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Proteins with intrinsically disordered regions (IDRs) often undergo phase separation to control their functions spatiotemporally. Changing the pH alters the protonation levels of charged sidechains, which in turn affects the attractive or repulsive force for phase separation. In a cell, the rupture of membrane‐bound compartments, such as lysosomes, creates an abrupt change in pH. However, how proteins' phase separation reacts to different pH environments remains largely unexplored. Here, using extensive mutagenesis, NMR spectroscopy, and biophysical techniques, it is shown that the assembly of galectin‐3, a widely studied lysosomal damage marker, is driven by cation‐π interactions between positively charged residues in its folded domain with aromatic residues in the IDR in addition to π–π interaction between IDRs. It is also found that the sole two negatively charged residues in its IDR sense pH changes for tuning the condensation tendency. Also, these two residues may prevent this prion‐like IDR domain from forming rapid and extensive aggregates. These results demonstrate how cation‐π, π–π, and electrostatic interactions can regulate protein condensation between disordered and structured domains and highlight the importance of sparse negatively charged residues in prion‐like IDRs. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of combined anti-vascular endothelial growth factor (VEGF) agents, oral glucocorticoid, and laser photocoagulation therapy for macular edema (ME) secondary to retinal vein occlusion (RVO)., Methods: This study included 16 eyes of 16 patients with RVO-associated ME. Patients were initially treated with oral prednisone and an intravitreal anti-VEGF agent. Two weeks later, patients underwent standard laser photocoagulation. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and retinal vessel oxygenation were examined over 12mo., Results: Patients received 1.43±0.81 anti-VEGF injections. Mean baseline and 12-month logMAR BCVA were 0.96±0.51 (20/178) and 0.31±0.88 (20/40), respectively, in eyes with central retinal vein occlusion (CRVO) ( P <0.00), and 1.02±0.45 (20/209) and 0.60±0.49 (20/80), respectively, in eyes with branch retinal vein occlusion (BRVO) ( P <0.00). At 12mo, CRT had significantly decreased in eyes with CRVO ( P <0.00) and BRVO ( P <0.00). Venous oxygen saturation had significantly increased in eyes with CRVO ( P <0.00) and BRVO ( P <0.00). No examined parameters were significantly different between the 2 RVO groups. No serious adverse effects occurred., Conclusion: Anti-VEGF, glucocorticoid, and photocoagulation combination therapy improves visual outcome, prolongs therapeutic effect, and reduces the number of intravitreal injections in eyes with RVO-associated ME.

Aim: To evaluate the efficacy and long-term outcome of infliximab combined with surgery to treat perianal fistulizing Crohn's disease (CD)., Methods: The work was performed as a prospective study. All patients received infliximab combined with surgery to treat perianal fistulizing CD, which was followed by an immunosuppressive agent as maintenance therapy., Results: A total of 28 patients with perianal fistulizing CD were included. At week 30, 89.3% (25/28) of the patients were clinically cured with an average healing time of 31.4 d. The CD activity index decreased to 70.07±77.54 from 205.47±111.13 (P<0.01) after infliximab treatment. The perianal CD activity index was decreased to 0.93±2.08 from 8.54±4.89 (P<0.01). C-reactive protein, erythrocyte sedimentation rate, platelets, and neutrophils all decreased significantly compared with the pretreatment levels (P<0.01). Magnetic resonance imaging results for 16 patients after therapy showed that one patient had a persistent presacral-rectal fistula and another still had a cavity without clinical symptoms at follow-up. After a median follow-up of 26.4 mo (range: 14-41 mo), 96.4% (27/28) of the patients had a clinical cure., Conclusion: Infliximab combined with surgery is effective and safe in the treatment of perianal fistulizing CD, and this treatment was associated with better long-term outcomes.

Aim: To retrospectively evaluate the magnetic resonance imaging (MRI) features of adult retrorectal tumors and compare with histopathologic findings., Methods: MRI features of 21 patients with preoperative suspicion of retrorectal tumors were analyzed based on the histopathological and clinical data., Results: Fourteen benign cystic lesions appeared hypointense on T1-weighted images, and hyperintense on T2-weighted images with regular peripheral rim. Epidermoid or dermoid cysts were unilocular, and tailgut cysts were multilocular. Presence of intracystic intermediate signal intensity was observed in one case of tailgut cyst with a component of adenocarcinoma. Six solid tumors were malignant lesions and showed heterogeneous intensity on MRI. Mucinous adenocarcinomas showed high signal intensity on T2-weighted and mesh-like enhancing areas on fat-suppressed T2-weighted images. There was a fistula between the mass and anus with an internal opening in mucinous adenocarcinomas arising from anal fistula. Gastrointestinal stromal tumors displayed low signal intensity on T1-weighted images, and intermediate to high signal intensity on T2-weighted images. Central necrosis could be seen as a high signal on T2-weighted images., Conclusion: MRI is a helpful technique to define the extent of the retrorectal tumor and its relationship to the surrounding structures, and also to demonstrate possible complications so as to choose the best surgical approach.