Studies of nanomedicine have achieved dramatic progress in recent decades.

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Tetralogy of Fallot (TOF) represents the most common form of cyanotic congenital heart disease and accounts for significant morbidity and mortality in humans. Emerging evidence has implicated genetic defects in the pathogenesis of TOF. However, TOF is genetically heterogeneous and the genetic basis for TOF in most patients remains unclear. In this study, the GATA4 gene were sequenced in 52 probands with familial TOF, and three novel heterozygous mutations, including A9P and L51V both located in the putative first transactivational domain and N285S in the C-terminal zinc finger, were identified in three probands, respectively. Genetic analysis of the pedigrees demonstrated that in each family the mutation cosegregated with TOF with complete penetrance. The missense mutations were absent in 800 control chromosomes and the altered amino acids were highly conserved evolutionarily. Functional analysis showed that the GATA4 mutants were consistently associated with diminished DNA-binding affinity and decreased transcriptional activity. Furthermore, the N285S mutation completely disrupted the physical interaction between GATA4 and TBX5. To our knowledge, this report associates GATA4 loss-of-function mutations with familial TOF for the first time, providing novel insight into the molecular mechanism involved in TOF and suggesting potential implications for the early prophylaxis and allele-specific therapy of TOF.

Maternal deprivation (MD) is frequently used as an early life stress model in rodents to investigate behavioral and neurological responses under stressful conditions. However, the effect of MD on the early postnatal development of rodents, which is when multiple neural systems become established, is rarely investigated due to methodological limitations. Ultrasonic vocalizations (USVs) are one of the few responses produced by neonatal rodents that can be quantitatively analyzed, and the quantification of USVs is regarded as a novel approach to investigate possible alterations in the neurobehavioral and emotional development of infant rodents under stress. To investigate the effect of MD on pup mice, we subjected C57BL/6J mice to MD and recorded the USVs of pups on postnatal days 1, 3, 7, 8, and 14. To determine whether the effect of MD on USVs was acute or cumulative, pre- and post-separation USV groups were included; sex differences in pup USV emission were also investigated. Our results suggest that (i) USV activity was high on postnatal days 3–8; (ii) the MD effect on USVs was acute, and a cumulative effect was not found; (iii) the MD mice vocalized more and longer than the controls at a lower frequency, and the effect was closely related to age; and (iv) female pups were more susceptible than males to the effect of MD on USV number and duration between postnatal days 3–8.

Organic thin-film transistors (OTFTs) exhibit great potential applications in flexible logic circuits, sensors, nonvolatile memory, etc. The vertical phase separation (VPS) structure, deriving from the blends of small molecules and polymers, can produce a high-quality crystalline semiconducting layer and an intrinsic and trap-free semiconductor/insulator interface. OTFTs with a VPS structure provide a promising route to accelerate their commercialization due to these desirable features including excellent device performance, good uniformity and reproducibility, environmental and mechanical stability, lowcost and large-area fabrication. Additionally, VPS OTFTs also exhibit a good balance between electronical properties and stretchability for intrinsic stretchable OTFTs. Herein, a comprehensive review is given on VPS structure for flexible and stretchable OTFTs. First, the evolution history of VPS structures and its formation mechanism are summarized. Based on the understanding of the VPS structure, the optimization strategies of VPS structures for highperformance OTFTs are presented. Subsequently, the large-area fabrication techniques of VPS structures, as well as the potential applications in flexible and stretchable OTFTs, are discussed. Finally, conclusions and outlook are provided for the further development of VPS structure in OTFTs. This review would promote the understanding and development of VPS structures in OTFTs, accelerating its applications in flexible and stretchable electronics.

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Congenital heart disease (CHD) is the most common form of developmental malformation and is the leading noninfectious cause of infant mortality. Emerging evidence indicates that genetic defects are involved in the pathogenesis of CHD. Nevertheless, CHD is genetically heterogeneous, and the molecular basis for CHD in a majority of patients remains unknown. In this study, the whole coding region of GATA6, a gene encoding a zinc-finger transcription factor crucial for normal cardiogenesis, was sequenced in 380 unrelated patients with CHD. The relatives of the index patients harboring the identified mutations and 200 unrelated control individuals were subsequently genotyped. The functional effect of the mutations was characterized using a luciferase reporter assay system. As a result, two novel heterozygous GATA6 mutations, p.D404Y and p.E460X, were identified in two families with ventricular septal defect and tetralogy of Fallot, respectively. The mutations co-segregated with CHD in the families with complete penetrance, and were absent in 400 control chromosomes. Functional analysis demonstrated that the mutated GATA6 proteins were associated with significantly decreased transactivational activity in comparison with their wild-type counterpart. These findings provide novel insight into the molecular mechanism implicated in CHD, suggesting potential implications for the early prophylaxis and personalized treatment of CHD.

Long noncoding RNAs have been reported to play important roles in the pathogenesis of diabetic retinopathy (DR), which has been considered as the most common disease leading to vision loss. However, it is still unclear whether KCNQ1 overlapping transcript 1 (KCNQ1OT1) could affect DR. In this study, regarding quantitative reverse transcription polymerase chain reaction assay, KCNQ1OT1 level was upregulated while microRNA‐1470 (miR‐1470) was decreased in DR patients and human retinal endothelial cells. High KCNQ1OT1 expression was correlated with DR stage and low visual function. Using miR‐1470 mimic or knockdown of KCNQ1OT1 could lead to the similar phenomenon; phospho‐AKT, Bax, B‐cell lymphoma 2, and cleaved poly‐ADP ribose polymerase (PARP) were regulated, while vascularization was inhibited and apoptosis was promoted. Regarding bioinformatics analysis and in vitro dual luciferase reporter assay, there should be a negative correlation between KCNQ1OT1 and miR‐1470. Additionally, mRNA of epidermal growth factor receptor (EGFR) was proved as the target of miR‐1470 and EGFR targeting by miR‐1470 initiated KCNQ1OT1 deficiency‐induced apoptosis and promoted proliferation. KCNQ1OT1 and miR‐1470 were proved to be the promoter and repressor of EGFR, respectively. The results suggested that KCNQ1OT1 could sponge miR‐1470 and further regulate EGFR in DR.