Selenite affected photosynthesis of Oryza sativa L. exposed to antimonite: Electron transfer, carbon fixation, pigment synthesis via a combined analysis of physiology and transcriptome.

Selenium (Se) is a microelement that can counteract (a)biotic stresses in plants. Excess antimony (Sb) will inhibit plant photosynthesis, which can be alleviated by appropriate doses of Se but the associated mechanisms at the molecular levels have not been fully explored. Here, a rice variety (Yongyou 9) was exposed to selenite [Se(IV), 0.2 and 0.8 mg L-1] alone or combined with antimonite [Sb(III), 5 and 10 mg L-1]. When compared to the 10 mg L-1 Sb treatment alone, addition of Se in a dose-dependent manner 1) reduced the heat dissipation efficiency resulting from the inhibited donors, Sb concentrations in shoots and roots, leaf concentrations of fructose, H2O2 and O2•-; 2) enhanced heat dissipation efficiency resulting from the inhibited accepters value, concentrations of Chl a, sucrose and starch, and the enzyme activity of adenosine diphosphate glucose pyrophosphorylase, sucrose phosphate synthase, and sucrose synthase; but 3) did not alter gas exchange parameters, concentrations of Chl b and total Chl, enzyme activity of soluble acid invertase, and values of maximum P700 signal, photochemical efficiency of PSI and electron transport rate of PSI. Se alleviated the damage caused by Sb to the oxygen-evolving complex and promoted the transfer of electrons from QA to QB. When compared to the 10 mg L-1 Sb treatment alone, addition of Se 1) up-regulated genes correlated to synthesis pathways of Chl, carotenoid, sucrose and glucose; 2) disturbed signal transduction pathway of abscisic acid; and 3) upregulated gene expression correlated to photosynthetic complexes (OsFd1, OsFER1 and OsFER2).

Discovery of novel hydroxyamidine based indoleamine 2,3-dioxygenase 1 (IDO1) and thioredoxin reductase 1 (TrxR1) dual inhibitors.

In order to take advantage of both immunotherapeutic and metabolic antitumor agents, novel dual indoleamine 2,3- dioxygenase 1 (IDO1) and thioredoxin reductase 1 (TrxR1) inhibitors were designed. Thioredoxin reductase 1 (TrxR1) is a main ROS modulator within CRC cells. Indoleamine 2,3-dioxygenase (IDO1) is crucial controller for tryptophan (Trp) metabolism that is also important for CRC immunotherapy. Herein, ten compounds 12a-j containing hydroxyamidine scaffold were designed, synthesized and evaluated for inhibitory activities against IDO1/TrxR1 enzyme and CRC cells. Among these compounds, the most active compound 12d (ZC0109) showed excellent and balanced activity against both IDO1 (IC50 = 0.05 µM) and TrxR1 (IC50 = 3.00 ± 0.25 µM) were selected for further evaluation. Compound ZC0109 exhibited good dual inhibition against IDO1 and TrxR1 both in vitro and in vivo. Further mechanistic studies reveal that, through IDO1 and TrxR1 inhibition by ZC0109 treatment, accumulated ROS effectively induced apoptosis and G1/S cell cycle arrest in cancer cells. In vivo evaluation demonstrated excellent anti-tumor effect of ZC0109 with the notable ability of promoting ROS-induced apoptosis, reducing kynurenine level in plasma and restoring anti-tumor immune response. Thus, ZC0109 represents a potential CRC therapy agent for further development.

Indexes of ferroptosis and iron metabolism were associated with the severity of diabetic nephropathy in patients with type 2 diabetes mellitus: a cross-sectional study.

Objective: To explore the correlations between diabetic nephropathy (DN) and serum levels of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), iron, transferrin (Tf), and ferritin in patients with type 2 diabetes mellitus (T2DM). Methods: According to the urinary albumin excretion rate(UAER) or estimated glomerular filtration rate (eGFR) levels, a total of 123 patients with T2DM were separately divided into normoalbuminuria (NO), microalbuminuria (MI), macroalbuminuria (MA) groups, and G1 (eGFR ≥ 90 mL/min), G2 (eGFR ≤ 60 mL/min to < 90 mL/min), and G3 groups (eGFR< 60 mL/min), with 33 healthy participants as the control (HC). The differences in serum GPX4, ACSL4, iron, Tf, and ferritin levels between groups were compared, and the relationships between these levels were analysed. The independent correlations between UAER or DN severity and serum GPX4, ACSL4, iron, Tf, and ferritin levels were analysed by multiple linear and multinomial logistic regression, respectively. Results: To the patients with T2DM, with the increase in UAER levels, GPX4, iron, and Tf levels gradually decreased, whereas ACSL4 levels increased, meanwhile with the decrease in eGFR levels, GPX4 and Tf levels gradually decreased, whereas ACSL4 levels increased. UAER were independently and positively correlated with ACSL4 [ß = 17.53, 95% confidence interval (CI; 11.94, 23.13)] and negatively correlated with GPX4 [ß = -1.633, 95% CI (-2.77, -0.496)] and Tf [ß = -52.94, 95% CI (-95.78, -10.11)].The NO and MI groups were considered as reference groups, respectively. The severity of DN was negatively correlated with serum GPX4 [odds ratio (OR) = 0.925 and 0.902, p =0.015 and 0.001], and Tf (OR = 0.109 and 0.119, p =0.043 and 0.034), and positively correlated with ACSL4 (OR = 1.952 and 1.865, both p <0.001) in the MA group. Conclusion: DN severity was negatively correlated with serum GPX4 and Tf levels and positively correlated with serum ACSL4 levels in patients with T2DM.

Toxicity of different forms of antimony to rice plants: Photosynthetic electron transfer, gas exchange, photosynthetic efficiency, and carbon assimilation combined with metabolome analysis.

Antimony (Sb) is a toxic metalloid, and excess Sb causes damage to the plant photosynthetic system. However, the underlying mechanisms of Sb toxicity in the plant photosynthetic system are not clear. Hydroponic culture experiments were conducted to illustrate the toxicity differences of antimonite [Sb(III)] and antimonate [Sb(V)] to the photosynthetic system in a rice plant (Yangdao No. 6). The results showed that Sb(III) showed a higher toxicity than Sb(V), judging from (1) lower shoot and root biomass, leaf water moisture content, water use efficiency, stomatal conductance, net photosynthetic rate, and transpiration rate; (2) higher water vapor deficit, soluble sugar content, starch content, and oligosaccharide content (sucrose, stachyose, and 1-kestose). To further analyze the direction of the photosynthetic products, we conducted a metabonomic analysis. More glycosyls were allocated to the synthesis pathways of oligosaccharides (sucrose, stachyose, and 1-kestose), anthocyanins, salicylic acid, flavones, flavonols, and lignin under Sb stress to quench excess oxygen free radicals (ROS), strengthen the cell wall structure, rebalance the cell membrane, and/or regulate cell permeability. This study provides a complete mechanism to elucidate the toxicity differences of Sb(III) and Sb(V) by exploring their effects on photosynthesis, saccharide synthesis, and the subsequent flow directions of glycosyls.

131I-Labeled Multifunctional Polyethylenimine/Doxorubicin Complexes with pH-Controlled Cellular Uptake Property for Enhanced SPECT Imaging and Chemo/Radiotherapy of Tumors.

INTRODUCTION: Smart theranostic nanosystems own a favorable potential to improve internalization within tumor while avoiding nonspecific interaction with normal tissues. However, development of this type of theranostic nanosystems is still a challenge. METHODS: In this study, we developed the iodine-131 (131I)-labeled multifunctional polyethylenimine (PEI)/doxorubicin (DOX) complexes with pH-controlled cellular uptake property for enhanced single-photon emission computed tomography (SPECT) imaging and chemo/radiotherapy of tumors. Alkoxyphenyl acylsulfonamide (APAS), a typical functional group that could achieve improved cellular uptake of its modified nanoparticles, was utilized to conjugate onto the functional PEI pre-modified with polyethylene glycol (PEG) with terminal groups of monomethyl ether and N-hydroxysuccinimide (mPEG-NHS), PEG with terminal groups of maleimide and succinimidyl valerate (MAL-PEG-SVA) through sulfydryl of APAS and MAL moiety of MAL-PEG-SVA. This was followed by conjugation with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), acetylating leftover amines of PEI, complexing DOX and labeling 131I to generate the theranostic nanosystems. RESULTS: The synthesized theranostic nanosystems exhibit favorable water solubility and stability. Every functional PEI can complex approximately 12.4 DOX, which could sustainably release of DOX following a pH-dependent manner. Remarkably, due to the surface modification of APAS, the constructed theranostic nanosystems own the capacity to achieve pH-responsive charge conversion and further lead to improved cellular uptake in cancer cells under slightly acidic condition. Above all, based on the coexistence of DOX and radioactive 131I in the single nanosystem, the synthesized nanohybrid system could afford enhanced SPECT imaging and chemo/radioactive combination therapy of cancer cells in vitro and xenografted tumor model in vivo. DISCUSSION: The developed smart nanohybrid system provides a novel strategy to improve the tumor theranostic efficiency and may be applied for different types of cancer.

Knockdown of carbohydrate sulfotransferase 12 decreases the proliferation and mobility of glioblastoma cells via the WNT/ß-catenin pathway.

Glioblastoma (GBM) is a common malignant tumor of the brain. Members of the carbohydrate sulfotransferase (CHST) family are deregulated in various cancer types. However, limited data are available on the role of the members of the CHST family in the development of GBM. The present study aimed to identify the role of significant members of the CHST family in GBM and explore the effects and molecular mechanisms of these significant members on GBM cell proliferation and mobility. In the current study, we demonstrated that CHST12 is the only member of CHST family that is upregulated in GBM tissues and associated with a lower survival rate according to the data obtained from The Cancer Genome Atlas. Similarly, the expression of CHST12 increased in GBM tissues than in adjacent tissues and had an important diagnostic value in distinguishing tumor tissues from adjacent tissues. The high expression of CHST12 indicated a lower overall survival rate, was negatively associated with the Karnofsky Performance Scale score, was positively associated with the KI67 expression rate, and was an independent risk factor for GBM. Knockdown of CHST12 significantly decreased GBM cell proliferation and mobility and inhibited the Wnt/ß-catenin pathway. Restoration of ß-catenin expression in GBM cells reversed the inhibitory effects of CHST12 knockdown on GBM cell proliferation and mobility. In conclusion, the present study demonstrated that CHST12 may be a novel biomarker for GBM; it regulates GBM cell proliferation and mobility via the WNT/ß-catenin pathway.

Charge-conversional polyethylenimine-entrapped gold nanoparticles with 131I-labeling for enhanced dual mode SPECT/CT imaging and radiotherapy of tumors.

Novel theranostic nanosystems demonstrate great potential to achieve timely diagnosis and effective therapy at the same time. However, due to the relatively low accumulation of theranostic nanosystems at the tumor site, the theranostic efficiency is limited. In this study, a novel theranostic nanosystem with a pH-responsive charge conversion property was constructed to improve the cellular uptake towards cancer cells for enhanced single photon emission computed tomography (SPECT)/computed tomography (CT) dual mode imaging and radiotherapy of tumors. In detail, polyethylenimine (PEI) was utilized as a nanoplatform to link with polyethylene glycol (PEG) monomethyl ether with one end of N-hydroxylsuccinimide (mPEG-NHS), PEG with ends of maleimide and succinimidyl valerate (MAL-PEG-SVA), alkoxyphenyl acylsulfonamide (APAS), 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), and fluorescein isothiocyanate (FI), successively. The formed functionalized PEI was then utilized to entrap gold nanoparticles, acetylate the remaining amines of PEI and label with radioactive iodine-131 (131I) to build theranostic nanosystems. The result demonstrated that the theranostic nanosystem has a 3.8 nm Au core and showed excellent colloidal stability. On account of the charge conversion property of APAS, the APAS linked PEI entrapped gold nanoparticles could switch from neutral to positive in a slightly acidic microenvironment, which induced improved cellular uptake. Above all, after 131I labeling, the generated theranostic nanosystem could achieve enhanced SPECT/CT dual mode imaging and radiotherapy of cancer cells in vitro and a xenograft tumor model in vivo. The constructed APAS-linked PEI nanosystem has great potential to be used as a model for SPECT/CT imaging and radiotherapy of various types of cancer.

Efficiency and risks of selenite combined with different water conditions in reducing uptake of arsenic and cadmium in paddy rice.

The co-contamination of arsenic (As) and cadmium (Cd) in soils is a common problem. Selenium (Se) can reduce the uptake of As and Cd in plants, and in practice, the alternate wetting and drying is a common culture mode in rice production. However, it is unknown whether Se can efficiently reduce As and Cd concentrations in crops suffering from a high-level contamination of As and Cd under different soil water conditions. In this study, we assessed the efficiency and risks of selenite [Se(IV)], in a pot experiment, to reduce the uptake of As and Cd in a rice plant (YangDao No 6) growing in a heavily contaminated soil by As and Cd (pH 7.28) under different soil water conditions. The results showed that Se(IV) failed to control the grain total As and Cd concentrations within their individual limited standard (0.2 mg kg-1) despite that Se(IV) significantly reduced the grain total As and Cd concentrations. The soil drying treatment alone could reduce the accumulation of arsenite [As(III)] in the grains, but additional Se(IV) stimulated the accumulation of As(III) in the grains under soil drying conditions. In addition, the addition of Se(IV) enhanced the As and Cd concentrations in the shoots and/or roots of rice plants under certain conditions. The above results all suggested that the utilization of Se(IV) in a high contaminated soil by As and Cd cannot well control the total concentrations of As and Cd in plants. In this study, the available concentrations of As and Cd in the rhizosphere soil, the rhizosphere soil pH, the formation of root iron/manganese plaques and the concentrations of essential elements in the grains were monitored, and the related mechanisms on the changes of these parameters were also discussed. This study will give a guideline for the safe production of rice plants in a heavily co-contaminated soil by As and Cd.

Amperometric immunoassay for the carcinoembryonic antigen by using a peroxidase mimic consisting of palladium nanospheres functionalized with glutathione-capped gold nanoparticles on graphene oxide.

A composite nanoenzyme was used in a sandwich-type electrochemical immunoassay for the carcinoembryonic antigen (CEA). Hierarchically porous palladium nanospheres (Pd NPs) were functionalized with glutathione-capped gold nanoparticles (G-Au NPs) and then loaded onto graphene oxide (GO) to obtain a peroxidase mimicking nanoenzyme of type GO-supported G-Au/Pd. The composite can catalyze the oxidation of the substrate tetramethylbenzidine (TMB) by H2O2 to give blue-colored oxidized TMB within only 20 s. This strong peroxidase activity, good conductivity and high specific surface area of the material make it a useful label for secondary antibodies (Ab2) for the detection of CEA. The cotton-like electrodeposited gold nanoparticles with good electrical conductivity were used to immobilize primary antibody (Ab1). The amperometric immunoassay has a detection range that extends from 10 fg·mL-1 to 100 ng·mL-1 at a working potential of -0.4 V with addition of 5 mmol·L-1 H2O2 as electrochemically active substrate, and the detection limit is as low as 3.2 fg·mL-1 (S/N = 3). Graphical abstract Schematic of sandwich electrochemical immunosensor for the carcinoembryonic antigen. Electrodeposited gold used as substrate material, and Graphene oxide supported G-Au NPs functionalized porous Pd nanospheres (GO supported G-Au/Pd) as signal amplification platform, which catalyze the oxidation of tetramethylbenzidine (TMB).

An organocatalytic method for constructing pyrroles via the cycloisomerisation of Z-1-iodo-4-N-methylbenzenesulfonyl-1,6-enynes.

A new cycloisomerisation of Z-1-iodo-4-N-methylbenzenesulfonyl-1,6-enynes to functionalized pyrroles was realized in the presence of an organomolecule (4,4'-bis(1,1-dimethylethyl)-2,2'-bipyridine) and KOtBu. The transformations were performed efficiently to produce different kinds of functionalized pyrroles within 10 min. This is the first example of an organomolecule promoted methodology with vinyl iodides from a non-aromatic system to an aromatic system, which offers an excellent option toward establishing a new horizon for cross-coupling reactions of vinyl halides. Preliminary mechanistic studies were performed and a crude radical pathway was proposed.

Sensitive amperometric immunosensor with improved electrocatalytic Au@Pd urchin-shaped nanostructures for human epididymis specific protein 4 antigen detection.

Sensitive detection of early ovarian cancer is imminent for women's health. Human epididymis specific protein 4 antigen (HE4 Ag), as a novel tumor marker, has good specificity and sensitivity in ovarian cancer markers, especially for the detection of early ovarian cancer. In this work, a novel and ultrasensitive sandwich-type amperometric electrochemical immunosensor was constructed using amine modified graphene supported gold nanorods (Au NRs/NH2-GS) as a sensor platform and core-shell Au@Pd urchin-shaped nanostructures (Au@Pd USs) as a label of the secondary antibodies (Ab2, Au@Pd USs-Ab2) to realize the quantitative determination of HE4 Ag. The Au NRs/NH2-GS were used for increasing the electrode surface area and effectively immobilizing primary antibodies (Ab1) due to its good water-solubility. The Au@Pd USs have special morphology with high crystal surface index and good stability, capable of loading secondary antibodies (Ab2) and providing a larger active site for the catalysis of hydrogen peroxide (H2O2). The proposed immunosensor displays excellent performance for HE4 Ag detection over the range from 1 pmol L-1 to 50 nmol L-1 with a detection limit of 0.33 pmol L-1 (signal-to-noise ratio of 3). Moreover, the designed immunosensor exhibits excellent reproducibility, selectivity, and stability, which shows great potential in clinical diagnosis.

Palladium-catalyzed intermolecular [4 + 2] formal cycloaddition with (Z)-3-iodo allylic nucleophiles and allenamides.

A highly chemo- and regioselective [4 + 2] formal cycloaddition of (Z)-3-iodo allylic nucleophiles and allenamides catalyzed by palladium is reported. The methodology proceeds under mild reaction conditions and is tolerant of alkyl and aryl functional groups. The SN2' substitution at the proximal C[double bond, length as m-dash]C bond performed against the Heck or SN2 pathway delivered a variety of 2-amino-dihydropyrans and 2-amino-tetrahydropiperidines in moderate to satisfactory yields. The [4 + 2] formal cycloaddition derivatives are convertible to interesting scaffolds 2,6,7,7a-tetrahydropyrano[2,3-b]pyrrole and 2,6,7,7a-tetrahydro-1H-pyrrolo[2,3-b]pyridine derivatives via ring-closing metathesis (RCM) with Grubbs catalyst II.

Validation of Housekeeping Genes as Reference for Reverse-Transcription-qPCR Analysis in Busulfan-Injured Microvascular Endothelial Cells.

Endothelial cells (ECs) could express some important cytokines and signal molecules which play a key role in normal hematopoiesis and repopulation. Busulfan-induced vascular endothelial injury is an important feature after hematopoietic stem cell transplantation (HSCT). But the molecular mechanism of how the injured ECs affect hematopoietic reconstruction is still unknown. It is possibly through modulation of the change of some gene expression. RT-qPCR is one of the most popular methods used to accurately determine gene expression levels, based on stable reference gene (RG) selection from housekeeping genes. So our aim is to select stable RGs for more accurate measures of mRNA levels during Busulfan-induced vascular endothelial injury. In this study, 14 RGs were selected to investigate their expression stability in ECs during 72 hours of EC injury treated with Busulfan. Our results revealed extreme variation in RG stability compared by five statistical algorithms. ywhaz and alas1 were recognized as the two idlest RGs on account of the final ranking, while the two most usually used RGs (gapdh and actb) were not the most stable RGs. Next, these data were verified by testing signalling pathway genes ctnnb1, robo4, and notch1 based on the above four genes ywha, alas1, gapdh, and actb. It shows that the normalization of mRNA expression data using unstable RGs greatly affects gene fold change, which means the reliability of the biological conclusions is questionable. Based on the best RGs used, we also found that robo4 is significantly overexpressed in Busulfan-impaired ECs. In conclusion, our data reaffirms the importance of RGs selection for the valid analysis of gene expression in Busulfan-impaired ECs. And it also provides very useful guidance and basis for more accurate differential expression gene screening and future expanding biomolecule study of different drugs such as cyclophosphamide and fludarabine-injured ECs.

Macrophages ameliorate bone marrow inflammatory injury and promote hematopoiesis in mice following hematopoietic stem cell transplantation.

Bone marrow macrophages have been demonstrated to serve a critical role in promoting maintenance and retention of hematopoietic stem cells (HSCs). Our previous study indicated increased macrophages infiltration in bone marrow after HSC transplantation (HSCT). However, it is not well understood whether macrophages affect hematopoietic reconstitution after HSCT. The present study aimed to investigate the role of macrophages in hematopoietic reconstitution after HSCT. BALB/c mice were divided into HSCT, HSCT+Clodronate Liposomes, HSCT+PBS Liposomes, HSCT+RS102895 and HSCT+Vehicle groups and sacrificed on day 7, 14, 21, 28 and 35 after HSCT. Analysis was performed to detect the changes of bone marrow pathology by H&E staining and the number of macrophages was assessed by immunohistochemical staining and western blot analysis. The number of c-kit+sca-1+ and c-kit+ was measured by flow cytometry. Mice with a depletion of bone marrow macrophages displayed significantly reduced overall survival, delayed hematopoietic recovery, a reduced number of hematopoietic stem/progenitor cells and bone marrow cells as well as exaggerated bone marrow injury. However, compared with the HSCT+Vehicle group, mice with an increased number of bone marrow macrophages exhibited no difference of overall survival, had accelerated hematopoietic reconstitution, a higher number of hematopoietic stem/progenitor cells and bone marrow cells and ameliorated bone marrow injury. In conclusion, the present study indicated that bone marrow macrophages serve a protective role in bone marrow injury and may promote hematopoiesis in mice after HSCT, suggesting manipulation of macrophages may be a novel strategy for improving the efficacy of HSCT.

Controlling the cleavage of the inter- and intra-molecular linkages in lignocellulosic biomass for further biorefining: A review.

The abundant intermolecular linkages among cellulose, hemicellulose and lignin significantly limit the utilization of the most promising renewable biomass. Process control with solvents, catalysts and temperature is of significant importance providing ways to break the above linkages, and benefiting to the further conversion of the main biomass components to small molecular products. This article discusses the effect of catalyst under hydrothermal and organosolv treatment emphasizing the cleavage of the intermolecular linkage. Acidic catalysts show good performance on cleaving the linkages between carbohydrates and lignin. Basic catalysts promoted the dissolution of lignin component. Hydrogenolysis assisted conversion of lignin can efficiently break the intermolecular linkages to yield lignin-derived bio-oil, especially in co-solvent reaction system. Besides, the effects of single solvent and co-solvent systems, as well as the cleavage of the intramolecular linkages to yield target chemicals are also included. Several further study strategies are proposed.

Effects of ezetimibe and anticoagulant combined therapy on progressing stroke: a randomized, placebo-controlled study.

Despite the high prevalence of progressing stroke in patients with acute stroke, preventative treatments are still the unmet needs for those patients. The aim of this study was to evaluate, prospectively, the efficacy and safety of ezetimibe in the prevention of acute progressing stroke and thereby the improvement of patient outcome. A total of 423 patients (267 men and 156 women with a mean age of 65.2 years) were randomly assigned to receive ezetimibe (10 mg daily oral administration, n = 209) or placebo (n = 214) for 14 consecutive days. Analytical procedures performed at baseline (i.e., day 1) and 14 days after the treatments were completed. These included a real-time three-dimensional ultrasound (RT-3DU) examination for carotid plaque volume, clinical laboratory analyses of serum levels of IL-6 and MMP-9, as well as lipid parameters and liver dysfunction marker ALT and TBIL. Ezetimibe significantly reduced the average NIHSS score after 14 days of treatment and attenuated the stroke progression rate, which was associated with reduction in carotid plaque volume and attenuation of serum levels of IL-6, MMP-9, and LDL, without inducing liver dysfunction. Ezetimibe treatment may be a beneficial and effective strategy for preventing progressing stroke.

The autism-related gene SNRPN regulates cortical and spine development via controlling nuclear receptor Nr4a1.

The small nuclear ribonucleoprotein polypeptide N (SNRPN) gene, encoding the RNA-associated SmN protein, duplications or deletions of which are strongly associated with neurodevelopmental disabilities. SNRPN-coding protein is highly expressed in the brain. However, the role of SNRPN protein in neural development remains largely unknown. Here we showed that the expression of SNRPN increased markedly during postnatal brain development. Overexpression or knockdown of SNRPN in cortical neurons impaired neurite outgrowth, neuron migration, and the distribution of dendritic spines. We found that SNRPN regulated the expression level of Nr4a1, a critical nuclear receptor during neural development, in cultured primary cortical neurons. The abnormal spine development caused by SNRPN overexpression could be fully rescued by Nr4a1 co-expression. Importantly, we found that either knockdown of Nr4a1 or 3, 3'- Diindolylmethane (DIM), an Nr4a1 antagonist, were able to rescue the effects of SNRPN knockdown on neurite outgrowth of embryonic cortical neurons, providing the potential therapeutic methods for SNRPN deletion disorders. We thus concluded that maintaining the proper level of SNRPN is critical in cortical neurodevelopment. Finally, Nr4a1 may serve as a potential drug target for SNRPN-related neurodevelopmental disabilities, including Prader-Willi syndrome (PWS) and autism spectrum disorders (ASDs).

Novel function of PIWIL1 in neuronal polarization and migration via regulation of microtubule-associated proteins.

BACKGROUND: Young neurons in the developing brain establish a polarized morphology for proper migration. The PIWI family of piRNA processing proteins are considered to be restrictively expressed in germline tissues and several types of cancer cells. They play important roles in spermatogenesis, stem cell maintenance, piRNA biogenesis, and transposon silencing. Interestingly a recent study showed that de novo mutations of PIWI family members are strongly associated with autism. RESULTS: Here, we report that PIWI-like 1 (PIWIL1), a PIWI family member known to be essential for the transition of round spermatid into elongated spermatid, plays a role in the polarization and radial migration of newborn neurons in the developing cerebral cortex. Knocking down PIWIL1 in newborn cortical neurons by in utero electroporation of specific siRNAs resulted in retardation of the transition of neurons from the multipolar stage to the bipolar stage followed by a defect in their radial migration to the proper destination. Domain analysis showed that both the RNA binding PAZ domain and the RNA processing PIWI domain in PIWIL1 were indispensable for its function in neuronal migration. Furthermore, we found that PIWIL1 unexpectedly regulates the expression of microtubule-associated proteins in cortical neurons. CONCLUSIONS: PIWIL1 regulates neuronal polarization and radial migration partly via modulating the expression of microtubule-associated proteins (MAPs). Our finding of PIWIL1's function in neuronal development implies conserved functions of molecules participating in morphogenesis of brain and germline tissue and provides a mechanism as to how mutations of PIWI may be associated with autism.

[Grey relational analysis on fingerprint of Vernonia anthelmintica extracts and its effect on proliferation of A375 human melanoma cells].

OBJECTIVE: To establish the fingerprint of Vernonia anthelmintica extracts of different ethanol concentrations to study the effect of common peak components on the proliferation of A375 human melanoma cells and the correlation between fingerprint and pharmacodynamics of V. anthelmintica extracts, in order to provide both theoretical basis and data support for establishing a traditional Chinese medicine quality control mode with the combination of fingerprint and pharmacology. METHOD: HPLC was applied to establish fingerprint of V. anthelmintica extracts of different ethanol concentrations and the similarity evaluation was made. MTT was used to study the proliferation of A375 human melanoma cells. Grey relation analysis was adopted to analyze the correlation between fingerprint and pharmacology of V. anthelmintica. RESULT: The HPLC fingerprint of different V. anthelmintica ethanol extracts showed 13 common peaks with the proliferation effect on A375 human melanoma cells. The 4th peak had the largest contribution and highest correlation to cell proliferation. CONCLUSION: Different V. anthelmintica ethanol extracts have different fingerprints, which show a certain correlation between their common peaks and effect on cell proliferation.

A polyoxometalate-based Pd(II)-coordinated ionic solid catalyst for heterogeneous aerobic oxidation of benzene to biphenyl.

An ionic solid catalyst by pairing Keggin polyoxometalate-anions with Pd(II)-coordinated nitrile-tethered ionic liquid cations was synthesized, characterized, and tested for aerobic oxidation of benzene to biphenyl. A unique heterogeneous intramolecular electron transfer mechanism is proposed to understand its high activity.