Effect and mechanism of surface pretreatment on desulfurization and desilication from low-grade high-sulfur bauxite using flotation

Surface pretreatment using a hot alkaline solution was carried out to improve the effect of desulfurization and desilication on low-grade bauxite with high sulfur content. The results demonstrated that, after surface pretreatment, a maximum grade and recovery of 66.17% and 87.27%, respectively, were achieved, and the sulfur content and ratio of A/S were 0.19% and 7.09, respectively. The surface pretreatment mechanism was further analysed by XRD and SEM analyses. The improved results of desulfurization and desilication were attributed to the selective corrosion of aluminosilicate minerals in coarse particles, reducing the active silicon sites on the surface of coarse particles as well as enhancing the cation exchange between the collector and aluminosilicate minerals

Genetic Diversity, Rather than Cultivar Type, Determines Relative Grain Cd Accumulation in Hybrid Rice

Cadmium (Cd) is a toxic element, and rice is known to be a leading source of dietary Cd for people who consume rice as their main caloric resource. Hybrid rice has dominated rice production in southern China and has been adopted worldwide. The characteristics of high yield heterosis of rice hybrids makes the public think intuitively that the hybrid rice accumulates more Cd in grain than do inbred cultivar. A detailed understanding of the genetic basis of grain Cd accumulation in hybrids and developing Cd-safe rice are of the top priorities for hybrid rice breeders at present. In this study, we investigated genetic diversity and grain Cd levels in 617 elite rice hybrids collected from the middle and lower Yangtze River Valley in China and 68 inbred cultivars from around the world. We found that there are large variations in grain Cd accumulation in both the hybrids and their inbred counterparts. However, we found similar grain Cd levels in the rice hybrids to the levels in indica rice inbreds, suggesting that the hybrids do not accumulate more Cd than do the inbred rice cultivars. Further analysis revealed that the high heritability of Cd accumulation in the grain and the single indica population structure increases the risk of Cd over-accumulation in hybrid rice. The genetic effects of Cd-related QTLs, which have been identified in related Cd-QTL mapping studies, were also determined in the hybrid rice population. Four QTLs were identified as being associated with the variation in grain Cd levels; three of these loci exhibited obvious indica-japonica differentiations. Our study will provide a better understanding of grain Cd accumulations in hybrid rice, and pave the way towards effective breeding for high-yielding, low grain-Cd hybrids in the future

Combination Regimens of Favipiravir Plus Interferon Alpha Inhibit Chikungunya Virus Replication in Clinically Relevant Human Cell Lines

Chikungunya virus (CHIKV) is an alphavirus associated with a broad tissue tropism for which no antivirals or vaccines are approved. This study evaluated the antiviral potential of favipiravir (FAV), interferon-alpha (IFN), and ribavirin (RBV) against CHIKV as mono- and combination-therapy in cell lines that are clinically relevant to human infection. Cells derived from human connective tissue (HT-1080), neurons (SK-N-MC), and skin (HFF-1) were infected with CHIKV and treated with different concentrations of FAV, IFN, or RBV. Viral supernatant was sampled daily and the burden was quantified by plaque assay on Vero cells. FAV and IFN were the most effective against CHIKV on various cell lines, suppressing the viral burden at clinically achievable concentrations; although the degree of antiviral activity was heavily influenced by cell type. RBV was not effective and demonstrated substantial toxicity, indicating that it is not a feasible candidate for CHIKV. The combination of FAV and IFN was then assessed on all cell lines. Combination therapy enhanced antiviral activity in HT-1080 and SK-N-MC cells, but not in HFF-1 cells. We developed a pharmacokinetic/pharmacodynamic model that described the viral burden and inhibitory antiviral effect. Simulations from this model predicted clinically relevant concentrations of FAV plus IFN completely suppressed CHIKV replication in HT-1080 cells, and considerably slowed down the rate of viral replication in SK-N-MC cells. The model predicted substantial inhibition of viral replication by clinical IFN regimens in HFF-1 cells. Our results highlight the antiviral potential of FAV and IFN combination regimens against CHIKV in clinically relevant cell types

WGCNA Analysis Identifies the Hub Genes Related to Heat Stress in Seedling of Rice (Oryza sativa L.)

Frequent high temperature weather affects the growth and development of rice, resulting in the decline of seed–setting rate, deterioration of rice quality and reduction of yield. Although some high temperature tolerance genes have been cloned, there is still little success in solving the effects of high temperature stress in rice (Oryza sativa L.). Based on the transcriptional data of seven time points, the weighted correlation network analysis (WGCNA) method was used to construct a co–expression network of differentially expressed genes (DEGs) between the rice genotypes IR64 (tolerant to heat stress) and Koshihikari (susceptible to heat stress). There were four modules in both genotypes that were highly correlated with the time points after heat stress in the seedling. We further identified candidate hub genes through clustering and analysis of protein interaction network with known–core genes. The results showed that the ribosome and protein processing in the endoplasmic reticulum were the common pathways in response to heat stress between the two genotypes. The changes of starch and sucrose metabolism and the biosynthesis of secondary metabolites pathways are possible reasons for the sensitivity to heat stress for Koshihikari. Our findings provide an important reference for the understanding of high temperature response mechanisms and the cultivation of high temperature resistant materials

Effect of Different Piperacillin-Tazobactam Dosage Regimens on Synergy of the Combination with Tobramycin against <i>Pseudomonas aeruginosa</i> for the Pharmacokinetics of Critically Ill Patients in a Dynamic Infection Model

We evaluated piperacillin-tazobactam and tobramycin regimens against Pseudomonas aeruginosa isolates from critically ill patients. Static-concentration time-kill studies (SCTK) assessed piperacillin-tazobactam and tobramycin monotherapies and combinations against four isolates over 72 h. A 120 h-dynamic in vitro infection model (IVM) investigated isolates Pa1281 (MICpiperacillin 4 mg/L, MICtobramycin 0.5 mg/L) and CR380 (MICpiperacillin 32 mg/L, MICtobramycin 1 mg/L), simulating the pharmacokinetics of: (A) tobramycin 7 mg/kg q24 h (0.5 h-infusions, t1/2 = 3.1 h); (B) piperacillin 4 g q4 h (0.5 h-infusions, t1/2 = 1.5 h); (C) piperacillin 24 g/day, continuous infusion; A + B; A + C. Total and less-susceptible bacteria were determined. SCTK demonstrated synergy of the combination for all isolates. In the IVM, regimens A and B provided initial killing, followed by extensive regrowth by 72 h for both isolates. C provided >4 log10 CFU/mL killing, followed by regrowth close to initial inoculum by 96 h for Pa1281, and suppressed growth to 10 CFU/mL for CR380. A and A + B initially suppressed counts of both isolates to 10 CFU/mL, before regrowth to control or starting inoculum and resistance emergence by 72 h. Overall, the combination including intermittent piperacillin-tazobactam did not provide a benefit over tobramycin monotherapy. A + C, the combination regimen with continuous infusion of piperacillin-tazobactam, provided synergistic killing (counts 10 CFU/mL) of Pa1281 and CR380, and suppressed regrowth to 10 CFU/mL, respectively, and resistance emergence over 120 h. The shape of the concentration–time curve was important for synergy of the combination

Novel cassette assay to quantify the outer membrane permeability of five β-lactams simultaneously in carbapenem-resistant klebsiella pneumoniae and enterobacter cloacae

Antimicrobial resistance is causing a global human health crisis and is affecting all antibiotic classes. While β-lactams have been commonly used against susceptible isolates of Klebsiella pneumoniae and Enterobacter cloacae, carbapenem-resistant isolates are spreading worldwide and pose substantial clinical challenges. Rapid penetration of β-lactams leads to high drug concentrations at their periplasmic target sites, allowing β-lactams to more completely inactivate their target receptors. Despite this, there are limited tangible data on the permeability of β-lactams through the outer membranes of many Gram-negative pathogens. This study presents a novel, cassette assay, which can simultaneously characterize the permeability of five β-lactams in multidrug-resistant clinical isolates. We show that carbapenems, and especially imipenem, penetrate the outer membrane of K. pneumoniae and E. cloacae substantially faster than noncarbapenem β-lactams. The ability to efficiently characterize the outer membrane permeability is critical to optimize the use of β-lactams and combat carbapenem-resistant isolates.Poor penetration through the outer membrane (OM) of Gram-negative bacteria is a major barrier of antibiotic development. While β-lactam antibiotics are commonly used against Klebsiella pneumoniae and Enterobacter cloacae, there are limited data on OM permeability especially in K. pneumoniae. Here, we developed a novel cassette assay, which can simultaneously quantify the OM permeability to five β-lactams in carbapenem-resistant K. pneumoniae and E. cloacae. Both clinical isolates harbored a blaKPC-2 and several other β-lactamases. The OM permeability of each antibiotic was studied separately (“discrete assay”) and simultaneously (“cassette assay”) by determining the degradation of extracellular β-lactam concentrations via multiplex liquid chromatography-tandem mass spectrometry analyses. Our K. pneumoniae isolate was polymyxin resistant, whereas the E. cloacae was polymyxin susceptible. Imipenem penetrated the OM at least 7-fold faster than meropenem for both isolates. Imipenem penetrated E. cloacae at least 258-fold faster and K. pneumoniae 150-fold faster compared to aztreonam, cefepime, and ceftazidime. For our β-lactams, OM permeability was substantially higher in the E. cloacae compared to the K. pneumoniae isolate (except for aztreonam). This correlated with a higher OmpC porin production in E. cloacae, as determined by proteomics. The cassette and discrete assays showed comparable results, suggesting limited or no competition during influx through OM porins. This cassette assay allowed us, for the first time, to efficiently quantify the OM permeability of multiple β-lactams in carbapenem-resistant K. pneumoniae and E. cloacae. Characterizing the OM permeability presents a critical contribution to combating the antimicrobial resistance crisis and enables us to rationally optimize the use of β-lactam antibiotics