Quantitative electroencephalography (qEEG), apolipoprotein A-I (APOA-I), and apolipoprotein epsilon 4 (APOE ɛ4) alleles for the diagnosis of mild cognitive impairment and Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is the most common type of dementia. Amnestic mild cognitive impairment (aMCI), a pre-dementia stage is an important stage for early diagnosis and intervention. This study aimed to investigate the diagnostic value of qEEG, APOA-I, and APOE ɛ4 allele in aMCI and AD patients and found the correlation between qEEG (Delta + Theta)/(Alpha + Beta) ratio (DTABR) and different cognitive domains. METHODS: All participants were divided into three groups: normal controls (NCs), aMCI, and AD, and all received quantitative electroencephalography (qEEG), neuropsychological scale assessment, apolipoprotein epsilon 4 (APOE ɛ4) alleles, and various blood lipid indicators. Different statistical methods were used for different data. RESULTS: The cognitive domains except executive ability were all negatively correlated with DTABR in different brain regions while executive ability was positively correlated with DTABR in several brain regions, although without statistical significance. The consequences confirmed that the DTABR of each brain area were related to MMSE, MoCA, instantaneous memory, and the language ability (p < 0.05), and the DTABR in the occipital area was relevant to all cognitive domains (p < 0.01) except executive function (p = 0.272). Also, occipital DTABR was most correlated with language domain when tested by VFT with a moderate level (r = 0.596, p < 0.001). There were significant differences in T3, T5, and P3 DTABR between both AD and NC and aMCI and NCs. As for aMCI diagnosis, the maximum AUC was achieved when using T3 combined with APOA-I and APOE ε4 (0.855) and the maximum AUC was achieved when using T5 combined with APOA-I and APOE ε4 (0.889) for AD diagnosis. CONCLUSION: These findings highlight that APOA-I, APOE ɛ4, and qEEG play an important role in aMCI and AD diagnosis. During AD continuum, qEEG DTABR should be taken into consideration for the early detection of AD risk.

Identification of novel diagnostic panel for mild cognitive impairment and Alzheimer's disease: findings based on urine proteomics and machine learning.

BACKGROUND: Alzheimer's disease is a prevalent disease with a heavy global burden. Proteomics is the systematic study of proteins and peptides to provide comprehensive descriptions. Aiming to obtain a more accurate and convenient clinical diagnosis, researchers are working for better biomarkers. Urine is more convenient which could reflect the change of disease at an earlier stage. Thus, we conducted a cross-sectional study to investigate novel diagnostic panels. METHODS: We firstly enrolled participants from China-Japan Friendship Hospital from April 2022 to November 2022, collected urine samples, and conducted an LC-MS/MS analysis. In parallel, clinical data were collected, and clinical examinations were performed. After statistical and bioinformatics analyses, significant risk factors and differential urinary proteins were determined. We attempt to investigate diagnostic panels based on machine learning including LASSO and SVM. RESULTS: Fifty-seven AD patients, 43 MCI patients, and 62 CN subjects were enrolled. A total of 3366 proteins were identified, and 608 urine proteins were finally included in the analysis. There were 33 significantly differential proteins between the AD and CN groups and 15 significantly differential proteins between the MCI and CN groups. AD diagnostic panel included DDC, CTSC, EHD4, GSTA3, SLC44A4, GNS, GSTA1, ANXA4, PLD3, CTSH, HP, RPS3, CPVL, age, and APOE ε4 with an AUC of 0.9989 in the training test and 0.8824 in the test set while MCI diagnostic panel included TUBB, SUCLG2, PROCR, TCP1, ACE, FLOT2, EHD4, PROZ, C9, SERPINA3, age, and APOE ε4 with an AUC of 0.9985 in the training test and 0.8143 in the test set. Besides, diagnostic proteins were weakly correlated with cognitive functions. CONCLUSIONS: In conclusion, the procedure is convenient, non-invasive, and useful for diagnosis, which could assist physicians in differentiating AD and MCI from CN.

Metabolic engineering of Paracoccus denitrificans for dual degradation of sulfamethoxazole and ammonia nitrogen.

Sulfamethoxazole (SMX), as one of the most widely used sulfonamide antibiotics, has been frequently detected in the aqueous environment, posing potential risks to the environment and human health. Although microbial degradation methods have been widely applied, some issues remain, including low degradation efficiency and poor environmental adaptability. In this regard, constructing efficient degrading bacteria by metabolic engineering is an ideal solution to these challenges. In this study, we used Paracoccus denitrificans DYTN-1, a superior nitrogen removal environment strain, as chassis to construct an SMX degradation pathway, obtaining a new bacteria for simultaneous degradation of SMX and removal of ammonia nitrogen. In doing this, we first identified and characterized four native promoters of P. denitrificans DYTN-1 with gradient strength to control the expression of the SMX degradation pathway. After degradation pathway expression level optimization and FMN reductase optimization, SMX degradation efficiency was significantly improved. The constructed P. d-pIAB4-PCS-sutR strain exhibited superior co-degradation of SMX and ammonia nitrogen contaminants with degradation rates of 44% and 71%, respectively. This study could pave the way for SMX degradation engineered strain design and evolution of environmental bioremediation. IMPORTANCE The abuse of sulfamethoxazole (SMX) had led to an increased accumulation in the environment, resulting in the disruption of the structure of microbial communities, further disrupting the bio-degradation process of other pollutants, such as ammonia nitrogen. To solve this challenge, we first identified and characterized four native promoters of Paracoccus denitrificans DYTN-1 with gradient strength to control the expression of the SMX degradation pathway. Then SMX degradation efficiency was significantly improved with degradation pathway expression level optimization and FMN reductase optimization. Finally, the superior nitrogen removal environment strain, P. denitrificans DYTN-1, obtained an SMX degradation function. This pioneering study of metabolic engineering to enhance the SMX degradation in microorganisms could pave the way for designing the engineered strains of SMX and nitrogen co-degradation and the environmental bioremediation.

Prebiotics modulate the microbiota-gut-brain axis and ameliorate cognitive impairment in APP/PS1 mice.

PURPOSE: Prebiotics, including fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), stimulate beneficial gut bacteria and may be helpful for patients with Alzheimer's disease (AD). This study aimed to compare the effects of FOS and GOS, alone or in combination, on AD mice and to identify their underlying mechanisms. METHODS: Six-month-old APP/PS1 mice and wild-type mice were orally administered FOS, GOS, FOS + GOS or water by gavage for 6 weeks and then subjected to relative assays, including behavioral tests, biochemical assays and 16S rRNA sequencing. RESULTS: Through behavioral tests, we found that GOS had the best effect on reversing cognitive impairment in APP/PS1 mice, followed by FOS + GOS, while FOS had no effect. Through biochemical techniques, we found that GOS and FOS + GOS had effects on multiple targets, including diminishing Aß burden and proinflammatory IL-1ß and IL-6 levels, and changing the concentrations of neurotransmitters GABA and 5-HT in the brain. In contrast, FOS had only a slight anti-inflammatory effect. Moreover, through 16S rRNA sequencing, we found that prebiotics changed composition of gut microbiota. Notably, GOS increased relative abundance of Lactobacillus, FOS increased that of Bifidobacterium, and FOS + GOS increased that of both. Furthermore, prebiotics downregulated the expression levels of proteins of the TLR4-Myd88-NF-κB pathway in the colons and cortexes, suggesting the involvement of gut-brain mechanism in alleviating neuroinflammation. CONCLUSION: Among the three prebiotics, GOS was the optimal one to alleviate cognitive impairment in APP/PS1 mice and the mechanism was attributed to its multi-target role in alleviating Aß pathology and neuroinflammation, changing neurotransmitter concentrations, and modulating gut microbiota.

Genetic Insights into Obesity and Brain: Combine Mendelian Randomization Study and Gene Expression Analysis.

As a major public-health concern, obesity is imposing an increasing social burden around the world. The link between obesity and brain-health problems has been reported, but controversy remains. To investigate the relationship among obesity, brain-structure changes and diseases, a two-stage analysis was performed. At first, we used the Mendelian-randomization (MR) approach to identify the causal relationship between obesity and cerebral structure. Obesity-related data were retrieved from the Genetic Investigation of ANthropometric Traits (GIANT) consortium and the UK Biobank, whereas the cortical morphological data were from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. Further, we extracted region-specific expressed genes according to the Allen Human Brian Atlas (AHBA) and carried out a series of bioinformatics analyses to find the potential mechanism of obesity and diseases. In the univariable MR, a higher body mass index (BMI) or larger visceral adipose tissue (VAT) was associated with a smaller global cortical thickness (pBMI = 0.006, pVAT = 1.34 × 10-4). Regional associations were found between obesity and specific gyrus regions, mainly in the fusiform gyrus and inferior parietal gyrus. Multivariable MR results showed that a greater body fat percentage was linked to a smaller fusiform-gyrus thickness (p = 0.029) and precuneus surface area (p = 0.035). As for the gene analysis, region-related genes were enriched to several neurobiological processes, such as compound transport, neuropeptide-signaling pathway, and neuroactive ligand-receptor interaction. These genes contained a strong relationship with some neuropsychiatric diseases, such as Alzheimer's disease, epilepsy, and other disorders. Our results reveal a causal relationship between obesity and brain abnormalities and suggest a pathway from obesity to brain-structure abnormalities to neuropsychiatric diseases.

Mechanism of ERK/CREB pathway in pain and analgesia.

Research has long centered on the pathophysiology of pain. The Transient Receiver Potential (TRP) protein family is well known for its function in the pathophysiology of pain, and extensive study has been done in this area. One of the significant mechanisms of pain etiology and analgesia that lacks a systematic synthesis and review is the ERK/CREB (Extracellular Signal-Regulated Kinase/CAMP Response Element Binding Protein) pathway. The ERK/CREB pathway-targeting analgesics may also cause a variety of adverse effects that call for specialized medical care. In this review, we systematically compiled the mechanism of the ERK/CREB pathway in the process of pain and analgesia, as well as the potential adverse effects on the nervous system brought on by the inhibition of the ERK/CREB pathway in analgesic drugs, and we suggested the corresponding solutions.

Ultraviolet-induced fluorescence of oil spill recognition using a semi-supervised algorithm based on thickness and mixing proportion-emission matrices.

In recent years, marine oil spill accidents have been occurring frequently during extraction and transportation, and seriously damage the ecological balance. Accurate monitoring of oil spills plays a vital role in estimating oil spill volume, determination of liability, and clean-up. The oil that leaks into natural environments is not a single type of oil, but a mixture of various oil products, and the oil film thickness on the sea surface is uneven under the influence of wind and waves. Increasing the mixed oil film thickness dimension and the mix proportion dimension has been proposed to weaken the effect of the detection environment on the fluorescence measurement results. To preserve the relationships between the data of oil films with different thicknesses and the relationships between the data of oil films with different mixing proportions, the three-dimensional fluorescence spectral data of mixed oil films on a seawater surface were measured in the laboratory, producing a thickness-fluorescence matrix and a proportion-fluorescence matrix. The nonlinear variation of the fluorescence spectra was investigated according to the fluorescence lidar equation. This work pre-processes the data by sum normalization and two-dimensional principal component analysis (2DPCA) and uses the dimensionality reduction results as two feature-point views. Then, semi-supervised classification of collaborative training (co-training) with K-nearest neighbors (KNN) and a decision tree (DT) is used to identify the samples. The results show that the average overall accuracy of this coupling model can reach 100%, which is 20.49% higher than that of the thickness-only view. Using unlabeled data can reduce the cost of data acquisition, improve the classification accuracy and generalization ability, and provide theoretical significance and application prospects for discrimination of spectrally similar oil species in natural marine environments.

Eat for better cognition in older adults at risk for Alzheimer's disease.

Alzheimer's disease is a worldwide public health problem. However, the treatment method and treatment effects are limited. The stages of preclinical Alzheimer's disease are thought to be a better intervention period. Thus, in this review, food is given focus and the intervention stage put forward. We summarized the role of diet, nutrient supplementation, and microbioecologics in cognitive decline and found that interventions such as modified Mediterranean-ketogenic diet, nuts, vitamin B, and Bifidobacterium breve A1 are beneficial to cognition protection. Eating, rather than just taking medicine, is suggested to be an effective treatment method for older adults at risk for Alzheimer's disease.

Higher serum triglyceride can predict recurrent coronary revascularization events in patients undergoing percutaneous coronary intervention with baseline LDL-C <55 mg/dL.

Patients with low baseline low-density lipoprotein cholesterol (LDL-C) but experiencing recurrent coronary revascularization events have been rarely investigated. In this retrospective cohort study, we enrolled patients undergoing percutaneous coronary intervention (PCI) with baseline LDL-C <55 mg/dL at the First Affiliated Hospital of Xi'an Jiaotong University between January and December 2017. Subsequent ischemia-driven coronary revascularization events and all-cause death were documented during a 4-year follow-up. Cox analysis was used to evaluate the association between baseline clinical characteristics and long-term events. As a result, among 388 patients (mean age 63 years; 79.1% male) enrolled, 32 patients underwent recurrent revascularization events, and 38 patients occurred all-cause death. After adjustment for age, diabetes mellitus, multi-vessel disease, and lipoprotein(a), multivariate Cox analysis showed that baseline serum triglyceride (TG) (HR 1.691, 95% CI 1.178 to 2.428, p=0.004) was an independent predictor of recurrent coronary revascularization events. Kaplan-Meier analysis revealed that a higher TG level (≥1.17 mmol/L, determined by receiver operating characteristic curve) was associated with increased risk of recurrent revascularization events than lower TG level (<1.17 mmol/L) (p=0.021). Female (HR 2.647, 95% CI 1.350 to 5.190, p=0.005) and previous atrial fibrillation (HR 3.163, 95% CI 1.403 to 7.132, p=0.006) were associated with increased risk of all-cause death. In conclusion, for patients undergoing PCI with baseline LDL-C <55 mg/dL, higher baseline TG can predict recurrent coronary revascularization events.

Urine metabolomics phenotyping and urinary biomarker exploratory in mild cognitive impairment and Alzheimer's disease.

Introduction: Alzheimer's disease is a prevalent disease with a heavy global burden and is suggested to be a metabolic disease in the brain in recent years. The metabolome is considered to be the most promising phenotype which reflects changes in genetic, transcript, and protein profiles as well as environmental effects. Aiming to obtain a comprehensive understanding and convenient diagnosis of MCI and AD from another perspective, researchers are working on AD metabolomics. Urine is more convenient which could reflect the change of disease at an earlier stage. Thus, we conducted a cross-sectional study to investigate novel diagnostic panels. Methods: We first enrolled participants from China-Japan Friendship Hospital from April 2022 to November 2022, collected urine samples and conducted an LC-MS/MS analysis. In parallel, clinical data were collected and clinical examinations were performed. After statistical and bioinformatics analyzes, significant risk factors and differential urinary metabolites were determined. We attempt to investigate diagnostic panels based on machine learning including LASSO and SVM. Results: Fifty-seven AD patients, 43 MCI patients and 62 CN subjects were enrolled. A total of 2,140 metabolites were identified among which 125 significantly differed between the AD and CN groups, including 46 upregulated ones and 79 downregulated ones. In parallel, there were 93 significant differential metabolites between the MCI and CN groups, including 23 upregulated ones and 70 downregulated ones. AD diagnostic panel (30 metabolites+ age + APOE) achieved an AUC of 0.9575 in the test set while MCI diagnostic panel (45 metabolites+ age + APOE) achieved an AUC of 0.7333 in the test set. Atropine, S-Methyl-L-cysteine-S-oxide, D-Mannose 6-phosphate (M6P), Spiculisporic Acid, N-Acetyl-L-methionine, 13,14-dihydro-15-keto-tetranor Prostaglandin D2, Pyridoxal 5'-Phosphate (PLP) and 17(S)-HpDHA were considered valuable for both AD and MCI diagnosis and defined as hub metabolites. Besides, diagnostic metabolites were weakly correlated with cognitive functions. Discussion: In conclusion, the procedure is convenient, non-invasive, and useful for diagnosis, which could assist physicians in differentiating AD and MCI from CN. Atropine, M6P and PLP were evidence-based hub metabolites in AD.

Identification of hsa-miR-365b-5p's role in Alzheimer's disease: A combined analysis of miRNA and mRNA microarrays.

BACKGROUND: Alzheimer's disease is a prevalent health problem with a heavy global burden. Definitely diagnosed by autopsy, the clear mechanism of Alzheimer's disease pathogenesis process needs to be illustrated. MicroRNAs are suggested to be involved in many diseases. We aimed to investigate the role of microRNA in Alzheimer's disease. METHODS: We attempted to discover the role of microRNA in Alzheimer's disease by microarray bioinformatics analysis using autopsy sample data from the GEO database. Temporal cortex samples were included in this study. Bioinformatics analyses and visualization were processed based on R. RESULTS: After filtering out significantly differential expressed microRNAs and genes, enrichment analyses of both microRNAs and genes were conducted, respectively. Then, we constructed a transcription factor-microRNA-mRNA network and a protein-protein interaction network. In parallel, we used the receiver operating characteristic curve to evaluate the diagnostic value of microRNA. Based on the evidence, we finally identified hsa-miR-365b-5p as a key target in Alzheimer's disease. CONCLUSIONS: Hsa-miR-365b-5p act as a key target in Alzheimer's disease. It regulates Alzheimer's disease pathogenesis process via neuroinflammation, Wnt and oxidative stress pathway which provides a potential target for Alzheimer's disease treatment.

Plasma tau proteins for the diagnosis of mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis.

Objective: Detecting plasma tau biomarkers used to be impossible due to their low concentrations in blood samples. Currently, new high-sensitivity assays made it a reality. We performed a systematic review and meta-analysis in order to test the accuracy of plasma tau protein in diagnosing Alzheimer's disease (AD) or mild cognitive impairment (MCI). Methods: We searched PubMed, Cochrane, Embase and Web of Science databases, and conducted correlation subgroup analysis, sensitivity analysis and publication bias analysis using R Programming Language. Results: A total of 56 studies were included. Blood t-tau and p-tau levels increased from controls to MCI to AD patients, and showed significant changes in pairwise comparisons of AD, MCI and normal cognition. P-tau217 was more sensitive than p-tau181 and p-tau231 in different cognition periods. In addition, ultrasensitive analytical platforms, immunomagnetic reduction (IMR), increased the diagnostic value of tau proteins, especially the diagnostic value of t-tau. Conclusion: Both t-tau and p-tau are suitable AD blood biomarkers, and p-tau217 is more sensitive than other tau biomarkers to differentiate MCI and AD. Detection techniques also have an impact on biomarkers' results. New ultrasensitive analytical platforms of IMR increase the diagnostic value of both t-tau and p-tau biomarkers. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, registration number: CRD42021264701.

Identification of TLR2 as a Key Target in Neuroinflammation in Vascular Dementia.

Vascular dementia (VaD) is the second most common cause of dementia. At present, precise molecular processes of VaD are unclear. We attempted to discover the VaD relevant candidate genes, enrichment biological processes and pathways, key targets, and the underlying mechanism by microarray bioinformatic analysis. We selected GSE122063 related to the autopsy samples of VaD for analysis. We first took use of Weighted Gene Co-expression Network Analysis (WGCNA) to achieve modules related to VaD and hub genes. Second, we filtered out significant differentially expressed genes (DEGs). Third, significant DEGs then went through Geno Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Fourth, Gene Set Enrichment Analysis (GSEA) was performed. At last, we constructed the protein-protein interaction (PPI) network. The results showed that the yellow module had the strongest correlation with VaD, and we finally identified 21 hub genes. Toll-like receptor 2 (TLR2) was the top hub gene and was strongly correlated with other possible candidate genes. In total, 456 significant DEGs were filtered out and these genes were found to be enriched in the Toll receptor signaling pathway and several other immune-related pathways. In addition, Gene Set Enrichment Analysis results showed that similar pathways were significantly over-represented in TLR2-high samples. In the PPI network, TLR2 was still an important node with high weight and combined scores. We concluded that the TLR2 acts as a key target in neuroinflammation which may participate in the pathophysiological process of VaD.

Tracing the Sources and Fate of NO3- in the Vadose Zone-Groundwater System of a Thousand-Year-Cultivated Region.

Excess nitrate (NO3-) loading in terrestrial and aquatic ecosystems can result in critical environmental and health issues. NO3--rich groundwater has been recorded in the Guanzhong Plain in the Yellow River Basin of China for over 1000 years. To assess the sources and fate of NO3- in the vadose zone and groundwater, numerous samples were collected via borehole drilling and field surveys, followed by analysis and stable NO3- isotope quantification. The results demonstrated that the NO3- concentration in 38% of the groundwater samples exceeded the limit set by the World Health Organization. The total NO3- stock in the 0-10 m soil profile of the orchards was 3.7 times higher than that of the croplands, suggesting that the cropland-to-orchard transition aggravated NO3- accumulation in the deep vadose zone. Based on a Bayesian mixing model applied to stable NO3- isotopes (δ15N and δ18O), NO3- accumulation in the vadose zone was predominantly from manure and sewage N (MN, 27-54%), soil N (SN, 0-64%), and chemical N fertilizer (FN, 4-46%). MN was, by far, the greatest contributor to groundwater NO3- (58-82%). The results also indicated that groundwater NO3- was mainly associated with the soil and hydrogeochemical characteristics, whereas no relationship with modern agricultural activities was observed, likely due to the time delay in the thick vadose zone. The estimated residence time of NO3- in the vadose zone varied from decades to centuries; however, NO3- might reach the aquifer in the near future in areas with recent FN loading, especially those under cropland-to-orchard transition or where the vadose zone is relatively thin. This study suggests that future agricultural land-use transitions from croplands to orchards should be promoted with caution in areas with shallow vadose zones and coarse soil texture.

Transcranial magnetic stimulation for sleep disorders in Alzheimer's disease: A double-blind, randomized, and sham-controlled pilot study.

BACKGROUND: Sleep disorders are commonly comorbid with Alzheimer's disease (AD), And these disorders interfere with each other in many aspects. To date, pharmacological treatments for sleep disorders are still limited, and studies investigating repetitive transcranial magnetic stimulation (rTMS) for sleep disorders in AD are still lacking. METHOD: A single-center, randomized, double-blind, parallel-arm, and sham-controlled pilot study was conducted in AD patients with sleep disorders. Seventy subjects were randomly divided into the following two groups: the sham group (SG) and the intervention group (IG). We evaluated sleep changes using the Pittsburgh Sleep Quality Index (PSQI) before and after the intervention. We also assessed the patients' cognitive function by the Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog). The intervention period was four weeks, and the patients were followed up in the 8th week to test the persistence of the effect of the rTMS intervention. RESULT: Significant differences in the PSQI scores were found between the SG and IG at the end of the 4-week intervention (P = 0.001) and the 8-week follow-up (P < 0.001). There was also significant improvement in ADAS-Cog scores (4 weeks: P = 0.048, 8 weeks: P = 0.038). Activities of daily living (ADL) did not significantly differ between the SG and IG. CONCLUSION: rTMS can effectively ameliorate sleep disorders in AD patients.

[Advances in denitrification microorganisms and processes].

Denitrification is an indispensable part of most sewage treatment systems. The biological denitrification process has attracted much attention in the past decades due to the advantages such as cost-effectiveness, process simplicity, and absence of secondary pollution. This review summarized the advances on biological denitrification processes in recent years according to the different physiological characteristics and denitrification mechanisms of denitrification microorganisms. The pros and cons of different biological denitrification processes developed based on nitrifying bacteria, denitrifying bacteria, and anaerobic ammonia-oxidizing bacteria were compared with the aim to identify the best strategy for denitrification in a complex wastewater environment. The rapid development of synthetic biology provides possibilities to develop highly-efficient denitrifying strains based on mechanistic understandings. Combined with the applications of automatic simulation to obtain the optimal denitrification conditions, cost-effective and highly-efficient denitrification processed can be envisioned in the foreseeable future.

The Association Between Plasma α-Synuclein (α-syn) Protein, Urinary Alzheimer-Associated Neuronal Thread Protein (AD7c-NTP), and Apolipoprotein Epsilon 4 (ApoE ε4) Alleles and Cognitive Decline in 60 Patients with Alzheimer's Disease Compared with 28 Age-Matched Normal Individuals.

BACKGROUND Accumulating evidence has shown that alpha-synuclein (alpha-syn) pathology is involved in the pathophysiology of Alzheimer's disease (AD). This study aimed to investigate the association between the levels of plasma alpha-syn protein, urinary Alzheimer-associated neuronal thread protein (AD7c-NTP), apolipoprotein epsilon 4 (ApoE ε4) alleles and cognitive decline in 60 AD patients compared with 28 age-matched normal controls (NCs) at a single center. MATERIAL AND METHODS All participants underwent alpha-syn, apolipoprotein E (ApoE), AD7c-NTP, cholesterol (CHO), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides (TGs) analyses, neuropsychological scale assessments and neuroimaging analysis. Moreover, urine and peripheral blood samples were collected from all participants. The levels of plasma alpha-syn and AD7c-NTP were assayed using an enzyme-linked immunosorbent assay (ELISA) kit. Other test results were obtained from China-Japan Friendship Hospital. RESULTS We found that plasma alpha-syn levels were significantly different between AD patients and NCs (p=0.045). alpha-Syn levels were also associated with AD7c-NTP (r=0.231, p=0.03) but not ApoE e4 (Z=-0.147, p=0.883) levels. Neither a-syn [CHO (p=0.432), HDL (p=0.484), LDL (p=0.733) or TGs (p=0.253)] nor AD7c-NTP [CHO (p=0.867), HDL (p=0.13), LDL (p=0.57) or TGs (p=0.678)] had a relationship with lipids. CONCLUSIONS This study showed that the levels of plasma alpha-syn protein and urinary AD7c-NTP were significantly increased in AD patients compared with NCs, but not with ApoE alleles or serum lipid levels.

Distributions of arsenic and other heavy metals, and health risk assessments for groundwater in the Guanzhong Plain region of China.

The aim of this study was to evaluate the quality of shallow groundwater and deep groundwater in the Guanzhong Plain region of China, as well as the related health risk to humans. In total, 130 groundwater samples were collected comprising 116 from shallow groundwater (dug wells) and 14 from deep groundwater (drilled wells). The water samples were analyzed to determine the levels of As and 12 other heavy metals (Al, Cd, Mn, Cr, V, Fe, Ni, Cu, Zn, Co, Pb, and Mo). The results showed that the concentrations of As and other heavy metals in the deep groundwater samples were lower than the safe limits, but the Cr concentrations in some shallow groundwater samples exceeded the safe limits. The heavy metal pollution index and heavy metal evaluation index both showed that As and other heavy metals were pollutants at low levels in all of the shallow and deep groundwater sample. Health risk assessments showed that the deep groundwater samples had no associated non-carcinogenic health risks, whereas the shallow groundwater samples had non-carcinogenic health risks due to contamination with Cr and As. Some shallow groundwater samples had associated carcinogenic health risks due to contamination with Cr and As, whereas the deep groundwater samples only had carcinogenic health risks because of contamination with Cr. These results suggest that local residents and government departments should be made aware of Cr and As pollution in shallow groundwater.

Mechanism investigation of ethosomes transdermal permeation.

Ethosomes are widely used to promote transdermal permeation of both lipophilic and hydrophilic drugs, but the mechanism of interaction between the ethosomes and the skin remains unclear. In this work, it was exploded with several technologies and facilities. Firstly, physical techniques such as attenuated total reflectance fourier-transform infrared and laser confocal Raman were used and the results indicated that the phospholipids configuration of stratum corneum changes from steady state to unstable state with the treatment of ethosomes. Differential scanning calorimetry reflected the thermodynamics change in stratum corneum after treatment with ethosomes. The results revealed that the skin of Bama mini-pigs, which is similar to human skin, treated by ethosomes had a relatively low Tm and enthalpy. Scanning electron microscopy and transmission electron microscopy showed that the microstructure and ultrastructure of stratum corneum was not damaged by ethosomes treatment. Furthermore, confocal laser scanning microscopy revealed that lipid labeled ethosomes could penetrate the skin via stratum corneum mainly through intercellular route, while during the process of penetration, phospholipids were retained in the upper epidermis. Cell experiments confirmed that ethosomes were distributed mainly on the cell membrane. Further study showed that only the drug-loaded ethosomes increased the amount of permeated drug. The current study, for the first time, elucidated the mechanistic behavior of ethosomes in transdermal application from molecular configuration, thermodynamic properties, ultrastructure, fluorescent labeling and cellular study. It is anticipated that the approaches and results described in the present study will benefit for better design of drug-loaded ethosomes.

Nanocarriers as a powerful vehicle to overcome blood-brain barrier in treating neurodegenerative diseases: Focus on recent advances.

Neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington disease and amyotrophic lateral sclerosis throw a heavy burden on families and society. Related scientific researches make tardy progress. One reason is that the known pathogeny is just the tip of the iceberg. Another reason is that various physiological barriers, especially blood-brain barrier (BBB), hamper effective therapeutic substances from reaching site of action. Drugs in clinical treatment of neurodegenerative diseases are basically administered orally. And generally speaking, the brain targeting efficiency is pretty low. Nano-delivery technology brings hope for neurodegenerative diseases. The use of nanocarriers encapsulating molecules such as peptides and genomic medicine may enhance drug transport through the BBB in neurodegenerative disease and target relevant regions in the brain for regenerative processes. In this review, we discuss BBB composition and applications of nanocarriers -liposomes, nanoparticles, nanomicelles and new emerging exosomes in neurodegenerative diseases. Furthermore, the disadvantages and the potential neurotoxicity of nanocarriers according pharmacokinetics theory are also discussed.