Shanghai Drug Administration

The high mutation rate of the influenza virus poses a significant challenge to global health, highlighting the urgent need for broad-spectrum vaccines. Here, we engineered Ad-Hex, a pan-influenza vaccine comprising three chimpanzee adenoviral vectors (Ad-H1H3, Ad-BYBV, and Ad-H5H7), each encoding the hemagglutinin (HA) genes from two distinct influenza virus subtypes/lineages in the △E1 region. A single intranasal dose of Ad-Hex induced robust humoral, cellular, and mucosal immunity, conferring complete protection against lethal challenge with six vaccine-matched strains in female C57BL/6 or Balb/c mice. Notably, the vaccine achieved 60% survival rates against mismatched strains. Mechanistic studies revealed that Ad-Hex activated germinal center B-cell responses not only against the cognate HAs but also against the conserved HA stalks. This drove the production of cross-reactive antibodies, which contributed to heterologous protection along with the CD8+ T cell response. Our study confirms the feasibility of this multivalent strategy by mixing multiple recombinant adenoviruses and provides insights into the development of multivalent vaccines against other respiratory pathogens.

ObjectiveCurrently, China regulatory authorities are committed to improving drug inspection by learning from international advanced experiences, such as the Pharmaceutical Inspection Co-operation Scheme (PIC/S), to boost the development of the pharmaceutical industry. In the past, there has been a lack of systematic discussion and comprehensive theoretical construction of the key elements affecting the improvement of China’s Good Manufacturing Practice (GMP) inspection. Through this study, the key elements and theoretical logic for applying PIC/S standards to improve China’s pharmaceutical GMP inspection work are constructed.MethodsThis study uses diverse data and applies grounded theory to construct a model, systematically presenting the key elements and theoretical logic of applying PIC/S standards in improving GMP inspections in China.ResultsThe study found that international recognized GMP regulations are external contextual elements, while internal driving elements include professionalization and specialization of inspectors, standardized inspection procedures, and maintain consistent quality levels. The internal dimensions of these four elements are independent, but they can not only individually influence but also partially overlap and have a combined impact Moreover, professionalization and specialization of inspectors, standardized inspection procedures, and maintain consistent quality levels have a dynamic, cyclical promoting effect on the application of PIC/S standards.ConclusionBased on China’s national conditions, this study deepens the theoretical framework and content of applying PIC/S standards to improve drug GMP inspections, providing a reference for public sectors to enhance the effectiveness of pharmaceutical regulation.

<h2>Summary</h2> Electric vehicles (EVs) are vital for a decarbonized society, but the rapid growth of the EV market highlights an impending lithium supply crisis. This study integrates supply-demand analysis with trade network simulations, using eight lithium demand scenarios and two supply scenarios to examine regional lithium dynamics and the impact of international trade. Results show that while domestic lithium production in China, Europe, and the USA—especially in Europe, where production may grow 10-fold between 2025 and 2030—will increase, it will not fully meet demand. The regions differ in their paths to self-sufficiency: China may reduce import reliance with lower battery capacity, the USA could ease shortages under a high-supply scenario, and Europe faces the largest deficit. Maximizing imports could bring Europe closer to balance than the USA, but interregional trade complicates this. Governance is urgently needed to prevent competition for scarce resources from hindering low-carbon technology adoption.

The aims of this study were to assess the adjuvant properties of an MF59-like adjuvant containing yeast-derived squalene (MF59-like YD) in a cell-based quadrivalent influenza vaccine (QIV) and to investigate the potential mechanisms of action. MF59-like adjuvants containing either yeast-derived or shark-derived squalene were incorporated into QIV formulations. Antigen-specific immune responses in mouse serum were evaluated via enzyme-linked immunosorbent assays (ELISAs), hemagglutination inhibition (HI) assays, and microneutralization (MN) assays. The effects and mechanisms of action of the adjuvants were further analyzed by analyzing mouse spleen germinal center (GC) cell activation via flow cytometry. MF59-like YD significantly increased the humoral immune responses induced by QIVs in mice, in particular, the titers of HI and MN antibodies against homologous and heterologous virus subtypes. Mechanistically, MF59-like YD increased the immune response to influenza vaccines by activating T follicular helper (Tfh) and B cells in the GC. Given the greater availability of yeast-derived squalene and the finding that its adjuvant efficacy was comparable to that of shark-derived squalene, we propose that the MF59-like YD adjuvant is a promising alternative adjuvant for future influenza vaccines.

Methylthioadenosine phosphorylase (MTAP)-deletion occurs in about 15% of all cancers. The metabolic enzyme methionine adenosyltransferase 2A (MAT2A) was found to elicit synthetic lethality in MTAP-deleted cancers. Here, we commented on a novel MAT2A inhibitor SCR-7952, and discussed the potential of MAT2A inhibitors as single agents or in combination for cancer therapy, including solid tumors and hematologic malignancies. Several MAT2A inhibitors with high efficacy and selectivity have been discovered. And MAT2A inhibitors synergize strongly with protein arginine N-methyltransferase 5 (PRMT5) inhibitors, taxanes, platinum, topoisomerase inhibitors, and antibody-drug conjugates (ADC). A MAT2A inhibitor IDE397 and the combination strategies with chemotherapies or other targeted therapies are under investigation in clinical. The promising preliminary clinical results demonstrate the potential of MAT2A inhibitors for the treatment of MTAP-deleted tumors.