Distribution, mobilization, risk assessment and source identification of heavy metals and nutrients in surface sediments of three urban-rural rivers after long-term water pollution treatment.

Sediments are critical pollution carriers in urban-rural rivers, which can threaten the water quality of the river and downstream lakes for a long time. However, it is still not clear whether conventional water pollution treatments could abate sediment pollution or not. In this study, heavy metals (HMs) and nutrient salts in the surface sediments and overlying water were investigated after decades' water pollution treatment in three urban-rural rivers. HM speciation was determined by the sequential extraction; diffusion fluxes were estimated using Fick's first law; HM ecological risk and nutrient pollution were evaluated; and pollution sources were identified by statistical analysis and GIS. The results showed that the HMs and nutrients were extremely serious in the urban regions. The accumulation level of Pb, Cu and Cd in the sediments of the three rivers were all much higher than the soil background value, and the labile fractions accounted for high proportions (57 % for Pb, 55 % for Cu and 43 % for Cd), which could be easily eluate from the sediments and caused hazards to the aquatic environment. The sediment diffusion fluxes of HMs and ammonia nitrogen were mostly positive, which indicated these sites currently released these pollutants from sediment to overlying water. Cd, Pb, Cu and Cr may mainly originate from industrial discharge and domestic sewage, while Cr was also greatly affected by crustal weathering; nutrient pollution may originate from agricultural activities and domestic sewage. Our study demonstrated that after decades' conventional water treatment in these rivers, the sediment pollution was still in a serious level with high ecological risk, and Cd was the dominant pollutant. At present, the external point source pollution has been effectively controlled, thus, the in-depth understanding of the sediment pollution characteristics after long-term water treatment could provide a scientific basis for the accurate elimination of river pollution.

Dyrk1a Phosphorylation of α-Synuclein Mediating Apoptosis of Dopaminergic Neurons in Parkinson's Disease.

Objective: To investigate the role of aberrant Dyrk1a expression in phosphorylation modification at the α-synuclein serine 129 (Ser129) site to analyze its molecular mechanism in mediating apoptosis of PD. Methods: The protein level of P-α-synuclein (Ser129), α-synuclein, Bcl-2, Bax, active caspase 3, GSK3ß, PI3K, AKT, and cyclinD1 were detected. The mRNA transcript levels of Dyrk1a and DAT and protein levels of IL-1ß, IL-6, COX-2, and TNF-α were detected. Results: P-α-synuclein (Ser129), α-synuclein, Bax, active caspase 3, GSK3ß, and cyclinD1 expressions were decreased in Dyrk1a-AAV-ShRNA (P < 0.05), and Bcl-2, AKT, and PI3K expressions were increased (P < 0.05). Increased TH protein expression was shown in Dyrk1a-AAV-ShRNA (P < 0.05). Dyrk1a mRNA was decreased in the Dyrk1a-AAV-ShRNA group (P < 0.05), and DAT mRNA was increased (P < 0.05). IL-1ß, IL-6, COX-2, and TNF-α protein levels were decreased in Dyrk1al-AAV-Sh-RNA (P < 0.05). Transcriptome sequencing showed that Fam220a, which was expected to activate STAT family protein binding activity and participate in the negative regulation of transcription through RNA polymerase II and protein dephosphorylation showed differentially upregulated expression. The untargeted metabolome showed that the major compounds in the Dyrk1a-AAV-ShRNA group were hormones and transmission mediators and the most metabolism-related pathways. Fam220a showed differentially upregulated expression, and differentially expressed genes were enriched for the neuroactive ligand-receptor interaction, vascular smooth muscle contraction, and melanogenesis-related pathways. Conclusion: Abnormal Dyrk1a expression can affect α-synuclein phosphorylation modifications, and dyrk1a knockdown activates the PI3K/AKT pathway and reduces dopaminergic neuron apoptosis. It provides a theoretical basis for the group to further investigate the molecular mechanism.

Mitochondrial Proteins Unveil the Mechanism by Which Physical Exercise Ameliorates Memory, Learning and Motor Activity in Hypoxic Ischemic Encephalopathy Rat Model.

BACKGROUND: Physical exercise has been shown to improve cognitive and motor functions, promoting neurogenesis and demonstrating therapeutic benefits in neurodegenerative disorders. Nonetheless, it is crucial to investigate the cellular and molecular mechanisms by which this occurs. The study aimed to investigate and evaluate the effect of swimming exercise on the changes of mitochondrial proteins in the brains of rats with hypoxic ischemic encephalopathy (HIE). METHODS: the vertical pole and Morris water maze tests were used to assess the animals' motor and cognitive functions, and western blot and immunofluorescence of brain tissue were used to assess the biomarkers of mitochondrial apoptosis and cristae stability in response to exercise training. Four groups of rats were used: (1) sham sedentary group (SHAM, NT), (2) sham exercise training group (SHAM, T) (3) hypoxic ischemic encephalopathy sedentary group (HIE, NT), and (4) hypoxic ischemic encephalopathy exercise training group (HIE, T). RESULTS: animals with HIE showed motor and cognitive deficits, as well as increased apoptotic protein expression. Exercise, on the other hand, improved motor and cognitive functions while also suppressing the expression of apoptotic proteins. CONCLUSIONS: By stabilizing the mitochondrial cristae and suppressing the apoptotic cascade, physical exercise provided neuroprotection in hypoxic ischemia-induced brain injury.

The distribution and density of monocarboxylate transporter 2 in cerebral cortex, hippocampus and cerebellum of wild-type mice.

Monocarboxylates cannot cross the blood-brain barrier freely to participate in brain energy metabolism. Specific monocarboxylate transporters (MCTs) are needed to cross cellular membranes. Monocarboxylate transporter 2 (MCT2) is a major monocarboxylate transporter encoded by the SLC16A7 gene. Recent studies reported that neurodegenerative diseases of the CNS, such as Alzheimer's disease (AD) and Parkinson's disease (PD), were related to energy metabolic impairment. MCT2 also plays an important role in energy metabolism in the CNS. To provide experimental evidence for future research on the role of MCT2 in the pathological process of CNS degenerative diseases, the distribution and density of MCT2 in different subregions of wild-type mouse brain was examined using immunohistochemistry, western blot and immunogold post-embedding electron microscopic techniques. The amount of MCT2 was higher in cerebellum than in cortex and hippocampus on western blots, and there was no statistical difference between cortex and hippocampus. Immunohistochemistry assay revealed the highest density of MCT2 in the CA3 of the hippocampus. The granular cell layer of the cerebellum contained more MCT2 than the molecular layer. The MCT2 density on the end feet of astrocytes of molecular layer was lower than in hippocampus, but the postsynaptic densities (PSDs) of asymmetric synapses in the molecular layer exhibited a high density using immunogold post-embedding electron microscopic techniques.

Regular Exercise Enhances Cognitive Function and Intracephalic GLUT Expression in Alzheimer's Disease Model Mice.

Brain energy metabolic impairment is one of the main features of Alzheimer's disease (AD) and is considered an underlying factor involved in cognitive impairment. Therefore, brain energy metabolism may represent a new therapeutic target for AD medical interventions. Among nutrients providing energy, glucose, the primary energy source, cannot cross the blood-brain barrier freely without specific glucose transporters (GLUTs), which are essential for the maintenance of cerebral energy metabolism homeostasis. Several converging lines of evidence suggest that GLUT1 deficiency in mice leads to synapse reduction and dysregulation coupled with mitochondrial morphological changes. In this study, the results revealed that regular exercise (RE) decreased the expression of amyloid-ß and phosphorylated tau by western blot, and enhanced the spatial learning and exploration ability of AD model mice as assessed by Morris water maze test. Mitochondrial cristae and edges were clear and intact, ATP production in the brain raised, the number of synapses increased, and GLUT1 and GLUT3 expression levels improved in the central nervous system (CNS) in AD model mice after RE. Changes in GLUT1 and GLUT3 expression at the protein level after RE are an important part of energy metabolic adaptation in AD model mice. Learning and memory improvement are highly associated with mitochondrial integrity and sufficient synapses in the CNS. This research suggests that increased brain energy metabolism attributed to RE exhibits promising therapeutic potential for AD.

Evaluation on curative effect and safety of interventional treatment for patients with acute myocardial infarction.

To evaluate the effectiveness and recent safety of emergency and selective percutaneous coronary intervention (PCI) in elderly patients (>80 years old) with acute myocardial infarction (AMI). 120 elderly patients with coronary heart disease (CHD) were divided into AMI group (with 55 cases) and non-myocardial infarction group (control group with 65 cases). Among the AMI group, there were 18 cases underwent emergency PCI within 12 hours after the onset, (AMI emergency PCI group), the rest 37 cases were AMI selective PCI group. In the control group, 2 cases had stable angina pectoris, 59 cases unstable angina pectoris and 4 patients old myocardial infarction. The lesions were classified according to the practice guidelines of American College of Cardiology/American Heart Association (ACC/AHA). The hospitalized major adverse cardiac events (MACE) and complications in the patients were recorded and statistically analyzed. The AMI group had a higher total Gensini score, lower left ventricular ejection fraction (LVEF), less mean stents and contrast agent dosage and shorter operation time, compared with the control group. The difference was statistically significant. Though the average postoperative length of stay in AMI emergency PCI group was longer than that of AMI selective PCI group, but the difference had no statistical significance. To all the included patients, there were 50 cases with lesions in one branch, 43 cases in two branches and 27 cases in three branches. And the immediate PCI success ratio in AMI group was lower than that in control group (80% VS. 96.9%, P= 0.003), without significant difference in the distribution number of diseased vessels and complete reconstruction ratio (P>0.05). The incidence of the total complications in AMI emergency PCI group was higher, compared with the non-emergency group (with 102 cases) and AMI selective PCI group (P<0.001, P=0.039); and the occurrence rate of complication in AMI group was higher than that of the control group (P<0.001). The emergency PCI for elder patients with AMI is safe and worthy of promotion.