The laurel family within the Magnoliids has attracted attentions owing to its scents, variable inflorescences, and controversial phylogenetic position. Here, we present a chromosomelevel assembly of the Litsea cubeba genome, together with low-coverage genomic and transcriptomic data for many other Lauraceae. Phylogenomic analyses show phylogenetic discordance at the position of Magnoliids, suggesting incomplete lineage sorting during the divergence of monocots, eudicots, and Magnoliids. An ancient whole-genome duplication (WGD) event occurred just before the divergence of Laurales and Magnoliales; subsequently, independent WGDs occurred almost simultaneously in the three Lauralean lineages. The phylogenetic relationships within Lauraceae correspond to the divergence of inflorescences, as evidenced by the phylogeny of FUWA, a conserved gene involved in determining panicle architecture in Lauraceae. Monoterpene synthases responsible for production of specific volatile compounds in Lauraceae are functionally verified. Our work sheds light on the evolution of the Lauraceae, the genetic basis for floral evolution and specific scents.

Male infertility is a major concern affecting human reproductive health. Asthenoteratospermia can cause male infertility through reduced motility and abnormal morphology of spermatozoa. Several genes, including DNAH1 and some CFAP family members, are involved in multiple morphological abnormalities of the sperm flagella (MMAF). However, these known genes only account for approximately 60% of human MMAF cases. Here, we conducted further genetic analyses by using whole-exome sequencing in a cohort of 65 Han Chinese men with MMAF. Intriguingly, bi-allelic mutations of TTC21A (tetratricopeptide repeat domain 21A) were identified in three (5%) unrelated, MMAF-affected men, including two with homozygous stop-gain mutations and one with compound heterozygous mutations of TTC21A. Notably, these men consistently presented with MMAF and additional abnormalities of sperm head-tail conjunction. Furthermore, a homozygous TTC21A splicing mutation was identified in two Tunisian cases from an independent MMAF cohort. TTC21A is preferentially expressed in the testis and encodes an intraflagellar transport (IFT)-associated protein that possesses several tetratricopeptide repeat domains that perform functions crucial for ciliary function. To further investigate the potential roles of TTC21A in spermatogenesis, we generated Ttc21a mutant mice by using CRISPR-Cas9 technology and revealed sperm structural defects of the flagella and the connecting piece. Our consistent observations across human populations and in the mouse model strongly support the notion that bi-allelic mutations in TTC21A can induce asthenoteratospermia with defects of the sperm flagella and head-tail conjunction.

The ring finger protein 8 (RNF8), a key component of protein complex crucial for DNA-damage response, consists of a forkhead-associated (FHA) domain and a really interesting new gene (RING) domain that enables it to function as an E3 ubiquitin ligase. However, the biological functions of RNF8 in estrogen receptor α (ERα)-positive breast cancer and underlying mechanisms have not been fully defined. Here, we have explored RNF8 as an associated partner of ERα in breast cancer cells, and co-activates ERα-mediated transactivation. Accordingly, RNF8 depletion inhibits the expression of endogenous ERα target genes. Interestingly, our results have demonstrated that RNF8 increases ERα stability at least partially if not all via triggering ERα monoubiquitination. RNF8 functionally promotes breast cancer cell proliferation. RNF8 is highly expressed in clinical breast cancer samples and the expression of RNF8 positively correlates with that of ERα. Up-regulation of ERα-induced transactivation by RNF8 might contribute to the promotion of breast cancer progression by allowing enhancement of ERα target gene expression. Our study describes RNF8 as a co-activator of ERα increases ERα stability via post-transcriptional pathway, and provides a new insight into mechanisms for RNF8 to promote cell growth of ERα-positive breast cancer.

Left ventricular hypertrophy is a maladaptive response to pressure overload and an important risk factor for heart failure. Intermedin (IMD), a multi-functional peptide, plays important roles in cardiovascular protection. In this study, we revealed an autophagy-dependent mechanism involved in IMD’s protection against cardiac remodeling and cardiomyocyte death in heart hypertrophy. We observed that transverse aortic contraction (TAC) induction, Ang II or ISO exposure induced remarkable increase in the expression of endogenous IMD and its receptor components, CRLR, RAMP1 and RAMP3, in mouse hearts and H9c2 cell cultures, respectively. Furthermore, the heart size, heart weight/body weight ratios, cardiomyocyte size and apoptosis, interstitial collagen, hypertrophic markers including ANP and BNP expression were also significantly increased, which were effectively suppressed by IMD supplementation. In addition, IMD induced capillary angiogenesis and improved functions in hypertrophic hearts. We further observed that IMD induced strong autophagy in hypertrophic hearts and cultured cells, which was paralleling with the decrease in cardiomyocyte size and apoptosis. Furthermore, an autophagy inhibitor, 3-MA, was used to block the IMD-augmented autophagy level, and then the protection of IMD on cardiomyocyte hypertrophy and apoptosis was almost abrogated. We also observed that IMD supplementation stirred intracellular cAMP production, and augmented the ERK1/2 phosphorylation induced by Ang II/ISO exposure in H9c2 cells. In addition, we inhibited PI3K, PKA and MAPK/ERK1/2 signaling pathways by using wortamannin, H89 and PD98059, respectively, in H9c2 cells co-incubating with both IMD and Ang II or ISO, and observed that these inhibitors effectively reduced IMD-augmented autophagy level, but only H89 and PD98059 pre-incubation abrogated the anti-apoptotic action of IMD. These results indicate that the endogenous IMD and its receptor complexes are induced in hypertrophic cardiomyocytes and proposed to play an important role in the pathogenesis of cardiac hypertrophy, and the autophagy stirred by IMD supplementation is involved in its protection against cardiomyocyte hypertrophy and apoptosis through the activation of both cAMP/PKA and MAPK/ERK1/2 pathways.

The Liverbase ( http://liverbase.hupo.org.cn ) integrates information on the human liver proteome, including the function, abundance, and subcellular localization of proteins as well as associated disease information. The overall objective of the Liverbase is to provide a unique public resource for the liver community by providing comprehensive functional annotation of proteins implicated in liver development and disease. The central database features are manually annotated proteins localized in or functionally associated with human liver. In this first version of Liverbase, the associated data includes the human liver proteome (6788 proteins) and transcriptome (11205 significantly expressed genes: 10224 from CHIP and 5422 from MPSS, respecively) from the Chinese human liver proteome project (CNHLPP). As a database made publicly available through the Web site, Liverbase provides browsing and searching capabilities and a compilation of external links to other databases and homepages. Liverbase enables (i) the establishment of liver GO slim with 51 nonredundant items; (ii) systematic searches for proteins within specific functional or metabolic pathways; (iii) systematic searches that aim to find the proteins that underlie common and rare liver diseases; and (iv) the integration of detailed protein annotations derived from the literature. Liverbase also contains an external links page with links to other biological databases and homepages, including GO, KEGG, pfam, SWISS-PROT, and GNF databases. Liverbase users can utilize all these information to conduct systems biology research on liver.

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P orcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important viruses affecting the swine industry worldwide, resulting in significant economic losses each year (1-3). PRRSV is a small, enveloped, linear, single positive-stranded RNA virus and a member of the order Nidovirales, family Arteriviridae (4). Current vaccination strategies cannot effectively control PRRSV infection because of the high antigenic heterogeneity (5, 6), the replication in and destruction of lung alveolar macrophages (7-9), and the observed antibody-dependent enhancement of PRRSV (10, 11). Therefore, it is imperative to study PRRSV pathogenesis mechanisms so that more effective control measures can be developed.Heme oxygenase-1 (HO-1) is the rate-limiting enzyme of heme degradation, and it functions to catabolize free heme into biliverdin, carbon monoxide, and iron. HO-1 and its end products have antioxidant, anti-inflammatory, and antiviral properties, and it is known to be a pivotal cytoprotective enzyme (12). Upregulation of HO-1 expression suppresses replication of a number of viruses, including hepatitis C virus (HCV), HIV-1, hepatitis B virus (HBV), and influenza virus (13-17). Our previous work showed that PRRSV significantly downregulates HO-1

Flexible supercapacitors have attracted increasing interests due to their high power density, long-term cycling life and excellent safety. Liking other energy storage devices, flexible supercapacitors show serious performance degradation as...