The combined formulation of brassinolide and pyraclostrobin increases biomass and seed yield by improving photosynthetic capacity in Arabidopsis thaliana.

In the context of global food crisis, applying the phytohormone-brassinosteroids (BRs) in combination with the fungicide-pyraclostrobin (Pyr) was beneficial for plant quality and productivity in several field trials. However, in addition to the benefits of disease control due to the innate fungicidal activity of Pyr, it remains to be understood whether the coapplication of BL+ Pyr exerts additional growth-promoting effects. For this purpose, the effects of BL treatment, Pyr treatment, and BL+ Pyr treatment in Arabidopsis thaliana were compared. The results showed that the yield increased at a rate of 25.6% in the BL+Pyr group and 9.7% in the BL group, but no significant change was observed in the Pyr group. Furthermore, the BL+Pyr treatment increased the fresh weight of both the leaves and the inflorescences. In contrast, the Pyr and BL treatments only increased the fresh weight of leaves and inflorescences, respectively. Additionally, the BL + Pyr treatment increased the Pn, Gs, Tr, Vc, max, Jmax, VTPU, ETR, Fv'/Fm', ΦPSII, Rd, AYE and Rubisco enzyme activity by 26%, 38%, 40%, 16%, 19%, 15%, 9%, 10%, 17%, 179%, 18% and 32%, respectively. While, these paraments did not change significantly by the BL or Pyr treatments. Treatment with BL + Pyr and Pyr, rather than BL, improved the chlorophyll a and chlorophyll b contents by upregulating genes related to chlorophyll biosynthesis and downregulating genes related to chlorophyll degradation. Additionally, according to transcriptomic and metabolomic analysis, the BL+ Pyr treatment outperformed the individual BL or Pyr treatments in activating the transcription of genes involved in photosynthesis and increasing sugar accumulation. Our results first validated that the combined usage of BL and Pyr exerted striking synergistic effects on enhancing plant biomass and yield by increasing photosynthetic efficiency. These results might provide new understanding for the agricultural effects by the co-application of BL and Pyr, and it might stimulate the efforts to develop new environment-friendly replacement for Pyr to minimize the ecotoxicology of Pyr.

Design, Synthesis, and Fungicidal Activities of Novel Piperidyl Thiazole Derivatives Containing Oxime Ether or Oxime Ester Moieties.

To explore the influence of the positions of the two nitrogen atoms on the thiazole ring and the isoxazoline ring on the activity, a series of novel piperidyl thiazole derivatives containing oxime ether and oxime ester moieties with two nitrogen atoms on the same or opposite sides have been designed, synthesized, and first evaluated for their fungicidal activities against Phytophthora capsici in vitro. The bioassay results showed that the target compounds possessed moderate to good fungicidal activities against P. capsici, among which oxime ether compound 11b shows the highest fungicidal activity in vitro (EC50 = 0.0104 µg/mL) which is higher than dimethomorph (EC50 = 0.1148 µg/mL) and diacetylenyl amide (EC50 = 0.040 µg/mL). Compared with oxime ether compounds (the two nitrogen atoms are on the opposite sides), the activities of oxime ester compounds were significantly reduced. It is different from the commercial fungicide fluoxapiprolin, and the activities of the compounds with the two nitrogen atoms on the same side were significantly reduced compared to the compounds with the two nitrogen atoms on the opposite sides. Moreover, compounds 11b, 11d, 11e, and 11g showed moderate to good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. Scanning electron microscopy of compound 11b on the hyphae morphology showed that compound 11b might cause mycelial abnormalities of P. capsici.

Design, synthesis and antifungal activity of threoninamide carbamate derivatives via pharmacophore model.

Thirty-six novel threoninamide carbamate derivatives were designed and synthesised using active fragment-based pharmacophore model. Antifungal activities of these compounds were tested against Oomycete fungi Phytophthora capsici in vitro and in vivo. Interestingly, compound I-1, I-2, I-3, I-6 and I-7 exhibited moderate control effect (>50%) against Pseudoperonospora cubensis in greenhouse at 6.25 µg/mL, which is better than that of control. Meanwhile most of these compounds exhibited significant inhibitory against P. capsici. The other nine fungi were also tested. More importantly, some compounds exhibited remarkably high activities against Sclerotinia sclerotiorum, P. piricola and R. solan in vitro with EC50 values of 3.74-9.76 µg/mL. It is possible that the model is reliabile and this method can be used to discover lead compounds for the development of fungicides.

Survival analysis of genome-wide profiles coupled with Connectivity Map database mining to identify potential therapeutic targets for cholangiocarcinoma.

Cholangiocarcinoma (CCA) is one of the most common epithelial cell malignancies worldwide. However, its prognosis is poor. The aim of the present study was to examine the prognostic landscape and potential therapeutic targets for CCA. RNA sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) dataset and processed. A total of 172 genes that were significantly associated with overall survival of patients with CCA were identified using the univariate Cox regression method. Bioinformatics tools were applied using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO). It was identified that 'Wnt signaling pathway', 'cytoplasm' and 'AT DNA binding' were the three most significant GO categories of CCA survival-associated genes. 'Transcriptional misregulation in cancer' was the most significant pathway identified in the KEGG analysis. Using the Drug-Gene Interaction database, a drug-gene interaction network was constructed, and 31 identified genes were involved in it. The most meaningful potential therapeutic targets were selected via protein-protein and gene-drug interactions. Among these genes, polo-like kinase 1 (PLK1) was identified to be a potential target due to its significant upregulation in CCA. To rapidly find molecules that may affect these genes, the Connectivity Map was queried. A series of molecules were selected for their potential anti-CCA functions. 0297417-0002B and tribenoside exhibited the highest connection scores with PLK1 via molecular docking. These findings may offer novel insights into treatment and perspectives on the future innovative treatment of CCA.

Small molecule inducers of ABCA1 and apoE that act through indirect activation of the LXR pathway.

apoE is the primary lipid carrier within the CNS and the strongest genetic risk factor for late onset Alzheimer's disease (AD). apoE is primarily lipidated via ABCA1, and both are under transcriptional regulation by the nuclear liver X receptor (LXR). Considerable evidence from genetic (using ABCA1 overexpression) and pharmacological (using synthetic LXR agonists) studies in AD mouse models suggests that increased levels of lipidated apoE can improve cognitive performance and, in some strains, can reduce amyloid burden. However, direct synthetic LXR ligands have hepatotoxic side effects that limit their clinical use. Here, we describe a set of small molecules, previously annotated as antagonists of the purinergic receptor, P2X7, which enhance ABCA1 expression and activity as well as apoE secretion, and are not direct LXR ligands. Furthermore, P2X7 is not required for these molecules to induce ABCA1 upregulation and apoE secretion, demonstrating that the ABCA1 and apoE effects are mechanistically independent of P2X7 inhibition. Hence, we have identified novel dual activity compounds that upregulate ABCA1 across multiple CNS cell types, including human astrocytes, pericytes, and microglia, through an indirect LXR mechanism and that also independently inhibit P2X7 receptor activity.

Aqua-[N-phenyl-2-(quinolin-8-yl-oxy)acetamide]dinitratozinc(II).

In the title complex, [Zn(NO(3))(2)(C(17)H(14)N(2)O(2))(H(2)O)], the six-coordinated Zn atom is in a distorted octa-hedral geometry, the donor centers being two O atoms and one N atom from the tridentate organic ligand, a water O atom and two O atoms from two monodentate nitrate ions. In the crystal, O-H⋯O hydrogen bonds between the coordinated water mol-ecules and nitrate O atoms and N-H⋯O hydrogen bonds between the main ligand and nitrate O atoms consolidate the three-dimensional network.

Bis[N-benzyl-2-(quinolin-8-yl-oxy)acetamide]dichloridocopper(II) acetonitrile solvate monohydrate.

In the title complex, [CuCl(2)(C(18)H(16)N(2)O(2))(2)]·CH(3)CN·H(2)O, the six-coordinated Cu atom is in a distorted octa-hedral geometry with the donor centers of two O atoms and two N atom from two bidentate ligands, and two chloride ions. In the crystal, pairs of inter-molecular N-H⋯ Cl hydrogen bonds form centrosymmetric dimers and inter-molecular O-H⋯ O hydrogen bonds between the ligand and the uncoordinated water mol-ecules link the dimers into chains parallel to the c axis.