Gene silencing of NR2B-containing NMDA receptor by intrathecal injection of short hairpin RNA reduces formalin-induced nociception in C57BL/6 mouse.

Spinal NR2B-containing N-methyl-D-aspartate receptors (NR2B) play a critical role in the formation of central sensitization and persistent pain. Previous studies show that gene silencing of the spinal NR2B subunit by small interfering RNA (siRNA) could alleviate nociception in animals. The siRNA is a 19- to 23-nt RNA duplex, which can be synthesized in vitro or derived from short hairpin RNAs (shRNAs). In the present study, we investigated whether intrathecal injection of shRNAs targeting NR2B (GRIN2B shRNA) could affect nociception on formalin-induced pain in mice. Our results showed that intrathecal injection of GRIN2B shRNA could decrease NR2B mRNA and protein expression levels and hence effectively relieve formalin-induced nociception in mice, suggesting that intrathecal delivery of GRIN2B shRNA can be an efficient way to silence the target gene and provide new insights into the treatment of chronic pain.

[Study on mechanism of thyroid cytotoxicity of ammonium perchlorate].

OBJECTIVE: To investigate the mechanism of thyroid cytotoxicity mechanism of ammonium perchlorate (AP). METHODS: Thyroid cells were cultured in vitro to a certain stage and then exposed to AP (0, 5, 10, 20, 40, and 60 mmol/L) in culture solution; the cultured cells and supernatant were collected. Cell viability was measured by MTT assay; cell apoptosis was determined by flow cytometry; the concentration of thyroglobulin was measured by enzyme-linked immunosorbent assay; the lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, and so on were measured by colorimetry. RESULTS: The cells exposed to 60 mmol/L AP for 12, 24, 48, and 72 h had cell viabilities of 74.93%, 42.26%, 2.66%, and 0.99%, respectively, and the cells exposed to 40 mmol/L AP for 24, 48, and 72 h had cell viabilities of 73.15%, 30.91%, and 3.03%, respectively, all significantly lower than that of the control group (100%)(P < 0.05 or P < 0.01). The overall apoptosis rate of all AP-exposed cells was significantly higher than that of the control group; the cells exposed to 20, 40, and 60 mmol/L AP had early apoptosis rates of 15.70%, 15.84%, and 16.96%, respectively, significantly higher than that of the control group (9.54%)(P < 0.05 or P < 0.01); the cells exposed to 60 mmol/L AP had a late apoptosis rate of 16.54%, significantly higher than that of the control group (6.11%)(P < 0.05 or P < 0.01). The cells exposed to 40 mmol/L AP had a significantly higher LDH activity than the control group (0.70 U/ml vs 0.55 U/ml, P < 0.01). The cells exposed to 5 mmol/L AP had a significantly higher MDA level than the control group (1.08 mmol/L vs 2.36 mmol/L, P < 0.05). CONCLUSION: AP can markedly change the cell morphology and decrease the cell viability of thyroid cells, which may be because AP inhibits cell proliferation, induces cell apoptosis, and destroys cell membranes. However, AP does not result in significant oxidative damage to thyroid cells.

Characteristic volatiles fingerprints in olive vegetable stored at different conditions by HS-GC-IMS.

The olive vegetable is popular food owing to its unique flavor. This study innovatively used headspace-gas chromatography-ion mobility spectrometry to evaluate olive vegetables' volatiles under different conditions. A total of 57 volatile compounds were determined from olive vegetables, including 30 aldehydes, 8 ketones, 5 alcohols, 2 esters, 8 hydrocarbons, 1 furans, 3 sulfur compounds. The PCA distinguished the olive vegetable stored at different conditions by volatiles. The gallery plot showed that olive vegetables stored at 4 °C for 21 d produced more limonene, which had a desirable fruity odor. The (E)-2-octenal, (E)-2-pentenal, (E,E)-2,4-heptadienal, 5-methylfurfural, and heptanal in fresh olive vegetables were lowest and increased with storage time. Furthermore, the change of volatiles was the least when the olive vegetable was stored at 0 °C. This study can provide theoretical bases for improving the flavor quality of olive vegetables and developing traditional food for standardized industrial production.

The effects of ammonium perchlorate on thyroid homeostasis and thyroid-specific gene expression in rat.

Perchlorate, a kind of inorganic chemical, is mainly used in defense industry and widely used in other civilian areas. It was well known that perchlorate exerts its thyrotoxicant effect on thyroid homeostasis via competitive inhibition of iodide uptake. However, some details of mechanism by which perchlorate disturb thyroid homeostasis are unknown and remain to be elucidated. The present study aimed to investigate if iodide insufficiency in the thyroid is the main mechanism by which perchlorate exerts its effect on the thyroid gland. We highlighted and measured the gene expression of NIS, Tg, and TPO which involved in thyroid hormone biosynthesis. Thyroid effects of perchlorate were identified by assessing different responses of these genes at the treatments of perchlorate and iodine deficiency. The results indicated that high dose perchlorate (520 mg kg(-1) b.wt.) can induce a significant decrease in body weight and cause hypertrophy of thyroid gland, with a decreased level of FT3, FT4 and a remarkable increased level of TSH. In addition, the significant decreased gene expression of Thyroglobulin (Tg) and thyroperoxidase (TPO) were both observed at the treatment of high dose perchlorate. These results suggested that perchlorate can suppress gene expression of Tg and TPO which directly involved in biosynthesis of thyroid hormones, and may therefore aggravate the perturbation of thyroid homeostasis in addition to competitive inhibition of iodide uptake.

Personalized nutrition: A review of genotype-based nutritional supplementation.

Nutritional disorders have become a major public health issue, requiring increased targeted approaches. Personalized nutrition adapted to individual needs has garnered dramatic attention as an effective way to improve nutritional balance and maintain health. With the rapidly evolving fields of genomics and nutrigenetics, accumulation of genetic variants has been indicated to alter the effects of nutritional supplementation, suggesting its indispensable role in the genotype-based personalized nutrition. Additionally, the metabolism of nutrients, such as lipids, especially omega-3 polyunsaturated fatty acids, glucose, vitamin A, folic acid, vitamin D, iron, and calcium could be effectively improved with related genetic variants. This review focuses on existing literatures linking critical genetic variants to the nutrient and the ways in which these variants influence the outcomes of certain nutritional supplementations. Although further studies are required in this direction, such evidence provides valuable insights for the guidance of appropriate interventions using genetic information, thus paving the way for the smooth transition of conventional generic approach to genotype-based personalized nutrition.

[The effects of ammonium perchlorate on thyroid function and testis in male rats].

OBJECTIVE: To study the effects of ammonium perchlorate (AP) on the levels of thyroid hormone and the testis function of male rats. METHODS: Twenty male rats were randomly divided into 4 groups: control group, low, middle and high AP group. The rats were exposed orally to 0, 130, 260 and 520 mg AP/kg a day for 80 days. The levels of thyroid hormone, testosterone in serum and sperm motility were measured and the testis histological change was observed as well. RESULTS: The increase of body weight in high AP group was significantly lower than that in the control group (P < 0.01). The organ coefficients of testis and thyroid in high AP group obviously enhanced, as compared with the control group (P < 0.01). The free thyroxin (FT4) levels of serum in all AP treated groups were significantly lower than that of the control group (P < 0.05). There were no differences of serum FT3 levels between all AP groups and control group, while serum TSH levels in middle and high AP groups decreased significantly, as compared with control group (P < 0.01). In terms of sperm motility, the percentage of Grade A and B sperm in middle and high groups were 12.3% +/- 2.52% and 14.8% +/- 5.93%, 17.7% +/- 4.63%, 15.8% +/- 2.28% respectively, which were significantly lower than that (27.8% +/- 8.70%) in control group (P < 0.01). The percentage of Grade D sperm in middle and high groups were 38.0% +/- 3.61% and 40.0% +/- 8.99%, respectively, which were significantly higher than that (17.0% +/- 5.00%) in control group (P < 0.01). No difference of serum testosterone level between all AP groups and control group was observed. CONCLUSION: AP can influence the levels of thyroid hormone and reduce the serum FT4 levels in rats. The main toxic effects on male reproductive system may decrease the sperm motility.

[The effects of ammonium perchlorate on thyroid function and mRNA expression of thyroglobulin and thyroperoxidase].

OBJECTIVE: To investigate the effects of ammonium perchlorate (AP) on thyroid functions and mRNA expression levels of thyroglobulin (Tg) and thyroperoxidase (TPO) genes of rats. METHODS: Thirty SD male rats were randomly divided into six groups: control group, iodine-deficient group, low dose AP group (130 mg/kg), moderate dose AP group (260 mg/kg), high dose AP group (520 mg/kg) and high iodine-combined group. After the rats were exposed orally for 90 days, serum free-thyroxine (FT(4)), free-triiodothyronine (FT(3)) and thyroid stimulating hormone (TSH) were measured using radioimmunoassays. mRNA expression levels of thyroglobulin (Tg) and thyroperoxidase (TPO) genes were detected by real-time quantitative PCR. RESULTS: Serum FT(4) levels in moderate dose AP group and high dose AP group were [(9.540 ± 1.327) fmol/ml] and [(6.509 ± 1.949) fmol/ml] respectively, which were significantly lower than that [(13.505 ± 1.276) fmol /ml] in control group (P < 0.05 or P < 0.01). Serum TSH level in high dose AP group was [(1.227 ± 0.295) mIU/L], which was significantly higher than that [(0.545 ± 0.282) mIU/L] in control group (P < 0.05). The mRNA expression levels of thyroglobulin (Tg) gene in all groups exposed to AP were significantly lower than that in control group (P < 0.01). The mRNA expression level of thyroperoxidase (TPO) gene in high dose AP group was significantly higher than that in control group (P < 0.05). CONCLUSION: AP can reduce the serum FT(3) and FT(4) levels of rats, increase the serum TSH level of rats and decrease obviously the mRNA expression levels of Tg and TPO genes. In addition, high iodine can reduce the toxic effects of AP on thyroid gland of rats to some extent.

Behavior Towards R&D Investment of Family Firms CEOs: The Role of Psychological Attribute.

INTRODUCTION: This study aims to explore the effects of the behavior of chief executive officers (CEOs) within family firms on investment in research and development (R&D). We also investigate the effect of CEOs' psychological attributes of overconfidence on R&D investment and the moderating effect between the types of CEOs and R&D investment. METHODS: We obtained data on Chinese A-share firms from China Stock Exchange and Accounting Research from 2010 to 2018 for analysis. Then, we used the ordinary least squares model for regression results; moreover, the Tobit regression, GMM and firm fixed effect model are applied to check the robustness of the results. RESULTS: Family CEOs with actual control rights are more open to R&D investment, whereas those without actual control rights exhibit negative behavior. The study found that non-family CEOs exhibit insignificant results and negative predicted signs toward R&D investment. Moreover, the results show that overconfident CEOs are more inclined to amplify innovation. Furthermore, results on the moderating effects of CEO psychological attribute of overconfidence indicate that the CEO overconfidence mitigates the negative relationship between family CEOs with actual control rights and R&D investment. However, no moderating effect is found between family CEOs without actual control and R&D investment. The CEO psychological attribute behavior is positive between non-family CEOs and R&D investment. DISCUSSION: This novel study explores the behavioral effect of different types of family firm CEOs on R&D investment. This study will assist corporate board members to make more informed decisions about retaining (or bringing back) family CEOs (with or without actual control rights) or hiring non-family CEOs.

Design, preparation, characterization, and application of MnxCu1-xOy/γ-Al2O3 catalysts in ozonation to achieve simultaneous organic carbon and nitrogen removal in pyridine wastewater.

In the process of treating high-concentration pyridine wastewater, problems such as low treatment efficiency and total nitrogen (TN) residues are always encountered. Catalytic ozonation can degrade pyridine wastewater well, and it also has the potential to remove TN. However, limited research has been conducted on the development of ozonation catalysts that can simultaneously remove the total organic carbon (TOC) and TN. Density functional theory (DFT) technology can determine the number of active components on the catalyst based on its composition; therefore, it can be used to guide the research and development of such catalysts. Here, we presented a strategy to guide the preparation of two-component Mn and Cu catalysts using DFT technology. By characterising and applying the prepared MnxCu1-xOy/γ-Al2O3 catalysts, it was confirmed that the DFT accurately predicted the changes in the active site content. The selected catalyst also achieved strong TOC and TN removal rates during the catalytic ozonation of high-concentration pyridine wastewater. A Box-Behnken design and response surface methodology was used to optimise the process conditions of catalytic ozonation and verify its stability. Under the optimal reaction conditions, the TOC and TN removal efficiencies from a 500 mg/L pyridine solution were 99.8% and 45.8%, respectively. This work indicated that the use of DFT for the design of catalytic materials was an effective method, which can provide a theoretical basis for material design and reduce the time for material screening.

Sulphur-based autotrophic denitrification of wastewater obtained following graphite production: Long-term performance, microbial communities involved, and functional gene analysis.

Sulphur-based autotrophic denitrification is an energy-efficient NO3--N removal process; it does not require carbon and may potentially replace traditional denitrification processes. This process was used to treat graphite production-derived wastewater and achieved almost complete removal of NO3--N (concentration in effluent: 5.2 mg/L; concentration in influent: 606 mg/L) at a salinity of 15 g/L with a 30 h hydraulic retention time. A unique microbial community was established, in which the abundance of Thiobacillus increased with the increase of the NO3--N concentration and salinity. Metagenomic analysis revealed that the denitrification metabolic pathway in the bioreactor was active. It also revealed the increased activation of nhaH, a gene encoding Na+/H+ antiporters; proA, proB, and proC, genes encoding proline; and Trk and Kdp systems during the treatment of graphite production-derived wastewater to maintain cell function, providing valuable information about utilizing the sulphur-based autotrophic denitrification process to treat graphite production-derived wastewater.

Nano ferrites (AFe2O4, A = Zn, Co, Mn, Cu) as efficient catalysts for catalytic ozonation of toluene.

Nano ferrites (AFe2O4, A = Zn, Co, Mn, Cu) were supported on the surface of γ-Al2O3 support by hydrothermal synthesis to prepare a series of novel composite catalysts (AFe2O4/γ-Al2O3) for catalytic ozonation for elimination of high concentration toluene at ambient temperature. The characterization results showed that the high-purity nano-AFe2O4 particles were uniformly loaded on mesoporous γ-Al2O3. Further, it was confirmed that among the several catalysts prepared, the amount of oxygen vacancies (Ovs), Lewis acid sites (LAS), and Brønsted acid sites (BAS) of the ZnFe2O4/γ-Al2O3 catalyst were the highest. This meant that the ZnFe2O4/γ-Al2O3 catalyst had a strong adsorption capacity for toluene and ozone (O3), and had a strong catalytic activity. When the temperature was 293 K and the space velocity was 1500 h-1, the mol ratio of O3 to toluene was 6, the degradation rate of toluene (600 mg m-3) can reach an optimum of 99.8%. The results of electron paramagnetic resonance (EPR) and Fourier infrared (FT-IR) proved superoxide radicals and hydroxyl radicals by catalytic ozonation. Moreover, the GC-MS analysis results indicated that the toluene degradation began with the oxidation of methyl groups on the benzene ring, eventually producing CO2 and H2O. After repeated experiments, the toluene degradation rate remained stable, and the residual content of O3 in each litre of produced gas was less than 1 mg L-1, thereby indicating that the ZnFe2O4/γ-Al2O3 catalyst had excellent reusability and showed great potential for the treatment of toluene waste gas.

Acoustically enhanced photodetection by a black phosphorus-MoS2 van der Waals heterojunction p-n diode.

We developed a new way to enhance the photoresponsivity of a van der Waals heterojunction p-n diode using surface acoustic waves (SAWs). The diode was constructed on top of a piezoelectric LiNbO3 substrate and composed of p-type black phosphorus (BP) and n-type molybdenum disulfide (MoS2) flakes that partly overlapped with each other. This layout facilitated the applied SAWs to rapidly drive carriers out of the depletion region. In this structural design, SAWs promoted the separation of photogenerated carriers, and thus greatly increased the photocurrent. The measured photocurrent for the device with SAWs was about 103 times higher than that of the device without SAWs. The device using SAWs showed a photoresponsivity as high as 2.17 A W-1 at the wavelength of 582 nm. This excellent performance was attributed to the SAWs suppressing electron-hole recombination in the device under light illumination. Our device exhibits promise as a high-performance photodetector and reveals new possibilities for acoustic devices in optoelectronics.

Gastro-floating bilayer tablets for the sustained release of metformin and immediate release of pioglitazone: preparation and in vitro/in vivo evaluation.

Owing to the complementary mechanisms of action of metformin hydrochloride (MH) and pioglitazone hydrochloride (PG), combination therapy for type 2 diabetes mellitus using the two drugs is highly desired; on the other hand, MH is not well absorbed in lower gastrointestinal tract and has a short half-life, therefore compromising the therapeutic effects. Herein, the present study was to develop gastro-floating bilayer matrix tablets in which the two drugs were incorporated into two separate layers, aiming at sustaining MH release with enhanced absorption and achieving immediate release of PG. The tablets of the optimized formulation floated on the test medium for more than 24 h with 5 min of floating lag time, and sustained MH release for 12 h via a diffusion-dependent manner; and complete release of PG within 5 min were achieved. Moreover, a steady plasma concentration of MH with a 1.5-fold increase in bioavailability, decreased C(max) and reduced T(max) was obtained, and the in vivo behavior of PG was similar to the marked product. Summarily, sustained MH release with improved absorption and immediate release of PG were obtained simultaneously using the gastro-floating bilayer tablet, allowing strengthened combination therapy for diabetes mellitus.

[The effect of ventricular fibrillation time and NYHA classification on defibrillation in intensive care unit patients].

OBJECTIVE: To investigate whether the sequence of defibrillation (DF) and cardiopulmonary resuscitation (CPR), duration of ventricular fibrillation (VF), and New York Heart Association (NYHA) classification would affect DF result in intensive care unit. METHODS: Ninety-three cases needing instantaneous DF were divided into three groups according to VF lasting time: <4 minute group (n=53), 4 - 8 minute group (n=24), >8 minute group (n=16), and each group was randomly divided into two sub-groups according to time sequence: the prior DF group or the prior CPR for five cycles followed by DF group (prior CPR group). The effect of VF time, the sequence of DF and CPR, and NYHA classification on success rate of DF were observed. RESULTS: With prolonging VF time, success rate of DF obviously lowered [success rate of DF for VF<4 minute, 4 - 8 minute, and >8 minute groups were 83.0% (44/53), 62.5% (15/24), and 25.0% (4/16), respectively, all P<0.01]. When VF time lasted less than 4 minutes, success rate of DF in the prior DF group was obviously higher than that in the prior CPR group [88.9% (24/27) vs. 76.9% (20/26), P<0.05]. When VF time lasted for 4 - 8 minutes, the prior DF group had slightly higher success rate of DF compared with the prior CPR group [66.7% (8/12) vs. 58.3% (7/12), P=0.09]. When VF time lasted longer than 8 minutes, the success rate of DF in the prior CPR group was obviously higher than that in the prior DF group [37.5% (3/8) vs. 12.5% (1/8), P<0.01]. The success rate of DF was lowered in higher NYHA classification [success rate of DF for NYHA classification I-IV was 96.4% (27/28), 80.0% (20/25), 47.8% (11/23), 29.4% (5/17), respectively, P<0.05 or P<0.01]. CONCLUSIONS: VF lasting time and NYHA classification are key factors to success rate of DF, and the choice of sequence of DF and CPR depends on the lasting time of VF. For cases with the high NYHA classification, we should make some judgement beforehand and prepare some preventive measures.

Pulmonary fibrosis effect of ammonium perchlorate exposure in rabbit.

Ammonium perchlorate (AP) is a kind of inorganic chemical. To evaluate the potential pulmonary fibrosis caused by occupational exposure to this compound, 25 male rabbits were randomly allocated into 5 groups to receive AP or bleomycin or saline by intratracheal injection. All rabbits were sacrificed and lung tissues were removed to prepare hematoxylin and eosin (HE) staining for microscope observation and to perform electron microscopy examine. In microscope observation, AP-instilled lung tissue showed inflammatory infiltrates, alveolar collapse, subpleural thickening, and lymphocyte proliferation. Electron microscopy examination of lung tissue showed massive fibroblast accumulation, collagen fiber hyperplasia, and dense collagen deposition. The histopathological changes were considered as effective indicator linking to the development of pulmonary fibrosis. These results demonstrated that chronic instillation of AP can induce pulmonary fibrosis. And these results revealed that AP has pulmonary toxic effect.