Molecular Analysis of Caprine Enterovirus Circulating in China during 2016–2021: Evolutionary Significance

Here, we report the characterization of 13 novel caprine/ovine enterovirus strains isolated from different regions in China during 2016–2021. Immunoperoxidase monolayer assay showed that these viral strains shared strong cross-reaction with the previously reported caprine enterovirus CEV-JL14. Alignment analysis of the complete nucleotide sequences revealed 79.2%–87.8% and 75.0%–76.7% sequence identity of these novel caprine enterovirus strains to CEV-JL14 and TB4-OEV, respectively. Phylogenetic analyses clustered these novel strains to EV-G based on the amino acid sequences of P1 and 2C+3CD. Moreover, phylogenetic analysis of these caprine enterovirus strains identified three new EV-G types using VP1 sequences. These results demonstrate the genetic variations and the evolution of caprine enterovirus.     

Ruthenium-catalyzed asymmetric hydrogenation of aromatic and heteroaromatic ketones using cinchona alkaloid-derived NNP ligands

A series of cinchona alkaloid-based NNP ligands, including a new one, have been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various aromatic and heteroaromatic ketones were smoothly reacted, yielding valuable chiral alcohols with extremely high 99.9% ee. Moreover, a proposed reaction mechanism was discussed and verified by NMR.

A series of cinchona alkaloid-based NNP ligands including a new one has been employed for the asymmetric hydrogenation of ketones. By combining ruthenium complexes, various ketones were smoothly reacted with up to 99.9% ee.

Since the well-known failure of using racemic thalidomide, attention has been paid to the manufacture of optically pure compounds as effective components in pharmaceuticals and agrochemicals. Asymmetric hydrogenation of ketones, especially heteroaromatic ketones, has emerged as a popular facile route to approach enantiopure secondary alcohols as essential intermediates for the construction of biologically active molecules.^1–4 Knowles et al.⁵ pioneered the production of enantioenriched chiral compounds in 1968, and Noyori and co-workers^6–8 laid the cornerstone of asymmetric hydrogenation in 1990s. Subsequently, numerous catalytic systems have been developed. Ru-BICP-chiral diamine-KOH was developed and proved to be effective for asymmetric hydrogenation of aromatic ketones by Xumu Zhang.⁹ Cheng-yi Chen reported asymmetric hydrogenation of ketone using trans-RuCl₂[(R)-xylbinap][(R)-daipen] and afforded secondary alcohol in 92–99% ee.¹⁰ Mark J. Burk and Antonio Zanotti-Gerosa disclosed Phanephos-ruthenium-diamine complexes catalyzing the asymmetric hydrogenation of aromatic and heteroaromatic ketones with high activity and excellent enantioselectivity.¹¹ Qi-Lin Zhou et al. designed and synthesized chiral spiro diphosphines as a new chiral scaffold applied in the asymmetric hydrogenation of simple ketones with extremely high activity and up to 99.5% ee.^12–15 Similarly, Kitamura and co-workers have developed a set of tridentate binan-Py-PPh₂ ligands for the asymmetric hydrogenation of ketones affording excellent results.¹⁶ Recently, chiral diphosphines and tridentate ligands based on ferrocene have been developed for the asymmetric hydrogenation of carbonyl compound with a remarkable degree of success.^17–21 Despite many ligands for asymmetric hydrogenation of ketones have been reported, expensive reagent and multistep complicated reactions were employed to synthesize most of them.^22–24 In light of increasing industrial demand, easily obtained, cheap and practical chiral ligands are still highly desirable. In addition to chiral ligands, the selection of metals was essential for asymmetric hydrogenation.^25–27 Although Mn,^28–30 Fe,^31–34 Co,^35–37 Ni^38,39 and Cu^40,41 metals were proved to be effective for asymmetric hydrogenation in recent years, Rh,^42–44 Ir^45,46 and especially Ru remained the most preferred metals. Ruthenium^47–51 was chosen owing to its superior performances in terms of low price, selectivity and activity. Takeshi Ohkuma,⁵² Hanmin Huang^53,54 and Johannes G. de Vries⁵⁵ all successfully used ruthenium catalysts for asymmetric hydrogenation of ketones. Admittedly, there is a continuing interest in the development of cheaper, simpler and more efficient catalysts for the asymmetric hydrogenation of ketones under mild conditions to access corresponding secondary alcohols. Recently, we developed new NNP chiral ligands derived from cinchona alkaloid for the asymmetric hydrogenation of various ketones in extremely excellent results using a iridium catalytic system.⁵⁶ Prompted by these encouraging results, we were interested in exploring a ruthenium-catalyzed asymmetric hydrogenation of ketones with NNP chiral ligands derived from cinchona alkaloid. Here, we showed that changing from iridium to ruthenium, with the same simple synthetic ligands, delivered a catalyst catalyzed asymmetric hydrogenation of ketones to give the industrially important chiral alcohols with up to 99.9% ee. Although the catalytic activity of ruthenium catalyst was not as high as that of the iridium catalyst, the enantioselectivity could be maintained, and even showed higher enantioselectivity in the hydrogenation of some substrates.Chiral tridentate ligand NNP (L1–L10) were synthesized and characterized as reported in our previous publication. With tridentate ligands in hand, we began to evaluate the catalytic performance in benzylidene-bis(tricyclohexylphosphine) dichlororuthenium-catalyzed asymmetric hydrogenation of acetophenone employed as a standard substrate (Fig. 2). MeOH was found to be a better one as the conversion and enantioselectivity were 99.9% and 98.2%, respectively. Bases screening showed that Ba(OH)₂ was superior to the others, giving >99.9% conversion and 98.8% ee in the present catalytic system (Fig. 1). Ligand screening revealed that the configuration of chiral centers of cinchona alkaloids of the ligand markedly affected the catalytic performance. NNP ligands derived from cinchonine and quinidine appeared to benefit both the reaction rate and enantioselectivity, while those derived from cinchonidine and quinine had the opposite effect. Further, different NNP ligands that bearing different substituents on the phenyl rings were evaluated. Similar to our previous research, ligands with electron-withdonating substituents showed better catalytic performance than those with electron-withdrawing substituents. However, it was noted that the more electron-withdonating substituents furnished lower activity but same enantioselectivity. The optimal ligand L5 derived from quinidine with one methoxy group on benzene ring provided the corresponding chiral alcohol with 99.9% conversion and 98.8% ee. Considering that L3 derived from cinchonine had similar catalytic performance to L4 derived from quinidine, new ligand L10 similar to L5 with one methoxy group on benzene ring was synthesized and applied to the asymmetric hydrogenation of template substrate. 99.6% conversion and 97.6% ee was obtained. Hence, L5 was employed as better ligand in subsequent experiments.Open in a separate windowFig. 1The effect of different bases for the asymmetric hydrogenation of acetophenone (substrate/Ru/L5 = 500/1/2, ketones: 0.429 mol L⁻¹, base: 0.15 mol L⁻¹, MeOH: 2 mL, 30 °C, 6 MPa, 2 h.).Open in a separate windowFig. 2The effect of different solvents for the asymmetric hydrogenation of acetophenone. (substrate/Ru/L5 = 1000/1/2, ketones: 0.858 mol L⁻¹, Ba(OH)₂: 0.15 mol L⁻¹, solvent: 2 mL, 30 °C, 6 MPa, 2 h.).The effect of different ligand for the asymmetric hydrogenation of acetophenone^a

Relationships between self-reflectiveness and clinical symptoms in individuals during pre-morbid and early clinical stages of psychosis

BackgroundSelf-reflectiveness, one dimension of cognitive insight, plays a protective role in an individual’s mental state. Both high and low levels of self-reflectiveness have been reported in patients with schizophrenia and individuals at clinical high risk for the illness.AimsThis study aimed to explore the relationship patterns between self-reflectiveness and clinical symptoms in individuals during the pre-morbid and early clinical stages of psychosis.MethodsA total of 181 subjects, including individuals with attenuated positive symptoms (APS, n=122) and patients with first-episode psychosis (FEP, n=59), completed the Beck Cognitive Insight Scale and were evaluated using the Schedule of Assessment of Insight and Positive and Negative Syndrome Scale. All subjects were classified into three groups according to their level of self-reflectiveness: low level (LSR, n=59), medium level (MSR, n=67) and high level (HSR, n=55). Both linear and non-linear relationships between self-reflectiveness and clinical symptoms were explored.ResultsMore individuals with APS were classified into the MSR group, while more patients with FEP were classified into the LSR group. The LSR group demonstrated less awareness of illness than the MSR and HSR groups, more stereotyped thinking and poorer impulse control but less anxiety than the MSR group, and lower levels of blunted affect and guilt feelings than the HSR group. The MSR group demonstrated lower stereotyped thinking than the HSR group. Compared to the LSR group, the MSR group had increased self-reflectiveness, improved awareness of illness, decreased stereotyped thinking, and better impulse control, but increased feelings of guilt. The HSR group showed increased stereotyped thinking when compared to the MSR group, but the other variables did not change significantly between these two groups. Overall, self-reflectiveness demonstrated an approximately inverse S-shaped relationship with the awareness of illness, a U-shaped relationship with stereotyped thinking and poor impulse control, and an almost linear relationship with anxiety and guilt feelings.ConclusionsSelf-reflectiveness demonstrates complex relationships with clinical symptoms and fails to exert significant positive effects when reaching a certain high level.     

病程长达一年的支气管肺发育不良一例

我院近两年使用肺表面活性物质加呼吸机抢救早产儿肺透明膜病共 97例 ,治愈 95例 ,2例家长放弃治疗。并发支气管肺发育不良 (BPD) 5例 ,4例住院 2～ 3月后痊愈出院 ,其中 1例住院时间长达 2 0 5d ,曾先后 4次上机 ,需用氧时间长达 1年 ,现报告如下。1　临床资料1 1　一般情况　男婴 ,胎龄 2 8周 ,出生体重 1 35kg。 1min及 5minApgar评分正常。G2 P1,第 1胎孕 2 6周出生后不明原因死亡。孕期无特殊。1 2　治疗经过及转归　患儿生后 2h开始出现呼气呻吟 ,胸片示肺透明膜病II期 ,予固尔苏 12 0mg气管内滴入及上呼吸机SIMV通气 ,初调参数…     

Incidence of brain injuries in premature infants with gestational age ≤34 weeks in ten urban hospitals in China

Background

There is a large number (1.5 million per year) of premature births in China. It is necessary to obtain the authentic incidences of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), the common brain injuries, in Chinese premature infants. The present multicenter study aimed to investigate the incidence of brain injuries in premature infants in ten urban hospitals in China.

Methods

The research proposal was designed by the Subspecialty Group of Neonatology of Pediatric Society of the Chinese Medical Association. Ten large-scale urban hospitals voluntarily joined the multicenter investigation. All premature infants with a gestational age ≤34 weeks in the ten hospitals were subjected to routine cranial ultrasound within three days after birth, and then to repeated ultrasound every 3–7 days till their discharge from the hospital from January 2005 to August 2006. A uniform data collection sheet was designed to record cases of brain injuries.

Results

The incidences of overall IVH and severe IVH were 19.7% (305/1551) and 4.6% (72/1551), respectively with 18.4% (56/305) for grade 1, 58.0% (177/305) for grade 2, 17.7% (54/305) for grade 3 and 5.9% (18/305) for grade 4 in nine hospitals. The incidences of overall PVL and cystic PVL were 5.0% (89/1792) and 0.8% (14/1792) respectively, with 84.3% (75/89) for grade 1, 13.5% (12/89) for grade 2, and 2.2% (2/89) for grade 3 in the ten hospitals. The statistically significant risk factors that might aggravate the severity of IVH were vaginal delivery (OR=1.883, 95% CI: 1.099–3.228, P=0.020) and mechanical ventilation (OR=4.150, 95% CI: 2.384–7.223, P=0.000). The risk factors that might result in the development of cystic PVL was vaginal delivery (OR=21.094, 95% CI: 2.650–167.895, P=0.000).

Conclusions

The investigative report can basically reflect the incidence of brain injuries in premature infants in major big cities of China. Since more than 60% of the Chinese population live in the rural areas of China, it is expected to undertake a further multicenter investigation covering the rural areas in the future.     

老年性白内障与正常晶状体蛋白质双向电泳的差异

目的:应用双向电泳技术对比研究老年性白内障与正常晶状体,寻找差异表达的蛋白质。方法:分别收集老年性白内障和正常晶状体,采用固相pH梯度(IPG)等电聚焦双向电泳技术进行蛋白质分离,使用ImageMaster图像分析软件分析电泳图像,对比分析蛋白质表达的差异。结果:大部分晶状体蛋白质分布在Mr14000～97000,等电点(pI)5～9的范围内;高丰度蛋白质斑点分布在Mr20000～31000、等电点(pI)6～8的区域内。经软件分析正常组共识别出133±7个蛋白质斑点,白内障组共识别出136±8个斑点,两组之间的匹配率为87%(115个),其中有8个点蛋白质表达量增加了300%以上,其中44号增加了480%,有6个点蛋白质表达量减少了300%以上,其中125号减少了336%。结论:老年性白内障与正常晶状体存在差异表达的蛋白质。     

环氧化酶-1在妇科恶性肿瘤诊断中的作用研究

目的　探讨血清环氧化酶 - 1(COX - 1)的检测在妇科恶性肿瘤诊断中的应用价值。方法　应用ELISA法检测血清COX - 1水平。结果　 31例卵巢癌 ,4 5例宫颈癌 ,4 0例子宫内膜癌的患者 ,其血清COX - 1的浓度较正常对照组显著升高 (P <0 0 0 1) ,阳性率分别为 6 5 %、 71%和 5 5 % ,卵巢囊肿阳性率仅 8% ,14例子宫良性肿瘤全部为阴性。结论　血清COX - 1浓度的检测可作为妇科恶性肿瘤 ,尤其是卵巢癌和宫颈癌的辅助诊断指标。