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Ultrahigh-voltage potassium-ion batteries (PIBs) with cost competitiveness represent a viable route towards high energy battery systems. Nevertheless, rapid capacity decay with poor Coulombic efficiencies remains intractable, mainly attributed to interfacial instability from aggressive potassium metal anodes and cathodes. Additionally, high reactivity of K metal and flammable electrolytes pose severe safety hazards. Herein, a weakly solvating fluorinated electrolyte with intrinsically nonflammable feature is successfully developed to enable an ultrahigh-voltage (up to 5.5 V) operation. Through breaking the anionic solvation barrier, synergistic interfacial modulation can be achieved by the formation of robust anion-derived inorganic-rich electrode-electrolyte interfaces on both the cathode and anode. As proof of concept, a representative KVPO4F cathode can sustain 1600 cycles with 84.4% of capacity retention at a high cutoff voltage of 4.95 V. Meanwhile, K plating/stripping process in our designed electrolyte also demonstrates optimized electrochemical reversibility and stability with effectively inhibited potassium dendrites. These findings underscore the critical impact of anion-dominated solvation configuration on synergistic interfacial modulation and electrochemical properties. This work provides new insights into rational design of ultrahigh-voltage and safe electrolyte for advanced PIBs., (© 2025 Wiley‐VCH GmbH.)

Despite the revolutionary achievements of chimeric antigen receptor (CAR) T cell therapy in treating cancers, especially leukemia, several key challenges still limit its therapeutic efficacy. Of particular relevance is the relapse of cancer in large part, as a result of exhaustion and short persistence of CAR-T cells in vivo. IL-2-inducible T cell kinase (ITK) is a critical modulator of the strength of T-cell receptor (TCR) signaling, while its role in CAR signaling is unknown. By electroporation of clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) ribonucleoprotein (RNP) complex into CAR-T cells, we successfully deleted ITK in CD19-CAR-T cells with high efficiency. Bulk and single-cell RNA sequencing (scRNA-seq) analyses revealed down-regulation of exhaustion and up-regulation of memory gene signatures in ITK-deficient CD19-CAR-T cells. Our results further demonstrated a significant reduction of T cell exhaustion and enhancement of T cell memory, with significant improvement of CAR-T cell expansion and persistence both in vitro and in vivo. Moreover, ITK-deficient CD19-CAR-T cells showed better control of tumor relapse. Our work provides a promising strategy of targeting ITK to develop sustainable CAR-T products for clinical use.

Objective To investigate the effect of insulin in combination with selenium on p38-mitogen-activated protein kinase/CREB-binding protein (p38MAPK/CBP) pathway in rats with diabetic cardiomyopathy. Methods Fifty SD rats were randomly grouped into control group, diabetic cardiomyopathy (DCM) group, diabetic cardiomyopathy with insulin treatment (DCM-In) group, diabetic cardiomyopathy with selenium treatment (DCM-Se) group, and diabetic cardiomyopathy with insulin and selenium combination treatment (DCM-In-Se) group. Flow cytometry was used to analyze cell cycle. TUNEL staining was used to detect cardiomyocyte apoptosis. Western blotting was used to examine the levels of cyclin D1, cyclin E, Bax, Bcl-2, p38MAPK, p-p38MAPK, CBP and Ku70. Co-immunoprecipitation was used to examine the acetylation status of Ku70. Results Insulin in combination with selenium significantly inhibited cardiomyocyte apoptosis, increased Bcl-2 levels and decreased Bax, cyclin D1, cyclin E, p38MAPK, p-p38MAPK, CBP, Ku70 and acetylated Ku70 levels. Conclusion The combined treatment of insulin and selenium suppresses cardiomyocyte apoptosis by inhibiting p38MAPK/CBP pathway.

Tyrosol galactoside (TG) is a new candidate anti-fatigue agent under development. In order to have a good understanding of its pharmacokinetic characters, the paper describes the dose-dependent pharmacokinetics of TG in rats after oral and intravenous administration. TG was rapidly absorbed after oral administration and cleared with first-order rate, for the plasma half-life was independent of dose. C(max) and AUC(0-infinity) after both intravenous and oral dosing were all linearly correlated with the dose, as the regression correlation coefficient (R) was 0.998, 0.989 and 0.994 for AUC(0-infinity) (i.v., P < 0.01) AUC(0-infinity) (i.g., P < 0.01) and C(max) (i. g., P < 0.01), respectively. However, these parameters increased less than proportionally with increasing dose. In addition, the apparent volume of distribution (Vd) and the apparent clearance (Cl) seemed to be affected by the dose.