Tumor-derived exosomal PD-L1: a new perspective in PD-1/PD-L1 therapy for lung cancer.

Exosomes play a crucial role in facilitating intercellular communication within organisms. Emerging evidence indicates that a distinct variant of programmed cell death ligand-1 (PD-L1), found on the surface of exosomes, may be responsible for orchestrating systemic immunosuppression that counteracts the efficacy of anti-programmed death-1 (PD-1) checkpoint therapy. Specifically, the presence of PD-L1 on exosomes enables them to selectively target PD-1 on the surface of CD8+ T cells, leading to T cell apoptosis and impeding T cell activation or proliferation. This mechanism allows tumor cells to evade immune pressure during the effector stage. Furthermore, the quantification of exosomal PD-L1 has the potential to serve as an indicator of the dynamic interplay between tumors and immune cells, thereby suggesting the promising utility of exosomes as biomarkers for both cancer diagnosis and PD-1/PD-L1 inhibitor therapy. The emergence of exosomal PD-L1 inhibitors as a viable approach for anti-tumor treatment has garnered significant attention. Depleting exosomal PD-L1 may serve as an effective adjunct therapy to mitigate systemic immunosuppression. This review aims to elucidate recent insights into the role of exosomal PD-L1 in the field of immune oncology, emphasizing its potential as a diagnostic, prognostic, and therapeutic tool in lung cancer.

Role in post-translational modification of M2-type pyruvate kinase in tumorigenesis and development. / M2åž‹ä¸™é ®é ¸æ¿€é ¶ç¿»è¯‘åŽä¿®é¥°åœ¨è‚¿ç˜¤å‘ç”Ÿå’Œå‘å±•ä¸­çš„ä½œç”¨.

PKM2, also known as M2-type pyruvate kinase, has attracted significant attention due to its crucial role in glycolysis and its abnormal expression in various tumors. With the discovery of PKM2's non-metabolic functions, the transition between its pyruvate kinase activity (in the tetrameric form in the cytoplasm) and protein kinase activity (in the dimeric form in the nucleus) has once again made PKM2 a target of interest in cancer research. Studies have shown that PKM2 is a protein susceptible to various post-translational modifications, and different post-translational modifications play important regulatory roles in processes such as PKM2 cellular localization, structure, and enzyme activity conversion. In this review, we focused on the recent progress of multiple post-translational modifications of PKM2 and their important roles in tumor initiation and development. For example, phosphorylation and acetylation promote nuclear translocation by altering PKM2 cell localization; glycosylation and ubiquitination can promote the formation of dimer structure by affecting the structural transformation of PKM2; succinylation and redox modification promoted the enhancement of PKM2 kinase activity by affecting the transformation of kinase activity. Both changes affect the structure and cell localization of PKM2 and they play a role in promoting or inhibiting tumor development via altering its kinase activity.

An MRI-Based Radiomics Nomogram to Assess Recurrence Risk in Sinonasal Malignant Tumors.

BACKGROUND: Sinonasal malignant tumors (SNMTs) have a high recurrence risk, which is responsible for the poor prognosis of patients. Assessing recurrence risk in SNMT patients is a current problem. PURPOSE: To establish an MRI-based radiomics nomogram for assessing relapse risk in patients with SNMT. STUDY TYPE: Retrospective. POPULATION: A total of 143 patients with 68.5% females (development/validation set, 98/45 patients). FIELD STRENGTH/SEQUENCE: A 1.5-T and 3-T, fat-suppressed fast spin echo (FSE) T2-weighted imaging (FS-T2WI), FSE T1-weighted imaging (T1WI), and FSE contrast-enhanced T1WI (T1WI + C). ASSESSMENT: Three MRI sequences were used to manually delineate the region of interest. Three radiomics signatures (T1WI and FS-T2WI sequences, T1WI + C sequence, and three sequences combined) were built through dimensional reduction of high-dimensional features. The clinical model was built based on clinical and MRI features. The Ki-67-based and tumor-node-metastasis (TNM) model were established for comparison. The radiomics nomogram was built by combining the clinical model and best radiomics signature. The relapse-free survival analysis was used among 143 patients. STATISTICAL TESTS: The intraclass/interclass correlation coefficients, univariate/multivariate Cox regression analysis, least absolute shrinkage and selection operator Cox regression algorithm, concordance index (C index), area under the curve (AUC), integrated Brier score (IBS), DeLong test, Kaplan-Meier curve, log-rank test, optimal cutoff values. A P value < 0.05 was considered statistically significant. RESULTS: The T1 + C-based radiomics signature had best prognostic ability than the other two signatures (T1WI and FS-T2WI sequences, and three sequences combined). The radiomics nomogram had better prognostic ability and less error than the clinical model, Ki-67-based model, and TNM model (C index, 0.732; AUC, 0.765; IBS, 0.185 in the validation set). The cutoff values were 0.2 and 0.7 and then the cumulative risk rates were calculated. DATA CONCLUSION: A radiomics nomogram for assessing relapse risk in patients with SNMT may provide better prognostic ability than the clinical model, Ki-67-based model, and TNM model. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 5.

Nickel phosphide on Ni foam as anode and peroxymonosulfate as the chemical oxidizer for effective direct urea fuel cell.

The direct urea fuel cell (DUFC) is a low cost and competitive approach for contemporaneous urine or urea-contaminated wastewater treatment and electricity generation. However, the lack of efficient urea oxidation reaction (UOR) electrocatalysts and suitable electron acceptors remains a challenge for practical applications. Here, we developed a DUFC system using Ni2P@Ni foam as the anode and peroxymonosulfate (PMS) as the chemical oxidizers. The Ni2P@Ni foam anode showed a high oxidation activity for UOR with an onset potential of 0.30 V vs. Ag/AgCl and Tafel slope of 34.4 mV/dec. PMS with high theoretical potential improved the cell voltage to 1.43 V. A power density of DUFC up to 4.91 mW/cm2 was achieved using PMS at room temperature, which was approximately twice as high as using H2O2 (2.38 mW/cm2). NiII/NiIII was the redox active species on the Ni2P anode in the DUFC process, and NiII was electrochemically oxidized to NiIII, which reverted to NiII by urea reduction. When real human urine was used as the fuel, a power density of 4.46 mW/cm2 can be achieved at room temperature. This DUFC with high cell performance showed potential application in urea wastewater treatment.