CD38 Coordinates with NF-κB to Promote Cochlear Inflammation in Noise-Induced Hearing Loss: the Protective Effect of Apigenin.

Noise exposure is one of the most common causes of sensorineural hearing loss. Although many studies considered inflammation to be a major contributor to noise-induced hearing loss, the process of cochlear inflammation is still unclear. Studies have found that activation of the NF-κB signaling pathway results in the accumulation of macrophages in the inner ear plays an important role in hair cell damage.

PK/PD Evaluation of Antibody-Drug Conjugates with Enhanced Immune Effector Functions.

Optimizing the interaction between antibody (mAb)-based therapeutics and immune effector functions (EFs) offers opportunities to improve the therapeutic window of these molecules. However, the role of EFs in antibody-drug conjugate (ADC) efficacy and toxicity remains unknown, with limited studies that have investigated how modulation of EF affects the pharmacology of ADCs. This study aimed to evaluate the effect of EF modulation on ADC efficacy using trastuzumab-vc-MMAE as a model ADC.

Microscopic Origins of Flow Activation Energy in Biomolecular Condensates.

The material properties of biomolecular condensates govern their dynamics and functions by influencing the molecular diffusion rates and biochemical interactions. A recent report has identified a characteristic timescale of temperature-dependent viscosity in biomolecular condensates arising from an activated dissociation events collectively referred to as flow activation energy. The microscopic origin of this activation energy is a complex function of sequence, stoichiometry, and external conditions.

Historical Perspective of Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Background: Advances in novel therapies have improved outcomes for multiple myeloma (MM) patients and the use of allo-SCT has decreased. Current guidelines no longer support allo-SCT as consolidation therapy for newly diagnosed MM, even in high-risk cases.

Summary: Allo-SCT is now typically considered only within clinical trials for young, high-risk patients with relapsed or refractory MM (RRMM).

Meta-Analysis of Exposure-Adverse Event Relationships for Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) have become a vital class of therapeutics in oncology because of their ability to selectively deliver potent drug molecules to tumor cells. However, ADC-associated toxicities cause high failure rates in the clinic and hinder their full potential. Due to the complex structure and pharmacokinetics of ADCs, it is challenging to identify the drivers of their toxicities.

Urban Zen integrative therapy: Understanding intervention delivery adherence.

Background: Complementary health approaches have shown therapeutic benefits in symptom reduction and improved patients' quality of life for chronic debilitating conditions such as cancer and pulmonary hypertension. Urban Zen Integrative Therapy (UZIT) is a mindfulness-based multicomponent complementary intervention shown to improve symptom management and quality of life in patients with pulmonary hypertension. Consistent intervention delivery across interventionists is critical to test mindfulness-based multicomponent interventions on a larger scale and further implementations as an augmented practice in routine care.

Fluoroscopic Procedure-Room Scatter-Dose Reduction Using a Region-of-Interest (ROI) Attenuator.

During fluoroscopically-guided interventional (FGI) procedures, dose to the patient as well as the scatter dose to staff can be high. However, a significant dose reduction can be possible by using a region-of-interest (ROI) attenuator that reduces the x-ray intensity in the peripheral x-ray field while providing full field of view imaging. In this work, we investigated the magnitude of scatter dose reduction to staff made possible by using an ROI attenuator composed of 0.

Sequence-specific interactions determine viscoelasticity and aging dynamics of protein condensates.

Biomolecular condensates are viscoelastic materials. Here, we investigate the determinants of sequence-encoded and age-dependent viscoelasticity of condensates formed by the prion-like low-complexity domain of the protein hnRNP A1 and its designed variants. We find that the dominantly viscous forms of the condensates are metastable Maxwell fluids.

Pulmonary Pharmacokinetics of Antibody and Antibody Fragments Following Systemic and Local Administration in Mice.

This study aimed to investigate the effect of molecular size on the pulmonary pharmacokinetics (PK) of proteins following systemic and local administration in wild-type mice. A non-cross-reactive antibody trastuzumab, and F(ab')2, Fab, and scFv fragments of this antibody were used for the investigation. Proteins were injected intravenously or via intratracheal instillation, and PK was measured in plasma, lungs, trachea, bronchi, and bronchoalveolar lavage (BAL) using ELISA.

Synthesis, Anti-Cancer Activity, Cell Cycle Arrest, Apoptosis Induction, and Docking Study of Fused Benzo[]chromeno[2,3-]pyrimidine on Human Breast Cancer Cell Line MCF-7.

Breast cancer is the predominant form of cancer among women and ranks as the second most prevalent cancer globally, affecting both developed and less developed countries. Presently, accessible cancer treatment methods either employ recently created, secure, and efficient chemotherapeutic medications or directly target innovative pathways that cause apoptosis. One of the indirect strategies for treating this fatal illness has mostly depended on its essential role in cell cycle arrest and apoptosis induction, as well as the antagonistic interaction between the Bcl-2 and Mcl-1 proteins, in order to avert major health repercussions.

A Synergistic Overview between Microfluidics and Numerical Research for Vascular Flow and Pathological Investigations.

Vascular diseases are widespread, and sometimes such life-threatening medical disorders cause abnormal blood flow, blood particle damage, changes to flow dynamics, restricted blood flow, and other adverse effects. The study of vascular flow is crucial in clinical practice because it can shed light on the causes of stenosis, aneurysm, blood cancer, and many other such diseases, and guide the development of novel treatments and interventions. Microfluidics and computational fluid dynamics (CFDs) are two of the most promising new tools for investigating these phenomena.

Effect of sintering cycle on the strength and translucency of multilayered zirconia.

Purpose: A newly introduced sintering protocol promises to offer higher translucency while not significantly compromising the flexural strength of the material. However, the effect of the novel sintering protocol has not been thoroughly validated. The purpose of this study was to measure and compare the effect of two sintering protocols on the translucency and flexural strength of two multilayered zirconia materials.

Leveraging bifactor modeling to test prospective direct and indirect effects of adolescent alcohol use and externalizing symptoms on the development of task-general executive functioning.

Adolescence is a period of substantial maturation in brain regions underlying Executive Functioning (EF). Adolescence is also associated with initiation and escalation of Alcohol Use (AU), and adolescent AU has been proposed to produce physiological and neurobiological events that derail healthy EF development. However, support has been mixed, which may be due to (1) failure to consider co-occurring externalizing symptoms (including other drug use) and poor social adaptation, and (2) heterogeneity and psychometric limitations in EF measures.

Poly(lactic-co-glycolic acid) nanoparticle fabrication, functionalization, and biological considerations for drug delivery.

Nanoparticles can be used for drug delivery and consist of many sizes and chemical compositions. They can accommodate a diverse population of drugs and can be made to target specific areas of the body. Fabrication methods generally follow either top-down or bottom-up manufacturing techniques, which have differing production controls, which determine nanoparticle characteristics including but not limited to size and encapsulation efficiency.

Direct computations of viscoelastic moduli of biomolecular condensates.

Biomolecular condensates are viscoelastic materials defined by time-dependent, sequence-specific complex shear moduli. Here, we show that viscoelastic moduli can be computed directly using a generalization of the Rouse model that leverages information regarding intra- and inter-chain contacts, which we extract from equilibrium configurations of lattice-based Metropolis Monte Carlo (MMC) simulations of phase separation. The key ingredient of the generalized Rouse model is a graph Laplacian that we compute from equilibrium MMC simulations.

Biosynthesis of Atypical Angucyclines Unveils New Ring Rearrangement Reactions Catalyzed by Flavoprotein Monooxygenases.

Six new angucycline structures, including spirocyclione A (), which contains an unusual oxaspiro[5.5]undecane architecture, and its ring-A-cleaved product spirocyclione B (), were discovered by heterologous expression of a type II polyketide biosynthetic gene cluster captured from a marine actinomycete strain sp. HDN155000.

Enzyme-Dynamic Extracellular Vesicles for Metalloimmunotherapy of Malignant Pleural Effusions.

Malignant pleural effusions (MPEs) are hard to treat, and their onset usually signals terminal cancer. Immunotherapies hold promise but must overcome the immunosuppressive MPE microenvironment. Herein, we treat MPEs synergistically combining two emerging cancer therapy modalities: enzyme-dynamic therapy (EDT) and metalloimmunotherapy.

Inter-Antibody Variability in the Clinical Pharmacokinetics of Monoclonal Antibodies Characterized Using Population Physiologically Based Pharmacokinetic Modeling.

The objective of this work was to develop a population physiologically based pharmacokinetic (popPBPK) model to characterize the variability in the clinical PK of monoclonal antibodies (mAbs) following intravenous (IV) and subcutaneous (SC) administration. An extensive literature search was conducted and clinical PK data for FDA-approved as well as non-approved mAbs were collected. Training and validation datasets of 44 and 9 mAbs exhibiting linear pharmacokinetics were used for model development.

Saccharin and aspartame excite rat retinal neurons.

Retinal sensitivity to a variety of artificial sweeteners was tested by monitoring changes in internal free calcium in isolated retinal neurons using Fluo3. Several ligands, including aspartame and saccharin elevated internal free calcium. The effects of these ligands were mediated by both ligand-gated membrane channels and G-protein coupled receptors.

The Impact of High-density Lipoprotein Cholesterol (HDL-C) Levels and Risk of Movement Disorders in Patients Taking Antipsychotics.

Introduction: Well-known adverse events of antipsychotics are movement disorders, or extrapyramidal symptoms, such as drug-induced parkinsonism and tardive dyskinesia.

Objective: With new evidence suggesting a link between low high-density lipoprotein cholesterol (HDL-C) and risk of Parkinson's disease, this study sought to investigate if that link also translated to patients taking antipsychotics with low HDL-C and an increased risk for developing a movement disorder.

Design: Adult patients (n=89) at an inpatient state psychiatric facility taking at least one antipsychotic with at least one HDL-C level were assessed for signs of a movement disorder through their history and physical, progress notes, and Abnormal Involuntary Movement Scale (AIMS) score.