Biocatalysis enables the scalable conversion of biobased furans into various furfurylamines.

Biobased furans have emerged as chemical building blocks for the development of materials because of their diverse scaffolds and as they can be directly prepared from sugars. However, selective, efficient, and cost-effective scalable conversion of biobased furans remains elusive. Here, we report a robust transaminase (TA) from Shimia marina (SMTA) that enables the scalable amination of biobased furanaldehydes with high activity and broad substrate specificity. Crystallographic and mutagenesis analyses provide mechanistic insights and a structural basis for understanding SMTA, which enables a higher substrate conversion. The enzymatic cascade process established in this study allows one-pot synthesis of 2,5-bis(aminomethyl)furan (BAMF) and 5-(aminomethyl)furan-2-carboxylic acid from 5-hydroxymethylfurfural. The biosynthesis of various furfurylamines, including a one-pot cascade reaction for BAMF generation using whole cells, demonstrates their practical application in the pharmaceutical and polymer industries.

The High-Resolution Structure Reveals Remarkable Similarity in PD-1 Binding of Cemiplimab and Dostarlimab, the FDA-Approved Antibodies for Cancer Immunotherapy.

Multiple tumors have responded well to immunotherapies, which use monoclonal antibodies to block the immune checkpoint proteins and reactivate the T-cell immune response to cancer cells. Significantly, the anti-PD-1 antibodies pembrolizumab and nivolumab, which were approved in 2014, have revolutionized cancer therapy, demonstrating dramatic improvement and longer duration. The US FDA authorized the third anti-PD-1 medication, cemiplimab, in 2018 for use in patients with cutaneous squamous cell carcinoma. To further understand the molecular mechanism of the antibody drug, we now reveal the intricate structure of PD-1 in complex with the cemiplimab Fab at a resolution of 1.98 Å. The cemiplimab-PD-1 interaction preoccupies the space for PD-L1 binding with a greater binding affinity than the PD-1/PD-L1 interaction, which is the basis for the PD-1 blocking mechanism. The structure reveals that cemiplimab and dostarlimab are significantly similar in PD-1 binding, although the precise interactions differ. A comparative investigation of PD-1 interactions with the four FDA-approved antibodies reveals that the BC, C'D, and FG loops of PD-1 adopt distinct conformations for optimal interaction with the antibodies. The structural characteristics in this work could be helpful information for developing more potent anti-PD-1 biologics against cancer.

Green-Light-Driven Fe(III)(btz)3 Photocatalysis in the Radical Cationic [4+2] Cycloaddition Reaction.

Green-light-driven FeIII(btz)3 photocatalysis for the radical cationic [4+2] cycloaddition of terminal styrenes and nucleophilic dienes has been investigated. The Fe-MIC (mesoionic carbene) complex forms a ligand-to-metal charge-transfer transition state with relatively high excited-state reduction potentials that can selectively oxidize terminal styrene derivatives. Unique multisubstituted cyclohexenes and structurally complex biorelevant cyclohexenes were constructed, highlighting the usefulness of this mild and practical first-row transition metal complex system.

Medication Adherence and Clinical Outcome of Fixed-Dose Combination vs. Free Combination of Angiotensin Receptor Blocker and Statin.

BACKGROUND: Non-compliance with angiotensin receptor blockers (ARB) or statin is one of the major hurdles to optimal medical treatment. This study investigated whether fixed-dose combination (FDC) improved compliance to medication compared with traditional free combination (FC).Methods and Results:In this retrospective nationwide cohort study, medication persistency, medication adherence measured by proportion of days covered (PDC), and all-cause death of 123,992 patients who started ARB and stain were investigated for 540 days. Patients had a mean age of 63 years and 48% were male. Persistency, PDC, and proportion of PDC ≥80% of FDC (N=34,776) were higher than those for FC (N=89,216) in both unadjusted analysis (54.5% vs. 27.8%; 84.1% vs. 63.1%; 75.5% vs. 48.1%) and propensity-score matched analysis (P<0.001, all). Death risk for the investigation period (0-540 days) was lower in FDC in unadjusted (1.8% vs. 2.6%, P<0.001) and adjusted cohort (P<0.05). In landmark analyses at days 180 and 360, there was no significant difference of death risk between FDC and FC (P>0.05). CONCLUSIONS: In this real-world data analysis, patients taking FDC of ARB and statin showed higher medication persistence and adherence compared to patients taking FC of ARB and statin up to 540 days. The risk of all-cause death was not different between FDC and FC despite better medication compliance in the FDC patients.

Electrochemically Deposited Polypyrrole for Counter Electrode of Quasi-Solid-State Dye-Sensitized Solar Cell.

In this study, quasi-solid-state dye-sensitized solar cells (QSS-DSSCs) were fabricated by employing polypyrrole (PPy)-functionalized counter electrodes and an iodine-based gel electrolyte. The PPy film was fabricated on a fluorine-doped tin oxide substrate by simple potentiostatic electrodeposition in an aqueous solution using a pyrrole monomer as the precursor. The prepared polypyrrole counter electrode was used in a QSS-DSSC and characterized by scanning electron microscopy and electrochemical impedance spectroscopy. The use of PPy counter electrodes was judged to be acceptable for practical applications because they were only 21% less efficient than counter electrodes fabricated with Pt.

Electronically Mismatched Cycloaddition Reactions via First-Row Transition Metal, Iron(III)-Polypyridyl Complex.

The iron(III)-polypyridyl complex and its derivatives showed sufficient oxidizing potential to act as a one-electron oxidant, producing radical cations from olefins and promoting the efficient radical cation [2 + 2] and [2 + 4] cycloaddition reactions. Subsequent chain propagation afforded trisubstituted cyclobutane or cyclohexene derivatives, and this facile route enables the replacement of rare metals with sustainable, green, and inexpensive iron in radical cation cycloadditions.