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Nickel hydroxide nanosheets embedded with NiMoO4 nanoparticles with controllable composition were prepared. The optimized hybrid electrode exhibits high energy density.

This study reports Pt-decorated ZnO nanorod arrays (Pt/ZnO NRs) fabricated by low-cost hydrothermal and sputtering processes, which have excellent field emission (FE) performance. The effects of the Pt thickness on the morphology, structure and FE properties of ZnO NRs were investigated. It was found that highly oriented ZnO NRs with sharp tips were grown on a Zn substrate and the surface of ZnO NRs were uniformly covered with Pt nanoparticles (NPs) with a diameter of around 2–3 nm. The FE properties of ZnO NRs were greatly improved by optimizing the amount of Pt NPs. The results found that the ZnO NR emitters coated with Pt NPs of 15 nm thickness (Pt15/ZnO NRs) exhibited the best FE characteristics, which have the lowest turn-on field at 1.45 V μm−1 and the highest field enhancement factor of around 5405. More importantly, the maximum emission current density of as-fabricated Pt15/ZnO NR emitters was about 1900 times that of the bare ZnO emitters. The Pt coating not only improves electron conduction and heat dissipation of the emitters but also balances the emission point density and the screening effect.

Palladium/nickel-foam (Pd/Ni) electrode is used as a typical efficient electrocatalytic electrode for the removal of 2,4-dichlorophenoxyacetic acid (2,4-D) in surface water and industrial wastewater. Many researches had reported how to enhance the dechlorination efficiency of the Pd/Ni electrode by using less Pd loading. However, there are few reports of choosing a suitable electrolyte solution to improve the efficiency of dechlorination. Efforts were made in this work of the different catholyte influenced the dechlorination efficiency. The results showed the fastest removal efficiency of 2,4-D in 34 mmol/L NaHCO3 than in 34 mmol/L NaCl, 34 mmol/L NaClO4, 17 mmol/L Na2SO4 catholyte, respectively on Pd/Ni electrode with pd loading of 0.202 mg/cm2 at constant potential of -0.55 V (vs saturated calomel electrode). The dechlorination current efficiency (CE) was 20.5% in the 34 mmol/L NaHCO3 catholyte more than three times that in 17 mmol/L Na2SO4 catholyte for that HCO3- was the most likely source of protons for adsorbed active hydrogen (H*) in Pd active centers.

On March 14, 2017, a thirty years old male severe burn patient accompanied by asphyxia, sudden cardiac arrest, and acute respiratory distress syndrome was admitted to Zhengzhou First People's Hospital. During the shock stage, the pulse contour cardiac output was monitored for the restrictive rehydration, tracheotomy was performed, and fibrobronchoscope lavage was performed for the treatment of inhalation injury and pulmonary infection. An alternate application of suspended bed and turning bed was conducted to balance the treatment of cerebral edema and pulmonary infection; targeted antibiotics were used for anti-infective treatment; multiple operations were performed for eschar excision and skin grafting. At last, the wounds were all healed, the lung infection was cured, and the patient was discharged with severe disturbance of consciousness. Asphyxia and acute respiratory distress syndrome post-cardiopulmonary resuscitation are serious complications in severe burn patients. The clinical treatment of such patients is very difficult and should be highly alerted.2017年3月14日郑州市第一人民医院收治1例30岁男性危重烧伤并发窒息、心搏骤停、急性呼吸窘迫综合征患者，休克期在脉搏轮廓心输出量监测下行限制性补液，行气管切开、纤维支气管镜灌洗治疗吸入性损伤及肺部感染，悬浮床及翻身床交替应用平衡脑水肿和肺部感染治疗需要，针对性应用抗生素抗感染，多次行手术切痂植皮后，患者创面全部愈合、肺部感染痊愈，伴重度意识障碍出院。窒息、心肺复苏术后并发急性呼吸窘迫综合征系危重烧伤患者较为严重的并发症，此类患者临床治疗难度大，应高度重视。.

Whether lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for non-metastatic renal carcinoma has still been controversial recently. We conducted a meta-analysis assessing oncologic outcomes of radical nephrectomy with lymph node dissection (LND) and without lymph node dissection (non-LND) in non-metastatic renal cell carcinoma (NMRCC).A systematic review was performed until April 2018 using a comprehensive search in PubMed, EMBASE, and Cochrane Library databases to identify eligible comparative studies. A formal meta-analysis was performed for studies comparing radical nephrectomy with LND and radical nephrectomy with non-LND for cT1-T4NxM0 tumors. Furthermore, a subgroup analysis for locally advanced renal cell carcinoma (cT3-T4NxM0) was conducted.Thirteen studies on patients with LND and non- LND were identified and included in the analysis. LND group did not have a significantly better survival than non-LND group for cT1-T4NxM0 tumors (HR 0.93, 95% CI 0.78-1.11, p=0.45), However, in the subgroup of locally advanced renal cell carcinoma (cT3-T4NxM0), it showed a significantly better OS rate in patients who had undergone LND compared to those without LND (HR 0.73, 95% CI 0.60-0.90; p=0.003).LND offers better cancer control and better long-term survival in locally advanced renal cell carcinomas (cT3-T4NxM0). This conclusion should be confirmed by a prospective randomized clinical trial.

To investigate the effect of triptolide (TP) on oxidative stress and apoptosis in TM4 sertoli cells and related molecular mechanism.TM4 cells were incubated with different concentrations of triptolide for 24 h, then collected for further experiments. Cell proliferation analysis was used to measure the inhibitive effect of triptolide on proliferation of TM4 cells; DCFH-DA (6-carboxy-2',7'-dichlorofluorescein diacetate) probe was used to stain the TM4 cells, the level change of intracellular ROS was discovered through flow cytometry; the TM4 cells were stained by Annexin V-FITC/PI to detect whether triptolide induced apoptosis in the TM4 cells; Protein was extracted from the TM4 cells in control and triptolide group. Western blot was performed to determine the expression of apoptosis marker protein cleaved-PARP and PI3K/Akt signaling pathway-related proteins [p-Akt (Ser473), Akt, p-mTOR (Ser2448), mTOR, p-p70S6K (Thr389), p70S6K].Cell proliferation analysis revealed that triptolide reduced the TM4 cells viability significantly compared with control group in a dosage-dependent manner [10 nmol/L: (73.77±20.95)%, 100 nmol/L: (51.60±10.43)%, 500 nmol/L: (44.34±5.78)%]; The level of intracellular ROS in the TM4 cells was significantly induced in a dosage-dependent manner (P0.01); triptolide remarkably induced early-stage and late-stage apoptosis in the TM4 cells [control: (3.84±1.50)%, 100 nmol/L: (13.04±2.03)%, 200 nmol/L: (16.24±1.34)%, 400 nmol/L: (18.76±3.45)%]; The expression of cleaved-PARP was significantly upregulated in the TM4 cells after incubation with triptolide (P0.01); The expression levels of p-Akt/Akt and p-p70S6K/p70s6k were significantly increased compared with control group (P0.01). No significant change was observed among the expression levels of p-mTOR/mTOR (P0.05).In vitro studies showed that triptolide could effectively suppress the proliferation and induce apoptosis of TM4 sertoli cells. The oxidative stress was upregulated after incubation with triptolide, which may be one of the mechanisms of cytotoxicity in TM4 cells. Treatment of triptolide led to activation of Akt and p70S6K, indicating that the PI3K/Akt signaling pathway may be involved in response to oxidative stress in TM4 cells. The activation of PI3K/Akt signaling pathway was one of the molecular mechanisms involved in triptolide-mediated oxidative stress in TM4 cells. Our study provides insight into alleviating reproductive toxicity of triptolide in clinical and developing male contraceptive.

SUMMARYHepatitis C virus (HCV) infection is one of the leading causes of death and morbidity associated with liver disease. Risk factors identified for the transmission of HCV include contaminated blood products, intravenous drug use, body piercing, an infected mother at birth, sexual activity, and dental therapy, among others. However, the exact diversity of the HCV genotype and genetic variation among patients with low-risk factors is still unknown. In this study, we briefly described and analysed the genotype distribution and genetic variation of HCV infections with low-risk factors using molecular biology techniques. The results suggested that genotype 1b was predominant, followed by genotypes 2a and 1a. Genetic variations in the 5′ UTR sequences of HCV were identified, including point mutations, deletions, and insertions. The frequency of genetic variations in 1b was higher than in 2a. This study provides considerable value for the prevention and treatment of liver disease caused by HCV among patients with low-risk factors and for the development of HCV diagnostic reagents and vaccines.

The optimum time interval for 10 ml boluses of bupivacaine 0.0625% + fentanyl 2 μg.ml

To evaluate the safety and effectiveness of femtosecond laser-assisted cataract surgery.The interventional case series enrolled 314 eyes undergoing cataract surgery in Xiamen Ophthalmic Center between April and December 2013, patients were randomized to femtosecond laser-assisted cataract surgery(153 eyes) and conventional phacoemulsification cataract surgery(161 eyes). The clincic parameters of preoperation, during operation and postoperation were compared and statistically studied. Quantitative data were analyzed using the analysis of variance, independent t tests. Qualitative datawere analyzed using the crosstabs analysis chi-square test or the Fisher's exact test.The patient's demographics parameters(age, gender, IOP, axial length, mean keratometry, AC depth, Cataract grade) did not differ significantly between groups (P0.05) . The CDE showing 4.78% (3.18%-8.88%) and EPT showing 14.05 s (10.07-20.85 s) in the laser group were significantly lower than the CDE showing 8.82% (6.01%-19.16%) and EPT showing 23.65 s (18.36-46.96 s) in the conventional group (z=2.30, 2.91; P0.05) . The relative diameter and circularity in laser-assisted capusulotomies were significantly more accurate (t=2.58, 3.92; P0.05). The corneal endothelial cell loss showing 73.50 (-69.51-111.03)/mm(2) was significantly lower in the laser group than the loss of 118.06 (53.55-299.03)/mm(2) in the conventional group 1 month postoperatively (z=2.44; P0.05). Postoperative anterial chamber flare was significantly greater in the conventional group at 1 day of 18.81 (13.32-20.23) ph/ms in laser group, 24.51(16.38-32.18)ph/m in conventional group and at 1 month of 13.01(9.23-16.28) ph/ms in laser group, 18.05(12.37-24.97) ph/ms in conventional group than the laser group (z=2.40, 2.31; P0.05). There were no severe surgical complications for both groups.The femtosecond laser-assisted cataract surgery was effective and safe. It reduced EPT and CDE during operation, therefore decreased endothelial damage and postoperative anterior chamber inflammation. It also provided more precise and reproducible capsulotomies.

Pollutants from various sources are entering groundwater systems due to changing land use and because groundwater environments are deteriorating at various scales worldwide. The health status of a groundwater environment can be used to indicate the degree of deterioration under natural or manmade stresses. This study proposes a concept for groundwater environment health and sets up an assessment index system to diagnose the health status of a groundwater environment based on a Bossel sustainable development index framework. The index system covers six basic categories (survival, effectiveness, freedom, security, adaptation and coexistence), which indicate various aspects of the health status of a groundwater environment. A projection pursuit (PP) model is developed for the assessment of groundwater environments and PP grade evaluation (PPGE) was used to evaluate the health status of a groundwater environment. The model was applied in Western Jilin province, China as a case study for groundwater environment management.

Huyou (Citrus changshanensis K. S. Chen et C. X. Fu) citrus is a natural hybrid with unidentified parents. Previous studies have hypothesized that pummelo and sweet orange might be parents, which contradicts the higher freezing resistance of huyou citrus than both the assumed parents. In this study, the parental analysis was based on internal transcribed spacer (ITS) sequences of huyou as well as six candidate parents: three mandarins, one sweet orange, one sour orange and one pummelo. Two different ITS1 sequences, with eight variable sites within the 250 bp region, were observed for huyou, which were identical only to that of sour orange and pummelo, respectively. The results indicated that huyou is most likely a hybrid between sour orange and pummelo. In addition, the application of ITS 1 sequences in the phylogenetic analysis of citrus was discussed.

A ribonuclease (RNase), possessing an N-terminal sequence disparate from those of ribonucleases from other mushrooms and previously isolated Pleurotus ostreatus RNases, was purified from the fruiting bodies of the edible mushroom Pleurotus ostreatus. The N-terminal sequence of Pleurotus ostreatus RNase did not manifest homology even to a previously reported RNase from the same mushroom. The ribonuclease was adsorbed on CM-Sepharose and Mono S. It exhibited a molecular mass of 12 kDa in both sodium dodecyl sulphate-polyacrylamide gel electrophoresis and gel filtration on Superdex 75. The ribonuclease displayed an activity of 11 490 U/mg on yeast tRNA. The highest ribonuclease activity was exhibited toward poly U, followed by poly A and poly C. No activity was shown toward poly G. The optimal pH for its activity was 7 and the optimal temperature was 55°C. It inhibited cell-free translation in a rabbit reticulocyte lysate with an IC50 of 240 nM. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.

A peptide, possessing a molecular mass of 5 kDa and demonstrating remarkable sequence homology to the cowpea 10 kDa protein precursor and garden pea disease resistance response protein, was isolated from rice bean seeds. The peptide was adsorbed on CM-Sepharose and Affi-gel blue gel. It inhibited mycelial growth in the fungi Botrytis cinerea, Fusarium oxysporum, Rhizoctonia solani and Mycosphaerella arachidicola. It stimulated incorporation of methyl [3H] thymidine into mouse splenocytes, inhibited the activity of human immunodeficiency virus type 1 reverse transcriptase and suppressed translation by rabbit reticulocyte lysate.

From the fresh fruiting bodies of the oyster mushroom a peptide with a molecular weight of 9 kDa and demonstrating a novel N-terminal sequence GPCYLVAFYESSGRR was isolated. The isolation procedure involved ion exchange chromatography on CM-Sepharose and Mono S. The peptide was adsorbed on both types of chromatographic media. The peptide demonstrated a ribonuclease activity of 650 U/mg toward yeast transfer RNA. It inhibited cell-free translation in a rabbit reticulocyte lysate system with an IC50 of 15 nM. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.

A protein designated hypogin, with a prominent suppressive action on the growth of the fungi Mycosphaerella arachidicola, Fusarium oxysporum and Coprinus comatus, was isolated from seeds of the peanut Arachis hypogaea. The protein inhibited human immunodeficiency virus (HIV) reverse transcriptase and enzymes associated with HIV infection including alpha-glucosidase and beta-glucosidase. The proliferative response of mouse splenocytes was attenuated in the presence of the protein. The protein exhibited a molecular mass of 7.2 kDa in tricine gel electrophoresis and gel filtration on Superdex 75 and an N-terminal sequence resembling peanut allergen Ara H1. The isolation procedure involved affinity chromatography on Affi-gel blue gel and ion-exchange chromatography on CM-Sepharose. The protein was adsorbed in both chromatographic media.

In this paper we study optimization problems with variational inequality constraints in finite dimensional spaces. Kuhn-Tucker type necessary optimality conditions involving coderivatives are given under certain constraint qualifications including one that ensures nonexistence of non-trivial abnormal multipliers. The result is applied to bilevel programming problems to obtain Kuhn-Tucker type necessary optimality conditions. The Kuhn-Tucker type necessary optimality conditions are shown to be satisfied without any constraint qualification by the class of bilevel programming problems where the lower level is a parametric linear quadratic problem.

According to the desalination high-pressure pump water lubricated bearing-rotor coupling systems flow field distribution of liquid film in the starting transient process and its power transmission mechanism can lay the foundation of further exploring and judging lubrication state at the boot process. By using the computational fluid dynamics Fluent secondary development platform and calling the relevant DEFINE macro function to achieve the translation and rotation movement of the journal, we will use the dynamic grid technique to realize the automatic calculation and grid update of water lubricated bearings 3d unsteady liquid film flow field, and finally we will dispose the results of numerical simulation and get the pressure. When the eccentricity is large, film thickness was negatively correlated with the pressure, and positive with the velocity. Differential pressure was negatively correlated with velocity. When the eccentricity is small, film thickness is no significant relationship with differential pressure and velocity. Differential pressure has little difference with velocity.

A permanent increase in acute-phase serum amyloid A (A-SAA) level is observed in obesity and insulin resistance. Recently, A-SAA has been shown to correlate with obesity and insulin resistance in human. However, what triggers A-SAA up-regulation is poorly understood, and the mechanism of elevated A-SAA to insulin resistance has not been elucidated. In this study, we used two cellular models of insulin resistance, one induced by treatment with tumor necrosis factor-alpha (TNF-alpha) and the other with the glucocorticoid dexamethasone. Gene expression analysis showed that SAA3 mRNA levels were increased in both models of insulin resistance, and ELISA showed that A-SAA levels were increased in both models too. To assess the potential impact of A-SAA on insulin resistance, we treated 3T3-L1 adipocytes with recombinant human SAA (Rh-SAA) and found that Rh-SAA attenuated cellular insulin sensitivity, up-regulated the level of phosphor-JNK, and down-regulated the level of phosphotyrosine-IRS-1 and the expression of glucose transporter 4 (GLUT4) in 3T3-L1 adipocytes. Pre-treatment of cells with C-Jun amino-terminal kinases (JNK) inhibitor brought about partial restoration of Rh-SAA-induced insulin resistance. In sum, our findings suggest that serum amyloid A might be a marker of insulin resistance, and it might play a major role in the development of obesity-related insulin resistance. Moreover, in our study it has been proved that JNK is indeed a crucial component of the pathway responsible for SAA-induced insulin resistance in 3T3-L1 adipocytes, which suggests that a selective interference with JNK activity might be a useful strategy in the treatment of Type 2 diabetes and other insulin-resistant states.

A protein with an N-terminal sequence displaying similarities to N-terminal sequences of human calcyon and barley endo-1,4-glucanase, and to C-terminal sequences of human translation initiation factor 4 gamma and yeast superkiller viralicidic activity, was isolated from the broad bean Vicia faba. The protein, termed fabin, has a molecular mass of 34 kDa in SDS-polyacrylamide gel electrophoresis. Antifungal activity of the protein was observed against several fungal species including Rhizoctonia solani, Botrytis cinerea, Fusarium oxysporum and Mycosphaerella arachidicola. Fabin inhibits HIV-1 reverse transcriptase with an IC50 of 34 microM and translation in a rabbit reticulocyte lysate with an IC50 of 2.4 microM. At a concentration of about 1.5 microM fabin is able to elicit a 9-fold increase in the mitogenic response of murine splenocytes.

An antifungal polypeptide bearing an N-terminal sequence with some homology to chitinases was purified from an extract of pinto beans. The polypeptide, designated vulgin, exerted antifungal activity toward Mycosphaerella arachidicola, Coprinus comatus, Fusarium oxysporum and Botrytis cinerea. Vulgin inhibited translation in a rabbit reticulocyte lysate system with an IC50 of 4.3 µM and HIV-1 reverse transcriptase activity with an IC50 of 58 µM. Vulgin stimulated in vitro incorporation of methyl [3H] thymidine into mouse splenocytes. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.

A new trypsin–chymotrypsin inhibitor, with an N-terminal sequence showing some differences from the previously reported trypsin–chymotrypsin inhibitor, was isolated from the broad bean Vicia faba. The inhibitor was a peptide with a molecular mass of 13 kDa. It was adsorbed on Affi-gel blue gel and CM-Sepharose. It exerted antifungal activity toward Mycosphaerella arachidicola and Physalospora piricola. In addition, the trypsin–chymotrypsin inhibitor elicited a mitogenic response from mouse splenocytes and inhibited the activity of human immunodeficiency virus-1 reverse transcriptase. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.

A peptide, possessing a molecular mass of 5 kDa and demonstrating remarkable sequence homology to the cowpea 10 kDa protein precursor and garden pea disease resistance response protein, was isolated from rice bean seeds. The peptide was adsorbed on CM-Sepharose and Affi-gel blue gel. It inhibited mycelial growth in the fungi Botrytis cinerea, Fusarium oxysporum, Rhizoctonia solani and Mycosphaerella arachidicola. It stimulated incorporation of methyl [3H] thymidine into mouse splenocytes, inhibited the activity of human immunodeficiency virus type 1 reverse transcriptase and suppressed translation by rabbit reticulocyte lysate.

An antifungal peptide was isolated from the adzuki bean with a procedure involving affinity chromatography on Affi-gel blue gel and ion exchange chromatography on CM-Sepharose. The protein designated angularin was adsorbed on both types of chromatographic media and possessed a molecular weight of 8 kDa. Angularin exhibited antifungal activity against a variety of fungal species including Mycospharella arachidiocola and Botrytis cinerea. It inhibited mycelial growth in B. cinerea with an IC50 of 14.3 microM. Fusarium oxysporum and Rhizoctonia solani were not inhibited. Angularin demonstrated inhibitory activity on translation in the rabbit reticulocyte lysate system (IC50 = 8.0 microM) but did not affect proliferation of splenocytes. The activity of HIV-1 reverse transcriptase was inhibited in the presence of angularin. Its N-terminal sequence was GEPGQKE.

A protein designated hypogin, with a prominent suppressive action on the growth of the fungi Mycosphaerella arachidicola, Fusarium oxysporum and Coprinus comatus, was isolated from seeds of the peanut Arachis hypogaea. The protein inhibited human immunodeficiency virus (HIV) reverse transcriptase and enzymes associated with HIV infection including alpha-glucosidase and beta-glucosidase. The proliferative response of mouse splenocytes was attenuated in the presence of the protein. The protein exhibited a molecular mass of 7.2 kDa in tricine gel electrophoresis and gel filtration on Superdex 75 and an N-terminal sequence resembling peanut allergen Ara H1. The isolation procedure involved affinity chromatography on Affi-gel blue gel and ion-exchange chromatography on CM-Sepharose. The protein was adsorbed in both chromatographic media.

In the multistage pump of high head, pressure difference in two ends of annular seal clearance and rotor eccentric would produce the sealing fluid force, the effect of which can be expressed by a damping and stiffness coefficient. It has a great influence on the critical speed of the rotor system. In order to research the influence of the annular seal to the rotor system, this paper used CFD method to conduct the numerical simulation for the flow field of annular seal clearance. The radial and tangential forces were obtained to calculate the annular dynamic coefficients. Also dynamic coefficient were obtained by Matlab. The rotor system was modeled using ANSYS finite software and the critical speed with and without annular seal clearance were calculated. The result shows: annular seal's fluid field is under the comprehensive effect of pressure difference and rotor entrainment. Due to the huge pressure difference in front annular seal, fluid flows under pressure difference; the low pressure difference results in the more obvious effect on the clearance field in back annular seal. The first order critical speed increases greatly with the annular seal clearance; while the average growth rate of the second order critical speed is only 3.2%; the third and fourth critical speed decreases little. Based on the above result, the annular seal has great influence to the first order speed, while has little influence on the rest.

An antifungal protein designated sativin was isolated from the legumes of the sugar snap (also known as honey pea) Pisum sativum var. macrocarpon. The procedure entailed extraction, affinity chromatography on Affi-gel blue gel and ion exchange chromatography on CM-Sepharose. The protein exhibited a molecular weight of 38 kDa in SDS-polyacrylamide gel electrophoresis. It possessed an N-terminal amino acid sequence which showed similarity to those of miraculin (a sweet protein) and pisavin (a ribosome-inactivating protein from Pisum sativum var arvense Poir manifesting similarity to miraculin). Unlike pisavin, however, sativin demonstrated negligible ribonuclease activity and inhibited translation in a rabbit reticulocyte lysate system with a very low potency (IC50= 14 microM). Sativin exerted antifungal activity against Fusarium oxysporum, Coprinus comatus and Pleurotus ostreatus but not against Rhizoctonia solani.

The HIV-1 encoded regulatory Rev protein acts to selectively increase the cytoplasmic concentration of incompletely spliced viral mRNAs through interaction with the Rev responsive element (RRE). In addition, the Rev activation domain, believed to be a nuclear export sequence, has been shown to modulate the export of non-RRE containing RNAs (e.g. 5S rRNA, splicesomal U snRNAs). Recent evidence suggests Rev activity depends on interactions with cellular cofactors, leading to speculation that Rev utilizes a cellular RNA and/or a protein export pathway. Rev interactions with cellular cofactors could lead to sequestration of those cofactors from normal cellular activities, suggesting potential Rev effects on cellular gene products and their resultant activity. We have examined the role of Rev in modulating the expression of cellular gene products. Through transient cotransfection assays, we observed a consistent and significant decrease in the levels of luciferase and B-galactosidase activity in the presence of a Rev expressing construct. Cell fractionation studies demonstrated the nuclear retention of the luciferase gene transcripts. Surprisingly, similar effects were observed on constitutively expressed RNAs such as gamma-actin transcripts, and the 18S and 28S rRNAs. These results suggest Rev can disrupt the nuclear export of multiple classes of RNAs.

Blood schizontocidal effect of antimalarials were compared by 4-day suppressive test with an extended observation period of 31 days. On a drug-sensitive Plasmodium berghei ANKA strain, pyronaridine (PND) exhibited the best effect, followed by amodiaquine (ADQ), mefloquine (MFQ), and qinghaosu (QHS). On a moderately chloroquine-resistant P. berghei NS line, the order of effects was the same, PND greater than ADQ greater than MFQ greater than QHS. On a highly pyronaridine-resistant P. berghei RP line, ADQ, MFQ and QHS showed cross resistance with PND.

The asexual stages of P. berghei ANKA were completely eliminated as revealed in a "4-day suppressive test" with the daily dose of pyronaridine 12.5 mg base/kg or amodiaquine 25 mg base/kg. Mefloquine 25 mg base/kg and qinghaosu 100 mg/kg though exerted obvious suppressive effect, the cure rates were only 50% and 0%, respectively. In treating chloroquine-sensitive P. berghei ANKA strain pyronaridine exhibited the best therapeutic activity, which was followed by amodiaquine, mefloquine and quinghaosu. In treating moderately chloroquine-resistant P. berghei NS line the cure rate of pyronaridine 12.5 mg/kg.d x 4 was 70%, but none of the 10 infected mice from any group was cured by amodiaquine 100 mg/kg.d, mefloquine 100 mg/kg.d or qinghaosu 200 mg/kg.d. Though the latter 3 drugs showed prominent suppressive effects, parasitemia remained positive or recrudesced after dosing. We demonstrate that parasites resistant to chloroquine had cross resistance to amodiaquine, mefloquine and inghaosu at various degrees. Amodiaquine 100 mg/kg.d, mefloquine 100 mg/kg.d and qinghaosu 200 mg/kg.d exhibited no obvious suppressive activity on highly pyronaridine-resistant line of P. berghei, indicating the existence of cross resistance to pyronaridine.

Trifluoroacetyl primaquine oxalate (M8506) was compared with primaquine phosphate for tissue schizontocidal action in rodent and simian malaria. In Plasmodium yoelii sporozoites infected mice, the causal prophylactic effects of M8506 at 5, 10 and 20 mg(base)/kg were 56.7%, 87.2% and 100%, respectively, comparable to those of primaquine (54.4%, 90.8% and 100%). In P. cynomolgi sporozoites infected rhesus monkeys 4 dosage regimens of the two agents were compared for radical curative effect. On the first day of treatment pyronaridine phosphate 10 mg(base)/kg twice a day were intramuscularly injected to eliminate erythrocytic stages of P. cynomolgi. At the dosage of 3.0 mg(base)/kg/day x 3, both M8506 and primaquine radically cured the monkeys. At 0.75 mg/kg/day x 3, 12 of 13 (92.3%) monkeys cured by M8506, 5 of 9 (55.6%) cured by primaquine. At 1.5 and 0.375 mg/kg/day x 3, the radical curative effects of M8506 were also better than those of primaquine. Since the toxicity of M8506 was significantly milder in mice, rats and dogs than that of primaquine, M8506 has potential as a tissue schizontocide.

The toxicity of combined use of blood schizontocide pyronaridine (PND) and primaquine (PQ) in mice and rats was significantly lower than that of chloroquine (CQ) plus primaquine (PQ). PND 1/2 LD50 (ca 600 mg/kg) in combination with PQ reduced the toxic action of PQ in mice, while CQ 1/2 LD50 (ca 300 mg/kg) plus PQ produced synergistic toxic effect. In animal models such as Plasmodium yoelii sporozoite infection in mice and P. cynomolgi sporozoite infection in rhesus monkeys, the tissue schizontocidal action of PQ was not affected by PND. Therefore, clinical evaluation of PND/PQ in comparison with CQ/PQ in treating vivax malaria is suggested.

Trifluoroacetyl primaquine (M-8506), 6-methoxy-5-trifluoroacetyl-8-(4-methyl-butyl-amino)-aminoquinoline oxalate, synthesized by the Institute of Parasitic Diseases was compared with primaquine for tissue schizontocidal action and acute ig LD50. In P yoelii sporozoite infected mice, the protection rates with ig M-8506 5, 10 and 20 mg (base)/kg on the day of infection were 56.7, 87.2 and 100%, respectively. These were comparable to the protection rates with primaquine 5, 10 and 20 mg(base)/kg (54.4, 90.8 and 100%, respectively). The radical curative effect was conducted in P cynomolgi sporozoite infected Macaca mulatta. Since im pyronaridine 10 mg/kg b.i.d. (6 h apart) completely eliminated the parasites in monkeys infected with erythrocytic stages of P cynomolgi, the tissue schizontocidal activities of M-8506 and primaquine were observed by im administration of pyronaridine 10 mg/kg b.i.d. on d 1. M-8506 at 0.75, 1.5 and 3 mg/(kg.d) x 3d plus pyronaridine were given to 7, 4 and 2 infected monkeys with parasitemia respectively. All the monkeys, except one receiving 0.75 mg/(kg.d) x 3 d, were radically cured. Primaquine 0.75, 1.5 and 3 mg/(kg.d) x 3 d were administered to 3, 3 and 2 monkeys respectively. Two monkeys receiving primaquine 0.75 mg/(kg.d) x 3 d relapsed on d 42. The parasitemia reappeared earlier than that treated with M-8506 0.75 mg/(kg.d) x 3 d and relapsed on d 62. Because M-8506 is less toxic than primaquine in mice and more effective in radical treatment of simian malaria, further studies on trifluoroacetyl primaquine are worthy to be considered.

Pyronaridine, a highly effective antimalarial drug, was synthesized and developed by this institute. In order to test whether the joint blood schizontocidal action of pyronaridine (PND) and 2:1 mixture of sulfadoxine/pyrimethamine (SP) resulted in a potentiation or an additive effect, groups of P berghei ANKA strain-infected mice were treated with various single oral doses of PND and SP. Thin blood smears were made after 72 h and the parasitemia-negative rates were calculated. The ED50 values obtained were plotted in isobolograms. An additive action of this triple combination was demonstrated. Mice were inoculated with P berghei ANKA strain-infected erythrocytes 3 and 2 d after the mice were given a single oral dose of PND 10 mg/kg alone, or combined with SP 3 mg/kg. Thin blood smears made on d 3, 5, 8 and 10 revealed that the parasitemia-positive rates and the duration of residual blood schizontocidal action of PND used alone was similar to that of PND used in combination (P greater than 0.05). Three groups of mice carrying P berghei ANKA strain gametocytes were administered orally with pyrimethamine 0.1 mg/kg, SP 0.3 mg/kg and SP 0.3 mg/kg plus PND 0.5 mg/kg, respectively. Anopheles stephensi were then fed on the mice 2 h after the medication. There resulted no significant differences of gametocytocidal and sporontocidal effects among the 3 groups, since the oocyst-positive rate and the glandpositive rate were similar in these groups.