Lauryl-NrTP6 lipopeptide self-assembled nanorods for nuclear-targeted delivery of doxorubicin.

Targeted delivery offers solutions for more efficient therapies with fewer side effects. Here, lipopeptides (LPs) prepared by conjugation of the nuclear-targeting peptide analogue H-YKQSHKKGGKKGSG-NH (NrTP6) and two lauric acid chains are used to encapsulate the chemotherapeutic agent doxorubicin (DX) through a solvent-exchange protocol. LPs spontaneously form nanosized rod-like assemblies in phosphate buffer.

Investigating Postoperative Urinary Retention: Risk Factors and Postsurgical Outcomes in Total Joint Arthroplasty.

Background: Postoperative urinary retention (POUR), a known complication following total joint arthroplasty (TJA), remains inconsistent in its diagnostic criteria, prevalence, and risk factors. This study aims to quantify POUR rates, identify risk factors, and assess complications associated with catheterization in TJA.

Methods: A single-center cohort undergoing TJA between January 2015 and December 2022 was retrospectively reviewed.

Solving the Mystery of Sir William Osler and Acupuncture: How Knowledge and Prevailing Attitudes Shaped a Physician.

Background: Medical education in North America was shaped by a biomedically bounded framework dating back to the early nineteenth century. Yet, one renowned physician, William Osler (1849-1919), seemed to stand out among his contemporaries by promoting acupuncture as a form of treatment. Some physicians in the early 1970s proposed that Osler was ahead of his time by including acupuncture in his medical textbook, (1892).

Atomically resolved imaging of the conformations and adsorption geometries of individual β-cyclodextrins with non-contact AFM.

Glycans, consisting of covalently linked sugar units, are a major class of biopolymers essential to all known living organisms. To better understand their biological functions and further applications in fields from biomedicine to materials science, detailed knowledge of their structure is essential. However, due to the extraordinary complexity and conformational flexibility of glycans, state-of-the-art glycan analysis methods often fail to provide structural information with atomic precision.

Modulators of the Hop-HSP90 Protein-Protein Interaction Disrupt KSHV Lytic Replication.

The central role of the chaperome in maintaining cellular proteostasis has seen numerous viral families evolve to parasitically exploit host chaperones in their life cycle. The HSP90 chaperone protein and its cochaperone Hop have both individually been shown to be essential factors for Kaposi sarcoma-associated herpesvirus (KSHV) lytic replication. Given the fundamental regulatory role that protein-protein interactions (PPIs) play in cellular biology, we reasoned that disrupting the Hop-HSP90 PPI may provide a new host-based target for inhibiting KSHV lytic replication.

Atomically Precise Control of Topological State Hybridization in Conjugated Polymers.

Realization of topological quantum states in carbon nanostructures has recently emerged as a promising platform for hosting highly coherent and controllable quantum dot spin qubits. However, their adjustable manipulation remains elusive. Here, we report the atomically accurate control of the hybridization level of topologically protected quantum edge states emerging from topological interfaces in bottom-up-fabricated π-conjugated polymers.

Food and Drug Administration (FDA) Approvals of Biological Drugs in 2023.

An increase in total drug (small molecules and biologics) approvals by the Food and Drug Administration (FDA) was seen in 2023 compared with the previous year. Cancer remained the disease most targeted by monoclonal antibodies (mAbs), followed by autoimmune conditions. Our data reveal the prevalence of approvals for biologics even during years when the total number of authorizations was low, such as in 2022.

Ga Radiolabeling of NODASA-Functionalized Phage Display-Derived Peptides for Prospective Assessment as Tuberculosis-Specific PET Radiotracers.

This research presents the development of positron emission tomography (PET) radiotracers for detecting Mycobacterium tuberculosis (MTB) for the diagnosis and monitoring of tuberculosis. Two phage display-derived peptides with proven selective binding to MTB were identified for development into PET radiopharmaceuticals: H8 (linear peptide) and PH1 (cyclic peptide). We sought to functionalize H8/PH1 with NODASA, a bifunctional chelator that allows complexation of PET-compatible radiometals such as gallium-68.

Anterior approach with or without liver hanging maneuver versus conventional approach in major liver resections. A systematic review and meta-analysis of randomized controlled trials.

Introduction: The anterior approach (AA), whether or not associated with the liver hanging maneuver (LHM), has been advocated to improve survival and postoperative outcomes in HCC patients undergoing major liver resection. This systematic review and meta-analysis of randomized controlled trials aims to explore intra/perioperative and long-term survival outcomes of AA ± LHM compared to CA regardless of tumor histology.

Methods: The study was conducted according to the Cochrane recommendations searching the PubMed, Scopus, and EMBASE databases until January 27, 2024 (PROSPERO ID: CRD42024507060).

[Severe hypereosinophilia as a paraneoplastic syndrome in a patient with differentiated thyroid cancer].

In solid tumors, hypereosinophilia is a rare phenomenon and is mainly associated with mucin-secreting carcinomas. Thyroid tumors associated with neutrophilia and/or eosinophilia have been described exclusively in patients with anaplastic thyroid cancer. Eosinophilia associated with papillary thyroid cancer is extremely rare and there are very few cases currently described.

Single-Molecule Identification of the Isomers of a Lipidic Antibody Activator.

Molecular structural elucidation can be accomplished by different techniques, such as nuclear magnetic resonance or X-ray diffraction. However, the former does not give information about the three-dimensional atomic arrangement, and the latter needs crystallizable solid samples. An alternative is direct, real-space visualization of the molecules by cryogenic scanning tunneling microscopy (STM).

First Bioprospecting Study of Skin Host-Defense Peptides in .

The adaptation of amphibians to diverse environments is closely related to the characteristics of their skin. The complex glandular system of frog skin plays a pivotal role in enabling these animals to thrive in both aquatic and terrestrial habitats and consists of crucial functions such as respiration and water balance as well as serving as a defensive barrier due to the secretion of bioactive compounds. We herein report the first investigation on the skin secretion of , as a potential source of bioactive peptides and also as an indicator of its evolutionary adaptations to changing environments.

1,3,5-Triazine as Branching Connector for the Construction of Novel Antimicrobial Peptide Dendrimers: Synthesis and Biological Characterization.

Peptides displaying antimicrobial properties are being regarded as useful tools to evade and combat antimicrobial resistance, a major public health challenge. Here we have addressed dendrimers, attractive molecules in pharmaceutical innovation and development displaying broad biological activity. Triazine-based dendrimers were fully synthesized in the solid phase, and their antimicrobial activity and some insights into their mechanisms of action were explored.

Atomistic description of the OCTN1 recognition mechanism via in silico methods.

The Organic Cation Transporter Novel 1 (OCTN1), also known as SLC22A4, is widely expressed in various human tissues, and involved in numerous physiological and pathological processes remains. It facilitates the transport of organic cations, zwitterions, with selectivity for positively charged solutes. Ergothioneine, an antioxidant compound, and acetylcholine (Ach) are among its substrates.

The synthesis of solid supports carrying base labile linkers to generate 3'-phosphate oligonucleotides.

Oligonucleotides carrying 3'-terminal phosphates and conjugates are important tools in molecular biology and diagnostic purposes. We described the preparation of solid supports carrying the base labile linker 4-((2-hydroxyethyl)sulfonyl)benzamide for the solid-phase synthesis of 3'-phosphorylated oligonucleotides. These supports are fully compatible with the phosphoramidite chemistry yielding the desired 3'-phosphate oligonucleotides in excellent yields.

Ti/Ta-based composite polysaccharide scaffolds for guided bone regeneration in total hip arthroplasty.

Guided bone regeneration can play an important role in orthopedic applications. This work presents the synthesis and characterization of composite scaffolds based on polysaccharides loaded with microparticles of titanium or tantalum as novel materials proposed for composite systems with promising characteristics for guided bone regeneration. Ti/Ta composite scaffolds were synthesized using chitosan and gellan gum as organic substrates and crosslinked with oxidized dextran resulting in stable inorganic-organic composites.

A native mass spectrometry approach to qualitatively elucidate interfacial epitopes of transient protein-protein interactions.

Native mass spectrometric analysis of TPR2A and GrpE with unpurified peptides derived from limited proteolysis of their respective PPI partners (HSP90 C-terminus and DnaK) facilitated efficient, qualitative identification of interfacial epitopes involved in transient PPI formation. Application of this approach can assist in elucidating interfaces of currently uncharacterised transient PPIs.

Safety-Catch Linkers for Solid-Phase Peptide Synthesis.

Solid-phase peptide synthesis (SPPS) is the preferred strategy for synthesizing most peptides for research purposes and on a multi-kilogram scale. One key to the success of SPPS is the continual evolution and improvement of the original method proposed by Merrifield. Over the years, this approach has been enhanced with the introduction of new solid supports, protecting groups for amino acids, coupling reagents, and other tools.

Neurobehavioral and molecular changes in a rodent model of ACTH-induced HPA axis dysfunction.

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is linked to the pathophysiology of depression. Although exogenous adrenocorticotropic hormone (ACTH) is associated with a depressive-like phenotype in rodents, comprehensive neurobehavioral and mechanistic evidence to support these findings are limited. Sprague-Dawley rats (male, n = 30; female, n = 10) were randomly assigned to the control (male, n = 10) or ACTH (male, n = 20; female n = 10) groups that received saline (0.

The Pharmaceutical Industry in 2023: An Analysis of FDA Drug Approvals from the Perspective of Molecules.

With the COVID-19 pandemic behind us, the U.S. Food and Drug Administration (FDA) has approved 55 new drugs in 2023, a figure consistent with the number authorized in the last five years (53 per year on average).

N,N-Dimethyl Formamide European Restriction Demands Solvent Substitution in Research and Development.

As of December 2023, the use of common solvent N,N-dimethyl formamide (DMF) will be restricted in the European Union because of its reproductive health hazard. Industrial facilities must comply with stricter exposure limits, and researchers are recommended to find alternative solvents. Here we explain the restrictions on DMF, which disciplines are affected, and how to substitute DMF to keep research and development commercially relevant.

The effect of water on gold supported chiral graphene nanoribbons: rupture of conjugation by an alternating hydrogenation pattern.

In the last few years we have observed a breakpoint in the development of graphene-derived technologies, such as liquid phase filtering and their application to electronics. In most of these cases, they imply exposure of the material to solvents and ambient moisture, either in the fabrication of the material or the final device. The present study demonstrates the sensitivity of graphene nanoribbon (GNR) zigzag edges to water, even in extremely low concentrations.