Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal ...adenocarcinoma
. Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial
(programmed death ligand-1 (PD-L1) combined positive score ≥5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries
. Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively
. Treatment combining 1 mg kg
nivolumab with 3 mg kg
ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer
. Here we report both long-term follow-up results comparing nivolumab plus chemotherapy versus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive score ≥5 (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score ≥ 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.
Cadmium (Cd) accumulation in rice grains poses a health risk for humans. In this study, a bacterium, Alishewanella sp. WH16-1-MT, was engineered to express metallothionein on the cell surface. ...Compared with the parental WH16-1 strain, Cd2+ adsorption efficiency of WH16-1-MT in medium was increased from 1.2 to 2.6 mg/kg dry weight. The WH16-1-MT strain was then incubated with rice in moderately Cd-contaminated paddy soil. Compared with WH16-1, inoculation with WH16-1-MT increased plant height, panicle length and thousand-kernel weight, and decreased the levels of ascorbic acid and glutathione and the activity of peroxidase. Compared with WH16-1, WH16-1-MT inoculation significantly reduced the concentrations of Cd in brown rice, husks, roots and shoots by 44.0 %, 45.5 %, 36.1 % and 47.2 %, respectively. Moreover, inoculation with WH16-1-MT reduced the bioavailability of Cd in soil, with the total Cd proportion in oxidizable and residual states increased from 29 % to 32 %. Microbiome analysis demonstrated that the addition of WH16-1-MT did not significantly alter the original bacterial abundance and community structure in soil. These results indicate that WH16-1-MT can be used as a novel microbial treatment approach to reduce Cd in rice grown in moderately Cd-contaminated paddy soil.
•The engineered WH16-1-MT strain increased Cd removal efficiency from medium and soil.•WH16-1-MT improved plant height, panicle length and thousand-kernel weight.•WH16-1-MT decreased the activities of antioxidant enzyme under Cd stress conditions.
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•C. testosteroni JL40 immobilizes and oxidizes Sb(III) for detoxification.•Strain JL40 reduces Sb toxicity, inhibiting the accumulation of Sb in brown rice and improves rice ...yield.•Strain JL40 reduces Sb toxicity by immobilization, oxidation, efflux, transport, etc. of Sb.
Antimony (Sb) is toxic to ecosystems and potentially to public health via its accumulation in the food chain. Bioavailability and toxicity of Sb have been reduced using various methods for the remediation of Sb-contaminated soil in most studies. However, Sb-contaminated soil remediation by microbial agents has been rarely evaluated. In this study, we evaluated the potential for the use of Comamonas testosteroni JL40 in the bioremediation of Sb-contamination. Strain JL40 immobilized more than 30 % of the Sb(III) in solution and oxidized over 18 % to Sb(V) for detoxification. Meanwhile, strain JL40 responds to Sb toxicity through such as Sb efflux, intracellular accumulation, biofilm production, and scavenging of reactive oxygen species (ROS), etc. The results of the pot experiment showed the average Sb content of the brown rice was decreased by 59.1%, 38.8%, and 48.4%, for 1.8, 50, and 100 mg/kg Sb spiked soils, respectively. In addition, the results of plant, soil enzyme activity, and rice agronomic trait observations showed that the application of strain JL40 could maintain the health of plants and soil and improve rice production. The single-step and sequential extraction of Sb from rhizosphere soil showed that strain JL40 also plays a role in Sb immobilization and oxidation in the soil environment. During rice potted cultivation, bacterial community analysis and plate counting showed that the strain JL40 could still maintain 103 CFU/g after 30 days of inoculation. With phenotypic and differential proteomics analysis, strain JL40 conferred Sb(III) tolerance by a combination of immobilization, oxidation, efflux and scavenging of ROS, etc. Our study demonstrates the application of Sb-immobilizing and oxidizing bacteria to lower soil Sb and reduce accumulation of Sb in rice. Our results provide guidance for bacterial remediation of Sb-contaminated soil.
A Gram-stain-negative, facultative anaerobic, non-motile and rod-shaped bacterial strain, designated LX32
, was isolated from arsenic and cadmium contaminated farmland soil. Phylogenetic analysis ...based on 16S rRNA gene sequence indicated that strain LX32
was closely related to Phenylobacterium hankyongense HKS-05
(97.7 % sequence similarity), Phenylobacterium kunshanense CCTCC AB 2013085
(97.4 %) and Phenylobacterium deserti CCTCC AB 2016297
(97.1 %). The average nucleotide identity values of the whole genome sequences of LX32
/P. hankyongense HKS-05
, LX32
/P. kunshanense CCTCC AB 2013085
and LX32
/P. deserti CCTCC AB 2016297
were 79.8, 77.9 and 77.5 %, respectively. Its genome size was 4.02 Mb, comprising 3998 predicted genes with a DNA G+C content of 70.1 mol%. The major fatty acids were C15 : 0, C16 : 0 and summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c). The polar lipid profiles consisted of phosphatidylglycerol, aminophospholipid, seven glycolipids and two unidentified polar lipids. The predominantly respiratory quinone was ubiquinone-10. Based on polyphasic analyses, the isolate is considered to represent a novel species of the genus Phenylobacterium, for which the name Phenylobacterium soli sp. nov. is proposed. The type strain is LX32
(=KCTC 62522=CCTCC AB 2018055).
The harvest index for many crops can be improved through introduction of dwarf stature to increase lodging resistance, combined with early maturity. The inbred line Shen5003 has been widely used in ...maize breeding in China as a key donor line for the dwarf trait. Also, one major quantitative trait locus (QTL) controlling plant height has been identified in bin 5.05-5.06, across several maize bi-parental populations. With the progress of publicly available maize genome sequence, the objective of this work was to identify the candidate genes that affect plant height among Chinese maize inbred lines with genome wide association studies (GWAS).
A total of 284 maize inbred lines were genotyped using over 55,000 evenly spaced SNPs, from which a set of 41,101 SNPs were filtered with stringent quality control for further data analysis. With the population structure controlled in a mixed linear model (MLM) implemented with the software TASSEL, we carried out a genome-wide association study (GWAS) for plant height. A total of 204 SNPs (P≤0.0001) and 105 genomic loci harboring coding regions were identified. Four loci containing genes associated with gibberellin (GA), auxin, and epigenetic pathways may be involved in natural variation that led to a dwarf phenotype in elite maize inbred lines. Among them, a favorable allele for dwarfing on chromosome 5 (SNP PZE-105115518) was also identified in six Shen5003 derivatives.
The fact that a large number of previously identified dwarf genes are missing from our study highlights the discovery of the consistently significant association of the gene harboring the SNP PZE-105115518 with plant height (P=8.91e-10) and its confirmation in the Shen5003 introgression lines. Results from this study suggest that, in the maize breeding schema in China, specific alleles were selected, that have played important roles in maize production.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Antimony (Sb) and copper (Cu) are toxic heavy metals that are associated with a wide variety of minerals. Sb(III)-oxidizing bacteria that convert the toxic Sb(III) to the less toxic Sb(V) are ...potentially useful for environmental Sb bioremediation. A total of 125 culturable Sb(III)/Cu(II)-resistant bacteria from 11 different types of mining soils were isolated. Four strains identified as Arthrobacter, Acinetobacter and Janibacter exhibited notably high minimum inhibitory concentrations (MICs) for Sb(III) (>10 mM),making them the most highly Sb(III)-resistant bacteria to date. Thirty-six strains were able to oxidize Sb(III), including Pseudomonas-, Comamonas-, Acinetobacter-, Sphingopyxis-, Paracoccus- Aminobacter-, Arthrobacter-, Bacillus-, Janibacter- and Variovorax-like isolates. Canonical correspondence analysis (CCA) revealed that the soil concentrations of Sb and Cu were the most obvious environmental factors affecting the culturable bacterial population structures. Stepwise linear regression was used to create two predictive models for the correlation between soil characteristics and the bacterial Sb(III) or Cu(II) resistance. The concentrations of Sb and Cu in the soil was the significant factors affecting the bacterial Sb(III) resistance, whereas the concentrations of S and P in the soil greatly affected the bacterial Cu(II) resistance. The two stepwise linear regression models that we derived are as follows: MIC(Sb(III))=606.605+0.14533 x C(Sb)+0.4128 x C(Cu) and MIC((Cu)(II))=58.3844+0.02119 x C(S)+0.00199 x CP where the MIC(Sb(III)) and MIC(Cu(II)) represent the average bacterial MIC for the metal of each soil (μM), and the C(Sb), C(Cu), C(S) and C(P) represent concentrations for Sb, Cu, S and P (mg/kg) in soil, respectively, p<0.01. The stepwise linear regression models we developed suggest that metals as well as other soil physicochemical parameters can contribute to bacterial resistance to metals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Corneal injuries are among the major causes of ocular morbidity and vision impairment. Optimal epithelial wound healing is critical for the integrity and transparency of the cornea after injury. ...Hepatocyte growth factor (HGF) is a mitogen and motility factor that primarily regulates epithelial cell function. Herein, we investigate the effect of HGF on proliferation of corneal epithelial cells (CECs) in inflamed conditions both in vitro and in vivo. We demonstrate that HGF not only promotes CEC proliferation in homeostatic conditions but also reverses the anti-proliferative effect of the inflammatory environment on these cells. Furthermore, using a mouse model of ocular injury, we show that HGF treatment suppresses ocular inflammation and actively augments CEC proliferation, leading to improved and accelerated corneal epithelial repair. These findings have potential translational implications and could provide a framework for the development of novel HGF-based therapies for corneal epithelial defects.
In this article, Omoto and colleagues report a novel role for hepatocyte growth factor (HGF) in accelerating corneal epithelial repair after injury. HGF promotes corneal epithelial cell proliferation in inflamed conditions and suppresses ocular inflammation.
Heterosis contributes a big proportion to hybrid performance in maize, especially for grain yield. It is attractive to explore the underlying genetic architecture of hybrid performance and heterosis. ...Considering its complexity, different from former mapping method, we developed a series of linear mixed models incorporating multiple polygenic covariance structures to quantify the contribution of each genetic component (additive, dominance, additive-by-additive, additive-by-dominance, and dominance-by-dominance) to hybrid performance and midparent heterosis variation and to identify significant additive and non-additive (dominance and epistatic) quantitative trait loci (QTL). Here, we developed a North Carolina II population by crossing 339 recombinant inbred lines with two elite lines (Chang7-2 and Mo17), resulting in two populations of hybrids signed as Chang7-2 × recombinant inbred lines and Mo17 × recombinant inbred lines, respectively. The results of a path analysis showed that kernel number per row and hundred grain weight contributed the most to the variation of grain yield. The heritability of midparent heterosis for 10 investigated traits ranged from 0.27 to 0.81. For the 10 traits, 21 main (additive and dominance) QTL for hybrid performance and 17 dominance QTL for midparent heterosis were identified in the pooled hybrid populations with two overlapping QTL. Several of the identified QTL showed pleiotropic effects. Significant epistatic QTL were also identified and were shown to play an important role in ear height variation. Genomic selection was used to assess the influence of QTL on prediction accuracy and to explore the strategy of heterosis utilization in maize breeding. Results showed that treating significant single nucleotide polymorphisms as fixed effects in the linear mixed model could improve the prediction accuracy under prediction schemes 2 and 3. In conclusion, the different analyses all substantiated the different genetic architecture of hybrid performance and midparent heterosis in maize. Dominance contributes the highest proportion to heterosis, especially for grain yield, however, epistasis contributes the highest proportion to hybrid performance of grain yield.
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