Nasal delivery of polymeric nanoDisc mobilizes a synergy of central and peripheral amyloid-ß clearance to treat Alzheimer's disease.

The disequilibrium of amyloid ß-peptide (Aß) between the central and peripheral pools has been claimed as an initiating event in Alzheimer's disease (AD). In this study, we employ discoidal high-density lipoproteins (HDL-Disc) mimicking Aß antibody for directional flux of Aß from central to peripheral catabolism, with desirable safety and translation potential. Structurally, HDL-Disc assembly (polyDisc) is prepared with aid of chitosan derivative polymerization. After intranasal administration and response to slightly acidic nasal microenvironment, polyDisc depolymerizes into carrier-free HDL-Disc with chitosan derivatives that adhere to the mucosal layer to reversibly open tight junctions, helping HDL-Disc penetrate the olfactory pathway into brain. Thereafter, HDL-Disc captures Aß into microglia for central clearance or ferries Aß out of the brain for liver-mediated compensatory catabolism. For synergy therapy, intranasal administration of polyDisc can effectively reduce intracerebral Aß burden by 97.3% and vascular Aß burden by 73.5%, ameliorate neurologic damage, and rescue memory deficits in APPswe/PS1dE9 transgenic AD mice with improved safety, especially vascular safety. Collectively, this design provides a proof of concept for developing Aß antibody mimics to mobilize a synergy of central and peripheral Aß clearance for AD treatment.

The necessarity of treatment for small gastric subepithelial tumors (1-2 cm) originating from muscularis propria: an analysis of 972 tumors.

BACKGROUND AND OBJECTIVES: Up till now, there are still controversies about the specific indication of endoscopic resection for small gastric subepithelial tumors (gSETs) originating from muscularis propria. We aimed to investigate the safety of endoscopic resection and postoperative pathology analysis. METHOD: The patients with primary small gSETs originating from muscularis propria, treated by endoscopic resection in the endoscopic center of Shengjing Hospital between January, 2011 and September, 2019 were enrolled. The complete resection rate, adverse events and clinicopathological features were recorded. RESULT: A total of 936 patients with 972 gastric SETs ≤ 2 cm originating from muscularis propria were included in our study. All the lesions were successfully treated by endoscopic resection. Nearly half of lesions were proved to be gastrointestinal stromal tumor (GIST) [n = 411 (42.3%)] according to postoperative pathology. All the objects were further subdivided into 2 groups, ≤ 1 cm, > 1 and ≤ 2 cm gSETs. The risk of gastric GIST of intermediate/high risk in the group (> 1 and ≤ 2 cm gSETs) is 8.41 times as that of gastric GIST in the group (the size of gastric ≤ 1 cm gSETs) (P < 0.05). CONCLUSION: Endoscopic resection is a safe and effective treatment for small gSETs. gSETs (1-2 cm) is more risky than gSETs (≤ 1 cm) and should be resected. This should be evaluated by further studies.

Methods to increase the diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesions: An updated review.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a means to procure adequate specimens for histological and cytologic analysis. The ideal EUS-FNA should be safe, accurate, and have a high sample adequacy rate and low adverse events rate. In recent years, many guidelines and trials on EUS-FNA have been published. The purpose of this article is to provide an update on the influence of some of the main factors on the diagnostic efficiency of EUS-FNA as well as a rare but serious complication known as needle tract seeding.

De novo assembly of Amorpha fruticosa L. transcriptome in response to drought stress provides insight into the tolerance mechanisms.

BACKGROUND: Amorpha fruticosa L. is a deciduous shrub that is native to North America and has been introduced to China as an ornamental plant. In order to clarify the drought resistance characteristics of Amorpha fruticosa L. and excavate the related genes involved in drought resistance regulation pathway, the mechanism of drought resistance stress of Amorpha fruticosa L. was revealed by the changes of transcriptome of Amorpha fruticosa L. under drought stress.Through the changes of the transcriptome of Amorpha fruticosa L. under drought stress, the mechanism of anti-stress of Amorpha fruticosa L. could be revealed. METHODS: Different concentrations of polyethylene glycol-6000 (PEG-6000) was used to simulate drought stress, and transcriptomic analysis was used to reveal the changes of gene expression patterns in Amorpha fruticosa L. seedlings. RESULTS: Results showed that Amorpha fruticosa L. seedlings were seriously affected by PEG-6000. As for the differently expressed genes (DEGs), most of them were up-regulated. The additional Go and KEGG analysis results showed that DEGs were functionally enriched in cell wall, signal transduction and hormonal regulation related pathways. DEGs like AfSOD, AfHSP, AfTGA, AfbZIP and AfGRX play roles in response to drought stress. CONCLUSION: In conclusion, Amorpha fruticosa L. seedlings were sensitive to drought, which was different from Amorpha fruticosa L. tree, and the genes functions in drought stress responses via ABA-independent pathways. The up-regulation of Salicylic acid signal related DEGs (AfTGA and AfPR-1) indicated that Salicylic acid play a key role in response to drought stress in Amorpha fruticosa L.

Recent Advances in the Potential Use of Circular RNA for the Diagnosis and Treatment of Pancreatic Cancer.

There are few biomarkers available for the early diagnosis and prognostic evaluation of pancreatic cancer. In addition, the development of targeted therapy for pancreatic cancer is an unmet need due to the lack of molecular targets. With the continuous progress in circular RNA (circRNA)-related research, its role in the occurrence and development of pancreatic cancer has been discovered and gradually recognized. Therefore, circRNA may represent a novel marker for early diagnosis of this disease and a focus of targeted clinical therapy. CircRNA is a type of non-coding RNA with a closed circular structure formed by covalent bonds. Some circRNAs can act as "sponges" to adsorb microRNAs (miRNAs) and play the role of competitive endogenous RNA (ceRNA) to remove their inhibitory effects on the target genes of miRNA. Thus, they can indirectly restore the expression of target genes. The circRNA-miRNA-mRNA network plays a regulatory role in the proliferation, invasion, metastasis, and other biological behaviors of pancreatic cancer. Given the recent advances in circRNA, this review seeks to provide an overview of the biological function of circRNA and highlights the recent research progress regarding the molecular mechanism of circRNA for the clinical diagnosis and treatment of pancreatic cancer.