A Donor-Acceptor 10-Cycloparaphenylene and Its Use as an Emitter in an Organic Light-Emitting Diode.

Here, we explored the possibility of using cycloparaphenylenes (CPP) within a donor-acceptor TADF emitter design. 4PXZPh-[10]CPP contains four electron-donating moieties connected to a [10]CPP. In the 15 wt % doped in CzSi film, 4PXZPh-[10]CPP showed sky-blue emission with λPL = 475 nm, ΦPL = 29%, and triexponential emission decays with τPL of 4.4, 46.3, and 907.8 ns. Solution-processed OLEDs using 4PXZPh-[10]CPP exhibited sky-blue emission with an λEL of 465 nm and an EQEmax of 1.0%.

Structure-Activity Studies of N-Heterocyclic Benzoyl Arylamine Derivatives Led to a Highly Fungicidal Candidate against Gaeumannomyces graminis var. tritici and Four Fusarium Wheat Pathogens.

Wheat root diseases can seriously reduce yields and quality of wheat. 1,2,4-Triazole benzoyl arylamine derivatives previously showed good activities against some wheat root fungal pathogens. To further systematically disclose the structure-activity relationship, a series of benzoyl arylamines were designed and prepared. Their structures were characterized and fungicidal activities against Gaeumannomyces graminis var. tritici and Fusarium graminearum were evaluated. The results indicated that the structure of the N-heterocyclic group and the substituted group and their position on the benzamide scaffold had an important influence on the activities, as predicted. Finally, compound 18f was found to show excellent activities against G. graminis var. tritici, F. graminearum, Fusarium culmorum, Fusarium pseudograminearum, and Fusarium moniliforme with half-maximum effective concentrations of 0.002, 0.093, 0.011, 0.881, and 0.287 µg/mL, respectively. These results proposed that compound 18f deserved serious consideration as a novel fungicide candidate for the control of wheat root diseases.

SOX30 Overexpression Reflects Tumor Invasive Degree, Lymph Node Metastasis and Predicts Better Survival in Colorectal Cancer Patients: A Long-Term Follow-Up Cohort Study.

Aims: Sex-determining region Y-box containing gene 30 (SOX30) takes part in the progression of several cancers, while its clinical engagement in colorectal cancer (CRC) is obscure. Therefore, this study aimed to explore the association of SOX30 with clinicopathological features and prognosis in CRC patients. Methods: Tumor and adjacent noncancerous specimens of 195 CRC patients who received resection were acquired. Furthermore, an immunohistochemistry assay was performed to detect SOX30 protein expression in these specimens; meanwhile, SOX30 mRNA expression was determined by reverse transcription-quantitative polymerase chain reaction assay in 95 out of 195 specimens. Moreover, clinical characteristics and survival data (follow-up duration median (range): 71.0 (7.0-95.0) months) of CRC patients were gathered. Results: SOX30 protein and mRNA expressions were both decreased in CRC tumor tissue compared to adjacent tissue (both P < 0.001). Furthermore, a negative correlation was found in tumor SOX30 protein expression with tumor size (P = 0.049), lymph node (LYN) metastasis (P = 0.018), T stage (P = 0.001), N stage (P = 0.034), and TNM stage (P = 0.001); tumor SOX30 mRNA expression was also negatively correlated with LYN metastasis (P = 0.001), T stage (P = 0.019), N stage (P = 0.004), and TNM stage (P < 0.001). Furthermore, tumor SOX30 protein expression was positively correlated with overall survival (OS) (P = 0.017), while tumor SOX30 mRNA expression was not correlated with OS (P = 0.070). Multivariate Cox's regression analysis illustrated that tumor SOX30 protein high expression was an independent factor for favorable OS (hazard ratio: 0.525, P = 0.034). Conclusions: SOX30 has potential as a biomarker for the progression and prognostication of CRC, which might improve the management of CRC.

Syntheses of Tetrasubstituted [10]Cycloparaphenylenes by a Pd-catalyzed Coupling Reaction. Remarkable Effect of Strain on the Oxidative Addition and Reductive Elimination.

A small library of tetrasubstituted [10]cycloparaphenylene ([10]CPP) derivatives bearing alkyl, alkenyl, alkynyl and aryl substituents was constructed by a Pd-catalyzed cross-coupling reaction starting from tetratriflate [10]CPP 5 e, which was readily available in high yields on a >2 g scale. The CPP skeleton increases the reactivity of aryl triflate for oxidative addition to the Pd species, and 5 e is 10 times more reactive than its linear paraphenylene analogue, as determined by competition experiments. Theoretical calculations suggest that the accumulation of the small strain relief from each paraphenylene unit not involved in the reaction is responsible for the observed enhanced reactivity.

Synthesis of 1, 2, 4-triazole benzoyl arylamine derivatives and their high antifungal activities.

Two series of novel 1, 2, 4-triazole benzoyl arylamine derivatives were prepared and screened for their activities against three pathogens of Gaeumannomyces graminis var.tritici, Sclerotinia sclerotiorum and Fusarium graminearum using the mycelium growth inhibition method in vitro. The results indicated that most of the synthesized derivatives displayed antifungal activities. Compounds 6c-d and 6f-g exhibited lower EC50s against all the three pathogens. Among of them, the compound 6g displayed the most potent antifungal activities with EC50 values of 0.01, 0.19 and 0.12 µg mL-1 respectively. The structure and activity relationship showed that election-withdrawing group at pata-position of aniline was favorable for high activities, and the preferred groups were alkoxy carbonyls. These results proposed that the compound 6g can be a lead compound for development of novel fungicide.

Gram-Scale Syntheses and Conductivities of [10]Cycloparaphenylene and Its Tetraalkoxy Derivatives.

[10]Cycloparaphenylene ([10]CPP) and its tetraalkoxy derivatives were synthesized on the gram scale in 7 steps starting from 1,4-benzoquinone or 2,5-dialkoxy-1,4-benzoquinone. The key steps involve the highly cis-selective bis-addition of 4-bromo-4'-lithiobiphenyl to the quinones to produce a five-ring unit containing cyclohexa-1,4-diene-3,6-diol moiety, the platinum-mediated dimerization of the five-ring unit, and the H2SnCl4-mediated reductive aromatization of cyclohexadienediol. The tetraalkoxy substituents increased the solubility of [10]CPP in common organic solvents. The carrier-transport properties of thin films of [10]CPP and its derivatives were measured for the first time and indicated that [10]CPP derivatives could rival phenyl-C61-butyric acid methyl ester, which is used widely as an n-type active layer in bulk heterojunction photovoltaics.

Alternative splice variants of phospholipase C-beta2 are expressed in platelets: effect on Galphaq-dependent activation and localization.

Phospholipase C (PLC) beta2 plays a pivotal role in G-protein dependent signal transduction in platelets. We have previously demonstrated in platelets, leukocytes and human erythroleukemia cells the presence of transcripts of two forms of PLC-beta2 generated by alternative splicing. They differ by 45 nucleotides in the carboxyl-terminal region and are designated as PLC-beta2a and PLC-beta2b, with and without by 15 amino acid residues (corresponding to 864-878). The presence of the two variants has not been shown at the protein level in cells. Moreover, the carboxy-terminal region of PLC-beta has been implicated in Galphaq activation, particulate association, and nuclear localization, suggesting that the PLC-beta2 splice variants may be regulated differentially. We demonstrate for the first time that both PLC-beta2 isoforms are expressed in platelets at the protein level. Studies in CV-1 cells transfected with PLC-beta2a or beta2b cDNAs, along with constitutively activated Galphaq (Q209L), showed that inositolphosphate formation was comparable between the two variants. However, the nuclear localization of the two isoforms was different with a higher cytoplasmic to nuclear ratio for PLC-beta2b compared to PLC-beta2a, suggesting that a great proportion of the total PLC-beta2a was in the nucleus relative to PLC-beta2b. There was no difference in the relative distribution of the two variants between the cytosol and particulate fractions. Both PLC-beta2 alternative splice variants are expressed at the protein level in platelets. In transfected CV-1 cells, PLC-beta2a is relatively more enriched in the nuclei than PLC-beta2b suggesting that the two variants may have different effects in cell proliferation and differentiation.

Inherited defects in platelet signaling mechanisms.

In the majority of patients with an inherited abnormality in platelet function and a bleeding diathesis, the underlying platelet molecular mechanisms are unknown. The usually considered entities, such as thrombasthenia, the Bernard-Soulier syndrome, and storage pool deficiency, occur in a small proportion of patients. A substantial number of patients present with decreased aggregation and secretion of dense granule contents upon activation, and are lumped in the category of primary secretion defects or platelet activation defects. Evidence is now available that defects in platelet signaling mechanisms may be the basis for the platelet dysfunction in some of these patients. This evidence is presented here. If the key components in signal transduction are the surface receptors, the G-proteins, and the effectors, evidence now exists for specific human platelet abnormalities at each of these levels. There is a pressing need for a concerted effort to delineate the molecular mechanisms in the large group of patients with impaired platelet function who represent an untapped reservoir of new information into normal platelet function.

Effects of recombinant human interleukin 11 on thrombocytopenia and neutropenia in irradiated rhesus monkeys.

The effects of recombinant human interleukin 11 (rhIL11) on thrombocytopenia and neutropenia in irradiated rhesus monkeys were evaluated after administration different doses at different times. Twenty-three rhesus monkeys were exposed to a total-body irradiation (TBI) with a single dose of 3 Gy 60Co gamma rays. Either placebo, rhIL11 at a dose of 30, 60 or 120 microg/kg day(-1) on days 0-13, or rhIL11 at a dose of 60 microg/kg day(-1) on days 13-26 after TBI was administered to the animals. The results showed that the immediate treatment with rhIL11 but not treatment on days 13-26 resulted in much higher platelet nadirs than in the placebo-treated group. The accelerated recovery of platelets to normal levels after TBI was demonstrated in all groups treated with rhIL11, but the effects of rhIL11 were independent of dose. However, rhIL11 treatment could also accelerate the recovery of leukocytes to normal levels. The numbers of colony-forming bone marrow cells (CFU-E, CFU-Mix, CFU-MK and CFU-GM) in all groups treated with rhIL11 were increased 4- to 14-fold relative to those of the placebo group on day 30. We conclude that rhIL11 may directly promote megakaryocyte development and ameliorate myelosuppression in irradiated monkeys.

Association of CBFA2 mutation with decreased platelet PKC-theta and impaired receptor-mediated activation of GPIIb-IIIa and pleckstrin phosphorylation: proteins regulated by CBFA2 play a role in GPIIb-IIIa activation.

The mechanisms by which agonists activate glycoprotein (GP) IIb-IIIa function remain unclear. We have reported data on a patient with thrombocytopenia and impaired receptor-mediated aggregation, phosphorylation of pleckstrin (a protein kinase C [PKC] substrate), and activation of the GPIIb-IIIa complex. Abnormalities in hematopoietic transcription factors have been associated with thrombocytopenia and platelet dysfunction. To define the molecular mechanisms, we amplified from patient platelet RNA exons 3 to 6 of core-binding factor A2 (CBFA2) cDNA, which encompasses the DNA-binding Runt domain; a 13-nucleotide (nt) deletion was found (796-808 nt). The gDNA revealed a heterozygous mutation (G>T) in intron 3 at the splice acceptor site for exon 4, leading to a frameshift with premature termination in the Runt domain. On immunoblotting, platelet CBFA2, PKC-, albumin, and IgG were decreased, but pleckstrin, PKC-alpha, -betaI, -betaII, -eta, -epsilon, -delta, and -zeta, and fibrinogen were normal. Our conclusions are that (1) CBFA2 mutation is associated with not only thrombocytopenia, but also impaired platelet protein phosphorylation and GPIIb-IIIa activation; (2) proteins regulated by CBFA2 are required for inside-out signal transduction-dependent activation of GPIIb-IIIa; and (3) we have documented the first deficiency of a human PKC isozyme (PKC-), suggesting a major role of this isozyme in platelet production and function.

[Direct Injection of Plasmid DNA Expressing IL-6 Gene Improves Recovery of Thrombocytopoiesis in Irradiated Mice]

Hemorrhage is one of major clinical features of the patients exposed to large dose of ionizing radiation and a sudden decrease of peripheral platelet counts in hemorrhage complication may bring the patients into life-threatening situation. Cytokines had been used to improve thrombocytopoiesis in various radiation induced thrombocytopenia. Current measures for this purpose involve repeated injection of recombinant cytokines, which bring much inconvenient and agony to the patients, or gene therapy with viral vectors that could not obviate the risk of infection. This work tried to determine the possibility of gene therapy with plasmid vectors for radiation-induced hematopoietic injury. After a single intramuscular injection of plasmid hIL-6 cDNA on 6.5 Gy irradiated mice, the IL-6 level began to increase from the day 4, reached the peak value about the day 11 and maintained at a higher level on the day 28, but the hIL-6 level showed less changes in unirradiated mice. Further experiments demonstrated the IL-6 level in 7.5 Gy irradiated mice was about three times higher than that of 5.0 Gy irradiated mice and the expression of hIL-6 in vivo showed significant effect on hematopoietic recovery. Not only the platelet nadir in peripheral blood, but also the number of colony-forming cells in bone marrow rose. It is concluded that radiation could significantly enhance the gene transfer efficiency of plasmid DNA and gene therapy with plasmid vectors for treating radiation-induced hematopoietic injury might be more effective than other diseases without DNA repair.

Therapeutic Effects of rhIL-11 on Irradiation-Induced Myelosuppression in Rhesus Monkeys.

The efficacy of rhIL-11 in treating thrombocytopenia and neutropenia in gamma-irradiated rhesus monkeys and the variation in curative effect due to difference of administration times were studied. Healthy rhesus monkeys were exposed to 3.0 Gy (60)Co total body irradiation (TBI) to result in pancytopenia for three weeks. Treatment with rhIL-11 (30, 60 or 120 micro g.kg(-1).day(-1)) on early days (days 0 - 13 after TBI) could significantly improve the nadir of platelet count. Although the nadir of leukocyte count was not improved, the duration below 50% of its baseline value was shortened similarly to that of platelet. During the first two weeks after TBI, erythrocyte numbers of the animals treated with these doses of rhIL-11 were lower than those of the control group at first but they became higher beginning from the third week. Four monkeys were treated with rhIL-11 at 60 micro g.kg(-1).day(-1) on days 13 - 26 after TBI. The numbers of their peripheral blood cells followed the similar decrease patterns as those of control group during the first three weeks, then they were improved rapidly. By semi-solid bone marrow cell culture it was demonstrated that rhIL-11 could stimulate bone marrow cells to form more CFU-Meg, CFU-Mix, CFU-E, BFU-E and CFU-GM in vitro. Histopathological observation revealed that bone marrow of the control group was devoid of hematopoietic cells and bleeding, being contrary to that of the group treated with rhIL-11, in which the cells proliferated actively. The results suggest that rhIL-11 can accelerate hematopoietic recovery of irradiated monkeys.