Key to the success of legumes is the ability to form and maintain optimal symbiotic nodules that enable them to balance the trade-off between symbiosis and plant growth. Cytokinin is essential for homeostatic regulation of nodulation, but the mechanism remains incompletely understood. Here, we show that a B-type response regulator GmRR11d mediates systemic inhibition of nodulation.GmRR11dis induced by rhizobia and low level cytokinin, and GmRR11d can suppress the transcriptional activity of GmNSP1 onGmNIN1ato inhibit soybean nodulation. GmRR11d positively regulates cytokinin response and its binding on theGmNIN1apromoter is enhanced by cytokinin. Intriguingly, rhizobial induction ofGmRR11dand its function are dependent upon GmNARK that is a CLV1-like receptor kinase and inhibits nodule number in shoots. Thus, GmRR11d governs a transcriptional program associated with nodulation attenuation and cytokinin response activation essential for systemic regulation of nodulation.

Background: Abscisic acid (ABA) plays an important role in plant growth and adaptation through the ABA signaling pathway. The ABA-responsive element binding (AREB/ABF) family transcriptional factors are central regulators that integrate ABA signaling with various signaling pathways. It has long been known that ABA inhibits rhizobial infection and nodule formation in legumes, but the underlying molecular mechanisms remain elusive.Results: Here, we show that nodulation is very sensitive to ABA and exogenous ABA dramatically inhibits rhizobial infection and nodule formation in soybean. In addition, we proved that GmbZIP1, an AREB/ABF transcription factor, is a major regulator in both nodulation and plant response to ABA in soybean.GmbZIP1was specifically expressed during nodule formation and development. Overexpression ofGmbZIP1resulted in reduced rhizobial infection and decreased nodule number. Furthermore,GmbZIP1is responsive to ABA, and ectopic overexpression ofGmbZIP1increased sensitivity of Arabidopsis plants to ABA during seed germination and postgerminative growth, and conferred enhanced drought tolerance of plants. Remarkably, we found that GmbZIP1 directly binds to the promoter ofGmENOD40–1, a marker gene for nodule formation, to repress its expression.Conclusion: Our results identified GmbZIP1 as a node regulator that integrates ABA signaling with nodulation signaling to negatively regulate nodule formation.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibition is recognized for its evident renoprotective benefits in diabetic renal disease. Recent data suggest that SGLT2 inhibition also slows down kidney disease progression and reduces the risk of acute kidney injury, regardless of whether the patient has diabetes or not, but the mechanism behind these observed effects remains elusive. The objective of this study is to utilize a mendelian randomization (MR) methodology to comprehensively examine the influence of metabolites in circulation regarding the impact of SGLT2 inhibition on kidney function.Methods: We used a MR study to obtain associations between genetic proxies for SGLT2 inhibition and kidney function. We retrieved the most recent and comprehensive summary statistics from genome-wide association studies (GWAS) that have been previously published and involved kidney function parameters such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and albuminuria. Additionally, we included blood metabolite data from 249 biomarkers in the UK Biobank for a more comprehensive analysis. We performed MR analyses to explore the causal relationships between SGLT2 inhibition and kidney function and two-step MR to discover potential mediating metabolites.Results: The study found that a decrease in HbA1c levels by one standard deviation, which is genetically expected to result in SGLT2 inhibition, was linked to a decreased likelihood of developing type 2 diabetes mellitus (T2DM) (odds ratio [OR] = 0.55 [95% CI 0.35, 0.85],P = 0.007). Meanwhile, SGLT2 inhibition also protects eGFR (β = 0.05 [95% CI 0.03, 0.08],P = 2.45 × 10^− 5) and decreased UACR (-0.18 [95% CI -0.33, -0.02],P = 0.025) and albuminuria (-1.07 [95% CI -1.58, -0.57],P = 3.60 × 10^− 5). Furthermore, the study found that of the 249 metabolites present in the blood, only one metabolite, specifically the concentration of small high-density lipoprotein (HDL) particles, was significantly correlated with both SGLT2 inhibition and kidney function. This metabolite was found to play a crucial role in mediating the improvement of renal function through the use of SGLT2 inhibition (β = 0.01 [95% CI 0.005, 0.018],P = 0.001), with a mediated proportion of 13.33% (95% CI [5.71%, 26.67%],P = 0.020).Conclusions: The findings of this investigation provide evidence in favor of a genetically anticipated biological linkage between the inhibition of SGLT2, the presence of circulating metabolites, and renal function. The findings demonstrate that the protective effect of SGLT2 inhibition on renal function is mostly mediated by HDL particle concentrations in circulating metabolites. These results offer significant theoretical support for both the preservation of renal function and a better comprehension of the mechanisms underlying SGLT2 inhibition.