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Highlights: Cardiac-specific Dsg2 deletion induces excessive cardiac fibrosis in mice. Fenofibrate alleviates cardiac fibrosis in CS-Dsg2−/− mice. Cardiac-specific activation of PPARα ameliorates cardiac fibrosis in CS-Dsg2−/− mice. The inhibitory effect of PPARα on cardiac fibrosis is mediated by STAT3 and TGF-β /SMAD3 signaling. PPARα is a promising target for the intervention of ACM by ameliorating cardiac fibrosis. Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease characterized by progressive fibro-fatty replacement of cardiac myocytes. Up to now, the existing therapeutic modalities for ACM are mostly palliative. About 50% of ACM is caused by mutations in genes encoding desmosomal proteins including Desmoglein-2 (Dsg2). In the current study, the cardiac fibrosis of ACM and its underlying mechanism were investigated by using a cardiac-specific knockout of Dsg2 mouse model. Methods: Cardiac-specific Dsg2 knockout (CS-Dsg2−/−) mice and wild-type (WT) mice were respectively used as the animal model of ACM and controls. The myocardial collagen volume fraction was determined by histological analysis. The expression levels of fibrotic markers such as α-SMA and Collagen I as well as signal transducers such as STAT3, SMAD3, and PPARα were measured by Western blot and quantitative real-time PCR. Results: Increased cardiac fibrosis was observed in CS-Dsg2−/− mice according to Masson staining. PPARα deficiency and hyperactivation of STAT3 and SMAD3 were observed in the myocardium of CS-Dsg2−/− mice. The biomarkers of fibrosis such as α-SMA and Collagen I were upregulated after gene silencing of Dsg2 in HL-1 cells. Furthermore, STAT3 gene silencing by Stat3 siRNA inhibited the expression of fibrotic markers. The activation of PPARα by fenofibrate or AAV9-Pparα improved the cardiac fibrosis and decreased the phosphorylation of STAT3, SMAD3, and AKT in CS-Dsg2−/− mice. Conclusions: Activation of PPARα alleviates the cardiac fibrosis in ACM. [ABSTRACT FROM AUTHOR]

Spacers are important components in reinforced concrete structures to provide cover between the steel reinforcement and the formwork. Cementitious spacers are of particular interest for coastal engineering structures, as they are compatible with cement-based chloride-resistant high-performance concrete compared to plastic and steel spacers. However, the cementitious spacer–concrete interface was found to be highly porous and microcracked. This study investigated the effect of surface treatment on the chloride ion transport at the cementitious spacer–concrete interface. A surface treatment technique for potential mass production was introduced and the state-of-practice tests of the hardened concrete were modified to evaluate the performance of the spacer–concrete composite specimens. The results showed that the surface treatment on a cementitious spacer improved the bonding between the spacer and concrete at the interface. The surface treatment of the spacer improved the compressive strength and the chloride resistance of the composite specimen locally compared to those without surface treatment. The advantage of surface treatment on the chloride resistance was partially represented in either the diffusion coefficient or the column electric flux. The maximum chloride ion penetration depth at the spacer–concrete interface was recommended as an additional proxy for the evaluation of the chloride resistance performance of composite specimens. [ABSTRACT FROM AUTHOR]

To enrich the molecular data of Pinus bungeana Zucc. ex Endl. and study the regulating factors of different morphology controled by apical dominance. In this study, de novo assembly of transcriptome annotation was performed for two varieties of Pinus bungeana Zucc. ex Endl. that are obviously different inmorphology. More than 147million reads were produced, which were assembled into 88,092 unigenes. Based on a similarity search, 11,692 unigenes showed significant similarity to proteins fromPicea sitchensis (Bong.) Carr. From this collection of unigenes, a large number of molecular markers were identified, including 2829 simple sequence repeats (SSRs). A total of 158 unigenes expressed differently between two varieties, including 98 up-regulated and 60 down-regulated unigenes. Furthermore, among the differently expressed genes (DEGs), five genes which may impact the plant morphology were further validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The five genes related to cytokinin oxidase/dehydrogenase (CKX), two-component response regulator ARR-A family (ARR-A), plant hormone signal transduction (AHP), andMADS-box transcription factors have a close relationship with apical dominance. This new dataset will be a useful resource for future genetic and genomic studies in Pinus bungeana Zucc. ex Endl. [ABSTRACT FROM AUTHOR]

The undesirable properties of conventional recycled fine aggregate (RFA) often limit its application in the construction industry. To overcome this challenge, a method for preparing completely recycled fine aggregate (CRFA), which crushes all concrete waste only into fine aggregate, was proposed. The obtained CRFA had high apparent density, and its water absorption was lower than that of the conventional RFA. To take advantage of the CRFA, this paper introduced the modified packing density method for the CRFA concrete mix design. The modified packing density method took account of the powder with a particle size of smaller than 75 μm in the CRFA and balanced both the void ratio and the specific surface area of the aggregate system. Concrete (grade C55) was prepared using the CRFA to validate the feasibility of the proposed method. The unit price of the prepared CRFA concrete was around 12.7% lower than that of the natural aggregate concrete. Additionally, the proposed procedure for the concrete mixture design could recycle all concrete waste into the new concrete and replace all the natural fine aggregate in the concrete mixture. [ABSTRACT FROM AUTHOR]