Metabolic pathways engineering for drought or/and heat tolerance in cereals

Drought (D) and heat (H) are the two major abiotic stresses hindering cereal crop growth and productivity, either singly or in combination (D/+H), by imposing various negative impacts on plant physiological and biochemical processes. Consequently, this decreases overall cereal crop production and impacts global food availability and human nutrition. To achieve global food and nutrition security vis-a-vis global climate change, deployment of new strategies for enhancing crop D/+H stress tolerance and higher nutritive value in cereals is imperative. This depends on first gaining a mechanistic understanding of the mechanisms underlying D/+H stress response. Meanwhile, functional genomics has revealed several stress-related genes that have been successfully used in target-gene approach to generate stress-tolerant cultivars and sustain crop productivity over the past decades. However, the fast-changing climate, coupled with the complexity and multigenic nature of D/+H tolerance suggest that single-gene/trait targeting may not suffice in improving such traits. Hence, in this review-cum-perspective, we advance that targeted multiple-gene or metabolic pathway manipulation could represent the most effective approach for improving D/+H stress tolerance. First, we highlight the impact of D/+H stress on cereal crops, and the elaborate plant physiological and molecular responses. We then discuss how key primary metabolism- and secondary metabolism-related metabolic pathways, including carbon metabolism, starch metabolism, phenylpropanoid biosynthesis, γ-aminobutyric acid (GABA) biosynthesis, and phytohormone biosynthesis and signaling can be modified using modern molecular biotechnology approaches such as CRISPR-Cas9 system and synthetic biology (Synbio) to enhance D/+H tolerance in cereal crops. Understandably, several bottlenecks hinder metabolic pathway modification, including those related to feedback regulation, gene functional annotation, complex crosstalk between pathways, and metabolomics data and spatiotemporal gene expressions analyses. Nonetheless, recent advances in molecular biotechnology, genome-editing, single-cell metabolomics, and data annotation and analysis approaches, when integrated, offer unprecedented opportunities for pathway engineering for enhancing crop D/+H stress tolerance and improved yield. Especially, Synbio-based strategies will accelerate the development of climate resilient and nutrient-dense cereals, critical for achieving global food security and combating malnutrition

A collaborative, individual-level analysis compared longitudinal outcomes across the International Network of Chronic Kidney Disease (iNETCKD) cohorts.

Rates of chronic kidney disease (CKD) progression, end stage kidney disease (ESKD), all-cause mortality, and cardiovascular (CVD) events among individuals with CKD vary widely across countries. Well-characterized demographic, comorbidity, and laboratory markers captured for prospective cohorts may explain, in part, such differences. To investigate whether core characteristics of individuals with CKD explain differences in rates of outcomes, we conducted an individual-level analysis of eight studies that are part of iNET-CKD, an international network of CKD cohort studies. Overall, the rate of CKD progression was 40 events/1000 person-year (95% confidence interval 39 - 41), 28 (27 - 29) for ESKD, 41 (40 - 42) for death, and 29 (28 - 30) for CVD events. However, standardized rates were highly heterogeneous across studies (over 92.5%). Interactions by study group on the association between baseline characteristics and outcomes were then identified. For example, the adjusted hazard ratio for CKD progression was 0.44 (95% confidence interval 0.35 - 0.56) for women vs. men among the Japanese (CKD-JAC), while it was 0.66 (0.59 - 0.75) among the Uruguayan (NRHP). The adjusted hazard ratio for ESKD was 2.02 (95% CI 1.88 - 2.17) per 10 units lower baseline eGFR among Americans (CRIC), while it was 3.01 (2.57 - 3.53) among Canadians (CanPREDDICT) (significant interaction for comparisons across all studies). The risks of CKD progression, ESKD, death, and CVD vary across countries even after accounting for the distributions of age, sex, comorbidities, and laboratory markers. Thus, our findings support the need for a better understanding of specific factors in different populations that explain this variation