Structural basis of nearest-neighbor cooperativity in the ring-shaped gene regulatory protein TRAP from protein engineering and cryo-EM.

The homo-dodecameric ring-shaped RNA binding attenuation protein (TRAP) from binds up to twelve tryptophan ligands (Trp) and becomes activated to bind a specific sequence in the 5' leader region of the operon mRNA, thereby downregulating biosynthesis of Trp. Thermodynamic measurements of Trp binding have revealed a range of cooperative behavior for different TRAP variants, even if the averaged apparent affinities for Trp have been found to be similar. Proximity between the ligand binding sites, and the ligand-coupled disorder-to-order transition has implicated nearest-neighbor interactions in cooperativity.

Clinical outcomes and cost-utility analysis of GKRS plus TKIs versus TKIs in patients with EGFR-mutant lung adenocarcinoma and brain metastases: a Markov decision model.

Objective: This study focuses on epidermal growth factor receptor-mutated lung adenocarcinoma, known for frequent brain metastasis. It aimed to compare the clinical outcomes and cost-effectiveness of combining Gamma Knife radiosurgery (GKRS) with tyrosine kinase inhibitors (TKIs) (GKRS+TKI group) versus TKIs alone (TKI group) for the treatment of patients with newly diagnosed brain metastasis in this condition.

Methods: Study characteristics of the two groups were matched using inverse probability of treatment weighting (IPTW).

Exosome-Mediated Lectin Pathway and Resistin-MIF-AA Metabolism Axis Drive Immune Dysfunction in Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet levels and heightened susceptibility to bleeding resulting from augmented autologous platelet destruction and diminished thrombopoiesis. Although antibody-mediated autoimmune reactions are widely recognized as primary factors, the precise etiological agents that trigger ITP remain unidentified. The pathogenesis of ITP remains unclear owing to the absence of comprehensive high-throughput data, except for the belated emergence of autoreactive antibodies.

On-Demand Controlled Release Multi-Drugs Delivery System for Spatiotemporally Synergizing Antitumor Immunotherapy.

Although cytotoxic T lymphocytes (CTLs) activation combined with programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis blockade have emerged as an effective strategy to improve immunotherapeutic potency, it remains challenging to realize the spatiotemporal synergy of these two components. Herein, the study reports an engineered bacterial-based delivery system that can simultaneously promote CTLs infiltration and control PD-L1 binding protein (PD-L1 trap) release on demand at tumor site. The drug release button of this tumor targeting system is the specific temperature, which is accomplished by dual-modified melanin nanoparticles with photothermal conversion capacity on the engineered bacterial.

Identification of a candidate sex determination region and sex-specific molecular markers based on whole-genome re‑sequencing in the sea star Asterias amurensis.

Sex determination systems are diverse in echinoderms, however, our understanding is still very limited in this research field, especially for Asteroidea species. The northern Pacific seastar, Asterias amurensis, has attracted widespread concern due to its population outbreaks and high-risk invasions. Using whole-genome re-sequencing data from 40 females and 40 males, we identified a candidate sex determination region in A.