Myocardial contractile dysfunction is associated with an increase in mitochondrial fission in patients with diabetes. However, whether mitochondrial fission directly promotes diabetes‐induced cardiac dysfunction is still unknown. Melatonin exerts a substantial influence on the regulation of mitochondrial fission/fusion. This study investigated whether melatonin protects against diabetes‐induced cardiac dysfunction via regulation of mitochondrial fission/fusion and explored its underlying mechanisms. Here, we show that melatonin prevented diabetes‐induced cardiac dysfunction by inhibiting dynamin‐related protein 1 (Drp1)‐mediated mitochondrial fission. Melatonin treatment decreased Drp1 expression, inhibited mitochondrial fragmentation, suppressed oxidative stress, reduced cardiomyocyte apoptosis, improved mitochondrial function and cardiac function in streptozotocin (STZ)‐induced diabetic mice, but not in SIRT1−/− diabetic mice. In high glucose‐exposed H9c2 cells, melatonin treatment increased the expression of SIRT1 and PGC‐1α and inhibited Drp1‐mediated mitochondrial fission and mitochondria‐derived superoxide production. In contrast, SIRT1 or PGC‐1α siRNA knockdown blunted the inhibitory effects of melatonin on Drp1 expression and mitochondrial fission. These data indicated that melatonin exerted its cardioprotective effects by reducing Drp1‐mediated mitochondrial fission in a SIRT1/PGC‐1α‐dependent manner. Moreover, chromatin immunoprecipitation analysis revealed that PGC‐1α directly regulated the expression of Drp1 by binding to its promoter. Inhibition of mitochondrial fission with Drp1 inhibitor mdivi‐1 suppressed oxidative stress, alleviated mitochondrial dysfunction and cardiac dysfunction in diabetic mice. These findings show that melatonin attenuates the development of diabetes‐induced cardiac dysfunction by preventing mitochondrial fission through SIRT1‐PGC1α pathway, which negatively regulates the expression of Drp1 directly. Inhibition of mitochondrial fission may be a potential target for delaying cardiac complications in patients with diabetes.

BackgroundThis meta-analysis aimed to evaluate the postoperative clinical outcomes and safety of the direct anterior approach (DAA) versus posterior approach (PA) in total hip arthroplasty (THA).MethodsWe searched PubMed, Embase, Web of Science, the Cochrane Library, and Google databases from inception to June 2018 to select studies that compared the DAA and PA for THA. Only randomized controlled trials (RCTs) were included. Outcomes included Harris hip score at 2 weeks, 6 weeks, 12 weeks, and 1 year; VAS at 24 h, 48 h, and 72 h; incision length, operation time, postoperative blood loss, length of hospital stay, and complications (intraoperative fracture, postoperative dislocation, heterotopic ossification (HO), and groin pain).ResultsNine RCTs totaling 754 THAs (DAA group = 377, PA group = 377) met the criteria to be included in this meta-analysis. The present meta-analysis indicated that, compared with PA group, DAA group was associated with an increase of the Harris hip score at the 2-week and 4-week time points. No significant difference was found between DAA and PA groups of the Harris hip scores at 12 weeks, 1 year length of hospital stay (p > 0.05). DAA group was associated with a reduction of the VAS at 24 h, 48 h, and 72 h with statistical significance (p < 0.05). What is more, DAA was associated with a reduction of the incision length and postoperative blood loss (p < 0.05). There was no significant difference between the operation time and complications (intraoperative fracture, postoperative dislocation, HO, and groin pain).ConclusionIn THA patients, compared with PA, DAA was associated with an early functional recovery and less pain scores. What is more, DAA was associated with shorter incision length and blood loss.

The Vespertilionidae is the largest family in the order Chiroptera and has a worldwide distribution in the temperate and tropical regions. In order to further clarify the karyotype relationships at the lower taxonomic level in Vespertilionidae, genome-wide comparative maps have been constructed between Myotis myotis (MMY, 2n = 44) and six vesper bats from China: Myotis altarium (MAL, 2n = 44), Hypsugo pulveratus (HPU, 2n = 44), Nyctalus velutinus (NVE, 2n = 36), Tylonycteris robustula (TRO, 2n = 32), Tylonycteris sp. (TSP, 2n = 30)and Miniopterus fuliginosus (MFU, 2n = 46) by cross-species chromosome painting with a set of painting probes derived from flow-sorted chromosomes of Myotis myotis. Each Myotis myotis autosomal probe detected a single homologous chromosomal segment in the genomes of these six vesper bats except for MMY chromosome 3/4 paint which hybridized onto two chromosomes in the genome of M. fuliginosus. Our results show that Robertsonian translocation is the main mode of karyotype evolution in Vespertilionidae and that the addition of heterochromatic material also plays an important role in the karyotypic evolution of the genera Tylonycteris and Nyctalus. Two conserved syntenic associations (MMY9 + 23 and 18 + 19) could be the synapomorphic features for the genus Tylonycteris. The integration of our maps with the published maps has enabled us to deduce chromosomal homologies between human and these six vesper bats and provided new insight into the karyotype evolution of the family Vespertilionidae.

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Bats are a unique but enigmatic group of mammals and have a world-wide distribution. The phylogenetic relationships of extant bats are far from being resolved. Here, we investigated the karyotypic relationships of representative species from four families of the order Chiroptera by comparative chromosome painting and banding. A complete set of painting probes derived from flow-sorted chromosomes of Myotis myotis (family Vespertilionidae) were hybridized onto metaphases of Cynopterus sphinx (2n = 34, family Pteropodidae), Rhinolophus sinicus (2n=36, family Rhinolophidae) and Aselliscus stoliczkanus (2n=30, family Hipposideridae) and delimited 27, 30 and 25 conserved chromosomal segments in the three genomes, respectively. The results substantiate that Robertsonian translocation is the main mode of chromosome evolution in the order Chiroptera, with extensive conservation of whole chromosomal arms. The use of M. myotis (2n=44) probes has enabled the integration of C. sphinx, R. sinicus and A. stoliczkanus chromosomes into the previously established comparative maps between human and Eonycteris spelaea (2n=36), Rhinolophus mehelyi (2n=58), Hipposideros larvatus (2n=32), and M. myotis. Our results provide the first cytogenetic signature rearrangement that supports the grouping of Pteropodidae and Rhinolophoidea in a common clade (i.e. Pteropodiformes or Yinpterochiroptera) and thus improve our understanding on the karyotypic relationships and genome phylogeny of these bat species.

Background/Aims: Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes and cancer progression. Whether lncRNAs play any functional role in colorectal carcinoma (CRC) remains largely unknown. The aim of this study was to investigate the role of lncRNA CPS1 intronic transcript 1 (CPS1-IT1) in CRC. Methods: Expression of CPS1-IT1 was initially assessed in human CRC tissues and in a series of CRC cell lines. The correlations between CPS1-IT1 levels and survival outcomes were analyzed to elucidate the clinical significance of CPS1-IT1 in CRC. The underlying mechanisms of CPS1-IT1 in CRC were analyzed through in vitro and in vivo functional assays. Results: Expression of CPS1-IT1 was significantly decreased in CRC tissues and cell lines, and patients with low CPS1-IT1 expression had poor survival outcomes. The results of in vitro assays revealed that CPS1-IT1 significantly reduced cell proliferation, migration and invasion capacities and accelerated cell apoptosis, thereby suppressing epithelial-mesenchymal transition (EMT). An in vivo animal model also demonstrated the tumor-suppressive role of CPS1-IT1. Conclusion: In this study, we found that CPS1-IT1 has a tumor-suppressive role in CRC. Our data suggest that CPS1-IT1 could be used as a new prognostic biomarker and therapeutic target for CRC.

Background: Colorectal cancer (CRC) is one of the causes of cancer-related death worldwide. The aim of our study was to disclose the expression pattern and underlying molecular mechanism of circular RNA TADA2A (circTADA2A) in CRC. Methods: The levels of circTADA2A, transcriptional adaptor 2A (TADA2A), microRNA-374a-3p (miR-374a-3p) and Kruppel like factor 14 (KLF14) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Xenograft tumor assay was used to uncover the function of circTADA2A in vivo. The miRNA targets of circTADA2A were searched using circbank and starbase softwares, while DIANA TOOL was used to explore miR-374a-3p-mRNA interactions. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to validate the target relationship of circTADA2A/miR-374a-3p/KLF14 axis. Cell cycle and apoptosis were analyzed by flow cytometry. The glycolysis of CRC cells was determined by Seahorse XF e 96 Extracellular Flux Analyzer, Glucose Uptake Colorimetric Assay kit, Lactate Assay Kit II and ATP Colorimetric Assay kit. KLF14 protein level was measured by Western blot assay. Results: CircTADA2A was abnormally down-regulated in CRC tissues and cell lines. CircTADA2A overexpression impeded CRC tumor growth in vivo. MiR-374a-3p was verified as a target of circTADA2A in CRC cells, and circTADA2A inhibited the malignant potential of CRC cells through targeting miR-374a-3p. MiR-374a-3p interacted with KLF14 messenger RNA (mRNA), and miR-374a-3p deteriorated CRC through down-regulating KLF14. CircTADA2A enhanced the abundance of KLF14 through targeting miR-374a-3p in CRC cells. Conclusion: CircTADA2A functioned as a tumor suppressor in CRC to inhibit the glycolysis and cell cycle and potentiate the apoptosis of CRC cells via miR-374a-3p/KLF14 axis.