Lnczc3h7a对结直肠癌细胞增殖和迁移的影响及其机制

目的 分析Lnczc3h7a在结直肠癌细胞中的表达及其对结肠癌细胞增殖和迁移的影响,并探讨其潜在的作用机制.方法 选择6种结直肠癌细胞株SW620、SW480、HCT116、DLD-1、Caco-2、HT-29与正常结直肠上皮细胞株FHC,采用RT-PCR法检测Lnczc3h7a在结直肠癌细胞株及正常结直肠上皮细胞株中...     

抗HIV药物研究进展及发展趋势

本文分类总结了近年来抗HIV药物的研究进展以及以后的发展趋势,着重介绍了抗HIV的新的作用靶点和天然活性产物在抗HIV方面的应用。     

Altereporenes A–E,five epoxy octa-hydronaphthalene polyketides produced by an endophytic fungus Alternaria sp. YUD20002

Five previously undescribed epoxy octa-hydronaphthalene polyketides, altereporenes A–E (1–5) were isolated from rice culture of the endophytic fungus Alternaria sp. YUD20002 derived from the tubers of Solanum tuberosum. Their structures were determined on the basis of comprehensive spectroscopic analyses, while the absolute configurations were elucidated by the comparison of experimental and calculated specific rotations. Meanwhile, the antimicrobial, cytotoxic, anti-inflammatory and acetylcholinesterase inhibitory activities of compounds 1–5 were also investigated.

Five previously undescribed epoxy octa-hydronaphthalene polyketides, altereporenes A–E (1–5) were isolated from rice culture of the endophytic fungus Alternaria sp. YUD20002 derived from the tubers of Solanum tuberosum.     

Improved nitrogen reduction activity of NbSe2 tuned by edge chirality

Efficient catalysts for the electroreduction of N₂ to NH₃ are of paramount importance for sustainable ammonia production. Recently, it was reported that NbSe₂ nanosheets exhibit an excellent catalytic activity for nitrogen reduction under ambient conditions. However, existing theoretical calculations suggested an overpotential over 3.0 V, which is too high to interpret the experimental observations. To reveal the underlying mechanism of the high catalytic activity, in this work, we assessed NbSe₂ edges with different chirality and Se vacancies by using first principles calculations. Our results show that N₂ can be efficiently reduced to NH₃ on a pristine zigzag edge via the enzymatic pathway with an overpotential of 0.45 V. Electronic structure analysis demonstrates that the N₂ molecule is activated by the back-donation mechanism. The efficient tuning of the local chemical environments by edge chirality provides a promising approach for catalyst design.

The zigzag edge of the NbSe₂ monolayer exhibits an overpotential as low as 0.45 V along the enzymatic pathway.     

真皮导管瘤一例

患者男,61岁,因头枕部丘疹3年就诊。患者于3年前无明显诱因下发现枕部丘疹,无自觉症状,后缓慢增大。否认病程中出血、溃疡、脱屑等。体检：一般情况好,各系统检查未见异常。皮肤科检查：枕部见一枚黄豆大小丘疹,直径约9 mm,淡红色,境界清晰,表面光滑,质地坚实（图1A）……     

Repurposing povidone-iodine to reduce the risk of SARS-CoV-2 infection and transmission: a narrative review

BackgroundAccumulating data suggest antiviral effects of povidone-iodine against the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This narrative review aims to examine the antiviral mechanisms of povidone-iodine, efficacy of povidone-iodine against the SARS-CoV-2 virus, and safety of povidone-iodine to human epithelial cells and thyroid function.MethodsWe searched the electronic databases PubMed, Embase, Cochrane Library, ClinicalTrials.gov and World Health Organization’s International Clinical Trials Registry Platform for articles containing the keywords “povidone-iodine”, “SARS-CoV-2” and “COVID-19” from database inception till 3 June 2021.ResultsDespite in vitro data supporting the anti-SARS-CoV-2 effects of povidone-iodine, findings from clinical studies revealed differences in treatment response depending on study settings (healthy vs. hospitalized individuals), treatment target (nasal vs. oral vs. pharynx), method of administration (oral rinse vs. gargle vs. throat spray) and choice of samples used to measure study endpoints (nasopharyngeal vs. saliva). One large-scale clinical trial demonstrated reduction in the incidence of SARS-CoV-2 infection among participants who administered povidone-iodine 3 times daily during an active outbreak. Povidone-iodine is also used to disinfect the oro-pharyngeal space prior to dental or otolaryngology procedures. Although existing data suggest minimal impact of povidone-iodine on thyroid function, high-quality safety data are presently lacking.ConclusionsPovidone-iodine application to the oropharyngeal space could complement existing non-pharmacological interventions to reduce SARS-CoV-2 infection especially in high exposure settings.

Key messages

• Accumulating data suggest antiviral effects of povidone-iodine against the SARS-CoV-2 virus.
• Findings from clinical studies reveal differences in treatment response depending on study settings, treatment target, method of administration and choice of samples used to measure study endpoints. One large-scale clinical trial observed reduction in the incidence of SARS-CoV-2 infection among participants who administered povidone-iodine 3 times daily during an active outbreak.
• Povidone-iodine application to the oropharyngeal space could complement existing non-pharmacological interventions to reduce SARS-CoV-2 infection especially in high exposure settings.

     

Differential Associations of Intakes of Whole Grains and Coarse Grains with Risks of Cardiometabolic Factors among Adults in China

There is a lack of studies on the association between whole grain intake and cardiometabolic risk factors in China and the current definition of whole grains is inconsistent. This study defined whole grains in two ways, Western versus traditional, and examined their associations with the risks of major cardiometabolic factors (CMFs) among 4706 Chinese adults aged ≥18 years, who participated in surveys both in 2011 and in 2015. Diet data were collected by consecutive 3 d 24 h recalls, together with household seasoning weighing. Whole grains were defined as grains with a ratio of fiber to carbohydrate of ≥0.1, while coarse grains were defined as grains except for rice and its products, and wheat and its products. Multivariable logistic regressions were modeled to analyze the associations of intakes of whole grains and coarse grains, respectively, with risks of major CMFs including obesity-, blood pressure-, blood glucose- and lipid-related factors, which were defined by International Diabetes Federation and AHA/NHLBI criteria. After adjusting for potential confounders, the odds of elevated LDL-C decreased with the increasing intake levels of whole grains (OR 0.64, 95% CI 0.46–0.88, p-trend < 0.05). Moreover, adults with the whole grain intake of 50.00 to 150.00 g/day had 27% lower odds of overweight and obesity (OR 0.73, 95% CI 0.54–0.99) and 31% lower odds of elevated LDL-C (OR 0.69, 95% CI 0.49–0.96), as compared with non-consumers. In conclusion, given the significant nutrient profiles of whole grains and coarse grains, the adults with higher intakes of whole grains only may have a lower risk of LDL-C and overweight and obesity.     

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

孤立肾上尿路结石的ESWL治疗

目的:总结孤立肾并发上尿路结石ESWL治疗的经验。方法:电压比非孤立肾者略低,JT-Ⅲ型机8～12kV,HB-V型机4～8kV;放电次数比非孤立肾者略少,Ⅲ型机1500～2000次,V型机3000～3500次;同时减慢冲击频率;间隔时间二周以上比非孤立肾者稍长。直径大于2cm或多发结石且颗粒较大者,先行经皮肾镜取石后残石再行ESWL,多发或直径大于1.5cm的结石留置双J管后再ESWL,梗阻引起急性肾功能减退者急诊ESWL或先行肾造瘘或逆行插管引流积水,肾功能基本恢复后再ESWL。结果:22例独肾结石除7例多发外,15例一次成功,6例输尿管结石除1例再碎石外,5例一次成功。结论:ESWL治疗孤立肾上尿路结石损伤小且疗效好。