Blood-based proteomic analysis is a routine practice for detecting the biomarkers of human disease. The results obtained from blood alone cannot fully reflect the alterations of nerve cells, including neurons and glia cells, in Alzheimer’s disease (AD) brains. Therefore, the present study aimed to investigate novel potential AD biomarker candidates, through an integrated multi-omics approach in AD. We propose a comprehensive strategy to identify high-confidence candidate biomarkers by integrating multi-omics data from AD, including single-nuclei RNA sequencing (snRNA-seq) datasets of the prefrontal and entorhinal cortices, as wells as serum proteomic datasets. We first quantified a total of 124,658 nuclei, 8 cell types, and 3701 differentially expressed genes (DEGs) from snRNA-seq dataset of 30 human cortices, as well as 1291 differentially expressed proteins (DEPs) from serum proteomic dataset of 11 individuals. Then, ten DEGs/DEPs (NEBL, CHSY3, STMN2, MARCKS, VIM, FGD4, EPB41L2, PLEKHG1, PTPRZ1, and PPP1R14A) were identified by integration analysis of snRNA-seq and proteomics data. Finally, four novel candidate biomarkers (NEBL, EPB41L2, FGD4, and MARCKS) for AD further stood out, according to bioinformatics analysis, and they were verified by enzyme-linked immunosorbent assay (ELISA) verification. These candidate biomarkers are related to the regulation process of the actin cytoskeleton, which is involved in the regulation of synaptic loss in the AD brain tissue. Collectively, this study identified novel cell type-related biomarkers for AD by integrating multi-omics datasets from brains and serum. Our findings provided new targets for the clinical treatment and prognosis of AD.

Context: Current medicine for Alzheimer's disease (AD) cannot effectively reverse or block nerve injury. Traditional Chinese Medicine practice and research imply Aconiti lateralis Radix Praeparata (Fuzi) may meet this goal. Objective: Analysing the anti-AD effect of Fuzi and its potential molecular mechanism. Materials and methods: AD model cells were treated with Fuzi in 0-300 mg/mL for 24 h in 37 C. The cell viability (CV) and length of cell projections (LCP) for each group were observed, analysed, and standardised using control as a baseline (CV s and LCP s ). The Fuzi and AD relevant genes were identified basing on databases, and the molecular mechanism of Fuzi anti-AD was predicted by network analysis. Results: Experiment results showed that Fuzi in 0.4 mg/mL boosted LCP (LCP s ¼ 1.2533, p 0.05), and in 1.6-100 mg/mL increased CV (CV s from 1.1673 to 1.3321, p 0.05). Bioinformatics analysis found 17 Fuzi target genes (relevant scores ! 20), showing strong AD relevant signals (RMS_p 0.05, related scores ! 5), enriched in the pathways regulating axon growth, synaptic plasticity, cell survival, proliferation, apoptosis, and death (p 0.05). Especially, GRIN1 and MAPK1 interacted with APP protein and located in the key point of the "Alzheimer's disease" pathway. Discussion and conclusions: These results suggest that Fuzi may have therapeutic and prevention potential in AD, and GRIN1 and MAPK1 may be the core of the pathways of the Fuzi anti-AD process. Fuzi should be studied more extensively, especially for the prevention of AD.

Air-dry density, modulus of rupture (MOR), modulus of elasticity (MOE), compressive strength parallel to grain, and hardness of Catalpa bungei clones were investigated in this study with feasibility of predicting these properties by near-infrared (NIR) spectroscopy. The best candidate 'Luoqiu 3' has been selected from three clones based on wood physical and mechanical property indices. Lower values of wood physical and mechanical properties have been found in the corewood compared to the outerwood. There were significant positive correlations between the air-dry density and mechanical properties. Information from cross section for air-dry density, compressive strength parallel to grain, and hardness yielded prediction models with better effects, along with the best MOR and MOE modeling effects resulted from average sections' spectra collection. Multiplicative scatter correction (MSC) + Savitzky-Golay (S-G) smoothing method has been proved to be the most applicable way. In addition, the predictions from five-point sampling method were slightly better than three-point one. Overall, results suggest NIR spectroscopy was viable to predict the physical and mechanical properties of C. bungei clones with methods developed in this study proved effective in preliminary screening.

Objectives This study was designed to investigate to test the effect of exosomes from urine-derived mesenchymal stem cells (USCs) on the survival and viability of aging retinal ganglion cells (RGCs), and explored the preliminary related mechanisms. Methods Primary USCs were cultured and identified by immunofluorescence staining. Aging RGCs models were established by D-galactose treatment and identified by β-Galactosidase staining. After treatment with USCs conditioned medium (with USCs removal), flow cytometry was performed to examine the apoptosis and cell cycle of RGCs. Cell viability of RGCs was detected by Cell-counting Kit 8 (CCK8) assay. Moreover, gene sequencing and bioinformatics analysis were applied to analyze the genetic variation after medium treatment in RGCs along with the biological functions of differentially expressed genes (DEGs). Results The number of apoptotic aging RGCs was significantly reduced in USCs medium-treated RGCs. Besides, USCs-derived exosomes exert significant promotion on the cell viability and proliferation of aging RGCs. Further, sequencing data analyzed and identified DEGs expressed in aging RGCs and aging RGCs treated with USCs conditioned medium. The sequencing outcomes demonstrated 117 upregulated genes and 186 downregulated genes in normal RGCs group vs aging RGCs group, 137 upregulated ones and 517 downregulated ones in aging RGCs group vs aging RGCs + USCs medium group. These DEGs involves in numerous positive molecular activities to promote the recovery of RGCs function. Conclusions Collectively, the therapeutic potentials of USCs-derived exosomes include suppression on cell apoptosis, enhancement on cell viability and proliferation of aging RGCs. The underlying mechanism involves multiple genetic variation and changes of transduction signaling pathways.

Glioma is considered as the most common primary tumour in the adult brain, with the highest degree of malignancy; among glioma types, glioblastoma is the most invasive and lethal. 1,2 Although multinational treatment strategies have improved in the past few decades, the prognosis of patients with glioma remains unfavourable. 3,4 In particular, the median survival time of patients with high-grade malignant glioma is ≤14 months. 5,6 And the 5-year survival rate of glioblastoma patients is <3%. 7 Therefore, there is an urgency to explore the mechanism of the invasiveness of glioma and to develop new therapeutic strategies, but particularly to find new anticancer drugs. Scutellarin, also known as Erigeron scutellarin, is a traditional Chinese medicine commonly found in Yunnan, Guizhou, Sichuan and other southwestern provinces. Its chemical name is 4′,5,6-trihydrox