Control of Pythium blight on turfgrass: Isolate characterization and strategies to delay fungicide resistance in Pythium aphanidermatum

Pythium blight, a serious disease ofturfgrass, is caused by Pythium spp., including P. aphanideramtum, an oomycete fungus. Tank-mixing strategies, which deploy a mixture of two or more fungicides with different modes of action, have been used to suppress problems of fungicide resistance. However, few studies have examined how interactions within P. aphanidermatum populations may affect the proliferation of resistance. The isolates present in populations of P. aphanidermatum may vary in their fitness characteristics, and those characteristics may play an important role in competition among isolates. Different fungicide treatments impose characteristic selection pressures on Pythium populations, which may differentially affect the survival of resistant and sensitive isolates. In order to improve effectiveness of current strategies, the influence of interaction of fitness characteristics and fungicide treatments on proliferation of fungicide-resistant isolates needs to be elucidated. A collection of 44 field isolates of P.aphanidermatum was used to investigate variation in fitness characteristics. Growth rate of mycelia, sporulation capacity, and aggressiveness on perennial ryegrass, along with sensitivity to mefenoxam, were quantified. Sixteen isolates showed complete resistance to mefenoxam. In 28 sensitive isolates, mefenoxam sensitivity was not correlated with the other three fitness characteristics. A wide variation in fitness characteristics was detected among the isolates. In the second phase of the research, two test populations were constructed by mixing two mefenoxam-sensitive isolates possessing different fitness characteristics with a mefenoxamresistant isolate in appropriate ratios. Changes in the proportion of resistant isolates within each population under six fungicide treatments were monitored during five cycles of selection on perennial ryegrass under controlled conditions. The rate of proliferation of mefenoxam-resistant isolates was lower under application of a half-rate fungicide mixture of mefenoxam with propamocarb than under application ofmefenoxam fungicide alone. No significant difference in the change of proportions of resistant isolates was detected between a test population containing a relatively fast-growing mefenoxam-sensitive isolate and a test population containing a relatively slow-growing isolate in any fungicide treatment. The results from this study indicated that half-rate tank mixing could delay the proliferation of mefenoxam-resistant isolates in a P. aphanideramtum population. An effect of fitness characteristics on rate of proliferation of mefenoxam resistance was not demonstrated

Phase 2 Study of Pemetrexed Plus Carboplatin, or Pemetrexed Plus Cisplatin with Concurrent Radiation Therapy Followed by Pemetrexed Consolidation in Patients with Favorable-Prognosis Inoperable Stage IIIA/B Non–Small-Cell Lung Cancer

IntroductionThere is no consensus chemotherapy regimen with concurrent radiotherapy (RT) for inoperable stage IIIA/B non–small-cell lung cancer. This trial evaluated pemetrexed with carboplatin (PCb) or cisplatin (PC) with concurrent RT followed by consolidation pemetrexed.MethodsIn this open-label, noncomparative phase II trial, patients with inoperable stage IIIA/B non–small-cell lung cancer (initially all histologies, later restricted to nonsquamous) were randomized (1:1) to PCb or PC with concurrent RT (64–68 Gy over days 1–45). Consolidation pemetrexed monotherapy was administered every 21 days for three cycles. Primary endpoint was 2-year overall survival (OS) rate.ResultsFrom June 2007 to November 2009, 98 patients were enrolled (PCb: 46; PC: 52). The 2-year OS rate was PCb: 45.4% (95% confidence interval [CI], 29.5–60.0%); PC: 58.4% (95% CI, 42.6–71.3%), and in nonsquamous patients was PCb: 48.0% (95% CI, 29.0–64.8%); PC: 55.8% (95% CI, 38.0–70.3%). Median time to disease progression was PCb: 8.8 months (95% CI, 6.0–12.6 months); PC: 13.1 months (95% CI, 8.3–not evaluable [NE]). Median OS (months) was PCb: 18.7 (95% CI, 12.9–NE); PC: 27.0 (95% CI, 23.2–NE). The objective response rates (ORRs) were PCb: 52.2%; PC: 46.2%. Grade 4 treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia, 6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. Most patients completed scheduled chemotherapy and RT during induction and consolidation phases. No drug-related deaths were reported during chemoradiotherapy.ConclusionsBecause of study design, efficacy comparisons cannot be made. However, both combinations with concurrent RT were active and well tolerated

A High-Resolution MRI Study of the Relationship Between Plaque Enhancement and Ischemic Stroke Events in Patients With Intracranial Atherosclerotic Stenosis

Purpose: To investigate the relationships among the degree of intracranial atherosclerotic stenosis (ICAS), plaque enhancement (PE), and ischemic stroke events (ISEs) using 3. 0 T high-resolution magnetic resonance imaging (HR-MRI).Materials and Methods: Fifty-two ICAS patients who underwent HR-MRI were retrospectively analyzed. The patients were divided into two groups according to the results of whole-brain digital subtraction angiography (DSA): the mild-moderate stenosis group (group MID) and the severe stenosis group (group SEV). According to the onset time of the ISEs, the plaques were divided into the acute/sub-acute phase culprit plaque group (group ACU, within 1 month), the chronic-phase culprit plaque group (group CHR, more than 1 month), and the non-culprit plaque group (group NON). Two neuroradiologists independently measured the signal intensity of PE and pituitary enhancement in the HR-MRI and calculated the ratio of the two indices. According to the ratio, the patients were divided into three groups: the marked enhancement group (group MA), the mild enhancement group (group ME), and the no enhancement plaque group (group NO). The relationships among the degree of ICAS, the degree of PE and ISEs were analyzed.Results: Seventy-two ICAS plaques were identified in 52 patients. The multiple independent samples Kruskal-Wallis H test showed that the differences among group ACU, CHR, and NON were significant in the degree of PE (P = 0.002). Group CHR and group NON were combined as the non-acute phase group (group non-ACU). Group NO and group ME were combined as the non-marked enhancement group (group non-MA). The comparison between group ACU and group non-ACU showed significant differences in the degree of both ICAS (P = 0.014) and PE (P = 0.006) according to the univariate logistic regression. The multivariate logistic regression model was used to analyze the impact of the degree of ICAS and PE on ISEs, and the results showed that severe stenosis (P = 0.036) and marked PE (P = 0.013) were independent risk factors for acute ISEs, respectively.Conclusion: Severe intracranial arterial stenosis and marked plaque enhancement are independent risk factors for acute ischemic stroke events, respectively. The study provides new ideas for further exploring the pathogenesis of stroke caused by intracranial atherosclerotic stenosis

Unveiling the additive-assisted oriented growth of perovskite crystallite for high performance light-emitting diodes.

Solution-processed metal halide perovskites have been recognized as one of the most promising semiconductors, with applications in light-emitting diodes (LEDs), solar cells and lasers. Various additives have been widely used in perovskite precursor solutions, aiming to improve the formed perovskite film quality through passivating defects and controlling the crystallinity. The additive's role of defect passivation has been intensively investigated, while a deep understanding of how additives influence the crystallization process of perovskites is lacking. Here, we reveal a general additive-assisted crystal formation pathway for FAPbI3 perovskite with vertical orientation, by tracking the chemical interaction in the precursor solution and crystallographic evolution during the film formation process. The resulting understanding motivates us to use a new additive with multi-functional groups, 2-(2-(2-Aminoethoxy)ethoxy)acetic acid, which can facilitate the orientated growth of perovskite and passivate defects, leading to perovskite layer with high crystallinity and low defect density and thereby record-high performance NIR perovskite LEDs (~800 nm emission peak, a peak external quantum efficiency of 22.2% with enhanced stability)

Randomized, Phase II Trial of Pemetrexed and Carboplatin with or without Enzastaurin versus Docetaxel and Carboplatin as First-Line Treatment of Patients with Stage IIIB/IV Non-small Cell Lung Cancer

Enzastaurin is an oral serine/threonine kinase inhibitor that targets protein kinase C-beta (PKC-β) and the phosphatidylinositol-3-kinase/AKT pathway. This trial assessed pemetrexed-carboplatin ± enzastaurin to docetaxel-carboplatin in advanced non-small cell lung cancer.Patients with stage IIIB (with pleural effusion) or IV non-small cell lung cancer and performance status 0 or 1 were randomized to one of the three arms: (A) pemetrexed 500 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to 6 cycles with a loading dose of enzastaurin 1125 or 1200 mg followed by 500 mg daily until disease progression, (B) the same regimen of pemetrexed-carboplatin without enzastaurin, or (C) docetaxel 75 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to six cycles. The primary end point was time to disease progression (TTP).Between March 2006 and May 2008, 218 patients were randomized. Median TTP was 4.6 months for pemetrexed-carboplatin-enzastaurin, 6.0 months for pemetrexed-carboplatin, and 4.1 months for docetaxel-carboplatin (differences not significant). Median survival was 7.2 months for pemetrexed-carboplatin-enzastaurin, 12.7 months for pemetrexed-carboplatin, and 9.2 months for docetaxel-carboplatin (log-rank = 0.05). Compared with the other arms, docetaxel-carboplatin was associated with lower rates of grade 3 thrombocytopenia and anemia but a higher rate of grade 3 or 4 febrile neutropenia.There was no difference in TTP between the three arms, but survival was longer with pemetrexed-carboplatin compared with docetaxel-carboplatin. Enzastaurin did not add to the activity of pemetrexed-carboplatin

Control of Pythium blight on turfgrass: Isolate characterization and strategies to delay fungicide resistance in Pythium aphanidermatum

Pythium blight, a serious disease ofturfgrass, is caused by Pythium spp., including P. aphanideramtum, an oomycete fungus. Tank-mixing strategies, which deploy a mixture of two or more fungicides with different modes of action, have been used to suppress problems of fungicide resistance. However, few studies have examined how interactions within P. aphanidermatum populations may affect the proliferation of resistance. The isolates present in populations of P. aphanidermatum may vary in their fitness characteristics, and those characteristics may play an important role in competition among isolates. Different fungicide treatments impose characteristic selection pressures on Pythium populations, which may differentially affect the survival of resistant and sensitive isolates. In order to improve effectiveness of current strategies, the influence of interaction of fitness characteristics and fungicide treatments on proliferation of fungicide-resistant isolates needs to be elucidated. A collection of 44 field isolates of P.aphanidermatum was used to investigate variation in fitness characteristics. Growth rate of mycelia, sporulation capacity, and aggressiveness on perennial ryegrass, along with sensitivity to mefenoxam, were quantified. Sixteen isolates showed complete resistance to mefenoxam. In 28 sensitive isolates, mefenoxam sensitivity was not correlated with the other three fitness characteristics. A wide variation in fitness characteristics was detected among the isolates. In the second phase of the research, two test populations were constructed by mixing two mefenoxam-sensitive isolates possessing different fitness characteristics with a mefenoxamresistant isolate in appropriate ratios. Changes in the proportion of resistant isolates within each population under six fungicide treatments were monitored during five cycles of selection on perennial ryegrass under controlled conditions. The rate of proliferation of mefenoxam-resistant isolates was lower under application of a half-rate fungicide mixture of mefenoxam with propamocarb than under application ofmefenoxam fungicide alone. No significant difference in the change of proportions of resistant isolates was detected between a test population containing a relatively fast-growing mefenoxam-sensitive isolate and a test population containing a relatively slow-growing isolate in any fungicide treatment. The results from this study indicated that half-rate tank mixing could delay the proliferation of mefenoxam-resistant isolates in a P. aphanideramtum population. An effect of fitness characteristics on rate of proliferation of mefenoxam resistance was not demonstrated.</p

Ortho-C–H Methoxylation of Aryl Halides Enabled by a Polarity Reversed N–O Reagent

Oxygen-substituted arenes not only commonly exist in biologically important molecules, but also serve as a versatile handle to install other functional groups. However, to date it remains challenging to install oxygen groups directly and site-selectively to common aromatic compounds, especially when additional arene functionalization is simultaneously required. Current arene C−H oxidation strategies generally require directing groups to control site-selectivity and/or use strong oxidants, whereas other approaches need precisely pre-functionalized substrates. While the palladium/norbornene (Pd/NBE) cooperative catalysis is promising for site-specific arene vicinal difunctionalization through simultaneous reactions with an electrophile and a nucleophile, respectively, at the ortho and ipso positions, the electrophile scope has been limited to species based on relatively “soft” elements, such as carbon, nitrogen, and sulfur. To shift the Pd/NBE-catalysis paradigm, here we report the development of an ortho oxygenation reaction with readily available aryl halides to rapidly deliver diverse methyl aryl ethers. The coupling of the “hard” oxygen-electrophile is enabled by a stable, polarity reversed, conformationally pre-distorted N−O reagent and facilitated by a C7-bromo-substituted NBE mediator. Mechanistic studies reveal a unique SN2-type pathway between the N−O reagent as the oxygen electrophile and an electron-rich Pd(II) nucleophile. This new C−H oxygenation reaction allows streamlined synthesis of complex bioactive compounds containing methyl aryl ethers and provides an efficient modular approach to access underrepresented benzenoid substitution patterns that are challenging to prepare otherwise

Rh-Catalyzed Reagent-Free Ring Expansion of Cyclobutenones and Benzocyclobutenones

Here we report a reagent-free rhodium-catalyzed ring-expansion reaction via C-C cleavage of cyclobutenones. A variety of poly-substituted cyclopentenones and 1-indanones can be synthesized from simple cyclobutenones and benzocyclobutenones. The reaction condition is near pH neutral without additional oxidants or reductants. The potential for developing a dynamic kinetic asymmetric transformation of this reaction has also been demonstrated. Further study supports the proposed pathway involving Rh-insertion into the cyclobutenone C-C bond, followed by beta-hydrogen elimination, olefin insertion and reductive elimination.CPRIT R 1118NIGMS R01GM109054-01Welch Foundation F 1781Chemistr

Efficient Benzimidazolidinone Synthesis via Rhodium-Catalyzed Double-Decarbonylative C–C Activation/Cycloaddition between Isatins and Isocyanates

The first decarbonylative cycloaddition of less-strained cyclic ketones (isatins) with isocyanates is reported. Initiated by C–C activation, this distinct [5 – 2 + 2] transformation provides a rapid entry to access various benzimidazolidinone derivatives, and a wide range of isocyanates can be efficiently coupled with broad functional group tolerance. A modified one-pot process combining a Curtius rearrangement and C–C activation was also achieved by using acyl azides as the starting materials. A detailed mechanistic study revealed a surprising double-decarbonylative reaction pathway. The novel reactivity discovered in this basic research is expected to shed light on the development of new heterocycle formation methods through C–C/isocyanate coupling