Anthropogenic nitrogen pollution inferred by stable isotope records of crustose coralline algae.

Since reef ecosystems can offer intricate habitats for various marine organisms, calcified reefs may contain valuable long-term environmental data. This study investigated stable isotopic composition of marine organisms from the Taoyuan and Linshanbi crustose coralline algae (CCA) reef ecosystems to understand sewage pollution. CCA samples from Taoyuan (Palaeo Xin A: ∼1000 years old and Palaeo G: ∼7000 years old) and Linshanbi (Palaeo L: ∼7000 years old and modern CCA) had significantly lower δ15N values (2.5-5.6 ‰) compared to modern CCA from Taoyuan (10.2 ± 1.2 ‰). Intertidal organisms from the Taoyuan CCA reef also showed higher δ15N values than those from Linshanbi CCA reef, indicating anthropogenic stress in both ecosystems. Long-term pollution monitoring and effective strategies to mitigate sewage pollution are recommended for these CCA reef ecosystems.

mTOR regulates cocaine-induced behavioural sensitization through the SynDIG1-GluA2 interaction in the nucleus accumbens.

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP2, and PIP3. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.

Inhibition of NLRP3 Inflammasome Activation and Pyroptosis in Macrophages by Taraxasterol Is Associated With Its Regulation on mTOR Signaling.

Taraxasterol (TAS) is an active ingredient of Dandelion (Taraxacum mongolicum Hand. -Mazz.), a medicinal plant that has long been used in China for treatment of inflammatory disorders. But the underlying mechanism for its therapeutic effects on inflammatory disorders is not completely clear. Inflammasome activation is a critical step of innate immune response to infection and aseptic inflammation. Among the various types of inflammasome sensors that has been reported, NLR family pyrin domain containing 3 (NLRP3) is implicated in various inflammatory diseases and therefore has been most extensively studied. In this study, we aimed to explore whether TAS could influence NLPR3 inflammasome activation in macrophages. The results showed that TAS dose-dependently suppressed the activation of caspase-1 in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin treatment, resulting in reduced mature interleukin-1ß (IL-1ß) release and gasdermin D (GSDMD) cleavage. TAS greatly reduced ASC speck formation upon the stimulation of nigericin or extracellular ATP. Consistent with reduced cleavage of GSDMD, nigericin-induced pyroptosis was alleviated by TAS. Interestingly, TAS time-dependently suppressed the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 signaling induced by LPS priming. Like TAS, both INK-128 (inhibiting both mTORC1 and mTORC2) and rapamycin (inhibiting mTORC1 only) also inhibited NLRP3 inflammasome activation, though their effects on mTOR signaling were different. Moreover, TAS treatment alleviated mitochondrial damage by nigericin and improved mouse survival from bacterial infection, accompanied by reduced IL-1ß levels in vivo. Collectively, by inhibiting the NLRP3 inflammasome activation, TAS displayed anti-inflammatory effects likely through regulation of the mTOR signaling in macrophages, highlighting a potential action mechanism for the anti-inflammatory activity of Dandelion in treating inflammation-related disorders, which warrants further clinical investigation.

Geochemical and U-Th isotopic insights on uranium enrichment in reservoir sediments.

Uranium (U) geochemistry and its isotopic compositions of reservoir sediments in U mine area were poorly understood. Herein, U and Th isotopic compositions were employed to investigate source apportionment and geochemical behavior of U in 41 reservoir sediments from a U mining area, Guangdong, China. The remarkably high contents of both total U (207.3-1117.7 mg/kg) and acid-leachable U (90.3-638.5 mg/kg) in the sediments exhibit a severe U contamination and mobilization-release risk. The U/Th activity ratios (ARs) indicate that all sediments have been contaminated apparently by U as a result of discharge of U containing wastewater, especially uranium mill tailings (UMT) leachate, while the variations of U/Th ARs are dominated by U geochemical behaviors (mainly redox process and adsorption). The U isotopic compositions (δ238U) showed a large variance through the sediment profile, varying from - 0.62 to - 0.04‰. The relation between δ238U and acid-leachable U fraction demonstrates that the U isotopic fractionation in sediments can be controlled by bedrock weathering (natural activity), UMT leachate (anthropogenic activity) and subsequent biogeochemical processes. The findings suggest that U-Th isotopes are a powerful tool to better understand U geochemical processes and enrichment mechanism in sediments that were affected by combined sources and driving forces.

Transiently Elevated TC and sdLDL-C Levels and Falsely Low LDL-C Levels in Patients with Extrahepatic Cholangiocarcinoma.

PURPOSE: Most patients diagnosed with extrahepatic cholangiocarcinoma (ECCA) exhibit cholestasis caused by obstruction of the bile duct. Cholestasis is associated with lipid disorders, but studies focused on the changing lipid parameters in patients with ECCA are lacking. Here, we observed lipid profiles in patients with ECCA and investigated whether the removal of biliary obstruction could correct dyslipidemia. PATIENTS AND METHODS: We consecutively included patients admitted to the hepatobiliary surgery department at the Affiliated Hospital of Xuzhou Medical University. The patients were divided into an ECCA group or a non-ECCA group based on the disease assessment. Patients with histological confirmation of ECCA were included in the ECCA group. Blood samples were collected on admission as well as five days after treatment. An automatic biochemistry analyzer was used to test liver function and serum lipid levels. Serum lipoprotein electrophoresis was performed using barbitone sodium buffer and Sudan black B. RESULTS: A total of 180 patients met inclusion criteria and were enrolled for this study. Of these, 76 patients were diagnosed with ECCA; all other patients were enrolled in the non-ECCA group. Total cholesterol (TC) and small and dense low-density lipoprotein cholesterol (sdLDL-C) levels were significantly elevated in the ECCA group. LDL-C levels were found to be slightly lower in the ECCA group. In the ECCA group, serum samples were detained in sample wells and lipoproteins failed to be separated. TC and sdLDL-C levels significantly decreased after cholestasis relief in the ECCA group. Lipoprotein electrophoresis revealed that patients with ECCA showed normal lipoprotein patterns after treatment. CONCLUSION: Patients with ECCA exhibited transiently elevated TC and sdLDL-C levels and falsely low LDL-C results. TC, sdLDL-C, and LDL-C levels could be restored to normal levels after biliary obstruction removal and cholestasis relief.

Ancient DNA and multimethod dating confirm the late arrival of anatomically modern humans in southern China.

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.

Pseudohyperkalemia caused by essential thrombocythemia in a patient with chronic renal failure: A case report.

BACKGROUND: Hyperkalemia is one of the most common complications of chronic renal failure. Pseudohyperkalemia is caused by elevated levels of serum potassium in vitro and is usually accompanied by thrombocythemia. Although an elevated level of potassium is typically correlated with impaired renal function, pseudo-hyperkalemia has been rarely reported in patients with chronic renal failure. Here, we conducted a review of the literature to study the case of pseudo-hyperkalemia caused by the essential thrombocythemia in a patient with chronic renal failure. CASE SUMMARY: A 73-year-old woman was admitted to our hospital with complaints of palpitation, dyspnea, and acratia for 2 d and a history of essential throm-bocythemia for 1 year. The routine blood test showed platelet count of 1460 × 109/L, and biochemistry tests showed that the patient suffered from hyperkalemia (potassium: 7.50 mmol/L) and renal failure (estimated glomerular filtration rate: 8.88 mL/min). Initial treatment included medicines to lower her potassium-levels and hemodialysis. However, the therapy did not affect her serum potassium levels. Plasma potassium concentration measurements and a history of essential thrombocythemia established the diagnosis of pseudohyperkalemia. The treatments of the platelet disorder gradually normalized serum potassium levels; however, the treatments had to be discontinued later due to the severe leukopenia, and enhanced levels of serum potassium concentrations were observable in the patient. Since plasma sampling was not permitted, doctors had to use a diuretic just in case. Finally, the patient collapsed into unconsciousness and died due to multiple organ dysfunction and electrolyte disturbance. CONCLUSION: We reviewed the literature and suggest that serum and plasma potassium values should both be measured for patients whose platelet counts exceed 500 × 109/L to eliminate chances of pseudohyperkalemia, especially for those with chronic renal failure. An inappropriate treatment for pseudohyperkalemia can aggravate a patient's condition.

Extrapyramidal side effect of donepezil hydrochloride in an elderly patient: A case report.

INTRODUCTION: Alzheimer disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction, which is mainly manifested as memory impairment and a reduced ability to self-care, often accompanied by neuropsychiatric and behavioral disorders. Donepezil is the second drug to be approved by the US FDA for the treatment of AD. Of the five FDA-approved drugs for AD treatment, donepezil is currently the most widely used. Here, we report an extrapyramidal adverse reaction to donepezil in an elderly patient with AD. PATIENT CONCERNS: An 87-year-old woman presented with a 1-year history of forgetfulness that was aggravated since the past 2 months. She had a long-term history of multiple major conditions, including hypertension, diabetes, osteoporosis, and arterial plaques. Brain imaging showed age-related changes, and her Mini Mental State Examination score was 20. Other tests revealed no abnormalities apart from multiple thyroid nodules on ultrasonography. DIAGNOSIS: She was diagnosed with AD, hypertension, type 2 diabetes mellitus, diabetic neuropathy, osteoporosis, carotid and lower-extremity arterial plaques, thyroid nodules. INTERVENTIONS: She was treated with donepezil (5 mg/day), amlodipine besylate (5 mg/day), glimepiride (4 mg/day), methylcobalamin (1.5 mg/day), calcium carbonate D3 (600 mg/day), simvastatin (20 mg/day) and enteric-coated aspirin (100 mg/day). OUTCOMES: Four days later, she experienced fatigue, panic, sweating, and one episode of vomiting. On the 5th day, she developed increased muscle tension, speech difficulty, and involuntary tremors. Imaging and blood tests revealed no obvious abnormality, and the patient was not receiving psychotropic drugs. An extrapyramidal adverse reaction to donepezil was considered, and the drug was discontinued, after which the symptoms gradually disappeared. CONCLUSION: Serious adverse reactions to donepezil can occur in elderly patients, who typically require multiple medications for a variety of comorbidities. In particular, extrapyramidal reactions have occurred when donepezil is administered in combination with psychotropic drugs. However, in our patient, an extrapyramidal adverse reaction occurred in the absence of psychotropic drugs. Thus, clinicians must be aware of inter-individual differences in drug actions and possible serious adverse reactions, and carefully monitor these patients to ensure the timely detection of adverse events and their safe treatment.

Decreased intracellular chloride promotes ADP induced platelet activation through inhibition of cAMP/PKA instead of activation of Lyn/PI3K/Akt pathway.

Decrease of chloride concentration contributes to cardiovascular diseases, however, whether decrease of chloride concentration is involved in platelet activation remains elusive. In the present study, we found that ACI patients had lower serum chloride which would be rescued after Aspirin administration. ADP induced chloride concentration reduction in platelets. Blockade of chloride channel prevented ADP-induced platelet adhesion, activation and aggregation, however, decreasing the extracellular chloride concentration promoted ADP-induced platelet adhesion and activation. Decrease of the extracellular chloride concentration facilitated the inactivation of Src family kinase Lyn, which was not involved in PI3K/Akt phosphorylation. Nevertheless, low chloride concentration promoted the production of platelet cytosol Gαi2 subunit. This subunit prevents AC from converting ATP into cAMP, which therefore, inhibited the phosphorylation of PKA to promote platelet activation. In conclusion, decreased intracellular chloride promotes ADP induced platelet activation through the Gαi2/cAMP/PKA pathway instead of the Lyn/PI3K/Akt signal pathway.

Aggravated intestinal apoptosis by ClC-3 deletion is lethal to mice endotoxemia.

Our previous study found that ClC-3 chloride channel functioned differently in the vascular and intestinal inflammation, the loss of ClC-3 reduced vascular inflammation but exacerbated intestinal inflammation. To furtherly clarify the role of ClC-3 chloride channels in systemic inflammation, we used LPS-induced endotoxemia model to investigate the response of wild-type and ClC-3 knockout mice to systemic inflammation. The results showed that in the LPS-induced endotoxemia model, the mortality of mice with ClC-3 deletion was significantly higher than that of wild-type mice. The liver and lung inflammations in mice with ClC-3 deletion were significantly less than those in wild-type mice, and the levels of TNF-α and MIP-2 in serum were lower than those of wild-type mice. However, intestinal inflammatory cytokines contents and intestinal permeability were higher than wild-type mice. After transfection of THP-1 cells with ClC-3 siRNA, the contents of TNF-α and IL-8 in LPS-induced cell supernatants were significantly decreased. Further experiments revealed that the level of Bax and Cleaved Caspase 3 in intestinal tissue of mice with ClC-3 deletion was significantly increased, while the level of Bcl2 did not change, which indicated that the intestinal apoptosis was increased after LPS-induced mice intestinal integrity destruction. Therefore, the regulation of intestinal tissue integrity by ClC-3 is crucial for maintaining LPS-induced survival in mice with endotoxemia.

A 60-year record of 129I in Taal Lake sediments (Philippines): Influence of human nuclear activities at low latitude regions.

The influence of human nuclear activities on environmental radioactivity is not well known at low latitude regions that are distant from nuclear test sites and nuclear facilities. A sediment core collected from Taal Lake in the central Philippines was analyzed for 129I and 127I to investigate this influence in a low-latitude terrestrial system. A baseline of 129I/127I atomic ratios was established at (2.04-5.14) × 10-12 in the pre-nuclear era in this region. Controlled by the northeasterly equatorial trade winds, increased 129I/127I ratios of (20.1-69.3) × 10-12 suggest that atmospheric nuclear weapons tests at the Pacific Proving Grounds in the central Pacific Ocean was the major source of 129I in the sediment during 1956-1962. The 129I/127I ratios, up to 157.5 × 10-12 after 1964, indicate a strong influence by European nuclear fuel reprocessing plants. The East Asian Winter Monsoon is found to be the dominant driving force in the atmospheric dispersion of radioactive iodine (129I) from the European nuclear fuel reprocessing plants to Southeast Asia, which is also important for dispersion of other airborne pollutants from the middle-high to low latitude regions. A significant 129I/127I peak at 42.8 cm in the Taal Lake core appears to be the signal of the Chernobyl accident in 1986. In addition, volcanic activities are reflected in the iodine isotope profiles in the sediment core, suggesting the potential of using iodine isotopes as an indicator of volcanic eruptions.

[Reduction in hypoxia-derived neuroinflammation and dysfunctional glutamate transporters by minocycline may restore hypoxia-injured cognition of neonatal rat].

The aim of the present study was to investigate the effects of minocycline on cognitive functions in neonatal rat after hypoxia exposure and the underlying mechanism. A model of hypoxic brain damage (HBD) was developed by exposing postnatal 1 day (P1) rats to systemic hypoxia. The rats were intraperitoneally injected with normal saline (Hy group) or minocycline (Hy + M group) 2 h after hypoxia exposure. Some other P1 rats that were not subjected to systemic hypoxia were used as normal control (NG group). The Y-maze test was used to evaluate learning and memory ability on postnatal day 30. Inflammatory mediators (Iba-1, IL-1ß, TNF-α and TGF-ß1), glutamate transporters (EAAT1 and EAAT2), total Tau and phosphorylated Tau (phosphorylation sites: Tyr18, Thr205, Thr231, Ser396 and Ser404) protein expressions in the hippocampus were detected by Western blot 7 d after hypoxic exposure. The results showed that hypoxia induced learning and memory impairments of the neonatal rats, and minocycline administration could reverse the effects of hypoxia. The protein expression levels of Iba-1, IL-1ß, TNF-α, EAAT2 and Tau phosphorylated at T231 were increased, but the total Tau expression was decreased in the hippocampus of the rats from Hy group 7 d after hypoxia exposure. In the hypoxia-treated rats, minocycline down-regulated Iba-1, IL-1ß, TNF-α and EAAT2 protein expressions significantly, but did not affect total Tau and phosphorylated Tau protein expressions. Our results suggest that minocycline can prevent cognitive deficits of rats with hypoxia exposure, and the underlying mechanism may involve the inhibition of neuroinflammation and dysfunctional glutamate transporters but not the regulation of the Tau hyperphosphorylation.

Kinetic and thermodynamic studies on removal of Cu(II) from aqueous solutions using soil nanoclays.

Soil clays (< 2,000 nm) (SC) and soil nanoclays (< 100 nm) (SNC) were used as adsorbents for removal of Cu(II) from aqueous solution. The experiments were conducted with variables including pH, interaction time, concentration of Cu(II) and temperature. Four kinetic models have been employed to investigate adsorption mechanisms, and the experimental data more closely resemble a second-order process of the kinetic model. Adsorption studies on soil nanoclays have been shown to be highly effective in removing of Cu(II) from aqueous solution. This adsorbent is widely available as a natural material, is mechanically stable and, most importantly, it is environmentally appealing. The maximum Cu(II) adsorption capacity of soil nanoclays (31.7 mg/g) is more than three times higher than natural soil clays (10.2 mg/g). Our study demonstrates that soil nanoclays can be used effectively for removal of Cu(II) from aqueous systems to achieve environmental cleaning purposes.

Some selected heavy metal concentrations in water, sediment, and oysters in the Er-Ren estuary, Taiwan: chemical fractions and the implications for biomonitoring.

Studies of heavy metal contamination and ecological risk in estuaries are an important emerging area of environmental science. However, there have been few detailed studies of heavy metal contamination that concern the spatial variation of heavy metal levels in water, sediment, and oyster tissue. Because of the effective uptake of heavy metals, cultured oysters are a cheap and effective subject for study. This study, conducts an experiment in the Er-Ren river to examine the biological uptake of heavy metals in farmed, cultured oysters. The distribution of copper, zinc, lead, cadmium, and arsenic concentrations in water, sediment, and oysters from the Er-Ren river is also evaluated. By sequential extraction of the sediments, the following order of mobilities is found for heavy metals Pb > Cd > As > Zn > Cu. The highest percentages of heavy metals are found in the residual phase. The mean uptake rates for young oysters are 7.24 mg kg(-1) day(-1) for Cu and 94.52 mg kg(-1) day(-1) for Zn, but that for adult oyster is 10.79 mg kg(-1) day(-1) for Cu and 137.24 mg kg(-1) day(-1) for Zn. With good policies and management, the establishment of cultured oyster frames in these contaminated tributaries and near shore environments is a potential method for removing Cu and Zn and protecting the coast.

Evidence from central Mexico supporting the Younger Dryas extraterrestrial impact hypothesis.

We report the discovery in Lake Cuitzeo in central Mexico of a black, carbon-rich, lacustrine layer, containing nanodiamonds, microspherules, and other unusual materials that date to the early Younger Dryas and are interpreted to result from an extraterrestrial impact. These proxies were found in a 27-m-long core as part of an interdisciplinary effort to extract a paleoclimate record back through the previous interglacial. Our attention focused early on an anomalous, 10-cm-thick, carbon-rich layer at a depth of 2.8 m that dates to 12.9 ka and coincides with a suite of anomalous coeval environmental and biotic changes independently recognized in other regional lake sequences. Collectively, these changes have produced the most distinctive boundary layer in the late Quaternary record. This layer contains a diverse, abundant assemblage of impact-related markers, including nanodiamonds, carbon spherules, and magnetic spherules with rapid melting/quenching textures, all reaching synchronous peaks immediately beneath a layer containing the largest peak of charcoal in the core. Analyses by multiple methods demonstrate the presence of three allotropes of nanodiamond: n-diamond, i-carbon, and hexagonal nanodiamond (lonsdaleite), in order of estimated relative abundance. This nanodiamond-rich layer is consistent with the Younger Dryas boundary layer found at numerous sites across North America, Greenland, and Western Europe. We have examined multiple hypotheses to account for these observations and find the evidence cannot be explained by any known terrestrial mechanism. It is, however, consistent with the Younger Dryas boundary impact hypothesis postulating a major extraterrestrial impact involving multiple airburst(s) and and/or ground impact(s) at 12.9 ka.

[Efficacy and safety of 308 nm excimer laser for vitiligo].

OBJECTIVE: To assess the efficacy and safety of the 308 nm excimer laser for the treatment of vitiligo. METHODS: We treated 170 patients with stable vitiligo by using the 308 nm excimer laser. The lesions of vitiligo were treated one to two times per week for 10-30 times. Efficacies were evaluated every 7 days and 3 days after the treatments were completed. Patients were followed up for two months. RESULTS: The rates of "remarkably improved" and "cured" were 67.97% and 32.03% in faces, 54.55% and 27.27% in necks, 63.26% and 26.53% in trunks, 38.84% and 15.70% in limbs, and 0 and 0 in hands and feet. The areas of faces had a better response than those of necks, trunks, or limbs (P < 0.01), and the areas of trunks or limbs had better response than that of hands and feet (P < 0.01). CONCLUSION: The 308 nm excimer laser is safe and effective in treating stable vitiligo and the efficacy varies in different lesion sites.

Predicting lipase types by improved Chou's pseudo-amino acid composition.

By proposing a improved Chou's pseudo amino acid composition approach to extract the features of the sequences, a powerful predictor based on k-nearest neighbor was introduced to identify the types of lipases according to their sequences. To avoid redundancy and bias, demonstrations were performed on a dataset where none of the proteins has > or =25% sequence identity to any other. The overall success rate thus obtained by the 10-fold cross-validation test was over 90%, indicating that the improved Chou's pseudo amino acid composition might be a useful tool for extracting the features of protein sequences, or at lease can play a complementary role to many of the other existing approaches.

Antioxidant N-acetylcysteine inhibits the activation of JNK3 mediated by the GluR6-PSD95-MLK3 signaling module during cerebral ischemia in rat hippocampus.

Cerebral ischemia induces kainate receptor glutamate receptor 6 (GluR6) binding to the postsynaptic density protein 95 (PSD95), which in turn anchors mixed lineage kinase 3 (MLK3) via SH3 domain in rat brain. MLK3 subsequently activates c-Jun NH(2)-terminal kinase (JNK) via MAP kinase kinases (MKKs). In this study, we investigated the association of PSD95 with GluR6 and MLK3, the autophosphorylation of MLK3, the combination of MLK3 with JNK3, and the phosphorylation of JNK3 during cerebral ischemia in rat hippocampus CA1. Our results indicate that the GluR6-PSD95-MLK3 complex quickly enhanced at 5 min of ischemia and peaked at 10 min of ischemia, and then gradually reduced with the prolonged time of ischemia. Interestingly, the combination of MLK3 and JNK3 gradually increased from 5 min to 30 min of ischemia. JNK3 phosphorylation first increased and then attenuated in cytosol, suggesting the translocation of activated JNK3 to nucleus during ischemia. To further investigate the possible mechanism of JNK3 activation, antioxidant N-acetylcysteine (NAC) was given to the rats 20 min prior to ischemia. Results indicate that NAC distinctly inhibited the association of PSD95 with GluR6 and MLK3, the autophosphorylation of MLK3, the combination of MLK3 with JNK3 and JNK3 activation. Taken together, these finding indicate that ischemic stimulation results in JNK3 activation through the GluR6-PSD95-MLK3 signaling module, and that the activation of JNK3 is closely related to oxidative stress.