Biallelic variants in POPDC2 cause a novel autosomal recessive syndrome presenting with cardiac conduction defects and variable hypertrophic cardiomyopathy.

POPDC2 encodes for the Popeye domain-containing protein 2 which has an important role in cardiac pacemaking and conduction, due in part to its cAMP-dependent binding and regulation of TREK-1 potassium channels. Loss of Popdc2 in mice results in sinus pauses and bradycardia and morpholino knockdown of popdc2 in zebrafish results in atrioventricular (AV) block. We identified bi-allelic variants in POPDC2 in 4 families that presented with a phenotypic spectrum consisting of sinus node dysfunction, AV conduction defects and hypertrophic cardiomyopathy. Using homology modelling we show that the identified POPDC2 variants are predicted to diminish the ability of POPDC2 to bind cAMP. In in vitro electrophysiological studies we demonstrated that, while co-expression of wild-type POPDC2 with TREK-1 increased TREK-1 current density, POPDC2 variants found in the patients failed to increase TREK-1 current density. While patient muscle biopsy did not show clear myopathic disease, it showed significant reduction of the expression of both POPDC1 and POPDC2, suggesting that stability and/or membrane trafficking of the POPDC1-POPDC2 complex is impaired by pathogenic variants in any of the two proteins. Single-cell RNA sequencing from human hearts demonstrated that co-expression of POPDC1 and 2 was most prevalent in AV node, AV node pacemaker and AV bundle cells. Sinoatrial node cells expressed POPDC2 abundantly, but expression of POPDC1 was sparse. Together, these results concur with predisposition to AV node disease in humans with loss-of-function variants in POPDC1 and POPDC2 and presence of sinus node disease in POPDC2, but not in POPDC1 related disease in human. Using population-level genetic data of more than 1 million individuals we showed that none of the familial variants were associated with clinical outcomes in heterozygous state, suggesting that heterozygous family members are unlikely to develop clinical manifestations and therefore might not necessitate clinical follow-up. Our findings provide evidence for POPDC2 as the cause of a novel Mendelian autosomal recessive cardiac syndrome, consistent with previous work showing that mice and zebrafish deficient in functional POPDC2 display sinus and AV node dysfunction.

Flame retardant cotton fabrics with ultra-fast and long-term fire early warning response.

Smart textiles with flame retardant and fire-warning functions have received more and more attention. However, improving the fire-warning response sensitivity and long-term responsiveness of the smart textiles is a top priority. In this research, flame retardant and fire-warning cotton fabrics were prepared by layer-by-layer assembly composite coating consisting of bio-based flame retardants composed of chitosan (CS) and phytic acid (PA) and carbon-based nanomaterials composed of carbon nanotubes (CNTs) and graphene oxide (GO). The PA-GO/CS-CNTs coated cotton fabric showed excellent flame retardancy with a limiting oxygen index (LOI) value of 31 %, and the coated fabrics could self-extinguish rapidly when the flame was removed. The fire hazard of the coated fabric was significantly reduced by reducing the 45.77 % of peak heat release rate, 29.69 % of total heat release and 81.9 % of total smoke production. The PA-GO/CS-CNTs coated cotton fabric showed ultra-fast fire warning response with the response time of 1.0 s. And the fire-warning response time of the coated cotton fabric could last longer than 600 s revealing it possessed the continuous fire warning response property. This research provides a new strategy to prepare the smart fireproof textiles with flame retardant and fire-warning functions to broaden its application in early fire-warning.

Multi-functionalization of cotton fabrics with excellent flame retardant, antibacterial and superhydrophobic properties.

Cotton fabric is widely used in many fields for its excellent comfortability, breathability and hygroscopicity. However, the development of multifunctional cotton fabrics to meet the requirements of different scenarios is a top priority. In this study, multifunctional coating was constructed through facile layer-by-layer assembly phytic acid and chitosan, and spraying divalent copper ion and polydimethylsiloxane (PDMS) on cotton fabrics, anticipating to endow them with flame retardancy, antibacterial and superhydrophobic properties simultaneously. The treated cotton fabric achieved a limiting oxygen index (LOI) value of 32 %, with the char length reducing to 10.7 cm revealing excellent flame retardancy. The water contact angle of multifunctional treated cotton fabric was above 150°, demonstrating it had superhydrophobicity. The antibacterial rates of multifunctional cotton fabrics against E. coli and S. aureus reached to higher than 99 %, indicating that the excellent antibacterial properties. Combined with the thermal stability of cotton fabrics and their char residues analysis, these results demonstrated that the multifunctional coating could act through intumescent flame retardant mechanism to flame retardant cotton fabrics. This research provides a facile way to prepare multifunctional cotton fabrics to broaden the application prospect.

Author Correction: Competitive endogenous RNA is an intrinsic component of EMT regulatory circuits and modulates EMT.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Competitive endogenous RNA is an intrinsic component of EMT regulatory circuits and modulates EMT.

The competitive endogenous RNA (ceRNA) hypothesis suggests an intrinsic mechanism to regulate biological processes. However, whether the dynamic changes of ceRNAs can modulate miRNA activities remains controversial. Here, we examine the dynamics of ceRNAs during TGF-ß-induced epithelial-to-mesenchymal transition (EMT). We observe that TGFBI, a transcript highly induced during EMT in A549 cells, acts as the ceRNA for miR-21 to modulate EMT. We further identify FN1 as the ceRNA for miR-200c in the canonical SNAIL-ZEB-miR200 circuit in MCF10A cells. Experimental assays and computational simulations demonstrate that the dynamically induced ceRNAs are directly coupled with the canonical double negative feedback loops and are critical to the induction of EMT. These results help to establish the relevance of ceRNA in cancer EMT and suggest that ceRNA is an intrinsic component of the EMT regulatory circuit and may represent a potential target to disrupt EMT during tumorigenesis.