Egg Consumption and Mortality: A Prospective Cohort Study of Australian Community-Dwelling Older Adults.

Background/objectives: Egg consumption in adults has been linked with a modestly increased risk of all-cause and CVD mortality. However, evidence on adults aged 65 y+ is limited. The objective of this study was to investigate the association between egg intake and mortality in community-dwelling older adults.

Nut consumption and disability-free survival in community-dwelling older adults: a prospective cohort study.

Objectives: The relationship between nut intake and disability-free survival (healthy lifespan) in later life is unclear. The objective was to evaluate the association between nut intake and disability-free survival in a cohort of adults aged ≥70 years, and whether this varied according to overall diet quality.

Methods: This prospective cohort study involved 9916 participants from the ASPREE Longitudinal Study of Older Persons.

Identification and detection of conserved G-quadruplex in monkeypox virus using conformation specific fluorogenic probe.

Identifying distinct noncanonical structures in pathogenic genomes is crucial for developing new diagnostic tools. This study uncovers stable G-quadruplex (GQ) structures in conserved DNA sequences unique to the monkeypox virus (MPV). Furthermore, we developed a method for the detection of target GQ using a fluorogenic probe.

A novel energy-efficiency framework for UAV-assisted networks using adaptive deep reinforcement learning.

In the air-to-ground transmissions, the lifespan of the network is based on the "unmanned aerial vehicle's (UAV)" life span because of the limited battery capacity. Thus, the enhancement of energy efficiency and the outage of the ground candidate's minimization are significant factors of the network functionality. UAV-aided transmission can highly enhance the spectrum efficacy and coverage.

Unambiguous Detection of LTR-III G-Quadruplex in the HIV Genome Using a Tailored Fluorogenic Probe-based Assay.

The noncanonical conformations within the genomes of viral pathogens is of significant diagnostic value, due to their unique secondary structures and interactions with specific fluorogenic molecules. In particular, adaptation of the G-quadruplex (GQ) conformation by the specific gene sequence leads to distinct topological features, resulting in unique binding sites that are crucial for the selective recognition of human immunodeficiency virus (HIV) by small molecules. Leveraging the selective fluorescence response of a benzobisthiazole-based fluorogenic probe to the LTR-III GQ target, we developed a GQ-based diagnostic platform for HIV detection.

Fluorescent Peptides Sequester Redox Copper to Mitigate Oxidative Stress, Amyloid Toxicity, and Neuroinflammation.

Alzheimer's disease is a progressive neurodegenerative disorder that significantly contributes to dementia. The lack of effective therapeutic interventions presents a significant challenge to global health. We have developed a set of short peptides (PN) conjugated with a dual-functional fluorophoric amino acid (N).

A Deep Auto-Optimized Collaborative Learning (DACL) model for disease prognosis using AI-IoMT systems.

In modern healthcare, integrating Artificial Intelligence (AI) and Internet of Medical Things (IoMT) is highly beneficial and has made it possible to effectively control disease using networks of interconnected sensors worn by individuals. The purpose of this work is to develop an AI-IoMT framework for identifying several of chronic diseases form the patients' medical record. For that, the Deep Auto-Optimized Collaborative Learning (DACL) Model, a brand-new AI-IoMT framework, has been developed for rapid diagnosis of chronic diseases like heart disease, diabetes, and stroke.

Does diet quality moderate the long-term effects of discrete but extreme PM exposure on respiratory symptoms? A study of the Hazelwood coalmine fire.

In 2014, a fire at an open cut coalmine in regional Victoria, Australia burned for 6 weeks. Residents of the nearby town of Morwell were exposed to smoke, which included high levels of fine particulate matter (PM). We investigated whether the long-term effects of PM on respiratory health were moderated by diet quality.

Role of Amyloidogenic and Non-Amyloidogenic Protein Spaces in Neurodegenerative Diseases and their Mitigation Using Theranostic Agents.

Neurodegenerative diseases (NDDs) refer to a complex heterogeneous group of diseases which are associated with the accumulation of amyloid fibrils or plaques in the brain leading to progressive loss of neuronal functions. Alzheimer's disease is one of the major NDD responsible for 60-80 % of all dementia cases. Currently, there are no curative or disease-reversing/modifying molecules for many of the NDDs except a few such as donepezil, rivastigmine, galantamine, carbidopa and levodopa which treat the disease-associated symptoms.

Polycatechols inhibit ferroptosis and modulate tau liquid-liquid phase separation to mitigate Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder that affects learning, memory, and cognition. Current treatments targeting amyloid-β (Aβ) and tau have shown limited effectiveness, necessitating further research on the aggregation and toxicity mechanisms. One of these mechanisms involves the liquid-liquid phase separation (LLPS) of tau, contributing to the formation of pathogenic tau aggregates, although their conformational details remain elusive.

Designer tryptophan-rich peptide modulates structural dynamics of HIF-1α DNA i-motif DNA.

Cytosine-rich DNA sequences can fold into intercalated motifs known as i-motifs, through noncanonical hydrogen bonding interactions. Molecular probes can provide valuable insights into the conformational stability and potential cellular functions of i-motifs. WK, a decapeptide composed of alternating tryptophan (W) and lysine (K) units, has been identified as a lead candidate to modulate the structural dynamics of the hypoxia-inducible factor 1-alpha (HIF-1α) DNA i-motif.

Biphasic modulation of tau liquid-liquid phase separation by polyphenols.

Molecular tools that modulate tau liquid-liquid phase separation (LLPS) promise to treat tauopathies. We screened a set of polyphenols and demonstrated concentration-dependent biphasic modulation of tau LLPS by gallic acid (GA), showcasing its ability to expedite the liquid-to-gel transition in tau condensates and effectively impede the formation of deleterious fibrillar aggregates.

Hybrid molecules synergistically mitigate ferroptosis and amyloid-associated toxicities in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the build-up of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Ferroptosis, an iron (Fe)-dependent form of cell death plays a significant role in the multifaceted AD pathogenesis through generation of reactive oxygen species (ROS), mitochondrial damage, lipid peroxidation, and reduction in glutathione peroxidase 4 (GPX4) enzyme activity and levels. Aberrant liquid-liquid phase separation (LLPS) of tau drives the growth and maturation of NFTs contributing to AD pathogenesis.

Introduction to the themed collection on 'Molecular and Nanotheranostics'.

Thimmaiah Govindaraju introduces the themed collection on molecular and nanotheranostics.

Cooperative dissolution of peptidomimetic vesicles and amyloid β fibrils.

The aggregation of amyloid proteins in the brain is a significant neurotoxic event that contributes to neurodegenerative disorders. The aggregation of amyloid beta (Aβ), particularly Aβ42 monomers, into various forms such as oligomers, protofibrils, fibrils, and amyloid plaques is a key pathological feature in Alzheimer's disease. As a result, Aβ42 is a primary target and the development of molecular strategies for the dissolution of Aβ42 aggregates is considered a promising approach to mitigating Alzheimer's disease pathology.

G-quadruplex structural dynamics at MAPK12 promoter dictates transcriptional switch to determine stemness in breast cancer.

P38γ (MAPK12) is predominantly expressed in triple negative breast cancer cells (TNBC) and induces stem cell (CSC) expansion resulting in decreased survival of the patients due to metastasis. Abundance of G-rich sequences at MAPK12 promoter implied the functional probability to reverse tumorigenesis, though the formation of G-Quadruplex (G4) structures at MAPK12 promoter is elusive. Here, we identified two evolutionary consensus adjacent G4 motifs upstream of the MAPK12 promoter, forming parallel G4 structures.

Intrinsically Disordered Ku Protein-Derived Cell-Penetrating Peptides.

Efficient delivery of bioactive ingredients into cells is a major challenge. Cell-penetrating peptides (CPPs) have emerged as promising vehicles for this purpose. We have developed novel CPPs derived from the flexible and disordered tail extensions of DNA-binding Ku proteins.

Small molecules and conjugates as theranostic agents.

Theranostics, the integration of therapy and diagnostics into a single entity for the purpose of monitoring disease progression and treatment response. Diagnostics involves identifying specific characteristics of a disease, while therapeutics refers to the treatment of the disease based on this identification. Advancements in medicinal chemistry and technology have led to the development of drug modalities that provide targeted therapeutic effects while also providing real-time updates on disease progression and treatment.

Glucose-Responsive Self-Regulated Injectable Silk Fibroin Hydrogel for Controlled Insulin Delivery.

Stimuli-responsive drug delivery systems are gaining importance in personalized medicine to deliver therapeutic doses in response to disease-specific stimulation. Pancreas-mimicking glucose-responsive insulin delivery systems offer improved therapeutic outcomes in the treatment of type 1 and advanced stage of type 2 diabetic conditions. Herein, we present a glucose-responsive smart hydrogel platform based on phenylboronic acid-functionalized natural silk fibroin protein for regulated insulin delivery.

Nanoclusters with specific DNA overhangs: modifying configurability, engineering contrary logic pairs and the parity generator/checker for error detection.

The most promising alternative for next-generation molecular computers is biocomputing, which uses DNAs as its primary building blocks to perform a Boolean operation. DNA nanoclusters (NCs) have emerged as promising candidates for biosensing applications due to their unique self-assembly properties and programmability. It has been demonstrated that adding DNA overhangs to DNA NCs improves their adaptability in identifying specific biomolecular interactions.

A natural polyphenol activates and enhances GPX4 to mitigate amyloid-β induced ferroptosis in Alzheimer's disease.

Ferroptosis, an iron-dependent cell death, plays a crucial role in the pathology of Alzheimer's disease (AD). Several characteristics of AD, including excessive iron accumulation, elevated lipid peroxide and reactive oxygen species (ROS) levels, and decreased glutathione peroxidase 4 (GPX4) levels, align with the features of ferroptosis. While traditional methods of inhibiting ferroptosis have centered on chelating Fe and trapping radicals, therapeutic strategies that modulate the GPX4 axis to mitigate ferroptosis in AD are yet to be explored.

Coronavirus genomic cDNA derived G-quadruplex as a selective target for fluorometric detection.

Pathogenic genomes harboring noncanonical G-quadruplex (GQ) forming sequences are potential targets for diagnosis. The GQ-forming cDNA sequences of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) are identified and validated as reliable diagnostic targets. The high fidelity fluorescence detection of specific cDNA GQs derived from the SARS-CoV-2 RNA genome is demonstrated using small molecular probes.

Multipronged diagnostic and therapeutic strategies for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and a major contributor to dementia cases worldwide. AD is clinically characterized by learning, memory, and cognitive deficits. The accumulation of extracellular amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs) of tau are the pathological hallmarks of AD and are explored as targets for clinical diagnosis and therapy.

Multifunctional Architectures of Cyclic Dipeptide Copolymers and Composites, and Modulation of Multifaceted Amyloid-β Toxicity.

Alzheimer's disease (AD) is a major neurodegenerative disorder primarily characterized by the β-amyloid (Aβ42) misfolding and aggregation-associated multifaceted amyloid toxicity encompassing oxidative stress, neuronal death, and severe cognitive impairment. Modulation of Aβ42 aggregation various structurally anisotropic macromolecular systems is considered effective in protecting neuronal cells. In this regard, we have developed a cyclic dipeptide (CDP)-based copolymer (CP) and explored its material and biomedical properties.

Cyclic dipeptide-based small molecules modulate zinc-mediated liquid-liquid phase separation of tau.

Liquid-liquid phase separation (LLPS) is a complex physicochemical phenomenon mediated by multivalent transient weak interactions among macromolecules like polymers, proteins, and nucleic acids. It has implications in cellular physiology and disease conditions like cancer and neurodegenerative disorders. Many proteins associated with neurodegenerative disorders like RNA binding protein FUS (FUsed in Sarcoma), alpha-synuclein (α-Syn), TAR DNA binding protein 43 (TDP-43), and tau are shown to undergo LLPS.