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When the external conditions change, such as the temperature or the pressure, the multi-component system sometimes separates into several phases with different components and structures, which is called phase separation. Increasing studies have shown that cells condense related biomolecules into independent compartments in order to carry out orderly and efficient biological reactions with the help of phase separation. Biomolecular condensates formed by phase separation play a significant role in a variety of cellular processes, including the control of signal transduction, the regulation of gene expression, and the stress response. In recent years, many phase separation events have been discovered in the immune response process. In this review, we provided a comprehensive and detailed overview of the role and mechanism of phase separation in the innate and adaptive immune responses, which will help the readers to appreciate the advance and importance of this field.

Despite numerous observational studies indicating an increased risk of cutaneous melanoma (CM) due to childhood sunburn, no studies have established a definitive cause‐and‐effect relationship. Therefore, our objective was to employ a Mendelian randomization (MR) design to explore a possible causal association between childhood sunburn and the risk of CM. To investigate the causal relationship between childhood sunburn and CM, we used large‐scale genetic summary‐level data from genome‐wide association studies (GWAS), including childhood sunburn (n = 346,955) and CM (n = 262,288), building upon previous observational studies. In the analysis, we mainly used the inverse‐variance weighted (IVW) method of the random effects model, supplemented by the weighted median method and MR‐Egger method. The results of the IVW method demonstrated that genetically predicted childhood sunburn was significantly associated with higher odds of CM, with an odds ratio (OR) of 2.418 (95%CI, 1.426–4.099; p = .001). The weighted median method and MR‐Egger regression also demonstrated directionally similar results (both p < .05). Furthermore, both the funnel plot and the MR‐Egger intercepts showed the absence of directional pleiotropy between childhood sunburn and CM. Our study offers potential evidence linking genetically predicted childhood sunburn with CM, underscoring the need for individuals with a history of childhood sunburn to be extra vigilant regarding the occurrence of CM. This article explores the potential causal relationship between childhood sunburn and the risk of melanoma through a Mendelian randomization design. The results suggest a positive correlation between genetically predicted childhood sunburn and the risk of melanoma. Therefore, this study provides potential evidence linking childhood sunburn to melanoma and suggests that individuals with a history of childhood sunburn should be more vigilant in preventing melanoma.

Magnesium (Mg) alloys, the lightest metal construction material used in industry, play a vital role in future development. However, the poor corrosion resistance of Mg alloys in corrosion environments largely limits their potential wide applications. Therefore, a micro-arc oxidation/graphene oxide/stearic acid (MAO/GO/SA) superhydrophobic composite coating with superior corrosion resistance was fabricated on a Mg alloy AZ91D through micro-arc oxidation (MAO) technology, electrodeposition technique, and self-assembly technology. The composition and microstructure of the coating were characterized by scanning electron microscopy, X-ray diffraction, energy dispersive spectroscopy, and Raman spectroscopy. The effective protection of the MAO/GO/SA composite coating applied to a substrate was evaluated using potentiodynamic polarization, electrochemical impedance spectroscopy tests, and salt spray tests. The results showed that the MAO/GO/SA composite coating with a petal spherical structure had the best superhydrophobicity, and it attained a contact angle of 159.53° ± 2°. The MAO/GO/SA composite coating exhibited high resistance to corrosion, according to electrochemical and salt spray tests.

Although numerous observational studies have indicated a potential association between autoimmune diseases, such as rheumatoid arthritis (RA) and alopecia areata (AA), the research reports lack a clear causal relationship. In this study, our objective is to utilize the Mendelian randomization (MR) design to examine the potential causal association between RA and AA. To investigate the causal relationship between RA and AA, we utilized large-scale gene aggregation data from genome-wide association studies (GWAS), including RA (n=58,284) and AA (n=361,822) based on previous observational studies. In our analysis, we mainly employed the inverse variance-weighted (IVW) method of the random effects model, supplemented by the weighted median (WM) method and the MR Egger method. The findings from the IVW methods revealed a significant association between genetically predicted RA and an increased likelihood of AA, as evidenced by an odds ratio of 1.21 (95%CI = 1.11-1.32; < 0.001. Both the WM method and MR-Egger regression consistently showed significant directional outcomes (Both < 0.05), indicating a robust association between RA and AA. Additionally, both the funnel plot and the MR-Egger intercepts provided evidence of the absence of directional pleiotropy, suggesting that the observed association is not influenced by other common genetic factors. The results of the study suggest a possible link between genetically predicted RA and AA. This finding highlights the importance for individuals diagnosed with RA to remain vigilant and aware of the potential development of AA. Regular monitoring and early detection can be crucial in managing and addressing this potential complication.

Plasma electrochemical oxidation (PEO) is a surface modification technology to form ceramic coatings on magnesium alloys. However, its application is limited due to its defects. This work reports a novel preparation of in-situ sealing of PEO coatings by four-layer voltage and sol addition. The morphology and structure were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and X-ray diffractometer (XRD). Image-Pro Plus 6.0 was used to determine the porosity of the coating, which was decreased from 8.53% to 0.51%. Simultaneously, the coating thickness was increased by a factor of four. The anti-corrosion performance of each sample was evaluated using electrochemical tests, and the findings revealed that the corrosion current density of coatings ( i corr ) of the samples were lowered from 9.152 × 10 −2 to 6.152 × 10− 4 mA·cm− 2 , and the total resistance ( R T ) of the samples were enhanced from 2.19 × 10 4 to 2.33 × 10 5 Ω·cm 2 . The salt spray test used to simulate the actual environment showed that corrosion points appeared on the surface of the coating only at the 336 h. In addition, the mechanism of PEO self-sealing behavior was described in this article.

PurposeThis paper aims to obtain the evolution law of dynamic performance of CR400BF electric multiple unit (EMU).Design/methodology/approachUsing the dynamic simulation based on field test, stiffness of rotary arm nodes and damping coefficient of anti-hunting dampers were tested. Stiffness, damping coefficient, friction coefficient, track gauge were taken as random variables, the stochastic dynamics simulation method was constructed and applied to research the evolution law with running mileage of dynamic index of CR400BF EMU.FindingsThe results showed that stiffness and damping coefficient subjected to normal distribution, the mean and variance were computed and the evolution law of stiffness and damping coefficient with running mileage was obtained.Originality/valueFirstly, based on the field test we found that stiffness of rotary arm nodes and damping coefficient of anti-hunting dampers subjected to normal distribution, and the evolution law of stiffness and damping coefficient with running mileage was proposed. Secondly stiffness, damping coefficient, friction coefficient, track gauge were taken as random variables, the stochastic dynamics simulation method was constructed and applied to the research to the evolution law with running mileage of dynamic index of CR400BF EMU.

Epstein‐Barr virus (EBV) nuclear antigen 1 (EBNA1) is necessary to maintain stability of EBV episomes, EBV replication, and causes host genomic instability and promotes tumor cells survival. Recent studies have shown that viruses utilize liquid–liquid phase separation (LLPS) within host cells to form sub‐cellular compartments known as “virus factories”. Prion‐like domains (PrLDs), which resemble structural domains of low complexity, are shown to drive LLPS in vivo. In the current study, a PrLD is identified in EBNA1 and aggregation of EBNA1 proteins is observed in EBV‐positive tumors. EBNA1 condensate interacting molecules are examined and are found that EBNA1 interacts with the splicing factor SRSF1 to regulate alternative splicing of SRRM1 and promote tumor progression. Deleting the EBNA1 PrLD results in defects in protein aggregation, LLPS, alternative splicing regulation, and nasopharyngeal carcinoma cells proliferation. Targeting the PrLD of EBNA1 inhibits the formation of protein aggregation, promotes alternative splicing of SRRM1, and inhibits the progression of nasopharyngeal carcinoma. Here, we report for the first time that EBNA1, a protein from the human oncogenic virus EBV, is a prion‐like protein, combining algorithm prediction and experimental validation. That implies a possible molecular pathogenic mechanism of EBNA1 in neurodegenerative diseases. This study discoveries that EBV EBNA1 behaves as a prion‐like protein, verified using cell‐based assays and the Saccharomyces cerevisiae Sup35p prion identification system. The prion‐like domain of EBNA1 drives liquid–liquid phase separation. EBNA1 interacts with the splicing factor SRSF1 to regulate the expression of the SRRM1 splicing isoforms, thereby promoting EBV‐associated tumor development.

Lactoferrin (Lf) is widely distributed in mammalian milk, various tissues, and their exocrine fluids and has many physiological functions, such as bacteriostasis, antivirus, and immunoregulation. Here, we provide evidence that lactoferrin is required for early stages of B cell development in mice. Lactoferrin-deficient ( Lf −/− ) C57BL/6 mice showed systematic reduction in total B cells, which was attributed to the arrest of early B cell development from pre-pro-B to pro-B stage. Although the Lf −/− B cell “seeds” generated greater pro-B cells comparing to wild type (WT) littermates, the Lf −/− mice bone marrow had less stromal cells, and lower CXCL12 expression, produced a less favorable “microenvironment” for early B cell development. The underlying mechanism was mediated through ERK and AKT signalings and an abnormality in the transcription factors related to early differentiation of B cells. The Lf −/− mice also displayed abnormal antibody production in T cell-dependent and T cell-independent immunization experiments. In a pristane-induced lupus model, Lf −/− mice had more serious symptoms than WT mice, whereas lactoferrin treatment alleviated these symptoms. This study demonstrates a novel role of lactoferrin in early B cell development, suggesting a potential benefit for using lactoferrin in B cell-related diseases.

Dear Editor, Alternative splicing of pre-mRNAs is a significant mRNA maturation process that increases RNA and protein diversity in eukaryotes.1–3 The Epstein–Barr Virus (EBV)-encoded nuclear antigen 2 (EBNA2) is a multifunctional transcriptional activator and is essential for EBV-induced cell transformation through activating multiple genes expression.4–6 We recently revealed that EBNA2 activates cellular genes transcription by phase separation.7 To investigate the components of these phase separation nuclear puncta that interact with EBNA2, we used mass spectrometry to analyze the EBNA2 co-immunoprecipitates and found that 193 cellular proteins were most likely to interact with EBNA2 (Figure 1A and Table S1). EBNA2-induced DAS genes were enriched for functional categories of defense responses and tumor-related signaling pathways (Figure S3B, C), whereas EBNA2-induced DEGs were enriched for functional categories related to mRNA processing and DNA repair (Figure S4B–D). Particularly, EBNA2 regulates MPPE1 aberrant splicing by recruiting SRSF1 and SRSF7 to its motif in the exon 11, and MPPE1 functions as an oncogene in tumor cells (Figure 4N, proposed working model). [...]the ability of EBNA2 in regulating gene-splicing requires EBNA2 phase separation.

In this study, branched layers formed under various conditions of the electrochemical etching of aluminum foils were observed. Tunnel clustering arose from the random distribution of high-density tunnels, greatly increasing the thickness of the branched layer; this occurred because the tunnel clustering increased the tunnel width, thereby facilitating electrolyte transport in vertical tunnels. In contrast, tunnel tapering blocked the branched tunnels generated at a certain depth. The thickened branched layer greatly reduced the foil thickness during tunnel widening, considerably reducing the surface area and the specific capacitance obtained for the etched aluminum foil.