No abstract

Objectives: The therapeutic efficacy of metal stents (MSs) for pancreatic fluid collections (PFCs) is invariably controversial. Here, we conducted a meta-analysis to summarize the results of efficacy of MSs and plastic stents (PSs) in PFC drainage. Subjects and Methods: We performed a literature search of PubMed/MEDLINE, EMBASE, and COCHRANE for all of the published studies regarding the use of MSs and PSs for endoscopic transmural drainage of PFCs from January, 1 2015 to June 1, 2020. We extracted data from 9 studies (1359 patients) that met the inclusion criteria. The main outcome measures were the rates of treatment success, including technique success and clinical success (CS), adverse events, recurrence, procedure time, and length of hospital stay (LOS). Results: There was no difference in overall technique success between patients treated with MSs and PSs for PFCs. However, MSs showed a higher CS rate 92% versus 82% (P<0.01) and a lower overall adverse event rate 20% versus 31% (P<0.01) than PSs. The recurrence rate of PFCs using MSs also had significant advantages over PSs 3% versus 10% (P<0.01) and MSs needed a shorter procedure time than PSs (26.73 vs. 45.40 min, P<0.01). In comparing direct endoscopic necrosectomy use and LOS, there was no difference between MSs and PSs. Conclusions: Bringing together the results of the current study, endoscopic ultrasound-guided drainage of PFCs using MSs may be superior to PSs in terms of CS, adverse events rates and recurrence rate, with similar LOS and direct endoscopic necrosectomy use.

CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6) is a master regulator of PD-L1. By binding PD-L1 at the plasma membrane and recycling endosomes, CMTM6 prevents the lysosomal degradation of PD-L1 and maintains its cell surface expression, thus stabilizing the inhibitory PD-1/PD-L1 axis. However, the mechanism of CMTM6/PD-L1 interaction is unknown. Here we report the first experimentally determined structure of CMTM6 from bovine. Combined with a low-resolution cryo-EM map, computational docking analysis and a protein binding assay an interaction model between CMTM6 and PD-L1 was proposed, providing a structural framework for the CMTM6 regulation on PD-L1.

Zinc transporter 8 (ZnT8) is mainly expressed in pancreatic islet β cells and is responsible for H+-coupled uptake (antiport) of Zn2+ into insulin secretory granules. Structures of human ZnT8 and its prokaryotic homolog YiiP have provided structural basis for constructing a plausible transport cycle for Zn2+. However, the mechanistic role that H+ plays in the transport process remains elusive. Here we present two cryo-EM structures of ZnT8 from Xenopus tropicalis (xtZnT8) captured in the presence of either abundant Zn2+ or abundant H+. Combined with a microscale thermophoresis analysis, our data suggest that binding of Zn2+ to the transmembrane Zn2+-binding site drives xtZnT8 to the outward-facing state. Surprisingly, binding of H+ to xtZnT8 is not sufficient to drive the transporter to an inward-facing state, suggesting that protonation alone is not a determining factor to establish an inward-facing conformation during Zn2+ transport. Instead, the role of protonation appears to unbind and release Zn2+ from the transmembrane site in the outward-facing state of xtZnT8, thus allowing an inward-facing isomerization to occur for the next cycle.