BACKGROUND & AIMS: BACKGROUND:Major advances in our understanding of the underlying biology of prostate cancer have helped to herald a new era in the treatment of castration-resistant prostate cancer (CRPC), with 5 new agents having shown a survival advantage in the last 3 years and an impressive number of promising novel agents now entering the clinic. CONTENT:We discuss the challenges facing drug development for CRPC and strategies to meet these challenges, with a focus not only on the development of predictive and intermediate endpoint biomarkers, but also on novel hypothesis-testing, biomarker-driven clinical trial designs. SUMMARY:With several promising agents now entering the clinic, there is increasing pressure to rethink drug development for CRPC to ensure that novel agents are appropriately evaluated and that patients and resources are appropriately allocated. We envision that biomarker-driven, reiterative clinical trials will have a major impact on CRPC treatment through the testing of robust scientific hypotheses with rationally designed drugs and drug combinations administered to selected patients.

背景与目标： 背景：我们对前列腺癌基础生物学的认识的重大进步帮助开创了去势抵抗性前列腺癌（CRPC）治疗的新时代，最近5年中有5种新药显示出生存优势，并且数量惊人的有希望的新型药物现已进入临床。
内容：我们讨论了针对CRPC的药物开发面临的挑战以及应对这些挑战的策略，不仅着眼于预测性和中间终点生物标志物的开发，还着重于新的假设检验，生物标志物驱动的临床试验设计。
摘要：随着一些有前途的药物现在进入临床，对CRPC进行药物开发的重新思考的压力越来越大，以确保正确评估新型药物以及适当分配患者和资源。我们设想，通过对合理设计的药物和给药于选定患者的药物进行可靠的科学假设测试，生物标记物驱动的重复性临床试验将对CRPC治疗产生重大影响。

BACKGROUND & AIMS: :Antitumor agents that bind to tubulin and disrupt microtubule dynamics have attracted considerable attention in the last few years. To extend our knowledge of the thiazole ring as a suitable mimic for the cis-olefin present in combretastatin A-4, we fixed the 3,4,5-trimethoxyphenyl at the C4-position of the thiazole core. We found that the substituents at the C2- and C5-positions had a profound effect on antiproliferative activity. Comparing compounds with the same substituents at the C5-position of the thiazole ring, the moiety at the C2-position influenced antiproliferative activities, with the order of potency being NHCH(3) > Me > N(CH(3))(2). The N-methylamino substituent significantly improved antiproliferative activity on MCF-7 cells with respect to C2-amino counterparts. Increasing steric bulk at the C2-position from N-methylamino to N,N-dimethylamino caused a 1-2 log decrease in activity. The 2-N-methylamino thiazole derivatives 3b, 3d and 3e were the most active compounds as antiproliferative agents, with IC(50) values from low micromolar to single digit nanomolar, and, in addition, they are also active on multidrug-resistant cell lines over-expressing P-glycoprotein. Antiproliferative activity was probably caused by the compounds binding to the colchicines site of tubulin polymerization and disrupting microtubule dynamics. Moreover, the most active compound 3e induced apoptosis through the activation of caspase-2, -3 and -8, but 3e did not cause mitochondrial depolarization.

背景与目标： 近年来，与微管蛋白结合并破坏微管动力学的抗肿瘤剂引起了相当大的关注。为了扩展我们对噻唑环作为康美他汀A-4中顺式烯烃的合适模拟物的认识，我们将3,4,5-三甲氧基苯基固定在噻唑核心的C4位。我们发现，在C2和C5位置的取代基对抗增殖活性具有深远的影响。比较噻唑环C5位上具有相同取代基的化合物，C2位上的部分影响抗增殖活性，效力顺序为NHCH（3）> Me> N（CH（3））（2） 。相对于C 2-氨基对应物，N-甲基氨基取代基显着提高了对MCF-7细胞的抗增殖活性。从N-甲基氨基到N，N-二甲基氨基的C2位增加的空间体积导致活性降低1-2 log。 2-N-甲基氨基噻唑衍生物3b，3d和3e是最有效的化合物作为抗增殖剂，其IC（50）值从低微摩尔到一位数纳摩尔，此外，它们还对耐多药细胞具有活性系过度表达P-糖蛋白。抗增殖活性可能是由于化合物与微管蛋白聚合的秋水仙碱位点结合并破坏了微管动力学而引起的。此外，活性最高的化合物3e通过激活caspase-2，-3和-8诱导细胞凋亡，但3e不会引起线粒体去极化。

BACKGROUND & AIMS: :A system which combined ASBR with pulsed SBR (PSBR) was introduced to enhance COD and nitrogen removal from the real landfill leachate. ASBR was used to degrade the organics from raw leachate mainly. Three equal feeds mode was applied in PSBR operation. The results obtained from the joint operation period (157 days) show that the COD removal rate of ASBR was 83-88% under the specific loading rate of 0.43-0.62 gCOD gVSS(-1) day(-1). PSBR's operation can be divided into four phases according to the different influent NH(4)(+)-N which increased to 800-1000 mg L(-1) finally, and total nitrogen (TN) removal rate of more than 90% with the effluent TN of less than 40 mg L(-1) was obtained. PHB and glycogen can act as electron donor for endogenous denitritation orderly with the hypothetical function from DNGAOs. Consequently, the system achieved COD and TN removal rate of 89.61-96.73% and 97.03-98.87%, respectively, without any extra carbon source addition.

背景与目标： ：引入了结合了ASBR和脉冲SBR（PSBR）的系统，以提高从真实垃圾填埋场渗滤液中去除COD和氮的能力。 ASBR主要用于降解原渗滤液中的有机物。在PSBR操作中应用了三个均等进给模式。从联合运行期（157天）获得的结果表明，在比加载率为0.43-0.62 gCOD gVSS（-1）day（-1）的条件下，ASBR的COD去除率为83-88％。 PSBR的操作可根据进水NH（4）-N的不同而分为四个阶段，最终将其增加至800-1000 mg L（-1），而总氮（TN）去除率超过90％，获得的废水总氮少于40 mg L（-1）。 PHB和糖原可以按DNGAOs的假设功能有序地充当内源性反硝化的电子供体。因此，该系统在不添加任何碳源的情况下，分别实现了89.61-96.73％和97.03-98.87％的COD和TN去除率。

BACKGROUND & AIMS: :In our screening program for antihypertensive plant constituents extracts of the leaves and bark of Badula barthesia showed strong in vitro inhibition of angiotensin converting enzyme (ACE). Rapanone (1), 2,5-dihydroxy-3-tridecyl-1,4-benzoquinone, was isolated as an active constituent of the leaves. The IC(50) values of rapanone and three 3-alkyl-2,5-dihydroxybenzoquinones, (2)-(4), (Z)-2,5-dihydroxy-3-(pentadec-8-enyl)-1,4-benzoquinone, (Z,Z)-2,5-dihydroxy-3-(heptadeca-8,11-dienyl)-1,4-benzoqui-none and (Z)-2,5-dihydroxy-3-(heptadec-8-enyl)-1,4-benzoquinone recently isolated from Embelia angustifolia were determined. The following IC(50) ± S.D. values have been obtained (1) 36 ± 4.6 μM, (2) 19 ± 6.2 μM, (3) 19 ± 8.7 μM and (4) 16 ± 3.0 μ.M. The IC(50) value for the reference compound Captopril was determined to 12 ± 2.6 nM. The antimicrobial activity of the four compounds was determined by thin layer chromatography agar overlay technique as minimum growth inhibitory amount in μg. One yeast, Candida albicans, and four bacteria, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were used as test organisms.

背景与目标： ：在我们针对降压植物成分的筛选程序中，Badula barthesia的叶子和树皮提取物显示出对血管紧张素转化酶（ACE）的强烈抑制作用。分离出2,5-二羟基-3-十三烷基-1,4-苯醌的雷帕酮（1）作为叶片的活性成分。雷帕酮和三个3-烷基-2,5-二羟基苯醌，（2）-（4），（Z）-2,5-二羟基-3-（pentadec-8-enyl）-1， 4-苯醌，（Z，Z）-2,5-二羟基-3-（十七烷-8,11-二烯基）-1,4-苯并喹酮和（Z）-2,5-二羟基-3-（庚二酮）确定了最近从安哥拉花（Embelia angustifolia）分离的-8-烯基）-1,4-苯醌。以下IC（50）±S.D.已获得（1）36±4.6μM，（2）19±6.2μM，（3）19±8.7μM和（4）16±3.0μM。参考化合物卡托普利的IC（50）值确定为12±2.6 nM。通过薄层层析琼脂覆盖技术确定这四种化合物的抗微生物活性，以μg为单位的最小生长抑制量。将一种酵母，白色念珠菌和四种细菌（枯草芽孢杆菌，大肠杆菌，铜绿假单胞菌和金黄色葡萄球菌）用作测试生物。

BACKGROUND & AIMS: :The study of the ultrastructure of spematozoa by means of transmission electron microscopy often presents with problems of interpretation according to the method employed, depending on whether samples are either centrifuged previously to the fixation or immersed in viscous gels. The major problems of interpretation are: changes in the location of vesicles originated during the maturation process and modifications in the adsorption of seminal plasma proteins to the sperm membrane surface. The aim of our study is to communicate an original new method for the treatment of spermatozoa for ultrastructural study. Our method is based on the use of animal tissues as biological containers, inside which the spermatic suspensions are included. We developed this method using fresh sperm samples taken from mature Rasa aragonesa rams. As biological container, we used 2.5-cm long segments of the intestine of 1-week-old chickens (Gallus gallus) (diameter around 4 mm). To avoid any influence of digestive enzymes of the mucosa on the sperm surface, we put each intestine fragment inside out by means of microdissection forceps under bifocal optical microscope and cold light. One of the edges was tied with thin suture silk. The sperm suspension was injected in the optimal experimental condition and amount. Finally, the still open edge of the intestine segment was tied with silk in the same way as the other segment edge. By using this technique, we can perform a suitable morphological study at an ultrastructural level. In addition, the functional relationship of the ultrastructural components of the target cells is correctly preserved.

背景与目标： ：根据透射电子显微镜对血吸虫超微结构的研究通常会遇到根据所用方法进行解释的问题，这取决于样品是预先离心至固定液还是浸入粘性凝胶中。解释的主要问题是：在成熟过程中产生的囊泡位置的变化以及精浆蛋白对精子膜表面的吸附作用的改变。我们研究的目的是为了交流用于超微结构研究的治疗精子的原始新方法。我们的方法是基于将动物组织用作生物容器，其中包含了精子悬浮液。我们使用从成熟的Rasa aragonesa公羊中提取的新鲜精子样本开发了这种方法。作为生物容器，我们使用了2.5周长的1周龄鸡（鸡胆）的肠段（直径约4毫米）。为了避免粘膜消化酶对精子表面的任何影响，我们在双焦点光学显微镜和冷光下通过显微解剖钳将每个肠段内翻。边缘之一用细缝线缝合。以最佳实验条件和最佳剂量注射精子悬浮液。最后，肠段的仍然敞开的边缘与另一段段的边缘用丝绸绑在一起。通过使用这种技术，我们可以在超微结构水平上进行合适的形态学研究。另外，正确保留了靶细胞超微结构成分的功能关系。

BACKGROUND & AIMS: :Chemical genetics employs diverse small-molecule compounds to elucidate biological processes in a manner analogous to the mutagenesis strategies at the core of classical genetics. Screening small-molecule libraries for compounds that induce a phenotype of interest represents the forward chemical genetic approach, whereas the reverse approach involves small molecules targeting a single protein. Here, we review key differences between the goals for small-molecule screening in industry versus academia, recent developments in high-throughput screening, and publicly available resources of compound collections, screening facilities, and databases. A particularly exciting outcome of a chemical genetic screen is the discovery of a previously unknown role for a protein in a pathway together with compounds that affect the function of that protein. In illustrative cases, such discoveries have led to progress toward therapeutic development and more commonly have increased the size of the small molecule "toolbox" available to the research community for the study of biological processes.

背景与目标： 化学遗传学采用多种小分子化合物来阐明生物学过程，其方式类似于经典遗传学的核心诱变策略。在小分子文库中筛选诱导目标表型的化合物代表了正向化学遗传方法，而反向方法则涉及靶向单个蛋白质的小分子。在这里，我们回顾了工业界和学术界对小分子筛选的目标，高通量筛选的最新发展以及化合物集合，筛选设施和数据库的公开可用资源之间的主要区别。化学遗传筛选的一个特别令人兴奋的结果是，发现一种蛋白质在通路中的作用是未知的，而化合物会影响该蛋白质的功能。在说明性情况下，这样的发现导致了治疗发展的进步，并且更普遍地增加了可供研究团体用于生物学过程研究的小分子“工具箱”的大小。

BACKGROUND & AIMS: :This account revolves around fascination and excitement with science. Early curiosity and fortunate opportunities can lead to a satisfying career. The privilege of performing basic research in biochemistry and molecular biology at a university coupled with teaching motivated students and working with dedicated co-workers makes for sustained thrust in the advance of knowledge. Research fields centered around cellular redox systems, oxidants and antioxidants, and the concept of oxidative stress. A noteworthy aspect is the global network of scientists joining in these endeavors worldwide.

背景与目标： ：这个科目围绕着对科学的迷恋和兴奋。早期的好奇心和幸运的机会可以带来令人满意的职业。在一所大学从事生物化学和分子生物学基础研究的特权，再加上积极进取的学生教学以及与敬业的同事一起工作的特权，为不断发展的知识提供了动力。研究领域围绕细胞氧化还原系统，氧化剂和抗氧化剂以及氧化应激的概念。一个值得注意的方面是参与全球这些努力的全球科学家网络。

BACKGROUND & AIMS: :A series of berberine-thiophenyl hybrids were designed, synthesised, and evaluated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and β-amyloid (Aβ) aggregation and as antioxidants. Among these hybrids, compounds 4f and 4i, berberine linked with o-methylthiophenyl and o-chlorothiophenyl by a 2-carbon spacer, were observed to be potent inhibitors of AChE, with IC50 values of 0.077 and 0.042 μM, respectively. Of the tested compounds, 4i was also the most potent inhibitor of BuChE, with an IC50 value of 0.662 μM. Kinetic studies and molecular modelling simulations of the AChE-inhibitor complex indicated that a mixed-competitive binding mode existed for these berberine derivatives. The biological studies also demonstrated that these hybrids displayed interesting activities, including Aβ aggregation inhibition and antioxidant properties.

背景与目标： ：设计，合成并评估了一系列小ber碱-硫代苯基杂化物，作为乙酰胆碱酯酶（AChE），丁酰胆碱酯酶（BuChE）和β-淀粉样蛋白（Aβ）聚集的抑制剂和抗氧化剂。在这些杂种中，观察到化合物4f和4i（通过2碳间隔基与邻甲基硫代苯基和邻氯硫代苯基连接的小ber碱）是有效的AChE抑制剂，IC50值分别为0.077和0.042μM。在测试的化合物中，4i也是BuChE的最强抑制剂，IC50值为0.662μM。 AChE-抑制剂复合物的动力学研究和分子建模模拟表明，这些小碱衍生物存在混合竞争结合模式。生物学研究还表明，这些杂种表现出有趣的活性，包括抑制Aβ聚集和抗氧化性能。

BACKGROUND & AIMS: :We recently reported the discovery of octahydropyrrolo[1,2-a]pyrazine A as a lead compound for an inhibitor of apoptosis proteins (IAP) antagonist. To develop IAP antagonists with favorable PK profiles, we designed novel tri-cyclic compounds, octahydro-1H-cyclopropa[4,5]pyrrolo[1,2-a]pyrazines 1 and 2 based on co-crystal structural analysis of A with cellular IAP-1 (cIAP-1). The additional cyclopropane moiety was used to block the predicted metabolic site of compound A without detriment to the binding affinity for cIAP. Compounds 1 and 2 were stereoselectively synthesized via intermediates 4a and 5b', which were obtained by Simmons-Smith cyclopropanation of ethylester 3a and silyl ether 3b'. Compounds 1 and 2 showed strong growth inhibition in MDA-MB-231 breast cancer cells and improved metabolic stability in comparison to A. Compound 2 exhibited significant in vivo PD effects to increase tumor necrosis factor-alpha mRNA in a dose dependent manner.

背景与目标： ：我们最近报道了八氢吡咯并[1,2-a]吡嗪A作为凋亡蛋白（IAP）拮抗剂抑制剂的先导化合物的发现。为了开发具有良好PK谱的IAP拮抗剂，我们基于A与细胞的共晶体结构分析，设计了新颖的三环化合物，八氢-1H-环丙[4,5]吡咯并[1,2-a]吡嗪1和2。 IAP-1（cIAP-1）。额外的环丙烷部分用于封闭化合物A的预测代谢位点，而不会损害对cIAP的结合亲和力。经由中间体4a和5b'立体选择性地合成化合物1和2，所述中间体通过乙酯3a和甲硅烷基醚3b'的Simmons-Smith环丙烷化获得。与A相比，化合物1和2在MDA-MB-231乳腺癌细胞中显示出强大的生长抑制作用，并改善了代谢稳定性。化合物2在剂量方面具有显着的体内PD效应，从而增加了肿瘤坏死因子-αmRNA的表达。

BACKGROUND & AIMS: :This review describes effects of miso with reference to prevention of radiation injury, cancer and hypertension with a twin focus on epidemiological and experimental evidence. Miso with a longer fermentation time increased crypt survival against radiation injury in mice. When evaluating different types of miso provided by different areas in Japan, miso fermented for a longer period increased the number of surviving crypts, and 180 days of fermentation was the most significant. Dietary administration of 180-day fermented miso inhibits the development of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and rat colon cancers in F344 rats. Miso was also effective in suppression of lung tumors, breast tumors in rats and liver tumors in mice. The incidence of gastric tumors of groups of rats given NaCl was higher than those of the groups given miso fermented for longer periods. Moreover, the systolic blood pressure of the Dahl male rat on 2.3% NaCl was significantly increased but that of the SD rat was not. However, the blood pressures of the rats on a diet of miso or commercial control diet (MF) did not increase. Even though miso contains 2.3% NaCl, their blood pressures were as stable as those of rats fed commercial diet containing 0.3% salt. So we considered that sodium in miso might behave differently compared with NaCl alone. These biological effects might be caused by longer fermentation periods.

背景与目标： ：这篇综述描述了味o在预防放射损伤，癌症和高血压方面的作用，并以流行病学和实验证据为重中之重。具有较长发酵时间的味iso增加了小鼠抗辐射损伤的隐窝存活率。在评估日本不同地区提供的不同类型的味o时，长时间发酵的味o增加了存活的隐窝的数量，最重要的是发酵180天。饮食中180天发酵味mis的饮食可抑制F344大鼠中乙氧基甲烷（AOM）诱导的异常隐窝灶（ACF）和大鼠结肠癌的发展。味iso在抑制肺肿瘤，大鼠乳腺肿瘤和小鼠肝肿瘤方面也有效。给予NaCl的大鼠胃肿瘤的发生率高于经长期不适当发酵的大鼠的胃肿瘤。此外，Dahl雄性大鼠在2.3％NaCl上的收缩压显着升高，而SD大鼠则没有。但是，以味o饮食或商业对照饮食（MF）饮食的大鼠血压并未增加。即使味o中含有2.3％的氯化钠，它们的血压也与喂食含有0.3％盐的商业饮食的老鼠的血压一样稳定。因此，我们认为味sodium中的钠与单独的NaCl相比可能具有不同的行为。这些生物学效应可能是由更长的发酵时间引起的。

BACKGROUND & AIMS: :One of the major challenges modern nephrology should face is the identification of biomarkers that are associated with histopathological patterns or defined pathogenic mechanisms that might aid in the non-invasive diagnosis of the causes of nephrotic syndrome, or in establishing prognosis sub-groups based on each type of disease, thus predicting response to treatment and/or recurrence. Advancements in the understanding of the pathogenesis of the different diseases that cause nephrotic syndrome, along with the progressive development and standardisation of plasma and urine proteomics techniques, have facilitated the identification of a growing number of molecules that might be useful for these objectives. Currently, the available information for many of the possible candidates identified to date, above all those discovered using proteomics, are still very preliminary. In this review, we summarise the available evidence for the different molecules that have been best assessed using clinical studies.

背景与目标： ：现代肾脏病应面临的主要挑战之一是与组织病理学模式或确定的致病机制相关的生物标志物的鉴定，这些标志物可能有助于无创诊断肾病综合征的原因，或根据其建立预后亚组每种类型的疾病，从而预测对治疗和/或复发的反应。在了解引起肾病综合征的不同疾病的发病机理方面的进步，以及血浆和尿液蛋白质组学技术的逐步发展和标准化，已经促进了越来越多的可能对这些目标有用的分子的鉴定。目前，迄今为止，对于许多可能的候选者（最重要的是使用蛋白质组学发现的），可用信息仍然非常初步。在这篇综述中，我们总结了可利用临床研究对不同分子进行最佳评估的现有证据。

BACKGROUND & AIMS: :Pharmacological response depends on multiple factors and one of them is sex-gender. Data on the specific effects of sex-gender on pharmacokinetics, as well as the safety and efficacy of numerous medications, are beginning to emerge. Nevertheless, the recruitment of women for clinical research is inadequate, especially during the first phases. In general, pharmacokinetic differences between males and females are more numerous and consistent than disparities in pharmacodynamics. However, sex-gender pharmacodynamic differences are now increasingly being identified at the molecular level. It is now even becoming apparent that sex-gender influences pharmacogenomics and pharmacogenetics. Sex-related differences have been reported for several parameters, and it is consistently shown that women have a worse safety profile, with drug adverse reactions being more frequent and severe in women than in men. Overall, the pharmacological status of women is less well studied than that of men and deserves much more attention. The design of clinical and preclinical studies should have a sex-gender-based approach with the aim of tailoring therapies to an individual's needs and concerns.

背景与目标： ：药理反应取决于多种因素，其中之一是性别。有关性别对药代动力学的特定作用以及多种药物的安全性和有效性的数据开始出现。然而，招募女性从事临床研究是不够的，特别是在第一阶段。通常，雄性和雌性之间的药代动力学差异比药效学上的差异更为广泛和一致。但是，现在越来越多地在分子水平上发现性别药效差异。现在甚至变得很明显，性别会影响药物基因组学和药物遗传学。已经报道了几个参数的性别相关差异，并且始终表明，女性的安全性较差，与男性相比，女性的药物不良反应更为频繁和严重。总体而言，与男性相比，女性的药理状况研究较少，应引起更多关注。临床和临床前研究的设计应采用基于性别的方法，目的是根据个体的需要和关注量身定制疗法。

BACKGROUND & AIMS: :In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P = .14). Gene expression profiles of t(8;16)(p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases.

背景与目标： ：在小儿急性髓细胞性白血病（AML）中，细胞遗传学异常是预后的重要指标。一些复发性细胞遗传学异常，如t（8; 16）（p11; p13）很少见，因此需要开展合作研究来确定其预后影响。我们收集了来自18个参加国际柏林-法兰克福-明斯特（I-BFM）AML研究组的国家的62例t（8; 16）（p11; p13）的小儿AML患者的临床特征，形态和免疫表型。我们使用1995-2005年诊断的AML-BFM队列（n = 543）作为参考队列。小儿t（8; 16）（p11; p13）AML患者的中位年龄明显较低（1.2岁）。大多数（97％）患有M4-M5法裔-美国-英国类型，与参考队列有显着差异。频繁发生红细胞吞噬作用（70％），皮肤角质白血病（58％）和弥散性血管内凝血（39％）。令人惊讶的是，有7例t（8; 16）（p11; p13）的新生儿自发缓解，其中3例持续缓解。 1993年后确诊的患者的5年总生存率为59％，与参考队列相似（P = 0.14）。 t（8; 16）（p11; p13）儿科AML病例的基因表达谱聚集在MLL重排的AML附近，但与MLL重排的AML不同。高度表达的基因包括HOXA11，HOXA10，RET，PERP和GGA2。总之，小儿t（8; 16）（p11; p13）AML是一种罕见的实体，由独特的基因表达特征和独特的临床特征所定义，这些特征在一部分新生儿病例中会自发缓解。

BACKGROUND & AIMS: :The strain denominated TRQ65 was isolated from wheat (Triticum turgidum subsp. durum) commercial fields in the Yaqui Valley, Mexico. Here, we report its draft genome sequence, which presented ~ 4.5 million bp and 45.5% G + C content. Based on the cutoff values on species delimitation established for average nucleotide identity (> 95 to 96%), genome-to-genome distance calculator (> 70%), and the reference sequence alignment-based phylogeny builder method, TRQ65 was strongly affiliated to Bacillus paralicheniformis. The rapid annotation using subsystem technology server revealed that TRQ65 contains genes related to osmotic, and oxidative stress response, as well as auxin biosynthesis (plant growth promotion traits). In addition, antiSMASH and BAGEL revealed the presence of genes involved in lipopeptides and antibiotic biosynthesis. The function of those annotated genes was validated at a metabolic level, observing that strain TRQ65 was able to tolerate saline (91.0%), and water (155.0%) stress conditions, besides producing 28.8 ± 0.9 µg/mL indoles. In addition, strain TRQ65 showed growth inhibition (1.6 ± 0.4 cm inhibition zone) against the causal agent of wheat spot blotch, Bipolaris sorokiniana. Finally, plant-microbe interactions assays confirm the ability of strain TRQ65 to regulate wheat growth, showing a significant increment in shoot height (26%), root length (40%), shoot dry weight (48%), stem diameter (55%), and biovolume index (246%). These findings provide insights for future agricultural studies of this strain.

背景与目标： ：命名为TRQ65的菌株是从墨西哥Yaqui谷地的小麦（Triticum turgidum subsp。durum）商业田中分离出来的。在这里，我们报告了它的基因组序列草案，呈现了约450万bp和45.5％的G C含量。基于为平均核苷酸同一性（> 95％至96％），基因组间距离计算器（> 70％）和基于参考序列比对的系统发育构建方法建立的物种定界的临界值，TRQ65与副芽孢杆菌。使用子系统技术服务器的快速注释显示，TRQ65包含与渗透和氧化应激反应以及生长素生物合成（植物生长促进性状）相关的基因。此外，antiSMASH和BAGEL揭示了涉及脂肽和抗生素生物合成的基因的存在。这些注释基因的功能在代谢水平上得到验证，观察到菌株TRQ65能够耐受盐水（91.0％）和水（155.0％）的胁迫条件，此外还可以产生28.8±0.9μg/ mL的吲哚。此外，菌株TRQ65对小麦斑斑病Bipolaris sorokiniana的病因有抑制作用（1.6（±0.4 cm抑制区）。最后，植物-微生物相互作用试验证实了TRQ65菌株调节小麦生长的能力，显示出苗高（26％），根长（40％），苗干重（48％），茎直径（55％）显着增加。 ）和生物量指数（246％）。这些发现为该菌株的未来农业研究提供了见识。

BACKGROUND & AIMS: :The below article presents the results of spectroscopic research, theoretical (time-dependent density functional theory (TD-DFT)), microbiological, and antioxidative calculations for three compounds from the group of 1,3,4-thiadiazoles: 2-amino-5-phenyl-1,3,4-thiadiazole (TB), 2-amino-5-(2-hydroxyphenyl)-1,3,4-thiadiazole (TS), 2-amino-5-(2-hydroxy-5-sulfobenzoyl)-1,3,4-thiadiazole (TSF). In the fluorescence emission spectra (TS) of solutions with varying concentrations of hydrogen ions, a particularly interesting effect of dual fluorescence was observed. The aforementioned effect was observed even more clearly in the environment of butan-1-ol, relative to the compound's concentration. Depending on the modification of the resorcylic substituent (TS and TSF), we observed the emergence of two separate, partially overlapping, fluorescence emission spectra or a single emission spectrum. Interpretation of the obtained spectra using stationary and time-resolved spectroscopy allowed the correlation of the effect's emergence with the phenomenon of molecular aggregation (of a particular type) as well as, above all, the structure of the substituent system. The overlap of said effects most likely induces the processes related to the phenomenon of charge transfer (in TS) and is responsible for the observed fluorescence effects. Also, the position of the -OH group (in the resorcylic ring) is significant and can facilitate the charge transfer (CT). The determinations of the changes in the dipole moment and TD-DFT calculations further corroborate the above assumption. The following paper presents the analysis (the first for this particular group of analogues) of the fluorescence effects relative to the changes in the structure of the resorcylic group combined with pH effects. The results of biological studies also indicate the highest pharmacological potential of the analogue in the case where the effects of dual fluorescence emission are observed, which predisposes this particular group of fluorophores as effective fluorescence probes or potential pharmaceuticals with antimycotic properties.

背景与目标： ：以下文章介绍了1,3,4-噻二唑类化合物中三种化合物的光谱学研究结果，理论研究（随时间变化的密度泛函理论（TD-DFT）），微生物学和抗氧化计算：2-氨基- 5-苯基-1,3,4-噻二唑（TB），2-氨基-5-（2-羟基苯基）-1,3,4-噻二唑（TS），2-氨基-5-（2-羟基-5 -磺基苯甲酰基）-1,3,4-噻二唑（TSF）。在具有变化的氢离子浓度的溶液的荧光发射光谱（TS）中，观察到了双重荧光特别有趣的效果。相对于该化合物的浓度，在丁烷-1-醇的环境中甚至更清楚地观察到上述效果。根据间苯二酚取代基（TS和TSF）的修饰，我们观察到出现了两个单独的，部分重叠的荧光发射光谱或单个发射光谱。使用固定和时间分辨光谱对获得的光谱进行解释，可以将这种效应的出现与分子聚集现象（一种特定类型）以及尤其是取代基系统的结构相关联。所述效应的重叠最有可能诱发与电荷转移现象有关的过程（在TS中），并且是观察到的荧光效应的原因。同样，-OH基团（在对苯二环中）的位置很重要，并且可以促进电荷转移（CT）。偶极矩变化的确定和TD-DFT计算进一步证实了上述假设。以下论文介绍了荧光效应相对于间苯二酚基团结构的变化与pH效应的关系的分析（这是该特定类似物组的第一个）。生物学研究的结果还表明，在观察到双重荧光发射的情况下，该类似物具有最高的药理学潜力，这使该特定种类的荧光团容易成为有效的荧光探针或具有抗真菌特性的潜在药物。