Design, synthesis, and biological evaluation of novel diphenylamine derivatives as tubulin polymerization inhibitors targeting the colchicine binding site.

A novel series of diphenylamine derivatives were designed and synthesized, and their biological activities were evaluated. The anti-proliferative activities of the derivatives were tested against five human cancer cell lines (MCF-7, MDA-MB-231, A549, HeLa and HT29). Among them, compound 5f exhibited the promising anti-proliferative activity against HT29 cell lines with the IC50 value of 23 nM. Further biological studies depicted that compound 5f inhibited cancer cell migration, colony formation and angiogenesis. Besides, dynamics studies and molecular docking studies revealed that compound 5f inhibited tubulin polymerization which may be a result of the compound binding to the colchicine site of tubulin. Furthermore, compound 5f arrested HT29 cell cycle at G2/M phase, and induced HT29 cell apoptosis by upregulating cyclin B1, Bcl-2, Bax, Cleaved-caspase9, Cleaved-caspase3, PARP, Cleaved-PARP proteins, and downregulating p-cdc25c (S216), p-cdc2 (T15) proteins. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were also determined to confirm the cell apoptosis process. Finally, compound 5f greatly inhibited the tumor growth in HT29 xenograft mice by 75.5% at 10 mg/kg. Meanwhile, compound 5f owned the good pharmacokinetic properties. All the results promised that 5f is of potential to act as an antitumor candidate and worthy of further investigation.

The first complete chloroplast genome of Tetradium daniellii (Benn.) T. G. Hartley.

Tetradium daniellii (Benn.) T. G. Hartley is an important medicinal, ornamental, and timber tree species and belongs to genus Tetradium in family of Rutaceae. It is widely distributed in warm temperate deciduous broad-leaved forest areas in northern China, Korean Peninsula and Japan. In this study, we sequenced its sample and determined complete chloroplast genome. The CP genome of T. daniellii has a circle structure with the length 158,446 bp, includes a small single copy region (17, 972 bp), a large single copy (86, 478 bp) and two inverted repeats (26,998 bp). There were 131 genes, which included 86 protein-coding genes, 8 rRNA and 37 tRNA, and overall GC content covered by 38.3%. The gene trnK-UUU, rps16, trnG-UCC, atpF, rpoC1, trnL-UAA, trnV-UAC, petB, petD, rpl16, rpl2, ndhB, trnI-GAU, trnA-UGC and ndhA contained an intron; gene clpP, ycf3 contained 2 introns. The phylogenetic result showed that T. daniellii had the closest relationship with Tetradium ruticarpum (NC_052830).

Skimmin protects diabetic cardiomyopathy in streptozotocin-induced diabetic rats.

Skimmin, a natural coumarin derivate, has been showed to be protective against experimental diabetic nephropathy; however, its protective effect on diabetic cardiomyopathy (DCM) is not clarified. By using in vitro and in vivo models, we investigated skimmin's protective effect on impaired heart tissues in DCM. DCM was induced by streptozotocin (STZ, 60 mg/kg) using Sprague Dawley rats, and diabetic rats were treated with either skimmin (15 or 30 mg/kg) or the vehicle for 16 weeks, and normal rats were used as a control. Hematoxylin and eosin and Masson's trichrome staining were performed to evaluate the cardiac histopathology, and the oxidative stress and proinflammation cytokines in heart tissues were measured. The protein levels of key mediators in fibrosis, pyroptosis, and autophagy in heart tissues were investigated using western blotting. In vitro, primary neonatal cardiomyocytes were treated with skimmin (2 and 10 µM) under stimulation by high glucose (30 mM) and low glucose (5 mM) respectively, and the molecular mechanisms on pyroptosis and autophagy were studied. Compared to the vehicle-treated DCM group, skimmin treatment significantly improved the ejection fraction and fractional shortening of the left ventricle and reduced the oxidative stress by increasing the glutathione level and activity of superoxide dismutase and catalase. Skimmin also reduced cardiac fibrosis, and decreased proinflammation cytokines in cardiac tissues. Mechanism studies showed skimmin may enhance the autophagy and ameliorate NLRP3 inflammasome activation to play a protective role in DCM. This study, for the first time, indicates that skimmin might be a promising lead compound for DCM.

Genome-Wide Profiles of Extra-cranial Malignant Rhabdoid Tumors Reveal Heterogeneity and Dysregulated Developmental Pathways.

Malignant rhabdoid tumors (MRTs) are rare lethal tumors of childhood that most commonly occur in the kidney and brain. MRTs are driven by SMARCB1 loss, but the molecular consequences of SMARCB1 loss in extra-cranial tumors have not been comprehensively described and genomic resources for analyses of extra-cranial MRT are limited. To provide such data, we used whole-genome sequencing, whole-genome bisulfite sequencing, whole transcriptome (RNA-seq) and microRNA sequencing (miRNA-seq), and histone modification profiling to characterize extra-cranial MRTs. Our analyses revealed gene expression and methylation subgroups and focused on dysregulated pathways, including those involved in neural crest development.

A long-term static immersion experiment on the leaching behavior of heavy metals from waste printed circuit boards.

Printed circuit boards (PCBs) are the main components of electrical and electronic equipment (EEE). Waste PCBs contain several kinds of heavy metals, including Cu, Pb and Zn. We characterize the leaching of heavy metals (Cu, Pb, Zn and Ni) from waste PCBs in a pH range of 3.0 to 5.6 using a novel approach based on batch pH-static leaching experiments in this work. The results indicate that the leaching behavior of Cu, Pb, Zn and Ni is strongly dependent on pH. Leaching behavior also varies with different pH values and leaching times. The maximum concentrations of Cu, Pb, Zn and Ni in leachate from waste PCBs were 335.00, 17.57, 2.40 and 2.33 mg L(-1), respectively. The highest Pb, Ni, and Cu concentrations leached significantly exceeded the European Union waste-acceptance limit values with respect to inert waste landfills. The leaching of metals follows the shrinking core model with surface reaction control.

Performance of hybrid vertical up- and downflow subsurface flow constructed wetlands in treating synthetic high-strength wastewater.

The performance and temporal variation of hybrid vertical-subsurface flow constructed wetlands (VFCWs) in response to two-stage combinations of vertical upflow (VUF) and vertical downflow (VDF) were analyzed in this research. The results of high carbon (C) treatment and high nitrogen (N) treatment were similar. The Lythrum salicaria treatment showed higher removal efficiency than CWs planted with Acorus calamus. Under high C- and N-loading treatments, the optimum two-stage combination was VDF-VUF VFCWs planted with A. calamus. Furthermore, the highest nutrient removal efficiencies were achieved in late summer (July and August) and early autumn (September). The chemical oxygen demand and total nitrogen removal efficiencies were significantly affected (P < 0.05) by season, system, and wetland plant.

Effect of C/N ratios on the performance of earthworm eco-filter for treatment of synthetics domestic sewage.

PURPOSE: The performances of filter systems that use earthworms and plants, combined with earthworm eco-filter (EE) systems in treating synthetic domestic sewage (SDS) with different C/N ratios, were investigated for a 9-month period. METHODS: The effects of the combination of filters, earthworms, plants, as well as the combination of earthworms and plants on SDS nutrient removal efficiency were separately investigated to select the optimum system for treating SDS. The results of the current study could be used to determine how treatment performance responds to different C/N ratios and to explain and predict the performance of an operating EE system. RESULTS: EE systems with earthworms and plants (EP groups) consistently performed better than the other types of systems (CK, E, and P; that is, without earthworms and without plants, with earthworms and without plants, and without earthworms and with plants, respectively) under all C/N ratios. The highest removal efficiencies of chemical oxygen demand, total nitrogen, total phosphorus, and total organic carbon were achieved under C/N ratios of 6:1, 6:1, 6:1, and 9:1, respectively. The optimum nutrient removal efficiency was achieved at C/N = 6, and the contribution order for nutrient removal was EP > P > E > CK. CONCLUSIONS: Influent C/N ratios, the time of year, and the synergetic effects of earthworm behavior and microorganisms significantly affected nutrient removal efficiencies. Considering the removal of all nutrients, EE systems with plants and earthworms achieved optimum removal effects in July when the influent C/N ratio was controlled at 6. Appropriate control of carbon and nitrogen source concentrations permitted the achievement of optimal nutrient removal effects.

Performance of pilot-scale vertical-flow constructed wetlands in responding to variation in influent C/N ratios of simulated urban sewage.

The performance response of planted and the unplanted wetlands to simulated wastewater with different ratios of carbon to nitrogen (C/N) was studied during a 9-month period in greenhouse conditions. With different C/N ratios for influent water (C/N ratios 2.5:1, 5:1 and 10:1), average removal efficiencies for the unplanted and the planted wetlands were as follows: COD (41-52% and 59-68%), TN (24-48% and 25-62%), TP (35-64% and 59-71%) and TOC (22-37% and 16-33%). At C/N 5:1, both systems performed most efficiently for removal of COD and TP. However, high N removal efficiency only occurred when C/N ratio ranged 2.5-5. Both wetlands exhibited good capabilities of total organic carbon removal at C/N 10:1. Maybe, appropriate control of the carbon or nitrogen source concentration and C/N ratio in the influent can achieve the optimal effect of nutrients removal.

[Surgical diagnosis and treatment of Castleman's disease].

OBJECTIVE: To investigate the clinical features and treatment of the surgical tumors associated with Castleman's disease. METHODS: The clinical data of 20 patients with Castleman's disease, 6 males and 14 females, aged 39 (15-70), with the tumor size ranging from 2 cm x 3 cm to 10 cm x 9 cm, and with the tumor located in the mediastinal cavity (n = 6), retroperitoneal area (n = 2), abdominal cavity (n = 1), adrenal area (n = 1), neck and armpit (n = 2), and multi-centers (n = 2), were analyzed. RESULTS: Nineteen of the 20 patients underwent surgical resection of the tumor or lymph node. All were diagnosed as Castleman's disease by pathological examination. Most of the tumor was benign. Three cases were diagnosed as with paraneoplastic pemphigus. CONCLUSION: Surgical resection of the tumor is the first choice for treatment of Castleman's disease.

[Principles and experimental analysis of a measuring system for measuring spacesuit joint's damping parameters].

OBJECTIVE: To measure the damping parameters of the spacesuit joint. METHOD: The principles of the passive robot system for measuring spacesuit joint's damping parameters were presented. Basing on its special mechanical structure, a 3 DOF model of the flexible IVA (intra-vehicular activity) spacesuit's sleeve was built. The optimal approximation of inverse calculation based on 6 dimension space interval was described. The damping parameters of an actual IVA spacesuit's sleeve were measured on the actual testbed. Also, the potential application of the measuring system was discussed. RESULT: The model of spacesuit sleeve and the forward/inverse kinematics were proved by experimental measurements and real time 3D simulation. CONCLUSION: The principles and the proposed method of the measurement were testified.