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Mitochondrial dysfunction plays a pivotal role in the development of age-related diseases, particularly neurodegenerative disorders. The etiology of mitochondrial dysfunction involves a multitude of factors that remain elusive. This review centers on elucidating the role(s) of excitotoxicity, oxytosis/ferroptosis and neurodegeneration within the context of mitochondrial bioenergetics, biogenesis, mitophagy and oxidative stress and explores their intricate interplay in the pathogenesis of neurodegenerative diseases. The effective coordination of mitochondrial turnover processes, notably mitophagy and biogenesis, is assumed to be critically important for cellular resilience and longevity. However, the age-associated decrease in mitophagy impedes the elimination of dysfunctional mitochondria, consequently impairing mitochondrial biogenesis. This deleterious cascade results in the accumulation of damaged mitochondria and deterioration of cellular functions. Both excitotoxicity and oxytosis/ferroptosis have been demonstrated to contribute significantly to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS). Excitotoxicity, characterized by excessive glutamate signaling, initiates a cascade of events involving calcium dysregulation, energy depletion, and oxidative stress and is intricately linked to mitochondrial dysfunction. Furthermore, emerging concepts surrounding oxytosis/ferroptosis underscore the importance of iron-dependent lipid peroxidation and mitochondrial engagement in the pathogenesis of neurodegeneration. This review not only discusses the individual contributions of excitotoxicity and ferroptosis but also emphasizes their convergence with mitochondrial dysfunction, a key driver of neurodegenerative diseases. Understanding the intricate crosstalk between excitotoxicity, oxytosis/ferroptosis, and mitochondrial dysfunction holds potential to pave the way for mitochondrion-targeted therapeutic strategies. Such strategies, with a focus on bioenergetics, biogenesis, mitophagy, and oxidative stress, emerge as promising avenues for therapeutic intervention.

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Pain is a multifaceted, multisystem disorder that adversely affects neuro-psychological processes. This study compares the effectiveness of central stimulation (transcranial direct current stimulation-tDCS over F3/F4) and peripheral stimulation (transcutaneous electrical nerve stimulation-TENS over the median nerve) in pain inhibition during a cognitive task in healthy volunteers and to observe potential neuro-cognitive improvements. Eighty healthy participants underwent a comprehensive experimental protocol, including cognitive assessments, the Cold Pressor Test (CPT) for pain induction, and tDCS/TENS administration. EEG recordings were conducted pre- and post-intervention across all conditions. The protocol for this study was categorized into four groups: G1 (control), G2 (TENS), G3 (anodal-tDCS), and G4 (cathodal-tDCS). Paired t-tests (p < 0.05) were conducted to compare Pre-Stage, Post-Stage, and neuromodulation conditions, with t-values providing insights into effect magnitudes. The result showed a reduction in pain intensity with TENS (p = 0.002, t-value = -5.34) and cathodal-tDCS (p = 0.023, t-value = -5.08) and increased pain tolerance with TENS (p = 0.009, t-value = 4.98) and cathodal-tDCS (p = 0.001, t-value = 5.78). Anodal-tDCS (p = 0.041, t-value = 4.86) improved cognitive performance. The EEG analysis revealed distinct neural oscillatory patterns across the groups. Specifically, G2 and G4 showed delta-power reductions, while G3 observed an increase. Moreover, G2 exhibited increased theta-power in the occipital region during CPT and Post-Stages. In the alpha-band, G2, G3, and G4 had reductions Post-Stage, while G1 and G3 increased. Additionally, beta-power increased in the frontal region for G2 and G3, contrasting with a reduction in G4. Furthermore, gamma-power globally increased during CPT1, with G1, G2, and G3 showing reductions Post-Stage, while G4 displayed a global decrease. The findings confirm the efficacy of TENS and tDCS as possible non-drug therapeutic alternatives for cognition with alleviation from pain.

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Porous organic frameworks (POFs) represent a significant subclass of nanoporous materials in the field of materials science, offering exceptional characteristics for advanced applications. Covalent organic frameworks (COFs), as a novel and intriguing type of porous material, have garnered considerable attention due to their unique design capabilities, diverse nature, and wide-ranging applications. The unique structural features of COFs, such as high surface area, tuneable pore size, and chemical stability, render them highly attractive for various applications, including targeted and controlled drug release, as well as improving the sensitivity and selectivity of electrochemical biosensors. Therefore, it is crucial to comprehend the methods employed in creating COFs with specific properties that can be effectively utilized in biomedical applications. To address this indispensable fact, this review paper commences with a concise summary of the different methods and classifications utilized in synthesizing COFs. Second, it highlights the recent advancements in COFs for drug delivery, including drug carriers as well as the classification of drug delivery systems and biosensing, encompassing drugs, biomacromolecules, small biomolecules and the detection of biomarkers. While exploring the potential of COFs in the biomedical field, it is important to acknowledge the limitations that researchers may encounter, which could impact the practicality of their applications. Third, this paper concludes with a thought-provoking discussion that thoroughly addresses the challenges and opportunities associated with leveraging COFs for biomedical applications. This review paper aims to contribute to the scientific community's understanding of the immense potential of COFs in improving drug delivery systems and enhancing the performance of biosensors in biomedical applications.

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Huntington's disease (HD) is a neurodegenerative genetic disorder characterized by a mutation in the huntingtin (HTT) gene, resulting in the production of a mutant huntingtin protein (mHTT). The accumulation of mHTT leads to the development of toxic aggregates in neurons, causing cell dysfunction and, eventually, cell death. Peptide therapeutics target various aspects of HD pathology, including mHTT reduction and aggregation inhibition, extended CAG mRNA degradation, and modulation of dysregulated signaling pathways, such as BDNF/TrkB signaling. In addition, these peptide therapeutics also target the detrimental interactions of mHTT with InsP3R1, CaM, or Caspase-6 proteins to mitigate HD. This Perspective provides a detailed perspective on anti-HD therapeutic peptides, highlighting their design, structural characteristics, neuroprotective effects, and specific mechanisms of action. Peptide therapeutics for HD exhibit promise in preclinical models, but further investigation is required to confirm their effectiveness as viable therapeutic strategies, recognizing that no approved peptide therapy for HD currently exists.

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Oxytosis/ferroptosis is an iron-dependent oxidative form of cell death triggered by lethal accumulation of phospholipid hydroperoxides (PLOOHs) in membranes. Failure of the intricate PLOOH repair system is a principle cause of ferroptotic cell death. Glutathione peroxidase 4 (GPX4) is distinctly vital for converting PLOOHs in membranes to non-toxic alcohols. As such, GPX4 is known as the master regulator of oxytosis/ferroptosis. Ferroptosis has been implicated in a number of disorders such as neurodegenerative diseases (amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), etc.), ischemia/reperfusion injury, and kidney degeneration. Reduced function of GPX4 is frequently observed in degenerative disorders. In this study, we examine how diminished GPX4 function may be a critical event in triggering oxytosis/ferroptosis to perpetuate or initiate the neurodegenerative diseases and assess the possible therapeutic importance of oxytosis/ferroptosis in neurodegenerative disorders. These discoveries are important for advancing our understanding of neurodegenerative diseases because oxytosis/ferroptosis may provide a new target to slow the course of the disease.

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We measure the elastic modulus of a single horizontal ZnO nanorod [NR] grown by a low-temperature hydrothermal chemical process on silicon substrates by performing room-temperature, direct load-controlled nanoindentation measurements. The configuration of the experiment for the single ZnO NR was achieved using a focused ion beam/scanning electron microscope dual-beam instrument. The single ZnO NR was positioned horizontally over a hole on a silicon wafer using a nanomanipulator, and both ends were bonded with platinum, defining a three-point bending configuration. The elastic modulus of the ZnO NR, extracted from the unloading curve using the well-known Oliver-Pharr method, resulted in a value of approximately 800 GPa. Also, we discuss the NR creep mechanism observed under indentation. The mechanical behavior reported in this paper will be a useful reference for the design and applications of future nanodevices.

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In this study, the low temperature aqueous chemical growth (ACG) method was employed to synthesized ZnO nanorods to process-organic hybrid white light emitting diodes (LEDs) on glass substrate. Electroluminescence spectra of the hybrid white LEDs demonstrate the combination of emission bands arising from radiative recombination of the organic and ZnO nanorods (NRs). Depth resolved luminescence was used for probing the nature and spatial distribution of radiative defects, especially to study the re-absorption of ultraviolet (UV) in this hybrid white LEDs structure. At room temperature the cathodoluminescence (CL) spectra intensity of the deep band emission (DBE) is increased with the increase of the electron beam penetration depth due to the increase of defect concentration at the ZnO NRs/Polyfluorene (PFO) interface and probably due to internal absorption of the UV. A strong dependency between the intensity ratio of the UV to the DBE bands and the spatial distribution of the radiative defects in ZnO NRs has been found. The comparison of the CL spectra from the PFO and the ZnO NRs demonstrate that PFO has a very weak violet-blue emission band, which confirms that most of the white emission components originate from the ZnO NRs.