hemiaminal pharmacophore.

Fuzzy and temporal reasoning can effectively improve the accuracy of fault diagnosis methods. However, there are challenges in practical applications, such as missing alarm messages, temporal reasoning with complex calculations, and complex modeling processes. Therefore, this study proposes an improved temporal fuzzy reasoning spiking neural P (ITFRSNP) system for power system fault diagnosis. First, the ITFRSNP system and its reasoning method are proposed to perform association reasoning between confidence degrees and temporal constraints. Second, a general fault diagnosis model and process are developed based on the ITFRSNP system to diagnose various faulty components and simplify the modeling process. In addition, a search method is provided for identifying suspected faulty components, considering the missing alarm message of the circuit breaker. Simulation results of fault cases demonstrate that the proposed method exhibits high accuracy and fault tolerance. It can precisely identify faulty components despite incorrect operations or inaccurate alarm messages of protective relays and circuit breakers. Moreover, the search method effectively narrows down the diagnostic scope without missing suspected faulty components in scenarios where alarms from boundary circuit breakers are missing, thereby enhancing the fault diagnosis efficiency. The fault diagnosis model features a straightforward structure and reasoning process with minimal computational complexity, making it suitable for real-time diagnosis of complex faults within power systems.

Abstract Dendritic cell (DC) migration is a fundamental step during execution of its adaptive immunity functions. Studying DC migration characteristics is critical for development of DC‐dependent allergy treatments, vaccines, and cancer immunotherapies. Here, a microfluidics‐based single‐cell migration platform is described that enables high‐throughput and precise bidirectional cell migration assays. It also allows selective retrieval of cell subpopulations that have different migratory potentials. Using this microfluidic platform, DC migration is investigated in response to different chemoattractants and inhibitors, quantitatively describe DC migration patterns and retrieve DC subpopulations of different migratory potentials for differential gene expression analysis. This platform opens an avenue for precise characterization of cell migration and potential discovery of therapeutic modulators.

It is an urgent need to tackle drug-resistance microbial infections that are associated with implantable biomedical devices. Host defense peptide-mimicking polymers have been actively explored in recent years to fight against drug-resistant microbes. Our recent report on lithium hexamethyldisilazide-initiated superfast polymerization on amino acid N-carboxyanhydrides enables the quick synthesis of host defense peptide-mimicking peptide polymers. Here we reported a facile and cost-effective thermoplastic polyurethane (TPU) surface modification of peptide polymer (DLL: BLG = 90 : 10) using plasma surface activation and substitution reaction between thiol and bromide groups. The peptide polymer-modified TPU surfaces exhibited board-spectrum antibacterial property as well as effective contact-killing ability in vitro. Furthermore, the peptide polymer-modified TPU surfaces showed excellent biocompatibility, displaying no hemolysis and cytotoxicity. In vivo study using methicillin-resistant Staphylococcus aureus (MRSA) for subcutaneous implantation infectious model showed that peptide polymer-modified TPU surfaces revealed obvious suppression of infection and great histocompatibility, compared to bare TPU surfaces. We further explored the antimicrobial mechanism of the peptide polymer-modified TPU surfaces, which revealed a surface contact-killing mechanism by disrupting the bacterial membrane. These results demonstrated great potential of the peptide-modified TPU surfaces for practical application to combat bacterial infections that are associated with implantable materials and devices.

Antibiotic resistance is a major issue in medicine and new antimicrobials for treating resistant infection are needed. Here, the authors report on antibacterial peptoid polymers, prepared via NNCA ring-opening polymerization, demonstrating antibacterial function against MRSA in vitro and in in vivo infection models.

One of the main factors in triggering cascading outages is the unexpected tripping of backup protection caused by load encroachment (LE). Hence, LE should be identified quickly to avoid unexpected tripping. This paper proposes a fast LE identification method based on the wide-area measurement system (WAMS), applicable to transmission grids with high wind power penetration. Firstly, based on the improved shortest path algorithm, the method searches for critical lines greatly affected by the LE to determine the collected range of wide-area information. Then, by analyzing the hidden dangers of the existing calculation method for the active power estimation value (APEV) in the power system with wind farms, a fast calculation method of the APEV based on the WAMS is proposed to ensure that the existing LE identification criterion is still applicable in the high-penetration system of wind power. Finally, based on the PSASP platform, the wind farm model is integrated into the IEEE 39-bus New England system for simulation. The simulation results show that the method proposed in this paper can quickly search for the critical line set (CLS) and accurately identify the LE under high wind power penetration, effectively avoiding the unexpected tripping of backup protection and preventing cascading outages.

This paper puts forward a fault location method combining the improved matrix algorithm and the genetic tabu algorithm based on multi-source information in view of the limitation of existing fault location methods in active distribution networks, such as long-time consumption, low accuracy, and low tolerance performance. Firstly, the fault region location method is proposed to simplify the active distribution network model and reduce the matrix calculation dimension. Secondly, the improved matrix algorithm is proposed to locate the fault section, and a positioning result verification method is proposed to improve the tolerance performance. Finally, the genetic tabu algorithm is proposed to optimize suspicious fault sections when the verification is incorrect and obtain the positioning result. The simulation results show that the fault location method proposed in this paper locates faster and performs better in both accuracy and tolerance in different fault conditions than others.

Polyethylene glycol (PEG)–doxorubicin (DOX) conjugation is an important strategy to improve toxicity and enhance clinically therapeutic efficacy. However, with the frequent use of PEG-modified drugs, the accumulation of anti-PEG antibodies has become a tough issue, which limits the application of PEG–drug conjugation. As an alternative solution, poly(2-oxazoline) (POX)−DOX conjugation has shown great potential in the anti-tumor field, but the reported conjugation process of POX with DOX has drawbacks such as complex synthetic steps and purification. Herein, we propose a convenient and controllable strategy for the synthesis of POX−DOX conjugation with different chain lengths and narrow dispersity by N-boc-2-bromoacetohydrazide-initiated 2-ethyl-oxazoline polymerization and the subsequent deprotection of the N-Boc group and direct reaction with DOX. The DOX−PEtOx conjugates were firstly purified, and the successful conjugations were confirmed through various characterization methods. The synthetic DOX−PEtOxn conjugates reduce the toxicity of DOX and increase the selectivity to tumor cells, reflecting the promising application of this POX−DOX conjugation strategy in drug modification and development.

BackgroundClear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor. The purpose of the present study was to establish a novel immunotype for different immune infiltration and overall survival (OS) of patients with ccRCC.MethodsBased on the Cancer Genome Atlas Project (TCGA) database (discovery set), a novel immunotype was established using ssGSEA methods. The databases of Fudan University Shanghai Cancer Center (FUSCC) and Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine (XHH) served as an external validation set. GSEA was carried out to identify the immunotype associated signal transduction pathways.ResultsA total of 652 ccRCC patients were included in our study. We constructed a novel immunotype of ccRCC to classify patients into three groups: high-immunity, moderate-immunity, and low-immunity. The high-immunity and moderate-immunity groups had higher ImmuneScores, ESTIMATEScores, StromalScores, and lower tumor purity than that of the low-immunity group in both sets. Additionally, the patients from the high-immunity and moderate-immunity groups had longer survival than patients from low-immunity group in both discovery set and validation set (HR = 2.54, 95% CI: 1.56–4.13, p < 0.01; HR = 2.75, 95% CI: 1.24–6.11, p = 0.01).ConclusionIn summary, we defined a novel immunotype of ccRCC. The immune types could be used as a clinical predictive tool to identify ccRCC patients with different survival. In addition, the immune-related biological signaling pathway also brought new insights on the mechanism of ccRCC.

Abstract Background The treatment of critically ill patients with COVID-19 who were hospitalized in Wuhan has been reported. However, the clinical characteristics of patients who died of COVID-19 in regions with relatively scarce healthcare resources remain unknown. Methods In this retrospective study, a total of 14 patients who were admitted from January 18 to February 11, 2020 and died of COVID-19 were evaluated. The epidemiological, symptomatic, laboratory, radiological and treatment records were reviewed and analyzed. Results The mean age of the 14 patients was 56.7 (SD 15.3) years, and 8 (57.1%) were older than 50 years. Eight (57.1%) were men, and 11 (78.6%) had one or more high risk factors. The most common chronic diseases among these patients were cardiovascular disease (7, 50.0%), hypertension (6, 42.9%), and chronic kidney disease (5, 35.7%). General symptoms included cough (12, 85.7%), fever (11, 78.6%), and dyspnea (10, 71.4%). The median duration from the onset of symptoms to death was 11 (IQR 6.5–19.5) days, and the median duration from admission to death was 4.5 (1.0–11.8) days. Patients who died within 4.5 days had more severe pulmonary lesions, significantly reduced lymphocytes and elevated C-reactive protein (CRP). Most patients had organ dysfunction, including 13 (92.9%) with acute respiratory distress syndrome (ARDS), 4 (28.6%) with cardiac injury, 3 (21.4%) with acute kidney injury, and 3 (21.4%) with liver dysfunction. Conclusions Elderly SARS-CoV-2-infected patients with comorbidities, especially those with ARDS and severe chest CT findings on admission, are at increased risk of death and deserve special attention and quality medical treatment.

Abstract Potent and selective antifungal agents are urgently needed due to the quick increase of serious invasive fungal infections and the limited antifungal drugs available. Microbial metabolites have been a rich source of antimicrobial agents and have inspired the authors to design and obtain potent and selective antifungal agents, poly(DL‐diaminopropionic acid) (PDAP) from the ring‐opening polymerization of β‐amino acid N‐thiocarboxyanhydrides, by mimicking ε‐poly‐lysine. PDAP kills fungal cells by penetrating the fungal cytoplasm, generating reactive oxygen, and inducing fungal apoptosis. The optimal PDAP displays potent antifungal activity with minimum inhibitory concentration as low as 0.4 µg mL−1 against Candida albicans, negligible hemolysis and cytotoxicity, and no susceptibility to antifungal resistance. In addition, PDAP effectively inhibits the formation of fungal biofilms and eradicates the mature biofilms. In vivo studies show that PDAP is safe and effective in treating fungal keratitis, which suggests PDAPs as promising new antifungal agents.

Abstract Background Studies have indicated that changed expression of hypoxia-inducible factor-1α (HIF-1α) in epithelial cells from the kidney could affect the renal function in chronic kidney disease (CKD). As Angiotensin II (Ang II) is a critical active effector in the renin-angiotensin system (RAS) and was proved to be closely related to the inflammatory injury. Meanwhile, researchers found that Ang II could alter the expression of HIF-1α in the kidney. However, whether HIF-1α is involved in mediating Ang II-induced inflammatory injury in podocytes is not clear. Methods Ang II perfusion animal model were established to assess the potential role of HIF-1α in renal injury in vivo. Ang II stimulated podocytes to observe the corresponding between HIF-1α and inflammatory factors in vitro. Results The expression of inflammatory cytokines such as MCP-1 and TNF-α was increased in the glomeruli from rats treated with Ang II infusion compared with control rats. Increased HIF-1α expression in the glomeruli was also observed in Ang II-infused rats. In vitro, Ang II upregulated the expression of HIF-1α in podocytes. Furthermore, knockdown of HIF-1α by siRNA decreased the expression of MCP-1 and TNF-α. Moreover, HIF-1α siRNA significantly diminished the Ang II-induced overexpression of HIF-1α. Conclusion Collectively, our results suggest that HIF-1α participates in the inflammatory response process caused by Ang II and that downregulation of HIF-1α may be able to partially protect or reverse inflammatory injury in podocytes.

In order to improve the efficiency of the devices’ fault diagnosis of the protection systems of intelligent substation, a fault diagnosis method based on a gradient boosting decision tree (GBDT) was proposed. Using the integrated alarm information, the device self-checking information, the link information of generic object-oriented substation event (GOOSE) and sampled value (SV) and the sampling value information generated during the fault of the protection system, the fault feature information set is constructed. According to different fault characteristics, the protection system faults are classified into simple faults and complex faults to improve the diagnosis efficiency. Using GBDT training rules, a fault diagnosis model of protection system based on GBDT is established and fault diagnosis steps are given. This study takes a 110 kV intelligent substation in southern China as an example, to verify the effectiveness and accuracy of the proposed fault diagnosis method, and compared it with the existing methods in terms of the accuracy. The diagnostic accuracy in the case of false alarms and the case of multiple faults are verified. The results show that the method can meet the practical engineering application.

Digital twin technology aims to build a map of physical entities in virtual space, and simulate the real-time state and dynamic characteristics of physical devices through bi-directional interactive data flow. In order to guarantee the safe and stable operation of protection system equipment in intelligent substations and improve the efficiency of protection system operation and condition maintenance, this paper proposes a protection system state evaluation and fault prediction method based on digital twin technology. The architecture, application and operation control mode of digital twin technology in a real-time state analysis of a protection system are studied. The state evaluation model based on matter-element extension and the fault prediction model based on clustering algorithm are constructed. By analyzing the historical data of an intelligent station protection system in actual operation, a database that can be updated and corrected in real time is constructed. The effectiveness and accuracy of the state evaluation and fault prediction method are verified with actual cases, which can provide technical support for the operation and maintenance of the protection system.

Accumulating evidence suggested that long noncoding RNAs (lncRNAs) possess a potential role in prostate cancer (PCa) diagnosis and prognosis. Rapid biochemical recurrence (BCR) is considered as a sign for clinical recurrence metastasis and PCa-specific mortality. Hence, the aim of the present study was to identify a lncRNA signature that can predict BCR of PCa accurately. Bioinformatics analysis, Kaplan–Meier analyses, Cox regression analyses, and Gene Set Enrichment Analysis (GSEA) were performed in a publicly available database with 499 PCa tissues and 52 matched normal tissues. A signature was identified. All these lncRNAs were differentially expressed between tumor and normal tissues and differentially expressed between high Gleason score and low Gleason score tissues. Furthermore, we developed a seven lncRNAs signature that can predict PCa BCR. Patients classified into low-risk group showed better BCR survival significantly than the patients in the high-risk group (hazard ratio = 0.32, 95% CI: 0.20–0.52, concordance index = 0.63). The area under the curve was 0.68 for BCR. The signature also had good discrimination for BCR in men with Gleason 7 PCa. In conclusion, our results suggest that the seven lncRNAs signature is a new biomarker of BCR and high risk in PCa. In addition, the individual lncRNA warrants further study to uncover the associated mechanisms of PCa progression and the signature could be used to design direct clinical trials for adjuvant therapy.

Summary: Comprehensive evaluation of single T cell functions such as cytokine secretion and cytolysis of target cells is greatly needed in adoptive cell therapy (ACT) but has never been fully fulfilled by current approaches. Herein, we develop a hierarchical loading microwell chip (HL-Chip) that aligns multiple cells and functionalized beads in a high-throughput microwell array with single-cell/bead precision based on size differences. We demonstrate the potential of the HL-Chip in evaluating single T cell functions by three applications: high-throughput longitudinal secretory profiling of single T cells, large-scale evaluation of cytolytic activity of single T cells, and integrated T cell-tumor cell interactions. The HL-Chip is a simple and robust technology that constructs arrays of defined cell/object combinations for multiple measurements and material retrieval. : Zhou et al. describe the hierarchical loading microwell chip, which enables cell/bead pairing with high efficiency in a high-throughput manner. They conduct coupled measurements of cytotoxicity and cytokine secretion from single lymphocytes and uncover the linkage of lymphocytes’ functions together with the cell behavior. Keywords: microfluidics, single cell, cell-bead pairing, T cell function, cytokine detection, cell-cell interaction, cytotoxicity, adoptive cell therapy

Abstract Background To compare the predictive value of the current AJCC stage grouping for renal cell carcinoma (RCC) to our modifications. Patients and methods A total of 2120 patients with RCC from Fudan University Shanghai Cancer Center (FUSCC) database and 74 506 counterparts from SEER database were included. Cox regression was used to calculate the relative impacts between prognostic groups. The predictive accuracy of overall survival (OS) was assessed using the concordance index (C‐index), which was compared by likelihood ratio test. Results In FUSCC cohort, the 5‐year‐OS rate for T3N0M0 patients was higher than T1‐3N1M0 (72.7% vs 38.1%). The 5‐year‐OS rate for T4N0M0 was 36.2%, which was close to T1‐3N1M0 but not to T4N1M0 (0%) and TanyNanyM1 (12.6%). The elements of AJCC groups were regrouped according to the ranks of hazard ratios. The modified stages II (T3N0M0), III (T1‐3N1M0, T4N0M0), and IV (T4N1M0, TanyNanyM1) exhibited greater survival stratification than AJCC groups. The modifications were validated in SEER cohort and yielded similar survival outcomes. The predictive accuracy of OS in modified prognostic groups was significantly higher than AJCC groups in stages II‐IV subgroups in both FUSCC (C‐index: 0.801 vs 0.779, P

Abstract Background To investigate the effect of miR-221-5p on cell proliferaton and metastasis of human prostate cancer in vitro and vivo. Methods We established PC3 cell lines with stable overexpression or silencing of miRNA-221-5p via lentivirus infection. miRNA-221-5p and its target gene SOCS1 expression levels in the stable cells were analyzed by real-time polymerase chain reaction (RT-PCR) and western blotting. Using luciferase reporter assays to study the relationship between miR-221-5p and SOCS1. Cell proliferative activity was measured using the MTT assay and colony formation assay. Migration ability was assessed using wound-healing assay and transwell assay. To further study the function of miR-221-5p in human prostate cancer we established nude mice xenograft model in vivo. Results miR-221-5p regulates the proliferation, migration of prostate cancer cells in vitro and tumorigenesis in vivo by regulating socs1 expression through targeted its 3’UTR, and miR-221-5p regulates MAPK/ERK signaling pathway and EMT features in prostate cancer cells. Conclusions Up-regulation and silencing of miR-221-5p expression in prostate cancer cells are correlated with cell proliferation, migration and tumorigenesis, which suggest that miR-221-5p plays an important role in prostate cancer progression.

Prostate cancer (PCa) is one of the most common malignancies in male. We aim to establish a novel gene signature for immune infiltration and outcome (biochemical recurrence (BCR) and overall survival (OS)) of patients with prostate cancer (PCa) to augment Gleason patterns for evaluating prognosis and managing patients undergoing radical prostatectomy (RP). Combined with our microarray data and the Cancer Genome Atlas Project (TCGA) database (discovery set), we identified a six-gene signature. The Gene Expression Omnibus (GEO) database served as the test set. The databases of Fudan University Shanghai Cancer Center (FUSCC) and Third Affiliated Hospital of Nantong University (TAHNU) served as an external validation set. Immunohistochemistry was used to investigate the relationship between risk groups and the immune infiltrate. We identified a six-gene signature to predict immune cell infiltration and outcome of PCa patients. The AUC values used to predict early BCR in the discovery, test, FUSCC, and TAHNU sets were 0.73, 0.76, 0.72, and 0.81, respectively. Low-risk score patients in each dataset experienced significantly longer OS (P = .01, 0.04, 0.02, respectively). The signature also predicted high regulatory T cells (Tregs) and M2-polarized macrophages infiltration in high-risk score patients with PCa. Additionally, high mutation load, related signal pathways, and sensitivity to anticancer drugs that correlated with high-risk score of cancer progression and death were also identified. The six-gene signature may improve prognostic information, serve as a prognostic tool to manage patients after RP, and advance basic studies of PCa.

Background: As conditional survival could provide more relevant prognostic information at each follow-up time, the present study aimed to assess conditional overall survival (COS) based on two cohorts and assess the risks of death due to renal cell carcinoma (RCC) vs. other causes.Methods: The Fudan University Shanghai Cancer Center (FUSCC) and Surveillance, Epidemiology, and End Results (SEER) database were used as the source of data for our analysis. COS and cancer-specific survival were evaluated using the Kaplan–Meier method.Results: A total of 90,927 patients (SEER cohort = 88,807, FUSCC cohort = 2,120) were enrolled. Our results suggest that hazards of other causes-related death were always higher than that of cancer-specific death in low-risk RCC patients, but lower in metastatic RCC patients. It exceeded that of cancer-specific death by 8 years in high-risk RCC patients. Only in metastatic RCC patients, the COS improved markedly with survivorship increasing. After surviving 1, 2, 3, 4, and 5 years, the 5 years COS increased by +10, +18, +23, +29, and 35% (the observed 5 years OS: 12%), respectively.Conclusions: COS can better help patients with metastatic RCC rather than other RCC patients. Additionally, COS brings optimism for metastatic RCC patients with expected poorer prognosis psychologically.

An amendment to this paper has been published and can be accessed via the original article.

Background/Aims: Primary glomerulonephritis (PGN) is the most common reason inducing end stage renal disease in China, however, its pathogenesis remains unclear. The present study was designed to test the hypothesis that the formation and activation of NLRP3 (Nod-like receptor family pyrin domain containing 3) inflammasomes is an important initiating mechanism resulting in PGN. Methods: Serum samples and frozen sections were collected from 38 cases with PGN, and renal tissues were obtained from 22 of them. NLRP3 inflammasomes were detected by RT-PCR and immunofluoresence methods. The relationship between NLRP3 and clinical/pathologic indexes was analyzed. Results: RT-PCR analyses demonstrated that the mRNA levels of NLRP3 and caspase-1 genes were elevated significantly in renal tissues of PGN patients compared to those from normal pericarcinoma tissues. Moreover, the increased level of NLRP3 mRNA was correlative with a decrease in nephrin mRNA level and an increase in desmin mRNA level, which indicates that NLRP3 participates in podocyte injury in PGN patients. Immunofluorescence analysis also showed the protein expressions of NLRP3 and caspase-1 were increased in the glomeruli of PGN patients. Neverthless, there was no obvious regularity was presented in further subgroup analysis according to pathological types. In addition, increased NLRP3 was associated with the deterioration of renal function and glomerulosclerosis. IL-1β, a product of NLRP3 inflammasome activation, had a significant correlation with proteinuria. Conclusions: The formation and activation of NLRP3 inflammasomes in podocytes has been importantly implicated in the development of PGN-associated glomerular injury.

Objective. This study is aimed at investigating whether exenatide (Exe) delays the progression of nonalcoholic fatty liver disease (NAFLD) in C57BL/6 mice by targeting the NLRP3 inflammasome through the autophagy/mitophagy pathway. Methods. Thirty male C57BL/6 mice were randomly divided into three groups: control group (n=10), model group (n=10), and Exe (exenatide) group (n=10). Mouse models of NAFLD and diabetes were established using a high-fat diet and streptozocin. Results. The levels of fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) in the serum were significantly reduced after Exe treatment. The body weight, liver weight/body weight, and number of lipid droplets in the liver significantly decreased in Exe-treated mice. Treatment with Exe markedly reduced the levels of liver lipids, malondialdehyde (MDA), and alanine aminotransferase (ALT) in serum and livers. The number of autophagosomes increased significantly in the Exe group. The expression of LC3A/B-II/I, Beclin-1, Parkin, and BNIP3L increased significantly, whereas NLRP3 and IL-1β proteins were suppressed after Exe treatment. Conclusion. We successfully established a mouse model of NAFLD and diabetes. Exe may reduce oxidative stress injury and inhibit the NLRP3 inflammasome by enhancing the autophagy/mitophagy pathway in liver, which has a protective effect on the liver in NAFLD and diabetes in C57BL/6 mice.

A wide range of microalbuminuria cutoff values are currently used for diagnosing the early stage of nephropathy in type 2 diabetes (T2D). This study analyzed the relationships between oxidant and antioxidant markers of nephropathy and the severity of microalbuminuria. The study included 50 healthy controls (Group 1), 50 diabetic patients with no nephropathy (Group 2), 50 diabetic patients with nephropathy and a urinary albumin excretion (UAE) of 30–200 mg/24 h (Group 3), and 50 diabetic patients with UAE 200–300 mg/24 h (Group 4). Serum nitrotyrosine, conjugated dienes, 8-hydroxy-2′-deoxyguanosine (8-OHdG), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) levels were determined. Oxidative stress is increased in the early stage of nephropathy in patients with T2D. There was a significant correlation between the extent of microalbuminuria and markers of oxidative stress. Multiple linear regression analysis identified lipid oxidative stress as a possible independent marker for evaluating the degree of renal damage in diabetic nephropathy. Stratifying microalbuminuria values during the early stage of nephropathy might be an important factor in facilitating earlier and more specific interventions.