Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Current treatment options for GBM include surgical resection, radiation, and chemotherapy, which predominantly slow cancer growth and reduce symptoms, resulting in a 5-year survival rate of no more than 10%. Chimeric antigen receptor (CAR) T-cell therapy is a new class of cellular immunotherapy that has made great progress in treating malignant tumors. Human epidermal growth factor receptor 2 (HER2) is overexpressed in GBM and may provide a potential therapeutic target for GBM treatment. In this study, we constructed third-generation CAR-T cells targeting the HER2 antigen in GBM. HER2-CAR-T cells showed effective anti-tumor activity both in vitro and in vivo. Furthermore, HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting abilities against GBM cells in vitro. Anti-HER2 CAR-T cells also exhibited increased cytotoxicity with increasing effector-to-target ratios. Anti-HER2 CAR-T cells delivered via peritumoral injection successfully stunted tumor progression in vivo. Moreover, peritumoral intravenous administration of anti-HER2 CAR-T cells resulted in therapeutic improvement against GBM cells compared with intravenous administration. In conclusion, our study shows that HER2 CAR-T cells represent an emerging immunotherapy for treating GBM.

The single-point insulin sensitivity estimator (SPISE) index is a surrogate marker for insulin resistance. However, its association with cardiovascular disease (CVD) risk remains unclear. The study included 5755 participants from the Chinese Longitudinal Healthy Longevity Survey (CHARLS) and 2598 from the English Longitudinal Study of Ageing (ELSA). Cox proportional hazards models were used to examine the association between the SPISE index and CVD incidence, reporting hazard ratios (HR) and 95 % confidence intervals (CI). Within the Cox proportional hazards model framework, restricted cubic splines were applied to evaluate non-linear associations, and cumulative hazard curves were generated to illustrate the dynamics of risk over time. Subgroup analyses were conducted to assess effect heterogeneity, and a mediation analysis was performed to explore potential underlying mechanisms. During the follow-up period (2004-2018 for ELSA and 2011-2018 for CHARLS), 935 (16.25 %) participants in CHARLS and 1026 (39.49 %) participants in ELSA developed CVD. In the fully adjusted Cox proportional hazards model, individuals in the highest tertile of the SPISE index had a significantly lower risk of CVD incidence compared with those in the lowest tertile (CHARLS: adjusted HR: 0.61, 95 % CI: 0.51-0.72; ELSA: adjusted HR: 0.83, 95 % CI: 0.71-0.98). RCS regression analysis showed a negative linear relationship between the SPISE index and the CVD incidence. A higher SPISE index had a lower cumulative incidence of CVD. Subgroup analyses, stratified by gender, marital status, education level, smoking status, and alcohol drinking status, revealed no significant modification of the SPISE index-CVD incidence association. Mediation analysis examined how the SPISE index is linked to CVD events, with CHO, LDL-C, CRP, and HbA1c as potential mediators. In the CHARLS cohort, CHO (3.36 %) and LDL-C (3.81 %) partially mediated the association; in the ELSA cohort, CRP showed a significant mediating effect (11.98 %). A higher SPISE index is associated with reduced CVD risk in middle-aged and older adults, indicating its value as a tool for CVD risk assessment.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Current treatment options for GBM include surgical resection, radiation, and chemotherapy, which predominantly only slow cancer growth and reduce symptoms, resulting in a 5-year survival rate of no more than 10%. Chimeric antigen receptor (CAR)-T cell therapy is a new class of cellular immunotherapies that has made great progress in the treatment of malignant tumors. Human epidermal growth factor receptor 2 (HER2) is over-expressed in GBM, and may provide a potential therapeutic target for GBM treatment. In this study, we constructed third-generation CAR-T cells targeting the HER2 antigen in GBM. HER2-CAR-T cells showed effective antitumor abilities both in vitro and in vivo. Furthermore, HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting ability against GBM cells in vitro. Anti-HER2 CAR-T cells also exerted increasing cytotoxicity from low to high effector-to-target (E: T) ratios. Importantly, anti-HER2 CAR-T cells delivered by peritumoral injection successfully stunted tumor progression in vivo. Moreover, peritumoral intravenous administration of anti-HER2 CAR-T exhibited a therapeutic improvement against GBM cells compared with intravenous administration. In conclusion, our studies show that HER2 CAR-T cells represent an emerging immunotherapy for the treatment of GBM.

Intestinal fucosylation, the enzymatic addition of fucose to glycoconjugates, represents a pivotal regulatory mechanism that modulates host–microbiota crosstalk in the gastrointestinal tract. This review comprehensively synthesizes current advances in the molecular mechanisms, multilevel regulatory networks, and functional implications of intestinal mucosal fucosylation. This review focuses on α(1,2)-fucosylation catalyzed by fucosyltransferase 2 (FUT2)—a reaction that determines the secretor status and modifies critical glycoconjugates, including mucins and human milk oligosaccharides. This review examines the dynamic regulation of epithelial fucosylation by host-derived factors—including immune mediators [notably interleukin-22 (IL-22) secreted by group 3 innate lymphoid cells (ILC3s)], the enteric nervous system (ENS), and microbial signals. Furthermore, this review details how fucosylated glycans shape the gut microbial ecosystem by serving as selective nutrient sources for beneficial symbionts—including Bifidobacterium and Bacteroides species—while concurrently enhancing colonization resistance against enteric pathogens. Dysregulation of this axis is increasingly associated with a spectrum of human pathologies, including inflammatory bowel disease (IBD), metabolic dysfunction, and enteric infections. Finally, this review discusses emerging therapeutic strategies targeting the modulation of intestinal fucosylation and its downstream physiological consequences, with particular emphasis on personalized approaches informed by host genetic determinants—most notably FUT2 secretor status.