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Actinidia arguta, the most widely distributed and the second cultivated species within Actinidiagenus, has distinguished difference from current kiwifruit in biological characters like small and smooth fruit, rapid-softening and excellent cold tolerance. Knowledge of adaptive evolution of the tetraploid Actinidiaspecies and genetic basis of its important agronomic traits is still unclear. A chromosome-scale genome assembly of an autotetraploid male A. argutahas been generated. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97Mb and anchored into 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed they could be divided into two geographical groups, Southern and Northern Groups, which first diverged 12.9 Mya ago. A. argutaunderwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition (MPT) to late-Pleistocene. Population genomics study using paleoclimate data allow us to discern the evolution of the species adaptation to different historical environments. Three genes (AaCEL1, AaPME1and AaDOF1) have been identified by multi-omics and verified their accelerating softening of flesh through transient assay. A set of genes localized in sex chromosome (Chr3), or autosomal chromosomes are biasedly expressed during stamen or carpel development, which characteristically regulate sexual dimorphism. This assembly of the autotetraploid genome at the chromosome level and detail uncover the genes related with important agronomic traits paves the way to facilitate functional genomics and improvement of A. arguta.

In the present work, 103 novel acyclic nucleosides were designed, synthesized, and evaluated for their anticancer activities in vitroand in vivo. The structure–activity relationship (SAR) studies revealed that most target compounds inhibited the growth of colon cancer cells in vitro, of which 3-(6-chloro-9H-purin-9-yl)dodecan-1-ol (9b) exhibited the most potent effect against the HCT-116 and SW480 cells with IC50values of 0.89 and 1.15 μM, respectively. Furthermore, all of the (R)-configured acyclic nucleoside derivatives displayed more potent anticancer activity compared to their (S)-counterparts. Mechanistic studies revealed that compound 9btriggered apoptosis in the cancer cell lines viadepolarization of the mitochondrial membrane and effectively inhibited colony formation. Importantly, compound 9binhibited the growth of the SW480 xenograft in a mouse model with low systemic toxicity. These results indicated that acyclic nucleoside compounds are viable as potent and effective anticancer agents, and compound 9bmay serve as a promising lead compound that merits further attention in future anticancer drug discovery.

The current study aimed to identify whether ultrasonographic measurements of optic nerve sheath diameter (ONSD) could dynamically and sensitively evaluate real-time intracranial pressure (ICP). ONSD measurements were performed approximately 5  min prior to and after a lumbar puncture (LP). A total of 84 patients (mean±SD age, 43.5±14.7 years; 41 (49%) men; 18 patients with elevated ICP) were included in the study. The Spearman correlation coefficients between the two observers were 0.779 and 0.703 in the transverse section and 0.751 and 0.788 in the vertical section for the left and right eyes, respectively. The median (IQR) change in ONSD (ΔONSD) and change in ICP (ΔICP) were 0.11 (0.05–0.21) mm and 30 (20–40) mmH2O, respectively, for all participants. With a reduction in cerebrospinal fluid pressure, 80 subjects (95%) showed an immediate drop in ONSD; the median (IQR) decreased from 4.13 (4.02–4.38) mm to 4.02 (3.90–4.23) mm (p<0.001). Significant correlations were found between ONSD and ICP before LPs (r=0.482, p<0.01) and between ΔONSD and ΔICP (r=0.451, p<0.01). Ultrasonic measurement of ONSD can reflect the relative real-time changes in ICP.

Since inhibiting cardiac remodeling is a critical treatment goal after myocardial infarction (MI), many drugs have been evaluated for this purpose. Acacetin is a flavonoid compound that has been shown to have anti-cancer, anti-mutagenic, anti-inflammatory and anti-peroxidative effects. In this study, we investigated whether acacetin is able to exert a protective effect against MI. One week after anterior wall standard MI surgeries or sham surgeries were performed in mice, acacetin was administered via gavage for two weeks. The results of echocardiographic and hemodynamic evaluation revealed that cardiac dysfunction significantly improved after acacetin treatment. H&E staining indicated that the ratio of the infarct size and the cardiomyocyte cross-sectional area was decreased by acacetin. Masson's staining detected that the fibrotic area ratio was evidently lower in the acacetin-treated MI group. TUNEL assays showed that acacetin ameliorated cardiomyocyte apoptosis after MI. RT-qPCR analysis showed that levels of hypertrophic and fibrotic markers were significantly decreased after acacetin treatment. Western blot analysis of various signaling pathway proteins showed that acacetin targets the MAPK and PI3K/Akt signaling pathways. Collectively, acacetin improves mouse left ventricular function and attenuates cardiac remodeling by inhibiting of the MAPK and PI3K/Akt signaling pathway.