Accumulating evidence shows that microRNA-210 (miR-210) holds great promise to improve angiogenesis for brain tissue repair after cerebral ischemia. However, safe and efficient delivery of miR-210 via intravenous administration is still a challenge. In the past decade, exosomes have emerged as a novel endogenous delivery system. Here, c(RGDyK) peptide is conjugated to exosomes, and they are loaded with cholesterol-modified miR-210 (RGD-exo:miR-210). In a transient middle cerebral artery occlusion (MCAO) mouse model, the RGD-exo:miR-210 targets the lesion region of the ischemic brain after intravenous administration, resulting in an increase in miR-210 at the site. Furthermore, RGD-exo:miR-210 are administered once every other day for 14 days, and the expressions of integrin β3, vascular endothelial growth factor (VEGF) and CD34 are significantly upregulated. The animal survival rate is also enhanced. These results suggest a strategy for the targeted delivery of miR-210 to ischemic brain and provide an angiogenic agent for the treatment of ischemic stroke.

Neuroinflammation plays a significant role in ischemic injury, which can be promoted by oxidized mitochondrial DNA (Ox-mtDNA). Cytidine/uridine monophosphate kinase 2 (CMPK2) regulates mtDNA replication, but its role in neuroinflammation and ischemic injury remains unknown. Here, we report that CMPK2 expression is upregulated in monocytes/macrophages and microglia post-stroke in humans and mice, respectively. Microglia/macrophage CMPK2 knockdown using the Cre recombination-dependent adeno-associated virus suppresses the inflammatory responses in the brain, reduces infarcts, and improves neurological outcomes in ischemic CX₃CR1^Cre/ERT2 mice. Mechanistically, CMPK2 knockdown limits newly synthesized mtDNA and Ox-mtDNA formation and subsequently blocks NLRP3 inflammasome activation in microglia/macrophages. Nordihydroguaiaretic acid (NDGA), as a CMPK2 inhibitor, is discovered to reduce neuroinflammation and ischemic injury in mice and prevent the inflammatory responses in primary human monocytes from ischemic patients. Thus, these findings identify CMPK2 as a promising therapeutic target for ischemic stroke and other brain disorders associated with neuroinflammation.

Objective: Oral squamous cell carcinoma (OSCC) is the most frequent oral malignancy with a poor prognosis, in which tumor-infiltrating immune cells may play a critical role. Therefore, our study aims to screen potential immune cells and immune-related genes for predicting OSCC prognosis. Methods: A total of 310 OSCC patients with full transcriptional data and clinical characteristics were extracted from the TCGA database. Then, we obtained their abundance of tumor-infiltrating immune cells on TIMER 2.0 and analyzed them using xCell method. Univariate and multivariate Cox regressions were applied successively to identify the immune cells associated with overall survival of OSCC patients. Furthermore, we screened the prognostic genes that related to the identified immune cells and validated their expressions by immunohistochemistry. Results: CD4⁺ central memory T (T_CM) cell was recognized as the sole independent immune cell correlated with OSCC prognosis (p = 0.0085). A novel nomogram based on CD4⁺ T_CM cell abundance was established for predicting the prognosis of OSCC patients, with calibration plots showing good performance for 1-, 3-, 5-year overall survival. Thirty-four related prognostic genes were screened according to the differential abundance of CD4⁺ T_CM cell infiltration. In immunohistochemistry analysis, DEFB1 showed a significant positive relationship with the density of CD4⁺ T_CM cells (p = 0.0075). Conclusion: CD4⁺ central memory T cell was proposed as an independent prognostic biomarker for OSCC patients. DEFB1 might positively regulate the abundance of tumor-infiltrating CD4⁺ T_CM cells, thus improving OSCC prognosis. Our findings may provide a new insight into better prognosis prediction and precise medicine for OSCC.

Stroke is a leading cause of adult disability worldwide, and better drugs are needed to promote functional recovery after stroke. Growing evidence suggests the critical role of network excitability during the repair phase for stroke recovery. Here, we show that β-hydroxybutyrate (β-HB), an essential ketone body (KB) component, is positively correlated with improved outcomes in patients with stroke and promotes functional recovery in rodents with stroke during the repair phase. These beneficial effects of β-HB depend on HDAC2/HDAC3-GABA transporter 1 (GAT-1) signaling-mediated enhancement of excitability and phasic GABA inhibition in the peri-infarct cortex and structural and functional plasticity in the ipsilateral cortex, the contralateral cortex, and the corticospinal tract. Together with available clinical approaches to elevate KB levels, our results offer a clinically translatable means to promote stroke recovery. Furthermore, GAT-1 can serve as a pharmacological target for developing drugs to promote functional recovery after stroke.

Attention has been paid to the early diagnosis of Alzheimer’s disease, due to the maximum benefit acquired from the early-stage intervention and treatment. However, the sensing techniques primarily depended upon for neuroimaging and immunological assays for the detection of AD biomarkers are expensive, time-consuming and instrument dependent. Here, we developed a multichannel fluorescent tongue consisting of four fluorescent dyes and GO through electrostatic and π–π interaction. The array distinguished multiple aggregation states of 1 µM Aβ40/Aβ42 with 100% prediction accuracy via 10-channel signal outputs, illustrating the rationality of the array design. Screening vital sensor elements for the simplified sensor array and the optimization of sensing system was achieved by machine learning algorithms. Moreover, our sensing tongue was able to detect the aggregation states of Aβ40/Aβ42 in serum, demonstrating the great potential of multichannel array in diagnosing the Alzheimer’s diseases.