AbstractBackground and Aims. Loss-of-function (LOF) mutations of the cardiac Na+ channel (SCN5A) are causatively associated with the Brugada Syndrome (BrS)

Aging is a natural process characterized by a progressive physiological decline that undermines health and well-being in the elderly population. Oxida…

Summary: The transcriptional regulators SOX2 and NR2F1 drive the development of the visual thalamus. Mutations in these genes cause visual impairment in humans.

The performance of artificial molecular machines relies on the interplay between molecular design and environmental factors, yet how solvation shapes their energy landscapes and kinetics remains poorl...

This study provides a comprehensive structural analysis of prenylflavonoids (PFs) interaction with Aβ1–42 oligomers, revealing their potential to modu…

[FeFe]-hydrogenases are highly efficient enzymes in the reversible catalysis of molecular hydrogen production and oxidation. Their active site, the H-cluster, consists of a [4Fe–4S]H subcluster linked to a binuclear [2Fe]H organometallic unit. Many [FeFe]-hydrogenases, such as the one from Desulfovibrio desulfuricans (DdHydAB), possess accessory Fe–S clusters (F and F′) that mediate electron transfer. This study employs hybrid quantum mechanics/molecular mechanics (QM/MM) methods to characterize the electronic structure and thermodynamic landscape associated with redox and protonation events in the complete Fe–S cluster network of DdHydAB. Our calculations indicate that the F′ cluster plays a key role in the initial reduction of the oxidized resting state, acting as the preferential site for the accumulation of the first electron. Analysis of protonated states, upon reduction events, reveals a strong correlation between protonation and electron transfer (PCET), with protonation at the H-cluster inducing electron transfer from the F′ cluster to the H-cluster. Calculations indicate that the formation of a terminal hydride is energetically favored over ADT protonation, and subsequent isomerization to a bridging hydride (μ-H) is further stabilizing, albeit potentially kinetically limiting. The study highlights how accessory clusters influence the electronic distribution and redox properties of the H-cluster, underscoring the importance of considering the entire Fe–S cluster system for a complete understanding of the catalytic mechanism of [FeFe]-hydrogenases.

Click on the article title to read more.

A novel synthetic biology strategy that allows standardized swapping or removal of expression cassettes already integrated into the yeast genome.

Scientific Reports - Animal pollination shapes fruits market features, seeds functional traits and modulates their chemistry

Psoriasis is a chronic inflammatory skin-disease associated with cardiovascular comorbidities. In patients, T cells with a skin-primed phenotype are expanded...

Photodynamic therapy (PDT) is an efficient, clinically approved, light-activated cancer treatment. However, it is mostly effective for superficial tre…

Transient receptor potential (TRP) channels are a large family of non-selective cation channels that play critical roles in cellular homeostasis and signal transduction. Recent investigations have cle...

Triple-negative breast cancer (TNBC) is a highly aggressive and treatment-resistant malignancy characterized by the lack of targeted therapies and poor clinical outcomes. Here, we present a dual-targeting strategy combining the anti-EGFR monoclonal antibody cetuximab (CTX) with H-ferritin (HFn), a nanoparticle targeting transferrin receptor 1 (TfR1), for potential immunotherapy in CTX-resistant tumors. The HFn–CTX nanoconjugate exhibited favorable biophysical properties and good tumor accumulation and significantly enhanced antibody-dependent cellular cytotoxicity (ADCC) in TNBC spheroids compared to CTX alone. Conversely, glioblastoma spheroids did not exhibit comparable reactivity. This effect correlated with elevated cell-surface EGFR expression and plasma-membrane lingering of the nanoconjugate in TNBC cells, facilitating robust immune activation. Biodistribution studies showed selective accumulation of the HFn–CTX nanoconjugate in TNBC tumors in vivo. These findings highlight the potential of HFn–CTX nanoconjugates to repurpose CTX for refractory cancers that express EGFR at high levels, such as TNBC, leveraging dual-receptor targeting to amplify immune-mediated cytotoxicity and overcome resistance.