Preparation of high-purity SiO2 by S-HGMS coupled with mixed-acid leaching: A case study on hematite tailings from Ansteel, China.

Hematite tailings (HTs) are rich in silica and are used as replacements for fine aggregates in the preparation of construction materials. However, there is scope for a more effective utilization of the valuable elements present in HTs. In this paper, a process for preparing high-purity SiO2 using HTs procured from Ansteel (China) is proposed. HTs were treated using the superconducting high-gradient magnetic separation (S-HGMS) technology, where the silica as part of the nonmagnetic fraction was obtained in the form of a high-silica concentrate, which was then subjected to mixed-acid leaching to dissolve impurities to achieve refined purification. The optimum process conditions for S-HGMS were determined, and the response surface methodology was applied to optimize the process parameters of the mixed-acid leaching process. The process indicators of the mixed-acid leaching step included the leaching time, leaching temperature, and molar ratio of the mixed acids. The optimum process conditions for S-HGMS were as follows: the magnetic strength-to-velocity ratio in the weak magnetic separation stage was set to 0.034 T·s/m whereas it was maintained at 0.076 T·s/m in the strong magnetic separation stage; the pulp concentration was 40 g/L, the pulp velocity was 500 mL/min, and the dispersant concentration was 1 mg/g. Under these conditions, the high-silica pulp was processed. The corresponding SiO2 grade increased from 71.788 % to 95.260 %, and its recovery and yield reached 56.330 % and 42.450 %, respectively. The SiO2 content in the sample increased from 95.260 % to 99.961 %. Further, the mechanisms of the S-HGMS and mixed-acid leaching were revealed. The proposed process is environmentally friendly and operationally inexpensive. It can reduce the amount of HTs by 42.450 %, and the obtained high-purity silica product has high economic value and good industrialization prospects.

Properties of Mucoid Serotype 3 Streptococcus pneumoniae From Children in China.

Objective: To investigate the characteristics of hosts, antimicrobial susceptibility, and molecular epidemiology of mucoid serotype 3 Streptococcus pneumoniae (S. pneumoniae) isolated from children in China. Method: S. pneumoniae isolates collected between January 2016 and December 2019 were analyzed. S. pneumoniae isolates with mucoid phenotype were selected visually, and serotype 3 isolates were confirmed by Quellung reaction. The antimicrobial susceptibility was measured by E-test. Multilocus sequence typing was used for clonal analysis. Results: Twenty (3.04%) isolates of mucoid serotype 3 S. pneumoniae were identified from 657 clinical isolates, and all of them were noninvasive strains. The mean age of the hosts was 5.69 ± 3.28 years. The isolates included: 50.0% from the dissected tonsil or adenoid tissue in children with obstructive sleep apnea-hypopnea syndrome, 45.0% from sputum or bronchial lavages in children with pneumonia, and 5.0% from vaginal secretions of one patient with vulvovaginitis. All isolates were susceptible to penicillin, cefuroxime, ceftriaxone, meropenem, vancomycin, levofloxacin, trimethoprim/sulfamethoxazole, and rifampin but resistant to erythromycin. Sequence type (ST)505 and its clonal complex (CC) were the main genotypes (95%). Antimicrobial susceptibility of ST180 and ST505 were compared, and the minimum inhibitory concentration (MIC) of ST505 isolates was significantly higher than that of ST180 for tetracycline, trimethoprim/sulfamethoxazole, and meropenem. Conclusions: Mucoid serotype 3 Streptococcus pneumoniae can be isolated from various body parts, among which the respiratory system is the most common. It can cause noninvasive infection in children, and it has high susceptibility to a variety of antibiotics, especially ß-lactams, but is resistant to macrolides. CC505 is the novel clonal complex found in China, which may be related to the worldwide mainstream clonal complex (CC180) but has its own biological characteristics.

Estrogenic and androgenic effects in mosquitofish (Gambusia affinis) from streams contaminated by municipal effluent in Guangzhou, China.

The study reported in this paper used mosquitofish to investigate the estrogenic and androgenic effects of municipal wastewater contamination on the stream system in Guangzhou, China. Western mosquitofish collected from a reference site and five study sites in streams forming part of the Pearl River network were dissected and analyzed for their morphological characteristics (anal fin and hemal spine characteristics) and target mRNA expression of genes (VTGα and ERα mRNA expression). Increased VTGα mRNA expression in males and decreased VTGα mRNA expression in females were observed in samples taken from four of the five study sites, with no such observations being made at the reference site. Correlation analysis indicated a significant correlation between the hemal spine morphology index and the gene transcription relative to the reference site. The multiple index also indicated that both male and female mosquitofish in contaminated streams were altered by discharged wastewater, as reflected in their morphological changes and relative induction of mRNA expression of genes in comparison to fish collected from the reference site.

Methylenedioxy- and ethylenedioxy-fused indolocarbazoles: potent human topoisomerase I inhibitors and antitumor agents.

The indolo[2,3-a]carbazole alkaloids constitute an important class of natural products with interesting and diverse biological activities. A series of novel ring-fused indolocarbazoles were synthesized and evaluated for inhibition of topoisomerase I-mediated relaxation of supercoiled DNA and in vitro antitumor activity. The derivatives bearing a methylenedioxy or an ethylenedioxy ring fused onto the nonglycosylated indole (1a, 1b) demonstrated more potent anti-topoisomerase I activity. The isopropylenedioxy analogue 1c was approximately half as active as 1a, while the O-dimethoxy analogue 1d and the regioisomers 2a and 2b were essentially devoid of measurable activity, implying that the stacking with the intact DNA strand has been impeded by these compounds due to steric hindrance. The newly synthesized indolocarbazoles were screened against the NCI's 60 tumor cell lines. The order of activity, based on the mean GI50 values, is as follows: 1a > 2a ~ 1d > 1b > MCR-47 > 2b. Though in general the analogues that showed potent activity against topoisomerase I (1a, 1b) also showed potent in vitro inhibition of tumor cell growth, the antitumor activity of the anti-topoisomerase I inactive 1d and 2a were intriguing. COMPARE analyses confirmed that the topoisomerase I is the primary target for 1a and 1b; however, other target(s) or pathway(s) may also be involved, with PLD1 and MERTK suggested. Further investigation of these molecular targets against these indolocarbazoles is warranted.

A type-II kinase inhibitor capable of inhibiting the T315I "gatekeeper" mutant of Bcr-Abl.

The second generation of Bcr-Abl inhibitors nilotinib, dasatinib, and bosutinib developed to override imatinib resistance are not active against the T315I "gatekeeper" mutation. Here we describe a type-II T315I inhibitor 2 (GNF-7), based upon a 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one scaffold which is capable of potently inhibiting wild-type and T315I Bcr-Abl as well as other clinically relevant Bcr-Abl mutants such as G250E, Q252H, Y253H, E255K, E255V, F317L, and M351T in biochemical and cellular assays. In addition, compound 2 displayed significant in vivo efficacy against T315I-Bcr-Abl without appreciable toxicity in a bioluminescent xenograft mouse model using a transformed T315I-Bcr-Abl-Ba/F3 cell line that has a stable luciferase expression. Compound 2 is among the first type-II inhibitors capable of inhibiting T315I to be described and will serve as a valuable lead to design the third generation Bcr-Abl kinase inhibitors.

A general strategy for creating "inactive-conformation" abl inhibitors.

Kinase inhibitors that bind to the ATP cleft can be broadly classified into two groups: those that bind exclusively to the ATP site with the kinase assuming a conformation otherwise conducive to phosphotransfer (type I), and those that exploit a hydrophobic site immediately adjacent to the ATP pocket made accessible by a conformational rearrangement of the activation loop (type II). To date, all type II inhibitors were discovered by using structure-activity-guided optimization strategies. Here, we describe a general pharmacophore model of type II inhibition that enables a rational "hybrid-design" approach whereby a 3-trifluoromethylbenzamide functionality is appended to four distinct type I scaffolds in order to convert them into their corresponding type II counterparts. We demonstrate that the designed compounds function as type II inhibitors by using biochemical and cellular kinase assays and by cocrystallography with Abl.