Alzheimer’s disease (AD) is the most prevalent form of dementia among elderly people worldwide. Cerebrospinal fluid (CSF) is the optimal fluid source for AD biomarkers, while serum biomarkers are much more achievable. To search for novel diagnostic AD biomarkers, we performed a quantitative proteomic analysis of CSF and serum samples from AD and normal cognitive controls (NC). CSF and serum proteomes were analyzed via data-independent acquisition quantitative mass spectrometry. Our bioinformatic analysis was based on Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. In comparison to the controls, 8 proteins were more abundant in AD CSF, and 60 were less abundant in AD CSF, whereas 55 proteins were more and 10 were less abundant in the serum samples. ATPase-associated activity for CSF and mitochondrial functions for CSF and serum were the most enriched GO terms of the DEPs. KEGG enrichment analysis showed that the most significant pathways for the differentially expressed proteins were the N-glycan biosynthesis pathways. The area under the curve (AUC) values for CSF sodium-/potassium-transporting ATPase subunit beta-1 (AT1B1), serglycin (SRGN), and thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) were 0.867 (p = 0.004), 0.833 (p = 0.008), and 0.783 (p = 0.025), respectively. A panel of the above three CSF proteins accurately differentiated AD (AUC = 0.933, p = 0.001) from NC. The AUC values for serum probable phospholipid-transporting ATPase IM (AT8B4) and SRGN were moderate. The AUC of the CSF SRGN + serum SRGN was 0.842 (p = 0.007). These novel AD biomarker candidates are mainly associated with inflammation, ATPase activity, oxidative stress, and mitochondrial dysfunction. Further studies are needed to investigate the molecular mechanisms by which these potential biomarkers are involved in AD.

Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.

Cerenkov radiation (CR) from radionuclides and megavoltage X-ray radiation can act as an in situ light source for deep cancer theranostics, overcoming the limitations of external light sources. Despite the blue-weighted emission and low quantum yield of CR, activatable probes-mediated CR can enhance the in-vivo diagnostic signals by Cerenkov resonance energy transfer and also can produce therapeutic effects by reactive species generation/drug release, greatly promoting the biomedical applications of CR. In this review, we describe the principles and sources of CR, construction of CR-activated probes and their application to tumor optical imaging and therapy. Finally, future prospects for the design and biomedical application of CR-activated probes are discussed.

Background: ¹⁸F-FAPI-04 PET/CT shows promise in detecting peritoneal metastases (PM), but its superiority over ¹⁸F-FDG PET/CT for lesion detection and predicting chemotherapy benefit remains unclear. Purpose: To compare ¹⁸F-FAPI-04 and ¹⁸F-FDG PET/CT imaging features in PM and assess predictive value of ¹⁸F-FAPI-04 for chemotherapy efficacy. Methods: 39 pathologically confirmed PM patients with digestive malignancies underwent concurrent ¹⁸F-FAPI-04 and ¹⁸F-FDG PET/CT. Semi-quantitative parameters, including SUV_max, tumor/liver ratio (T/L), tumor/mediastinal blood pool ratio (T/B), were analyzed. The tracer uptake was compared via Wilcoxon tests. The relationships between ¹⁸F-FAPI-04 uptake with FAP and α-SMA expression were analyzed using Pearson correlation. Patients were divided into different short-term outcome groups (responders vs. non-responders) according to RECIST criteria (v.1.1) after chemotherapy. Post-chemotherapy outcomes were evaluated using logistic regression. Results: Patients (median age 62; 16 females, 23 males) included pancreatic (n = 17), cholangiocarcinoma (n = 8), gastric (n = 6), and colorectal cancers (n = 8). ¹⁸F-FAPI-04 demonstrated significantly higher SUV_max, T/L, and T/B than ¹⁸F-FDG (P < 0.05). Pancreaticobiliary cancers (pancreatic/cholangiocarcinoma) exhibited higher 18F-FAPI-04 uptake than gastroenteric cancers (gastric/colorectal) (P < 0.05), though no differences existed within subgroups. ¹⁸F-FAPI-04 parameters positively correlated with FAP and α-SMA expression. In univariate analysis, ¹⁸F-FAPI-04 uptake differed significantly between responders and non-responders. Multivariate analysis identified SUV_max as an independent predictor (OR = 1.354, 95%CI:1.025–1.788, P = 0.033). Optimal ¹⁸F-FAPI-04 cut-offs for distinguishing outcomes were SUV_max=11.05 (AUC = 0.783; sensitivity = 70.60%, specificity = 80.40%), T/L = 7.53 (AUC = 0.717; 58.82%, 81.82%), and T/B = 8.76 (AUC = 0.751; 64.71%, 86.37%). Conclusion: ¹⁸F-FAPI-04 PET/CT outperforms ¹⁸F-FDG in PM detection, with semi-quantitative parameters predicting chemotherapy response.