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1.
Mil Med Res ; 10(1): 66, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38111039

ABSTRACT

BACKGROUND: The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. METHODS: A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. RESULTS: In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-ß (IFN-ß) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. CONCLUSIONS: Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-ß-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.


Subject(s)
Radiation Injuries , Thrombocytopenia , Thrombosis , Humans , Animals , Mice , Megakaryocytes/metabolism , Megakaryocytes/pathology , Thrombocytopenia/etiology , Apoptosis , Nucleotidyltransferases/metabolism , Thrombosis/metabolism
2.
Plant Physiol Biochem ; 199: 107706, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37119548

ABSTRACT

In this study, we characterized a WRKY family member gene, SsWRKY1, which is located in the nucleus and contains multiple stress-related cis-acting elements. In addition, constructed SsWRKY1-overexpressing Arabidopsis thaliana had higher antioxidant enzyme activity and proline content under drought stress conditions, with lower malondialdehyde content and reactive oxygen species (ROS) accumulation, and the expression levels of six stress-related genes were significantly upregulated. This indicates that the overexpression of SsWRKY1 in Arabidopsis thaliana improves resistance to drought stress. SsWRKY1 does not have transcriptional autoactivation activity in yeast cells. The yeast two-hybrid (Y2H) system and the S. spontaneum cDNA library were used to screen 21 potential proteins that interact with SsWRKY1, and the interaction between SsWRKY1 and ATAF2 was verified by GST pull-down assay. In summary, our results indicate that SsWRKY1 plays an important role in the response to drought stress and provide initial insights into the molecular mechanism of SsWRKY1 in response to drought stress.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Saccharum , Arabidopsis/genetics , Arabidopsis/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Saccharum/genetics , Drought Resistance , Plant Proteins/genetics , Plant Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Plants, Genetically Modified/genetics , Gene Expression Regulation, Plant , Droughts , Antioxidants/metabolism , Stress, Physiological/genetics
3.
Build Environ ; 232: 110066, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36779167

ABSTRACT

The pandemic of COVID-19 and its transmission ability raise much attention to ventilation design as indoor-transmission outstrips outdoor-transmission. Impinging jet ventilation (IJV) systems might be promising to ventilate densely occupied large spaces due to their high jet momentum. However, their performances in densely occupied spaces have rarely been explored. This study proposes a modified IJV system and evaluates its performance numerically in a densely occupied classroom mockup. A new assessment formula is also proposed to evaluate the nonuniformity of target species CO2. The infector is assumed as the manikin with the lowest tracer gas concentration in the head region. The main results include: a) Indoor air quality (IAQ) in the classroom is improved significantly compared with a mixing ventilation system, i.e., averaged CO2 in the occupied zone (OZ) is reduced from 1287 ppm to 1078 ppm, the OZ-averaged mean age of air is reduced from 439 s to 177 s; b) The mean infection probability is reduced from 0.047% to 0.027% with an infector, and from 0.035% to 0.024% with another infector; c) Cooling coil load is reduced by around 21.0%; d) Overall evaluation indices meet the requirements for comfortable environments, i.e., the temperature difference between head and ankle is within 3 °C and the OZ-averaged predictive mean vote is in the range of -0.5 - 0.5; e) Thermal comfort level and uniformity are decreased, e.g., overcooling near diffuser at ankle level. Summarily, the target system effectively improves IAQ, reduces exhaled-contaminant concentration in head regions, and saves energy as well.

4.
Biomed Res Int ; 2022: 3918045, 2022.
Article in English | MEDLINE | ID: mdl-35463971

ABSTRACT

This study reports the risk factors, trends, and burden of cancer in China from 1990 to 2019 from the Global Burden of Diseases. The incidence, mortality, and DALY of all cancers in China for the past 30 years were analyzed. In 2019, the age-standardized rates (ASRs) of cancer incidence, mortality, and DALY in China were 232.42/100 000, 136.72/100 000, and 3288.22/100 000, respectively. The five cancers with the highest age-standardized incidence rates were lung, stomach, colorectal, breast, and prostate cancers. From 1990 to 2019, the number of new cancer cases, deaths, and DALY increased by 168.78%, 86.89%, and 51.20%, respectively. The ASR increased by 22.21% for incidence and decreased by 19.01% and 27.19% for mortality and DALY, respectively, and their corresponding average annual percent change values were 0.71, -0.80, and -1.26, respectively. The main risk factors for cancer in China were smoking, air pollution, dietary factors, and alcohol use. From 1990 to 2019, the cancer incidence rate was on the rise, and cancer mortality and DALY rates were declining; however, these characteristics vary by cancer site. Therefore, current prevention strategies should be reoriented, and specific strategies for cancers in different sites should be established to prevent the increase in cancer cases.


Subject(s)
Global Burden of Disease , Prostatic Neoplasms , China/epidemiology , Humans , Incidence , Male , Quality-Adjusted Life Years
5.
Article in English | MEDLINE | ID: mdl-35055693

ABSTRACT

BACKGROUND: Oral cancer (OC) is a common tumour that poses a threat to human health and imposes a heavy burden on countries. This study assessed the burden imposed by OC on the 10 most populous countries from 1990 to 2019 on the basis of gender, age and socio-demographic index. METHODS: Data on incidence, mortality, disability-adjusted life years (DALY) and corresponding age-standardised rates (ASR) for OC in the 10 most populous countries from 1990 to 2019 were derived from the Global Burden of Disease Study 2019. Estimated annual percentage changes were calculated to assess the trends of morbidity, mortality and DALY. The indicator that served as a proxy for survival rate was the supplement of mortality-to-incidence ratio (SMIR) (1 - (M/I)). RESULTS: The number of new cases, deaths and DALY have increased in all 10 countries in the past 30 years. Trends in age-standardised incidence rates (ASIR), age-standardised mortality rate (ASMR) and age-standardised DALY for OC in the 10 most populous countries varied. The SMIR increased in all countries, with most countries having an SMIR between 30% and 50%. In 2019, the United States had the highest SMIR at 76%, whereas Russia had the lowest at 21.7%. Incidence and mortality were close between male and female subjects in Japan, Indonesia, Mexico, India, Bangladesh and Pakistan. The incidence and mortality in male subjects in the United States, Russia, China and Brazil were two or more times those of female subjects. Gender difference was highest among patients aged 40-69 years. CONCLUSION: Trends and gender differences in ASIR, ASMR and age-standardised DALY for OC vary in the 10 most populous countries. Government cancer programs are often expensive to run, especially in countries with large populations. Policy makers need to take these differences into account when formulating policies.


Subject(s)
Global Burden of Disease , Mouth Neoplasms , Adult , Aged , Female , Global Health , Humans , Incidence , India , Male , Middle Aged , Morbidity , Mouth Neoplasms/epidemiology , Quality-Adjusted Life Years , Risk Factors
6.
Luminescence ; 36(5): 1306-1316, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33880879

ABSTRACT

Novel strategies still need to be proposed that can be used to identify and detect toxic environmental pollutants. In this paper, two channels of colorimetry and fluorescence 'turn-on' fluorescent probe 1 (7-hydroxy-8-[(2-hydroxy-phenylimino)- methyl]-4-methylbenzopyran-2-one) for the simple yet highly selective detection of CN¯ have been successfully designed and synthesized. Crystal features of probe 1 were defined using X-ray single crystal diffractometry. Probe 1 showed a strongly colorimetric and fluorescence response to CN¯ that induced obvious naked-eye colour changes in aqueous solution (DMSO/H2 O, 3:1 v:v). In addition, probe 1 for CN¯ detection displayed low detection limits of 3.91 × 10-8 M, which were significantly lower than the 1.9 × 10-6 M maximum level specified by the World Health Organization (WHO) for potable water. The sensing mechanism for probe 1 was attributed to the deprotonation process as shown by 1 H NMR titration. Moreover, based on the visible colorimetry and fluorescence change for probe 1 to CN¯, measurement was performed for simulated water samples containing CN¯. This study provides a broad prospect for solving other pollution problems and promoting the design of new fluorescent materials.


Subject(s)
Cyanides , Schiff Bases , Coumarins , Fluorescent Dyes , Spectrometry, Fluorescence , Water
7.
J Fluoresc ; 31(2): 437-446, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33410088

ABSTRACT

A highly selective turn-on fluorescent and naked-eye colourimetric dual-channel probe for cyanide anions (CN-) has been designed and characterized. In the mixed solution (DMSO / H2O, 9:1, v / v), only CN- could cause an increase in the UV absorption intensity and the corresponding fluorescence intensity increased, and other anions had no significant effect on the probe. After treatment with cyanide in the probe solution, the solution showed a noticeable colour change, from light yellow to purple. Moreover, a fluorescence spectrophotometer can be used to observe that the fluorescence intensity of the solution is significantly enhanced. The response of the colourimetric and fluorescent dual-channel probe to CN- was attributed to nucleophilic addition, and the mechanism was determined by 1H NMR spectroscopy. In addition, this probe was used to detect CN- in actual water samples, including river water, drinking water, and tap water. The spiked CN- recovery rate is very high (97.2%-100.06%), and analytical precision is also very high (RSD < 2%), which shows its feasibility and reliability for detecting cyanide ions in actual water samples.


Subject(s)
Colorimetry , Cyanides/analysis , Fluorescent Dyes/chemistry , Water Pollutants, Chemical/analysis , Anions/analysis , Fluorescent Dyes/chemical synthesis , Molecular Structure , Spectrometry, Fluorescence
8.
Kaohsiung J Med Sci ; 36(3): 171-177, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31894898

ABSTRACT

Numb is a conserved protein plays important roles in the development of cancer. Two Numb isoforms have been found produced by alternative splicing and play contrast roles in regulating cellular functions. It is reported that the expression of Numb long isoform (Numb-L) was increased in various kinds of cancers, but in endometrial cancer, the condition is still unknown. The level of two Numb transcripts and protein isoforms were detected by semiquantitative polymerase chain reaction and immunoblotting in 47 paired endometrial tumor and adjacent non-tumor control tissues. The level of three alternative splicing related proteins: RBM5, RBM6, and RBM10 was determined by immunoblotting. MiRNAs targeting RBM10 were predicted by bioinformatics tools and their interaction with RBM10 was confirmed by luciferase assay and immunoblotting. The function of miR-335 in endometrial cancer was examined in xenograft mouse model. Numb-L level was increased in tumors and negatively correlated with RBM10 protein level. RBM10 mRNA level was not significantly altered in endometrial tumors suggesting its expression may regulated by post transcriptional regulators such as miRNAs. We identified miR-133a, miR-133b, and miR-335 directly target RBM10, but only miR-335 level increased in tumors and negatively correlated with RBM10 protein level. miR-335 overexpression promoted tumor growth by downregulating RBM10 and upregulating Numb-L level in xenograft mouse model. miR-335 overexpression promoted Numb-L expression via targeting RBM10 in endometrial cancer, which may provide new biomarkers for EC diagnosis.


Subject(s)
Alternative Splicing/physiology , Endometrial Neoplasms/metabolism , MicroRNAs/metabolism , RNA-Binding Proteins/metabolism , Adult , Alternative Splicing/genetics , Animals , Blotting, Western , Cell Line, Tumor , Cell Proliferation/genetics , Cell Proliferation/physiology , Endometrial Neoplasms/genetics , Female , Humans , Mice , MicroRNAs/genetics , Middle Aged , RNA-Binding Proteins/genetics
9.
Kaohsiung J Med Sci ; 36(1): 13-19, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31587503

ABSTRACT

Vascular endothelial growth factor A (VEGFA) gene has three alternative exons which results in multiple isoforms. VEGFA has been found overexpressed in patients with endometrial cancer, but the VEGFA expression pattern and how it is regulated are still unknown. The level of VEGFA transcripts and protein isoforms were detected by semi-quantitative Polymerase chain reaction (PCR) and immunoblotting in 29 paired endometrial tumor and adjacent nontumor control tissues. The level of three alternative splicing related proteins: RBM5, RBM6, and RBM10 was determined by immunoblotting. The H3K27Ac level in RBM10 promoter region was detected by ChIP-PCR. The RBM10 promoter region methylation level were quantified by methylation-sensitive high resolution melting. VEGFA165a was overexpressed and VEGFA165b level was reduced in tumors. RBM10 level was reduced in tumors. RBM10 level was negatively correlated with VEGFA165a level and positively correlated with VEGFA165b level in tumors. Using HEC-1-A and RL95-2 cells, we confirmed that VEGFA165a/b expressed pattern was controlled by RBM10. MALAT1 level was increased in tumors but not involved in VEGFA alternative splicing. Reduced H3K27Ac level and increased DNA methylation in the promoter region controlled RBM10 expression in tumors. VEGFA alternative splicing in endometrial cancer was regulated by RBM10, the expression of which was controlled by histone acetylation and DNA methylation.


Subject(s)
Alternative Splicing/genetics , Endometrial Neoplasms/genetics , Vascular Endothelial Growth Factor A/genetics , Adult , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Chromatin Immunoprecipitation , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Endometrial Neoplasms/metabolism , Female , Humans , In Vitro Techniques , Middle Aged , Protein Binding , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Vascular Endothelial Growth Factor A/metabolism
10.
BMC Med ; 17(1): 204, 2019 11 15.
Article in English | MEDLINE | ID: mdl-31727112

ABSTRACT

BACKGROUND: Brain innate immunity is vital for maintaining normal brain functions. Immune homeostatic imbalances play pivotal roles in the pathogenesis of neurological diseases including Parkinson's disease (PD). However, the molecular and cellular mechanisms underlying the regulation of brain innate immunity and their significance in PD pathogenesis are still largely unknown. METHODS: Cre-inducible diphtheria toxin receptor (iDTR) and diphtheria toxin-mediated cell ablation was performed to investigate the impact of neuron-glial antigen 2 (NG2) glia on the brain innate immunity. RNA sequencing analysis was carried out to identify differentially expressed genes in mouse brain with ablated NG2 glia and lipopolysaccharide (LPS) challenge. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to evaluate neuroinflammatory response in the presence or absence of NG2 glia. The survival of dopaminergic neurons or glial cell activation was evaluated by immunohistochemistry. Co-cultures of NG2 glia and microglia were used to examine the influence of NG2 glia to microglial activation. RESULTS: We show that NG2 glia are required for the maintenance of immune homeostasis in the brain via transforming growth factor-ß2 (TGF-ß2)-TGF-ß type II receptor (TGFBR2)-CX3C chemokine receptor 1 (CX3CR1) signaling, which suppresses the activation of microglia. We demonstrate that mice with ablated NG2 glia display a profound downregulation of the expression of microglia-specific signature genes and remarkable inflammatory response in the brain following exposure to endotoxin lipopolysaccharides. Gain- or loss-of-function studies show that NG2 glia-derived TGF-ß2 and its receptor TGFBR2 in microglia are key regulators of the CX3CR1-modulated immune response. Furthermore, deficiency of NG2 glia contributes to neuroinflammation and nigral dopaminergic neuron loss in MPTP-induced mouse PD model. CONCLUSIONS: These findings suggest that NG2 glia play a critical role in modulation of neuroinflammation and provide a compelling rationale for the development of new therapeutics for neurological disorders.


Subject(s)
Antigens/physiology , Brain/immunology , Immunity, Innate , Neuroglia/physiology , Parkinson Disease/immunology , Proteoglycans/physiology , Receptor, Transforming Growth Factor-beta Type II/metabolism , Transforming Growth Factor beta2/metabolism , Animals , Brain/metabolism , CX3C Chemokine Receptor 1/metabolism , Disease Models, Animal , Dopaminergic Neurons/physiology , Lipopolysaccharides/immunology , Mice , Mice, Inbred C57BL , Microglia/physiology , Rats , Rats, Sprague-Dawley , Signal Transduction
11.
Plant Physiol Biochem ; 144: 455-465, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31655344

ABSTRACT

Sugarcane is an important sugar and energy crop worldwide. It utilises highly efficient C4 photosynthesis and accumulates sucrose in its culms. The sucrose content in sugarcane culms is a quantitative trait controlled by multiple genes. The regulatory mechanism underlying the maximum sucrose level in sugarcane culms remains unclear. We used transcriptome sequences to identify the potential regulatory genes involved in sucrose accumulation in Saccarum officinarum L. cv. Badila. The sucrose accumulating internodes at the elongation and mature growth stage and the immature internodes with low sucrose content at the mature stage were used for RNA sequencing. The obtained differentially expressed genes (DEGs) related to sucrose accumulation were analysed. Results showed that the transcripts encoding invertase (beta-fructofuranosidase, EC: 3.2.1.26) which catalyses sucrose hydrolysis and 6-phosphofructokinase (PFK, EC: 2.7.1.11), a key glycolysis regulatory enzyme, were downregulated in the high sucrose accumulation internodes. The transcripts encoding key enzymes for ABA, gibberellin and ethylene synthesis were also downregulated during sucrose accumulation. Furthermore, regulated protein kinase, transcription factor and sugar transporter genes were also obtained. This research can clarify the molecular regulation network of sucrose accumulation in sugarcane.


Subject(s)
Saccharum/metabolism , Sucrose/metabolism , Transcriptome/genetics , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , Saccharum/genetics
12.
Transl Neurodegener ; 8: 3, 2019.
Article in English | MEDLINE | ID: mdl-30675347

ABSTRACT

BACKGROUND: Parkinson's disease (PD) is characterized by a chronic loss of dopaminergic neurons and the presence of proteinaceous inclusions (Lewy bodies) within some remaining neurons in the substantia nigra. Recently, astroglial inclusion body has also been found in some neurodegenerative diseases including PD. However, the underlying molecular mechanisms of how astroglial protein aggregation forms remain largely unknown. Here, we investigated the contribution of αB-crystallin (CRYAB), a small heat shock protein, in α-synuclein inclusion formation in astrocytes. METHODS: Small interfering RNA (siRNA)-mediated CRYAB (siCRYAB) knockdown or CRYAB overexpression was performed to investigate the impact of CRYAB on the autophagy in human glioblastoma cell line U251 cells. Co-immunoprecipitation (co-IP) and immunoblotting were used to dissect the interaction among multiple proteins. The clearance of α-synuclein in vitro was evaluated by immunocytochemistry. CRYAB transgenic mice and transgenic mice overexpressing A30P mutant form of human α-synuclein were used to examine the influence of CRYAB to α-synuclein accumulation in vivo. RESULTS: We found that knockdown of CRYAB in U251 cells or primary cultured astrocytes resulted in a marked augmentation of autophagy activity. In contrast, exogenous CRYAB disrupted the assembly of the BAG3-HSPB8-HSC70 complex via binding with BAG3, thereby suppressing the autophagy activity. Furthermore, CRYAB-regulated autophagy has relevance to PD pathogenesis. Knockdown of CRYAB remarkably promoted cytoplasmic clearance of α-synuclein preformed fibrils (PFFs). Conversely, selective overexpression of CRYAB in astrocytes markedly suppressed autophagy leading to the accumulation of α-synuclein aggregates in the brain of transgenic mice expressing human α-synuclein A30P mutant. CONCLUSIONS: This study reveals a novel function for CRYAB as a natural inhibitor of astrocytic autophagy and shows that knockdown of CYRAB may provide a therapeutic target against proteinopathies such as synucleinopathies.

13.
Front Plant Sci ; 8: 1535, 2017.
Article in English | MEDLINE | ID: mdl-29033953

ABSTRACT

Genetically modified crops which had been commercial applied extensively majorly are the insect resistance and herbicide tolerance events. In this study, the Bt insecticidal gene Cry1Ab, the glyphosate-tolerant gene EPSPS, and the selection marker gene PMI were combined into a single transferred DNA fragment and introduced into sugarcane by Agrobacterium-mediated transformation. Thirty-three resistant plantlets were obtained after selection using a PMI/mannose selection system. Thirty of these resistant plantlets were PCR positive for the three target genes. Southern blot assay revealed that the copy number of the integrated fragment in the transformed plantlets varied from 1 to 7. ELISA analysis showed that 23 of the 33 resistant plantlets expressed Cry1Ab and EPSPS protein. Five single-copy and ELISA-positive transgenic lines were tested under laboratory and field conditions to determine their resistance to insects and herbicides, and also evaluated their agronomic characteristics and industrial traits. Results showed that larvae fed with fodder mixture containing stem tissues from single-copy transgenic lines were weak and small, moreover, pupation and eclosion were delayed significantly during voluntary feeding bioassays. None of transgenic sugarcane was destroyed by cane borer while more than 30% of wild type sugarcane was destroyed by cane borer. For herbicide resistance, the transgenic plantlets grew healthy even when treated with up to 0.5% roundup while wild type plantlets would die off when treated with 0.1% roundup. Thus demonstrate that these transgenic lines showed strong insect resistance and glyphosate tolerance under both laboratory and field conditions. But in the field most of the transgenic plants were shorter and more slender than non-transformed control plants. So they presented poor agronomic characteristics and industrial traits than non-transformed control plants. Thus, a considerable number of embryogenic calli should be infected to obtain transgenic lines with potential for commercial use.

14.
Stem Cells Int ; 2016: 2452985, 2016.
Article in English | MEDLINE | ID: mdl-26770203

ABSTRACT

Somatic cells can be directly converted into functional neurons by ectopic expression of defined factors and/or microRNAs. Since the first report of conversion mouse embryonic fibroblasts into functional neurons, the postnatal mouse, and human fibroblasts, astroglia, hepatocytes, and pericyte-derived cells have been converted into functional dopaminergic and motor neurons both in vitro and in vivo. However, it is invasive to get all these materials. In the current study, we provide a noninvasive approach to obtain directly reprogrammed functional neurons by overexpression of the transcription factors Ascl1, Brn2, NeuroD, c-Myc, and Myt1l in human urine cells. These induced neuronal (iN) cells could express multiple neuron-specific proteins and generate action potentials. Moreover, urine cells from Wilson's disease (WD) patient could also be directly converted into neurons. In conclusion, generation of iN cells from nonneural lineages is a feasible and befitting approach for neurological disease modeling.

15.
Biol Open ; 4(12): 1744-52, 2015 Nov 30.
Article in English | MEDLINE | ID: mdl-26621826

ABSTRACT

Paroxysmal kinesigenic dyskinesia (PKD) is a monogenic movement disorder with autosomal dominant inheritance. We previously identified the proline-rich transmembrane protein 2 (PRRT2) as a causative gene of PKD. However, the pathogenesis of PKD remains largely unknown so far. In addition, applicable modeling tools to investigate the underlying mechanisms of PKD are still lacking. The combination of disease-specific human induced pluripotent stem cells (iPSCs) and directed cell differentiation offers an ideal platform for disease modeling. In this study, we generated two iPSC lines from the renal epithelial cells of one PKD patient with the hotspot c.649dupC mutation (PKD-iPSCs). These cell lines were positive for alkaline phosphatase Nanog, Tra-1-80, Tra-1-60, SSEA-3 and SSEA-4. Teratomas with three blastoderms including ectoderm, mesoderm, and endoderm were obtained two months after injection of PKD-iPSCs into NOD/SCID mice. The expression of PRRT2 mRNA was decreased in PKD-iPSCs compared with that of the control iPSCs. Furthermore, PKD-iPSCs possessed the differentiation potential of functional glutamatergic, dopaminergic and motor neurons in vitro. Electrophysiological examinations revealed that the current densities of fast activated and deactivated sodium channels as well as voltage gated potassium channels were not different between the neurons from PKD-iPSCs and control iPSCs. Thus, PKD-iPSCs are a feasible modeling tool to investigate the pathogenic mechanisms of PKD.

16.
Huan Jing Ke Xue ; 36(10): 3697-705, 2015 Oct.
Article in Chinese | MEDLINE | ID: mdl-26841601

ABSTRACT

In order to investigate the pollution characteristics of stormwater runoff in the southern developed rural region, the runoff samples were collected from four different underlying surfaces during three storm events in Caoqiao and Pujia Tou, which are two typical villages and are located in Yuhang District of Hangzhou. The content of nutrition (nitrogen and phosphorus) and heavy metals (Mn, Cu, Zn, Ni, Cr, Cd, As, Pb) in the simples were analyzed, and the difference of EMC ( event mean concentration) and pollution load of the contaminants in the runoff on different underlying surfaces were compared. The results showed that the EMC of TSS, COD, NH4(+)-N, TP and TN were 16.19, 21.01, 0.74, 1.39 and 2.39 mg x L(-1) in the Caoqiao, respectively; as to Pujia Tou, they were 3.10, 15.69, 0.90, 0.78 and 3.58 mg x L(-1), respectively. The content of heavy metals was all lower than the national surface water quality of two type water in the runoff. Compared with the quality standards for surface water, the EMC of TP was 9 times and 3. 5 times higher and TN was 1. 8 times and 1. 2 times higher in two areas. Besides, the pollution loads of TSS and COD were the highest in farmland.


Subject(s)
Environmental Monitoring , Rain , Water Movements , Water Pollutants, Chemical/analysis , Water/chemistry , China , Metals, Heavy/analysis , Nitrogen/analysis , Phosphorus/analysis , Water Quality
17.
Ying Yong Sheng Tai Xue Bao ; 25(4): 1069-75, 2014 Apr.
Article in Chinese | MEDLINE | ID: mdl-25011301

ABSTRACT

Sulfur (S) forms in two contrasting soils (a red soil and a black soil) under different long-term fertilization treatments (from 1990 to 2011) from the National Long-term Monitoring Network of Soil Fertility and Fertilizer Effects of China were investigated using a fractionation scheme in order to explore the distribution and transportation of S with different forms in the soils. The soil samples were collected from the topsoil (0-20 cm) and subsoil (20-40 cm) horizons that were treated with no fertilizers (CK), nitrogen, phosphorus, and potassium fertilizers (NPK), or NPK plus organic manures (MNPK) since 1990. The results indicated that when compared with the CK, total S contents in the topsoil layers treated with NPK and MNPK were increased by 42% and 33% for the red soil, and by 6% and 76% for the black soil, respectively, while the total S in the subsoil layer was less affected by the fertilization treatments and obviously lower than in the topsoil layer except for the red soil treated with NPK. The main forms of inorganic S in the red soil and black soil were found to be available S and HCl-extracted S, respectively. The application of NPK and MNPK increased the available S by 447% and 102% in the topsoil layer of the red soil compared with CK, and facilitated the transportation of available S into the lower depth. In contrast, NPK and MNPK only increased the available S by 54% and 93% in the topsoil layer of the black soil, and showed a slight influence on available S in the subsoil. The organic S forms were predominantly composed of ester S and residual S in the two soils. Under long-term fertilization, the residual S significantly increased over 32% and 55% in the topsoil and subsoil layers, respectively, compared with CK. The ester S and carbon-bonded S, which were relatively active, were less affected by the fertilization treatments, but positively related to the level of organic carbon in each soil (P < 0.05). In addition, the results from the long-term experiments indicated that the contribution of S input from atmospheric deposition was significant and should not be neglected.


Subject(s)
Fertilizers , Soil/chemistry , Sulfur/chemistry , Carbon , Manure , Nitrogen , Phosphorus , Potassium
18.
Nature ; 494(7435): 90-4, 2013 Feb 07.
Article in English | MEDLINE | ID: mdl-23242137

ABSTRACT

Chronic neuroinflammation is a common feature of the ageing brain and some neurodegenerative disorders. However, the molecular and cellular mechanisms underlying the regulation of innate immunity in the central nervous system remain elusive. Here we show that the astrocytic dopamine D2 receptor (DRD2) modulates innate immunity through αB-crystallin (CRYAB), which is known to suppress neuroinflammation. We demonstrate that knockout mice lacking Drd2 showed remarkable inflammatory response in multiple central nervous system regions and increased the vulnerability of nigral dopaminergic neurons to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Astrocytes null for Drd2 became hyper-responsive to immune stimuli with a marked reduction in the level of CRYAB. Preferential ablation of Drd2 in astrocytes robustly activated astrocytes in the substantia nigra. Gain- or loss-of-function studies showed that CRYAB is critical for DRD2-mediated modulation of innate immune response in astrocytes. Furthermore, treatment of wild-type mice with the selective DRD2 agonist quinpirole increased resistance of the nigral dopaminergic neurons to MPTP through partial suppression of inflammation. Our study indicates that astrocytic DRD2 activation normally suppresses neuroinflammation in the central nervous system through a CRYAB-dependent mechanism, and provides a new strategy for targeting the astrocyte-mediated innate immune response in the central nervous system during ageing and disease.


Subject(s)
Astrocytes/immunology , Astrocytes/metabolism , Inflammation/immunology , Receptors, Dopamine D2/metabolism , alpha-Crystallin B Chain/metabolism , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Animals , Astrocytes/drug effects , Dopaminergic Neurons/drug effects , Immunity, Innate/drug effects , Inflammation/chemically induced , Inflammation/genetics , Inflammation/pathology , Male , Mice , Mice, Inbred C57BL , Microglia/cytology , Microglia/immunology , Neuroprotective Agents/metabolism , Quinpirole/pharmacology , Receptors, Dopamine D2/agonists , Receptors, Dopamine D2/deficiency , Receptors, Dopamine D2/genetics , Substantia Nigra/cytology , Substantia Nigra/drug effects , alpha-Crystallin B Chain/genetics
19.
J Agric Food Chem ; 60(5): 1251-7, 2012 Feb 08.
Article in English | MEDLINE | ID: mdl-22242825

ABSTRACT

In this study, an endophytic Streptomyces sp. neau-D50 with strong antifungal activity against Phytophthora sojae was isolated from healthy soybean root, using an in vitro screening technique. A bioactivity-guided approach was then employed to isolate and determine the chemical identity of bioactive constituents with antifungal activity from strain neau-D50. The structure of the antifungal metabolite was elucidated as borrelidin on the basis of spectral analysis. To our knowledge, this is the first report that borrelidin has strong antifungal activity against dominant race 1 of P. sojae with EC(50) and EC(95) of 0.0056 and 0.026 mg/L, respectively. The values were respectively 62.5- and 262.3-fold lower than those of the commercial fungicide metalaxyl, which has been used to treat soybean seed for the control of P. sojae . The in situ bioassays demonstrated that borrelidin at 10 mg/L reduced P. sojae race 1 lesions on soybean seedlings by 94.72% without affecting root growth. Thus, borrelidin might be a promising candidate for new antifungal agents against P. sojae.


Subject(s)
Glycine max/microbiology , Streptomyces/metabolism , Antifungal Agents/isolation & purification , Antifungal Agents/metabolism , Antifungal Agents/pharmacology , Fatty Alcohols/isolation & purification , Fatty Alcohols/metabolism , Fatty Alcohols/pharmacology , Phytophthora/drug effects , Streptomyces/chemistry , Streptomyces/isolation & purification
20.
J Insect Sci ; 12: 91, 2012.
Article in English | MEDLINE | ID: mdl-23427912

ABSTRACT

RNA interference (RNAi) is a technology for conducting functional genomic studies and a potential tool for crop protection against insect pests. Development of reliable methods for production and delivery of double-stranded RNA (dsRNA) is the major challenge for efficient pest control. In this study, Chilo infuscatellus Snellen (Crambidae: Lepidoptera) was fed with CiHR3 dsRNA expressed in bacteria or synthesized in vitro. The dsRNA ingested by C. infuscatellus successfully triggered silencing of the molt-regulating transcription factor CiHR3, an important gene for insect growth and development, and caused significant abnormalities and weight loss in insects within seven days of treatment. This study is an ideal example of feeding-based RNAi mediated by dsRNA expressed in bacteria or synthesized in vitro. The results also suggested that feeding-based RNA interference is a potential method for the management of C. infuscatellus.


Subject(s)
Insect Proteins/genetics , Moths/genetics , RNA, Double-Stranded/metabolism , Transcription Factors/genetics , Animals , Cloning, Molecular , Gene Silencing , Insect Proteins/metabolism , Larva/genetics , Larva/growth & development , Larva/metabolism , Molecular Sequence Data , Molting , Moths/growth & development , Moths/metabolism , Phylogeny , RNA Interference , Real-Time Polymerase Chain Reaction , Sequence Analysis, Protein , Sequence Analysis, RNA , Sequence Homology , Transcription Factors/metabolism
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