In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus

Zika virus (ZIKV) causes significant human diseases without specific therapy. Previously we found erythrosin B, an FDA-approved food additive, inhibited viral NS2B−NS3 interactions, leading to inhibition of ZIKV infection in cell culture. In this study, we performed pharmacokinetic and in vivo studies to demonstrate the efficacy of erythrosin B against ZIKV in 3D mini-brain organoid and mouse models. Our results showed that erythrosin B is very effective in abolishing ZIKV replication in the 3D organoid model. Although pharmacokinetics studies indicated that erythrosin B had a low absorption profile, mice challenged by a lethal dose of ZIKV showed a significantly improved survival rate upon oral administration of erythrosin B, compared to vehicle control. Limited structure−activity relationship studies indicated that most analogs of erythrosin B with modifications on the xanthene ring led to loss or reduction of inhibitory activities towards viral NS2B−NS3 interactions, protease activity and antiviral efficacy. In contrast, introducing chlorine substitutions on the isobenzofuran ring led to slightly increased activities, suggesting that the isobenzofuran ring is well tolerated for modifications. Cytotoxicity studies indicated that all derivatives are nontoxic to human cells. Overall, our studies demonstrated erythrosin B is an effective antiviral against ZIKV both in vitro and in vivo.KEY WORDS: Flavivirus, Zika virus, Dengue virus, Antiviral, Protease inhibitor, Erythrosin B     

Combination of C‐reactive protein,procalcitonin, IL‐6, IL‐8, and IL‐10 for early diagnosis of hyperinflammatory state and organ dysfunction in pediatric sepsis

BackgroundAlthough early diagnosis and management are critical for prognosis of pediatric sepsis, there are no specific diagnostic biomarkers for the hyperinflammatory state and organ dysfunction, important stages of sepsis.MethodsWe enrolled 129 children with infection into three groups: non‐sepsis infection (33), Sepsis 1.0 (hyperinflammatory state, 67), and Sepsis 3.0 (organ dysfunction, 29). Another 32 children with no infections were included as controls. Serum C‐reactive protein (CRP), procalcitonin (PCT), interleukin (IL)‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐17, tumor necrosis factor (TNF)‐α, interferon (IFN)‐α, and IFN‐γ were assessed to diagnose the two stages, and their diagnostic capacities were evaluated using receiver operating characteristic (ROC) curves. We also examined whether combining biomarkers improved diagnostic efficiency.ResultsSignificantly higher CRP, PCT, and IL‐6 levels were detected in the Sepsis 1.0 than the non‐sepsis infection group (p < 0.001). The areas under the curve (AUCs) for diagnosing Sepsis 1.0 were 0.974 (CRP), 0.913 (PCT) and 0.919 (IL‐6). A combination of any two biomarkers increased diagnostic sensitivity to ≥92.54% and specificity to 100.00%. Significantly higher PCT, IL‐8, and IL‐10 levels were found in the Sepsis 3.0 than the Sepsis 1.0 group (p ≤ 0.01), with AUCs for diagnosing Sepsis 3.0 0.807 (PCT), 0.711 (IL‐8), and 0.860 (IL‐10). Combining these three biomarkers increased diagnostic sensitivity to 96.55% and specificity to 94.03%.ConclusionIn pediatric sepsis, combining any two of CRP, PCT, and IL‐6 can accurately diagnose the hyperinflammatory state and increase diagnostic specificity. Early diagnosis of organ dysfunction requires a combination of PCT, IL‐8, and IL‐10.     

Self-assembled sonogels formed from 1,4-naphthalenedicarbonyldinicotinic acid hydrazide

In this paper, we report self-assembled sonogels formed from 1,4-naphthalenedicarbonyldinicotinic acid hydrazide (NDC-NN3) in some liquids including ethanol, tetrahydrofuran (THF), 1,4-dioxane, n-propanol, n-butanol and n-pentanol. When the clear solution of NDC-NN3 in the selected liquids mentioned above at a suitable concentration was irradiated with ultrasound waves at room temperature, a sonogel was formed. Upon heating, the sonogel dissolved gradually and finally became a clear solution again. Upon cooling the hot solution to room temperature, the solution state did not change even after standing for a few days. Nevertheless, if the solution underwent sonication for a certain time, a stable gel was obtained again. The critical gelation concentrations (CGCs) of NDC-NN3 in ethanol, THF, 1,4-dioxane, n-propanol, n-butanol and n-pentanol are 10, 8, 6, 8, 6 and 8 mg mL⁻¹, respectively. The obtained sonogels display excellent mechanical properties. The crystal structure of NDC-NN3 suggests that the naphthalene ring, hydrazide group and the position of N in the pyridine ring mediate the self-assembly process. Upon sonication, the formation of suitable π–π stacking and intermolecular hydrogen bonding drives the gelator molecules to self-assemble into fibers, spheres and micro-burdock-shaped balls in various solvents, which ultimately confine the liquids.

Ultrasound-induced gelation of a novel type of gelator, 1,4-naphthalenedicarbonyl- dinicotinic acid hydrazide, is reported. The gelator self-assembled into various architectures in different solvents.     

Effect of concentration of glycidol on the properties of resorcinol-formaldehyde aerogels and carbon aerogels

By using glycidol as a catalyst, high porosity, low-density resorcinol (R) and formaldehyde (F) aerogels and carbon aerogels (CAs) were synthesized via a sol-gel method. The effect of glycidol and water on the color, density, morphology, textual characteristics and adsorption properties of the resultant RF aerogels and CAs were investigated in detail. The results revealed that the properties of RF aerogels and CAs can be controlled by adjusting the amount of glycidol and water. The resultant RF aerogels and CAs were porous materials, the minimum densities of RF aerogels and CAs were 96 and 110 mg cm⁻³ respectively while the maximum specific surface areas of RF aerogels and CAs were 290 and 597 m² g⁻¹. The maximum adsorption capacity of CAs was about 125 mg g⁻¹ on Rhodamine B, which was higher than that of some reported CAs catalyzed by base and acid catalysts. The sol-gel mechanisms of RF aerogels and CAs can be attributed to the opening of the epoxy group of glycidol in the mixture of R and F.

The sol-gel mechanism of glycidol-catalyzed RF aerogels is the opening of the epoxy ring rather than the preservation the of epoxy ring.     

Diagnostic significance of long non-coding RNAs expression in tuberculosis patients: A systematic review and meta-analysis

Objectives:It is crucial to identify effective diagnostic biosignatures of tuberculosis (TB) to optimize its treatment. Herein, we conducted a systematic review to elucidate the diagnostic efficacy of long noncoding RNA (lncRNAs) as TB biomarkers.Methods:We searched Medline, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, VIP, and China Biology Medicine disc databases up to February 18, 2020. These studies focusing on lncRNAs as diagnosis markers of TB were collected. STATA 12.0 and Meta-disc1.4 software were used to analyze the data extracted from eligible studies.Results:We included 8 articles with 1058 TB patients, and 1896 healthy controls in our study. The values of pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.63, 0.86, 4.48, 0.43, and 10.31, respectively. Additionally, we plotted the summary receiver operating characteristic curve to evaluate the diagnostic accuracy, and the area under the curve was 0.80.Conclusion:The present study is the first meta-analysis to assess the diagnostic accuracy of lncRNAs in TB patients. We found that lncRNAs might constitute potential biomarkers for the diagnosis of TB patients. More population-based high-quality research should be conducted to validate the efficacy lncRNAs in TB patients.     

Development and Primary Application of an Indirect ELISA Based on Rep Protein to Analyze Antibodies against Porcine Cocirvirus-like Virus (PCLV)

Porcine circovirus-like virus (PCLV) is a member of circovirus that contains a single-strand DNA genome, which may be one of the pathogens that causes diarrheal symptoms in pigs. The Rep protein encoded by the genome of PCLV may be responsible for viral genome replication. The development of serological detection methods for PCLV is of great necessity for clinical diagnosis, as well as epidemiological investigations. Therefore, this study attempted to build an indirect enzyme-linked immunosorbent assay (ELISA) to examine antibodies against PCLV based on the His-tagged recombinant Rep protein. Full-length PCLV Rep protein was induced and expressed in E. coli and was purified as an antigen to establish an ELISA detection kit. The purified Rep protein was used to inject into mice to produce specific antibodies. There was no cross-reaction of Rep-based ELISA with antisera against other porcine viruses. The intra-assay and inter-assay coefficient variations (CVs) were 0.644–8.211% and 0.859–7.246%, respectively, indicating good repeatability. The non-cross-reaction with TGEV, PRRSV and PCV2 testing showed high sensitivity and high specificity for this ELISA assay. A total of 1593 serum samples collected from different pig farms in Jiangxi Province were tested for anti-PCLV Rep antibodies, and 284 (17.83%) of the 1593 samples were Rep antibody positive. Altogether, the indirect ELISA detection tool developed in this study could be applied to examine serum of PCLV antibodies with good repeatability, high sensitivity and high specificity. In addition, field sample detection results suggested that the PCLV antibody has a low prevalence in pig populations in Jiangxi Province of China.     

颈动脉内膜剥脱术在颈动脉狭窄患者中的应用

目的探讨颈动脉内膜剥除术（CEA）在颈动脉狭窄患者中的治疗效果。方法回顾分析我院2009～2013年,12例颈动脉粥样硬化伴狭窄的患者,通过术前颈动脉B超、CTA检查明确诊断,探讨相关手术适应证、手术方法、术后处理及治疗效果。结果患者均治愈出院,无死亡病例,所有患者均在全麻下行CEA,5例放置颈动脉转流管,7例未放置;头晕及TIA症状明显改善者8例;5例术后出现高血压、头痛;3例术后6h发生切口渗血,1例术后朐闷不适,冠脉CTA提示左前降支病变狭窄（85％）。结论CEA在治疗颈动脉粥样硬化伴狭窄中效果良好,需严格把握适应证,做好围手术期准备,合理使用转流管。     

脂蛋白脂酶活化剂NO-1886抑制糖尿病兔动脉粥样硬化的形成

目的　合成化合物NO 1886 ,一种脂蛋白脂酶活化观察脂蛋白脂酶活化剂是否降低高脂 /高蔗糖饲料诱发的糖尿病新西兰兔的血浆葡萄糖并减轻其动脉粥样硬化。方法　给予高脂 /高蔗糖饲料升高新西兰兔血浆总胆固醇 ,甘油三酯和葡萄糖及降低高密度脂蛋白胆固醇而导致动脉粥样硬化。饲料中加入 1 0 %NO 1886进行治疗观察。分别在 0、4、8、12、16、2 0及 2 4wk从禁食过夜的兔耳静脉抽取血样测定葡萄糖和脂质水平。第 2 4周末 ,处死动物 ,分离主动脉 ,经苏丹Ⅳ染色固定脂质后 ,计算脂纹病变面积。结果　应用NO 1886后 ,实验动物血浆葡萄糖 ,总胆固醇和甘油三酯降低 ,高密度脂蛋白胆固醇增加。对动脉粥样硬化的发展具有抑制作用。结论　NO 1886不仅可改善脂质紊乱 ,而且可降低血浆葡萄糖 ,减轻糖尿病兔动脉粥样硬化     

实验室信息管理系统的技术与应用进展

实验室信息管理系统(LIMS)自问世以来,在世界范围内取得了令人惊叹的技术进展和应用成就。该文从现代化实验室实施LIMS的意义,LIMS主要的技术发展阶段,目前国内LIMS的应用情况,分析测试性实验室在实施LIMS后预期达到的目标,以及当前LIMS项目实施中存在的问题和应用前景等方面进行综述。     

蜂海绵Haliclonasp.化学成分的研究

对采自我罱海的蜂海绵Ｈａｌｉｃｌｏｍａｓｐ．的化学成分进行了研究。结果表明：从Ｈａｌｉｃｌｏｎａｓｐ．中分离出２个结晶性化合物１和２。应用波谱分析和元素分析鉴定１和２的结构分别为１，３－二甲基黄嘌呤和对羟基苯甲酸。这是从海绵中分离出上述化合物的首次报道。