Endoscopic closure of large gastric defects with a novel through-the-scope closing device in a porcine model (with videos).

BACKGROUND AND AIM: After endoscopic full-thickness resection (EFTR), defects require a reliable and sustained closure. We present a novel, through-the-scope "bow-tie" (TTS-BT) closing device enabling direct defect closure without scope withdrawal. This preclinical study aimed to evaluate the feasibility and safety of this device for large defect closure after EFTR in a porcine model. METHODS: Exposed EFTR was performed for virtual lesions > 2 cm in the stomach of twelve pigs. Subsequently, TTS-BT closing devices were used for defect closure. Conventional metal clips were used to close any remaining defects. Gastroscopy was performed for 8 weeks to examine the wound sites and the pigs were subsequently sacrificed. After sacrificing the pigs, the wound healing was histologically verified by hematoxylin-eosin (HE) staining. The primary outcome was a successful closure rate, while the secondary outcomes were complete healing rate, closure time, and incidence of adverse events. RESULTS: The median long and short diameters of perforations were 4.0 (3.0-6.0) cm and 3.0 (2.0-4.0) cm, respectively. Defect closure using novel TTS-BT closure devices and conventional metal clips was successfully performed in all pigs. Complete healing was achieved in the defects of 12 pigs. The median closure time was 13 (9-38) minutes. No serious adverse events occurred during the 8-week follow-up. CONCLUSIONS: The novel TTS-BT closure device is feasible and safe for closing large gastric perforations and could be a promising tool for clinical practice.

Modular synthesis of clickable peptides via late-stage maleimidation on C(7)-H tryptophan.

Cyclic peptides have attracted tremendous attention in the pharmaceutical industry owing to their excellent cell penetrability, stability, thermostability, and drug-like properties. However, the currently available facile methodologies for creating such peptides are rather limited. Herein, we report an efficient and direct peptide cyclization via rhodium(III)-catalyzed C(7)-H maleimidation. Notably, this catalytical system has excellent regioselectivity and high tolerance of functional groups which enable late-stage cyclization of peptides. This architecture of cyclic peptides exhibits higher bioactivity than its parent linear peptides. Moreover, the Trp-substituted maleimide displays excellent reactivity toward Michael addition, indicating its potential as a click functional group for applications in chemical biology and medicinal chemistry. As a proof of principle, RGD-GFLG-DOX, which is a peptide-drug-conjugate, is constructed and it displays a strong binding affinity and high antiproliferative activity toward integrin-αvß3 overexpressed cancer cell lines. The proposed strategy for rapid preparation of stapled peptides would be a robust tool for creating peptide-drug conjugates.

CITEdb: a manually curated database of cell-cell interactions in human.

MOTIVATION: The interactions among various types of cells play critical roles in cell functions and the maintenance of the entire organism. While cell-cell interactions are traditionally revealed from experimental studies, recent developments in single-cell technologies combined with data mining methods have enabled computational prediction of cell-cell interactions, which have broadened our understanding of how cells work together, and have important implications in therapeutic interventions targeting cell-cell interactions for cancers and other diseases. Despite the importance, to our knowledge, there is no database for systematic documentation of high-quality cell-cell interactions at the cell type level, which hinders the development of computational approaches to identify cell-cell interactions. RESULTS: We develop a publicly accessible database, CITEdb (Cell-cell InTEraction database, https://citedb.cn/), which not only facilitates interactive exploration of cell-cell interactions in specific physiological contexts (e.g. a disease or an organ) but also provides a benchmark dataset to interpret and evaluate computationally derived cell-cell interactions from different tools. CITEdb contains 728 pairs of cell-cell interactions in human that are manually curated. Each interaction is equipped with structured annotations including the physiological context, the ligand-receptor pairs that mediate the interaction, etc. Our database provides a web interface to search, visualize and download cell-cell interactions. Users can search for cell-cell interactions by selecting the physiological context of interest or specific cell types involved. CITEdb is the first attempt to catalogue cell-cell interactions at the cell type level, which is beneficial to both experimental, computational and clinical studies of cell-cell interactions. AVAILABILITY AND IMPLEMENTATION: CITEdb is freely available at https://citedb.cn/ and the R package implementing benchmark is available at https://github.com/shanny01/benchmark. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Double anchor lock fixing method to prevent stent displacement in endoscopic ultrasound-guided gastroenterostomy: a porcine study.

BACKGROUND: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is widely used in patients with gastric outlet obstruction (GOO). Recurrence of obstruction symptoms caused by stent migration is the major reason for reintervention in EUS-GE. To solve this problem, we proposed developing a double anchor lock (DAL) fixing stent method for EUS-GE. The safety and efficacy of the DAL fixing stent method were evaluated in this study. METHODS: Sixteen Bama miniature pigs were randomly divided into an experimental group (n = 8) and a control group (n = 8). A gastric outlet obstruction model was established for all the pigs. The experimental group was treated with the DAL fixing stent method for EUS-GE, while the control group was treated with EUS-GE. Three-month stent migration rate, remission rate of GOO, re-occlusion intervention rate, weight change, and incidence of procedure-related complications of EUS-GE were analyzed and estimated in the two groups. RESULTS: EUS-GE was successfully completed in every subject in both groups. Symptoms of digestive tract obstruction can be relieved in all animals. The stent existence rate in the 3 months was higher in the experimental group than in the control group (87.5% vs. 12.5%, P = 0.012). Except for one animal in the experimental group in which there was pneumoperitoneum due to a stent insertion failure, no animal experienced bleeding or perforation. CONCLUSION: The DAL fixing stent method, which can effectively prevent stent migration, is safe and simple. EUS-GE can effectively relieve the symptoms of digestive tract obstruction.

Flexural Behavior of Fire-Damaged Prefabricated RC Hollow Slabs Strengthened with CFRP versus TRM.

In this paper, carbon fiber reinforced polymer (CFRP) and textile reinforced mortar (TRM) strengthening techniques were proposed to retrofit and strengthen fire-damaged prefabricated concrete hollow slabs. A total of six slabs, from an actual multi-story masonry building, were tested to investigate the flexural performance of reinforced concrete (RC) hollow slabs strengthened with TRM and CFRP. The investigated parameters included the strengthening method (CFRP versus TRM), the number of CFRP layers, and with or without fire exposure. One unstrengthened slab and one TRM strengthened slab served as the control specimens without fire exposure. The remaining four slabs were first exposed to ISO-834 standard fire for 1 h, and then three of them were strengthened with CFRP or TRM. Through the four-point bending tests at ambient temperature, the failure modes, load and deformation response were recorded and discussed. Both CFRP and TRM strengthening methods can significantly increase the cracking load and peak load of the fire-damaged hollow slabs, as well as the stiffness in the early stage. The prefabricated hollow slabs strengthened by CFRP have better performance in the ultimate bearing capacity, but the ductility reduced with the increase of CFRP layers. Meanwhile, the TRM strengthening technique is a suitable method for the performance improvement of fire-damaged hollow slabs, in terms of not only the load capacity, especially the cracking load, but also the flexural stiffness and deformation capacity.