Enhanced removal performance of magnesium-modified biochar for cadmium in wastewaters: Role of active functional groups, processes, and mechanisms.

In this study, a series of biochar products with different active functional groups were developed by one-pot coprecipitation method, including magnesium-modified biochar (MgBC) and functional group-grafted MgBC (Cys@MgBC, Try@MgBC, and Glu@MgBC), for effective adsorption of cadmium (Cd(II)) from wastewaters. These biochars exhibited excellent removal performance for Cd(II), particularly Cys@MgBC, whose maximum Cd(II) adsorption capacity reached 223.7 mg g-1. The highly active and weakly crystalline Mg could adsorb Cd(II) through precipitation and ion exchange, which was further promoted by the introduced functional groups through complexation and precipitation. After 120 d of natural process, the immobilization efficiency of Cd(II) by Cys@MgBC, Try@MgBC, and Glu@MgBC was still maintained at 98.7%, 95.2%, and 82.7% respectively. This study proposes and clarifies the complexation mechanism of functional group-grafted Mg-modified biochar for heavy metals, providing new insights into the practical application of these biochars.

Disrupted Balance of Gray Matter Volume and Directed Functional Connectivity in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: Alterations in functional connectivity have been demonstrated in Alzheimer's disease (AD), an age-progressive neurodegenerative disorder that affects cognitive function; however, directional information flow has never been analyzed. OBJECTIVE: This study aimed to determine changes in resting-state directional functional connectivity measured using a novel approach, granger causality density (GCD), in patients with AD, and mild cognitive impairment (MCI) and explore novel neuroimaging biomarkers for cognitive decline detection. METHODS: In this study, structural MRI, resting-state functional magnetic resonance imaging, and neuropsychological data of 48 Alzheimer's Disease Neuroimaging Initiative participants were analyzed, comprising 16 patients with AD, 16 with MCI, and 16 normal controls. Volume-based morphometry (VBM) and GCD were used to calculate the voxel-based gray matter (GM) volumes and directed functional connectivity of the brain. We made full use of voxel-based between-group comparisons of VBM and GCD values to identify specific regions with significant alterations. In addition, Pearson's correlation analysis was conducted between directed functional connectivity and several clinical variables. Furthermore, receiver operating characteristic (ROC) analysis related to classification was performed in combination with VBM and GCD. RESULTS: In patients with cognitive decline, abnormal VBM and GCD (involving inflow and outflow of GCD) were noted in default mode network (DMN)-related areas and the cerebellum. GCD in the DMN midline core system, hippocampus, and cerebellum was closely correlated with the Mini- Mental State Examination and Functional Activities Questionnaire scores. In the ROC analysis combining VBM with GCD, the neuroimaging biomarker in the cerebellum was optimal for the early detection of MCI, whereas the precuneus was the best in predicting cognitive decline progression and AD diagnosis. CONCLUSION: Changes in GM volume and directed functional connectivity may reflect the mechanism of cognitive decline. This discovery could improve our understanding of the pathology of AD and MCI and provide available neuroimaging markers for the early detection, progression, and diagnosis of AD and MCI.

High exogenous humus inhibits greenhouse gas emissions from steppe lakes.

Although freshwater lakes are considered to be an important source of greenhouse gas (GHG) emissions, the potential driving mechanisms of such emissions are not well understood, especially in steppe lakes. In this study, the GHG emission characteristics in Hulun Lake Basin, including Hulun Lake, Beier Lake, Wulannuoer Lake, and their surrounding watersheds were investigated. The average methane (CH4) and nitrous oxide (N2O) emission fluxes released from rivers were 67.84 ± 20.53 and 0.11 ± 0.04 µg m-2·min-1, which were larger than those of lakes, with values of 28.60 ± 13.02 and 0.06 ± 0.02 µg m-2·min-1, respectively. Conversely, the average carbon dioxide (CO2) emission flux from lakes (1816.58 ± 498.98 µg m-2·min-1) was higher than that of rivers of (1795.41 ± 670.49 µg m-2·min-1). The water in Hulun Lake Basin was rich in organic matter and had a high chemical oxygen demand (COD). Three-dimensional fluorescence combined with a parallel factor analysis (3D-EEM-PARAFAC) demonstrated that the organic matter was composed of four humus types (from Component 1 (C1) to Component 4 (C4)), of which, C1 and C4 were terrestrial humus. The fluorescence index (FI) and humification index (HIX) indicated that the organic matter in the water was mainly imported from exogenous humus. The GHG emission fluxes were negatively correlated with these four components, indicating that GHG emissions were mainly affected by the organic matter source and components, and humus was the most important factor that inhibited GHG emissions in steppe lakes. However, the GHG emission flux was relatively high in some areas of the lake, especially in areas with high nutrient levels or where algal blooms occurred, as evidenced by the significantly positive correlations with total nitrogen (TN), total phosphorous (TP), and chlorophyll-a (chl-a) (p < 0.01). The algae-derived organic matter simulated the decomposition of refractory humus, thus, promoting GHG emissions. These findings are crucial for accurately evaluating the GHG emission fluxes, understanding the carbon cycle, and proposing future management strategies for steppe lakes.

Altered Functional Connectivity of Basal Ganglia in Mild Cognitive Impairment and Alzheimer's Disease.

(1) Background: Alzheimer's disease (AD), an age-progressive neurodegenerative disease that affects cognitive function, causes changes in the functional connectivity of the default-mode network (DMN). However, the question of whether AD-related changes occur in the functional connectivity of the basal ganglia has rarely been specifically analyzed. This study aimed to measure the changes in basal ganglia functional connectivity among patients with AD and mild cognitive impairment (MCI) in their resting state using the functional connectivity density (FCD) value, the functional connectivity (FC) intensity, and the graph theory index, and to confirm their influence on clinical manifestations. (2) Methods: Resting-state functional MRI (rs-fMRI) and neuropsychological data from 48 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used for analyses. The 48 ADNI participants comprised 16 patients with AD, 16 patients with MCI, and 16 normal controls (NCs). The functional connectivity of basal ganglia was evaluated by FCDs, FC strength, and graph theory index. We compared voxel-based FCD values between groups to show specific regions with significant variation and significant connectivity from ROI conduction to ROI analysis. Pearson's correlation analyses between functional connectivity and several simultaneous clinical variables were also conducted. Additionally, receiver operating characteristic (ROC) analyses associated with classification were conducted for both FCD values and graph theory indices. (3) Results: The level of FCD in patients with cognitive impairment showed obvious abnormalities (including short-range and long-range FCD). In addition to DMN-related regions, aberrant functional connectivity was also found to be present in the basal ganglia, especially in the caudate and amygdala. The FCD values of the basal ganglia (involving the caudate and amygdala) were closely related to scores from the Mini-Mental State Examination (MMSE) and the Functional Activities Questionnaire (FAQ); meanwhile, the graph theory indices (involving global efficiency and degree) of the basal ganglia (involving the caudate, amygdala, and putamen) were also found to be closely correlated with MMSE scores. In ROC analyses of both FCD and graph theory, the amygdala was of the utmost importance in the early-stage detection of MCI; additionally, the caudate nucleus was found to be crucial in the progression of cognitive decline and AD diagnosis. (4) Conclusions: It was systematically confirmed that there is a phenomenon of change in the functional connections in the basal ganglia during cognitive decline. The findings of this study could improve our understanding of AD and MCI pathology in the basal ganglia and make it possible to propose new targets for AD treatment in further studies.

Berberine Improves Cognitive Impairment by Simultaneously Impacting Cerebral Blood Flow and ß-Amyloid Accumulation in an APP/tau/PS1 Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is accompanied by ß-amyloid (Aß), neurofibrillary tangles, and neuron cell death, and is one of the most commonly occurring diseases among the elderly. The pathology of AD is complex, involving Aß overproduction and accumulation, tau hyperphosphorylation, and neuronal loss. In addition, chronic cerebral hypoperfusion (CCH) is ubiquitous in the AD patients and plans a pivotal role in triggering and exacerbating the pathophysiological progress of AD. The goal of this study was to investigate the neuroprotective properties of berberine (BBR) and the underlying mechanism. During the study, BBR was administrated to treat the triple-transgenic mouse model of Alzheimer's disease (3×Tg AD). To thoroughly evaluate the effects of the BBR administration, multiple manners were utilized, for instance, 3D arterial spin labeling technique, Morris water maze assay, immunofluorescence staining, TUNEL assay, laser speckle contrast imaging, western blotting, etc. The results showed that BBR ameliorated cognitive deficits in 3×Tg AD mice, reduced the Aß accumulation, inhibited the apoptosis of neurons, promoted the formation of microvessels in the mouse brain by enhancing brain CD31, VEGF, N-cadherin, Ang-1. The new vessels promoted by BBR were observed to have a complete structure and perfect function, which in turn promoted the recovery of cerebral blood flow (CBF). In general, berberine is effective to 3×Tg AD mice, has a neuroprotective effect, and is a candidate drug for the multi-target prevention and treatment of AD.

Berberine Improves Behavioral and Cognitive Deficits in a Mouse Model of Alzheimer's Disease via Regulation of ß-Amyloid Production and Endoplasmic Reticulum Stress.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by ß-amyloid (Aß), neurofibrillary tangles, and neuronal cell death. Aggressive Aß accumulation accelerates senile plaque formation and perturbs endoplasmic reticulum (ER) function. Aß accumulation-induced changes stimulate the unfolded protein response (UPR), which can trigger neuronal apoptosis. Protein kinase RNA-like endoplasmic reticulum kinase (PERK), whose activation is stress-dependent, increases the phosphorylation of eukaryotic translation initiation factor-2α (eIF2α). eIF2α promotes the synthesis of ß-site APP cleavage enzyme 1 (BACE1), which in turn facilitates Aß generation and subsequent neuronal apoptosis. In this study, we investigated whether berberine could improve cognitive deficits in the triple-transgenic mouse model of Alzheimer's disease (3 × Tg AD) mice. Our results revealed that berberine treatment may inhibit PERK/eIF2α signaling-mediated BACE1 translation, thus reducing Aß production and resultant neuronal apoptosis. Further, berberine may have neuroprotective effects, via attenuation of ER stress and oxidative stress. In sum, our study demonstrates the therapeutic potential of berberine for treating AD.

Strong Adsorption of Phosphorus by ZnAl-LDO-Activated Banana Biochar: An Analysis of Adsorption Efficiency, Thermodynamics, and Internal Mechanisms.

Zn-Al layered bimetallic composites were prepared by ethanol strengthening and co-precipitation using banana straw as a raw material. A high-efficiency phosphorus adsorbent (ZnAl-LDO-BC) was obtained by calcination at a high temperature. The kinetics and thermodynamics of phosphorus adsorption on ZnAl-LDO-BC were then studied. The results showed that the adsorption process of ZnAl-LDO-BC corresponds with the pseudo-second-order (PSO) kinetic equation and the Langmuir model. The theoretical maximum adsorption capacity of ZnAl-LDO-BC is 111.11 mg/g (at 45 °C, 500 mg/L phosphorus initial concentration). The influence of anions on phosphorus adsorption decreased in strength in the following order: CO3 2- > SO4 2- > NO3 -. Scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) were used to characterize the adsorption of phosphorus on ZnAl-LDO-BC and showed that ZnAl-LDO-BC can efficiently adsorb phosphorus. The adsorption mechanism utilizes both O-H and C-H on the surface of ZnAl-LDO-BC for the adsorption of PO4 3-, forming Zn3(PO4)2·4H2O via complexation precipitation; additionally, biochar surface adsorption and interlayer adsorption are indispensable forms of phosphate adsorption. With the systematic study of phosphorus adsorption by ZnAl-LDO-BC, a novel green technology was developed for addressing phosphorus pollution.

Key Molecules and Pathways Underlying Sporadic Amyotrophic Lateral Sclerosis: Integrated Analysis on Gene Expression Profiles of Motor Neurons.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive loss of motor neurons. The complex mechanisms underlying ALS are yet to be elucidated, while the lack of disease biomarkers and therapeutic options are associated with the poor prognosis of ALS patients. In this study, we performed bioinformatics analysis to clarify potential mechanisms in sporadic ALS (sALS). We compared three gene expression profiles (GSE18920, GSE56500, and GSE68605) of motor neurons obtained from sALS patients and healthy controls to discover differentially expressed genes (DEGs), and then performed integrated bioinformatics analyses to identify key molecules and pathways underlying sALS. We found that these DEGs were mainly enriched in the structure and functions of extracellular matrix (ECM), while functional enrichment in blood vessel morphogenesis was less correlated with motor neurons. The clustered subnetworks of the constructed protein-protein interaction network for DEGs and the group of selected hub genes were more significantly involved in the organization of collagen-containing ECM. The transcriptional factors database proposed RelA and NF-κB1 from NF-κB family as the key regulators of these hub genes. These results mainly demonstrated the alternations in ECM-related gene expression in motor neurons and suggested the role of NF-κB regulatory pathway in the pathogenesis of sALS.

Fabrication and Characterization of Novel ZnAl-Layered Double Hydroxide for the Superadsorption of Organic Contaminants from Wastewater.

An imidazole ester skeleton (zeolitic imidazolate framework (ZIF)) was grown on the surface of a ZnAl-layered double hydroxide (ZnAl-LDH) material to form a porous composite (ZIF-ZnAl-LDH). To understand the adsorption characteristics of the two materials, the effects of pH, adsorption time, and adsorption concentration on the adsorption of Congo red (CR) solution were investigated comprehensively. In addition, ZnAl-LDH and ZIF-ZnAl-LDH were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), and X-ray photoelectron spectroscopy (XPS). The results clearly showed that ZnAl-LDH had a lamellar structure with a diameter of approximately 200-500 nm and ZIF-ZnAl-LDH had a regular three-dimensional hexagonal structure. The kinetics and thermodynamics of the CR adsorption by ZnAl-LDH and ZIF-ZnAl-LDH can be described using pseudo-second-order (PSO) and Langmuir models, respectively. The highest value of adsorption capacity obtained from the Langmuir equation was equal to 625.00 and 909.09 mg/g for these two compounds, respectively. The values of the standard Gibbs free energy (ΔG°), entropy (ΔS°), and enthalpy (ΔH°) obtained for these adsorption processes prove that the adsorption of CR by ZnAl-LDH and ZIF-ZnAl-LDH is a spontaneous endothermic process. Furthermore, through the analysis of the characterization results, it is concluded that the adsorption mechanisms of ZnAl-LDH and ZIF-ZnAl-LDH on CR are mainly dominated by electrostatic action, functional group action, surface pore adsorption, and anion exchange.

High-Efficiency Removal of Cr(VI) from Wastewater by Mg-Loaded Biochars: Adsorption Process and Removal Mechanism.

Biochars were produced with magnesium chloride as an additive for the sorption of hexavalent chromium dissolved in water using five types of straw (from taro, corn, cassava, Chinese fir, and banana) and one type of shell (Camellia oleifera) as the raw materials. The removal of hexavalent chromium by the six biochars mainly occurred within 60 min and then gradually stabilized. The kinetics of the adsorption process were second order, the Langmuir model was followed, and the adsorption of Cr(VI) by the six biochars was characterized by Langmuir monolayer chemisorption on a heterogeneous surface. Banana straw biochar (BSB) had the best performance, which perhaps benefitted from its special structure and best adsorption effect on Cr(VI), and the theoretical adsorption capacity was calculated as 125.00 mg/g. For the mechanism analysis, Mg-loaded biochars were characterized before and after adsorption by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), and scanning electron microscopy/energy dispersive spectroscopy (SEM-EDS). The adsorption mechanism differed from the adsorption process of conventional magnetic biochar, and biochar interactions with Cr(VI) were controlled mainly by electrostatic attraction, complexation, and functional group bonding. In summary, the six Mg-loaded biochars exhibit great potential advantages in removing Cr(VI) from wastewater and have promising potential for practical use, especially BSB, which shows super-high adsorption performance.

Rare, low-frequency and common coding variants of ARHGEF28 gene and their association with sporadic amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Over 90% of cases are sporadic (sALS) and 5%-10% are familial (fALS). So far, more than 20 genes/loci have been linked to ALS. C9orf72, SOD1, TARDBP, and FUS are noted as the most common ALS genes; however, mutations of these genes explain <10% of sALS cases. Recently, Rho guanine nucleotide exchange factor, encoded by ARHGEF28, has been linked to the ALS pathogenesis, possibly by binding low-molecular-weight neurofilament mRNA and affects its stability. However, a systemic screening of ARHGEF28 mutations in ALS is lacking. In this study, we sequenced the entire coding sequence of ARHGEF28 in a Chinese cohort of 399 sporadic ALS and 327 elderly controls. A total of 73 coding variants were identified, including 26 synonymous and 47 nonsynonymous. Among the nonsynonymous variants, 33 were rare (minor allele frequency [MAF]<0.01), in which 18 were only identified in cases and 12 were only in controls. Three loss-of-function mutations were identified, including 2 truncations (p.Arg231Ter and p.Ser561Ter) and a frameshift deletion (p.Lys1070fs) in 2 cases and 1 control subject. The frequency of total and case-only rare variants was 7.5% (30/399) and 5.0% (20/399), respectively, in the patients. SKAT-O test suggested that the novel coding variants were marginally enriched in the cases (p = 0.049). Single-variant analysis suggested that the p.Asn1046Ser variant had a higher frequency in cases (8/399, 0.02) than in controls (1/327, 0.003) (OR: 6.67, 95% CI: 0.83-53.61; p = 0.046). By contrast, none of the low-frequency (MAF: 0.01-0.05) or common (MAF > 0.05) variants was associated with ALS (p > 0.05). Among all patients, 9 (2.3%) carried rare variants predicted to be deleterious, and the age at onset of these carriers (45.6 ± 10.9 years) was marginally younger than noncarriers (51.9 ± 10.7 years) (p = 0.11). Our results supported a possible genetic contribution of rare but not low-frequency and common coding variants to ALS. These data may have implications in the mechanisms and genetic counseling of the disease.

Phosphate adsorption from wastewater using ZnAl-LDO-loaded modified banana straw biochar.

ZnAl-layered double hydroxide-loaded banana straw biochar (ZnAl-LDH-BSB) was prepared via the hydrothermal method, and the efficient phosphorus removal agent ZnAl-LDO-BSB was obtained by calcination at 500 °C. Based on the ZnAl-LDO-BSB adsorption characteristics, the adsorption mechanism was evaluated via TG/DTA, FTIR, XRD, SEM, HRTEM, and other characterization methods. The results showed that the ZnAl-LDO-BSB assembled into microspheres with typical hexagonal lamellar structures and presented good thermal stability. The adsorption of total phosphate (TP) by ZnAl-LDO-BSB conforms to the Langmuir model, and the theoretical maximum adsorption capacity is 185.19 mg g-1. The adsorption kinetics were in accordance with the second-order kinetic model, and the anion influence on TP adsorption followed the order CO32- > SO42- > NO3-. The combination of zeta potential measurements with the FTIR, XRD, SEM, HRTEM, and XPS results suggested that ZnAl-LDO-BSB adsorbs TP mainly by electrostatic adsorption, surface coordination, and anion intercalation. Graphical abstract.

Characteristics of nitrogen and phosphorus adsorption by Mg-loaded biochar from different feedstocks.

Herein, biochars from 6 different feedstocks (taro straw, corn straw, cassava straw, Chinese fir straw, banana straw, and Camellia oleifera shell) were produced using magnesium chloride (MgCl2) as a modifier due to their sorption behavior toward NH4+-N and phosphorus in an aqueous solution. The biochar characteristics were evaluated, including pH, pHPZC, biochar magnesium content, and total pore volume (PVtot). The experimental results in terms of the kinetics and equilibrium isotherms showed that the cassava straw and banana straw biochars exhibited the theoretical maximum saturated adsorption capacities of 24.04 mg·g-1 (NH4+-N) and 31.15 mg·g-1 (TP), respectively. Biochar produced from these feedstocks had higher magnesium contents and greater total pore volumes, reflecting the significant contributions from magnesium and steric effects. FTIR, XRD, and SEM/EDS analyses demonstrated that NH4+-N and TP sorption mechanisms predominantly involved surface electrostatic attraction, Mg2+ precipitates and complexation with surface hydroxyl functional groups.

Paeonolum protects against MPP(+)-induced neurotoxicity in zebrafish and PC12 cells.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting 2% of the population aged over 65 years old. Mitochondrial defects and oxidative stress actively participate in degeneration of dopaminergic (DA) neurons in PD. Paeonolum, a main component isolated from Moutan cortex, has potent antioxidant ability. Here, we have examined the effects of paeonolum against MPP(+)-induced neurotoxicity in zebrafish and PC12 cells. METHODS: The overall viability and neurodegeneration of DA neurons was assessed in ETvmat2:green fluorescent protein (GFP) transgenic zebrafish, in which most monoaminergic neurons are labeled by GFP. Damage to PC12 cells was measured using a cell viability assay and assessment of nuclear morphology. Intracellular reactive oxygen species (ROS) and the level of total GSH were assessed. The mitochondrial cell death pathway including mitochondrial membrane potential, cytochrome C release and caspase-3 activity were also examined in PC12 cells. RESULTS: Paeonolum protected against MPP(+)-induced DA neurodegeneration and locomotor dysfunction in zebrafish in a concentration-dependent manner. Similar neuroprotection was replicated in the PC12 cellular model of MPP(+) toxicity. Paeonolum attenuated MPP(+)-induced intracellular ROS accumulation and restored the level of total GSH in PC12 cells. Furthermore, paeonolum significantly inhibited the mitochondrial cell death pathway induced by MPP(+). CONCLUSIONS: Collectively, the present study demonstrates that paeonolum protects zebrafish and PC12 cells against MPP(+)-induced neurotoxicity.

Absence of mutations in exon 6 of the TARDBP gene in 207 Chinese patients with sporadic amyotrohic lateral sclerosis.

Mutations in the TARDBP gene, which encodes the Tar DNA binding protein, have been shown to causes of both familial amyotrophic lateral sclerosis (FALS) and sporadic ALS (SALS). Recently, several novel TARDBP exon 6 mutants have been reported in patients with ALS in Europe and America but not in Asia. To further examine the spectrum and frequency of TARDBP exon 6 mutations, we investigated their frequency in ethnic Chinese patients with sporadic ALS. TARDBP exon 6 was screened by direct sequencing in 207 non-SOD1 SALS patients and 230 unrelated healthy controls but no mutations were identified. Our data indicate that exon 6 mutations in TARDBP are not a common cause of SALS in Han Chinese population from Southern Mainland China.

Motoneuron differentiation of induced pluripotent stem cells from SOD1G93A mice.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder mainly affecting motor neurons. Mutations in superoxide dismutase-1 (SOD-1) account for about 20% of familial ALS patients. A robust supply of motoneurons carrying the mutated gene would help understand the causes of motoneuron death and develop new therapeutics for the disease. Here, we established induced pluripotent stem (iPS) cell lines from SOD1G93A mice and compared their potency in motoneuron generation with normal iPS cells and mouse embryonic stem cells (E14). Our results showed that iPS cells derived from SOD1G93A mice possessed the similar potency in neuronal differentiation to normal iPS cells and E14 cells and can be efficiently driven to motoneuron-like phenotype. These cells exhibited typical neuronal morphology, expressed key motoneuron markers, including ChAT and HB9, and generated repetitive trains of action potentials. Furthermore, these neurons highly expressed human SOD-1 and exhibited shorter neurites compared to controls. The present study provides evidence that ALS-iPS cells can be used as disease models in high-throughput screening and mechanistic studies due to their ability to efficiently differentiate into specific neuronal subtypes.

Marine cyclotripeptide X-13 promotes angiogenesis in zebrafish and human endothelial cells via PI3K/Akt/eNOS signaling pathways.

Cyclotripeptide X-13 is a core of novel marine compound xyloallenoide A isolated from mangrove fungus Xylaria sp. (no. 2508). We found that X-13 dose-dependently induced angiogenesis in zebrafish embryos and in human endothelial cells, which was accompanied by increased phosphorylation of eNOS and Akt and NO release. Inhibition of PI3K/Akt/eNOS by LY294002 or L-NAME suppressed X-13-induced angiogenesis. The present work demonstrates that X-13 promotes angiogenesis via PI3K/Akt/eNOS pathways.

Protecting against wayward human induced pluripotent stem cells with a suicide gene.

The generation of human induced pluripotent stem cells (hiPSCs) opens a prospect for regenerative medicine. However, transplantation of somatic cells derived from hiPSCs still harbor many risks such as cells' incorrect differentiation or over-proliferation, and the worst, tumor formation. Therefore, it's essential to ravel out these obstacles before their clinical application. Herein, we genetically modified hiPSCs and human embryonic stem cells (hESCs) with a truncated herpes simplex virus delta thymidine kinase (deltaTK) gene driven by EF1α or Nanog promoter to selectively ablate wayward pluripotent stem cells. The results showed that insertion of deltaTK gene did not alter their pluripotency and self-renewal capacity but rendered them sensitive to ganciclovir, which induced elimination of deltaTK(+) cells in vitro in a dose and time-dependent manner, most importantly, facilitated both prevention and ablation of tumors in vivo. Furthermore, comparative analysis between transduced hiPSCs and hESCs showed that there was no difference in ganciclovir sensitivity between them. This approach may help to develop safety strategies for clinical application of hiPSCs in regenerative medicine in the future.

Neuronal differentiation potential of mouse induced pluripotent stem cells.

Induced pluripotent stem (iPS) cells have been generated from somatic cells by ectopic expression of defined transcription factors. The important issues for clinical applications of iPS cells are the defined methods for somatic cell differentiation and how to effectively enrich desired cell population. Here we used humanized renilla green fluorescent protein under the control of Tα1 α-tubulin promoter as lineage selection marker for neuronal differentiation of iPS cells. Using fluorescence-activated cell sorting, green fluorescent protein positive cells were isolated and enriched to near-purity. These results indicated that the neuronal differentiation potential of iPS cells derived from adult somatic cells is similar to that of embryonic stem cells and the high-purity neurons may have important implications for neurodevelopmental studies, safety pharmacological studies, and transplantation studies.

[Protective effects of Lycium barbarum extract against MPP(+) -induced neurotoxicity in Caenorhabditis elegans and PC12 cells].

OBJECTIVE: To investigate the neuroprotective effects of Lycium barbarum extract against MPP(+) -induced neurotoxicity in Caenorhabditis elegans and PC12 cells and its mechanism. METHODS: Pretreated MPP(+) -induced nearotoxicity in C. elegans and PC12 cells with Lycium barbarum at different dosages. The viability and DA neurodegeneration was assessed in C. elegans selectively expressing green fluorescent protein (GFP) in DA neurons. PC12 cell damage was measured using MTT and nuclear morphology. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential and total GSH were assessed. RESULTS: Lycium barbarum extract protected against MPP(+) -induced loss of viability and DA neurodegeneration in C. elegans in a dose-dependent manner. Similar neuroprotection was replicated in MPP + PC12 cell model. Lycium barbarum extract attenuated MPP(+) -induced intracellular ROS accumulation, loss of mitochondrial membrane potential and restored total GSH levels in PCl2 cells. CONCLUSIONS: Lycium barbarum extract protects against MPP(+) -induced neurotoxicity in C. elegans and PC12 cells and its machanism may be related to its antioxidative property and restoration of total GSH level.