Asymmetrical branched PEG-modified liposomes evade anti-PEG antibody recognition to abolish accelerated blood clearance and amplify tumor drug accumulation.

The prevalence of anti-polyethylene glycol (PEG) antibodies poses a significant challenge for the clinical translation of PEGylated liposomes, leading to an accelerated blood clearance (ABC) phenomenon and diminishing therapeutic effectiveness. To address this limitation, we designed an asymmetrical branched PEG derivative (mPEG-DSPE) and prepared mPEG-DSPE-modified liposomes, which included 1,1'-dioctadecyl-3,3,3,3'-tetramethylindo dicarbocyanine iodide liposomes (P-DiR) and mitomycin C lipid prodrug (MSC) liposomes (P-MSC) to minimize the binding of anti-PEG antibodies. Cellular binding assays revealed that the anti-PEG antibody binding rate for P-DiR was only 0.

Structures of two LarA-like nickel-pincer nucleotide cofactor-utilizing enzymes with a single catalytic histidine residue.

The nickel pincer nucleotide (NPN) cofactor catalyzes the racemization/epimerization of α-hydroxy acids in enzymes of the LarA family. The established proton-coupled hydride transfer mechanism requires two catalytic histidine residues that alternately act as general acids and general bases. Notably, however, a fraction of LarA homologs (LarAHs) lack one of the active site histidine residues, replacing it with an asparaginyl side chain that cannot participate in acid/base catalysis.

PathCare: Integrating Clinical Pathway Information to Enable Healthcare Prediction at the Neuron Level.

Electronic Health Records (EHRs) offer valuable insights for healthcare prediction. Existing methods approach EHR analysis through direct imputation techniques in data space or representation learning in feature space. However, these approaches face the following two critical limitations: first, they struggle to model long-term clinical pathways due to their focus on isolated time points rather than continuous health trajectories; second, they lack mechanisms to effectively distinguish between clinically relevant and redundant features when observations are irregular.

Antimicrobial Peptides Expressed by the Polyaminoglycoside Nanosystem for Bacterial Peritonitis Management via Inflammation Modulation.

Peritonitis, a prevalent and dangerous condition, can result from trauma, surgery, liver cirrhosis, peritoneal dialysis, and gastrointestinal issues. If not effectively managed, it can cause systemic infection, leading to complications, such as sepsis and bacteremia. LL37, an antimicrobial peptide of the innate immune system, exhibits broad-spectrum antibacterial activity and potent immune-modulating functions, serving as a critical defense against infections.

Therapeutic Mechanism of Kynurenine, a Metabolite of Probiotics, on Atopic Dermatitis in Mice.

Atopic Dermatitis (AD) is a common inflammatory skin disease characterized primarily by its chronic and recurrent nature. This has a significant impact on productivity and human longevity. Dysbiosis of gut flora has been demonstrated to be significantly associated with the progression of AD.