A high rain-erosion resistant bio-based nanogel with continuous immunity induction for plant virus inhibition.

Tobacco mosaic virus (TMV) is the most widely spread and harmful virus in the world, causing serious economic losses annually. However, the low anti-erosion ability of the pesticides for TMV management make it easy to be washed by the rain, which makes the effective duration of the pesticides shorter. In this paper, a new bio-based nanogel with superior antiviral activity was reported, and its slow-release behavior, rain erosion resistance and the antiviral mechanism was systematically studied. The results determined that the nanogels (Zn2+@ALGNP and Zn2+@ALGNP@PL) exhibited sustained releasing of Zn2+ with a 7 days duration, and the ε-PL coating could enhance the releasing rate of Zn2+. Moreover, Zn2+@ALGNP@PL displayed a lower contact angle, indicating greater adhesion to the leaf surface, and in consequence imposed better resistance to simulate rain erosion than pure Zn2+. Strikingly, Zn2+@ALGNP@PL could inhibit plant virus infection by aggregating the virions and reducing its coat protein stability, as well as inducing the efficient expression of reactive oxygen species, antioxidant enzymes and resistance genes to enhance plant resistance and promote plant growth. Overall, this study had successfully developed a high rain-erosion resistant bio-based nanogel capable of continue to induce resistant plants and promote plant growth.

Folate deficiency reduced aberrant level of DOT1L-mediated histone H3K79 methylation causes disruptive SHH gene expression involved in neural tube defects.

BACKGROUND: Neural tube defects (NTDs) are one of the most severe congenital abnormalities characterized by failures of the neural tube to close during early embryogenesis. Maternal folate deficiency could impact the occurrence of NTDs, however, the mechanisms involved in the cause of NTDs are poorly defined. RESULTS: Here, we report that histone H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) expression was significantly downregulated, and low levels of H3K79me2 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Using ChIP-seq assays, we found that a decrease of H3K79me2 downregulates the expression of Shh and Sufu in mouse embryonic stem cells (mESC) under folate deficiency. Interestingly, folate antagonist methotrexate treatment led to attenuation of H3K79me2 due to Dot1l, affecting Shh and Sufu genes regulation. Upon further analysis, we find that the genes Shh and Sufu are both downregulated in the brain tissues of mice and humans with NTDs. There was a positive correlation between the transcription levels of Shh, Sufu and the protein levels of DOT1L by Pearson correlation analysis. CONCLUSION: Our results indicate that abnormal Shh and Sufu genes expression reduced by aberrant Dot1l-mediated H3K79me2 levels could be the cause of NTDs occurrence.

Fabrication of an alginate-based ZhiNengCong gel showed an enhanced antiviral and plant growth promoting functions.

Tobacco mosaic disease is a worldwide viral disease that can cause huge economic losses. Plant immune inducers have become the main force in the prevention and treatment of viral disease own to their high efficiency and rapid effect. However, since tobacco mosaic disease can occur at any point in the plant growth cycle, a single application period cannot guarantee the completely management. In this study, an extract from Paecilomyces variotii named ZhiNengCong (ZNC), which can fight against tobacco mosaic disease with 65% control effect, and improve the promotion of tobacco stem girth, was selected from five commercial antiviral medicines, and a sustained release sodium alginate (Alg)-based ZNC (ZNC@Alg) was prepared by physical absorption. ZNC@Alg, who contains only 5 mg/mL ZNC, can release ZNC for 7 consecutive days, and displayed an enhanced effect in inducing the PAL-mediated salicylic acid signaling pathway activation to participate in the inhibition of green fluorescent protein (GFP)-tagged tobacco mosaic virus (TMV-GFP) infection, even after 7 days of the application. Notably, field experiments showed that the control effect of ZNC@Alg was up to 88%, which was significantly better than that of ZNC with the same concentration (10 µg per plant). In addition, ZNC@Alg exhibited a stronger growth-promoting effect than ZNC, which significantly increased the wet weight of tobacco. Taken together, we screened out a plant immune inducer ZNC that can effectively inhibit tobacco virus disease, and created ZNC@Alg with higher control effect and growth promotion effect, laying a foundation for effective field management of tobacco mosaic disease.

Tobacco mosaic virus hijacks its coat protein-interacting protein IP-L to inhibit NbCML30, a calmodulin-like protein, to enhance its infection.

Calcium is an important plant immune signal that is essential for activating host resistance, but how RNA viruses manipulate calcium signals to promote their infections remains largely unknown. Here, we demonstrated that tobacco mosaic virus (TMV) coat protein (CP)-interacting protein L (IP-L) associates with calmodulin-like protein 30 (NbCML30) in the cytoplasm and nucleus, and can suppress its expression at the nucleic acid and protein levels. NbCML30, which lacks the EF-hand conserved domain and cannot bind to Ca2+ , was located in the cytoplasm and nucleus and was downregulated by TMV infection. NbCML30 silencing promoted TMV infection, while its overexpression inhibited TMV infection by activating Ca2+ -dependent oxidative stress in plants. NbCML30-mediated resistance to TMV mainly depends on IP-L regulation as the facilitation of TMV infection by silencing NbCML30 was canceled by co-silencing NbCML30 and IP-L. Overall, these findings indicate that in the absence of any reported silencing suppressor activity, TMV CP manipulates IP-L to inhibit NbCML30, influencing its Ca2+ -dependent role in the oxidative stress response. These results lay a theoretical foundation that will enable us to engineer tobacco (Nicotiana spp.) with improved TMV resistance in the future.

Transcriptome analysis reveals the mechanism of zinc ion-mediated plant resistance to TMV in Nicotiana benthamiana.

Zinc ions (Zn2+) are used to promote plant growth and treat multiple diseases. However, it is still unclear which pathways in plants respond to Zn2+. In this study, we found that supplying (CH3COO)2Zn can effectively delay tobacco mosaic virus (TMV) replication and movement in Nicotiana benthamiana. To further understand the regulatory mechanism of antiviral activity mediated by Zn2+, we examined the transcriptomic changes of leaves treated with Zn2+. Three days after treatment, 7575 differential expression genes (DEGs) were enriched in the Zn2+ treatment group compared with the control group. Through GO and KEGG analysis, the pathway of phosphatidylinositol signaling system and inositol phosphate metabolism were significantly enriched after treated with Zn2+, and a large number of ethylene-responsive transcription factors (ERFs) involved in inositol phosphate metabolism were found to be enriched. We identified ERF5 performed a positive effect on plant immunity. Our findings demonstrated that Zn2+-mediated resistance in N. benthamiana activated signal transduction and regulated the expression of resistance-related genes. The results of the study uncover a global view of mRNA changes in Zn2+-mediated cellular processes involved in the competition between plants and viruses.

Nicotiana benthamiana asparagine synthetase associates with IP-L and confers resistance against tobacco mosaic virus via the asparagine-induced salicylic acid signalling pathway.

Asparagine synthetase is a key enzyme that catalyses the conversion of amide groups from glutamine or ammonium to aspartate, which leads to the generation of asparagine. However, the role of asparagine synthetase in plant immunity remains largely unknown. Here, we identified a Nicotiana benthamiana asparagine synthetase B (NbAS-B) that associates with tomato mosaic virus coat protein-interacting protein L (IP-L) using the yeast two-hybrid assay and examined its role in tobacco mosaic virus (TMV) resistance. The association of IP-L with NbAS-B was further confirmed by in vivo co-immunoprecipitation, luciferase complementation imaging, and bimolecular fluorescence complementation assays. IP-L and NbAS-B interact in the nucleus and cytosol and IP-L apparently stabilizes NbAS-B, thus enhancing its accumulation. The expressions of IP-L and NbAS-B are continuously induced on TMV-green fluorescent protein (GFP) infection. Co-silencing of IP-L and NbAS-B facilitates TMV-GFP infection. Overexpression of NbAS-B in tobacco reduces TMV-GFP infection by significantly improving the synthesis of asparagine. Furthermore, the external application of asparagine significantly inhibits the infection of TMV-GFP by activating the salicylic acid signalling pathway. These findings hold the potential for the future application of asparagine in the control of TMV.

The Enhancement of Antiviral Activity of Chloroinconazide by Aglinate-based Nanogel and Its Plant Growth Promotion Effect.

Improving the efficiency and prolonging the duration of pesticides are of great significance in agricultural production. In this work, based on the antiviral compound chloroinconazide (CHI) synthesized previously, the improvement of the fabricated CHI-loaded alginate-based nanogel (CHI@ALGNP) was studied. It was found that CHI@ALGNP showed higher foliar adhesion than CHI and exhibited a sustained release for up to 7 days. CHI@ALGNP could also continuously activate the reactive oxygen species and antioxidant levels and induce the increase of salicylic acid content and the expression of its responsive gene PR2 for a long time, thus achieving sustained resistance to tobacco mosaic virus infection in Nicotiana benthamiana. Strikingly, CHI@ALGNP could release Ca2+ and Mg2+ to promote the growth of N. benthamiana. Taken together, for the first time, we have shown the improvement of a nanogel carrier to the antiviral activity and growth promotion of small molecular pesticides. As the alginate-based nanogel can be easily applied to the spray-based pesticide delivery technology, our study provides a new strategy for the development of new pesticide preparations and the application of multifunctional pesticides.

Novel FUS mutation Y526F causing rapidly progressive familial amyotrophic lateral sclerosis.

FUS gene is one of the most common mutated genes in amyotrophic lateral sclerosis (ALS). We sequenced for FUS mutations in a cohort of 15 familial ALS and 275 sporadic ALS of Chinese origin. All 15 exons of the FUS gene were sequenced by targeted next-generation sequencing in a cohort of 15 familial ALS indexes and 275 sporadic ALS patients of Chinese origin. One novel p.Y526F mutation in FUS was detected in one familial ALS proband. Another novel FUS p.Q140R variant and two known FUS mutations (p.R495Efs*33 and p.R521C) were identified in four sporadic ALS cases. The frequency of FUS mutation in our cohort is 6.7% in familial ALS and 1.5% in sporadic ALS. The familial ALS proband carrying the FUS p.Y526F mutation presented with juvenile-onset lower limbs weakness and demonstrated an aggressive course, with respiratory muscles involvement 6 months after onset. The other patients in the family all had limbs weakness and died 1-2 years after disease onset. Our results strengthen that FUS mutations are the most frequent genetic causes of young-onset aggressive ALS. Genetic testing of the FUS gene should be performed in early-onset ALS patients especially those with a rapid progression.

Synthetic chloroinconazide compound exhibits highly efficient antiviral activity against tobacco mosaic virus.

BACKGROUND: Development of anti-plant-virus compounds and improvement of biosafety remain hot research topics in controlling plant viral disease. Tobacco mosaic virus (TMV) infects all tobacco species as well as many other plants worldwide and causes severe losses in tobacco production. To date, no efficient chemical treatments are known to protect plants from virus infection. Therefore, the search for a highly active antiviral compound with high efficacy in field application is required. RESULTS: We reported the synthesis of a novel antiviral halogenated acyl compound Chloroinconazide (CHI) using tryptophan as a substrate and examined its anti-TMV activity. We found that CHI displayed the ability to strongly inhibit the infection of TMV on Nicotiana benthamiana via multiple mechanisms. We observed that CHI was able to impair the virulence of TMV by directly altering the morphological structure of virions and increasing the activity of anti-oxidative enzymes, resulting in reduced TMV-induced ROS production during infection of the plant. In addition, the expression of salicylic acid-responsive genes was significantly increased after CHI application. However, after application of CHI on SA-deficient NahG plants no obvious anti-TMV activity was observed, suggesting that the SA signaling pathway was required for CHI-induced anti-TMV activity associated with reduced infection of TMV. CHI exhibited no effects on plant growth and development. CONCLUSION: The easily synthesized CHI can actively induce plant resistance against TMV as well as act on virus particles and exhibits high biosafety, which provides a potential for commercial application of CHI in controlling plant virus disease in the future. © 2020 Society of Chemical Industry.

Foliar exposure of Fe3O4 nanoparticles on Nicotiana benthamiana: Evidence for nanoparticles uptake, plant growth promoter and defense response elicitor against plant virus.

Nanoparticles are recently employed as a new strategy to directly kill pathogens (e.g., bacteria and fungus) and acted as nanofertilizers. However, the influences of this foliar deposition of nanoparticles on plant physiology particularly plant immunity are poorly understood. The uptake and physiological effects of Fe3O4 nanoparticles (Fe3O4NPs), and plant resistance response against Tobacco mosaic virus (TMV) after foliar spraying were studied. Specifically, Fe3O4NPs entered leaf cells and were transported and accumulated throughout the whole Nicotiana benthamiana plant, and increased plant dry and fresh weights, activated plant antioxidants, and upregulated SA synthesis and the expression of SA-responsive PR genes (i.e., PR1 and PR2), thereby enhancing plant resistance against TMV. Conversely, the viral infection was not inhibited in the NahG transgenic plants treated by Fe3O4NPs, suggesting the involvement of salicylic acid (SA) induced by Fe3O4NPs in the production of plant resistance. Moreover, no inhibition was observed of the infection after inoculating with the pretreated TMV mixtures. Thus, the deposition of Fe3O4NPs induced the accumulation of endogenous SA, which was correlated with the plant resistance against TMV infection. Such information is vital for valuing the risk of Fe3O4NPs products and broadens the researching and applying nanoparticles in the fight against plant diseases meantime.

Identification of histone acetylation markers in human fetal brains and increased H4K5ac expression in neural tube defects.

BACKGROUND: Neural tube defects (NTDs) are severe common birth defects that result from a failure in neural tube closure (NTC). Our previous study has shown that decreased histone methylation altered the regulation of genes linked to NTC. However, the effect of alterations in histone acetylation in human fetuses with NTDs, which are another functional posttranslation modification, remains elusive. Thus, we aimed to identify acetylation sites and changes in histone in patients with NTDs. METHODS: First, we identified histone acetylation sites between control human embryonic brain tissue and NTDs using Nano-HPLC-MS/MS. Next, we evaluated the level of histone acetylation both groups via western blotting (WB). Finally, we used LC-ESI-MS and WB to compare whether histone H4 acetylation was different in NTDs. RESULTS: A total of 43 histone acetylation sites were identified in human embryonic brain tissue, which included 16 novel sites. Furthermore, we found an increased histone acetylation and H4K5ac in tissue with NTDs. CONCLUSION: Our result present a comprehensive map of histone H4 modifications in the human fetal brain. Furthermore, we provide experimental evidence supporting a relationship between histone H4K5ac and NTDs. This offers a new insight into the pathological role of histone modifications in human NTDs.

Dual-Action Pesticide Carrier That Continuously Induces Plant Resistance, Enhances Plant Anti-Tobacco Mosaic Virus Activity, and Promotes Plant Growth.

Improving plant resistance against systemic diseases remains a challenging research topic. In this study, we developed a dual-action pesticide-loaded hydrogel with the capacity to significantly induce plant resistance against tobacco mosaic virus (TMV) infection and promote plant growth. We produced an alginate-lentinan-amino-oligosaccharide hydrogel (ALA-hydrogel) by coating the surface of an alginate-lentinan drug-loaded hydrogel (AL-hydrogel) with amino-oligosaccharide using electrostatic action. We determined the formation of the amino-oligosaccharide film using various approaches, including Fourier transform infrared spectrometry, the ζ potential test, scanning electron microscopy, and elemental analysis. It was found that the ALA-hydrogel exhibited stable sustained-release activity, and the release time was significantly longer than that of the AL-hydrogel. In addition, we demonstrated that the ALA-hydrogel was able to continuously and strongly induce plant resistance against TMV and increase the release of calcium ions to promote Nicotiana benthamiana growth. Meanwhile, the ALA-hydrogel maintained an extremely high safety to organisms. Our findings provide an alternative to the traditional approach of applying pesticide for controlling plant viral diseases. In the future, this hydrogel with the simple synthesis method, green synthetic materials, and its efficiency in the induction of plant resistance will attract increasing attention and have good potential to be employed in plant protection and agricultural production.

Over-expression of 5-HT6 Receptor and Activated Jab-1/p-c-Jun Play Important Roles in Pilocarpine-Induced Seizures and Learning-Memory Impairment.

Cognitive impairment is a common comorbidity in patients with temporal lobe epilepsy (TLE) that severely affects patients' quality of life. Also, serotonin 5-hydroxytryptamine 6 (5-HT6) receptor plays an important role in cognition. This study aimed to investigate effects of 5-HT6 receptor on learning-memory capacities in epileptic rats. Total of 36 adult Sprague-Dawley (SD) rats were divided into vehicle (n = 6) and epileptic group (n = 30). Status epilepticus (SE) was induced via systemic injection of pilocarpine. Epileptic group was sub-divided into vehicle, 10, 20, and 30 µg SB-271046 groups, six mice per group. Learning-memory performance of rats was evaluated by using Y maze and Morris water maze test. 5-HT6 receptor expression was examined using immunostaining and Western blot. The other six rats were used to make epileptic model and Jab-1/p-c-Jun were detected. Results showed that frequency of spontaneous recurrent seizures (SRSs) was significantly decreased in pilocarpine-induced epileptic rats that treated with SB-271046. Alternation rate and new arm percentage were decreased in epileptic rats compared to control. The 5-day mean latency was prolonged in epileptic rats compared to control rats. During retention stage, mean latency, number of target crossings, and percentage of time spent in target zone were decreased in epileptic rats, but not in those treated with SB-271046. The number of apoptotic neurons was significantly increased in epileptic rats, which was decreased by SB-271046. 5-HT6 expression was significantly increased in hippocampus and cortex following recurrent seizures. Jab-1 level was decreased after SB-271046 administration. p-c-Jun level was elevated in epileptic rats and decreased in a dose-dependent manner after the SB-271046 administration. In conclusion, the over-expression of 5-HT6 receptor and activated Jab-1/p-c-Jun plays an important role in pilocarpine-induced seizures and learning-memory impairment.

Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

Surgical treatment of pituitary apoplexy in association with hemispheric infarction.

We report a patient with pituitary apoplexy in whom cerebral infarction developed, possibly secondary to vasospasm. Pituitary apoplexy is a clinical syndrome caused by acute hemorrhage or infarction of the pituitary gland. Our patient's clinical symptoms and radiographic findings greatly improved after surgical resection of the apoplectic pituitary gland. An extensive literature review was performed, including all previously reported cases of pituitary apoplexy leading to cerebral infarction. The clinical features, pathophysiological mechanisms, management and outcome of cerebral infarction following pituitary apoplexy are discussed. We show that cerebral infarction following pituitary apoplexy is associated with much poor prognosis. Early surgical decompression of the tumor and hemisphere should be performed in patients with severe or progressive neurological deficits, however, those with less severe presentations may be treated conservatively or with delayed elective surgery.

Characteristics of white coat hypertension in Chinese Han patients with type 2 diabetes mellitus.

OBJECTIVES: This study documented the prevalence and clinical features of white coat hypertension (WCH) among Chinese Han patients with type 2 diabetes mellitus (T2DM). METHODS: Clinic and ambulatory blood pressure (BP) measurements were compared in 856 patients with T2DM to determine the frequency of WCH (WCH was defined as clinical blood pressure ≥140/90 mmHg and daytime blood pressure <135/85 mmHg and/or 24-h ambulatory BP (ABP) mean value of <130/80 mmHg on ambulatory BP monitoring (ABPM). Weight, waist circumference (WC), body mass index (BMI), waist to height ratio (WHtR), fasting blood glucose, glycosylated hemoglobin level and circadian BP patterns were also measured to find clinical features predictive of WCH in T2DM. RESULTS: The prevalence of WCH was 7.36% (63/856) in the overall population, 6.13% (29/473) in male and 8.88% (34/383) in female (p < 0.05). WCH accounted for 14.03% (63/449) of diagnosed hypertension. Age, course of T2DM, male WC were independent protective factors, whereas female sex, smoking and alcohol consumption were independent risk factors for WCH in T2DM. Non-dippers and reverse dippers made up larger proportion of the WCH group (p < 0.01). CONCLUSION: WCH is relatively common among T2DM patients, it is a unique condition distinct from essential hypertension (EH), and WCH patients also exhibit significant differences in clinical parameters.

Prevalence and distinguishing features of masked hypertension in type 2 diabetic patients.

OBJECTIVE: The prevalence and clinical features of masked hypertension (MH) in type 2 diabetes mellitus patients (T(2)DM) were investigated to define clinical indices which may aid diagnosis and treatment. METHODS: Clinical blood pressure (CBP) and ambulatory blood pressure (ABP) were measured in 856 T(2)DM patients to differentiate normotensive (NT), essential hypertensive (EH), and MH. Waist circumference (WC), abdominal circumference (AC), body mass index (BMI), waist to height ratio (WHtR), fasting blood glucose (FBG), and glycated hemoglobin levels were measured and compared between BP groups. RESULTS: In total, 359 patients had normal CBP, of which 13.37% were diagnosed with MH based on established criteria. Males had significantly higher rates of MH (15.30%) than females (11.36%) (P=0.036). The MH detection rate increased with age and T(2)DM duration. There were no significant differences in BMI, WC or WHtR between total MH and EH groups. MH females, however, had lower BMIs than female EH females (P=0.023). Smoking, alcohol, and familial EH history were lower in MH than EH patients (smoking, P=0.029; alcohol ,P=0.001; and EH history, P=0.000), while BMI (male, P=0.037, female, P=0.015), WC (male, P=0.012, female, P=0.021), WHtR (P=0.011), smoking (P=0.016), and alcohol consumption (P=0.000) were higher in MH than NT patients. BMI, WHtR, 6-15 year disease course of diabetes, smoking and alcoholism were independent risk factors of T(2)DM complicated with MH. The dipper BP circadian pattern was significantly lower in MH than NT patients (P=0.001). The non-dipper pattern was lower in MH than EH (P=0.018) but higher than in NT (P=0.000). CONCLUSIONS: A significant fraction of T(2)DM patients were diagnosed with MH. Clinical presentation also contrasted sharply from EH, MH is a specific blood pressure status that may severely damage target organs in T(2)DM.

[Risk factors for Tourette syndrome].

OBJECTIVE: To identify the risk factors for Tourette syndrome (TS) in children. METHODS: Through a genetic epidemiologic case control study, segregation ratio was estimated using the method of Li-Manted-Gart in 80 children with TS. Heritability for the first- and second-degree relatives was estimated using the Falconer regression method. In addition, the 80 children and 80 controls with other diseases were evaluated using the Family Environment Scale and a self-designed questionnaire. Risk factors for TS were investigated using single factor and multifactor regression analysis. RESULTS: The segregation ratio of TS was 0.1176. Heritabilities for the first- and second-degree relatives were (49.7±2.6)% and (21.5±3.4)% respectively. The weighted mean heritability of the first-degree and second-degree relatives was (39.5±2.1)%. Significantly decreased scores were noted in independence, active-recreational orientation and organization and increased scores were noted in the conflict and control in the TS group compared with the control group (P<0.01). Single factor analysis indicated that the risk factors for TS included family history, type of home education, maternal smoking, family conflict, low level of parental education, family control and fetal anoxia. Multifactor regression analysis indicated that there were five important risk factors for TS: family history, family conflict, type of family education, low level of parental education and maternal smoking. CONCLUSIONS: Both heredity and environment are involved in the pathogenesis of TS. The mode of inheritance for TS is polygenic. Improving the living environments of children with a family history of TS is of prime importance.

[Effect of iron on peroxidation and non-enzymatic glycation in diabetic rats].

SD rats were peritoneally injected with streptozotocin to establish diabetes mellitus animal model. The changes of nonenzymatic glycation and peroxidation in rats supplemented with low iron high iron during five weeks were investigated. It was found that MDA in serum or renal cortex but not glycated hemoglobin, glycated LDL, renal cortical AGEs increased significantly after supplementation of high iron in diabetic rats. There was no change in serum MDA, renal cortical MDA, glycated hemoglobin, glycated LDL and AGEs after supplementation of low iron in diabetic rats. The results suggested that peroxidation could be enhanced obviously by supplementation of high iron so that chronic complications could be promoted by high dose iron in diabetic rats.