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Suppressor of Mek1 (Smek1) is a regulatory subunit of protein phosphatase 4. Genome-wide association studies have shown the protective effect of SMEK1 in Alzheimer's disease (AD). However, the physiological and pathological roles of Smek1 in AD and other tauopathies are largely unclear. Here, the role of Smek1 in preventing neurodegeneration is investigated in tauopathy. Smek1 is downregulated in the aged human brain. Through single-cell sequencing, a novel neuronal cluster is identified that possesses neurodegenerative characteristics in Smek1 -/- mice. Smek1 deficiency caused markedly more severe motor and cognitive impairments in mice, as well as neuronal loss, gliosis, and tau hyperphosphorylation at major glycogen synthase kinase 3β (Gsk3β) sites. Protein-protein interaction analysis revealed that the Ran-binding domain (RanBD) in the N-terminus of Smek1 facilitated binding with kinesin family member 2A (Kif2a). Depletion of Smek1 resulted in cytoplasmic aggregation of Kif2a, axon outgrowth defects, and impaired mitochondrial axonal trafficking. Downregulation of Kif2a markedly attenuated tau hyperphosphorylation and axon outgrowth defects in shSmek1 cells. For the first time, this study demonstrates that Smek1 deficiency progressively induces neurodegeneration by exacerbating tau pathology and mitochondrial dysfunction in an age-dependent manner., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Blood vessels constitute a closed pipe system distributed throughout the body, transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys. Changes in blood vessels are related to many disorders like stroke, myocardial infarction, aneurysm, and diabetes, which are important causes of death worldwide. Translational research for new approaches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems. Although mice or rats have been widely used, applying data from animal studies to human-specific vascular physiology and pathology is difficult. The rise of induced pluripotent stem cells (iPSCs) provides a reliable in vitro resource for disease modeling, regenerative medicine, and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells. This review summarizes the latest progress from the establishment of iPSCs, the strategies for differentiating iPSCs into vascular cells, and the in vivo transplantation of these vascular derivatives. It also introduces the application of these technologies in disease modeling, drug screening, and regenerative medicine. Additionally, the application of high-tech tools, such as omics analysis and high-throughput sequencing, in this field is reviewed., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The clinical and molecular genetic data of 6 patients with genetically confirmed tyrosine hydroxylase deficiency(THD) diagnosed in Department of Neurology, Qilu Hospital of Shandong University from March 2017 to February 2022 were retrospectively collected and analyzed. The 6 patients were from 5 families. Among them, 5 patients had persistent or paroxysmal abnormal walking posture, 4 patients had dystonia of head and face, including spasm of perioral and oculopharyngeal muscles, hyperactivity, and binocular upvision, 4 patients showed obvious morning light and evening heavy phenomenon, 2 patients had postural tremor of limbs, 2 patients had psychomotor retardation from childhood, 1 patient only had limb and cervical muscle weakness, 1 patient had epileptic seizures. Of the 6 patients, only 1 was adult-onset, and the rest were child-onset. Four patients had good response to low-dose dopa preparation, 2 patients from the same family had poor response to dopamine treatment, requiring extremely low dose initiation and multi-frequency titration treatment. However, the long-term treatment effect was poor with obvious abnormalities. Gene testing of 5 families revealed 8 mutations in the TH gene, with c.698G>A (p.R233H) being the hot spot mutation site. The clinical manifestations of THD are complex. Besides paroxysmal or persistent dystonia, it can also be accompanied by eye movement crisis, muscle weakness, epilepsy, and delayed mental and motor development. Most patients respond well to low-dose dopamine preparations, but a small number of patients require titration treatment with extremely low-dose dopamine preparations, and the long-term effect is not satisfactory.

Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification., (© 2022. The Author(s).)

The pollution of micro/nanoplastics in the natural environment is becoming increasingly serious, but the potential effects of nanoplastics on crops remain unclear. In the present study, the effects of polystyrene nanoplastics (PS-NPs) with a particle size of 80 nm on the chlorophyll content, antioxidant enzyme activity, and nutritional quality of Allium sativum L. were explored via hydroponic culture. The results showed that the chlorophyll contents in leaves of A. sativum treated with PS-NPs were significantly lower than those in the control, indicating that the synthesis of chlorophyll was inhibited. The superoxide dismutase (SOD), ascorbate peroxidase (APX) activities, and proline contents in leaves of A. sativum initially increased but then decreased with the increase in ρ (PS-NPs). The activity of guaiacol peroxidase (POD) increased with the increase in ρ (PS-NPs) for 10 days of treatment; however, it was inhibited for 20 days of treatment. The malondialdehyde (MDA) content increased with the rise in ρ (PS-NPs). When ρ (PS-NPs) increased to 100 mg·L -1 , the MDA content in leaves of A. sativum increased by 43.24% and 89.70% for 10 and 20-day treatments, respectively, compared with those in the control. Meanwhile, the contents of soluble protein, soluble sugar, and vitamin C were higher than those in the control for 10-day treatments; however, the vitamin C content decreased by 26.53% after 20 days of treatment. These results indicated that PS-NPs had a significant oxidative stress on A. sativum , and a high concentration of PS-NPs stress would have deleterious effects on the nutritional quality of A. sativum .

Objective: This study aims to establish an optimization procedure to define the cut-offs of quantitative assays for acetylcholine receptor antibody (AChRAb), evaluate their diagnostic performance in myasthenia gravis (MG), and explore the association with clinical features., Methods: Samples from a representative cohort of 77 MG patients, 80 healthy controls (HC) and 80 other autoimmune diseases (OAD) patients were tested using competitive inhibition ELISA and RIA. Raw values (OD and cpm) and processed values (inhibition rate, binding rate and concentration) were used to define the cut-offs with statistical methods, a rough method, and receiver operating characteristic (ROC) curve. Optimal cut-offs were selected by comparing false positive rates in HC and OAD individuals. The diagnostic performance was evaluated in whole MG cohort and subgroups. Agreement between ELISA and RIA for AChRAb positivity were examined with Kappa test and McNemar test. Clinical association with AChRAb was explored by comparison among subgroups and with Spearman rank correlation., Results: The optimal cut-offs for AChRAb positivity were determined as OD ≤ 1.79 for ELISA and cpm ≥ 1234.12 for RIA, which derived from statistical method and performed better than those derived from ROC curves. The sensitivity and specificity were 74.03%, 100% for ELISA, and 74.03%, 99.37% for RIA. There was good agreement between ELISA and RIA for AChRAb positivity in whole cohort and subgroups (weighted к ≥ 0.71, p < 0.01; McNemar test, p > 0.05). Levels of AChRAb were different in MG subgroups (p < 0.01). Correlation between Quantitative Myasthenia Gravis scores and AChRAb levels was moderate for ELISA and RIA (r s  = -0.60 and 0.57, p < 0.01)., Conclusion: The raw testing values of ELISA and RIA were found as optimal quantitative measures of AChRAb levels. There are good agreements on diagnostic performance between two assays. Quantitative values are more informative than positivity in association with clinical features., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: GNE myopathy is the most common distal myopathy in China. We summarized the clinical, genetic, and pathological characteristics of 125 Chinese patients with GNE myopathy., Methods: We collected clinical data of 21 patients diagnosed at our hospital and 104 patients from previous reports. Clinical, genetic, and pathological characteristics were summarized. According to the location of mutations, patients were classified into groups to analyze genotype-phenotype correlation. We reviewed the pathological features and studied the expressions of neural cell adhesion molecule., Results: The severity of involvement of lower limb muscles was in the following order: tibialis anterior > biceps femoris > gastrocnemius > iliopsoas > quadriceps femoris. Mutation p.D207V was the most common variant in China. Patients carrying p.D207V tended to show later disease onset. In the epimerase/epimerase group, men had earlier disease onset than women (p < 0.05). In other groups, age at disease onset in females was earlier than that in males. Protein analysis showed decreased sialylation of NCAM and upregulation of LC3 in patients with different mutations., Conclusions: Mutation p.D207V is the most common GNE variant in China. Involvement of flexor muscles in lower limbs was more obvious than extensor muscles. NCAM expression in patients with various mutations may be a useful diagnostic biomarker in GNE myopathy., (© 2022. Fondazione Società Italiana di Neurologia.)

Background and Purpose: Breast cancer (BRCA) is the most frequent female malignancy and is potentially life threatening. The amino acid metabolism (AAM) has been shown to be strongly associated with the development and progression of human malignancies. In turn, long noncoding RNAs (lncRNAs) exert an important influence on the regulation of metabolism. Therefore, we attempted to build an AAM-related lncRNA prognostic model for BRCA and illustrate its immune characteristics and molecular mechanism. Experimental Design: The RNA-seq data for BRCA from the TCGA-BRCA datasets were stochastically split into training and validation cohorts at a 3:1 ratio, to construct and validate the model, respectively. The amino acid metabolism-related genes were obtained from the Molecular Signature Database. A univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression, and a multivariate Cox analysis were applied to create a predictive risk signature. Subsequently, the immune and molecular characteristics and the benefits of chemotherapeutic drugs in the high-risk and low-risk subgroups were examined. Results: The prognostic model was developed based on the lncRNA group including LIPE-AS1, AC124067.4, LINC01655, AP005131.3, AC015802.3, USP30-AS1, SNHG26, and AL589765.4. Low-risk patients had a more favorable overall survival than did high-risk patients, in accordance with the results obtained for the validation cohort and the complete TCGA cohort. The elaborate results illustrated that a low-risk index was correlated with DNA-repair-associated pathways; a low TP53 and PIK3CA mutation rate; high infiltration of CD4 + T cells, CD8 + T cells, and M1 macrophages; active immunity; and less-aggressive phenotypes. In contrast, a high-risk index was correlated with cancer and metastasis-related pathways; a high PIK3CA and TP53 mutation rate; high infiltration of M0 macrophages, fibroblasts, and M2 macrophages; inhibition of the immune response; and more invasive phenotypes. Conclusion: In conclusion, we attempted to shed light on the importance of AAM-associated lncRNAs in BRCA. The prognostic model built here might be acknowledged as an indispensable reference for predicting the outcome of patients with BRCA and help identify immune and molecular characteristics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dai, Wen, Wu, Wu, Lv, Yan, Liu, Wang and Zheng.)

Tumor microenvironment (TME) regulated the development of the Lung squamous cell carcinoma (LUSC). To know more about the LUSC, this study tried to figure the role of fscin actin-bundling protein 1 (FSCN1) in the TME. We identified the FSCN1 as the hub immune gene in LUSC, with the use of weighted gene co-expression network analysis (WGCNA) and the Human Protein Atlas. Furthermore, we verified the higher expression of FSCN1 in LUSC compared with the normal tissues by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry. We then explored the associations among FSCN1, immune infiltrations, and inflammatory factors with the use of Gene Expression Profiling Interactive Analysis (GEPIA) and Tumor IMmune Estimation Resource (TIMER). As a result, the expressions of FSCN1 was negatively related to the immune infiltrations, and positively related to the expressions of IL1A, IL1B, TGFB1 and TGFA. Moreover, we used the single-cell RNA-sequencing (scRNA-seq) data of LUSC to figure out the expressions level of FSCN1, IL1A, IL1B, TGFB1 and TGFA in the different cell type's of the TME. Finally, through the cytological experiments, we found that FSCN1 affected by TGFB1 contributes to the proliferation, anti-apoptotic effect, migration and invasion of the LUSC cells. In summary, this study Identified FSCN1 as the potential therapeutic target of LUSC, and reveals a complicated immune and inflammatory net in the TME., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

This study used vertical and horizontal subsurface constructed wetlands with continuous inflow, to compare and analyze the effects of four hydraulic residence times on the removal efficiency of conventional pollutants. Using the optimal hydraulic retention time, the two types of wetlands were examined in terms of the stromal layer nitrification, denitrification, and ammonia oxidation abundance of functional genes, as well as the intensity of nitrification and denitrification. In addition, redundancy analysis and variance decomposition analysis were used to determine the main factors affecting nitrogen removal in the two kinds of wetlands, so that targeted improvement measures can be suggested. The best removal efficiency of conventional pollutants (COD, TP, TN, and NH 4 + -N) was achieved with a hydraulic retention time of 24 h, resulting in a removal rate of more than 70%. With a 24 h retention time, the removal rate of NH 4 + -N and TN and the intensity of nitrification and denitrification exhibited a gradually decreasing trend along the flow direction. Among the three functional genes, the abundance of denitrification functional genes ( nirS ) was much higher than that of nitrification functional genes ( nxrA ) and ammonia oxidation functional genes (AOB- amoA ). In this study, the nitrogen removal ability of the two subsurface flow constructed wetlands was jointly affected by environmental factors and microbial factors, among which microbial factors contributed the most to nitrogen removal (55% and 48%). In addition, the removal rates of TN and NH 4 + -N were proportional to DO, specific surface area of substrate, COD concentration, as well as nitrification and denitrification functional genes, but inversely proportional to pH. Therefore, in order to improve the nitrogen removal efficiency of both systems, the amount of dissolved oxygen and carbon sources in the substrate layer should be increased, while the pH value should be appropriately reduced. Moreover, the horizontal subsurface constructed wetland significantly improves the nitrogen removal efficiency of the system, as the substrate layer has a larger specific surface area. This study provides a theoretical basis for the design of constructed wetlands and the selection of an optimal hydraulic residence time. Quantitative analysis of nitrogen removal pathways is of great significance for understanding the nitrogen removal mechanism and improving the nitrogen removal rate in constructed wetlands.

Background: Experimental autoimmune encephalomyelitis (EAE) is an animal disease model of multiple sclerosis (MS) that involves the immune system and central nervous system (CNS). However, it is unclear how genetic predispositions promote neuroinflammation in MS and EAE. Here, we investigated how partial loss-of-function of suppressor of MEK1 (SMEK1), a regulatory subunit of protein phosphatase 4, facilitates the onset of MS and EAE., Methods: C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55 ) to establish the EAE model. Clinical signs were recorded and pathogenesis was investigated after immunization. CNS tissues were analyzed by immunostaining, quantitative polymerase chain reaction (qPCR), western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Single-cell analysis was carried out in the cortices and hippocampus. Splenic and lymph node cells were evaluated with flow cytometry, qPCR, and western blot analysis., Results: Here, we showed that partial Smek1 deficiency caused more severe symptoms in the EAE model than in controls by activating myeloid cells and that Smek1 was required for maintaining immunosuppressive function by modulating the indoleamine 2,3-dioxygenase (IDO1)-aryl hydrocarbon receptor (AhR) pathway. Single-cell sequencing and an in vitro study showed that Smek1-deficient microglia and macrophages were preactivated at steady state. After MOG 35-55 immunization, microglia and macrophages underwent hyperactivation and produced increased IL-1β in Smek1 -/+ mice at the peak stage. Moreover, dysfunction of the IDO1-AhR pathway resulted from the reduction of interferon γ (IFN-γ), enhanced antigen presentation ability, and inhibition of anti-inflammatory processes in Smek1 -/+ EAE mice., Conclusions: The present study suggests a protective role of Smek1 in autoimmune demyelination pathogenesis via immune suppression and inflammation regulation in both the immune system and the central nervous system. Our findings provide an instructive basis for the roles of Smek1 in EAE and broaden the understanding of the genetic factors involved in the pathogenesis of autoimmune demyelination.

Objective: The striatum is unevenly impaired bilaterally in Parkinson's disease (PD). Because the striatum plays a key role in cortico-striatal circuits, we assume that lateralization affects cortico-striatal functional connectivity in PD. The present study sought to evaluate the effect of lateralization on various cortico-striatal circuits through resting-state functional magnetic resonance imaging (fMRI). Methods: Thirty left-onset Parkinson's disease (LPD) patients, 27 right-onset Parkinson's disease (RPD) patients, and 32 normal controls with satisfactory data were recruited. Their demographic, clinical, and neuropsychological information was collected. Resting-state fMRI was performed, and functional connectivity changes of seven subdivisions of the striatum were explored in the two PD groups. In addition, the associations between altered functional connectivity and various clinical and neuropsychological characteristics were analyzed by Pearson's or Spearman's correlation. Results: Directly comparing the LPD and RPD patients demonstrated that the LPD patients had lower FC between the left dorsal rostral putamen and the left orbitofrontal cortex than the RPD patients. In addition, the LPD patients showed aberrant functional connectivity involving several striatal subdivisions in the right hemisphere. The right dorsal caudate, ventral rostral putamen, and superior ventral striatum had decreased functional connectivity with the cerebellum and parietal and occipital lobes relative to the normal control group. The comparison between RPD patients and the controls did not obtain significant difference in functional connectivity. The functional connectivity between the left dorsal rostral putamen and the left orbitofrontal cortex was associated with contralateral motor symptom severity in PD patients. Conclusions: Our findings provide new insights into the distinct characteristics of cortico-striatal circuits in LPD and RPD patients. Lateralization of motor symptoms is associated with lateralized striatal functional connectivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Su, Li, Li, Ma, Zhao, Chen, Li, Wang, Lou, Chen and Yan.)

Method: Mice were randomly assigned to the sham, I/R, Oxy, and I/R with Oxy groups. Oxy was injected intraperitoneally 30 min before tourniquet placement. Morphological changes of the gastrocnemius muscle in these mice were assessed by hematoxylin-eosin (HE) staining and electron microscopy. Expression levels of TLR4, NF- κ B, SIRT1, and PGC-1 α in the skeletal muscles were detected by western blot. Blood TNF- α levels, gastrocnemius muscle contractile force, and ATP concentration were examined., Results: Compared with the I/R group, Oxy pretreatment attenuated skeletal muscle damage, decreased serum TNF- α levels, and inhibited the expression levels of TLR4/NF- κ B in the gastrocnemius muscle. Furthermore, Oxy treatment significantly increased serum ATP levels and the contractility of the skeletal muscles. SIRT1 and PGC-1 α levels were significantly reduced in gastrocnemius muscle after I/R. Oxy pretreatment recovered these protein expression levels., Conclusion: Tourniquet-induced acute limb I/R results in morphological and functional impairment in skeletal muscle. Pretreatment with Oxy attenuates skeletal muscle from acute I/R injury through inhibition of TLR4/NF- κ B-dependent inflammatory response and protects SIRT1/PGC-1 α -dependent mitochondrial function., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Yue-Xian Guo et al.)

A water-controlled experiment with four treatments (no rain, half raining, natural raining and double raining) was carried out in a Platycladus orientalis forest. The factors including soil water content (SWC), precipitation, sap flow density ( J s ), leaf area index (LAI), vapor pressure deficit (VPD) were monitored during August 2016 to August 2017. We further analyzed the response of canopy stomatal conductance ( g s ) to changes of SWC. The results showed that the SWC of plots (half, natural and double raining) showed a positive correlation with precipitation, and the range of SWC was 4.9%-16.0%, 7.2%-22.9%, 7.4%-29.6%, respectively. The SWC in the plot with no rain decreased by 50% from August to October. The daily g s reached a peak of 166.64 mmol·m -2 ·s -1 at 14:00 in July, which was significantly higher than other months. A bimodal phenomenon occurred. The daily g s reached a peak of 54.1 mmol·m -2 ·s -1 at 12:00 in January. Under the three rain plots, diurnal variation of g s and SWC showed a negative quadratic correlation. The SWC corresponding to the peak of g s was 8.5%, 12.5% and 18.5%, respectively, close to the annual average SWC. Sensitivity ( δ ) of g s to VPD /reference canopy stomatal conductance ( g sref ) was more than or equal to 0.6 in different water-controlled plots, indicating that soil water condition was more suitable for water demand of P. orientalis . When SWC was between 3.7% and 7.5%, the δ and g sref increased rapidly, indicating that stomata had better regulation ability, and that plant stomata was more sensitive to VPD. When SWC increased to 11%, SWC alteration did not affect the response sensitivity of g sref and g s to VPD. There might be a SWC threshold value for the adaptation of P. orientalis . By closing or reducing stomatal aperture, leaf water potential decreased, P. orientalis could adapt to excessive VPD and avoid excessive transpiration, which was more effective in regulating transpiration.

Objective: Motor asymmetry is characteristic in Parkinson disease (PD). This phenomenon is originated from uneven degeneration of bilateral substantia nigra. However, this asymmetry may not restrict to substantia nigra or striatum. We aimed to determine the effect of asymmetry on spontaneous brain activity across the whole brain. Methods: We consecutively recruited 71 patients with PD, as well as 35 healthy controls, and collected relevant demographic, clinical, and neuropsychological information. The PD patients were divided into two groups according to the side of motor symptom onset. All the participants underwent resting-state functional magnetic resonance imaging, and spontaneous brain activity was assessed using amplitude of low-frequency fluctuation (ALFF). The associations between areas showing significant group differences and various clinical and neuropsychological measures were analyzed. Results: Finally, the data of 30 PD patients with left-onset (LPD), 27 PD patients with right-onset (RPD), and 32 healthy controls were obtained. The three groups had similar age and gender ratios. Our results demonstrated that LPD patients had increased ALFF in the left inferior temporal gyrus and decreased ALFF in bilateral thalamus and cerebellum anterior lobes than the control group. The value of ALFF of the left inferior temporal gyrus was correlated with motor function, and ALFF value of the thalamus was associated with cognition. Comparisons between LPD and RPD patients and between RPD patients and the controls did not yield significant difference. Conclusions: The present study provides new insights into the distinct characteristics of spontaneous brain activity in LPD, which may be associated with motor and cognitive function., (Copyright © 2020 Li, Su, Chen, Li, Ma, Wang, Lou, Zhao, Chen and Yan.)

To identify the sources of nitrogen pollutants in the Muli River basin in the Guangdong-Hong Kong-Macao Greater Bay Area, ammonium salt isotope tracer technology, nitrate isotope tracer technology, and a multiple linear mixing model were applied in this study to effectively identify the changes of nitrogen sources in the basin. The results showed that nitrogen pollution in the Muli River basin was serious, and the concentrations of NH 4 + -N and NO 3 - -N in the confluence were higher than in the two tributaries. In addition, although there was no obvious population residence at the upstream or downstream of the Muli River basin, higher nitrogen pollution still occurred at some sites (Dakengshan tributary and aquiculture area). Qualitative analysis of ammonium salt and nitrate isotopes showed that nitrogen pollution in the Muli River basin mainly came from soil, fertilizer, atmospheric particles, and animal and human excreta. The results of the multiple linear mixing model showed that the main source of nitrogen in the upper reaches of the Dakengshan tributary is atmospheric subsidence, with a contribution rate of about 80%. The average contribution rate of soil organic nitrogen in the upper reaches of the Jilongkeng tributary was 33%, higher than those of the Dakengshan tributary (9%) and Muli River (24%). The contribution rate of sewage and manure to nitrogen pollution was up to 70% in the lower reaches of the Dakengshan tributary, the lower reaches of the Jilongkeng tributary, and the middle and upper reaches of the Muli River. In addition, while all forms of livestock and poultry farming and aquiculture activity were stopped, the contribution rate of sewage and manure in Yangzhiqu was found to be still as high as 56%, which is much higher than that at the Danshui River Dam section in the lower part of the Muli River (3%); this may be due to residual livestock waste in the sediment. This study qualitatively and quantitatively analyzed the nitrogen sources of the Muli River basin, which provids a theoretical basis for pollution source management in the Greater Bay Area.

Background and Purpose- Pontine autosomal dominant microangiopathy and leukoencephalopathy, a recently defined subtype of cerebral small vessel disease, is associated with mutations in COL4A1 (collagen type IV alpha 1 chain) 3' untranslated region. We here describe a pontine autosomal dominant microangiopathy and leukoencephalopathy pedigree with COL4A1 mutation presenting both pontine and cervical spinal cord involvement. Methods- For the diagnostic purpose, brain and spinal magnetic resonance imaging scanning, skin biopsy, and whole-exome sequencing were performed on the patients in the pedigree. Suspected pathogenic variants were further confirmed by cosegregation analysis using Sanger sequencing in the family members. Results- We identified a mutation located at the binding site of miR-29 (microRNA-29) in 3' untranslated region of COL4A1(c.*32G>A). The pontine autosomal dominant microangiopathy and leukoencephalopathy patients in this pedigree carried this variant, whereas other healthy family members but one did not. Magnetic resonance imaging showed lesions in the pons, white matter, and cervical spinal cord. Skin biopsy revealed thickened basal lamina in vessels. Conclusions- For the first time, we reported cervical spinal involvement in pontine autosomal dominant microangiopathy and leukoencephalopathy and expanded the clinical spectrum of this disease.

Background: Abnormally activated mechanistic target of rapamycin (mTOR) pathway has been reported in several model animals with inherited metabolic myopathies (IMMs). However, the profiles of mTOR pathway in skeletal muscles from patients are still unknown. This study aimed to analyze the activity of mTOR pathway in IMMs muscles., Methods: We collected muscle samples from 25 patients with mitochondrial myopathy (MM), lipid storage disease (LSD) or Pompe disease (PD). To evaluate the activity of mTOR pathway in muscle specimens, phosphorylation of S6 ribosomal protein (p-S6) and p70S6 kinase (p-p70S6K) were analyzed by Western blotting and immunohistochemistry., Results: Western blotting results showed that p-p70S6K/p70S6K in muscles from LSD and MM was up-regulated when compared with normal controls (NC) (NC vs. LSD, U = 2.000, P = 0.024; NC vs. MM: U = 6.000, P = 0.043). Likewise, p-S6/S6 was also up-regulated in muscles from all three subgroups of IMMs (NC vs. LSD, U = 0.000, P = 0.006; NC vs. PD, U = 0.000, P = 0.006; NC vs. MM, U = 1.000, P = 0.007). Immunohistochemical study revealed that p-S6 was mainly expressed in fibers with metabolic defect. In MM muscles, most p-S6 positive fibers showed cytochrome C oxidase (COX) deficiency (U = 5.000, P = 0.001). In LSD and PD muscles, p-S6 was mainly overexpressed in fibers with intramuscular vacuoles containing lipid droplets (U = 0.000, P = 0.002) or basophilic materials (U = 0.000, P = 0.002)., Conclusion: The mTOR pathway might be activated in myofibers with various metabolic defects, which might provide evidence for mTOR inhibition therapy in human IMMs.

Acetyl metabolites are the major metabolites of sulfonamides. In order to investigate the removal mechanism of four commonly used sulfonamides and their metabolites in wastewater treatment plants, sulfonamides and their corresponding acetyl metabolites in wastewater and sludge in a wastewater treatment plant equipped with A 2 /O in Xiamen City were sampled. Sample selection was based on the hydraulic retention time. Solid phase extraction followed by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was applied to analyze the target compounds. Results showed that six out of eight of the target compounds were detected in the wastewater, while five were detected in the sludge. Based on the removal efficiencies overall and of the different compartments, the concentration of sulfamethazine was almost unchanged during wastewater treatment plant (WWTP) processes, the other sulfonamides were removed with different removal efficiencies. Removal efficiencies varied for every compartment. The potential removal pathways were analyzed based on the mass balance of the target compounds. The removal pathway of sulfamethazine was sludge adsorption, while the potential removal mechanism of sulfamerazine, sulfadiazine, and sulfamethoxazole was biodegradation.

Objective: The Cobalamin C (cblC) disease is an inborn error of cobalamin metabolism. Late-onset cblC disease was diagnosed in patients having overt symptoms after 4 years of age. The late-onset cblC disease patients were rare and easily misdiagnosed. This study analyzed the clinical presentations, gene mutations, and treatments of Chinese patients with late-onset cblC disease., Methods: The clinical data of 26 Han Chinese patients diagnosed with late-onset cblC disease were retrospectively analyzed. All patients underwent serum homocysteine level exam, urine concentrations of organic acids measurement, neuroimaging scans, gene analysis, and treatments evaluations., Results: The mean age at disease onset and diagnosis was 17.8±7.0 years. The most frequent neuropsychiatric disturbances were lower limb weakness (50%), psychiatric disturbances (46.2%), and gait instability (42.3%). The mean methylmalonic acid level in urine was 107.4±56.6 μmol/L, and mean serum total homocysteine was 105.4±41.0 μmol/L. The most common abnormal radioimaging changes were observed in the spinal cord (88%) and brain (32%). Scoliosis was detected in 85.7% of patients. The methylmalonic aciduria and homocystinuria type C protein gene analysis showed that c.482G>A (57.7%) and c.609G>A (34.6%) mutations were the most frequent genotypes. After treatments with hydroxycobalamin, betaine, folic acid, L-carnitine, and compound vitamin B, the clinical features and biochemical parameters of patients with late-onset cblC disease were found to be alleviated., Conclusion: In our late-onset cblC disease cases, lower limb weakness, psychiatric disturbances, and gait instability were the most frequent manifestations. Patients responded well to the drug treatments with hydrocobalamin and betaine. When juvenile or adult patients with hyperhomocysteinemia present with neurological symptoms, cblC disease needs to be considered., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Leigh syndrome (LS) is a rare disease caused by mitochondrial defects and has high phenotypic and genotypic heterogeneity. We analyzed the clinical symptoms, neuroimaging, muscular histopathology, and genotypes of 13 Chinese LS patients with mitochondrial DNA (mtDNA) mutations., Methods: Mutations in mtDNA were identified by targeted sequencing. The brain imaging features on magnetic resonance imaging (MRI) were analyzed. The levels of lactate in fasting blood and cerebrospinal fluid (CSF) were routinely tested. The levels of urinary organic acids, plasma amino acids, and acylcarnitines were examined with gas chromatography-mass spectrometry and tandem mass spectrometry. The histopathological traits of skeletal muscles were analyzed under microscope., Results: Among 13 patients, mutations of MT-NDs (n = 8) and MT-ATP6 (n = 4) genes were most common. Strabismus (8/13), muscle weakness (8/13), and ataxia (5/13) were also common, especially for the patients with late-onset age after 2 years old. However, respiratory distress was common in patients with early-onset age before 2 years old. The most frequently affected brain area in these patients was the brain stem (12/13), particularly the dorsal part of midbrain, followed by basal ganglia (6/13), thalamus (6/13), cerebellum (5/13), and supratentorial white matter (2/13). Besides, the elevated lactate levels in CSF (6/6) were more common than those in serum (7/13). However, the analysis of abnormal plasma amino acid and urinary organic acid showed limited results (0/3 and 1/4, respectively). Muscular histopathology showed mitochondrial myopathy in the three late-onset patients but not in the early-onset ones., Conclusions: Noninvasive genetic screening is recommended for mtDNA mutations in MT-NDs and MT-ATP6 genes in patients with ophthalmoplegia, muscle weakness, ataxia, and respiratory disorder. Furthermore, the lactate detection in CSF and the brain MRI scanning are suggested as the diagnosis methods for LS patients with mtDNA mutations., Competing Interests: There are no conflicts of interest

We present the experimental results of an optimal recycling method for waste carbon fibre reinforced plastics (CFRPs) that is based on the application of a set of unit mechanochemical processes. The objectives of this study were to highlight the influence of process factors that are inherent in the chemical recycling process of waste CFRP. We investigated the influence of the soaking period, the application of a catalyst and impurities on the recycling process and recovery efficiency of the waste CFRP. Different combinations of the unit mechanochemical processes were investigated, and the effectiveness of the combination was analysed. The chemical recycling process was conducted using benzyl alcohol under ordinary pressure at initial solvent temperatures lower/equivalent to its flash point temperature. Experimental results showed that the solvent temperature increased up to boiling temperature levels when the mechanochemical process was initiated, thereby enhancing the mechanochemical process. The presence of impurities did not influence the recovery rate. Likewise, this experimental study highlighted the importance of accounting for the soaking period during the chemical recycling process: an extended soaking period resulted in a higher recovery rate, a lower portion of undissolved solids and recovered fibres of better quality. This research highlighted the significance of choosing the proper combination for the chemical recycling process as well as the benefits of recycling the waste CFRP with negligible application of the catalyst.

The Cobalamin C deficiency (cblC), characterized with elevated methylmalonic acidemia and homocystinuria in plasma, is an inborn error of cobalamin metabolism. The late-onset cblC siblings patients were rarely reported. In this study, we analyzed the clinical presentations and treatment outcomes of late-onset cblC in Chinese sibling patients with neuropsychiatric presentations. The clinical data of four pairs of Chinese patients were retrospectively analyzed. Serum homocysteine, urine organic acids measurements, neuroimaging exams and gene analysis were carried out in all patents. Patients were reevaluated after treatments with cobalamin, folate, betaine, L-carnitine and compound vitamin B. The mean age at disease onset was 13.7 (range 2-19) years. The neuropsychiatric disturbances including cognitive decline (3/8), psychiatric disturbances (4/8), gait instability (2/8), lower extremity weakness and numbness (3/8) and thromboembolic events (1/8). Two patients suffered nephropathy. The mean serum homocysteine when patients were diagnosed was 109.4 (range 69.5-138) μM/L. The abnormal radioimaging included scoliosis by X-ray (5/6), cerebral atrophy (4/6) and spinal cord atrophy (3/6) by MRI scan. Three pairs of siblings showed heterozygous mutations of MMACHC gene including c.482G > A (4/6), c.354G > C (2/6), c.570insT (2/6), c.445&#95;446del (2/6) and c.656&#95;4658del (2/6). The other two siblings showed homozygous mutation with c.452A > G in MMACHC gene. After treatments, the psychiatric symptoms were obviously relieved in all the patients. In Chinese siblings with late-onset cblC, the main clinic manifestation and abnormal radioimaging were cognitive decline and cerebral atrophy respectively. The most common gene mutation was c.482G > A of MMACHC gene. The patients responded well to the treatments.

Background: The immunopathologic mechanism underlying dermatomyositis (DM) and polymyositis (PM) remains poorly understood. Many cytokines play a pathogenic role in DM and PM. Interleukin 21 (IL-21) has a pleiotropic effect on inflammation regulation. This study aimed to detect the serum IL-21 level and investigate the expression of IL-21 and IL-21 receptor (IL-21R) in muscle tissues of patients with DM and PM., Methods: Biopsied muscle samples were obtained from 11 patients with DM, 12 with PM, and six controls; mRNA levels of IL-21 and IL-21R were analyzed by real-time quantitative reverse transcription-polymerase chain reaction; and immunohistochemical staining was used to evaluate the protein expression of IL-21 and IL-21R. Serum samples were obtained from 36 patients with DM, 19 with PM, and 20 healthy controls. The serum IL-21 level was detected by enzyme-linked immunosorbent assay., Results: The expression of IL-21 was upregulated in patients with DM and PM. The IL-21 mRNA level was significantly increased in muscle tissues of patients with DM and PM (DM vs. control, P= 0.001; PM vs. control, P= 0.001), whereas IL-21R mRNA level in patients with DM/PM was not statistically different from that of healthy controls. Immunohistochemical staining showed both IL-21 and IL-21R were significantly expressed in the inflammatory cells in muscle tissues of patients with DM and PM. The serum IL-21 level was also significantly higher in patients with DM/PM than in controls (DM vs. control, 49.12 [45.28, 60.07] pg/ml vs. 42.54 [38.69, 48.85] pg/ml, P= 0.001; PM vs. control, 50.77 [44.19, 60.62] pg/ml vs. 42.54 [38.69, 48.85] pg/ml, P= 0.005)., Conclusions: IL-21 expression is upregulated in patients with DM and PM in both muscle tissue and serum. In addition, IL-21R protein is highly expressed in affected muscle tissues of patients with DM and PM. IL-21 may play a pathogenic role through IL-21R in patients with DM and PM.

Storage conditions are considered to be an important factor as far as waste material characteristics are concerned. This experimental investigation was conducted using municipal solid waste (MSW) with a high moisture content and varying composition of organic waste. The objective of this study was to understand the effect of storage conditions and temperature on the moisture content and calorific value of the waste. Samples were subjected to two different storage conditions and investigated at specified temperatures. The composition of sample materials investigated was varied for each storage condition and temperature respectively. Gross calorific value was determined experimentally while net calorific value was calculated using empirical formulas proposed by other researchers. Results showed minimal changes in moisture content as well as in gross and net calorific values when the samples were subjected to sealed storage conditions. Moisture content reduced due to the ventilation process and the rate of moisture removal increased with a rise in storage temperature. As expected, rate of moisture removal had a positive effect on gross and net calorific values. Net calorific values also increased at varying rates with a simultaneous decrease in moisture content. Experimental investigation showed the effectiveness of ventilation in improving the combustion characteristics of the waste.

Inflammatory responses involving microglia and astrocytes contribute to the pathogenesis of neurodegenerative diseases (NDs). In addition, inflammation is tightly linked to iron metabolism dysregulation. However, it is not clear whether the brain inflammation-induced iron metabolism dysregulation contributes to the NDs pathogenesis. Herein, we demonstrate that the expression of the systemic iron regulatory hormone, hepcidin, is induced by lipopolysaccharide (LPS) through the IL-6/STAT3 pathway in the cortex and hippocampus. In this paradigm, activated glial cells are the source of IL-6, which was essential in the iron overload-activated apoptosis of neurons. Disrupting astrocyte hepcidin expression prevented the apoptosis of neurons, which were able to maintain levels of FPN1 adequate to avoid iron accumulation. Together, our data are consistent with a model whereby inflammation initiates an intercellular signaling cascade in which activated microglia, through IL-6 signaling, stimulate astrocytes to release hepcidin which, in turn, signals to neurons, via hepcidin, to prevent their iron release. Such a pathway is relevant to NDs in that it links inflammation, microglia and astrocytes to neuronal damage.

A detailed field survey of arsenic species and water quality parameters was conducted in different eutrophicated regions of Lake Taihu (Zhushan Bay, Meiliang Bay, Gonghu Bay and Southern Taihu) in summer and winter. Furthermore, spatial and seasonal distributions of arsenic species and their relations to water quality parameters were investigated with multivariate analysis techniques. Higher average contents of total arsenic (TAs), arsenate[As(Ⅴ)], arsenite[ As(Ⅲ)] and methylarsenicals [sum of monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA)] were observed in northern regions (including Zhushan Bay, Meiliang Bay, and Gonghu Bay) (TAs:2.58-3.34 μg·L -1 , As(Ⅴ):1.37-2.34 μg·L -1 , As(Ⅲ):0.53-0.64 μg·L -1 , methylarsenicals:0.16-0.36 μg·L -1 ), compared to those in Southern Taihu (1.73, 1.10, 0.31, 0.10 μg·L -1 ). The results exhibited obvious spatial characteristics of arsenic species in the surface water of Lake Taihu. Besides, average values of TAs, As(Ⅴ), As(Ⅲ) and methylarsenicals in summer were 3.40, 2.06, 0.73 and 0.25 μg·L -1 , respectively, higher than those in winter (1.78, 1.10, 0.30, 0.17 μg·L -1 ), reflecting significant seasonal characteristics of arsenic distribution. Factor analysis revealed the significant relationships of TAs and As(Ⅴ) with several water quality parameters, which suggested that spatial and seasonal distributions of TAs and As(Ⅴ) in Lake Taihu were affected by external pollution and internal arsenic release from sediments. Redundancy analysis further indicated significant effects of total phosphorus (TP) and total iron (TFe) on the distributions of TAs and As(Ⅴ). At the mean time, the above statistical analyses exhibited that As(Ⅲ) and methylarsenicals were positively correlated with chlorophyll-a (Chl-a). A large amount of microalgae could accumulate As(Ⅴ) and transform it more strongly to As(Ⅲ) and methylarsenicals in eutrophic regions when compared to mesotrophic region,especially in summer, reflecting the regulation of microalgae on arsenic biotransformation.

Anti-inflammatory cytokine and its serological detection may have an important role in the process of cardiovascular and cerebrovascular diseases. We investigated whether serum interleukin-10 (IL-10) is associated with cerebral infarction or not in the general population. Identified comprehensive searching was performed covering PubMed, EMBASE, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine, and China National Knowledge Infrastructure databases. Two reviewers extracted data and assessed studies independently. Information was extracted separately and classed into Asians and Caucasians. Summary standardized mean differences (SMDs) with 95 % confidence intervals (CI) were used with the utilization of Z test. Nine studies ranged from 2003 to 2014 were collected for meta-analysis. Results identified a negative association between serum IL-10 levels and cerebral infarction (SMD = 1.80, 95 % CI 0.79-2.81, P < 0.001). Country-subgroup analysis showed that low IL-10 level may be the main risk factor for cerebral infarction in India (SMD = 1.44, 95 % CI 1.13-1.75, P < 0.001) and Croatia (SMD = 2.96, 95 % CI 2.48-3.44, P < 0.001). In the ethnicity-stratified subgroup analysis, serum IL-10 levels were negatively correlated with cerebral infarction in Asians (SMD = 2.52, 95 % CI 0.47-4.57, P = 0.016), while not in Caucasians (P > 0.05). The lower serum IL-10 concentration was significantly associated with an increased likelihood of cerebral infarction in this meta-analysis. More prospective studies should be conducted to provide stronger evidence justifying the use of IL-10 as new biomarker to identify a predisposition toward cerebral infarction.

Cylindrical spirals (CSs) are rare but distinct subsarcolemmal accumulations in skeletal muscle fibers. To date, CSs have been reported in only 16 patients with a variety of neuromuscular conditions. The origin and composition of CSs are unknown, although there are some morphologic similarities between CSs and tubular aggregates (TAs). To clarify the nature of CSs, we characterized the sarcoplasmic reticulum (SR) and other intracellular membrane system proteins in CSs of muscle biopsies from 2 adult Chinese siblings. Immunohistochemical studies revealed subsarcolemmal immunoreactivity for sarco/endoplasmic reticulum Ca2þ-ATPase 1 (SERCA 1) in the longitudinal SR, but no immunoreactivity for calsequestrin in the terminal cisternae or type 1 ryanodine receptor (RYR1) in the junctional SR. Muscles biopsied from 2 patients with TAs showed immunoreactivity not only for SERCA1 but also for other SR proteins, including calsequestrin and RYR1. CSs exhibited no immunoreactivity for the Golgi apparatus marker GM130, the nuclear membrane emerin, desmin, the autophagosome marker LC3, the lysosomal membrane marker LAMP2, dystrophin, or myosin. Our results suggest CSs may originate only from the longitudinal SR, whereas TAs are composed of both the junctional and longitudinal SR. Immunochemical staining with antibodies against calsequestrin and RYR1 help to distinguish these 2 pathological alterations.

Objective: To establish the rat model of acute pulmonary embolism, and study the changes of vascular active substances in pulmonary embolism rats, and investigate the interventive effect of anticoagulant drugs on vascular active substances., Methods: One hundred and twenty-eight rats were randomly divided into four groups: control group, model group, low-molecular-weight heparin and warfarin treated group and rivaroxaban-treated group (n = 32 in each group). The method of autologous thrombosis was used to establish the animal model of acute pulmonary embolism. The animals were treated with saline or different anticoagulant drugs. The physiological and biochemical parameters were detected at different time points after embolization. The rats were killed after embolism of 24 h, 3 d, 5 d or 1 week respectively and the pathologic samples of lung tissues were collected to analyze the pulmonary pathological changes in different groups., Results: Rats in embolization group after blood clots injection showed shortness of breath, oral cyanosis; quicken heart rates and other symptoms. All embolization groups had pulmonary hypertension, the levels of type B natriuretic peptide (BNP) were increased significantly. The ratio of endothelin-1 (ET-1)/NO and thromboxane (TXB2) and prostacyclin (6-k-PGFla) were abnormal. After treated with effective anticoagulant drugs, the levels of BNP, ET-1, NO, TXB2 and 6-k-PGF1a were tended to the normal levels in the control group. The pulmonary hypertensions were gradually decreased. The efficacy of rivaroxaban on pulmonary embolism was the same as that of the low molecular weight heparin or warfarin., Conclusion: Anticoagulation therapy can effectively improve endothelial function after pulmonary embolism, reduce pulmonary hypertension, and revise the increased BNP levels to normal levels. The efficacy of rivaroxaban is not inferior to that of low molecular weight heparin and warfarin.

Objective: We performed this study to investigate the effect of blood pressure control in ultra-early basal ganglia intracerebral hemorrhage., Patients and Methods: 120 patients with ultra-early basal ganglia intracerebral hemorrhage were randomly divided into experimental group (strengthened antihypertensive) and control (normal antihypertensive). Each group consists of 60 patients, whose contractive pressure were controlled by intravenous antihypertensive drugs among 130-140 mmHg and 160-180 mmHg respectively for 24 h, after 1 h of beginning treatment. They were all evaluated by NIH Stroke Scale (NIHSS) before and after the treatment. Cranial CT, hematoma volume, hematoma enlargement, edema volume, serum matrix metalloproteinase-9 level were performed and compared between groups., Results: After 24 h, hematoma volume and hematoma enlargement in the experimental group was significantly lower than control (p < 0.05). After 14 days, NIHSS score in the experimental group was significantly lower than control (p < 0.05). Cerebral edema amount and serum MMP-9 level in the experimental group were significantly lower than control after 5 days and 14 days., Conclusions: Ultra-early basal ganglia intracerebral hemorrhage can remarkably reduce hematoma enlargement, cerebral edema, serum MMP-9 level, and improve the neurological function.

Increasing evidence has revealed that glibenclamide has a wide range of anti-inflammatory effects. However, it is unclear whether glibenclamide can affect the resting and adenosine triphosphate (ATP)-induced intracellular calcium ([Ca(2+)]i) handling in Raw 264.7 macrophages. In the present study, [Ca(2+)]i transient, reactive oxygen species (ROS) and mitochondrial activity were measured by the high-speed TILLvisION digital imaging system using the indicators of Fura 2-am, DCFDA and rhodamine-123, respectively. We found that glibenclamide, pinacidil and other unselective K(+) channel blockers had no effect on the resting [Ca(2+)]i of Raw 264.7 cells. Extracellular ATP (100 µM) induced [Ca(2+)]i transient elevation independent of extracellular Ca(2+). The transient elevation was inhibited by an ROS scavenger (tiron) and mitochondria inhibitor (rotenone). Glibenclamide and 5-hydroxydecanoate (5-HD) also decreased ATP-induced [Ca(2+)]i transient elevation, but pinacidil and other unselective K(+) channel blockers had no effect. Glibenclamide also decreased the peak of [Ca(2+)]i transient induced by extracellular thapsigargin (Tg, 1 µM). Furthermore, glibenclamide decreased intracellular ROS and mitochondrial activity. When pretreated with tiron and rotenone, glibenclamide could not decrease ATP, and Tg induced maximal [Ca(2+)]i transient further. We conclude that glibenclamide may inhibit ATP-induced [Ca(2+)]i transient elevation by blocking mitochondria KATP channels, resulting in decreased ROS generation and mitochondrial activity in Raw 264.7 macrophages.

Bio-electrochemical reactor provides a promising technology to remove nitrogen contaminants in water. In this study, a heterotrophic biofilm for denitrification process was developed, and stable total nitrogen removal efficiencies (>80%) were achieved. Fluorescence in situ hybridization showed that genes norB mainly transcribed in inner biofilm while genes nosZ showed similar transcription activities in the entire biofilm. The microelectrodes of pH and nitrous oxide (N₂O) were applied to profile the microenvironment of denitrification biofilm. In all measurements, the microenvironment pH decreased as a function of biofilm depth. The highest N₂O concentration of 90 μM in biofilm was detected when the bulk solution pH was 7.3, and an applied potential of -0.2V did not decrease the yield of N₂O in biofilm at pH 7.3. Nevertheless, pH 9.5 or an applied potential of -0.4V seemed not to suppress the yield of N₂O in biofilm., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The purpose of this study was to characterize the decomposition process of different plant litters and its controlling factors, and to quantify the different contribution rates to sediments organic matter throughout the decomposition of different plant litters. Results showed that the decomposition rates of plant litters buried at medium tidal level were 0.655 a(-1) for mangrove and 1.723 a(-1) for Spartina, which were greater than those with 0.651 a(-1) for mangrove and 1.586 a(-1) for Spartina at high tidal level. The reduction of carbon concentration in plant litters at high tidal level was lower than that at medium tidal level, while the increment of nitrogen and sulfur concentrations in plant litters at high tidal level was greater than those at medium tidal. And the isotope abundance of carbon (delta13C) in plant litters at medium tidal level reduced much more significantly than that at high tidal level. The contribution rates of plant litters carbon to sediments organic matter differed among tidal levels, plant species and decomposition duration. Specifically, the decomposition of mangrove litters contributed 5.96% to the sediment organic matter at medium tidal level, which was greater than that (3.03%) at high tidal level. Similarly, the decomposition of Spartina litters contributed 14.81% to the sediment organic matter at medium tidal level, which was also greater than that (13.97%) at high tidal level. The contribution of the decomposition of Spartina litters organic matter (average with 14.39%) was greater than that of mangrove litters (4.50%). The decomposition of plant litters requires a long process. The contribution of plant litters to sediments organic matter throughout one year decomposition was lower than that in complete decomposition, in particular, mangrove litters. Our study showed that the quantitative differences in plant litters-derived sediment organic matter would improve the proper estimation of the contribution of litters to wetland organic matter.

Dissolved oxygen (DO) is one of the important environmental factors influencing the ammonia oxidation process. In order to examine the effects of DO on ammonia oxidation process and its potential mechanisms, surface sediments from Jiulong River Estuarine Wetland were collected and cultured to obtain enrichment cultures. Then the enrichment cultures were inoculated under different levels of DO, and the diversity of ammonia-oxidizing microorganisms was analyzed using PCR-DGGE technique to determine the effect of DO on the ammonia oxidation rate and the ammonia-oxidizing microorganism diversity. Results showed that the Shannon index was 2. 00 and 2.05 for ammonia-oxidizing bacteria (AOB) under saturated and aerobic conditions, respectively, and the values were 2.49 (saturated) and 2.03 (aerobic) for ammonia-oxidizing archaea (AOA). However, this index was 1.76 and 1.80 for AOB under hypoxia and anaerobic condition, and 1.27 and 2. 21 for AOA. Under saturated and aerobic conditions ( higher DO level), the ammonia-oxidizing rates were 14.20 mg.(L.d)-1 and 13.36 mg.(L.d)-1 and the related conversation rates of NH+4 -N were 93.8% and 88. 2% , respectively. In comparison, under hypoxia and anaerobic conditions (lower DO level), the ammonia-oxidizing rates were 7.82 mg.(L.d) -1 and 5.66 mg.(L.d)-1 and the related conversation rates of NH+4 -N were 51.7% and 37.4% , respectively. The correlation analysis showed that DO concentration was highly significantly positively correlated with the ammonia oxidation rate, and was significantly positively correlated with the AOB diversity index; DO and ammonia oxidation rate had no correlation with indices of AOA community.

To overcome the shortcoming of existing studies, this paper put forward a statistical vegetation-climate relationship model with integrated temporal and spatial characteristics. Based on this model, we quantitatively discriminated on the grid scale the relative role of climate change and human activities in the desertification dynamics from 1986 to 2000 in Yulin region. Yulin region's desertification development occurred mainly in the southern hilly and gully area and its reverse in the northwest sand and marsh area. This spatial pattern was especially evident and has never changed thoroughly. From the first time section (1986-1990) to the second (1991-1995), the desertification was developing as a whole, and either in the desertification development district or in the reverse district human activities' role was always occupying an overwhelmingly dominant position (they were 98.7% and 101.4%, respectively), the role of climate change was extremely slight. From the second time section (1991-1995) to the third (1996-2000), the desertification process was reaching a state of stability, in the desertification development district the role of climate change was nearly equivalent to that of human activities (they were 46.2% and 53.8% separately), and yet in the desertification reverse district, the role of human activities came up to 119.0%, the role of climate change amounted to -19.0%. In addition, the relative role of climate change and human activities possessed great spatial heterogeneity. The above conclusion rather coincides with the qualitative analysis in many literatures, which indicates that this method has certain rationality and can be utilized as a reference for the monitoring and studying of desertification in other areas.

In order to clarify the distribution characteristics and risk levels of heavy metals in typical drinking water sources of towns in Dongjiang River Basin, several regular water quality indexes as well as concentrations of Fe, Cu, Mn, Zn, As, Cr, Hg, Pb and Cd were analyzed in the 45 random water samples of 9 towns in the study area. The risk assessment was conducted according to different drinking water types using the environmental health risk assessment model recommended by U. S. EPA. The results indicated that the metal carcinogenic risk is relatively high in this area. The highest carcinogenic risk was from Cr in reservoir water, with the risk for adult people reaching 1.14 x 10(-4) x(-1) and the risk of children reaching 2.14 x 10(-4) x a(-1). Total carcinogenic risk of reservoir, river and underground water exceeded the accepted level of 5.0 x 10(5) x a(-1) as suggested by ICRP while all the non-carcinogenic risk levels were within the acceptable range. The primary control sequence of metal pollution in this area was Cr > As > Pb > Fe > Zn; the risk value of different drinking water sources descended in this order: reservoir > river > underground water > mountain spring.

The ADAM10 gene encodes a member of a disintegrin and metalloprotease family, which, after overexpression in Alzheimer's disease (AD), prevents amyloid pathology and improves long-term potentiation and memory. A common polymorphism (rs2305421) within ADAM10 has been recently associated with the risk of developing AD in Europeans. In order to assess the involvement of the ADAM10 polymorphism in the risk of developing late-onset AD (LOAD), we analyzed the genotype and allele distributions of the ADAM10 (rs2305421) polymorphism in 788 Northern Han Chinese subjects. The results revealed no significant differences in the distributions of allele or genotype between LOAD and control groups. However, when these data were stratified by the Apolipoprotein E (ApoE) ε4 status, in the subjects with ApoE ε4, there were significant differences in the allele (P=0.037) and genotype (P=0.035). Moreover, logistic regression analysis revealed that the rs2305421 polymorphism presented strong associations with LOAD in the recessive model (OR=0.611, 95% CI=0.408-0.931, P=0.023). This study suggests that the rs2305421 polymorphism in ADAM10 gene could modify the risk for LOAD in a Northern Han Chinese population., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Worldwide contamination of arsenic in aquatic systems requires the development of a cost-effective, in situ phytoremediation technology. Hydrilla verticillata (L.f.) Royle, a submerged macrophyte widely distributed throughout the world, has the potential to effectively remove heavy metals from water. In order to understand the potential of H. verticillata for As phytofiltration and its impacts on As cycling in the water system, we investigated As accumulation, speciation and translocation in H. verticillata plants. Plant shoots showed a significant accumulation of As, with a maximum of >700 μg g(-1) dry weight (DW) after exposure to 20 μM arsenate [As(V)] or arsenite [As(III)] for 4d, with no significant differences between the As(V) and As(III) treatments (P>0.05). In addition, results of an in planta transport experiment showed that, after exposure of root and shoot to 2μM As(V) and As(III) for 4d, the bioconcentration factor (BCF) in roots for As(V) was almost twofold than that of As(III). Higher As BCFs in roots compared to shoots was also observed. Arsenic accumulated primarily in the cell walls of root cells (>73% of the total As in roots) and in the soluble parts of leaves (>60% of the total As in leaves). Regardless of the form of As supplied [As(III) or As(V)], As(V) was the dominant form in roots and As(III) was the dominant form in leaves. Further, basipetal translocation of As in this plant (≥17%) was markedly higher than acropetal translocation (≤3%). Because of accumulation of As in the shoot and immobilization of As below ground in roots, H. verticillata is a potential As phytofiltrator for bioremediation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Primary angiitis of the central nervous system is a rare and difficult entity. Here we represented the clinical and pathological features of a patient with little response to steroid before definite diagnosis. The 50-year-old male had a fluctuating disease course for more than 3 years. He presented visual disorders, seizure, cognitive impairment, hypersomnia, unsteady gait, dysphasia, dysphagia, and incontinence. Magnetic resonance imaging showed multiple, supratentorial and infratentorial abnormal signals, while cerebrospinal fluid and cerebral angiography were normal. Magnetic resonance spectrum showed a decrease of N-acetyl-aspartate. Brain biopsy revealed nongranulomatous lymphatic vasculitis with reactive gliosis, cicatrization, demyelination and focal hemorrhages.

Using submerged aquatic plant is a cheap and clean technique to remediate heavy metals in wastewaters. Batch experiments were conducted to assess the biosorption characteristics of Pb (II) ions by fresh tissues of Hydrilla verticallata. The biosorption of Pb(II) was examined for single, binary and ternary solutions at different initial concentrations and different pH values. The experimental results showed that the biosorption capacity increased with increasing pH from 2.0 to 6.0. The biosorption value reached 44.65 mg/g when initial lead concentration was 250 mg/L and pH = 5. Both Cu (II) and Zn(II) ions were found to have an adverse effect on the biosorption of Pb(II) for binary and ternary solutions. In Pb-Cu binary metal solution, when both initial concentrations of lead and copper ions were 250 mg/L, the biosorption capacity for lead ions was decreased to 49.29% of that in single lead ion solution. The biosorption equilibrium data for the Pb-Cu binary metal solution fitted the Langmuir competitive model well (R2 = 0.966). The theoretical q(max) value (58.02 mg/g) was in excellent consistent with that obtained experimentally, and the average relative error between calculated q(e) and experimental q(e) values was only 15.6%. Comparison between biosorption of Pb (II) and Cu (II) by H. verticallata in the binary solution could lead to the conclusion that H. verticallata has no preference of Pb(II) over Cu(II).

Oxidative stress plays an important role in neuronal injuries caused by cerebral ischemia. It is well established that free iron increases significantly during ischemia and is responsible for oxidative damage in the brain. However, the mechanism of this ischemia-induced increase in iron is not completely understood. In this report, the middle cerebral artery occlusion (MCAO) rat model was performed and the mechanism of iron accumulation in cerebral ischemia-reperfusion was studied. The expression of L-ferritin was significantly increased in the cerebral cortex, hippocampus, and striatum on the ischemic side, whereas H-ferritin was reduced in the striatum and increased in the cerebral cortex and hippocampus. The expression level of the iron-export protein ferroportin1 (FPN1) significantly decreased, while the expression of transferrin receptor 1 (TfR1) was increased. In order to elucidate the mechanisms of FPN1 regulation, we studied the expression of the key regulator of FPN1, hepcidin. We observed that the hepcidin level was significantly elevated in the ischemic side of the brain. Knockdown hepcidin repressed the increasing of L-ferritin and decreasing of FPN1 invoked by ischemia-reperfusion. The results indicate that hepcidin is an important contributor to iron overload in cerebral ischemia. Furthermore, our results demonstrated that the levels of hypoxia-inducible factor-1α (HIF-1α) were significantly higher in the cerebral cortex, hippocampus and striatum on the ischemic side; therefore, the HIF-1α-mediated TfR1 expression may be another contributor to the iron overload in the ischemia-reperfusion brain.