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Aims: According to the gut–kidney axis theory, gut microbiota (GM) has bidirectional crosstalk with the development of diabetic kidney disease (DKD). However, empirical results have been inconsistent, and the causal associations remain unclear. This study was aimed at exploring the causal relationship between GM and DKD as well as the glomerular filtration rate (GFR) and urinary albumin‐to‐creatinine ratio (UACR). Materials and Methods: Two‐sample Mendelian randomisation (MR) analysis was performed with inverse‐variance weighting as the primary method, together with four additional modes (MR–Egger regression, simple mode, weighted mode, and weighted median). We utilised summary‐level genome‐wide association study statistics from public databases for this MR analysis. Genetic associations with DKD were downloaded from the IEU Open GWAS project or CKDGen consortium, and associations with GM (196 taxa from five levels) were downloaded from the MiBioGen repository. Results: In forward MR analysis, we identified 13 taxa associated with DKD, most of which were duplicated in Type 2 diabetes with renal complications but not in Type 1 diabetes. We observed a causal association between genetic signature contributing to the relative abundance of Erysipelotrichaceae UCG003 and that for both DKD and GFR. Similarly, host genetic signature defining the abundance of Ruminococcaceae UCG014 was found to be simultaneously associated with DKD and UACR. In reverse MR analysis, the abundance of 14 other GM taxa was affected by DKD, including the phylum Proteobacteria, which remained significant after false discovery rate correction. Sensitivity analyses revealed no evidence of outliers, heterogeneity, or horizontal pleiotropy. Conclusion: Our findings provide compelling causal genetic evidence for the bidirectional crosstalk between specific GM taxa and DKD development, contributing valuable insights for a comprehensive understanding of the pathological mechanisms of DKD and highlighting the possibility of prevention and management of DKD by targeting GM. [ABSTRACT FROM AUTHOR]

This study demonstrated that incorporation of Ca2+-responsive β-roll peptides arising from repeat-in-toxin (RTX) into elastomeric proteins provided an approach to construct hydrogels that exhibit Ca2+-responsive mechanical properties through a force analysis-based approach. Use of circular dichroism spectroscopy confirmed that there was a Ca2+-induced conformational change of RTX-based recombinant polyproteins. The polyproteins could be crosslinked into solid hydrogels. Shrinking/swelling measurements showed a Ca2+-responsive dimensional change of the RTX-based hydrogels. Mechanical measurements at constant pulling speed and at constant extension suggested that the mechanical properties of the RTX-based hydrogels were Ca2+-responsive. Experimental single molecule force spectroscopies were used to investigate the nano-mechanical stability of the RTX domains. Single molecule atomic force microscopy and optical tweezers provided evidence that the Ca2+-dependent refolding of the intrinsically disordered RTX led to the force increase. The results indicated that the unique Ca2+-responsive mechanical properties of the RTX-based hydrogels at the macroscopic level could be attributed to the nano-mechanical properties of the RTX domains engineered into individual polyproteins at the single molecule level. [ABSTRACT FROM AUTHOR]

Correction for 'Using single molecule force spectroscopy to facilitate a rational design of Ca2+-responsive β-roll peptide-based hydrogels' by Lichao Liu et al., J. Mater. Chem. B, 2018, 6, 5303–5312, DOI: 10.1039/C8TB01511B. [ABSTRACT FROM AUTHOR]

This study demonstrated that incorporation of Ca 2+ -responsive β-roll peptides arising from repeat-in-toxin (RTX) into elastomeric proteins provided an approach to construct hydrogels that exhibit Ca 2+ -responsive mechanical properties through a force analysis-based approach. Use of circular dichroism spectroscopy confirmed that there was a Ca 2+ -induced conformational change of RTX-based recombinant polyproteins. The polyproteins could be crosslinked into solid hydrogels. Shrinking/swelling measurements showed a Ca 2+ -responsive dimensional change of the RTX-based hydrogels. Mechanical measurements at constant pulling speed and at constant extension suggested that the mechanical properties of the RTX-based hydrogels were Ca 2+ -responsive. Experimental single molecule force spectroscopies were used to investigate the nano-mechanical stability of the RTX domains. Single molecule atomic force microscopy and optical tweezers provided evidence that the Ca 2+ -dependent refolding of the intrinsically disordered RTX led to the force increase. The results indicated that the unique Ca 2+ -responsive mechanical properties of the RTX-based hydrogels at the macroscopic level could be attributed to the nano-mechanical properties of the RTX domains engineered into individual polyproteins at the single molecule level.