Yi Yang

Abstract Background The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma (HCC) remains poor. Although serine‐ and arginine‐rich splicing factor (SRSF) family members play crucial roles in tumors, their impact on tumor immunology remains unclear. This study aimed to elucidate the role of SRSF10 in HCC immunotherapy. Methods To identify the key genes associated with immunotherapy resistance, we conducted single‐nuclear RNA sequencing, multiplex immunofluorescence, and The Cancer Genome Atlas and Gene Expression Omnibus database analyses. We investigated the biological functions of SRSF10 in immune evasion using in vitro co‐culture systems, flow cytometry, various tumor‐bearing mouse models, and patient‐derived organotypic tumor spheroids. Results SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 + T cell activity. Mechanistically, SRSF10 interacted with the 3′‐untranslated region of MYB , enhancing MYB RNA stability, and subsequently upregulating key glycolysis‐related enzymes including glucose transporter 1 ( GLUT1 ), hexokinase 1 ( HK1 ), lactate dehydrogenase A ( LDHA ), resulting in elevated intracellular and extracellular lactate levels. Lactate accumulation induced histone lactylation, which further upregulated SRSF10 expression. Additionally, lactate produced by tumors induced lactylation of the histone H3K18la site upon transport into macrophages, thereby activating transcription and enhancing pro‐tumor macrophage activity. M2 macrophages, in turn, inhibited the enrichment of CD8 + T cells and the proportion of interferon‐γ + CD8 + T cells in the tumor microenvironment (TME), thus creating an immunosuppressive TME. Clinically, SRSF10 could serve as a biomarker for assessing immunotherapy resistance in various solid tumors. Pharmacological targeting of SRSF10 with a selective inhibitor 1C8 enhanced the efficacy of programmed cell death 1 (PD‐1) monoclonal antibodies (mAbs) in both murine and human preclinical models. Conclusions The SRSF10/MYB/glycolysis/lactate axis is critical for triggering immune evasion and anti‐PD‐1 resistance. Inhibiting SRSF10 by 1C8 may overcome anti‐PD‐1 tolerance in HCC.

Abstract Gram-positive (G + ) bacterial infection is a great burden to both healthcare and community medical resources. As a result of the increasing prevalence of multidrug-resistant G + bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), novel antimicrobial agents must urgently be developed for the treatment of infections caused by G + bacteria. Endolysins are bacteriophage (phage)-encoded enzymes that can specifically hydrolyze the bacterial cell wall and quickly kill bacteria. Bacterial resistance to endolysins is low. Therefore, endolysins are considered promising alternatives for solving the mounting resistance problem. In this review, endolysins derived from phages targeting G + bacteria were classified based on their structural characteristics. The active mechanisms, efficacy, and advantages of endolysins as antibacterial drug candidates were summarized. Moreover, the remarkable potential of phage endolysins in the treatment of G + bacterial infections was described. In addition, the safety of endolysins, challenges, and possible solutions were addressed. Notwithstanding the limitations of endolysins, the trends in development indicate that endolysin-based drugs will be approved in the near future. Overall, this review presents crucial information of the current progress involving endolysins as potential therapeutic agents, and it provides a guideline for biomaterial researchers who are devoting themselves to fighting against bacterial infections.

Abstract Developing green and efficient preparation strategies is a persistent pursuit in the field of 2D transition metal nitrides and/or carbides (MXenes). Traditional etching methods, such as HF‐based or high‐temperature Lewis‐acid‐molten‐salt etching route, require harsher etching conditions and exhibit lower preparation efficiency with limited scalability, severely constraining their commercial production and practical application. Here, an ultrafast low‐temperature molten salt (LTMS) etching method is presented for the large‐scale synthesis of diverse MXenes within minutes by employing NH 4 HF 2 as the etchant. The increased thermal motion and improved diffusion of molten NH 4 HF 2 molecules significantly expedite the etching process of MAX phases, thus achieving the preparation of Ti 3 C 2 T x MXene in just 5 minutes. The universality of the LTMS method renders it a valuable approach for the rapid synthesis of various MXenes, including V 4 C 3 T x , Nb 4 C 3 T x , Mo 2 TiC 2 T x , and Mo 2 CT x . The LTMS method is easy to scale up and can yield more than 100 g Ti 3 C 2 T x in a single reaction. The obtained LTMS‐MXene exhibits excellent electrochemical performance for supercapacitors, evidently proving the effectiveness of the LTMS method. This work provides an ultrafast, universal, and scalable LTMS etching method for the large‐scale commercial production of MXenes.

Abstract Lithium iron phosphate (LFP)/graphite batteries have long dominated the energy storage battery market and are anticipated to become the dominant technology in the global power battery market. However, the poor fast‐charging capability and low‐temperature performance of LFP/graphite batteries seriously hinder their further spread. These limitations are strongly associated with the interfacial lithium (Li)‐ion transport. Here we report a wide‐temperature‐range ester‐based electrolyte that exhibits high ionic conductivity, fast interfacial kinetics and excellent film‐forming ability by regulating the anion chemistry of Li salt. The interfacial barrier of the battery is quantitatively unraveled by employing three‐electrode system and distribution of relaxation time technique. The superior role of the proposed electrolyte in preventing Li 0 plating and sustaining homogeneous and stable interphases are also systematically investigated. The LFP/graphite cells exhibit rechargeability in an ultrawide temperature range of −80 °C to 80 °C and outstanding fast‐charging capability without compromising lifespan. Specially, the practical LFP/graphite pouch cells achieve 80.2 % capacity retention after 1200 cycles (2 C) and 10‐min charge to 89 % (5 C) at 25 °C and provide reliable power even at −80 °C.