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African Swine Fever (ASF) is a highly contagious viral disease threatening the global pig industry. Currently, only two gene-deleted live attenuated vaccines are approved, exclusively in Vietnam, and their long-term effectiveness and safety are unproven, prompting the need for safer alternatives. This study assessed a cocktail of African Swine Fever Virus (ASFV) antigens delivered via a recombinant Newcastle Disease Virus (rNDV) vector against the genotype II ASFV-SY18. Antigens pB602L, pEP84R, and p22 (pKP177R) were selected based on virus neutralization and lymphocyte proliferation assays in mice and combined with capsid protein p72 (pB646L) for vaccination and challenge in pigs. The antigen cocktail delayed ASF symptoms by 3–4 days but did not prevent the lethal ASFV-SY18 infection. Significant ASFV-specific gamma interferon (IFN-γ) positive responses and NDV antibodies were detected post-inoculation, showing an induced immune response, though ASFV-specific p72 antibodies were absent. The cocktail did not cause cytokine imbalance, indicating the vector's safety in pigs. Despite some delay in disease progression, the protection against genotype II ASFV was inadequate, underscoring the need to select more effective antigens and enhance immune responses for virus-vectored vaccines. [ABSTRACT FROM AUTHOR]

Aims: N6‐Methyladenosine (m6A) has been confirmed to play a dynamic role in osteoporosis and bone metabolism. However, whether m6A is involved in the osteogenic differentiation of human periodontal ligament cells (hPDLCs) remains unclear. The present study aimed to verify the role of methyltransferase‐like 3 (METTL3)‐mediated m6A modification in the osteogenic differentiation of hPDLCs. Methods: The METTL3, Runx2, Osx, and YAP mRNA expression was determined by qPCR. METTL3, RUNX2, OSX, YTHDF1, YAP, IGF2BP1, and eIF3a protein expression was measured by Western blotting and immunofluorescence assays. The levels of m6A modification were evaluated by methylated RNA immunoprecipitation (MeRIP) and dot blot analyses. MeRIP‐seq and RNA‐seq were used to screen potential candidate genes. Nucleic acid and protein interactions were detected by immunoprecipitation. Alizarin red staining was used to evaluate the osteogenic differentiation of hPDLCs. Gene transcription and promoter activities were assessed by luciferase reporter assays (n ≥ 3). Results: The expression of METTL3 and m6A modifications increased synchronously with the osteogenic differentiation of hPDLCs (p =.0016). YAP was a candidate gene identified by MeRIP‐seq and RNA‐seq, and its mRNA and protein expression levels were simultaneously increased. METTL3 increased the m6A methylated IGF2BP1‐mediated stability of YAP mRNA (p =.0037), which in turn promoted osteogenic differentiation (p =.0147). Furthermore, METTL3 increased the translation efficiency of YAP by recruiting YTHDF1 and eIF3a to the translation initiation complex (p =.0154), thereby promoting the osteogenic differentiation of hPDLCs (p =.0012). Conclusion: Our study revealed that METTL3‐initiated m6A mRNA methylation promotes osteogenic differentiation of hPDLCs by increasing IGF2BP1‐mediated YAP mRNA stability and recruiting YTHDF1 and eIF3a to the translation initiation complex to increase YAP mRNA translation. Our findings reveal the mechanism of METTL3‐mediated m6A modification during hPDLC osteogenesis, providing a potential therapeutic target for periodontitis and alveolar bone defects. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells display elevated reactive oxygen species (ROS) and an altered redox status. For this study, taking advantage of these characteristics, we designed a multifunctional MRI-visualizable multi-drug delivery platform, AMB@PDAP-Fe (APPF), based on magnetotactic bacteria (AMB) for MRI-visualized tumor photo-thermotherapy (PTT) and enhanced chemodynamic therapy (CDT). Upon magnetic navigation, APPF accumulated in the tumor microenvironment. The PDAP-Fe in the composite was reduced by glutathione (GSH) in the tumor microenvironment and produced Fe2+, which catalyzed the generation of reactive oxygen species (ROS) through the Fenton reaction and induced tumor cell apoptosis. The magnetosomes in AMB displayed good dual-mode contrast capability in an MRI, which was later used to visualize the process of tumor treatment. Upon NIR light irradiation, the magnetosomes in magnetotactic bacteria immediately converted the light energy into heat energy and the tumor tissue was heated up, thus causing the death of tumor cells. It is noteworthy that the heat generated during the synergistic PTT process (to which PDAP partly contributed) accelerated the releasing of Fe2+ from PDAP-Fe, which enhanced the catalytic conversion of endogenous H2O2 into ·OH, and, thus, achieved synergistic photothermal-enhanced Fenton-reaction-mediated cancer therapy. This study demonstrates the feasibility of developing an MRI-visualizable multi-drug delivery platform from magnetic bacteria, which, compared with other manmade inorganic multi-drug delivery platforms, are lively, self-propelled, and magnetically navigated. This study also highlights the synergistic tumor-curing effect between magnetic bacteria and PDAP-Fe and the importance of understanding the underlying cooperative molecular mechanism between different drugs when scheduling combination therapy. Cancer cells display elevated reactive oxygen species (ROS) and altered redox status. Herein, based on these characteristics, we present a multi-drug delivery platform, AMB@PDAP-Fe (APPF), from the magnetotactic bacterium AMB-1 and realize MRI-visualized tumor-microenvironment-responsive photothermal–chemodynamic therapy. The Fe3+ in PDAP-Fe is reduced by the GSH at the tumor site and is released in the form of highly active Fe2+, which catalyzes the generation of ROS through the Fenton reaction and inhibits tumor growth. At the same time, the significant absorption of the mineralized magnetosomes in AMB-1 cells in the NIR region enables them to efficiently convert near-infrared light into heat energy for photothermal therapy (PTT), to which PDAP also contributes. The heat generated in the PTT process accelerates the process of Fe2+ release, thereby achieving an enhanced Fenton reaction in the tumor microenvironment. In addition, the magnetosomes in AMB-1 are used as an MRI contrast agent, and the curing process is visualized. This tumor microenvironment-responsive MTB-based multi-drug delivery platform displays the potency to combat tumors and demonstrates the utility and practicality of understanding the cooperative molecular mechanism when designing multi-drug combination therapies. [ABSTRACT FROM AUTHOR]