Targeted G-to-T base editing for generation of novel herbicide-resistance gene alleles in rice.

A newly developed rice guanine base editor (OsGTBE) achieves targeted and efficient G-to-T editing (C-to-A in the opposite strand) in rice. Using OsGTBE to edit endogenous herbicide-resistant loci generated several novel alleles conferring herbicide resistance, highlighting its utility in creating valuable germplasm and enhancing genetic diversity..

Comparative transcriptomics of stem bark reveals genes associated with bast fiber development in Boehmeria nivea L. gaud (ramie).

BACKGROUND: Boehmeria nivea L. Gaud (Ramie) produces one of the longest natural fibers in nature. The bark of ramie mainly comprises of the phloem tissue of stem and is the raw material for fiber. Therefore, identifying the molecular regulation of phloem development is important for understanding of bast fiber biosynthesis and improvement of fiber quality in ramie. RESULTS: In this study, we collected top bud (TB), bark from internode elongating region (ER) and bark from internode fully elongated region (FER) from the ramie variety Zhongzhu No. 1. Histological study indicated that these samples contain phloem tissues at different developmental and maturation stages, with a higher degree of maturation of phloem tissue in FER. RNA sequencing (RNA-seq) was performed and de novo transcriptome was assembled. Unigenes and differentially expressed genes (DEGs) in these three samples were identified. The analysis of DEGs by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed clear differences in gene expression between ER and FER. Some unigenes involved in secondary cell wall biosynthesis were up-regulated in both ER and FER, while unigenes for some cell wall components or cell wall modifications showed differential expression between ER and FER. In addition, the ethylene respond factors (ERFs) in the ethylene signaling pathway were up-regulated in FER, and ent-kaurenoic acid oxidase (KAO) and GA 20-oxidase (GA20ox) for gibberellins biosynthesis were up-regulated while GA 2-oxidase (GA2ox) for gibberellin inactivation was down-regulated in FER. CONCLUSIONS: Both morphological study and gene expression analysis supported a burst of phloem and vascular developmental processes during the fiber maturation in the ramie stem, and ethylene and gibberellin are likely to be involved in this process. Our findings provide novel insights into the phloem development and fiber maturation in ramie, which could be useful for fiber improvement in ramie and other fiber crops.

TPST is involved in fructose regulation of primary root growth in Arabidopsis thaliana.

KEY MESSAGE: TPST is involved in fructose signaling to regulate the root development and expression of genes in biological processes including auxin biosynthesis and accumulation in Arabidopsis. Sulfonation of proteins by tyrosine protein sulfotransferases (TPST) has been implicated in many important biological processes in eukaryotic organisms. Arabidopsis possesses a single TPST gene and its role in auxin homeostasis and root development has been reported. Here we show that the Arabidopsis tpst mutants are hypersensitive to fructose. In contrast to sucrose and glucose, fructose represses primary root growth of various ecotypes of Arabidopsis at low concentrations. RNA-seq analysis identified 636 differentially expressed genes (DEGs) in Col-0 seedlings in response to fructose verses glucose. GO and KEGG analyses of the DEGs revealed that fructose down-regulates genes involved in photosynthesis, glucosinolate biosynthesis and IAA biosynthesis, but up-regulates genes involved in the degradation of branched amino acids, sucrose starvation response, and dark response. The fructose responsive DEGs in the tpst mutant largely overlapped with that in Col-0, and most DEGs in tpst displayed larger changes than in Col-0. Interestingly, the fructose up-regulated DEGs includes genes encoding two AtTPST substrate proteins, Phytosulfokine 2 (PSK2) and Root Meristem Growth Factor 7 (RGF7). Synthesized peptides of PSK-α and RGF7 could restore the fructose hypersensitivity of tpst mutant plants. Furthermore, auxin distribution and accumulation at the root tip were affected by fructose and the tpst mutation. Our findings suggest that fructose serves as a signal to regulate the expression of genes involved in various biological processes including auxin biosynthesis and accumulation, and that modulation of auxin accumulation and distribution in roots by fructose might be partly mediated by the TPST substrate genes PSK-α and RGF7.

A comprehensive meta-analysis on the association of SGLT2is and GLP-1RAs with vascular diseases, digestive diseases and fractures.

AIM: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) are two new classes of antidiabetic agents. We aimed to evaluate the association between these two drug classes and risk of various vascular diseases, digestive diseases and fractures. METHODS: Large randomized trials of SGLT2is and GLP-1RAs were included. Outcomes of interest were the various serious adverse events related to vascular diseases, digestive diseases and fractures. We performed meta-analyses using synthesize risk ratio (RR) and 95% confidence interval (CI) as effect size. RESULTS: We included 27 large trials. SGLT2is had significant association with less hypertension (RR 0.70, 95% CI 0.54-0.91), hypertensive crisis (RR 0.63, 95% CI 0.47-0.84), varicose vein (RR 0.34, 95% CI 0.13-0.92), and vomiting (RR 0.55, 95% CI 0.31-0.97); but more spinal compression fracture (RR 1.73, 95% CI 1.02-2.92) and tibia fracture. GLP-1RAs had significant association with more deep vein thrombosis (RR 1.92, 95% CI 1.23-3.00), pancreatitis (RR 1.54, 95% CI 1.07-2.22), and cholecystitis acute (RR 1.51, 95% CI 1.08-2.09); but less rib fracture (RR 0.59, 95% CI 0.35-0.97). Sensitivity analyses suggested that our findings were robust. CONCLUSIONS: SGLT2is may have protective effects against specific vascular and digestive diseases, whereas they may increase the incidence of site-specific fractures (e.g., spinal compression fracture). GLP-1RAs may have protective effects against site-specific fractures (i.e., rib fracture), whereas they may increase the incidence of specific vascular and digestive diseases. These findings may help to make a choice between SGLT2is and GLP-1RAs in clinical practice.

Efficient and heritable A-to-K base editing in rice and tomato.

Cytosine and adenosine base editors (CBE and ABE) have been widely used in plants, greatly accelerating gene function research and crop breeding. Current base editors can achieve efficient A-to-G and C-to-T/G/A editing. However, efficient and heritable A-to-Y (A-to-T/C) editing remains to be developed in plants. In this study, a series of A-to-K base editor (AKBE) systems were constructed for monocot and dicot plants. Furthermore, nSpCas9 was replaced with the PAM-less Cas9 variant (nSpRY) to expand the target range of the AKBEs. Analysis of 228 T0 rice plants and 121 T0 tomato plants edited using AKBEs at 18 endogenous loci revealed that, in addition to highly efficient A-to-G substitution (41.0% on average), the plant AKBEs can achieve A-to-T conversion with efficiencies of up to 25.9 and 10.5% in rice and tomato, respectively. Moreover, the rice-optimized AKBE generates A-to-C conversion in rice, with an average efficiency of 1.8%, revealing the significant value of plant-optimized AKBE in creating genetic diversity. Although most of the A-to-T and A-to-C edits were chimeric, desired editing types could be transmitted to the T1 offspring, similar to the edits generated by the traditional ABE8e. Besides, using AKBEs to target tyrosine (Y, TAT) or cysteine (C, TGT) achieved the introduction of an early stop codon (TAG/TAA/TGA) of target genes, demonstrating its potential use in gene disruption.

Comparative efficacy and safety of pharmacological interventions for osteoporosis in postmenopausal women: a network meta-analysis (Chongqing, China).

OBJECTIVE: The aim of this study was to assess the comparative effectiveness and safety of different pharmacological agents, including abaloparatide and romosozumab, for treatment of osteoporosis in postmenopausal women. METHODS: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Google Scholar for relevant randomized controlled trials published up to July 16, 2018. After study selection according to the preplanned criteria, we performed data extraction and quality assessment. With statistical heterogeneity and inconsistency being examined, pairwise and network meta-analyses were conducted to synthesize risk ratio and 95% CI. Finally, we calculated the surface under the cumulative ranking curve to rank the interventions, and carried out three sensitivity analyses to assess the robustness of our main results. RESULTS: Our searches yielded 2,584 records in total, of which 21 were finally included in quantitative synthesis and all of them were of high quality. Our 5 outcomes of interest involved a total of 13 interventions and 67,524 participants. For each outcome, the estimated τ values all were less than or equal to 0.0747, and the P values for test of consistency varied from 0.097 to 0.941, respectively, suggesting low heterogeneity and no inconsistency. Abaloparatide and teriparatide, without statistical difference between them, had a statistically lower risk of new vertebral or nonvertebral fractures than placebo, strontium ranelate, risedronate, raloxifene, lasofoxifene (0.25 mg/d), lasofoxifene (0.5 mg/d), denosumab, and alendronate. Zoledronic acid and romosozumab, without statistical difference between them, were significantly more efficacious than placebo, risedronate, and alendronate in preventing clinical fractures. Denosumab was statistically superior to placebo in preventing new vertebral and nonvertebral fractures, and to placebo, risedronate, and alendronate in preventing clinical fractures. For the outcomes of adverse events and serious adverse events, all of treatments were not statistically different from one another, except that zoledronic acid was statistically worse than placebo in terms of adverse events. Based on surface under the cumulative ranking curves, abaloparatide and teriparatide were two of the most effective treatments in preventing new vertebral and nonvertebral fractures; zoledronic acid and romosozumab were two of the most effective treatments in preventing clinical fractures, and denosumab and romosozumab were two of the best interventions for the outcome of adverse events. Three sensitivity analyses revealed the robustness of the main results. CONCLUSIONS: Abaloparatide and teriparatide are most efficacious in preventing new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis, whereas zoledronic acid and romosozumab are in preventing clinical fractures. Meanwhile, there is no statistical difference between abaloparatide, teriparatide or romosozumab, and placebo in terms of safety. Furthermore, in terms of adverse events, zoledronic acid is statistically worse than placebo, and two of the best interventions are denosumab and romosozumab, of which denosumab also reduces the risk of different kinds of fractures.

Life-cycle assessment of tobacco stalk utilization.

The aim of this work was to investigate the environmental performance of different tobacco stalk methods using Life Cycle Assessment (LCA). Three scenarios were established: biodegradable plant nursery tray (PNT) making, open burning, and indoor incineration. The results showed that 3380, 1590, 1320 kg CO2-eq, 25.7, 1.97,1.99 kg SO2-eq are generated for global warming and acidification in biodegradable PNT making, open burning, and indoor incineration scenarios respectively. The overall environmental impact for biodegradable PNT making is higher than that of open burning, and indoor incineration. The dominant factors contributing to environmental impact in biodegradable PNT making include electricity consumption, solid waste landfill etc. Through technical optimization, the environmental impact of biodegradable PNT making could be reduced greatly. Biodegradable PNT making with tobacco stalk, which follows the cyclic economy principles of maximum material utilization and waste minimization, provides an alternative for agricultural residue utilization.