A secondary function of trehalose-6-phosphate synthase is required for resistance to oxidative and desiccation stress in Fusarium verticillioides

The disaccharide trehalose has long been recognized for its role as a stress solute, but in recent years some of the protective effects previously ascribed to trehalose have been suggested to arise from a function of the trehalose biosynthesis enzyme trehalose-6-phosphate (T6P) synthase that is distinct from its catalytic activity. In this study, we use the maize pathogenic fungus Fusarium verticillioides as a model to explore the relative contributions of trehalose itself and a putative secondary function of T6P synthase in protection against stress as well as to understand why, as shown in a previous study, deletion of the TPS1 gene coding for T6P synthase reduces pathogenicity against maize. We report that a TPS1-deletion mutant of F. verticillioides is compromised in its ability to withstand exposure to oxidative stress meant to simulate the oxidative burst phase of maize defense and experiences more ROS-induced lipid damage than the wild-type strain. Eliminating T6P synthase expression also reduces resistance to desiccation, but not resistance to phenolic acids. Expression of catalytically-inactive T6P synthase in the TPS1-deletion mutant leads to a partial rescue of the oxidative and desiccation stress-sensitive phenotypes, suggesting the importance of a T6P synthase function that is independent of its role in trehalose synthesis.     

Automatic Detection of Severely and Mildly Infected COVID-19 Patients with Supervised Machine Learning Models

ObjectivesWhen the prognosis of COVID-19 disease can be detected early, the intense-pressure and loss of workforce in health-services can be partially reduced. The primary-purpose of this article is to determine the feature-dataset consisting of the routine-blood-values (RBV) and demographic-data that affect the prognosis of COVID-19. Second, by applying the feature-dataset to the supervised machine-learning (ML) models, it is to identify severely and mildly infected COVID-19 patients at the time of admission.Material and methodsThe sample of this study consists of severely (n = 192) and mildly (n = 4010) infected-patients hospitalized with the diagnosis of COVID-19 between March-September, 2021. The RBV-data measured at the time of admission and age-gender characteristics of these patients were analyzed retrospectively. For the selection of the features, the minimum-redundancy-maximum-relevance (MRMR) method, principal-components-analysis and forward-multiple-logistics-regression analyzes were used. The features set were statistically compared between mild and severe infected-patients. Then, the performances of various supervised-ML-models were compared in identifying severely and mildly infected-patients using the feature set.ResultsIn this study, 28 RBV-parameters and age-variable were found as the feature-dataset. The effect of features on the prognosis of the disease has been clinically proven. The ML-models with the highest overall-accuracy in identifying patient-groups were found respectively, as follows: local-weighted-learning (LWL)-97.86%, K-star (K*)-96.31%, Naive-Bayes (NB)-95.36% and k-nearest-neighbor (KNN)-94.05%. Also, the most successful models with the highest area-under-the-receiver-operating-characteristic-curve (AUC) values in identifying patient groups were found respectively, as follows: LWL-0.95%, K*-0.91%, NB-0.85% and KNN-0.75%.ConclusionThe findings in this article have significant a motivation for the healthcare professionals to detect at admission severely and mildly infected COVID-19 patients.     

Novel (E)-3-(3-Oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides as Histone Deacetylase Inhibitors: Design,Synthesis and Bioevaluation

Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides ( 4 a – i , 7 a – g ) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI−H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a – i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a – g in all biological assays. Compounds 7 e – f were found to be the most active HDAC inhibitors with IC₅₀ of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC₅₀ values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity.     

八段锦联合抗阻运动对老年2型糖尿病患者糖脂代谢、氧化应激及生活质量的影响

摘要 目的：探讨八段锦联合抗阻运动对老年2型糖尿病（T2DM）患者糖脂代谢、氧化应激及生活质量的影响。方法：选取2021年4月~2022年5月期间在我院接受治疗的老年T2DM患者238例。按照随机数字表法分为对照组（在常规治疗的基础上,接受抗阻运动干预,119例）和联合组（在对照组的基础上,接受八段锦干预,119例）。观察两组糖脂代谢、氧化应激及生活质量的改善情况。结果：干预12周后,联合组体质量指数、腰臀比低于对照组（P<0.05）。干预12周后,联合组空腹血糖（FBG）、餐后2 h血糖（2hPG）、糖化血红蛋白（HbAlc）低于对照组（P<0.05）。干预12周后,联合组高密度脂蛋白胆固醇（HDL-C）高于对照组（P<0.05）,低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、甘油三酯（TG）低于对照组。干预12周后,联合组丙二醛（MDA）低于对照组,超氧化物歧化酶（SOD）、过氧化氢酶（CAT）高于对照组（P<0.05）。干预12周后,联合组的健康调查简表（SF-36）各维度评分均高于对照组（P<0.05）。结论：八段锦联合抗阻运动用于老年T2DM患者中,可有效改善患者的氧化应激、糖脂代谢,并提高患者的生活质量。     

基于蛋白组学的脓毒症补体凝血级联通路及标志物KLKB1研究

摘要 目的：通过蛋白质组学方法鉴定脓毒症关键通路及诊断标志物。方法：选取2019年1月至12月西南医科大学附属医院急诊科收治的56例脓毒症患者（脓毒症组）,另取同期50名健康体检志愿者（对照组）。采用随机抽样法分别选取两组中12名脓毒症患者和8名健康体检志愿者,利用非数据依赖模式（DIA）进行血清蛋白数据采集,将数据上传至iDEP在线平台分析脓毒症患者外周血中差异表达蛋白,进一步对这些差异蛋白进行生物信息学分析,包括主成分分析（PCA）、基因本体富集分析（GO）、通路富集分析和蛋白-蛋白相互作用网络（PPI）分析,进而筛选出脓毒症关键蛋白。采用酶联免疫吸附试验（ELISA）对脓毒症组、对照组进行关键蛋白表达验证分析。采用受试者工作特征（ROC）曲线分析关键蛋白对脓毒症的诊断效能。结果：蛋白质组学分析共鉴定出690个蛋白,筛选出171个差异表达蛋白（DEPs）,其中39个蛋白显著下调,132个蛋白显著上调。DEPs富集的核心通路为补体和凝血级联通路。该条通路中的血清激肽释放酶 1（KLKB1）在脓毒症组的表达水平为（121.80±55.63 ng/mL）,显著高于对照组的（68.30±57.11 ng/mL）,差异具有统计学意义（t=4.881,P=0.000）。根据ELISA结果进行脓毒症诊断ROC曲线分析得出,KLKB1蛋白诊断脓毒症的 AUC（95%CI）为0.759（0.594～0.923）。结论：补体和凝血级联通路为脓毒症免疫途径的重要通路,KLKB1具有较好的脓毒症诊断特性,可能是脓毒症潜在的诊断生物标志物。     

MiR-150-5p靶向TP53对结直肠癌细胞侵袭和增殖的影响

摘要 目的：探索miR-150-5p靶向调控TP53基因对结直肠癌（colorectal cancer, CRC）在临床和生物学的相关性,研究miR-150-5p调控TP53基因在结直肠癌细胞增殖和侵袭病变中的作用。方法：收集临床手术切除并病理证实的结直肠癌患者的手术及血浆样本（结直肠癌和癌旁组织）60例,另选取癌旁正常粘膜10例,腺瘤30例。根据瘤体直径分为肿瘤＞5 cm（n=30）和≤5 cm（n=30）。qRT-PCR法测定样本中miR-150-5p表达,荧光素酶活性测定以确定TP53是否为miR-150-5p的靶基因。使用SW480细胞株,进行Transwell小室检测细胞侵袭能力,CCK-8检测细胞增值能力,对miR-150-5p进行生物信息学分析。结果：TP53是miR-150-5p的下游基因。癌组织及血浆中miR-150-5p表达量低于癌旁组织,直径＞5 cm瘤体中的miR-150-5p表达量显著低于直径≤5 cm瘤体,Ⅰ-Ⅱ期结直肠癌组织中的miR-150-5p表达显著高于Ⅲ-Ⅳ期（P＜0.05）。上调miR-150-5p后,细胞中TP53表达下降,下调miR-150-5p后,TP53表达升高;CCK-8增殖试验显示细胞中miR-150-5p过表达组抑制细胞增殖（P＜0.05）。结论：MiR-150-5p在结直肠癌组织和细胞中显著低表达,miR-150-5p通过靶向调节TP53抑制人CRC细胞的侵袭和增殖,有望成为结直肠癌治疗的新靶点。     

比较CSPO和ISR治疗超低位直肠癌的保肛效果

摘要 目的：比较适形切除保肛术（CSPO）和经内外括约肌间切除术（ISR）治疗超低位直肠癌的保肛效果。方法：选择2020年6月至2022年3月选择在本院诊治的超低位直肠癌患者63例作为研究对象,根据随机分配原则把患者分为ISR组31例与CSPO组32例,ISR组予经内外括约肌间切除术治疗,CSPO组予适形切除保肛术治疗,记录与随访患者的近期与远期预后。结果：所有患者都顺利完成保肛,两组的术中出血量、淋巴结清扫数目对比无差异（P>0.05）,CSPO组的手术时间、术后肠道功能恢复时间、术后住院时间明显少于ISR组（P<0.05）。CSPO组的术后7 d的切口感染、泌尿系感染、吻合口狭窄、吻合口瘘等并发症发生率为6.3 %,明显低于ISR组的29.0 %（P<0.05）。CSPO组术后1 d、3 d、7 d的血清降钙素原（PCT）、超敏C-反应蛋白（hs-CRP）含量都明显少于ISR组（P<0.05）。ISR组术后3个月的满意度为80.6 %,明显低于CSPO组100.0 %（P<0.05）。结论：相对经内外括约肌间切除术,适形切除保肛术治疗超低位直肠癌能有效抑制血清PCT与hs-CRP的表达,具有很好的保肛效果,能减少并发症的发生,还可促进患者康复,从而持续提高患者的随访生存率。     

失眠障碍患者脑部CT影像学变化与学习记忆功能变化、临床特征相关性分析

摘要 目的：探讨失眠障碍患者脑部CT影像学变化与学习记忆功能变化、临床特征相关性。方法：回顾性选择2018年6月至2021年6月来我院诊治的失眠障碍患者50例,选择同期来我院体检的健康人群30例。两组受试者均使用飞利浦64排CT进行扫描,检测计算额角指数与海马指数,对比两组受试者的额角指数、海马指数,对比两组受试者的临床记忆评分、睡眠质量评分、WCST评分,分析两组受试者的临床症状,分析观察组患者额角指数、海马指数与临床记忆评分、睡眠指数评分、WCST评分、临床症状评分的相关性。结果：观察组的额角指数、海马指数明显较对照组低（P<0.05）。观察组的临床记忆评分明显较对照组低（P<0.05）。观察组的睡眠质量评分明显较对照组低（P<0.05）。观察组的完成测验数、选择错误率、完成第一个应答数、持续错误率、错误应答数明显较对照组高,完成分类数、概念化水平百分比明显较对照组低（P<0.05）。观察组的躯体感觉评分及心理感觉评分明显较对照组高（P<0.05）。额角指数、海马指数与临床记忆评分呈正比,与睡眠质量评分、临床症状评分呈反比,与WCST评分中的完成分类数、概念化水平百分比呈正比,与WCST评分中的完成测验数、选择错误率、完成第一个应答数、持续错误率、错误应答数呈反比（P<0.05）。结论：脑部CT影像学结果发现,失眠障碍存在学习记忆功能变化,与患者的临床特征相关性、睡眠质量存在存在一定相关性。     

丹参素注射液对急性心肌梗死大鼠的心室重构、心室功能及肢体导联与胸导联心电图参数的影响

摘要 目的：探讨丹参素注射液对急性心肌梗死大鼠的心室重构、心室功能及肢体导联与胸导联心电图参数的影响。方法：选择SD大鼠40只,将其鼠随机模型组、假手术组、硝酸甘油组、丹参注射液组。假手术组大鼠给予只在冠状动脉处穿针,不进行结扎,其余步骤同其余3组,其余3组均进行动物模型构建。假手术组、模型组大鼠均腹腔注射氯化钠注射液,硝酸甘油组腹腔注射硝酸甘油,丹参注射液组腹腔注射丹参注射液。对比4组大鼠的肢体导联与胸导联心电图参数,对比4组大鼠的血液流变学指标、左心室功能及左心室重构。结果：模型组的Ⅰ、Ⅱ、Ⅲ、aVL、aVF、V1、V2、V5、血浆粘度、纤维蛋白原、红细胞聚集指数、舒张末期室间隔厚度、左室舒张末期内径、左室收缩末期内径、左室舒张末期容积、左室收缩末期容积明显较假手术组、硝酸甘油组、丹参注射液组高,硝酸甘油、丹参注射液组以上指标明显较假手术组高,模型组的的左室舒张末期厚度、左室射血分数、左室短轴缩短率明显较假手术组、硝酸甘油组、丹参注射液组低,硝酸甘油、丹参注射液组的左室舒张末期厚度、左室射血分数、左室短轴缩短率明显较假手术组低。模型组的左心室重量指数、左心室截面直径明显较假手术组、硝酸甘油组、丹参注射液组高,硝酸甘油、丹参注射液组的左心室重量指数、左心室截面直径、梗死面积明显较假手术组高（P<0.05）,硝酸甘油组与丹参注射液组以上指标对比无差异（P>0.05）。结论：丹参素注射液可改善急性心肌梗死大鼠的心室重构、左心室功能及肢体导联与胸导联心电图参数,可能与其可降低大鼠的血液流变学指标水平有关。     

淋巴细胞及其亚群、NK细胞与儿童原发性免疫性血小板减少症复发的相关性研究

摘要 目的：为探讨淋巴细胞及其亚群、NK细胞与儿童原发性免疫性血小板减少症（ITP）复发的关系,评估其预测价值,为临床评估患者预后提供理论支持。方法：回顾性分析2017年12月-2021年12月于新疆医科大学第一附属医院儿科中心初发首诊为原发性免疫性血小板减少症的165例患儿,根据是否复发分为复发组与无复发组,评估ITP复发的影响因素,利用ROC曲线评估淋巴细胞计数绝对值对儿童ITP复发的预测价值,运用Kaplan-Meier法绘制与淋巴细胞计数绝对值相关的儿童ITP无复发生存曲线。结果：共纳入165名ITP患儿,复发率24.8%。淋巴细胞计数绝对值对儿童ITP无复发的ROC曲线下面积为0.704,95%CI为0.613-0.795（P＜0.05）,最佳截断值为3.21×10⁹/L。儿童ITP是否复发与年龄、淋巴细胞计数、出血评分、ESR有关,两组比较差异有统计学意义（P<0.05）。儿童ITP是否复发与CD3⁺CD19^-细胞计数、CD3⁺CD4⁺细胞计数、CD3⁺CD8⁺细胞计数、CD4⁺/CD8⁺细胞比例、NK细胞计数有关,两组比较差异有统计学意义（P<0.05）。结论：淋巴细胞计数绝对值可作为评估儿童ITP复发的预测指标,儿童ITP复发与初始T淋巴细胞亚群、NK细胞计数具有一定相关性。