Development of novel isatin–nicotinohydrazide hybrids with potent activity against susceptible/resistant Mycobacterium tuberculosis and bronchitis causing–bacteria

Joining the global fight against Tuberculosis, the world''s most deadly infectious disease, herein we present the design and synthesis of novel isatin-nicotinohydrazide hybrids (5a–m and 9a–c) as promising anti-tubercular and antibacterial agents. The anti-tubercular activity of the target hybrids was evaluated against drug-susceptible M. tuberculosis strain (ATCC 27294) where hybrids 5d, 5g and 5h were found to be as potent as INH with MIC = 0.24 µg/mL, also the activity was evaluated against Isoniazid/Streptomycin resistant M. tuberculosis (ATCC 35823) where compounds 5g and 5h showed excellent activity (MIC = 3.9 µg/mL). Moreover, the target hybrids were examined against six bronchitis causing-bacteria. Most derivatives exhibited excellent antibacterial activity. K. pneumonia emerged as the most sensitive strain with MIC range: 0.49–7.81 µg/mL. Furthermore, a molecular docking study has proposed DprE1 as a probable enzymatic target for herein reported isatin-nicotinohydrazide hybrids, and explored the binding interactions within the vicinity of DprE1 active site.     

The effects of hair density of beef cattle on Haematobia irritans horn fly populations

Abstract We show the relationships that exist between the amount of hair and quantity of sebum on cattle skin and the population density of the horn fly, Haematobia irritans. Brahman and Chianina steers had means of 2390 and 1587 hairs per cm², respectively, significantly more than the mean number of hairs on Angus, Brahman x Angus Crossbred, Charolais, and Red Poll steers. The Chianina steers had > 30% more sebum present on their skin and hair (0.58g/929cm²) than the Angus, Charolais, and Red Poll steers at the Beef Cattle Research Station Savoy, Arkansas. The Brahman steers had a significantly greater amount of sebum present on the skin (1.51 g/ 929 cm²) than the Crossbred and purebred Angus steers (0.55 and 0.25g/929cm², respectively) at the South Central Family Farms Research Centre Booneville, Arkansas. The Brahman and Chianina steers had means of 61.9 and 17.0 horn flies per steer, respectively, during the fly season, whereas the Angus, Crossbred, Charolais and Red Poll steers had fly season means that ranged from 76.9 to 265.8 flies per steer. Regression analysis showed that an increase of 100 hairs per cm², was associated with a reduction of 11 horn flies in the Angus II, 5 in Angus I, 20 in Charolais, 37 in Red Poll, and 0.4 in Chianina steers at the Savoy Station and a reduction of 6.6 horn flies for the Angus, Brahman, and Crossbred steers at the Booneville Centre. Regardless of cattle breed, an increase of 1.0 g of sebum per 929 cm² output by the steer was associated with 478.5 additional hairs per cm² on the animal. Each increase of 0.25 g of sebum per 929 cm² resulted in a decrease of 9.2 horn flies per steer. We conclude that some of the factors responsible for fly-resistance in cattle are hair density and the corresponding amount of sebum present on cattle skin and hair.     

植物体细胞胚发生中抗氧化系统代谢动态和程序性细胞死亡

在胚性细胞分化过程中ＳＯＤ活性明显高于对照，同时ＳＯＤ活性与胚性细胞分化密切相关，表明胚性细胞具有较强的抗氧化能力。低浓度的Ｈ２Ｏ２对胚性细胞的分化有促进作用，并认为Ｈ２Ｏ２可能是作为一种细胞信号物，通过细胞信号系统调节相关基因表达，或通过提高细胞内Ｃａ＾２＋浓度而促进细胞分化。在胚性细胞分化和发育过程中存在程序性细胞死亡（ｐｒｏｇｒａｍｍｅｄ ｃｅｌｌ ｄｅａｔｈ，ＰＣＤ）。活性氧在诱发植物ＰＣ     

Ethylene induced cyanide resistant respiration in orchid petal cells

Respiration of isolated Aranda orchid petal cells increased markedly after cut flowers were treated with ethylene. An increase in respiration was observed 15 to 20h after treatment which was further enhanced in the presence of oxygen and ethylene. Ethylene induces the development of a cyanide resistant pathway in fully opened orchid flower tissues where the cyanide resistant capacity is negligible. However, there appears a shift back to the cyanide sensitive pathway some time after induction.     

Innovative approaches to novel antibacterial drug discovery

Increasing antibiotic resistance in microorganisms and new emerging pathogens have become a major problem in our society. Rising to satisfy this urgent medical need is a recent confluence of powerful new drug discovery technologies: combinatorial chemistry; sequence and functional genomic analysis; and novel methods of high-throughput screening. The combination of these technologies will bring to bear untapped power in the search for new antimicrobials.     

Screening Rate for Primary Aldosteronism Among Patients With Apparent Treatment-Resistant Hypertension: Retrospective Analysis of Current Practice

ObjectivePrimary aldosteronism (PA) is the most common secondary cause of hypertension. Patients with PA experience significant cardiovascular and other complications compared with patients with primary hypertension with the same degree of blood pressure control as those with PA. Guidelines have recommended screening all patients with resistant hypertension for PA. The objective of this study was to assess the screening rate for PA among patients with apparent treatment-resistant hypertension and determine the rate of positive screening test result among the group screened.MethodsThis was a retrospective chart review of electronic medical record data of all patients with hypertension aged ≥18 years within a single health system in Minnesota from September 2018 to September 2020.ResultsOf 140 734 patients who were aged ≥18 years and had a diagnosis of hypertension, 18 908 (13.4%) met the criteria for apparent treatment-resistant hypertension after those with congestive heart failure were excluded. Only 795 (4.2%) patients with apparent treatment-resistant hypertension underwent screening for PA in our cohort. Of the 795 patients who underwent screening for PA, 134 (16.9%) had a positive screening test result.ConclusionThe screening rate for PA among patients with resistant hypertension was low. Clinical and public health strategies directed at improving the screening rate for PA are vital.     

一种预测个体肿瘤的抗癌药物反应分类计算模型及其应用

目的 不同患者对同一抗癌药物的反应可能不同,了解患者之间对抗癌药物的反应差异对癌症精准医疗具有重大参考价值。方法 高通量测序数据为构建抗癌药物反应分类预测模型提供了强大的数据支撑。针对两大经典数据集癌症细胞百科全书(CCLE)和癌症药物敏感性基因组学数据集(GDSC),本文提出了基于最大相关最小冗余(mRMR)算法和支持向量机(SVM)的计算模型mRMR-SVM。利用基因表达数据,通过方差排序和mRMR算法提取特征基因,借助SVM实现抗癌药物对细胞系的“敏感-抑制”二分类预测。结果 对于CCLE中的22种药物,mRMR-SVM的平均准确率为0.904;对于GDSC中的11种药物,平均准确率为0.851。结论 mRMR-SVM不仅在预测性能方面优于传统的支持向量机、随机森林、深度反应森林、深度神经网络和细胞系-药物复杂网络模型,而且具有良好的泛化能力,对于三类特定组织的抗癌药物反应分类预测也取得了令人满意的结果。此外,mRMR-SVM可以识别与癌症发生发展密切相关的生物标志物。