Pulmonary fibroblast-specific delivery of siRNA exploiting exosomes-based nanoscaffolds for IPF treatment

Idiopathic pulmonary fibrosis(IPF)is a progressive pulmonary disease that leads to interstitial inflammation,lung damage,and eventually life-threatening complications.Among various pathologic factors,Smad4 is a pivotal molecule involved in the progression and exacerbation of IPF.It mediates nuclear transfer of Smad2/Smad3 complexes and initiates the transcription of fibrosis-promoting genes.Thus,the inhibition of Smad4 expression in pulmonary fibroblasts by small interfering RNAs(siRNAs)might be a promising therapeutic strategy for IPF.Herein,we engineered exosome membranes(EM)by cationic lipid(i.e.,DOTAP)to load siRNAs against Smad4(DOTAP/siSmad4@EM),and investigated their specific delivery to pulmonary fibroblasts for treating IPF in a mouse model via pulmonary administration.As reference nanoscaffolds,undecorated DOTAP/siSmad4 complexes(lipoplexes,consisting of cationic lipid DOTAP and siRNAs)and siSmad4-loaded lipid nanoparticles(DOTAP/siSmad4@lipo,consisting of lipoplexes fused with DPPC–Chol liposomes)were also prepared.The results showed that DOTAP/siSmad4@EM exhibited a higher cellular uptake and gene silencing efficacies in mouse pulmonary fibroblasts(viz.,MLg2908)as compared to the two reference nanoscaffolds.Furthermore,the outcomes of the in vivo experiments illustrated that DOTAP/siSmad4@EM could significantly down-regulate the Smad4 expression with augmented anti-fibrosis efficiency.Additionally,the DOTAP/siSmad4@EM conferred excellent biocompatibility with low cytokine levels in bronchoalveolar lavage fluid and proinflammatory responses in the pulmonary area.Taken together,the outcomes of our investigation imply that specific inhibition of Smad4 expression in pulmonary fibroblasts by pulmonary administrated DOTAP/siSmad4@EM is a promising therapeutic strategy for IPF,which could safely and effectively deliver siRNA drugs to the targeted site of action.

The anisotropy of suprathermal electrons in the Martian ionosphere

Suprathermal electrons are an important population of the Martian ionosphere, either produced by photoionization of atmospheric neutrals or supplied from the Solar Wind (SW). This study is dedicated to an in-depth investigation of the pitch angle distribution of suprathermal electrons at two representative energies, 19−55 eV and 124−356 eV, using the extensive measurements made by the Solar Wind Electron Analyzer on board the Mars Atmosphere and Volatile Evolution. Throughout the study, we focus on the overall degree of anisotropy, defined as the standard deviation of suprathermal electron intensity among different directions which is normalized by the mean omni-directional intensity. The available data reveal the following characteristics: (1) In general, low energy electrons are more isotropic than high energy electrons, and dayside electrons are more isotropic than nightside electrons;(2) On the dayside, the anisotropy increases with increasing altitude at low energies but remains roughly constant at high energies, whereas on the nightside, the anisotropy decreases with increasing altitude at all energies;(3) Electrons tend to be more isotropic in strongly magnetized regions than in weakly magnetized regions, especially on the nightside. These observations indicate that the anisotropy is a useful diagnostic of suprathermal electron transport, for which the conversion between the parallel and perpendicular momenta as required by the conservation of the first adiabatic invariant, along with the atmospheric absorption at low altitudes, are two crucial factors modulating the observed variation of the anisotropy. Our analysis also highlights the different roles on the observed anisotropy exerted by suprathermal electrons of different origins.

The beneficial effects of Tartary buckwheat (Fagopyrum tataricum Gaertn.) on diet-induced obesity in mice are related to the modulation of gut microbiota composition

The gut is home to a large number of intestinal microbiota that play an important role in the metabolism and immune system of the host.A growing body of evidence suggests that a high-fat diet is closely associated with many metabolic disorders,including fatty liver and type 2 diabetes.According to reports,Tartary buckwheat extract has a positive effect on intestinal microbiota in animals.The effects of Tartary buckwheat on biochemical indexes and intestinal microflora in mice were studied.Tartary buckwheat protein(FGP),Tartary buckwheat resistant starch(FGS)and Tartary buckwheat flour(FGF)alleviated organ damage in mice and lowered the atherosclerotic index(AI)in plasma.Otherwise,principal coordinate analysis(PCoA)showed that intestinal bacterial structure of FGF were separated apparently from other groups.The Firmicutes/Bacteroidetes(F/B)value of the high-fat(HF)-FGF group was significantly lower than that of the HF-FGP and HF-FGS groups.FGF significantly increases the abundance of beneficial bacteria such as Bifidobacterium,while decreasing the abundance of lipopolysaccharide(LPS)-producing bacteria.Observation of blood lipid metabolism parameters and analysis of the intestinal microbiota suggested that FGF can be more effective than FGP and FGS to reduce the effects of a high-fat diet in mice,restoring the blood parameters to values similar of those in mice fed a low-fat diet.FGF may be used to prevent or treat blood lipid metabolism disorders and intestinal microbiota disorders in mice fed a high-fat diet.

Effects of a dipole-like crustal field on solar wind interaction with Mars

A three-dimensional four species multi-fluid magnetohydrodynamic (MHD) model was constructed to simulate the solar wind global interaction with Mars. The model was augmented to consider production and loss of the significant ion species in the Martian ionosphere, i.e., H^+, O2^+, O^+, CO^+2, associated with chemical reactions among all species. An ideal dipole-like local crustal field model was used to simplify the empirically measured Martian crustal field. Results of this simulation suggest that the magnetic pile-up region (MPR) and the velocity profile in the meridian plane are asymmetric, which is due to the nature of the multi-fluid model to decouple individual ion velocity resulting in occurrence of plume flow in the northern Martian magnetotail. In the presence of dipole magnetic field model, boundary layers, such as bow shock (BS) and magnetic pile-up boundary (MPB), become protuberant. Moreover, the crustal field has an inhibiting effect on the flux of ions escaping from Mars, an effect that occurs primarily in the region between the terminator (SZA 90°) and the Sun Mars line of the magnetotail (SZA 180°), partially around the terminator region. In contrast, near the tailward central line the crustal field has no significant impact on the escaping flux.

Self-embedding Image Watermarking based on Combined Decision Using Pre-offset and Post-offset Blocks

To detect and recover random tampering areas,a combined-decision-based self-embedding watermarking scheme is proposed herein.In this scheme,the image is first partitioned into 2×2 size blocks.Next,the high 5 bits of a block’s average value is embedded into its offset block.The tampering type of block is detected by comparing the watermarks of its pre-offset and post-offset blocks.The theoretical analysis and experiments demonstrate that the proposed scheme not only has a lower ratio of false detection but also better performance with regard to avoiding random tampering.

Wavelike perturbations in Titan’s ionosphere and their compositional variation:A preliminary survey of Cassini Ion Neutral Mass Spectrometer measurements

Wavelike perturbations in the ionosphere of Titan,the largest satellite of Saturn,are explored based on the Cassini Ion Neutral Mass Spectrometer(INMS)measurements.Strong wavelike perturbations are identified for more than twenty ion species,from simple ones such as N^(+)and CH_(4)^(+)to complex ones such as C_(2)H_(3)CNH^(+)and C_(4)H_(7)^(+).Simultaneous wavelike perturbations in background N_(2),indicative of atmospheric gravity waves,are also observed,motivating us to speculate that the INMS-derived ion perturbations are wave-driven.The amplitudes of the ion perturbations are found to be larger than that of the N_(2)perturbations.Clear compositional variation is revealed by the data:heavier ion species exhibit greater amplitudes.Such observations might be understood based on considerations either of force balance or chemical loss in Titan’s ionosphere.

Cross-modal Contrastive Learning for Generalizable and Efficient Image-text Retrieval

Cross-modal image-text retrieval is a fundamental task in bridging vision and language. It faces two main challenges that are typically not well addressed in previous works. 1) Generalizability: Existing methods often assume a strong semantic correlation between each text-image pair, which are thus difficult to generalize to real-world scenarios where the weak correlation dominates. 2) Efficiency: Many latest works adopt the single-tower architecture with heavy detectors, which are inefficient during the inference stage because the costly computation needs to be repeated for each text-image pair. In this work, to overcome these two challenges, we propose a two-tower cross-modal contrastive learning (CMCL) framework. Specifically, we first devise a two-tower architecture, which enables a unified feature space for the text and image modalities to be directly compared with each other, alleviating the heavy computation during inference. We further introduce a simple yet effective module named multi-grid split (MGS) to learn fine-grained image features without using detectors. Last but not the least, we deploy a cross-modal contrastive loss on the global image/text features to learn their weak correlation and thus achieve high generalizability. To validate that our CMCL can be readily generalized to real-world scenarios, we construct a large multi-source image-text dataset called weak semantic correlation dataset (WSCD). Extensive experiments show that our CMCL outperforms the state-of-the-arts while being much more efficient.