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Background The rhizosphere microbiome, which is shaped by host genotypes, root exudates, and plant domestication, is crucial for sustaining agricultural plant growth. Despite its importance, how plant domestication builds up specific rhizosphere microbiomes and metabolic functions, as well as the importance of these affected rhizobiomes and relevant root exudates in maintaining plant growth, is not well understood. Here, we firstly investigated the rhizosphere bacterial and fungal communities of domestication and wild accessions of tetraploid wheat using amplicon sequencing (16S and ITS) after 9 years of domestication process at the main production sites in China. We then explored the ecological roles of root exudation in shaping rhizosphere microbiome functions by integrating metagenomics and metabolic genomics approaches. Furthermore, we established evident linkages between root morphology traits and keystone taxa based on microbial culture and plant inoculation experiments. Results Our results suggested that plant rhizosphere microbiomes were co-shaped by both host genotypes and domestication status. The wheat genomes contributed more variation in the microbial diversity and composition of rhizosphere bacterial communities than fungal communities, whereas plant domestication status exerted much stronger influences on the fungal communities. In terms of microbial interkingdom association networks, domestication destabilized microbial network and depleted the abundance of keystone fungal taxa. Moreover, we found that domestication shifted the rhizosphere microbiome from slow growing and fungi dominated to fast growing and bacteria dominated, thereby resulting in a shift from fungi-dominated membership with enrichment of carbon fixation genes to bacteria-dominated membership with enrichment of carbon degradation genes. Metagenomics analyses further indicated that wild cultivars of wheat possess higher microbial function diversity than domesticated cultivars. Notably, we found that wild cultivar is able to harness rhizosphere microorganism carrying N transformation (i.e., nitrification, denitrification) and P mineralization pathway, whereas rhizobiomes carrying inorganic N fixation, organic N ammonification, and inorganic P solubilization genes are recruited by the releasing of root exudates from domesticated wheat. More importantly, our metabolite-wide association study indicated that the contrasting functional roles of root exudates and the harnessed keystone microbial taxa with different nutrient acquisition strategies jointly determined the aboveground plant phenotypes. Furthermore, we observed that although domesticated and wild wheats recruited distinct microbial taxa and relevant functions, domestication-induced recruitment of keystone taxa led to a consistent growth regulation of root regardless of wheat domestication status. Conclusions Our results indicate that plant domestication profoundly influences rhizosphere microbiome assembly and metabolic functions and provide evidence that host plants are able to harness a differentiated ecological role of root-associated keystone microbiomes through the release of root exudates to sustain belowground multi-nutrient cycles and plant growth. These findings provide valuable insights into the mechanisms underlying plant-microbiome interactions and how to harness the rhizosphere microbiome for crop improvement in sustainable agriculture. CBzZNC2FEDswGcHctbDosa Video Abstract

Summary N6‐methyladenosine (m6A) RNA methylation, one of the most pivotal internal modifications of RNA, is a conserved post‐transcriptional mechanism to enrich and regulate genetic information in eukaryotes. The scope and function of this modification in plants has been an intense focus of study, especially in model plant systems. The characterization of plant m6A writers, erasers and readers, as well as the elucidation of their functions, is currently one of the most fascinating hotspots in plant biology research. The functional analysis of m6A in plants will be booming in the foreseeable future, which could contribute to crop genetic improvement through epitranscriptome manipulation. In this review, we systematically analysed and summarized recent advances in the understanding of the structure and composition of plant m6A regulatory machinery, and the biological functions of m6A in plant growth, development and stress response. Finally, our analysis showed that the evolutionary relationships between m6A modification components were highly conserved across the plant kingdom.

Clustered regularly interspaced short palindromic repeats (CRISPR) system provides adaptive immunity against plasmids and phages in prokaryotes. This system inspires the development of a powerful genome engineering tool, the CRISPR/CRISPR-associated nuclease 9 (CRISPR/Cas9) genome editing system. Due to its high efficiency and precision, the CRISPR/Cas9 technique has been employed to explore the functions of cancer-related genes, establish tumor-bearing animal models and probe drug targets, vastly increasing our understanding of cancer genomics. Here, we review current status of CRISPR/Cas9 gene editing technology in oncological research. We first explain the basic principles of CRISPR/Cas9 gene editing and introduce several new CRISPR-based gene editing modes. We next detail the rapid progress of CRISPR screening in revealing tumorigenesis, metastasis, and drug resistance mechanisms. In addition, we introduce CRISPR/Cas9 system delivery vectors and finally demonstrate the potential of CRISPR/Cas9 engineering to enhance the effect of adoptive T cell therapy (ACT) and reduce adverse reactions.

Background The systemic immune-inflammation index (SII), based on peripheral platelet, neutrophil and lymphocyte counts, has been proven to be a promising prognostic indicator in various diseases. Hip fracture is a common injury among the older adults, and has become a global public health problem with high mortality and disability rates. However, the relationship between SII and the prognosis of hip fracture is not yet well-known. The aim of the this study was to explore the predictive value of SII in older adults with hip fracture undergoing surgery. Methods This was a prospective cohort study performed from January 2014 to December 2018 at a orthopaedic center, China. The SII was calculated as platelet×neutrophil/lymphocyte counts. Univariable and multivariable Cox proportional hazard models were used to assess the association between SII and all-cause mortality. Results A total of 290 older adults with hip fracture were included, and the mean (SD) age was 77.6 (8.6) years, and 189 (65.2%) were female. The median (IQR) SII was 759.4 (519.0–1128.7) × 10 9 /L. After a median follow-up time of 33.4 months, 13 (4.5%), 26 (9.0%) and 54 (18.6%) patients died within the 30-day, 1-year and last follow-up, respectively. Multivariable Cox analysis revealed that each increase of 100 units of SII was associated with a 8% increased hazard of death at 1-year follow-up (HR = 1.08, 95% CI: 1.01–1.17, p  = 0.033), and 9% increased hazard of death at last follow-up (HR = 1.09, 95% CI: 1.03–1.15, p  = 0.003). Conclusions SII is associated with poor all-cause mortality in older adults with hip fracture undergoing surgery, and deserves further investigation and application in clinical practice.

Background The effects of body mass index (BMI) on the prognosis of acute respiratory distress syndrome (ARDS) are controversial. We aimed to further determine the relationship between BMI and the acute outcomes of patients with ARDS. Methods We searched the Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and ISI Web of Science for trials published between 1946 and July 2016, using “BMI” or “body mass index” or “overweight” or “obese” and “ARDS” or “ALI” or “acute respiratory distress syndrome” or “acute lung injury”, without limitations on publication type or language. Heterogeneity and sensitivity analyses were conducted, and a random-effects model was applied to calculate the odds ratio (OR) or mean difference (MD). Review Manager (RevMan) was used to test the hypothesis using the Mann-Whitney U test. The primary outcome was unadjusted mortality, and secondary outcomes included mechanical ventilation (MV)-free days and length of stay (LOS) in the intensive care unit (ICU) and in hospital. Results Five trials with a total of 6268 patients were pooled in our final analysis. There was statistical heterogeneity between normal-weight and overweight patients in LOS in the ICU ( I 2  = 71%, χ 2  = 10.27, P  = 0.02) and in MV-free days ( I 2  = 89%, χ 2  = 18.45, P  < 0.0001). Compared with normal weight, being underweight was associated with higher mortality (OR 1.59, 95% confidence interval (CI) 1.22, 2.08, P  = 0.0006), while obesity and morbid obesity were more likely to result in lower mortality (OR 0.68, 95% CI 0.57, 0.80, P  < 0.00001; OR 0.72, 95% CI 0.56, 0.93, P  = 0.01). MV-free days were much longer in patients with morbid obesity (MD 2.64, 95% CI 0.60, 4.67, P  = 0.01), but ICU and hospital LOS were not influenced by BMI. An important limitation of our analysis is the lack of adjustment for age, sex, illness severity, comorbid illness, and interaction of outcome parameters. Conclusions Obesity and morbid obesity are associated with lower mortality in patients with ARDS.

A bstract We investigate the “complexity equals anything” proposal with codimension-one and codimension-zero gravitational observables for multi-horizon black holes, using the Bardeen-AdS class black hole as an example. In particular, we compare the results with the “complexity equals volume” (CV) proposal and find that the generalized volume complexitiy enables the probing of a more complete black hole interior, that is, all spacetime regions where the blackening factor f ( r ) < 0. This is the advantage brought by the flexibility of this holographic complexity conjecture. In addition, we compute the codimension-zero gravitational observables derived from various geometric quantities and show that these constructions can effectively differentiate the distinct interior regions of the black hole.

Overexpression of Jumonji domain-containing 6 (JMJD6) has been reported to be associated with more aggressive breast cancer characteristics. However, the precise role of JMJD6 in breast cancer development remains unclear. Here, we demonstrate that JMJD6 has intrinsic tyrosine kinase activity and can utilize ATP and GTP as phosphate donors to phosphorylate Y39 of histone H2A.X (H2A.X Y39ph ). High JMJD6 levels promoted autophagy in triple negative breast cancer (TNBC) cells by regulating the expression of autophagy-related genes. The JMJD6-H2A.X Y39ph axis promoted TNBC cell growth via the autophagy pathway. We show that combined inhibition of JMJD6 kinase activity and autophagy efficiently decreases TNBC growth. Together, these findings suggest an effective strategy for TNBC treatment.