A comparative analysis of alternative splicing patterns in Atlantic salmon (Salmo salar) in response to Moritella viscosa and sea lice (Lepeophtheirus salmonis) infection.

Moritella viscosa (M. viscosa) and sea lice (Lepeophtheirus salmonis) are severe pathogens that primarily infect the skin of Atlantic salmon (Salmo salar), which cause significant economic losses in the farming industry. However, the pathogenesis and molecular mechanisms underlying the host's immune defence at the post-transcriptional level remain unclear. Alternative splicing (AS) is an evolutionarily conserved post-transcriptional mechanism that can greatly increase the richness of the transcriptome and proteome. In this study, transcriptomic data derived from skin tissues of Atlantic salmon after M. viscosa and sea lice infections were used to examine the AS profiles and their differential expression patterns. In total, we identified 33,044 AS events (involving 13,718 genes) in the control (CON) group, 35,147 AS events (involving 14,340 genes) in the M. viscosa infection (MV) group, and 30,364 AS events (involving 13,142 genes) in the sea lice infection (LC) group, respectively. Among the five types of AS identified in our study (i.e., SE, A5SS, A3SS, MXE, and RI), SE was the most prevalent type in all three groups (i.e., CON, MV, and LC groups). Decreased percent-spliced-in (PSI) levels were observed in SE events under both MV- and LC-infected conditions, suggesting that MV or LC infection elevated exon-skipping isoforms and promoted the selection of shorter transcripts in numerous DAS genes. In addition, most of the differential AS genes were found to be associated with pathways related to mRNA regulation, epithelial or muscle development, and immune response. These findings provide novel insights into the role of AS in host-pathogen interactions and represent the first comparative analysis of AS in response to bacterial and parasitic infections in fish.

Demonstration of a superluminal laser using electromagnetically induced transparency in Raman gain.

We report the realization of a superluminal laser in which the dip in the gain profile necessary for anomalous dispersion is produced via electromagnetically induced transparency caused by the optical pumping laser. This laser also creates the ground state population inversion necessary for generating Raman gain. Compared to a conventional Raman laser with similar operating parameters but without the dip in the gain profile, the spectral sensitivity of this approach is explicitly demonstrated to be enhanced by a factor of ∼12.7. Compared to an empty cavity, the peak value of the sensitivity enhancement factor under optimal operation parameters is inferred to be ∼360.

Interactions between vaginal local cytokine IL-2 and high-risk human papillomavirus infection with cervical intraepithelial neoplasia in a Chinese population-based study.

Background: Although interleukin-2 (IL-2) has long been associated with cancer development, its roles in the development of cervical cancer remains unclear. Few studies examined the associations between IL-2 and high-risk human papillomavirus (HPV) with risk of cervical intraepithelial neoplasia (CIN). Objective: We aimed to assess the association of IL-2 and high-risk HPV infection with risk of CIN as well as their interactions on the risk of CIN. Design: We performed a cross-sectional analysis of screening data in 2285 women aged 19-65 years who participated in an ongoing community-based cohort of 40,000 women in Shanxi, China in 2014-2015. Both categorical and spline analyses were used to evaluation the association between IL-2 in the local vaginal fluids and prevalence of CIN. In addition, 1503 controls were followed up until January 31, 2019), the nested case-control study design was adopted to evaluate the association of vaginal lavage IL-2 levels and the risk of CIN progression. Results: After adjusting for potential confounders, IL-2 levels were statistically inversely associated with prevalence of CIN (the 1st versus 4th quartile IL-2 levels: the respective odds ratio [OR] and 95% confidence intervals [CI] was: = 1.75 [1.37, 2.23] for CIN, 1.32 [1.01, 1.73] for CIN I, and 3.53 [2.26, 5.52] for CIN II/III). Increased IL-2 levels were inversely associated with prevalence of CIN (P-overall<0.01, P-nonlinearity<0.01 for CIN; P-overall<0.01, P-nonlinearity = 0.01 for CIN I; P-overall <0.01, P-nonlinearity = 0.62 for CIN II/III). The highest prevalence of CIN was observed in women with high-risk HPV, who also had the lowest IL-2 levels (P-interaction < 0.01). Nested case-control study observed an inverse association between IL-2 levels and risk of CIN progression (OR=3.43, [1.17, 10.03]). Conclusions: IL-2 levels in the local vaginal fluids were inversely associated with the risk of CIN in Chinese women either with or without high-risk HPV infection.

Sphingosine-1-Phosphate Alleviates Irradiation Induced Salivary Gland Hypofunction through Preserving Endothelial Cells and Resident Macrophages.

Radiotherapy for head-and-neck cancers frequently causes long-term hypofunction of salivary glands that severely compromises quality of life and is difficult to treat. Here, we studied effects and mechanisms of Sphingosine-1-phosphate (S1P), a versatile signaling sphingolipid, in preventing irreversible dry mouth caused by radiotherapy. Mouse submandibular glands (SMGs) were irradiated with or without intra-SMG S1P pretreatment. The saliva flow rate was measured following pilocarpine stimulation. The expression of genes related to S1P signaling and radiation damage was examined by flow cytometry, immunohistochemistry, quantitative RT-PCR, Western blotting, and/or single-cell RNA-sequencing. S1P pretreatment ameliorated irradiation-induced salivary dysfunction in mice through a decrease in irradiation-induced oxidative stress and consequent apoptosis and cellular senescence, which is related to the enhancement of Nrf2-regulated anti-oxidative response. In mouse SMGs, endothelial cells and resident macrophages are the major cells capable of producing S1P and expressing the pro-regenerative S1P receptor S1pr1. Both mouse SMGs and human endothelial cells are protected from irradiation damage by S1P pretreatment, likely through the S1pr1/Akt/eNOS axis. Moreover, intra-SMG-injected S1P did not affect the growth and radiosensitivity of head-and-neck cancer in a mouse model. These data indicate that S1P signaling pathway is a promising target for alleviating irradiation-induced salivary gland hypofunction.

Chain Engineering of Benzodifuran-Based Wide-Bandgap Polymers for Efficient Non-Fullerene Polymer Solar Cells.

Two novel benzo[1,2-b:4,5-b' ]difuran (BDF)-based wide-bandgap polymers, PBDFT-FBz and PBDFF-FBz, featuring a difluorobenzotriazole (FBz) acceptor unit, are designed and synthesized. The first attempt through main-chain engineering to alter thiophene units to furan units in the main chain of PBDFT-FBz, and further side-chain engineering eliminate the 2-ethylthiophenyl side chains of PBDFT-FBz by 2-ethylfuryl side chains to generate the "all-furan" polymer PBDFF-FBz. By taking the benefit of the oxygen atom in furan, both PBDFT-FBz and PBDFF-FBz exhibit lower HOMO energy levels and enhanced polymer chain interactions compared to their benzo[1,2-b:4,5-b' ]dithiophene (BDT)-based counterparts. As a result, while applying both polymers in non-fullerene polymer solar cells with non-fullerene acceptor m-ITIC, both devices exhibit highly promising photovoltaic performance. The power conversion efficiency (PCE) in the PBDFT-FBz device reaches 7.57% with increased open circuit voltage (Voc ) and fill factor (FF) compared to the PCE of 5.98% in its BDT counterpart (J52). A further increased PCE is obtained (8.79%) in the PBDFF-FBz:m-ITIC device, which shows ≈47% enhancement in device performance compared to that of J52. The large increase in photovoltaic performance is attributed to the lower-lying HOMO energy levels and better chain interactions in these BDF-based polymers.