Early Laparoscopic Cholecystectomy Versus Percutaneous Cholecystostomy Followed by Delayed Laparoscopic Cholecystectomy in Patients with Grade II Acute Cholecystitis According to Tokyo Guidelines TG18.

In the past, most patients with acute cholecystitis (AC) were treated conservatively. However, strong evidence from various studies has shown that laparoscopic cholecystectomy (LC) is safe and should be the primary treatment for AC. However, this may not be the case for all AC grades.

An Efficient and Accessible Hectogram-Scale Synthesis for the Selective O-GlcNAcase Inhibitor Thiamet-G.

Altered levels of intracellular protein glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) have emerged as being involved in various cancers and neurodegenerative diseases. OGA inhibitors have proven critically useful as tools to help understand the roles of O-GlcNAc, yet accessing large quantities of inhibitors necessary for many animal studies remains a challenge. Herein is described a scalable method to produce Thiamet-G, a potent, selective, and widely used brain-permeable OGA inhibitor.

Chemical Tools for Monitoring and Targeting Collagen Cross-linking.

The formation of collagen, the most abundant protein in mammals, is vital for the integrity of skin, tendons, and tissue in essentially any organ. Excessive collagen formation is, however, characteristic of fibrotic and malignant diseases, which include major global health issues. The diagnosis of abnormal collagen production and deposition is, therefore, critical for disease prognosis and helps guide treatment decisions.

Direct and indirect regulation of β-glucocerebrosidase by the transcription factors USF2 and ONECUT2.

Mutations in GBA1 encoding the lysosomal enzyme β-glucocerebrosidase (GCase) are among the most prevalent genetic susceptibility factors for Parkinson's disease (PD), with 10-30% of carriers developing the disease. To identify genetic modifiers contributing to the incomplete penetrance, we examined the effect of 1634 human transcription factors (TFs) on GCase activity in lysates of an engineered human glioblastoma line homozygous for the pathogenic GBA1 L444P variant. Using an arrayed CRISPR activation library, we uncovered 11 TFs as regulators of GCase activity.