The aim of the present study was to examine the concurrent validity of 2 Chinese versions of the short version of the Montreal Cognitive Assessment (MoCA) in patients with stroke, i.e., MoCA 5-minute protocol and National Institute for Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) 5-minute Protocol. A total of 54 patients and 27 healthy controls were enrolled in this study. In this study, the Neurobehavioural Cognitive Status Examination (NCSE) was used as an external criterion of cognitive impairment. We found that the 5-min protocol did not differ from the MoCA in differentiating patients with cognitive impairments from those without (area under the receiver operating characteristic curve, AUC, of 0.948 for the MoCA 5-min protocol v.s. 0.984 for MoCA, P = 0.097). These three assessments demonstrated equal performance in differentiating patients with stroke from controls. The Chinese version of the MoCA 5-min protocol can be used as a valid screening for patients with stroke.

Background: The molecular features of fibroblasts and the role of fibrosis in neoadjuvant chemotherapy (NAC) response and breast cancer (BRCA) prognosis remain unclear. Therefore, this study aimed to investigate the impact of interstitial fibrosis on the response and prognosis of patients with BRCA undergoing NAC treatment. Materials and Methods: The molecular characteristics of pathologic complete response (pCR) and non-pCR (npCR) in patients with BRCA were analyzed using multi-omics analysis. A clinical cohort was collected to investigate the predictive value of fibrosis in patients with BRCA. Results: Fibrosis-related signaling pathways were significantly upregulated in patients with npCR. npCR may be associated with distinct and highly active fibroblast subtypes. Patients with high fibrosis had lower pCR rates. The fibrosis-dependent nomogram for pCR showed efficient predictive ability (training set: area under the curve [AUC]=0.871, validation set: AUC=0.792). Patients with low fibrosis had a significantly better prognosis than those with high fibrosis, and those with a high fibrotic focus index had significantly shorter overall and recurrence-free survival. Therefore, fibrosis can be used to predict pCR. Our findings provide a basis for decision-making in the treatment of BRCA. Conclusions: npCR is associated with a distinct and highly active fibroblast subtype. Furthermore, patients with high fibrosis have lower pCR rates and shorter long-term survival. Therefore, fibrosis can predict pCR. A nomogram that includes fibrosis can provide a basis for decision-making in the treatment of BRCA. Export

Glioblastoma (GBM) is the most aggressive form of brain cancer, with limited therapeutic options. While microglia contribute to GBM progression, the mechanisms by which they foster a protumorigenic immune environment remain poorly understood. We identify the zinc transporter Zrt- And Irt-Like Protein 4 (ZIP4) as a pivotal regulator of the GBM immune landscape. In orthotopic mouse models, ZIP4 drives tumor growth and behavioral changes. Mechanistically, ZIP4 modulates microglial plasticity through tumor-derived extracellular vesicles carrying triggering receptor expressed on myeloid cells-1 (TREM1), a process regulated by the zinc-dependent transcription factor Zinc Finger E-box Binding Homeobox 1 in GBM cells. TREM1 enhances microglial plasticity through the spleen associated tyrosine kinase-Pyruvate dehydrogenase kinase-signal transducer and activator of transcription 3 (SYK-PDK-STAT3) signaling axis, ultimately promoting an immune environment favorable to tumor progression. ZIP4 depletion or TREM1 inhibition attenuates tumor growth and behavioral effects in vivo by disrupting the tumor–microglia interaction. These findings establish ZIP4 as a key modulator of the GBM immune landscape and suggest a promising therapeutic target to counteract microglia-mediated tumor progression.

Background: Selinexor is a selective inhibitor of exportin-1 (XPO1), a key mediator of the nucleocytoplasmic transport for molecules critical to tumor cell survival. Selinexor’s lethality is generally associated with the induction of apoptosis, and in some cases, with autophagy-induced apoptosis. We performed this study to determine Selinexor’s action in glioblastoma (GBM) cells, which are notoriously resistant to apoptosis. Methods: Patient-derived GBM cells were treated with Selinexor, and drug response and autophagy levels were monitored. Homozygous C528S XPO1 mutant GBM43 cells were generated by CRISPR/Cas9 editing. Single Selinexor or combination treatment with autophagy inhibitors was evaluated. In addition, bulk-tissue, single-cell, and spatial transcriptome were analyzed, and molecular docking was performed. Results: Although all cell lines exhibited a dose- and time-dependent reduction of cell viability, the most profound molecular response to Selinexor was induction of autophagy instead of apoptosis. Selinexor-induced autophagy was an on-target consequence of XPO1 inhibition, and could be mitigated by expression of a mutant, Selinexor-resistant form of XPO1, and Selinexor-induced autophagy was related at least in part to nuclear trapping of the transcription factor TFEB. Furthermore, genetic or pharmacologic suppression of autophagy sensitized the cells to Selinexor-induced toxicity in association with the induction of apoptosis. Finally, in intracranial PDX studies, the combination of Selinexor with the autophagy inhibitor chloroquine significantly impeded tumor growth and extended mouse survival relative to single-agent treatment. Conclusion: These results suggest that activation of autophagy confers a protective mechanism against Selinexor in GBM cells, and that the combination of Selinexor with autophagy inhibitors may serve as a viable means to enhance Selinexor-induced cell death.

Non‐small cell lung cancer (NSCLC) is the leading cause of brain metastases (BMs) and is characterized by a poor prognosis and limited response to standard treatments. Multi‐omics sequencings, integrating spatial transcriptomics, metabolomics, single‐cell RNA sequencing, bulk proteomics, and metabolomics, are conducted to analyze tumor and blood specimens from 34 patients with NSCLC with or without BMs from the Xiangya Hospital NSCLC (XY‐NSCLC) and Queen Mary Hospital NSCLC (QMH‐NSCLC) cohorts. This investigation identified LOX ⁺ Malig‐5 cells as metastasis‐initiating cells (MICs) that are significantly associated with poor prognosis. MICs colocalize with specific neutrophil subtypes, which facilitate the formation of neutrophil extracellular traps (NETs) within the metastatic niche. Mechanistically, a NET‐KRT10 signaling axis that mediates the interaction between NET‐releasing neutrophils and LOX ⁺ Malig‐5 cells is discovered, thereby promoting epithelial–mesenchymal transition (EMT) and metastasis. Furthermore, metabolic profiling reveals elevated palmitic acid levels in the resulting metastatic niche, which emerges as a crucial metabolic driver in BMs. Using an AI‐driven prediction model and in vitro/in vivo assays, fatty acid synthase inhibitor TVB‐2640 is identified as a potential therapeutic agent for disrupting metabolic vulnerability and suppressing NSCLC BMs. These findings provide novel insights into NET‐dependent cellular interactions that sustain the pro‐metastatic microenvironment underlying NSCLC BMs, offering robust development of novel metabolism‐based therapeutic strategies to combat this lethal complication.