Conotoxins Targeting Voltage-Gated Sodium Ion Channels.

Voltage-gated sodium (Na) channels are intimately involved in the generation and transmission of action potentials, and dysfunction of these channels may contribute to nervous system diseases, such as epilepsy, neuropathic pain, psychosis, autism, and cardiac arrhythmia. Many venom peptides selectively act on Na channels. These include conotoxins, which are neurotoxins secreted by cone snails for prey capture or self-defense but which are also valuable pharmacological tools for the identification and/or treatment of human diseases.

Gradiently Foaming Ultrasoft Hydrogel with Stop Holes for Highly Deformable, Crack-Resistant and Sensitive Conformal Human-Machine Interfaces.

Hydrogels are considered as promising materials for human-machine interfaces (HMIs) owing to their merits of tailorable mechanical and electrical properties; nevertheless, it remains challenging to simultaneously achieve ultrasoftness, good mechanical robustness and high sensitivity, which are the pre-requisite requirements for wearable sensing applications. Herein, for the first time, this work proposes a universal phase-transition-induced bubbling strategy to fabricate ultrasoft gradient foam-shaped hydrogels (FSHs) with stop holes for high deformability, crack-resistance and sensitive conformal HMIs. As a typical system, the FSH based on polyacrylamide/sodium alginate system shows an ultralow Young's modulus (1.

An atlas of epithelial cell states and plasticity in lung adenocarcinoma.

Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers.

Teclistamab in Relapsed or Refractory Multiple Myeloma.

Background: Teclistamab is a T-cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma.

Methods: In this phase 1-2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody.

Cellular and Humoral Immunity to SARS-CoV-2 Infection in Multiple Sclerosis Patients on Ocrelizumab and Other Disease-Modifying Therapies: A Multi-Ethnic Observational Study.

Objective: The objective of this study was to determine the impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on the development of cellular and humoral immunity to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection.

Methods: Patients with MS aged 18 to 60 years were evaluated for anti-nucleocapsid and anti-Spike receptor-binding domain (RBD) antibody with electro-chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N-terminal domain with multiepitope bead-based immunoassays (MBI); live virus immunofluorescence-based microneutralization assay; T-cell responses to SARS-CoV-2 Spike using TruCulture enzyme-linked immunosorbent assay (ELISA); and IL-2 and IFNγ ELISpot assays. Assay results were compared by DMT class.

Slide-Ring Structure-Based Double-Network Hydrogel with Enhanced Stretchability and Toughness for 3D-Bio-Printing and Its Potential Application as Artificial Small-Diameter Blood Vessels.

Artificial small-diameter blood vessels (SDBVs) are extremely limited in their thrombosis and still present significant clinical challenges worldwide. In recent years, 3D-bio-printing has offered a powerful technique to fabricate vessel channels in tissue engineering applications. Hydrogels are attractive bio-inks for SDBVs 3D-bio-printing, but they usually present weak mechanical properties.

Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCM), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCM). Genotype-specific differences have been reported in cardiac function.

Dopamine-Modified Hyaluronic Acid Hydrogel Adhesives with Fast-Forming and High Tissue Adhesion.

Commercial or clinical tissue adhesives are currently limited due to their weak bonding strength on wet biological tissue surface, low biological compatibility, and slow adhesion formation. Although catechol-modified hyaluronic acid (HA) adhesives are developed, they suffer from limitations: insufficient adhesiveness and overfast degradation, attributed to low substitution of catechol groups. In this study, we demonstrate a simple and efficient strategy to prepare mussel-inspired HA hydrogel adhesives with improved degree of substitution of catechol groups.

Salsalate, but not metformin or canagliflozin, slows kidney cyst growth in an adult-onset mouse model of polycystic kidney disease.

Background: Multiple preclinical studies have highlighted AMP-activated protein kinase (AMPK) as a potential therapeutic target for autosomal dominant polycystic kidney disease (ADPKD). Both metformin and canagliflozin indirectly activate AMPK by inhibiting mitochondrial function, while salsalate is a direct AMPK activator. Metformin, canagliflozin and salsalate (a prodrug dimer of salicylate) are approved for clinical use with excellent safety profile.

Parenchymal and stromal tissue regeneration of tooth organ by pivotal signals reinstated in decellularized matrix.

Cells are transplanted to regenerate an organs' parenchyma, but how transplanted parenchymal cells induce stromal regeneration is elusive. Despite the common use of a decellularized matrix, little is known as to the pivotal signals that must be restored for tissue or organ regeneration. We report that Alx3, a developmentally important gene, orchestrated adult parenchymal and stromal regeneration by directly transactivating Wnt3a and vascular endothelial growth factor.

Super tough magnetic hydrogels for remotely triggered shape morphing.

Despite their potential in various fields such as soft robots, drug delivery and biomedical engineering, magnetic hydrogels have always been limited by their poor mechanical properties. Here a universal soaking strategy has been presented to synthesize tough magnetic nanocomposite (NC) hydrogels. We can simultaneously solve two common issues for magnetic hydrogels: the poor mechanical properties and poor distribution of magnetic particles.

Effects of Ambient Temperature and Forced-air Warming on Intraoperative Core Temperature: A Factorial Randomized Trial.

Background: The effect of ambient temperature, with and without active warming, on intraoperative core temperature remains poorly characterized. The authors determined the effect of ambient temperature on core temperature changes with and without forced-air warming.

Methods: In this unblinded three-by-two factorial trial, 292 adults were randomized to ambient temperatures 19°, 21°, or 23°C, and to passive insulation or forced-air warming.

[CHRONIC CONTINUOUS NOR-MOBARIC HYPOXIA AUGMENTS CELL TOLERANCE TO ANOXIA(REOXYGE-NATION: THE ROLE OF PROTEIN KINASES].

The study evaluated the role of protein kinase C, PI3-kinase and tyrosine kinases in the cardi-oprotective effect of the chronic continuous normobaric hypoxia (CCNH). Adaptation to CCNH was provided by placing the rats in an atmosphere with a low content of O2 (12 %) during 21 days. Anoxia-reoxygenation of isolated cardiomyocytes of intact rats caused the deaths of 16.

Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia.

Background: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults.

Methods: We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL.