Photoactive “Bionic Virus” Robustly Elicits the Synergy Anticancer Activity of Immunophotodynamic Therapy

Coronavirus represents an inspiring model for designing drug delivery systems due to its unique infection machinery mechanism. Herein, we have developed a biomimetic viruslike nanocomplex, termed SDN, for improving cancer theranostics. SDN has a unique core–shell structure consisting of photosensitizer chlorin e6 (Ce6)-loaded nanostructured lipid carrier (CeNLC) (virus core)@poly­(allylamine hydrochloride)-functionalized MnO2 nanoparticles (virus spike), generating a virus-mimicking nanocomplex. SDN not only prompted cellular uptake through rough-surface-mediated endocytosis but also achieved mitochondrial accumulation by the interaction of cationic spikes and the anionic mitochondrial surface, leading to mitochondria-specific photodynamic therapy. Meanwhile, SDN could even mediate oxygen generation to relieve tumor hypoxia and, consequently, improve macrophage-associated anticancer immune response. Importantly, SDN served as a robust magnetic resonance imaging (MRI) contrast agent due to the fast release of Mn2+ in the presence of intracellular redox components. We identified that SDN selectively accumulated in tumors and released Mn2+ to generate a 5.71-fold higher T1-MRI signal, allowing for effectively detecting suspected tumors. Particularly, SDN induced synergistic immunophotodynamic effects to eliminate malignant tumors with minimal adverse effects. Therefore, we present a novel biomimetic strategy for improving targeted theranostics, which has a wide range of potential biomedical applications

Additional file 1 of Replacing of sedentary behavior with physical activity and the risk of mortality in people with prediabetes and diabetes: a prospective cohort study

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Additional file 2 of Replacing of sedentary behavior with physical activity and the risk of mortality in people with prediabetes and diabetes: a prospective cohort study

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Cell Membrane Camouflaged Metal Oxide–Black Phosphorus Biomimetic Nanocomplex Enhances Photo-chemo-dynamic Ferroptosis

Despite the availability of various treatment options, the inherent complexity of tumors significantly impairs therapeutic efficacy. Recently, combination treatments exhibited great anticancer potential due to low cross-resistance and good therapeutic additivity. Herein, a photoactive metal oxide–black phosphorus biomimetic nanocomplex (photophage) is developed for improving the antitumor combination of ferroptosis and photodynamic therapy (PDT). The photophage is composed of M1 macrophage membrane camouflaged MnO2 and Fe3O4 nanoparticles anchored black phosphorus nanosheets (BPNs), which together trigger a synergistic antitumor action. Fe3O4 acts as an iron source to activate Fenton-reaction-dependent ferroptosis, which can be further strengthened by BPN-mediated PDT. Besides the original antitumor effects, PDT also generates reactive oxygen species to enhance lipid peroxidation and glutathione depletion, which in turn reinforce ferroptosis and PDT efficacy. Importantly, MnO2 can in situ generate oxygen to relieve tumor hypoxia and consequently leverage cell behaviors to improve therapeutic responses. Particularly, M1 macrophage membrane modification endows the photophage with good tumor targeting capability and tumor penetration, which promote synergistic ferroptosis and PDT to destroy tumors while reducing systemic side effects, resulting in the prolonged survival of tumor-bearing mice. Therefore, we present a biomimetic nanoplatform for overcoming tumor barriers and advancing tumor-targeted treatment

DataSheet1_Shipborne Observations of Chemical Characterization and Light Extinction of Aerosol Along the Yangtze River, China.pdf

The study of air quality over the Yangtze River is important for the pollution of urban agglomeration along the longest river in China. A comprehensive 15-day shipborne observation was conducted in the Yangtze River of the Jiangsu section in the summer of 2019. Through online observation and offline chemistry analysis of aerosol and gaseous pollutants, the result showed that the air pollution over the Yangtze River was more severe than that in surrounding cities. Sulfate, nitrate, and ammonium (SNA) dominated the water-soluble inorganic species and accounted for 35.0% ± 7.3% of the fine particle concentration (PM2.5) along the Yangtze River. The high concentration of sulfate in the droplet mode (0.56–1.0 μm) was due to the formation of sulfate through in-cloud processes under high sulfur dioxide (SO2) concentration by ship emission and high relative humidity along the river. The strong correlation between the measured mass absorption efficiency value by carbon analyzer and that simulated based on the assumption of core–shell suggested that the core–shell mode was the main composition form of aerosol in the Yangtze River. The scattering effect was the main part of the aerosol light extinction, and the scattering coefficient of 0.4- to 1.1-μm particles accounted for 85.0% of the total extinction coefficient. Positive matrix factorization model was applied for the source apportionment of particle size segment of main extinction contribution (0.4–2.1 μm), and the result showed that secondary nitrate, ship emission, coal combustion, fugitive dust, and biomass burning were the main sources of aerosols in the Yangtze River. After source reanalysis, the result indicated that the contribution of secondary nitrate from nitrogen oxide (NOx) by ship emission and coal combustion should not be ignored.</p

Mitoxantrone- and Folate-TPGS2k Conjugate Hybrid Micellar Aggregates To Circumvent Toxicity and Enhance Efficiency for Breast Cancer Therapy

Mitoxantrone (MTO) is a potent drug used to treat breast cancer; however, efforts to expand its clinical applicability have been restricted because of its high risk for cardiotoxicity. In this study, we successfully conjugated MTO or folic acid (FA) to a synthesized D-α-tocopheryl polyethylene glycol 2000 succinate (TPGS2k), herein, shortened to MCT and FCT, respectively. The two produced conjugates could self-assemble to form MCT micelles or MCT/FCT mixed micelles (FMCT) aiming to lower systemic toxicity, enhance entrapment efficiency, and provide a platform for targeted delivery. Moreover, these micellar materials showed a significantly low CMC and could be used to load MTO. The diameters of MTO-loaded micelles (MTO-MCT and MTO-FMCT) were less than 100 nm with a negative zeta potential. We further characterized the pH-responsive drug release of MTO-MCT and MTO-FMCT and then assessed their cellular uptake and antitumor efficacy in human breast cancer cell lines (MCF-7) via confocal microscopy, flow cytometry, and cytotoxicity studies. All the results revealed that both MTO-MCT and MTO-FMCT increased drug loading and entrapment efficiency and possessed sufficient pH-sensitive release. Additionally, MTO-FMCT displayed an improved uptake through folate-mediated endocytosis, resulting in a higher cytotoxic effect on MCF-7 cells compared with that of MTO-MCT. Meanwhile, both MTO-MCT and MTO-FMCT exhibited a low toxicity on hCMEC/D3 normal cells. More importantly, pharmacokinetic study demonstrated that, in comparison with free MTO injection, MTO-MCT and MTO-FMCT, respectively, achieved half-lives 11.5 and 13 times longer and a 9.7- and 5.8-fold increase in AUC. In vivo, both MTO-MCT and MTO-FMCT formulations significantly prolonged the survival time of MCF-7 tumor-bearing mice and had a better efficacy/toxicity ratio. Promisingly, MTO-FMCT micelles remarkably increased MTO accumulation in tumors in vivo, induced higher tumor cell apoptosis, and showed lower toxicity toward major organs. These results imply that MTO-FMCT may be used as a potential drug delivery system for breast cancer targeted therapy

Identification of Conserved and Novel microRNAs in Cashmere Goat Skin by Deep Sequencing

<div><p>MicroRNAs (miRNAs) are a class of small RNAs that play significant roles in regulating the expression of the post-transcriptional skin and hair follicle gene. In recent years, extensive studies on these microRNAs have been carried out in mammals such as mice, rats, pigs and cattle. By comparison, the number of microRNAs that have been identified in goats is relatively low; and in particular, the miRNAs associated with the processes of skin and hair follicle development remain largely unknown. In this study, areas of skin where the cashmere grows in anagen were sampled. A total of 10,943,292 reads were obtained using Solexa sequencing, a high-throughput sequencing technology. From 10,644,467 reads, we identified 3,381 distinct reads and after applying the classification statistics we obtained 316 miRNAs. Among them, using conservative identification, we found that 68 miRNAs (55 of these are confirmed to match known sheep and goat miRNAs in miRBase ) are conserved in goat and have been reported in NCBI; the remaining 248 miRNA were conserved in other species but have not been reported in goat. Furthermore, we identified 22 novel miRNAs. Both the known and novel miRNAs were confirmed by a second sequencing using the same method as was used in the first. This study confirmed the authenticity of 316 known miRNAs and the discovery of 22 novel miRNAs in goat. We found that the miRNAs that were co-expressed in goat and sheep were located in the same region of the respective chromosomes and may play an essential role in skin and follicle development. Identificaton of novel miRNAs resulted in significant enrichment of the repertoire of goat miRNAs.</p> </div