g., by repairing SOD1 mutations or the SMN2 splicing defect or deleting C9orf72 expanded repeats. These studies have shown promising results to approach therapeutic trials that should significantly lower the progression of these deadly disorders.A self-transcribing and replicating RNA (STARR)-based vaccine (LUNAR-COV19) has been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based replicon and the SARS-CoV-2 full-length spike glycoprotein. Translation of the replicon produces a replicase complex that amplifies and prolongs SARS-CoV-2 spike glycoprotein expression. A single prime vaccination in mice led to robust antibody responses, with neutralizing antibody titers increasing up to day 60. Activation of cell-mediated immunity produced a strong viral antigen-specific CD8+ T lymphocyte response. Assaying for intracellular cytokine staining for interferon (IFN)γ and interleukin-4 (IL-4)-positive CD4+ T helper (Th) lymphocytes as well as anti-spike glycoprotein immunoglobulin G (IgG)2a/IgG1 ratios supported a strong Th1-dominant immune response. Finally, single LUNAR-COV19 vaccination at both 2 μg and 10 μg doses completely protected human ACE2 transgenic mice from both mortality and even measurable infection following wild-type SARS-CoV-2 challenge. Our findings collectively suggest the potential of LUNAR-COV19 as a single-dose vaccine.The functions of mRNAs are closely correlated with their locations in cells. Knowledge about the subcellular locations of mRNA is helpful to understand their biological functions. In recent years, it has become a hot topic to develop effective computational models to predict eukaryotic mRNA subcellular localizations. However, existing state-of-the-art models still have certain deficiencies in terms of prediction accuracy and generalization ability. Therefore, it is urgent to develop novel methods to accurately predict mRNA subcellular localizations. In this study, a novel method called mRNALocater was proposed to detect the subcellular localization of eukaryotic mRNA by adopting the model fusion strategy. To fully extract information from mRNA sequences, the electron-ion interaction pseudopotential and pseudo k-tuple nucleotide composition were used to encode the sequences. Moreover, the correlation coefficient filtering algorithm and feature forward search technology were used to mine hidden feature information, which guarantees that mRNALocater can be more effectively applied to new sequences. The results based on the independent dataset tests demonstrate that mRNALocater yields promising performances for predicting eukaryotic mRNA subcellular localizations and is a powerful tool in practical applications. A freely available online web server for mRNALocater has been established at http//bio-bigdata.cn/mRNALocater.The emerging clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genome editing technologies have progressed remarkably in recent years, opening up the potential of precise genome editing as a therapeutic approach to treat various diseases. The CRISPR-CRISPR-associated (Cas) system is an attractive platform for the treatment of Duchenne muscular dystrophy (DMD), which is a neuromuscular disease caused by mutations in the DMD gene. CRISPR-Cas can be used to permanently repair the mutated DMD gene, leading to the expression of the encoded protein, dystrophin, in systems ranging from cells derived from DMD patients to animal models of DMD. selleck kinase inhibitor However, the development of more efficient therapeutic approaches and delivery methods remains a great challenge for DMD. Here, we review various therapeutic strategies that use CRISPR-Cas to correct or bypass DMD mutations and discuss their therapeutic potential, as well as obstacles that lie ahead.Considerable amounts of previously deposited persistent organic pollutants (POPs) are stored in the Arctic cryosphere. Transport of freshwater and terrestrial material to the Arctic Ocean is increasing due to ongoing climate change and the impact this has on POPs in marine receiving systems is unknown This study has investigated how secondary sources of POPs from land influence the occurrence and fate of POPs in an Arctic coastal marine system. Passive sampling of water and sampling of riverine suspended particulate matter (SPM) and marine sediments for analysis of polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) was carried out in rivers and their receiving fjords in Isfjorden system in Svalbard. Riverine SPM had low contaminant concentrations ( less then level of detection-28 pg/g dw ΣPCB14, 16-100 pg/g dw HCB) compared to outer marine sediments 630-880 pg/g dw ΣPCB14, 530-770 pg/g dw HCB). There was a strong spatial gradient in sediment PCB and HCB concentrations with lowest concentrations in river estuaries and in front of marine-terminating glaciers and increasing concentrations toward the outer fjord. This suggests that rather than leading to increased concentrations, inputs of SPM from land lead to a dilution of contaminant concentrations in nearshore sediments. Preliminary estimates of SPMwater activity ratios suggest that terrestrial particles (with low contaminant concentrations) may have the potential to act as sorbents of dissolved contaminants in the coastal water column, with implications for bioavailability of POPs to the marine food web. There is concern that ongoing increases in fluxes of freshwater, sediments and associated terrestrial material (including contaminants) from land to the Arctic Ocean will lead to increased mobilization and transport of POPs to coastal ecosystems. However, the results of this study indicate that on Svalbard, inputs from land may in fact have the opposite effect, leading to reduced concentrations in coastal sediments and waters.The increasing use of metal oxide nanoparticles (MONPs) as TiO2 NPs or ZnO NPs has led to environmental release and human exposure. The respiratory system, effects on lamellar bodies and surfactant protein A (SP-A) of pneumocytes, can be importantly affected. Exposure of human alveolar epithelial cells (A549) induced differential responses; a higher persistence of TiO2 in cell surface and uptake (measured by Atomic Force Microscopy) and sustained inflammatory response (by means of TNF-α, IL-10, and IL-6 release) and ROS generation were observed, whereas ZnO showed a modest response and low numbers in cell surface. A reduction in SP-A levels at 24 h of exposure to TiO2 NPs (concentration-dependent) or ZnO NPs (the higher concentration) was also observed, reversed by blocking the inflammatory response (by the inhibition of IL-6). Loss of SP-A represents a relevant target of MONPs-induced inflammatory response that could contribute to cellular damage and loss of lung function.