Mi-2β promotes immune evasion in melanoma by activating EZH2 methylation

Recent development of new immune checkpoint inhibitors has been particularly successfully in cancer treatment, but still the majority patients fail to benefit. Converting resistant tumors to immunotherapy sensitive will provide a significant improvement in patient outcome. Here we identify Mi-2β as a key melanoma-intrinsic effector regulating the adaptive anti-tumor immune response. Studies in genetically engineered mouse melanoma models indicate that loss of Mi-2β rescues the immune response to immunotherapy in vivo. Mechanistically, ATAC-seq analysis shows that Mi-2β controls the accessibility of IFN-γ-stimulated genes (ISGs). Mi-2β binds to EZH2 and promotes K510 methylation of EZH2, subsequently activating the trimethylation of H3K27 to inhibit the transcription of ISGs. Finally, we develop an Mi-2β-targeted inhibitor, Z36-MP5, which reduces Mi-2β ATPase activity and reactivates ISG transcription. Consequently, Z36-MP5 induces a response to immune checkpoint inhibitors in otherwise resistant melanoma models. Our work provides a potential therapeutic strategy to convert immunotherapy resistant melanomas to sensitive ones

Willingness to engage in and current status of social participation among Chinese merchant sailors.

China has the largest population of sailors in the world, but little is known of their social participation. This study examined Chinese merchant sailors' social participation using a nationwide survey. Across 12 Chinese provinces, 7,296 merchant sailors completed the questionnaire on sailor' willingness to engage in and status of social participation. The results showed that most Chinese merchant sailors were willing to participate in social affairs, but few of them reported having joined relevant social organizations, over half of sailors reported never having participated in public affairs, and half of them chose to ignore when they faced with an obvious mistake in shipping-related information in the media. Most of sailors reported unknowing the role of the labor union related to Chinese seafarers and NGO related to navigation well, and their evaluation of these organizations were mostly negative. Chinese merchant sailors reported higher expectations of services in terms of protection of rights, providing information and technology, and providing employment opportunity. We conclude that Chinese merchant sailors have willingness to social participation although the reality is not positive and discuss implications for improving the social participation of Chinese merchant sailors

An Alternative to Lithium Metal Anodes: Non-dendritic and Highly Reversible Sodium Metal Anodes for Li-Na Hybrid Batteries

Highly reversible, stable, and non-dendritic metal anode (Li, Na etc.) is a crucial requirement for next-generation high-energy batteries. Herein, we have built a Li-Na hybrid battery (LNHB) based on Na plating/stripping, which features a high and stable coulombic efficiency of 99.2 % after 100 cycles, low voltage hysteresis (42 mV at 2 mA cm−2), and fast charge transfer. As a result of the Li+electrostatic shield layer, the Na deposition showed cubic morphology rather than dendritic, even at high current density of 5 mA cm−2. The solvation/desolvation of Li+and Na+were modelled by density functional theory calculations, demonstrating the fast desolvation kinetics of Na+. Owing to the superior performance of the Na metal anode, the LNHB coupled with LiFePO4cathode exhibited low voltage hysteresis and stable cycling performance that demonstrates its feasibility in practical applications

Longitudinal Changes in Milk Microorganisms in the First Two Months of Lactation of Primiparous and Multiparous Cows

The present experiment was carried out to analyze the longitudinal changes in milk microorganisms. For this purpose, milk samples were collected from 12 healthy cows (n = 96; six primiparous cows and six multiparous cows) at eight different time points. The characteristics and variations in microbial composition were analyzed by 16S rRNA gene high-throughput sequencing. In the primiparous group, higher and more stable alpha diversity was observed in transitional and mature milk compared with the colostrum, with no significant difference in alpha diversity at each time point in the multiparous group. Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteriota were the most dominant phyla, and Pseudomonas, UCG-005, Acinetobacter, Vibrio, Lactobacillus, Bacteroides, Serratia, Staphylococcus, and Glutamicibacter were the most dominant genera in both primiparous and multiparous cow milk. Some typically gut-associated microbes, such as Bacteroides, UCG-005, and Rikenellaceae_RC9_gut_group, etc., were enriched in the two groups. Biomarker taxa with the day in time (DIM) were identified by a random forest algorithm, with Staphylococcus showing the highest degree of interpretation, and the difference in milk microbiota between the two groups was mainly reflected in 0 d–15 d. Additionally, network analysis suggested that there were bacteria associated with the total protein content in milk. Collectively, our results disclosed the longitudinal changes in the milk microbiota of primiparous and multiparous cows, providing further evidence in dairy microbiology

Flexible and Free-Standing Organic/Carbon Nanotubes Hybrid Films as Cathode for Rechargeable Lithium-Ion Batteries

Organic carbonyl compounds are promising electrode materials for high-performance lithium-ion batteries (LIBs), but generally suffer from poor cycling stability, low utilization, inferior rate performance, and relatively low reduction potential. In order to solve these problems, we report a dissolution-recrystallization method to prepare flexible, binder-free, and free-standing hybrid films of sodium 1,4-dioxonaphthalene-2-sulfonate and multiwalled carbon nanotubes (NQS/MWNTs) as high-performance cathode for rechargeable LIBs. The hybrid films demonstrate high utilization of NQS, stable cycling, and high-rate capability. The superior electrochemical performance is attributed to decreased size and high polarity of NQS, three-dimensional intertwined conductive network formed by MWNTs. Moreover, NQS/MWNTs show high initial reduction potential at 2.97 V, which is well explained via density functional theory (DFT) calculations. Meanwhile, the reversible redox mechanism of NQS/MWNTs during discharge/charge process is revealed by in situ infrared spectroscopy (IR) test and the stability of fully discharged product is further confirmed by DFT calculations. This study illustrates a facile method to build high-performance flexible rechargeable batteries with sustainable organic materials

Effect of biodegradable PBAT microplastics on the C and N accumulation of functional organic pools in tropical latosol

Microplastics (MPs) pollution is becoming an emerging global stressor for soil ecosystems. However, studies on the impacts of biodegradable MPs on soil C sequestration have been mainly based on bulk C quantity, without considering the storage form of C, its persistency and N demand. To address this issue, the common poly (butylene adipate-co-terephthalate) (PBAT) was used as the model, and its effects on soil functional organic pools, including mineral-associated (MAOM), particulate (POM) and dissolved organic matter (DOM), were investigated from the novel coupled perspective of C and N stocks. After adding PBAT-MPs, the contents of soil POM-C, DOM-C, and MAOM-C were increased by 546.9 %–697.8 %, 54.2 %–90.3 %, and 13.7 %–18.9 %, respectively. Accordingly, the total C increased by 116.0 %–191.1 %. Structural equation modeling showed that soil C pools were regulated by PBAT input and microbial metabolism associated with C and N enzymes. Specifically, PBAT debris could be disguised as soil C to promote POM formation, which was the main pathway for C accumulation. Inversely, the MAOM-C and DOM-C formation was attributed to the PBAT microbial product and the selective consumption in DOM-N. Random forest model confirmed that N-activated (e.g., Nitrospirae) and PBAT-degrading bacteria (e.g., Gemmatinadetes) were important taxa for soil C accumulation, and the key enzymes were rhizopus oryzae lipas, invertase, and ammonia monooxygenase. The soil N accumulation was mainly related to the oligotrophic taxa (e.g., Chloroflexi and Ascomycota) associated with aggregate formation, decreasing the DOM-N by 46.9 %–84.3 %, but did not significantly change the total N storage and other N pools. Collectively, the findings highlight the urgency to control the nutrient imbalance risk of labile N loss and recalcitrant C enrichment in POM to avoid the depressed turnover rate of organic matter in MPs-polluted soil

Molecular Electrostatic Potential: A New Tool to Predict the Lithiation Process of Organic Battery Materials

This work is pioneering to introduce molecular electrostatic potential (MESP) to investigate the interaction between lithium ions and organic electrode molecules. The electrostatic potential on the van der Waals surface of the electrode molecule is calculated, and then the coordinates and relative values of the local minima of MESP can be correlated to the Li binding sites and sequence on an organic small molecule, respectively. This suggests a gradual lithiation process. Similar calculations are extended to polymers and even organic crystals. The operation process of MESP for these systems is explained in detail. Through providing accurate and visualizable lithium binding sites, MESP can give precise prediction of the lithiated structures and reaction mechanism of organic electrode materials. It will become a new theoretical tool for determining the feasibility of organic electrode materials for alkali metal ion batteries