3D Printed Fused Deposition Modeling (FDM) Capillaries for Chemiresistive Gas Sensors.

This paper discusses the possible use of 3D fused deposition modeling (FDM) to fabricate capillaries for low-cost chemiresistive gas sensors that are often used in various applications. The disadvantage of these sensors is low selectivity, but 3D printed FDM capillaries have the potential to increase their selectivity. Capillaries with 1, 2 and 3 tiers with a length of 1.

Neutral sphingomyelinase 2 inhibitors based on the pyrazolo[1,5-a]pyrimidin-3-amine scaffold.

Neutral sphingomyelinase 2 (nSMase2) has gained increasing attention as a therapeutic target to regulate ceramide production in various disease conditions. Phenyl (R)-(1-(3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[1,2-b]pyridazin-8-yl)-pyrrolidin-3-yl)carbamate (PDDC) is a submicromolar nSMase2 inhibitor and has been widely used to study the pharmacological effects of nSMase2 inhibition. Through screening of compounds containing a bicyclic 5-6 fused ring, larotrectinib containing a pyrazolo[1,5-a]pyrimidine ring was identified as a low micromolar inhibitor of nSMase2.

Design, Synthesis, Biological Evaluation, and Crystallographic Study of Novel Purine Nucleoside Phosphorylase Inhibitors.

Purine nucleoside phosphorylase (PNP) is a well-known molecular target with potential therapeutic applications in the treatment of T-cell malignancies and/or bacterial/parasitic infections. Here, we report the design, development of synthetic methodology, and biological evaluation of a series of 30 novel PNP inhibitors based on acyclic nucleoside phosphonates bearing a 9-deazahypoxanthine nucleobase. The strongest inhibitors exhibited IC values as low as 19 nM (human PNP) and 4 nM ( () PNP) and highly selective cytotoxicity toward various T-lymphoblastic cell lines with CC values as low as 9 nM.

Hyperprogression on anti-PD-1 treatment. Is subsequent therapy feasible? A case report and review of the literature.

Background: Hyperprogressive disease (HPD) is a new phenomenon that has emerged in the immunotherapy era. HPD is defined as a rapid tumour growth with detrimental effect on the patient condition and disease course. The management and treatment following HPD is not defined.

Acyclic nucleoside phosphonates with 2-aminothiazole base as inhibitors of bacterial and mammalian adenylate cyclases.

A series of novel acyclic nucleoside phosphonates (ANPs) was synthesized as potential adenylate cyclase inhibitors, where the adenine nucleobase of adefovir (PMEA) was replaced with a 5-substituted 2-aminothiazole moiety. The design was based on the structure of MB05032, a potent and selective inhibitor of fructose 1,6-bisphosphatase and a good mimic of adenosine monophosphate (AMP). From the series of eighteen novel ANPs, which were prepared as phosphoroamidate prodrugs, fourteen compounds were potent (single digit micromolar or submicromolar) inhibitors of Bordetella pertussis adenylate cyclase toxin (ACT), mostly without observed cytotoxicity in J774A.