FLAMES overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review.

BACKGROUND: In recent years, simultaneous or sequential occurrence of MOG antibody disease and anti-NMDAR encephalitis in the same patient has been reported with increasing frequency. Scholars refer to the overlapping occurrence of these two disorders as MOG antibody disease and anti-NMDAR encephalitis overlap syndrome (MNOS). Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR) -hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) is a rare clinical phenotype of MOGAD in which cortical FLAIR high-signal lesions are unilateral, with little spread to the cortex and meninges bilaterally. Although cases of FLAMES have been consistently reported. However, to our knowledge, such cases of FLAMES combined with NMDARE are rare. CASE PRESENTATION: Here, we describe a case of FLAMES combined with anti-NMDARE. The patient was a young male, 29 years old, admitted to our hospital with isolated seizures, whose MRI showed unilateral thalamic and bilateral frontal and parietal leptomeningeal involvement. Since we were unaware of the possibility of bilateral meningo-cortical MOGAD manifestations, the case was initially diagnosed as viral encephalitis and was given antiviral therapy. The diagnosis was not clarified until anti-NMDAR-IgG and MOG-IgG positivity was detected in the cerebrospinal fluid and serum. The patient was then treated with high-dose corticosteroids and his symptoms responded well to the steroids. Therefore, this case expands the clinical spectrum of MNOS overlap syndrome. In addition, we describe the clinical features of MNOS by summarizing the existing literature and exploring the possible mechanisms of its immune response. CONCLUSIONS: Our case serves as a reminder to clinicians that when patients present with atypical clinical manifestations such as seizures, consideration should be given to MNOS and conduct testing for various relevant autoantibodies (including MOG abs) and viruses in both serum and cerebrospinal fluid, as it is easy to misdiagnose the disease as other CNS diseases, such as viral meningoencephalitis. This syndrome exhibits a high responsiveness to steroids, highlighting the critical importance of recognizing the clinical and neuroimaging features of this overlap syndrome for prompt diagnosis and treatment. Furthermore, it enriches the disease spectrum of MNOS.

Spatial patterns and drivers of ecosystem multifunctionality in China: Arid vs. humid regions.

Ecosystem multifunctionality (EMF) refers to an ecosystem's capacity to simultaneously uphold multiple ecological functions or services. In terrestrial ecosystems, the potential patterns and processes of EMF remain largely unexplored, limiting our comprehension of how ecosystems react to various driving factors. We collected environmental, soil and plant nutrient data, investigate the spatial distribution characteristics of EMF in China's terrestrial ecosystems, differentiating between arid and humid regions and examining the underlying drivers. Our findings reveal substantial spatial heterogeneity in the distribution of EMF across China's terrestrial ecosystems, with pronounced variations between arid and humid regions. In arid regions, the EMF index predominantly falls within the range of -1 to 1, including approximately 66.8 % of the total area, while in humid regions, the EMF index primarily falls within the range of 0 to 2, covering around 55.2 % of the total area. Climate, soil, and vegetation factors account for 61.4 % and 51.9 % of the total EMF variation in arid and humid regions, respectively. Notably, climate emerges as the dominant factor governing EMF variation in arid regions, whereas soil physicochemical properties take precedence in humid regions. Specifically, mean annual temperature (MAT) emerges as the primary factor influencing EMF variation in arid regions, while the normalized difference vegetation index (NDVI) and soil biodiversity index (SBI) play pivotal roles in regulating EMF variation in humid regions. Indeed, climate can exert both direct and indirect influences on EMF. In summary, our study not only compared the disparities in the spatial distribution of EMF in arid and humid regions but also unveiled the distinct controlling factors that govern EMF changes in these different regions. Our research has contributed novel insights for evaluating the drivers responsible for mediating EMF in diverse ecosystems, shedding light on the adaptability and response mechanisms of ecosystems under varying environmental conditions.

Relationship among Parkinson's disease, constipation, microbes, and microbiological therapy.

This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson's disease (PD), a prevalent non-motor symptom contributing significantly to patients' morbidity. A marked alteration in the gut microbiota, predominantly an increase in the abundance of Proteobacteria and Bacteroidetes, is observed in PD-related constipation. Conventional treatments, although safe, have failed to effectively alleviate symptoms, thereby necessitating the development of novel therapeutic strategies. Microbiological interventions such as prebiotics, probiotics, and fecal microbiota transplantation (FMT) hold therapeutic potential. While prebiotics improve bowel movements, probiotics are effective in enhancing stool consistency and alleviating abdominal discomfort. FMT shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with PD. Despite promising developments, the causal relationship between changes in gut microbiota and PD-related constipation remains elusive, highlighting the need for further research in this expanding field.

Soil organic carbon fractions in China: Spatial distribution, drivers, and future changes.

Soil is the world's largest terrestrial carbon pool and plays an important role in the global carbon cycle, which may be greatly affected by global change. Recently, research frameworks have indicated that division of soil organic carbon (SOC) into two forms particulate organic carbon (POC) and mineral-associated organic carbon (MAOC) can help us better understand SOC cycle. However, there is a lack of the use of meta-analysis combined with machine learning models to explore the spatial distribution of SOC fractions at large scales. Based on 356 studies conducted in Chinese terrestrial ecosystems, we performed a meta-analysis of extracted data and measured data combined with machine learning models to reveal the spatial distribution of soil POC density (POCD) and MAOC density (MAOCD) and the main drivers of variations in POCD and MAOCD. Our study demonstrated that POCD and MAOCD in China's soil were 3.24 and 2.61 kg m-2, with stocks of 31.10 and 25.06 Pg, respectively. Climate, soil, and vegetation properties together explained 44.9 % and 27.2 % of the variation in POCD and MAOCD, respectively. Climate was more important than other variables in controlling the changes in POCD, with mean annual temperature being specifically the main driver. Soil, however, was more important than other variables in controlling changes in MAOCD, with soil clay content being the main driver. Compared to the other climate scenarios, the rate of change in POCD and MAOCD was higher with a 1.5 °C increase in temperature. In the future, we should pay more attention to the impact of climate change on POCD, which provides a theoretical basis for achieving the "dual-carbon" target. Our study contributes to the understanding of the potential mechanisms of the changes in SOC fractions under global change and provides useful information for future prediction models to simulate the impacts of global change.

Efficient separation of impurities Fe/Al/Ca and recovery of Zn from electroplating sludge using glucose as reductant.

Electroplating sludge (ES), a hazardous waste containing heavy metals and Fe/Al/Ca impurities, is conventionally disposed of in landfills. In this study, a pilot-scale vessel with an effective capacity of 20 L was applied to recycle Zn from real ES. The sludge contained 6.3 wt% Fe, 6.9 wt% Al, 2.6 wt% Si, 6.1 wt% Ca, and 17.6 wt% Zn and was treated using a four-step method. First, ES was dissolved in nitric acid after washing in a water bath at 75 °C for 3 h to produce an acidic solution with Fe, Al, Ca, and Zn concentrations of 4527.2, 3116.1, 3357.7, and 21,275 mg/L, respectively. Second, the acidic solution was added with glucose at an Mglucose/Mnitrate ratio of 0.08 and hydrothermally treated at 160 °C for 4 h. During this step, nearly 100 % Fe and 100 % Al were simultaneously removed as a mixture containing 53.1 wt% Fe2O3 and 45.7 wt% Al2O3. This process was repeated five times, during which the Fe/Al removal and Ca/Zn loss rates remained unchanged. Third, the residual solution was adjusted with sulfuric acid, and over 99 % Ca was removed as gypsum. The residual Fe, Al, Ca, and Zn concentrations were 0.44, 0.88, 52.59, and 31,177.1 mg/L, respectively. Finally, Zn in the solution was precipitated as ZnO with a concentration of 94.3 %. Economic calculations showed that each 1 t of ES processed created revenue of about $122. This is the first study of high-value metal resource recovery using real electroplating sludge at the pilot scale. This work highlights the pilot-scale application of resource utilization of real ES and provides new insights into the recycling of heavy metals from hazardous waste.

Effective recovery of Ti as anatase nanoparticles from waste red mud via a coupled leaching and boiling route.

Red mud (RM) a solid waste generated by the bauxite smelting industry, is a rich source of metal resources, especially Ti, and its recycling can bring significant environmental and economic benefits. In this study, precious metal Ti was efficiently recovered from red mud using a coupled acid leaching and boiling route for the effective separation of low-value metals. The red mud which contained mainly 10.69% Si, 12.1% Al, 15.2% Ca, 10.99% Fe, and 4.37% Ti, was recovered in five steps. First, a nitric acid solution was used to leach the metals in multiple stages, resulting in an acidic leach solution with high concentrations of Fe, Al, Ti, and Ca ions 2.7 g/L, 4.7 g/L, 5.43 g/L, and 1.8 g/L, respectively. Then, a small amount of sucrose was added as a catalyst to recover Ti from the leach solution under hydrothermal conditions, resulting in the targeted recovery of 98.6% of Ti in the form of high-purity anatase while Fe, Al, and Ca remained in the solution. Next, the Fe in solution was separated as hematite products at a temperature of 110°C and a reaction time of 4 h. Similarly, the Al in the solution was separated and precipitated as boehmite by heating it at 260°C for a reaction time of 20 h. Finally, the remaining Ca in solution was recovered by simple pH regulation. Economic accounting assessment showed that the method yields $101.06 for 1 t of red mud treated, excluding labor costs. This study provides a novel approach to recover precious metals from metal wastes through the whole process resource recovery of solid waste red mud.

Plasma Metabolic Analysis Reveals the Dysregulation of Short-Chain Fatty Acid Metabolism in Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by high morbidity, high disability rate, and slow course of disease. The clinical diagnostic method of PD is complex and time-consuming, and there is no clear biomarker for clinical use. We aimed to investigate the plasma metabolites in PD and find out potential biomarkers with diagnostic ability. In the analysis of more than 40 metabolites including short-chain fatty acids, long-chain fatty acids, amino acids, and carbohydrates, the difference of short-chain fatty acids was observed. Acetic acid concentration was higher in PD than in healthy controls, and propanoic acid and 2,3,4-trihydroxybutyric acid were lower in PD. Compared with the early stage of PD, acetic acid increased significantly in the advanced stage of PD. Propanoic acid increased significantly in medicated PD compared with drug naïve PD. ROC analysis revealed acetic acid discriminated PD from healthy controls with 100% sensitivity, 88.9% specificity, and an area under the curve (AUC) of 0.981, and propanoic acid discriminated PD from healthy controls with an AUC of 0.981, 100% sensitivity, and 94.4% specificity. Acetic acid and propanoic acid may be a potential biomarker for differentiating PD from health, and the propanoic acid was evaluated as the most potential diagnostic marker because of its extremely high sensitivity and specificity.

The multi-scale meso-mechanics model of viscoelastic dentin.

Human dentin is a hierarchical material with multi-level micro-/nano-structures, consisting of tubule, perti-tubular dentin (PTD) and intertubular dentin (ITD) as the major constituents at microscale; and the PTD and ITD are further composed of collagen and hydroxyapatite (HAp) crystals with different volume fractions at nanoscale. In most cases, the HAp is considered as elastic while the collagen as viscoelastic material. It is of great significance to study the hierarchical structure and viscoelasticity of human dentin to understand the mechanical properties of dentin for further development of restorative materials. Based on this, this paper focuses on multiscale modeling of the elastic properties and dynamic viscoelastic response of dentin and establishes a bottom-up micromechanics model from nano-to macro-scale. In order to study the nanostructural effect on the viscoelastic behavior of hierarchical structures, the homogenization theories of random platelets composites (HTRPC) and the locally-exact homogenization theory (LEHT) are introduced for the homogenization of heterogeneous materials of microstructures at different levels. The HTRPC, based on Eshelby Inclusion theory, is used to predict the effective modulus of PTD and ITD. The LEHT is a method for homogenizing multiphase dentin characterized by repeated unit cells (RUCs). The resulting predictions are in very good agreement with several experimental data from the literature. In addition, the results of nanostructrual effect on dentin show that the viscoelasticity of dentin is majorly contributed by collagen and the HAp greatly provide the strength and hardness of dentin. Furthermore, the ageing effect on dentin's viscoelasticity is considered from the proposed multiscale micromechanics model. It is demonstrated that the ageing effect is much more influential in affecting the loss moduli of dentin than the storage.

The multiscale meso-mechanics model of viscoelastic cortical bone.

Cortical bone is a complex hierarchical structure consisting of biological fiber composites with transversely isotropic constituents, whose microstructures deserve extensive study to understand the mechanism of living organisms and explore development of biomimetic materials. Based on this, we establish a three-level hierarchical structure from microscale to macroscale and propose a multiscale micromechanics model of cortical bone, which considers Haversian canal, osteonal lamellae, cement line and interstitial lamellae. In order to study the microstructural effect on the elastic behavior of hierarchical structures, the Mori-Tanaka model and locally exact homogenization theory are introduced for the homogenization of heterogeneous materials of microstructure at each level. Within sub-microscale, Haversian canal and Osteonal lamella are treated as fiber and matrix, whose homogenization is surrounded with cement line matrix in microstructure (or what we called "osteon") for the second homogenization; finally, osteon and interstitial lamella establish the meso-structure for the third homogenization, predicting the effective moduli of cortical bone. The correctness of the model in this paper is verified against the data in literature with good agreement. Finally, the dynamic viscoelastic response of cortical bones is investigated from a multiscale perspective, where the measured data are substituted into the present models to study the hydration and aging effect on bones' stiffness and viscoelasticity. It is demonstrated that the hydration is much more influential in affecting the storage and loss moduli of cortical bone than the aging effect. We also present a few numerical investigations on microstructural material and geometric parameters on the overall mechanical properties of cortical bone.

Patients with SERPINC1 rs2227589 polymorphism found to have multiple cerebral venous sinus thromboses despite a normal antithrombin level: A case report.

BACKGROUND: The hereditary antithrombin (AT) deficiency caused by SERPINC1 gene mutation is an autosomal dominant thrombotic disorder. An increasing number of studies have shown that mutations in the SERPINC1 rs2227589 polymorphic site are correlated with a risk of venous thromboembolism (VTE) at common sites, such as lower extremity deep venous thrombosis and pulmonary thromboembolism. Currently, there are no reports of cerebral venous sinus thrombosis (CVST), a VTE site with a low incidence rate and rs2227589 polymorphism. CASE SUMMARY: Here, we report a Chinese CVST case with a mutation of the SERPINC1 rs2227589 polymorphic site, which did not cause significant AT deficiency. In a 50-year-old male patient presenting with multiple cerebral venous sinus thromboses no predisposing factors were detected, although a relative had a history of lower extremity deep venous thrombosis. We performed sequencing of the SERPINC1 gene for the patient and his daughter, which revealed the same heterozygous mutation at the rs2227589 polymorphic site: c.41+141G>A. CONCLUSION: The results showed that more studies should be conducted to assess the correlation between rs2227589 polymorphism and CVST.

Limitations in activities of daily living increase the risk of stroke in older Chinese adults: a population-based longitudinal study.

It remains unclear whether limitations in activities of daily living (ADL) increase the risk of stroke in older Chinese adults. This longitudinal study used data from the Chinese Longitudinal Healthy Longevity Survey to investigate the effects of limitations in ADL on the incidence of stroke in older adults. Between 2002 and 2011, 46,728 participants from 22 provinces in China were included in this study. Of participants, 11,241 developed limitations in ADL at baseline. A 3-year follow-up was performed to determine the incidence of stroke. During the 3-year follow-up, 929 participants (8.26%) and 2434 participants (6.86%) experienced stroke in the ADL limitations group and non-ADL limitations group, respectively. Logistic regression was used to analyze the effect of ADL limitations on the risk of stroke. The results showed that after adjusting for the confounding factors gender, age, weight, hypertension, diabetes, heart disease, natural teeth, hearing impairment, visual impairment, smoking, alcohol abuse, exercise, ethnicity, literacy, residential area, and poverty, the ADL limitations group had a 77% higher risk of developing stroke than the non-ADL limitations group. After propensity score matching, the ADL limitations group still had a 33% higher risk of developing stroke than the non-ADL limitations group (OR = 1.326, 95% CI: 1.174-1.497). These findings suggest that limitations in ADL are a stroke risk factor.

Targeted fatty acid metabolomics to discover Parkinson's disease associated metabolic alteration.

The pathogenesis of Parkinson's disease (PD) remains to be elucidated, and the metabolomics analysis has the potential to identify metabolic profiles that are involved in PD pathogenesis. Here we applied a target metabolomics approach to measure the plasma levels of 158 fatty acid metabolites in a discovery cohort including 42 PD patients and 54 health volunteers, and found two upregulated (arachidonic acid and 13-hydroxy-octadecatrienoic acid) and eleven down-regulated (docosahexaenoic acid, lyso-platelet-activating factor, 12-hydroxy-eicosatetraenoic acid, dihydroxy-eicosatrienoic acids, dihidroxy-octadecenoic acids, 17,18-dihydroxy-eicosatetraenoic acid, and hydroperoxy-octadecadienoic acids) metabolites as primary candidate marker of PD. A support vector machine algorithm with primary candidate marker was used in an independent validation cohort to identify PD. Arachidonic acid and 13-hydroxy-octadecatrienoic acid were evaluated as an effective tool in that area under the receiver operating characteristic curve reached 0.995 and 0.912 in the validation set for diagnosing PD from healthy volunteers. Besides, the sensitivity and specificity of arachidonic acid as diagnostic factor of PD in validation set were 100% and 94.10%. Similarly, the sensitivity and specificity of 13-hydroxy-octadecatrienoic acid were 100% and 82.40% for identifying PD. This target fatty acid metabolomics demonstrated a series of plasma fatty acid metabolite as PD candidate marker with high efficiency and provided insights into the understanding of PD metabolic regulation.

DNA Methylation Signature of Epileptic Encephalopathy-Related Pathogenic Genes Encoding Ion Channels in Temporal Lobe Epilepsy.

Epilepsy is characterized by highly abnormal synchronous discharge of brain neurons, and ion channels are fundamental in the generation and modulation of neural excitability. Considering that abnormal methylation can either activate or repress genes, this study was designed to explore the DNA methylation signature of pathogenic genes encoding ion channels in temporal lobe epilepsy (TLE). In total, 38 TLE patients and 38 healthy controls were enrolled in the study, and genomic DNA and total protein of the lymphocytes were extracted from peripheral blood samples to assess methylation and protein levels. The DNA methylation levels of all 12 genes examined were significantly lower in the TLE group than in the control group. After false-positive correction, 83.3% (10/12) of these genes, namely, gamma-aminobutyric acid type A receptor subunit beta1 (GABRB1), gamma-aminobutyric acid type A receptor subunit beta2 (GABRB2), gamma-aminobutyric acid type A receptor subunit beta1 (GABRB3), glutamate ionotropic receptor NMDA type subunit 1 (GRIN1), glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A), glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B), hyperpolarization activated cyclic nucleotide gated potassium channel 1 (HCN1), potassium voltage-gated channel subfamily A member 2 (KCNA2), potassium voltage-gated channel subfamily B member 1 (KCNB1), and potassium sodium-activated channel subfamily T member 1 (KCNT1), were still differentially expressed. Among these ion channels, HCN1 and KCNA2 were selected to evaluate the effects of DNA methylation, and the levels of these proteins were inversely upregulated in the TLE group compared to the control group. As the genes identified as having differential methylation levels are involved in both excitatory and inhibitory ion channels, this study observed by binary logistic regression that hypermethylated GARAB1 was an independent risk factor for TLE, indicating that the overwhelming effect of ion channels on TLE is probably inhibitory from the perspective of DNA methylation. All these findings support the involvement of DNA methylation in TLE pathologies, but the mechanisms need to be further investigated.

Metabolomic profiling of fatty acid biomarkers for intracerebral hemorrhage stroke.

The identification of new biomarkers (e.g., metabolic biomarkers) will facilitate not only the diagnosis of stroke but also the differentiation of stroke subtypes, especially the discrimination of ischaemic stroke from intracerebral hemorrhage. Herein, we develop for the first time an ultra-high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS)-based targeted metabolomic method to screen the metabolic biomarkers of stroke and identify the fatty acid metabolite 20-hydroxy-leukotriene B4 (20-OH-LTB4) and its key enzyme cytochrome P450 family 4 subfamily F member 2 (CYP4F2) as the potential biomarkers for differentiating healthy persons, acute ischemic stroke (AIS) patients, and intracerebral hemorrhage stroke (ICH) patients. We evaluated 158 fatty acids and their metabolites in 177 serum samples obtained from 65 healthy volunteers, 70 AIS patients and 42 ICH patients, and identified the potential biomarkers associated with ICH by using multivariate statistical analysis. We found that 20-OH-LTB4 and arachidonic acid can be used to discriminate ICH patients from healthy individuals, and 20-OH-LTB4 and 17, 18-epoxy-eicosatetraenoic acid (7,18-EpETE) can be used to differentiate the subtypes of ICH and AIS. Especially, 20-OH-LTB4 may function as a potential biomarker for ICH diagnosis and risk assessment, and it can discriminate ICH patients from healthy individuals and AIS patients. Moreover, we identified CYP4F2 protein as a potential biomarker of ICH for prevention and treatment assessment. This method may provide a powerful platform for ICH diagnosis, prevention, and treatment assessment.

Plasma endothelial microvesicles and their carrying miRNA-155 serve as biomarkers for ischemic stroke.

Endothelial microvesicles (EMVs) could reflect the status of endothelial cells (ECs) which are involved in the pathogenesis of ischemic stroke (IS). MiR-155 could regulate EC functions. However, their roles in IS remain unclear. This study aimed to investigate the levels of plasma EMVs and EMVs carrying miRNA-155 (EMVs-miR-155) in IS patients to explore their potential roles as biomarkers. Ninety-three IS patients and 70 controls were recruited in this study. The levels of circulating EMVs and EMVs-miR-155 were detected by fluorescence nanoparticle tracking analysis and quantitative real-time PCR, respectively. The correlations between level of EMVs/EMVs-miR-155 and the onset time, severity, infarct volume, and subtypes of IS were analyzed. The severity and infarct volume were assessed by NIHSS and magnetic resonance imaging, respectively. Multivariate logistic regression analysis was used to investigate the risk factors of IS. The ROC curve and area under ROC curve (AUC) of EMVs and EMVs-miR-155 were determined. The levels of plasma EMVs and EMVs-miR-155 were increased significantly in acute and subacute stages of IS and remained unchanged in chronic stage, and were positively related to the infarct volume and NIHSS scores and were associated with large artery atherosclerosis and cardioembolism subtypes defined by Trial of Org 10 172 in acute stroke treatment (TOAST) classification. Multivariate logistic regression analysis demonstrated that plasma EMVs and EMVs-miR-155 were significant and independent risk factors of IS and their AUC were 0.778 and 0.851, respectively, and increased to 0.892 after combination. Our study suggests that plasma EMVs and EMVs-miR-155 are promising biomarkers for IS. The diagnostic value of EMVs-miR-155 is higher and their combination is the best.

Integration of ultra-high-pressure liquid chromatography-tandem mass spectrometry with machine learning for identifying fatty acid metabolite biomarkers of ischemic stroke.

We report for the first time the integration of ultra-high-pressure liquid chromatography-tandem mass spectrometry with machine learning for identifying fatty acid metabolite biomarkers of ischemic stroke. In particular, we develop an optimal model to discriminate ischemic stroke patients from healthy persons with 100% sensitivity and 93.18% specificity. This research may facilitate understanding the roles of fatty acid metabolites in stroke occurrence, holding great potential in clinical stroke diagnosis.

SAP97 polymorphisms associated with early onset Parkinson's disease.

OBJECTIVE: To investigate the relationship between SAP97 genetic polymorphisms and sporadic Parkinson's disease (PD) in Han Chinese population with the expectation of offering genetic data for the early prevention and treatment of the disease. METHODS: In this study, we genotyped single-nucleotide polymorphisms (SNPs) (rs3915512 and rs9843659) in theSAP97 gene in 317 patients with PD and 317 healthy-matched controls in a Han Chinese population through the improved multiplex ligation detection reaction (imLDR) technique. Then, we analyzed the association of each SNP, alone or in combination, with risk or age of onset of PD. RESULTS: The SAP97 rs3915512 and rs9843659 polymorphisms were not associated with the risk of PD. However, the minor allele of the rs3915512 and rs9843659 were significantly more common in PD patients with an early age of onset. Additionally, significant differences in the distribution of the onset age of the PD among different genotypes of the rs9843659 polymorphism. The CA haplotype was significantly related to early onset PD. CONCLUSIONS: Our data are the first to suggest that the SAP97 SNPs rs3915512 and rs9843659 and the CA haplotype may be significantly associated with early onset PD in China.

Associations of ATG7 rs1375206 polymorphism and elevated plasma ATG7 levels with late-onset sporadic Parkinson's disease in a cohort of Han Chinese from southern China.

Background: Autophagy-related gene 7 (ATG7) plays a key role in autophagy and is strongly implicated in Parkinson's disease (PD). This study investigated the associations of rs1375206 polymorphism in ATG7 gene promoter and plasma ATG7 levels with late-onset sporadic PD in a cohort of Han Chinese from southern China.Methods: Variant genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism and gene sequencing in 124 patients with late-onset sporadic PD, as well as in 105 age- and sex-matched healthy controls. Plasma ATG7 levels were determined using an enzyme-linked immunosorbent assay.Results: No significant differences in genotype distributions were found between the two groups. Stratification analyses by sex and clinical motor subtypes revealed that the differences remained non-significant in each subgroup (all p > 0.05). Plasma ATG7 protein levels were significantly higher in the PD group than in the control group (p = 0.000). Haplotype analysis demonstrated that the A-T haplotype was significantly associated with late-onset sporadic PD (p = 0.045).Conclusion: Our study suggests that the rs1375206 polymorphism in ATG7 may not be associated with late-onset sporadic PD; however, high plasma ATG7 levels and the A-T haplotype may be associated with susceptibility to late-onset sporadic PD in the Han population from Zhejiang and Guangdong provinces.

Rs2015 Polymorphism in miRNA Target Site of Sirtuin2 Gene Is Associated with the Risk of Parkinson's Disease in Chinese Han Population.

Accumulating evidence reveals that the sirtuin family is involved in the pathology of Parkinson's disease (PD). However, the association between the polymorphisms of the sirtuin gene and the risk of PD remains elusive. Here, we investigated the possible association of nine SIRT1 and SIRT2 SNPs with the risk of PD through a clinical case-control study from the Chinese Han population. Our results showed that rs12778366 in the promoter region of SIRT1 and rs2015 in the 3'untranslated region (3'UTR) of the SIRT2 were significantly associated with the risk of PD. Five SNPs related to SIRT1, rs3740051, rs7895833, rs7069102, rs2273773, and rs4746720 and two SNPs related to SIRT2, rs10410544, and rs45592833 did not show an association with PD risk in this study. Moreover, we found that mRNA level of SIRT2 was upregulated, and mRNA level of SIRT1 was downregulated in the peripheral blood of PD patients compared with healthy controls, and we also observed that SNPs rs12778366 and rs2015 influenced the SIRT1 and SIRT2 expression levels, respectively. Further functional assays suggest that rs2015 may affect the expression of SIRT2 by affecting the binding of miR-8061 to the 3'UTR of SIRT2, ultimately contributing to the risk of PD.

Microvesicles-mediated communication between endothelial cells modulates, endothelial survival, and angiogenic function via transferring of miR-125a-5p.

Endothelial cells (ECs) released microvesicles (EMVs) could modulate the functions of target cells by transferring their microRNAs (miRs). We have reported that miR-125a-5p protected EC function. In this study, we determined whether EMVs provided beneficial effects on ECs by transferring miR-125a-5p. Human brain microvessel ECs were transfected with miR-125a-5p mimic or miR-125a-5p short hairpin RNA to obtain miR-125a-5p overexpressing ECs and miR-125a-5p knockdown ECs, and their derived EMVs. For the functional study, ECs or hypoxia/reoxygenation injured ECs were coincubated with various EMVs. The survival and angiogenic function of ECs were measured. Western blot and quantitative real time polymerase chain reaction (qRT-PCR) were used for measuring the levels of phosphoinositide 3-kinase (PI3K), phosphorylation-Akt (p-Akt)/Akt, p-endothelial nitric oxide synthase (p-eNOS), cleaved caspase-3, and miR-125a-5p. PI3K inhibitor was used for pathway analysis. EMVs promoted the proliferation, migration, and tube formation ability of ECs, and alleviated the apoptotic rate of ECs. These effects were associated by an increase in p-Akt/Akt and p-eNOS, and a decrease in cleaved caspase-3 could be abolished by LY294002. Overexpression or downregulation of miR-125a-5p in EMVs promoted or inhibited those effects of EMVs. EMVs could enhance the survival and angiogenic function of ECs via delivering miR-125a-5p to modulate the expression of PI3K/Akt/eNOS pathway and caspase-3.